What are natural treatments for memory and mental function impairment?

Introduction

Mental function often declines particularly under conditions of stress or fatigue. In addition, most people age forty and older experience some memory loss, technically known as age-related cognitive decline or age-associated memory impairment. It is not known what causes this normal experience, and there is no conventional treatment available for it. A few natural treatments might be helpful.

Principal Proposed Natural Treatments

Statistically speaking, it is easier to demonstrate a big improvement than a small
one, and for that reason, it is more difficult to prove the effectiveness of a
treatment in a mild condition than in a severe one. Because of this, there is far
more evidence supporting the use of natural supplements for treating
Alzheimer’s
disease than for improving mental function in healthy people.
Nonetheless, there is some evidence for the latter.

Ginkgo biloba. An extract made from the herb Ginkgo
biloba is a well-established herbal treatment for Alzheimer’s disease.
Ginkgo may also be helpful for improving normal age-related
memory loss and even for enhancing mental function in younger people.

Age-related mental decline. In six of nine double-blind studies, the use of Ginkgo biloba extract significantly improved age-related mental decline compared with placebo. For example, in a double-blind, placebo-controlled trial, 241 elderly people complaining of mildly impaired memory were given either placebo or ginkgo for twenty-four weeks. The results showed that ginkgo produced modest improvements in certain types of memory.

Another double-blind, placebo-controlled trial examined the effects of ginkgo extract in forty men and women (age fifty-five to eighty-six years) who were not mentally impaired. In a six-week period, the results showed improvements in measurements of mental function. Benefits were seen in four other trials too, involving about 135 participants.

Set against these positive findings is a large (214 people) twenty-four-week study that found no benefit in ordinary age-related memory loss. It has been suggested that flaws in the trial’s design led to this negative outcome. However, three other studies enrolling about four hundred elderly persons also failed to find significant benefit with daily use of ginkgo. Another double-blind, placebo-controlled study used a one-time dose of ginkgo and found no benefits. Also, a small, double-blind, placebo-controlled study looking for immediate mind-stimulating effects did not find them.

Besides these negative trials, there is another weakness in the evidence. There are numerous measurable aspects of memory and mental function, and studies of ginkgo for improving memory and mental function have examined a great many of these. The exact areas of benefits seen vary widely. For example, in one positive study, ginkgo may speed up the ability to memorize letters but not expand the number of letters that can be retained, while in another positive study, the reverse may be true. This type of inconsistency tends to decrease the confidence one can place in these apparently positive studies, because if ginkgo were really working, one would expect its effects to be more reproducible. Ginkgo may help normal age-related memory loss, but more research is necessary to determine whether this is the case.

Improving memory and mental function in younger people. Several studies enrolling about 250 people have examined the effects of ginkgo on memory and mental function in younger people. However, the benefits seen in the positive trials were inconsistent, and the largest study failed to find any effect. One study hints that benefits may occur initially and then decline after several weeks.

Besides ginkgo alone, several double-blind, placebo-controlled studies evaluated
combined treatment with ginseng and ginkgo, or vinpocetine and ginkgo, for
enhancing mental function in young people, and most found some evidence of
benefit. Weak evidence suggests that combining phosphatidylserine with ginkgo
might increase its efficacy. However, in two studies, ginkgo combined with the
Ayurvedic herb brahmi failed to improve mental function.

Phosphatidylserine. Like ginkgo, the supplement phosphatidylserine (PS) is widely used in Europe to treat
various forms of dementia. There is some evidence that PS can also help people
with ordinary age-related memory loss.

In one double-blind study that enrolled 149 people with memory loss (but not dementia), PS provided significant benefits compared with placebo. Persons with the most severe memory loss showed the most improvement.

Another double-blind trial of 120 older people with memory complaints (but not dementia) found no benefits. This discrepancy may have to do with the type of PS used (the second trial used the more modern soy-derived form of the supplement). Phosphatidylserine might enhance the effectiveness of ginkgo.

Ginseng. Several studies have found indications that the herb
ginseng might enhance mental function. However, the specific
benefits seen have varied considerably from trial to trial, tending to make the
actual cognitive effects of ginseng (if there are any) difficult to discern.

For example, in a two-month, double-blind, placebo-controlled study of 112 healthy, middle-aged adults given either ginseng or placebo, results showed that ginseng improved abstract thinking ability. However, there was no significant change in reaction time, memory, concentration, or overall subjective experience between the two groups.

