What is sciatica?

Causes and Symptoms

The two sciatic nerves are the largest nerves in the body. One runs from the spine down the left leg, the other down the right leg; they supply the tissues of the thigh, lower leg, and foot. The roots of the sciatic nerves are in the lower spinal column. It is here that difficulty is most likely to occur. Inflammation of these nerves is most often caused by a pinching of one or more spinal nerve roots between the vertebrae of the lower back.

Sciatica is characterized by shooting pain down the sciatic nerve and extending into the hip, the thigh, and the back portion of the leg. The pain may occur in all these points at once or skip about from point to point. Sciatica often begins with a long period of intermittent, mild low back
pain. Suddenly, however, the slightest movement, such as lifting a weight or merely bending over, may bring about intense sciatic pain.

A mild case of sciatica can be brought on by vitamin deficiencies or by arthritic inflammation in the lower spine. Prolonged constipation can build pressure on the nerve and cause sciatic pain. Occasionally, a tumor may develop near the nerve and press on it. Sometimes, a herniated, or slipped, disk at the level where the nerve roots emerge in the low back may protrude and press on the nerve, thereby causing sciatica.

Treatment and Therapy

If the sciatic nerve is being compromised, surgery may be indicated. More than 50 percent of patients with sciatica, however, recover on their own in six weeks. In the acute stage, reducing one's activity level is important; however, bed rest is not recommended. The patient should gradually return to his or her daily activities and stay active. Applying ice for the first two to three days, and then heat after, may give temporary relief from pain. The type of medication used depends on the cause of the sciatica. Ultimately, a therapeutic exercise program to develop stabilizing strength and endurance in the trunk
muscles is essential for functional recovery.

Bibliography

Brown, Mark D., and Björn L. Rydevik, eds. Causes and Cure of Low Back Pain and Sciatica. Philadelphia: W. B. Saunders, 1991.

Fishman, Loren, and Carol Ardman. Back Pain: How to Relieve and Cure Low Back Pain and Sciatica. New York: W. W. Norton, 1999.

Gillette, Robert D. “A Practical Approach to the Patient with Back Pain.” American Family Physician 53, no. 2 (February 1, 1996): 670–678.

Hildreth, Carolyn J., Cassio Lynm, and Richard M. Glass. "Sciatica." Journal of the American Medical Association 302, no. 2 (July 8, 2009): 216.

Hooper, Paul D. Preventing Low Back Pain. Baltimore: Williams & Wilkins, 1992.

Ogiela, Dennis, and David Zieve. "Sciatica." MedlinePlus, June 7, 2012.

"Sciatica." American Academy of Orthopaedic Surgeons, Oct. 2007.

"Sciatica." MedlinePlus, Mar. 8, 2013.

Smoots, Elizabeth, and Brian Randall. "Sciatica." Health Library, Nov. 26, 2012.

In Romeo and Juliet, what is your impression of Romeo's feelings for Rosaline as they are depicted in Act 1, scene 1?

In this scene, Lord and Lady Montague express their concern for their son, Romeo, who has come across as quite depressed. They tell Benvolio that he often keeps to himself in a darkened room and does not want to speak to them about his distress. They have consulted many others to establish a reason for their son's sadness but have not had much success.

As Romeo approaches, Benvolio promises that he will make it his duty to find out what is troubling his friend. Before they depart, Lord Montague tells Benvolio that he wishes that he would successful in his quest, for he would surely like to know what is wrong with his son.

Romeo and Benvolio indulge in some small talk and Benvolio asks him why he feels that the day is so long since he remarked about it still being morning. Romeo replies that it is because he does not have that which would make his days seem shorter. Benvolio asks him if he is in love and Romeo says that he is out, which Benvolio interprets as meaning 'out of love' but Romeo says that he is out of her favour, implying that the one he loves does not return his affection.

Romeo is clearly distraught and in torment, for he uses a number of oxymoronic phrases to explain his pain:

Why, then, O brawling love! O loving hate!
O any thing, of nothing first create!
O heavy lightness! serious vanity!
Mis-shapen chaos of well-seeming forms!
Feather of lead, bright smoke, cold fire,
sick health!
Still-waking sleep, that is not what it is!
This love feel I, that feel no love in this.

The poor lad is obviously deeply infatuated and in romantic purgatory, for he cannot make sense of the fact that his endearment is unrequited. He obviously does not want to speak more about what he feels and wishes to go. Benvolio, however, refuses to leave his side, for he wants to know more.

Romeo tells him that he is not himself and Benvolio asks him to tell him who it is that he loves. Romeo does not name Rosaline, we only learn this later, but he does mention that it is a woman he loves and that she is beautiful (fair). When Benvolio comments that such a mark is easier to hit, his friend tells him that that is where he is wrong, for this mark refuses to be hit, saying:

Well, in that hit you miss: she'll not be hit
With Cupid's arrow; she hath Dian's wit;
And, in strong proof of chastity well arm'd,
From love's weak childish bow she lives unharm'd.
She will not stay the siege of loving terms,
Nor bide the encounter of assailing eyes,
Nor ope her lap to saint-seducing gold:
O, she is rich in beauty, only poor,
That when she dies with beauty dies her store.

He states that Rosaline has made a vow of chastity and that her determination to remain so is an unbreakable resolve. She will not allow herself to be persuaded in any way and that, although she has a wealth of beauty, she is poor since her bounty (which is her good looks) will die with her and would not have profited in any way.

When Benvolio wants confirmation that she has indeed promised to remain chaste, Romeo responds by saying that she has and for that, is wasting what she has. He says that she is too wise and too beautiful to be persuaded and, in doing so, has denied him happiness and has denied her beauty to live on forever for she is so harsh. Rosaline has renounced love and in that has brought about his death, metaphorically speaking. 

Benvolio, out of concern for his friend asks Romeo to follow his advice and forget about thinking of her. Romeo asks him how he should do that and is told that he should look at other women. Romeo, who is obviously steeped in his self-inflicted misery, responds:

...Show me a mistress that is passing fair,
What doth her beauty serve, but as a note
Where I may read who pass'd that passing fair?
Farewell: thou canst not teach me to forget.

Romeo is too disconsolate to contemplate even looking at another girl for it would just serve as a reminder that he had missed out on having won Rosaline's affection. He believes that Benvolio cannot teach him to forget. The determined Benvolio, though, insists that he will definitely teach him to dismiss thoughts of Rosaline or die indebted to him if he cannot.

Romeo is clearly completely infatuated with Rosaline. She has become his focal point at this stage. He cannot get her out of his mind and his thoughts constantly dwell on her, specifically because she refuses to return his affections. He is more in love with the idea of being in love and because this sentiment does not receive a proper outlet and is not resolved, he becomes miserable. In the end, he is the reason for his misery, not Rosaline.

What is one internal and one external conflict of Julius Caesar in the Shakespeare play Julius Caesar?

Caesar's external conflict is very straight-forward: man vs. man. Caesar is positioned in direct opposition to the men who are trying to assassinate him for his supposed ambition. This conflict is strongest between Caesar and Cassius, who Caesar says has "a lean and hungry look" (1.2.194). Caesar doesn't trust Cassius' ambition, just as Cassius doesn't trust Caesar's.

Caesar's internal conflict is harder to pinpoint, mainly because his character is so ambiguous. One internal struggle might be his decision to aim for the position of king of Rome. When Mark Antony offers the crown to Caesar and he refuses it despite the crowd's cheers, he could be playing out a public relations scene or genuinely reacting to a natural moment. Either way, it seems that he both wants and avoids crowning himself king of Rome, though the audience never gets to see that conflict play out. 

Another internal conflict that Caesar seems to be experiencing is with his physical limitations. He suffers from epilepsy, he can't hear out of one ear, Cassius recalls him getting very sick and losing a swimming contest in a very embarrassing way. It could certainly be the case that Caesar has been in constant struggle against handicaps and various disabilities his whole life. 

What is sedative-hypnotic abuse?

History of Use

Bromide, the first sedative-hypnotic, originated in 1838 and was followed by chloral hydrate, paraldehyde, and barbiturates. Bromide compounds were frequently used as sedatives and anticonvulsants in the nineteenth and early twentieth century.

Barbiturates were first introduced for medical use in the early twentieth century. Since then, approximately fifty barbiturates were marketed but less than fifteen remain in medical use. Barbiturates became popular in the 1960s as treatment for anxiety, insomnia, and seizure disorders, but the dependence-producing potential and the dangers of overdose restricted their use significantly. Since the 1970s, barbiturates were largely replaced by the safer BDZ group.

The first BDZs, chlordiazepoxide and diazepam, were introduced in clinical practice in the early 1960s. Although more than two thousand different BDZs have been synthesized, less than twenty are currently approved in the United States. BDZ usage increased dramatically in the 1970s, with total sales accounting for about 10 percent of all prescriptions in many Western countries. The perceived desirable properties of anxiety alleviation, euphoria, disinhibition, and sleep promotion have led to the compulsive misuse of virtually all of the drugs classed as sedative-hypnotics.

Effects and Potential Risks

Graded, dose-dependent depression of the central nervous system (CNS) function is characteristic of sedative-hypnotics. At low doses, they produce sedation (relieving anxiety and promoting relaxation), whereas at higher doses they have a hypnotic effect.

Barbiturates

Barbiturates are classified three ways. Those three ways, and the associated barbiturate, are ultrashort-acting methohexital (Brevital), thiamyl (Surital), and thiopental (Pentothal); short- and intermediate-acting amobarbital (Amytal), pentobarbital (Nembutal), secobarbital (Seconal), butalbital (Fiorinal), butabarbital (Butisol), talbutal (Lotusate), and aprobarbital (Alurate); and long-acting phenobarbital (Luminal) and mephobarbital (Mebaral).

Barbiturates produce a wide spectrum of CNS depression, from mild sedation to coma, and are used as sedatives, hypnotics, anesthetics, and anticonvulsants. The ultrashort-acting barbiturates produce anesthesia within one minute of intravenous administration and are used for minor surgery or as preoperative anesthetics for major surgery. The long-acting barbiturates are used in some forms of epilepsy or to treat convulsions caused by cocaine and other stimulant drugs. Barbiturates have a narrow therapeutic index and can cause coma or death if taken inappropriately, especially in children and elderly persons.

The toxicity of barbiturates is likely when the dose exceeds five to ten times the hypnotic dose. The potentially fatal dose for phenobarbital is 6 to 10 grams, but only 2 to 3 grams for pentobarbital or secobarbital. Barbiturates also are addictive if taken daily for longer than about one month and can cause a life-threatening withdrawal syndrome upon discontinuation.

Symptoms of withdrawal include tremors, difficulty sleeping, agitation, hallucinations, high temperature, and seizures. In pregnant women barbiturates can cause dependence and newborn withdrawal syndrome. Barbiturates are commonly used in suicide attempts. Although the medical use and street abuse of barbiturates declined after the 1970s, surveys suggest that abuse has been rising since about 2000. Barbiturates are commonly abused to counteract the symptoms of such stimulating drugs as cocaine and methamphetamine.

BDZs

BDZs (also known as minor tranquilizers) are effective in a wide range of medical and psychiatric conditions, such as anxiety and sleep disorders, panic attacks, agoraphobia, acute stress reactions, convulsive and spastic disorders, presurgical sedation, and detoxification from alcohol. They are usually classified by their duration of action, which ranges from less than six hours to more than twenty-four hours as ultra-short acting midazolam (Versed) and triazolam (Halcion); as short-acting alprazolam (Xanax), lorazepam (Ativan), estazolam (ProSom), temazepam (Restoril), and oxazepam (Serax); and as long-acting chlordiazepoxide (Librium), diazepam (Valium), clonazepam (Klonopin), flurazepam (Dalmane), and clorazepate (Tranxene).

BDZs are widely prescribed, and four of them—alprazolam, clonazepam, diazepam, and lorazepam—are among the top forty prescription medications sold. Alprazolam and diazepam are the two most frequently encountered BDZs on the illicit market.

Signs and symptoms of acute toxicity or overdose may include drowsiness, confusion, dizziness, blurred vision, weakness, slurred speech, lack of coordination, difficulty breathing, and coma. Fatal overdoses usually involve the combination of BDZ and alcohol. When used chronically, for longer than four to eight weeks, BDZ can be addicting. BDZ, particularly those having a rapid onset—the highly lipophilic (such as diazepam) and the short-acting/high-potency BDZ (such as alprazolam or lorazepam)—are the most reinforcing and, therefore, most likely to be associated with abuse. They are used recreationally to induce relaxation and are abused to produce a euphoric effect.

BDZ also are used to augment alcohol’s effects and to manage withdrawal states. BDZ have a relatively low potential for abuse in persons without a history of substance use disorders but moderate-to-high potential for people with a history of substance abuse or dependence.

NB-NBDZs

NB-NBDZs include chemically heterogeneous compounds that do not fall into either the barbiturate or the BDZ group. Chloral hydrate (Somnote, Aquachloral) is a fast-acting sedative-hypnotic with long-lasting effects. It had widespread use (including recreationally) in the late nineteenth century. A solution of chloral hydrate in alcohol was known as knock-out drops or Mickey Finn (a drink designed to incapacitate the person who drinks it).

Methaqualone (Quaalude) possesses sedative-hypnotic, anticonvulsant, antispasmodic, local anesthetic, antitussive, and weak antihistaminic properties. It produces a dissociative high that resembles those of opiates (heightened sensitivity and euphoria) without the drowsiness caused by barbiturates. Methaqualone became a popular recreational drug in the 1960s and 1970s. Because of its high abuse potential, methaqualone has been removed from the market in many countries. In the United States, the marketing of methaqualone stopped in 1984.

Other Uses of Sedative-Hypnotics

Some of the sedative-hypnotics are used to commit sexual assaults. Because these drugs are sedating and induce a temporary amnesia, they are sometimes added to alcoholic beverages and soft drinks to incapacitate the intended victim of a rape. Flunitrazepam (Rohypnol), also known with the street names rophies, roofies, and roach, is a long-acting BDZ used as a favored sedative of abuse among adolescents and adults, and it is typically used in combination with alcohol as a party drug and a date rape drug .

Flunitrazepam has never been approved for medical use in the United States. Gamma-hydroxy butyrate (GHB), a natural CNS depressant resulting from the metabolism of the inhibitory neurotransmitter GABA, has emerged as a significant drug of abuse. It gained popularity for recreational use because of its pleasant, alcohol-like, hangover-free high with aphrodisiac properties.

Body-builders abuse GHB for its alleged utility as an anabolic agent. GHB is often taken by young polydrug abusers (who are called clubbers and ravers) in combination with amphetamines to produce euphoria and a hallucinatory state. Because of concerns about GHB abuse and date rape usage, in 2000 this drug was made a schedule I controlled substance. Because flunitrazepam and GHB are illegal in the United States, they are available only through the underground market.

Those who chronically abuse sedative-hypnotics prefer the short-acting barbiturates, the barbiturate-like depressants glutethimide and methaqualone, and the faster-acting BDZs diazepam, alprazolam, and lorazepam. Persons who abuse sedative-hypnotics are most likely to be those who use drugs to relieve stress; who use drugs to counteract unpleasant effects of other drugs of abuse; and who combine CNS depressants with alcohol or opiates to potentiate their effects.

Significant safety concerns with sedative-hypnotics include important drug interactions (for example, the inhibitors of drug metabolism such as antifungals, erythromycin, clarithromycin, or cimetidine significantly prolong their effect and increase their toxicity) and their appropriate use in special populations (elderly people, pregnant women, and persons with a history of substance abuse). Overdosing on sedative-hypnotics is among the most common methods for attempting suicide.

Bibliography

Hanson, Glen R., Peter J. Venturelli, and Annette E. Fleckenstein. Drugs and Society. 11th ed. Sudbury, MA: Jones, 2012. Print.

Heller, Jacob L. "Barbiturate Intoxication and Overdose." MedlinePlus. National Library of Medicine, 15 Jan. 2014. Web. 30 Oct. 2015.

Lader, Malcolm. “History of Benzodiazepine Dependence.” Journal of Substance Abuse Treatment 8.1–2 (1991): 53–59. Print.

O’Brien, Charles P. “Benzodiazepine Use, Abuse, and Dependence.” Journal of Clinical Psychiatry 66, suppl. 2 (2005): 28–33. Print.

Posternak, M. A., and T. I. Mueller. “Assessing the Risks and Benefits of Benzodiazepines for Anxiety Disorders in Patients with a History of Substance Abuse or Dependence.” American Journal on Addictions 10.1 (2001): 48–68. Print.

What does the house in Berlin look like in Boyne's The Boy in the Striped Pajamas?

Bruno absolutely loves his house in Berlin.  As a result, the narrator happily describes this house to the reader at the very beginning of the novel.  Therefore, the reader learns quite a bit about this part of the setting in Chapter 1 of The Boy in the Striped Pajamas. 

It was a very beautiful house and had five floors in total, if you included the basement, ... and if you added the little room at the top of the house with the slanted windows where Bruno could see right across Berlin if he stood up on his tiptoes and held on to the frame tightly.

This should confirm for the reader that Bruno's family is very wealthy.  They own a five-story home within the city of Berlin.  Bruno is enamored of this home.  He is especially enamored of two particular things:  the long banister and the proximity to his grandparents.

He wondered whether the new house ... would have as fine banister to slide down as this one did.  For the banister in this house stretched from the very top floor--just outside the little room ... to the ground floor, just in front of the two enormous oak doors.

Bruno goes on to say that he liked nothing better than a good slide down that fabulous banister.  This should not be a surprise for the reader.  A slide down an amazing banister can be a wonderful ride for a nine-year-old boy.  Further, these paragraphs hold marvelous descriptions of setting.  The reader is given many specifics even down to the "enormous oak door" of the front of the house. 

Unfortunately for Bruno, the new house near Auschwitz looks nothing like his home in Berlin.  Bruno's feelings about his old home are directly contrasted with his feelings about his new home.

What happens again after Tom gets back into the apartment and how does he respond?

The last two paragraphs of Jack Finney’s short story “Contents of the Dead Man’s Pocket” describe Tom Benecke’s actions after he enters the apartment through the broken window, leaving the perils of the eleventh story ledge behind. While on the ledge, Tom imagines if he can save himself and get back into the apartment, he will celebrate by running through it, or falling to the carpet in gratitude. He does not chose to do either of those things. Instead, he calmly removes the wrinkles from the yellow worksheet, and places it on his desk. He remembers to anchor the piece of paper with a pencil before he grabs his coat and hat while heading out the door to find his wife. As he opens the door to the hallway, a breeze blows through the apartment. Tom watches as the paper is lifted off the desk, and once again is sucked out the window. Instead of panicking as he did at the beginning of the story, he cackles and rushes out the door.

Please explain what themes are evident in chapters 7 and 8 of To Kill A Mockingbird.

Chapters 7 and 8 of Lee's To Kill a Mockingbird are filled with coming-of-age experiences for Jem and Scout. The story is called a bildungsroman, which means the development and education of the protagonists are part of the central theme. Jem and Scout are still learning about Boo Radley and Jem seems to know more than his sister. He's learning that Boo might be more of a friend than a ghost because they've been finding gifts in the Radley's tree (knothole); and Jem found his pants mended after getting them caught and forsaken on the Radley's fence. Jem therefore decides to write a thank you letter to whomever has been leaving them gifts in the tree, but he suspects that it is Boo and really wants to show his appreciation. However, just before they want to give him the letter, Mr. Nathan Radley fills the hole up with cement claiming that the tree is dying. This is a life lesson to the children that sometimes, just when we are about to achieve a goal or get what we want, it is stripped away from us and we are left with disappointment. Scout cries and Jem tells her not to worry, but their friendship and communication with Boo has been stopped.

Next, in chapter 8, the children are enjoying their friendship with Miss Maudie and their first experience with snow falling in Maycomb. Unfortunately, Miss Maudie's house is claimed by a house fire during the night. While the kids are watching the fire in front of the Radley house, Boo wraps a blanket around Scout. They discover it later and Jem says to her, "Boo Radley. You were so busy looking at the fire you didn't know it when he put the blanket around you" (72). Ironically, the kids lose a second chance to communicate with Boo. They were so close, yet so far away! But they experience another minor disappointment. In each case, too, there is an element of irony that keeps them from achieving their goals. 

Even though there are unexpected outcomes (irony) and disappointment in these two chapters, there are other themes of hope and love that can be sensed. For instance, when Scout cries about the knothole being filled with cement, her brother sweetly comforts her with love and hope by saying, "Don't you cry, now, Scout. . . don't cry now, don't you worry" (62).

Then, when Scout talks to Miss Maudie after the fire, Maudie says the following:

"Don't you worry about me, Jean Louise Finch. There are ways of doing things you don't know about. Why, I'll build me a little house and take me a couple of roomers and--gracious, I'll have the finest yard in Alabama" (73).

It's interesting to note that both Maudie and Jem tell Scout not to worry, which can be a theme as well. When times get tough, difficult, or disappointing, don't worry. 

What did Socrates mean by the phrase "Know Thyself"?

The phrase "know thyself" (Greek: γνῶθι σεαυτόν) was a maxim actually inscribed near the entrance to the temple of Apollo at Delphi. Although Plato has Socrates discuss it in several dialogues, he was not the originator of the phrase; instead, it was a well known maxim in his period. 

The first important element of Socrates' appropriation of the phrase has to do with his self-positioning with respect both the sophists and natural philosophers of his period. At his trial, he was accused both of speculating about natural philosophy and of being a sophist. Part of how Plato refutes this is by showing him mainly to be interested in ethics and in helping people develop self-knowledge as opposed to speculating about religion or physics. 