Another double-blind, placebo-controlled study of fifty men found that eight-week treatment with a ginseng extract improved ability to complete a detail-oriented editing task. A double-blind trial of sixteen healthy males found favorable changes in the ability to perform mental arithmetic in those given ginseng for twelve weeks.

More comprehensive benefits were seen in a double-blind, placebo-controlled trial of sixty elderly persons given fifty or one hundred days of treatment. The results showed that Panax ginseng produced improvements in numerous measures of mental function, including memory, attention, concentration, and ability to cope. Benefits were still evident at the fifty-day follow-up. However, virtually no improvement was seen in the placebo group, a result that is highly unusual and raises doubts about the accuracy of the study. Finally, four double-blind, placebo-controlled studies evaluated combined treatment with ginseng and ginkgo and found inconsistent evidence of improved mental function.

Bacopa monniera (brahmi). The Ayurvedic herb Bacopa
monniera (brahmi) has a traditional reputation
for improving memory. However, a twelve-week, double-blind, placebo-controlled
trial of seventy-six persons that tested the potential memory-enhancing benefits
of brahmi generally failed to find much evidence of benefit. The only significant
improvement seen among all the many measures used was one that evaluated retention
of new information. A randomized trial involving forty-eight healthy elderly
persons found some memory-enhancing effects of B. monniera
compared with placebo, but the outcomes measured were too numerous to be
convincing.

In another double-blind, placebo-controlled study of thirty-eight persons, short-term use of brahmi failed to produce any measurable improvements in memory, while in a third double-blind, placebo-controlled study, the use of brahmi over a two-week period did produce some benefits, but in quite a different pattern. Finally, a study found that one-time combined treatment with ginkgo (120 milligrams [mg]) and brahmi (300 mg) failed to improve mental function.

Slightly more promising results have been seen in studies of a proprietary
Ayurvedic mixture containing brahmi and about thirty other
ingredients. However, these studies were generally not up to modern scientific
standards.

Other Proposed Natural Treatments

On the basis of one small double-blind study, a proprietary mixture of substances called neuropeptides has been extensively marketed for improving mental function. Radio, television, and Web advertisements state that this product has been shown to bring about “a reversal of ten years of short-term memory decline.” However, this claim is not founded in reliable evidence. Another single study suggests that the supplement nicotinamide adenine dinucleotide might help improve temporary mental impairment caused by jet lag.

Evidence conflicts on whether multivitamin-multimineral tablets may improve cognitive function in people of various age groups. In general, the best-designed studies have failed to find benefit. However, it is quite possible that multivitamin-multimineral supplements are helpful for people with marked vitamin or mineral malnutrition. Studies of isoflavone-rich soy or red clover for enhancing mental function in women have found little to no beneficial effects at best.

Huperzine
A is a potent chemical derived from a particular type of club
moss (Huperzia serrata). This substance is really more a drug
than an herb, but it is sold over the counter as a dietary supplement for memory
loss and mental impairment. Some evidence indicates that it may be helpful for
Alzheimer’s disease and related conditions; very weak evidence suggests benefit
for healthy people. Much the same can be said about the substance vinpocetine.

Creatine, best known for its use as a sports-performance
enhancer, may improve mental function in sleep-deprived, but not necessarily
well-rested, young persons. Sage and vitamin B17 have slight supporting
evidence from preliminary double-blind trials.

Mild vitamin B12 deficiency may impair mental function. Because such deficiency is relatively common in the elderly, it has been suggested that vitamin B12 supplements may be appropriate in this age group. However, in the two studies that tried it, no benefits were seen.

The elderly are also commonly deficient in vitamin B6, but a review of the literature failed to find meaningful evidence that vitamin B6 offers any benefits. One study failed to find folate helpful either; however, in another study, folate supplementation improved mental function in older persons with high levels of homocysteine. Combinations of B vitamins, including B12, B6, and folate, have proved ineffective.

One study failed to find any benefit with zinc. Other preliminary double-blind trials suggest that the amino acid tyrosine may improve memory and mental function under conditions of sleep deprivation or other forms of stress. Other double-blind trials suggest that a proprietary extract of the herb Rhodiola rosacea may offer a similar benefit.