The next aspect of the phrase is its relationship to "Socratic ignorance." Rather than claiming to have knowledge, as did the sophists, Socrates claimed to be wise only in knowing that he was ignorant. He sees knowing the limits of one's knowledge and admitting to ignorance as the first step to wisdom.

In the middle dialogues, Socrates advances the theory of recollection. According to this theory, the soul had perfect knowledge of the "forms" and the divine before it descended into the body. Thus the best way to obtain knowledge of these things is not by trusting our senses but by looking inside ourselves to recover these memories of the knowledge our soul had before we were born.

What is chronobiology?

Science and Profession

Chronobiology refers to the study of various cycles or rhythms that are fundamental to living organisms, including human beings. Many of the early observations were made on plants and nonhuman animals, but the basic concepts also apply to human biology and medicine. In the twentieth century, early findings about cyclical changes in symptoms, body weight, pulse rate, and body temperature were substantiated and broadly expanded to include numerous aspects of human biology and medicine. Well-informed physicians now expect rhythms in their patients’ behavior, physiology, and response to therapy. The extensive research on biological rhythms in diverse organisms makes up the specialized field called chronobiology. The presence of circadian, menstrual, weekly, seasonal, and other rhythms in humans necessitates a consideration of these cycles in any comprehensive approach to medical practice.

Despite their importance, the exact nature of these rhythms has not been resolved. Living organisms behave as though they have internal oscillators or biological clocks that time their activities. Some research provides evidence that many of the body’s cells each have such internal timers. Until the exact causes for the various biological rhythms have been identified, there will be some limitations to the benefits derived from knowledge of their characteristics. An unsettled dispute concerns whether the actual timing information for circadian and other rhythms comes from within the organism (endogenous) or from the environment (exogenous). It is expected that travel to space beyond the moon may ultimately answer this question. Astronauts may have sufficient internal timing information to survive, or it may be necessary to create a rhythmic environment of change in light-dark cycles and perhaps magnetic field variations to provide vital timing information. In the meantime, there is much that is known in chronobiology.

In mammals, an important circadian timing mechanism resides in a cluster of cells called the suprachiasmatic nuclei, or SCN, which are located in the hypothalamus of the forebrain. From studies on laboratory mammals, it has been learned that removal of the SCN abolishes many of the body’s circadian rhythms. In humans, chance tumors in this area are often found to disrupt the circadian rhythms of the patient. In laboratory mammals, it has been shown that there is a separate pathway from the eyes to the SCN that allows information about changes in the light-dark schedule to reach this part of the brain. Therefore, there is intense interest in learning more about the SCN and how they regulate circadian rhythms.

Additionally, the pineal gland, a small gland attached to the epithalamus of the forebrain, receives information from the SCN about the light-dark schedule. A hormone produced by the pineal gland called melatonin is released into the bloodstream at night and suppressed during daylight. Melatonin plays a significant role in the timing of body rhythms and sleep cycles. When melatonin levels rise, the brain interprets this as bedtime, a factor that has led to its increasing use as a treatment for jet lag.

The general physiology of the other tissues of the body is organized according to rhythmic processes. The exact question of whether such rhythms are dependent on the SCN is still a point of controversy. Nevertheless, the greater application of chronobiology to medicine does not have to await the solution of such theoretical questions. Even now, a wide variety of examples can be cited of the utility of chronobiologic principles in medicine.

Diagnostic and Treatment Techniques

Four medical applications of chronobiology will be discussed. One area from psychiatry is the treatment of seasonal affective disorder. Three from other areas of medicine are the chronobiological treatment of asthma, cancer, and jet lag.

Seasonal affective disorder, or SAD, is characterized by depression beginning each year as daylight shortens and fully remitting when days start to lengthen, sometimes switching to mania. The condition is related to where people live and the corresponding hours of sunlight; the condition remits in a few days when sufferers travel to sunnier climes and worsens as they travel to areas where the days are shorter. As many as one in four persons in the northern latitudes may suffer from SAD, and female sufferers outnumber male ones. Although the disorder has been recognized only recently, for years writers and poets have noted seasonal depression in themselves and others.

Some patients take a midwinter vacation to a sunny climate to alleviate the condition. For those who cannot travel, the use of artificial lights has been introduced. Glow lights are placed in the homes of SAD patients and used early in the morning as well as after sunset to lengthen daylight hours. Morning lights appear to bring particularly prompt relief. Relapses have been reported when light is withdrawn. Research is currently under way to determine when during the day light is most effective, how much light is needed, and the mechanisms by which light works to fight SAD.

Some details are emerging about this process. The human forebrain contains a small organ about the size of a pea that produces the hormone melatonin according to a circadian schedule. Melatonin is usually released into the bloodstream during the night. The use of bright light therapy seems to inhibit the release of melatonin and thereby to cause other changes in the brain chemistry. In some mammals, this mechanism may be important in regulating their seasonal behavior. In humans, the situation is more complex, and an adequate theory for the neurochemical basis of SAD and other mental disorders has yet to be advanced.

Asthma sufferers have long known that their symptoms worsen at night. This increase in coughing, wheezing, and breathlessness at night has been identified only recently with circadian rhythms rather than environmental factors. At first, some researchers thought that asthma was worse at night because the patients were lying down. It has been shown, however, that the symptoms show their circadian periodicity whether the person is lying down or not. The normal nightly decrease in airway passage diameter in the lungs of normal persons is exaggerated in the asthmatic. The most dangerous hours for the asthmatic are the very early morning hours, a time when there are more deaths among asthmatics. Interestingly, asthmatics who become adapted to a nighttime work schedule shift their most severe asthma symptoms to the daytime sleep period.

Experts in the field such as Michael H. Smolensky of the University of Texas contend that much more research needs to be done on the role of circadian rhythms in asthma and its treatment. For example, adrenocortical hormones, which are powerful anti-inflammatory agents, have been used successfully to treat asthmatics. It was discovered that the time of day when the hormones were given was of great importance. If the hormones are given in the evening, the patient’s own adrenal gland is inhibited. Therefore, the best time to give such hormones is in the early morning, near the time when they are normally released in the body.

Theophylline is a drug that has been very successful in ameliorating the symptoms of asthmatics. It has been found that certain types of sustained-release theophylline are effective in reducing the early morning symptoms if the drug is taken the night before. In the study of asthma, the benefit of considering chronobiology has become obvious, and any new products to treat asthma need to be evaluated chronobiologically before they are made available to the general public.

Cancer diagnosis and treatment are aspects of medicine that are receiving increased consideration by chronobiologists. The normal growth of tissues occurs by cell division, or mitosis, a rhythmic process that is normally precisely regulated. Cancer is essentially unregulated mitosis, resulting in the growth of a tumor that is no longer subject to the control mechanisms of the body. Yet even this breakdown in regulation has its seasons. In human males, some types of testicular cancer are more often diagnosed in the winter, and in females some types of cervical cancer have a peak occurrence in the summer.

The treatment of cancer involves the use of surgery, radiation therapy, or chemotherapy in an attempt to remove or kill the cancerous cells without substantial damage to the normal tissues. Early studies in animal models demonstrated that there are often specific times of the day that these types of cancer treatment can be most effective. In a few cases, the tumor may have a rhythm of mitosis that is no longer synchronized to the rhythm of the surrounding tissue. In these cases, it may be possible to administer drugs or radiation that inhibits mitosis according to a schedule that will affect the cancer cells but will not harm the host tissue. More often, there will be a mixed effect of the timed treatment, so that some suppression of mitosis occurs along with some side effects.

The application of chronobiology to the treatment of breast cancer has raised hopes that there can be a marked improvement for survival rates of women who undergo breast surgery. William J. M. Hrushesky of Albany Medical College found that women who had breast surgery near the time of menses had a higher risk of recurrence and death than those patients who had surgery near the middle of the menstrual cycle. It has also been observed that the diagnosis of breast cancer in the United States has a two-peaked seasonal rhythm in the spring and the fall. There is also evidence that the body temperature of the breast in normal women has a circadian rhythm along with perhaps an additional seven-day periodicity, whereas breasts with tumors have abnormal temperature rhythms of about twenty hours. This information may help in the early diagnosis of breast cancer if suitable automatic monitoring devices are used to measure breast temperature.

Jet lag may appear to be more of an inconvenience than a serious medical problem until one considers the disastrous consequences of a plane crash caused by pilot error or a poorly made decision by a diplomat in an international crisis. Wiley Post and Harold Gatty, on their 1931 plane trip around the world, were the first persons to suffer from this disorder. Essentially, the body is subjected to a shift in the day-night schedule, with sleep and meal times shifted earlier or later depending on the number of time zones crossed and the direction of the flight. The symptoms are general malaise, headaches, fatigue, disruptions of the sleep-wake cycle, and gastrointestinal disorders. There are individual differences in the time required to overcome jet lag. In general, younger and healthier people are better able to cope with such change.

A shift of six hours, such as a flight between New York and Paris, requires a substantial reorganization of one’s circadian rhythms. It can take from two days to two weeks to resynchronize. Adaptation is slowest when one stays indoors and continues on a “home-time” schedule. Eastward flights are less easily tolerated than westward flights; the delays in resynchronization can take almost twice as long. The reason for the difference is that when one flies east, the sun comes up earlier relative to “home time.” It is easier for most people to “advance” than to shift “backward”—that is, to go from day to night than to go backward from night to day. For this reason, it is suggested that travelers fly early in the day when flying east and later in the day when flying west.

Unfortunately, little consideration has been given to chronobiology in scheduling work time and time off. Pilots, diplomats, businesspersons, and other time zone travelers often perform poorly when their body rhythms are disturbed by jet lag. Similarly, people who must change their work shift every few weeks often find their performance levels dropping.

It should be realized that the living body has myriad hormones, enzymes, and other important constituents that have rhythms of several different periods. Maintaining the correct time relationship between the rhythms can be critical for normal health. In the diagnosis of disease, chronobiology has to be taken into account. Erhard Haus of the St. Paul-Ramsey Medical Center has spent many years detailing the circadian and other rhythms that must be considered. What is normal for the morning hours may be pathological for the evening hours. These rhythmic values are yet to be determined for many important diagnostic measurements.

In 2005, a research study by the Feinberg School of Medicine and Northwestern University confirmed previous findings that school start times for adolescents are too early. In adolescents, melatonin, the hormone that helps induce sleep, increases later in the evening, causing melatonin levels to stay at high levels until approximately 8:00 a.m. There is no known way to change melatonin levels; for example, going to bed earlier does not cause melatonin to decrease earlier. The researchers encouraged parents and school districts to start later, as research consistently shows that adolescents have their poorest academic performance in the morning and have consistently better cognitive functioning later in the day. The researchers noted that school start times are easily modified. Many previous studies have shown the same effect, and some school districts have instituted later start times, with many schools reporting improved cognitive functioning and mood among students.

Perspective and Prospects

One of the earliest written observations of a biological cycle was by Androsthenes, a soldier marching with Alexander the Great in the fourth century BCE, who recorded that the tamarind tree opens its leaves during the day and closes them at night. In experiments on similar leaf movements in other plants, the astronomer Jean Jacques d’Ortous de Mairan in 1729 found that plants held in the dark continued to open and close their leaves on a roughly twenty-four-hour schedule. Thus, circadian rhythms in plants were shown not to be simple responses to the rising and setting of the sun but rather internal oscillations.

Early observers more interested in humans also identified rhythms. In the fifth century BCE, Hippocrates reported that his patients had twenty-four-hour fluctuations as well as longer-term rhythms in their symptoms. Herophilus of Alexandria in the third century BCE observed a daily change in the human pulse rate. The Italian scientist Sanctorius in 1711 made repeated measurements of his own body weight and the turbidity of his urine, both of which he found to vary during the month. Later, he went to the extreme measure of constructing a giant scale and living on its huge pan so that a frequent record could be made of his changing weight. The French scientists Armand Seguin and Antoine-Laurent Lavoisier in 1790 did research that revealed circadian rhythms in the body weight of men. These researchers suggested that men who did not show such circadian rhythms in body weight should be suspected of being ill. The British scientist John Davy in 1845 reported that he had found both circadian and seasonal rhythms in his own body temperature.

The historical citations of persons taking an interest in chronobiology in past centuries were of only passing concern and did not, in most cases, help to establish this field. Chronobiology as a discipline has received attention from the medical community only since about the 1970s, and many of its contributions to improving health are yet to be realized. The foremost student of chronobiology as applied to medicine has been Franz Halberg of the University of Minnesota. He has repeatedly called the attention of the medical community to the importance of biological rhythms in maintaining health and in the diagnosis and treatment of disease. Halberg has promoted the use of “autorhythmometry,” or the self-measurement of one’s physiological variables to monitor one’s changing health. It has been shown that this method can be used effectively even by groups of schoolchildren.

The phase or the timing of the peaks and troughs of circadian rhythms is germane in both diagnosis and treatment. The advent of portable automatic recording devices that store physiological data on computer chips is opening up a means of documenting a patient’s circadian rhythms around the clock for weeks at a time.

The diagnosis of diabetes mellitus has been shown to depend to an extent on the time of day that the various tests, such as the glucose tolerance test, are administered. Some diabetics are “matinal” diabetics and do not have trouble regulating their blood glucose levels until the afternoon. These persons need to have glucose tolerance tests administered in the afternoon in order to reveal their diabetes. Many additional examples of the importance of chronobiology in diagnosis and treatment exist. As more physicians and health professionals become familiar with the concepts and application of chronobiology, the effectiveness of health care will be enhanced.

Bibliography

Coleman, Richard M. Wide Awake at 3:00 A.M.: By Choice or by Chance? New York: W. H. Freeman, 1990.

Columbus, Frank, ed. Frontiers in Chronobiology Research. New York: Nova Science, 2006.

Dunlap, Jay, Jennifer Loros, and Patricia Decourse, eds. Chronobiology: Biological Timekeeping. Sunderland, Mass.: Sinauer, 2003.

Endres, Klaus-Peter, and Wolfgang Schad. Moon Rhythms in Nature: How Lunar Cycles Affect Living Organisms. Translated by Christian von Arnim. Edinburgh, Scotland: Floris Books, 2002.

Garaulet, Marta, and Jose M. Ordovás, eds. Chronobiology and Obesity. New York: Springer, 2013.

Lee-Chiong, Teofilo L., ed. Sleep Medicine Essentials. Malden: Wiley-Blackwell, 2011.

Palmer, John D. The Living Clock: The Orchestrator of Biological Rhythms. New York: Oxford University Press, 2002.

Roenneberg, Till. Internal Time: Chronotypes, Social Jet Lag, and Why You're So Tired. Cambridge: Harvard University Press, 2012.

Rosenthal, Norman E. Winter Blues: Everything You Need to Know to Beat Seasonal Affective Disorder. New York: Guilford Press, 2006.

Sehgal, Amita. Molecular Biology of Circadian Rhythms. Hoboken, N.J.: Wiley-Liss, 2004.

Waterhouse, J. M., et al. Keeping in Time with Your Body Clock. New York: Oxford University Press, 2003.

What is teen dating?

Teen dating refers to interpersonal relations between two adolescents who may be of a different or the same gender. Today's teens do not date in the traditional way their parents and grandparents did. In the past, a boy usually asked a girl to go on a date with him (and she often waited by the phone for him to do so). Then, he drove to her house and met her parents. After this, the couple often headed to dinner and a movie.

Teen dating today often relies on technology. Many teens use social networking and teen-dating websites to search for dates—a trend called
cyber-dating
. They are also more likely to pair off while in groups than to date in the traditional sense. "Hooking up," having a casual sexual encounter without a commitment, is popular among older teens today, and girls are just as likely to initiate hookups as boys. While experts believe that hooking up is now more prevalent than traditional dating, some older teens still value long-term, exclusive relationships. Such relationships teach teens important life lessons and help them determine the kind of long-term relationship they would like to have as an adult.

How Teen Dating Begins

The age at which teens begin dating depends on an individual's maturity level, hormones, and desire to date—and sometimes parents' permission. Peer pressure is also a factor. Most teens begin dating between the ages of twelve and fourteen. This early dating usually occurs while teens are out together in groups when those who are attracted to one another "pair off." Being with a group helps teens avoid the awkwardness they might feel if alone on a date. Teens mainly form these early relationships to have fun and impress peers. These relationships do not usually last long; most end after a few months. These first encounters are essentially practice for the mature relationships teens will experience a few years later.

A small number of young teens will engage in intimate, exclusive relationships. Some experts consider such relationships a learning experience that helps teens discover their individuality. However, most consider these relationships problematic because young teens have not yet formed a strong sense of identity—they cannot effectively share themselves with others because they do not yet know themselves well. Research indicates that becoming intimately involved at such a young age also puts teens at risk of poor academic performance, drug use, depression, and teen pregnancies.

Fortunately, most teens do not become involved in serious relationships until they are sixteen or older. By this time, teens are better prepared to handle the complexities of an intimate relationship. Older teens seek companionship, affection, and intimacy, as well as social support from an exclusive relationship. Serious older-teen relationships may last several years.

Cyber-Dating

More and more teens today are using the Internet to find romance. Cyber-dating, or searching for a romantic partner online, became popular in the early 2000s and is now common among teens as well as adults. Shy teens may find communicating with a potential partner online easier. They may feel more confident meeting an individual face to face after they have spent time getting to know him or her online first. Connecting with peers online also helps teens increase their dating pool and meet others with similar interests, such as music or sports.

Teens may connect with other teens on social networking sites, including Facebook, Instagram, and Tumblr, where they can post messages and pictures. Today's teens make dozens of friends and find potential dates on such sites.

Teens may also join numerous teen-dating sites to look for potential partners. These sites include MyLOL, Flirtbox, and Chatpit. Most of these sites work in a similar way—teens register, create a profile, and search profiles of others of the same age who share similar interests.

Teens who spend time online need to be aware of Internet predators, which are adults who pretend to be teenagers. These individuals create fake profiles on social networking sites and teen-dating sites and interact with teens in chat rooms. Internet predators attempt to gain a teen's trust so the teen will agree to a face-to-face meeting. These predators are often sexual offenders, and teens risk physical and sexual assault if they meet them in person. For these reasons, some experts contend that teen cyber-dating is a bad idea, especially for younger teens because they lack mature decision-making skills. Teens of all ages should never post personal information such as addresses and cell phone numbers online.

"Hooking Up"

Many older teens today say they do not date—they "hook up" instead. Hooking up is a phrase used to describe casual relationships that lack commitment. Hooking up is not a new phrase—it has been used for about fifty years—but its meaning has changed. It used to refer to simply meeting someone, perhaps for lunch, or a one-night stand. Today, however, hooking up with someone can refer to anything from kissing to intercourse with a person who may be a friend or stranger. It is a noncommittal, casual sexual encounter.

Experts theorize why hooking up is so attractive to teens. One theory is that people today marry much later in life. With marriage so many years ahead of them, teens may not see the value in trying to maintain a committed relationship. Another is that today's teens are more accustomed to impersonal relationships than those of generations past. Modern teens have grown up watching people have casual relationships on television and in movies. Perhaps more importantly, today's teens maintain many of their own impersonal relationships. They communicate with others via text and the Internet. Because of this, they are comfortable—and perhaps even more comfortable—with brief, uncommitted encounters.

Bibliography

Cornell, Scott. "Online Dating for Teenagers." Opposing Views. OpposingViews.com. Web. 5 Dec. 2014. http://science.opposingviews.com/online-dating-teenagers-1747.html

Fogarty, Kate. "Teens and Dating." Education.com. Education.com. 11 Mar. 2008. Web. 5 Dec. 2014. http://www.education.com/reference/article/Ref_Teens_Dating_Tips/

Mazzella, Randi. "Hooking Up in High School." TeenLife Blog. TeenLife Media, LLC. 24 Jan. 2014. Web. 5 Dec. 2014. https://www.teenlife.com/blogs/articles/hooking-high-school

McKay, Hollie. "Seventeen Magazine Slammed for Article Promoting Online Dating to Young Readers." FoxNews.com. FOX News Network, LLC. 26 Jul. 2013. Web. 5 Dec. 2014. http://www.foxnews.com/entertainment/2013/07/26/seventeen-magazine-slammed-for-article-promoting-online-dating-to-young-readers/

Taylor, Kate. "Sex on Campus: She Can Play That Game, Too." New York Times. New York Times Company. 12 Jul. 2013. Web. 5 Dec. 2014. http://www.nytimes.com/2013/07/14/fashion/sex-on-campus-she-can-play-that-game-too.html?pagewanted=all&_r=0

Watson, Stephanie. "Teen Dating: What You Need to Know About Teens Hooking Up." WebMD. WebMD, LLC. 5 Dec. 2014. http://www.webmd.com/parenting/features/teen-dating-what-you-need-to-know-about-hooking-up

Whitaker, Barbara. "Teen Dating: A Mom's Guide." WebMD. WebMD, LLC. Web. 5 Dec. 2014. http://www.webmd.com/parenting/features/teen-dating-guide-for-mom

How did women contribute to ancient Chinese history?

In ancient China, men were largely regarded as the heads of families. Confucian thought, with its emphasis on filial piety and deference, emphasized the roles of women as deferential to their fathers and later their husbands. During the Han dynasty (202 BCE-220 CE), Confucianism became part of the way China was administered, and women's roles in the family became even more entrenched. Men generally served as the heads of families, though a widowed woman could become head until her sons were old enough to serve as head. The literature of the time stressed that women's virtues should include submissiveness, industry, and loyalty. When women married, they left their families and went to live with their husbands and their families. In addition, ancestor worship took place through men, so women were prized for giving birth to boys rather than girls. However, women also held important roles as midwives, Buddhist nuns, weavers, innkeepers, and other roles.

During the Song Dynasty (960-1279), it can be argued that women's status declined. The society placed importance on widow chastity, meaning that widows could not remarry and had to remain part of their dead husbands' families. In addition, the practice of foot binding became common. Mothers would bind the feet of their young daughters to prevent them from being very mobile and to require them to have servants to wait on them. This practice continued into the Qing Dynasty (1644-1911), the last dynasty in China. 

What kind of person was Scout before the end of Harper Lee's To Kill a Mockingbird?

Scout changes a great deal all throughout Harper Lee's To Kill a Mockingbird.

In the beginning of the novel, Scout has a very hot temper and is prone to violence. Anytime she feels she or one of her family members has been insulted, she is quick to lash out physically, such as when she rubs Walter Cunningham's nose in the dirt or when she punches her cousin Francis in the face. However, her father is resolved to teach her to remain calm in the face of adversity, especially since she'll be facing a great deal of ridicule as a result of his determination to defend Tom Robinson. We see Atticus warn her about the need to stay calm in the following:

You might hear some ugly talk about [the case] at school, but do one thing for me if you will: you just hold your head high and keep those fists down. No matter what anybody says to you, don't you let 'em get your goat. Try fighting with your head for a change ... it's a good one, even if it does resist learning. (Ch. 9)

As a result of her lesson in keeping her head, Scout remains calm when Mrs. Dubose insults them by calling their father trash, whereas Jem, who is usually very calm, flies off the handle and seeks revenge by whacking the camellias off of every bush in Mrs. Dubose's garden.

Part of what contributes to Scout's ability to remain calm is her lesson in being able to see from others' perspectives. When Scout feels offended by her first-grade teacher, Atticus teaches her one of the most famous lessons in the book:

You never really understand a person until you consider things from his point of view-- ... --until you climb into his skin and walk around in it. (Ch. 3)

Prior to this lesson, Scout was primarily only able to see situations from her own young, self-serving perspective. Scout practices her lesson by trying to see many things from Jem's perspective, as well as from the perspectives of other characters. By the end of the book, Scout has let go of all previous prejudices she had as she stands on Arthur Radley's porch, after having escorted him home, and visualizes him looking out at the neighborhood, watching "his children," meaning Scout and Jem, play, grow, and struggle with sorrows and problems (Ch. 31). By being able to see things from Arthur's perspective, she is finally able to see him as the kind and caring man he truly is.

Prior to these lessons, though a generally good person, we can see that Scout was a young, aggressive, and somewhat selfish person.

What is the irony in the poem "Julia Miller" from Spoon River Anthology by Edgar Lee Masters?

The irony presented in this poem is situational irony. Situational irony is when something happens in a narrative that is very different or opposite from the expected outcome. In the poem "Julia Miller," the narrator chooses to marry a man 35 years her senior in order to provide a life for the baby she conceived with a man who has abandoned her. One would typically expect that she continues to live with this man she does not love, sacrificing her own happiness for her child's future. Instead, she becomes overwhelmed by her feelings for the man who betrayed her, and, after reading a letter he sent her, kills herself (and, obviously, the unborn child she was trying to provide for in the marriage that made her so miserable in the first place).

In the novel The Absolutely True Diary of a Part-time Indian, how was the relationship between Junior and his father?

In The Absolutely True Diary of a Part-time Indian, Junior and his father have a strong relationship, although Junior worries about his father's battle with alcohol.  Junior recognizes that his parents are not living the lives they had dreamed, and in an early chapter, Junior draws a picture of who his parents would have been if they had been able to follow their dreams.  Junior's father would have become a musician.  However, the hardships on the reservation have created a different path for Junior's parents, and his father resorts to alcohol abuse to cope with the difficulties he faces such as lack of opportunity and low income.  When Junior goes to Reardan, he often worries that his father will get drunk and forget to come pick him up from school (and sometimes he does forget).  Yet despite Junior's concern over his father's alcoholism, Junior and his father remain close mainly because his father supports him and his efforts.  When Junior announces that he wants to go to Reardan for a better education, his father is happy that Junior wants to take this risky step, knowing that many Indians on the reservation will brand him a traitor for leaving the school at Wellpinit.  Junior's father makes the commitment of driving him the 20+ miles to and from school when he is able.  So through this sense of understanding, Junior and his father are able to maintain a strong relationship.

When a base is dipped in methyl orange what is the color change?

Methyl orange is a compound commonly used in dying textiles. It is also a pH indicator. pH indicators turn particular colors when exposed to environments that are acidic or basic. Methyl orange is commonly used to monitor pH changes during the titration of weak bases with strong acids. Methyl orange is created from a reaction of sulfanilic acid, sodium nitrite, and dimethylaniline.

The color changes that occur in methyl orange are due to changes in the electrons associated with the attachment or detachment of hydrogen ions. Normally, the methyl orange molecule absorbs blue-green light. This causes solutions of methyl orange to appear red. When methyl orange is exposed to a basic solution, it loses a hydrogen ion resulting in changes that cause the solution to turn yellow. 

What is valproic acid? How does it interact with other drugs?

Carnitine

Effect: Supplementation Possibly Helpful

Carnitine is an amino acid that has been used for heart conditions, Alzheimer’s disease, and intermittent claudication. Intermittent claudication is a possible complication of atherosclerosis in which impaired blood circulation causes severe pain in calf muscles during walking or exercising.

Long-term therapy with anticonvulsant agents, particularly valproic acid, is associated with low levels of carnitine. However, it is not clear whether the anticonvulsants cause the carnitine deficiency or whether it occurs for other reasons. It has been hypothesized that low carnitine levels may contribute to valproic acid’s damaging effects on the liver. The risk of this liver damage increases in children younger than twenty-four months, and carnitine supplementation does seem to be protective. However, in one double-blind crossover study, carnitine supplementation produced no real improvement in “well-being” as assessed by parents of children receiving either valproic acid or carbamazepine. L-carnitine supplementation may be advisable in certain cases, such as in infants and young children (especially those younger than two years) who have neurologic disorders and are receiving valproic acid and multiple anticonvulsants.

Vitamin D

Effect: Supplementation Possibly Helpful

Valproic acid slows down the liver’s conversion of vitamin D into the active form of the vitamin that can be used by the body. This effect might lead to reduced calcium absorption, since the body needs active vitamin D to absorb calcium properly. Therefore, it might be advisable to take vitamin D supplements at the U.S. Adequate Intake (AI) dosage.

Folate

Effect: Supplementation Possibly Helpful

Folate (also known as folic acid) is a B vitamin that plays an important role in many vital aspects of health, including preventing neural tube birth defects and possibly reducing the risk of heart disease. Because inadequate intake of folate is widespread, if one is taking any medication that depletes or impairs folate even slightly, one may need supplementation. Valproic acid appears to decrease the body’s absorption of folate, and other antiseizure drugs can also reduce levels of folate in the body. The low serum folate caused by anticonvulsants can raise homocysteine levels, a condition believed to increase the risk of heart disease.

Adequate folate intake is also necessary to prevent neural tube birth defects, such as spina bifida and anencephaly. Because anticonvulsant drugs deplete folate, babies born to women taking anticonvulsants are at increased risk for such birth defects. Anticonvulsants may also play a more direct role in the development of birth defects.

However, the case for taking extra folate during anticonvulsant therapy is not as simple as it might seem. It is possible that folate supplementation might itself impair the effectiveness of anticonvulsant drugs, and physician supervision is necessary.

Melatonin

Effect: Supplementation Possibly Helpful

One double-blind study in children found that use of melatonin improved general quality of life in children on valproic acid. The most obvious way melatonin might help would involve improvements in sleep, as melatonin is a widely used treatment for insomnia. Another rather theoretical study by the same author suggests it might help in other more subtle ways that involve the body’s biochemistry.

Biotin

Effect: Supplementation Possibly Helpful, but Take at a Different Time of Day

Many antiseizure medications, including valproic acid, are believed to interfere with the absorption of biotin. For this reason, persons taking valproic acid may benefit from extra biotin. Biotin should be taken two to three hours apart from antiseizure medication. One should not exceed the recommended daily intake, because it is possible that too much biotin might interfere with the effectiveness of the medication.

Vitamin A

Effect: Possible Increased Risk of Birth Defects

Both valproic acid and vitamin A can increase the risk of birth defects. The effect might be additive, indicating that pregnant women should avoid such combination treatment.

Glutamine

Effect: Theoretical Harmful Interaction

Because valproic acid works (at least in part) by blocking glutamate pathways in the brain, high dosages of glutamine might possibly overwhelm the drug and increase the risk of seizures.

White Willow

Effect: Possible Negative Interaction

The herb white willow contains substances very similar to aspirin. On this basis, it might not be advisable to combine white willow with valproic acid.

Ginkgo

Effect: Possible Harmful Interaction

The herb ginkgo is widely used for improving memory and mental function. Seizures also have been reported with the use of ginkgo leaf extract in people with previously well-controlled epilepsy; in one case, the seizures were fatal. One possible explanation is contamination of ginkgo leaf products with ginkgo seeds. It has also been suggested that ginkgo might interfere with the effectiveness of some antiseizure medications, including phenytoin. Finally, it has been noted that the drug tacrine (also used to improve memory) has been associated with seizures, and ginkgo may affect the brain in ways similar to tacrine.

Dong Quai, St. John’s Wort

Effect: Possible Harmful Interaction

Valproic acid has been reported to cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash. Because St. John’s wort and dong quai may also cause this problem, taking them during treatment with this drug might add to this risk.

Bibliography

De Vivo, D. C., et al. “L-carnitine Supplementation in Childhood Epilepsy: Current Perspectives.” Epilepsia 39 (1998): 1216-1225.

Granger, A. S. “Ginkgo biloba Precipitating Epileptic Seizures.” Age and Ageing 30 (2001): 523-525.

Gupta, M., S. Aneja, and K. Kohli. “Add-on Melatonin Improves Quality of Life in Epileptic Children on Valproate Monotherapy.” Epilepsy and Behavior 5 (2004): 316-321.

Kupiec, T., and V. Raj. “Fatal Seizures Due to Potential Herb-Drug Interactions with Ginkgo biloba.” Journal of Analytical Toxicology 29 (2006): 755-758.

Lewis, D. P., et al. “Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes: Part 1–Antiepileptic Drugs, Contraceptives, Smoking, and Folate.” Annals of Pharmacotherapy 32 (1998): 802-817.

Does the low level of unemployment indicate that the labor market is in good shape?

While a low unemployment rate is almost always better than a high unemployment rate, a low unemployment rate does not necessarily mean that the labor market is in good shape.  This is because of the way that unemployment is defined.  Because of the way that we define unemployment, people can be in unfavorable economic situations without being unemployed.  Let us look at two ways in which this could be so.

First, people could be working, but in situations where they are underemployed.  Someone might wish to work full time, but only be able to get a part-time job.  Someone might be working two low-wage jobs just to get by.  A person with a college degree might be working in a job that requires no more than a high school diploma and for which they are overqualified.  All of these people are in bad situations and yet they are simply counted as “employed.”

Second, it is possible to not be working and still not count as unemployed.  One group of people like this is called discouraged workers.  These people do not have jobs, but they have given up and have stopped trying to find jobs.  They keep failing to find a job so they stop looking.  You have to be looking for a job to count among the unemployed, so a discouraged worker is not unemployed.  That person is simply not part of the labor force.

When there are large numbers of discouraged workers and/or people who are underemployed, the unemployment rate can be low even though the labor market really is not in good shape.

What is embryology?

Science and Profession

The study of human embryology is the study of human prenatal development. The three stages of development are cleavage (the first week), embryonic development (the second through eighth weeks), and fetal development (the ninth through thirty-eighth weeks).

After an egg is fertilized by sperm in the fallopian tube, the resulting zygote begins to divide rapidly. This period of rapid cell division is known as cleavage. By the third day, the zygote has divided into a solid ball containing twelve to sixteen cells. The small ball of cells resembles a mulberry and is called the morula, which is Latin for “mulberry.” The morula moves from the uterine tube into the uterus.

The morula develops a central cavity as spaces begin to form between the inner cells. At this stage, the developing human is called a blastocyst. The ring of cells on the outer edge of the hollow ball is called the trophoblast and will form a placenta, while the cluster of cells within becomes the inner cell mass and will form the embryo. By the end of the first week, the surface of the inner cell mass has flattened to form an embryonic disc, and the blastocyst has attached to the lining of the uterus and begun to embed itself.

During the second week of development, the trophoblast makes connections with the uterus into which it has burrowed to form the placenta. Blood vessels from the embryo link it to the placenta through the umbilical cord, through which the embryo receives food and oxygen and releases wastes. Two sacs develop around the embryo: the fluid-filled amniotic sac that surrounds and cushions the embryo and the yolk sac that hangs beneath to provide nourishment. Finally, a large chorionic sac develops around the embryo and the two smaller sacs.

During the third week, the cells of the embryo are arranged in three layers. The outer layer of cells is called the ectoderm, the middle layer is the mesoderm, and the inner layer is the endoderm. The ectoderm gives rise to the epidermis (outer layer) of the skin and to the nervous system; the mesoderm gives rise to blood, bone, cartilage, and muscle; and the endoderm gives rise to body organ linings and glands.

Other significant events of the third week are the development of the primitive streak and notochord. The primitive streak is a thickened line of cells on the embryonic disk indicating the future embryonic axis. Development of the primitive streak stimulates the formation of a supporting rod of tissue beneath it called the notochord. The presence of the notochord triggers the ectoderm in the primitive streak above it to thicken, and the thickened area will give rise to the brain and spinal cord. Later, when vertebrae and muscles develop around the neural tissue, the notochord will disappear, leaving the center of the vertebral disk as its remnant.

The important event of the fourth week is the formation of the neural tube. After the thickened neural plate tissue has formed, an upward folding forms a groove, finally closing to form a neural tube. Closure begins at the head end and proceeds backward. The neural tube then sinks beneath surrounding ectodermal surface cells, which will become the skin covering the embryo.

Blocks of mesoderm cells line up along either side of the notochord and neural tube. These blocks are called somites, and eventually forty-two to forty-four pairs will form. They give rise to muscle, the cartilage of the head and trunk, and the inner layer of skin. At the same time, embryonic blood vessels develop on the yolk sac. Because the human embryo is provided little yolk, there is need for the early development of a circulatory system to provide nutrition and gas exchange through the placenta.

The heart is formed and begins to beat in the fourth week, though it is not yet connected to many blood vessels. During the fourth through eighth weeks, all the organ systems develop, and the embryo is especially vulnerable to teratogens (environmental agents that interfere with normal development). A noticeable change in shape is seen during the fourth week, because the rapidly increasing number of cells causes a folding under at the edges of the embryonic disk. The flattened disk takes on a cylindrical shape, and the folding process causes curvature of the embryo and it comes to lie on its side in a C-shaped position.

The beginnings of arms and legs are first seen in the fourth week and are called limb buds, appearing first as small bumps. The lower end of the embryo resembles a tail, and the swollen cranial part of the neural tube constricts to form three early sections of the brain. The eyes and ears begin to develop from the early brain tissue.

During the fifth through eighth weeks, the head enlarges as a result of rapid brain development. The head makes up almost half the embryo, and facial features begin to appear. Sexual differences exist but are difficult to detect. Nerves and muscles have developed enough to allow movement. By the end of the eighth week the limb buds have grown and differentiated into appendages with paddle-shaped hands and feet and short, webbed digits. The tail disappears, and the embryo begins to demonstrate human characteristics. By convention, the embryo is now called a fetus.

The fetal stage of development is the period between the ninth and thirty-eighth weeks, until birth. Organs formed during the embryonic stage grow and differentiate during the fetal stage. The body has the largest growth spurt between the ninth and twentieth weeks, but the greatest weight gain occurs during the last weeks of pregnancy.

In the third month, the difference between the sexes becomes apparent, urine begins to form and is excreted into the amniotic fluid, and the fetus can blink its eyelids. The fetus nearly doubles in length during the fourth month, and the head no longer appears to be so disproportionately large. Ossification of the skeleton begins, and by the end of the fourth month, ovaries are differentiated in the female fetus and already contain many cells destined to become eggs.

During the fifth month, fetal movements are felt by the mother, and the heartbeat can be heard with a stethoscope. Movements until this time usually go unnoticed. The average length of time that elapses between the first movement felt by the mother and delivery is twenty-one weeks.

During the sixth month, weight is gained by the fetus, but it is not until the seventh month that a baby usually can survive premature birth, when the body systems, particularly the lungs, are mature enough to function. During the eighth month, the eyes develop the ability to control the amount of light that enters them. Fat accumulates under the skin and fills in wrinkles. The skin becomes pink and smooth, and the arms and legs may become chubby. In the male fetus, the testes descend into the scrotal sac. Growth slows as birth approaches. The usual gestation length is 266 days, or thirty-eight weeks, after fertilization.

Diagnostic and Treatment Techniques

Knowledge of normal embryonic development is very important both in helping women provide optimal prenatal care for their children and in promoting scientific research for improved prenatal treatment, better understanding of malignant growths, and insight into the aging process.

Environmental stress to the embryo during the fourth through eighth weeks can cause abnormal development and result in congenital malformation, which may be defined as any anatomical defect present at birth. Environmental agents that cause malformations are known as teratogens. Malformations may develop from genetic or environmental factors, but most often they are caused by a combination of the two. Some of the common teratogens are viral infections, drug use, a poor diet, smoking, alcohol consumption, and irradiation.

The genetic makeup of some individuals makes them particularly sensitive to certain agents, while others are resistant. The abnormalities may be immediately apparent at birth or hidden within the body and discovered later. Embryos with severe structural abnormalities often do not survive, and such abnormalities represent an important cause of miscarriages. In fact, up to half of all conceptions spontaneously abort, with little or no notice by the prospective mother.

Genetic birth defects are passed on from one generation to another and result from a gene mutation at some time in the past. Mutations are caused by the accidental rearrangement of deoxyribonucleic acid (DNA), the material of which genes are made, and range in severity from mild to life-threatening. They may cause such conditions as extra fingers and toes, cataracts, dwarfism, albinism, and cystic fibrosis. Gene mutations on a sex chromosome are described as sex-linked and are usually passed from mother to son; these include hemophilia, hydrocephalus (an excessive amount of cerebrospinal fluid), color blindness, and a form of baldness.

Abnormalities in the embryo may result because of an unequal distribution of chromosomes in the formation of eggs or sperm. This imbalance can cause a variety of problems in development, such as Down syndrome and abnormal sexual development. The normal human cell contains twenty-three chromosomes, twenty-two pairs of which are nonsex chromosomes, or autosomes. The last pair consists of the two sex chromosomes. Females normally have two X chromosomes, and males have an X and a Y chromosome.

When females have only one X, a set of conditions known as Turner syndrome results. The embryo will develop as a normal female, though ovaries will not fully form and there may be congenital heart defects. Because the single X chromosome does not cause enough estrogen to be produced, sexual maturity will not occur. If a male embryo should receive only the Y chromosome, it cannot survive. Sometimes a male will receive two (or more) X chromosomes along with a Y chromosome (XXY), producing Klinefelter syndrome. The appearance of the child is normal, but at puberty the breasts may enlarge and the testes will not mature, causing sterility. Males receiving two Y chromosomes (XYY) develop normally, but they may be quite tall and find controlling their impulses to be difficult.

Viral infections in the mother during the embryonic stages can cause problems in organ formation by disturbing normal cell division, fetal vascularization, and the development of the immune system. The organs most vulnerable to infection will be those undergoing rapid cell division and growth at the time of infection. For example, the lens of the eye forms during the sixth week of development, and infection at this time could cause the formation of cataracts.

While most microorganisms cannot pass through the placenta to reach the embryo or fetus, those that can are capable of causing major problems in embryonic development. Rubella, the virus that causes German measles, often causes birth defects in children should infection occur shortly before or during the first three months of pregnancy. The developing ears, eyes, and heart are especially susceptible to damage during this time. When a rubella infection occurs during the first five weeks of pregnancy, interference with organ development is most pronounced. After the fifth week, the risks of infection are not as great, but central nervous system impairment may occur as late as the seventh month.

The most common source of fetal infection may be the cytomegalovirus (CMV), a form of herpes that causes abortion during the first three months of pregnancy. If infection occurs later, the liver and brain are especially vulnerable and impairment in vision, hearing, and mental ability may result. Evidence has also suggested that the immune system of the fetus is adversely affected.

Other viruses may affect fetal development as well. When herpes simplex infects the fetus several weeks before birth, blindness or developmental disabilities may result. Toxoplasma gondii, a parasite of animals often kept as pets, may adversely affect eye and brain development without the mother having known that she had the infection. Syphilis infection in the mother leads to death or serious fetal abnormalities unless it is treated before the sixteenth week of pregnancy; if it is untreated, the fetus may possess hearing impairment, hydrocephalus, facial abnormalities, and developmental disabilities. Women infected with human immunodeficiency virus (HIV) or who have acquired immunodeficiency syndrome (AIDS) may transmit the virus to their infants before or during birth.

Certain chemicals can cross the placenta and produce malformation of developing tissues and organs. During an embryo’s first twenty-five days, damage to the primitive streak can cause malformation in bone, blood, and muscle. While bones and teeth are being formed, they may be adversely affected by antibiotics such as tetracycline.

At one time, thalidomide was widely used as an antinauseant in Great Britain and Germany and to some extent in the United States. Large numbers of congenital abnormalities began to appear in newborns, and the drug was withdrawn from the market after two years. Thalidomide caused the failure of normal limb development and was especially damaging during the third to seventh weeks.

Exposure to other chemicals causes central nervous system disorders when the neural tube fails to close. When the anterior end of the tube does not close, development of the brain and spinal cord will be absent or incomplete and anencephaly results. Babies can live no more than a few days with this condition because the higher control centers of the brain are undeveloped. If the posterior end of the tube fails to close, one or more vertebrae will not develop completely, exposing the spinal cord; this condition is called spina bifida. This condition varies in severity with the level of the defect and the amount of neural tissue that remains exposed, because exposed tissue degenerates.

It has been long believed that neural tube disorders accompany maternal depletion of folic acid, one of the B vitamins, and research has substantiated that relationship. Anencephaly and spina bifida rarely occur in the infants of women taking folic acid supplements. One of the harmful effects of alcohol and anticonvulsants is their depletion of the body’s natural folic acid. A decrease in the mother’s folic acid levels in the first through third months of pregnancy can cause abortion or growth deformities.

Maternal smoking is strongly implicated in low infant birth weights and higher fetal and infant mortality rates. Cigarette smoke may cause cardiac abnormalities, cleft lip and palate, and a missing brain. Nicotine decreases blood flow to the uterus and interferes with normal development, allowing less oxygen to reach the embryo.

Alcohol use may be the number one cause of birth defects. Exposure of the fetus to alcohol in the blood results in fetal alcohol syndrome. Symptoms may include growth deficiencies, an abnormally small head, facial malformation, and damage to the heart and the nervous and reproductive systems. Behavioral disorders such as hyperactivity, attention deficit, and an inability to relate to others may accompany fetal alcohol syndrome.

Radiation treatments given to pregnant women may cause cell death, chromosomal injury, and growth retardation in the developing embryo. The effect is proportional to the dosage of radiation. Malformations may be visible at birth, or a condition such as leukemia may develop later. Abnormalities caused by radiation include cleft palate, an abnormally small head, developmental disabilities, and spina bifida. Diagnostic x-rays are not believed to emit enough radiation to cause abnormalities in embryonic development, but precautions should be taken.

Oxygen deficiency to the embryo or fetus occurs when mothers use cocaine. Maternal blood pressure fluctuates with the use of this drug, and the embryonic brain is deprived of oxygen, resulting in vision problems, lack of coordination, and developmental disabilities. Too little oxygen to the fetus may also cause death from lung collapse soon after birth.

Obvious physical malformations resulting from embryonic exposure to drugs have been recognized for a number of years, but recent investigators have found that there are more subtle levels of effect that may show up later as behavioral problems. Physical abnormalities have been easily documented, but more attention is needed regarding the behavioral effects caused by teratogens.

Perspective and Prospects

The first recorded observations of a developing embryo were performed on a chick by Hippocrates in the fifth century BCE. In the fourth century BCE, Aristotle wondered whether a preformed human unfolded in the embryo and enlarged with time, or whether a very simple embryonic structure gradually became more and more complex. This question was debated for nearly two thousand years until the early nineteenth century, when microscopic studies of chick embryos were carefully conducted and described.

Understanding human embryology is foundational for recognizing the relationships that exist between the body systems and congenital malformations in newborns. This field of study takes on new importance in light of advances in modern technology, which have made prenatal diagnosis and treatment a reality.

The study of embryology is also making contributions toward finding the causes of malignant growth. Malignancy is a breakdown in the mechanisms for normal growth and differentiation first seen in the early embryo. Questions about uninhibited malignant growth may be answered by studying embryonic tissues and organs.

The study of old age is another area in which embryological research is valuable. Understanding the clock mechanisms of embryonic cells has led to greater understanding of the “winding down” of cells in old age. It is also important that researchers discover how environmental conditions modify rates of growth and affect the cell’s clock. The degree to which the human life span can be expanded remains one of the most challenging questions in the area of aging.

In addition to the health benefits that may be derived from embryological research, this field is an important source of insight into some of the moral and ethical dilemmas facing humankind. Artificial insemination, contraception, and abortion regulations are some of the problems that should require close collaboration between ethicists and scientists, especially embryologists.

Bibliography

"Birth Defects." MedlinePlus, 23 July 2013.

"Fetal Health and Development." MedlinePlus, 23 July 2013.

"How Your Baby Grows During Pregancy." American College of Obstetricians and Gynecologists, Aug. 2011.

Mader, Sylvia S. Inquiry into Life. 14th ed. New York: McGraw-Hill, 2014.

Marieb, Elaine N. Essentials of Human Anatomy and Physiology. 10th ed. San Francisco: Pearson/Benjamin Cummings, 2012.

Moore, Keith L., and T. V. N. Persaud. The Developing Human. 9th ed. Philadelphia: Saunders/Elsevier, 2013.

Riley, Edward P., and Charles V. Vorhees, eds. Handbook of Behavioral Teratology. New York: Plenum Press, 1986.

Tortora, Gerard J., and Bryan Derrickson. Principles of Anatomy and Physiology. 13th ed. Hoboken, N.J.: John Wiley & Sons, 2012.

Tsiaras, Alexander, and Barry Werth. From Conception to Birth: A Life Unfolds. New York: Doubleday, 2002.

What are three spiritual lessons from The Canterbury Tales?

Because The Canterbury Tales is written about a pilgrimage during the medieval time period, spiritual lessons are prevalent in the text. Some examples include:

The Man of Law's Tale is about a woman named Constance who suffers for the majority of her life, but who is rewarded for her pain. Several miracles occur in her presence, and she is the emblem of Christianity in the tale. Her faithfulness to her husband, overall purity, and her unwavering perseverance are rewarded by her salvation and by her son being crowned king. The lesson is that purity and perseverance are holy practices that will be rewarded. 

The Prioress's Tale is about a small schoolboy who faces persecution for being a Christian. He refuses to stop singing praises to Mother Mary, and is killed by Jews as a martyr. Even after his death, the boy continues to sing! The spiritual lesson is that faithfulness and bravery will bring favour in the eyes of Mary and God. 

A final example is found in The Parson's Tale. He preaches a long and lengthy sermon on the importance of penitence. This is the clearest spiritual lesson found in The Canterbury Tales as it is basically spelled out for readers and listeners alike - penitence is the only way to salvation.

What is Parkinson's disease?

Causes and Symptoms

In 1817, James Parkinson, a British physician, wrote a description of six patients
suffering from a slowly progressing disease characterized by “involuntary
tremulous motion, with lessened muscular power in parts not in action even when
supported, with a propensity to bend their trunks forward from a walking to a
running pace.” Throughout the modern world, this disease—which Parkinson named
shaking palsy—is called Parkinson’s disease.

Parkinson’s disease, also called paralysis agitans, is now defined as a medical
condition characterized by a combination of symptoms including involuntary shaking
(tremor) of the limbs at rest, stiffness of the muscles
(rigidity), slowed or reduced ability to move the limbs and facial muscles
(bradykinesia), and general muscular weakness. Onset usually occurs after the age
of fifty.

The clinical scale most often used to describe the extent of severity of
Parkinson’s disease is that of Melvin Yahr and Margaret Hoehn, which is divided
into five stages. In stage 1, mild tremor or rigidity is seen on one side of the
body. In stage 2, tremor, rigidity, and bradykinesia occur on both sides of the
body, without any loss of balance. In stage 3, added to the symptoms of stage 2
are balance difficulty, loss of posture control, and hunching over. With stage 4,
the extent of the functional disability increases, but some independent function
is still possible. Such severe symptoms occur in stage 5 that patients require a
wheelchair or are bedridden without assistance.

The body site of Parkinson’s disease is clear, but most cases are idiopathic,
meaning that although their site of action is known, the basic cause is not and
their occurrence is spontaneous. Parkinson's disease is estimated to have a 30 to
40 percent rate of heritability. Mutations in the parkin (PARK2)
gene on chromosome 6 are found in approximately 8.6 percent of patients with
early-onset Parkinson's disease; researchers have identified more than two hundred
PARK2 gene mutations involved in the development of
Parkinson's disease. Multiple genes may be involved in idiopathic late-onset
Parkinson's disease; the tau gene is being investigated as a possible cause of
idiopathic Parkinson's disease.

Although a genetic susceptibility may be responsible for some cases of
Parkinson's, many researchers increasingly believe that the root of Parkinson’s
disease is related to environmental factors. While a handful of gene mutations
have been identified for early-onset Parkinson’s, which strikes before the age of
forty, these cases account for fewer than one out of every ten patients. Some
scientists believe that the genes involved in Parkinson's may be “activated” by
exposure to an environmental agent, such as solvents, pesticides, or viruses, and
that such agents may prompt the onset of the disease even in those individuals who
carry none of the suspected genes. Recent findings seem to support such expert
hypotheses. For example, common clusters of individuals with the disease have been
discovered, most notably three people who worked in Canada during the 1980s with
Michael J. Fox, the television and film actor who announced in 1998 that he was
suffering from Parkinson’s disease. Medical detectives are examining whether any
shared environmental exposure among this group of four can be found. Moreover,
Japanese scientists showed that a virulent strain of influenza A accumulates in
the same area of the brain attacked in Parkinson’s disease. Other studies have
shown that health care workers and teachers, individuals in fields exposed at a
greater rate to influenza strains, show a twofold increased risk of
developing the disease. Finally, epidemiological studies show that people living
in rural areas and farmers are much more likely to develop the disease than their
urban counterparts, a fact that could point to pesticide exposure or the use of
well water.

The symptoms of Parkinson’s disease begin slowly, most often presenting as stage 1
tremor. After this, the progression to stage 3 usually takes five to ten years.
This progression appears to be caused by the deterioration of several of the four
brain structures called basal ganglia (the corpus striatum, thalamus, substantia
nigra, and globus pallidus), which is related to depletion of the neurotransmitter
dopamine. Dopamine depletion is most extreme in the normally dark-pigmented
substantia nigra, which is often colorless in the autopsied brains of parkinsonism
patients.

The side effects of some drugs can produce symptoms of Parkinson’s disease that
are difficult to distinguish from non-drug-induce Parkinsonism, and they have
provided clues about the disease. Many of these drugs affect dopamine levels in
the brain and include antipsychotic medications, metoclopramide, reserpine,
tetrabenazine, some calcium channel blockers, and stimulants such as amphetamines
and cocaine. Drug-based symptoms do not appear to be causes of permanent
Parkinson’s disease because the symptoms diminish and slowly disappear after
discontinuation of the causative drugs. Many have been linked, however, to
decreased dopamine levels. Similarly, many stroke-related symptoms appear to be
caused by drug therapy that diminished brain dopamine content. The effects of
tumors have also offered helpful data because their location
can better identify the brain areas associated with the disease. For example,
information of this sort first linked the substantia nigra and corpus striatum to
Parkinson’s disease. In addition, viral encephalitis is still suspected by many of
being an important causative factor. Belief in its involvement arose, however,
from a 1918–1925 epidemic that damaged the basal ganglia, and contemporary
Parkinson’s disease as a result of encephalitis is very rare. Finally, discovery
of the MPTP connection, a neurotoxin precursor to MPP+, has yielded a useful model
for Parkinson’s disease related to psychoactive drugs that cause it.

Tremor is the most conspicuous symptom. Despite the fact that it is usually the
least disabling aspect of the disease, tremor is often embarrassing to the
affected person and it is usually the phenomenon that brings patients to a
physician for initial diagnosis. In stage 1 of Parkinson’s disease, tremor appears
only when afflicted people are very fatigued. Later in the course of the disease,
it becomes increasingly widespread and continual. It is interesting to note that
tremor ceases when a parkinsonism patient is asleep.

Although Parkinson’s disease does not alter the mental abilities of afflicted
persons, it eventually impairs their ability to carry out tasks that require
rapid, repetitive movement and manual dexterity. For example, Parkinson’s disease
very often causes handwriting to deteriorate to an illegible scrawl, makes it
impossible to fasten a shirt’s collar buttons or a brassiere, and turns shaving or
brushing the teeth into a difficult chore.

Bradykinesia is the most incapacitating aspect of Parkinson’s disease because it
impairs communication by characteristic gestures; results in an awkward gait, with
failure to swing the arms normally when walking; and produces an immobile facial
expression common to later stages. Other symptoms include drooling, caused by
problems with swallowing, and the development of a slow, muffled speech. Both are
caused by diminished mobility of the muscles of the mouth, jaws, and throat.

The nature of Parkinson’s disease is best understood after considering nerve
impulse transmission between the cells of nervous tissue (neurons) and the
arrangement and interactive function of the brain and nerves.

Nerve impulse transport between neurons is an electrochemical process that
generates the weak electric current that makes up the impulse. The impulse leaves
each neuron via an outgoing extension, called an axon, passes across a tiny
synaptic gap that separates the axon from the next neuron in line, and then enters
an incoming extension (dendrite) of that cell. This process is repeated many times
in order to transmit a nervous impulse to its site of action. The cell bodies of
neurons constitute the impulse-causing gray matter, and axons and dendrites (white
matter) may be viewed as their connecting wires (nerve fibers). Nerve impulse
passage across the synaptic gaps between neurons is mediated by chemical
messengers called neurotransmitters, such as dopamine.

The brain and nerves—the central nervous system—are a complex arrangement of
neurons designed to enable an organism to respond in a coordinated way to external
stimuli. The brain may be viewed as the central computer in the system. Its most
sophisticated structure is the cerebrum, which controls the higher mental
functions. Underneath the cerebrum are the cerebellum and the brain stem, which
connects both the cerebrum and the cerebellum to the spinal cord.
This cord, a meter-long trunk of nerve fibers, carries nerve impulses between the
brain and the peripheral nerves that control muscles and other body tissues. Most
important to Parkinson’s disease are the motor nerves, which control body motions.
This control involves a portion of the cerebrum that deals with skilled motor
patterns; the cerebellum, which controls posture and balance; and the basal
ganglia, which are processing centers for movement information.

Particularly important to Parkinson’s disease are the substantia nigra and the corpus striatum. Discovery of a functional interface between dopamine and Parkinson’s disease began when it was found that this neurotransmitter was associated with the substantia nigra and connected the substantia nigra and the corpus striatum. Next, it was discovered that temporary Parkinson’s disease mediated by reserpine was associated with dopamine depletion and that the brains of patients contained very little dopamine in the substantia nigra. Soon, it was confirmed that dopamine controlled movement in an inhibitory fashion that arose in the substantia nigra and occurred in the corpus striatum. From these observations, it has been inferred that bradykinesia results from the damage of the dopamine-containing nerve tissue that connects the substantia nigra to the corpus striatum. It is also suggested that decreased function of these fibers—and lack of their inhibitory action because of dopamine—allows excess, undesired nerve impulses to cause both the tremor and the rigidity seen in Parkinson’s
disease.

Treatment and Therapy

Parkinson's disease can be difficult to diagnose, particularly in the early
stages. Parkinson’s disease is most often identified by physical evidence (such as
tremor and bradykinesia), coupled with a careful study of the medical history of
the patient being evaluated. In all but a few cases, no diagnostic information can
be obtained via the three powerful tools useful in many other neurologic exams:
The complex X-ray method, computed tomography (CT) scanning, is
informative only when stroke or tumor is involved; magnetic resonance imaging
(MRI) gives no more information than do CT scans; and electroencephalograms (EEGs)
do not show abnormal electrical discharge such as that observed in brains of
patients with epilepsy. In practice, however, many physicians carry out CT scans,
MRI, and EEGs and count their negative results into a diagnostic positive for
Parkinson’s disease.

Once Parkinson’s disease is diagnosed, three main methods exist for managing it:
medications, physical therapy, and surgery. All these methods—alone or in
combination—are intended for symptom reversal because there is no cure for the
disease. Medications are the first-line treatment mode in most cases. Many
different medications are used, such as levodopa (L-Dopa), dopamine agonists,
monoamine oxidase type B inhibitors, and anticholinergic drugs.

The anticholinergics were the first drugs used for Parkinson’s disease, and they
are still often prescribed for younger patients with severe tremors, but they are
now associated with limited efficacy and neuropsychiatric side effects. The first
anticholinergic drug used, in the 1890s, was scopolamine, initially isolated from
Datura stramonium (jimsonweed). Other anticholinergics include
atropine and the antihistamine diphenhydramine (Benadryl). These drugs operate by
interfering with the action of acetylcholine, a neurotransmitter
involved in nerve impulse transport. High doses of anticholinergic drugs produce
many side effects, including confusion, slurred speech, blurred vision, and
constipation because of the wide influence of cholinergic nerves on body
operation.

Levodopa, the amino acid that is made into dopamine by the body, is a first-line
choice in the treatment of Parkinson's. Levodopa is a metabolic precursor of
dopamine and can improve motor impairment. Dopamine itself is not used because a
blood-brain barrier prevents brain dopamine uptake from the blood. The blood-brain
barrier does not stop levodopa uptake, and its administration reverses symptoms
dramatically. Therefore, it has become the mainstay of modern chemotherapy for the
disease.

A difficulty associated with use of levodopa is that the biochemical mechanism
that converts it to brain dopamine also occurs outside the brain. When this
happens in patients given high doses of levodopa, body (nonbrain) dopamine levels
rise. This dopamine and the chemicals into which it transforms outside the brain
cause such side effects as nausea, fainting, flushing, confusion, and the
involuntary muscular movements called dyskinesia. The dose should be kept low
to maintain function and reduce motor complications. To minimize these
unwanted—and sometimes irreversible—side effects, modern levodopa therapy
sometimes combines the drug with its chemical cousin, carbidopa. Carbidopa
prevents the conversion of levodopa to dopamine. Because it cannot cross the
blood-brain barrier, carbidopa has no effect on the brain’s conversion of levodopa
to dopamine.

Another first-line medication for treating Parkinson’s disease is dopamine
agonists. These chemicals mimic dopamine action, reacting with the brain’s
receptors that produce dopamine effects in the corpus striatum and other sites.
Monoamine oxidase type B (MAO-B) inhibitors may be used for patients with early
disease. MAO-B inhibitors such as selegiline can delay the onset of motor
complications compared to levodopa but may be less effective in the treatment of
functional impairment.

Furthermore, it is not uncommon for those afflicted with Parkinson’s disease to
suffer from depression as they lose control of their motor functions.
This is probably the case because, as noted by James Parkinson, “the senses and
intellect are unimpaired” in such patients. However, traditional antidepressants
may not reduce depression in patients with Parkinson's disease, and several
antidepressant medications can have negative interactions with the medical
treatment of Parkinson's. Pramipexole, a dopamine agonist, is associated with
improvement in depressive symptoms in patients with Parkinson's disease.
Venlafaxine, an antidepressant and serotonin-norepinephrine reuptake inhibitor,
may also be used in the treatment of depression in patients with Parkinson's.

Surgical treatment of Parkinson’s disease was once attempted quite often, but it
became relatively rare by the 1970s, after modern medications were developed.
Since then, its utilization occurs when CT scanning or MRI indicates the presence
of a tumor or brain damage caused by a severe trauma. An implant that provides
deep brain
stimulation has been used to suppress tremors and improve
quality of life. Thalamotomy, the destruction of the thalamus—the brain region
that controls some involuntary movements, was also once more commonly used in the
surgical treatment of Parkinson's, but it is a highly invasive procedure and it is
only rarely used for the treatment of severe drug-resistant tremors. More
recently, thalamic stimulation appears to be as effective as thalamotomy with
fewer adverse effects.

Two final topics worth mentioning are cognitive-behavioral therapy and physical
therapy. Part of their purpose is to address the depression that often accompanies
severe Parkinson’s disease. Cognitive-behavioral therapy for Parkinson's diseases
often includes exercise, behavioral activation, thought monitoring and
restructuring, relaxation training, worry control, and sleep hygiene.
Cognitive-behavioral therapy provides emotional support to patients with
Parkinson's and has been found to improve global symptom severity. Physical
therapy can help patients to overcome some motor effects of the disease, not only
improving the lifestyle possible for them but also elevating morale and curing
depression. Endurance exercises and progressive resistance exercises have been
found to improve physical performance in patients with Parkinson's disease.

Perspective and Prospects

Treatment of Parkinson’s disease has evolved tremendously, particularly since the
late 1960s, when wide use of levodopa began. At that time, most physicians were
astounded to observe that its use converted many stage-5 patients, who were
bedridden or wheelchair-bound, to much more functional, mobile states. A temporary
setback occurred when severe levodopa side effects were observed at high
doses.

The discovery of carbidopa and related inhibitors of nonbrain dopamine
decarboxylase ended this problem and produced a new generation of chemotherapy.
Patients could take levodopa at lower concentrations, which minimized its side
effects, because diminished nonbrain levodopa conversion to dopamine left more
levodopa available to enter the brain. In addition, carbidopa was the forerunner
of a group of dopamine agonists that became candidates for independent use or use
in mixed therapy.

Researchers at the turn of the twenty-first century closely examined the genetic
links in familial forms of Parkinson’s disease. One gene, α-synuclein, is a
presynaptic neuronal protein that is believed to play a significant role in
neuronal plasticity. α-synuclein was previously associated with Alzheimer’s
disease as the nonamyloid component of Alzheimer’s amyloid plaques (NAC peptide),
and it is a component of the Lewy inclusion bodies found in the
Parkinson’s-associated Lewy body dementia. Mutations in another gene, Parkin
(PARK2), were found to underlie the development of
juvenile-onset Parkinson’s disease. Parkin is believed to play a role in cellular
protein degradation by interacting with ubiquitin, a protein that targets other
proteins for degradation. It is hoped that the identification of these genes will
lead to a better understanding of the pathogenic mechanisms underlying nonfamilial
(sporadic) Parkinson’s disease.

Discovery that cognitive-behavioral therapy and exercise can ease the depression
observed in many afflicted people and help to control the disease’s progression
has also been of great value. Perhaps even more exciting have been reports that
the injection of human fetal cells into the brains of those afflicted with
Parkinson’s disease may be able to reverse the disease. It is too soon, however,
to judge the results of this procedure.

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