Whey protein contains alpha-lactalbumin, a protein that in turn contains high levels of the amino acid tryptophan. Tryptophan is the body’s precursor for serotonin and is thought to affect mental function. In a small double-blind study, the use of alpha-lactalbumin in the evening improved morning alertness, perhaps by enhancing sleep quality. Another small double-blind study found weak evidence that alpha-lactalbumin improved mental function in people sensitive to stress. A third study failed to find that alpha-lactalbumin significantly improved memory in women experiencing premenstrual symptoms.

Herbs that contain caffeine would be expected to enhance
mental function in healthy people, at least temporarily. These herbs include green
tea, black tea, maté, and guarana. For example, in a double-blind,
placebo-controlled study of 129 healthy young adults, the one-time use of
guarana plus vitamins and minerals improved mental function
and reduced mental fatigue among those undergoing a battery of cognitive tests. In
another double-blind, placebo-controlled study, the use of guarana alone or
guarana plus ginseng appeared to improve mental function. However, these studies
had some design problems. In two other studies, no benefits were seen.

Some reports suggested that declining levels of the hormone dehydroepiandrosterone (DHEA) cause impaired mental function in the elderly. On this basis, DHEA has been promoted as a brain-boosting supplement. However, large studies have failed to find any correlation between DHEA levels and mental function, and there is no direct evidence that DHEA supplements provide any benefit in the elderly. One study did find potential benefits in younger people.

Weak evidence culled from a large, double-blind, placebo-controlled study hints that the use of beta-carotene over many years might enhance mental function. However, long-term use of beta-carotene might present safety risks.

Other herbs and supplements that have been proposed for enhancing memory and mental function, but that lack meaningful supporting evidence, include gotu kola, rosemary, saffron, muira puama, sage, and lobelia. In one small double-blind study, the supplement ribose failed to prove effective for enhancing mental function. However, the researchers suggested that the dose they used (2 grams daily) may have been insufficient.

A large study failed to find that the use of vitamin E helped maintain healthy mental function in women older than age sixty-five years. Also, women who are marginally deficient in iron may experience improved mental function when they correct this deficiency. Carnitine has shown some benefit for reducing mental fatigue and enhancing cognitive function in centenarians.

Bibliography

Ataka, S., et al. “Effects of Oral Administration of Caffeine and D-Ribose on Mental Fatigue.” Nutrition 24 (2008): 233-238.

Balk, E. M., et al. “Vitamin B6, B12, and Folic Acid Supplementation and Cognitive Function.” Archives of Internal Medicine 167 (2007): 21-30.

Calabrese, C., et al. “Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly.” Journal of Alternative and Complementary Medicine 14 (2008): 707-713.

Crews, W. D., et al. “A Double-Blinded, Placebo-Controlled, Randomized Trial of the Neuropsychologic Efficacy of Cranberry Juice in a Sample of Cognitively Intact Older Adults.” Journal of Alternative and Complementary Medicine 11 (2005): 305-309.

Durga, J., et al. “Effect of Three-Year Folic Acid Supplementation on Cognitive Function in Older Adults in the FACIT Trial.” The Lancet 369 (2007): 208-216.

Fournier, L. R., et al. “The Effects of Soy Milk and Isoflavone Supplements on Cognitive Performance in Healthy, Postmenopausal Women.” Journal of Nutrition, Health, and Aging 11 (2007): 155-164.

Grodstein, F., et al. “A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men: The Physicians’ Health Study II.” Archives of Internal Medicine 167 (2007): 2184-2190.

Hvas, A. M., et al. “No Effect of Vitamin B-12 Treatment on Cognitive Function and Depression.” Journal of Affective Disorders 81 (2004): 269-273.

Kang, J. H., et al. “A Randomized Trial of Vitamin E Supplementation and Cognitive Function in Women.” Archives of Internal Medicine 166 (2006): 2462-2468.

Kennedy, D. O., C. F. Haskell, et al. “Improved Cognitive Performance and Mental Fatigue Following a Multi-vitamin and Mineral Supplement with Added Guarana (Paullinia cupana).” Appetite 50 (2008): 506-513.

Kennedy, D. O., P. A. Jackson, et al. “Modulation of Cognitive Performance Following Single Doses of 120 mg Ginkgo biloba Extract Administered to Healthy Young Volunteers.” Human Psychopharmacology 22 (2007): 559-566.

Kennedy, D. O., S. Pace, et al. “Effects of Cholinesterase Inhibiting Sage (Salvia officinalis) on Mood, Anxiety, and Performance on a Psychological Stressor Battery.” Neuropsychopharmacology 31 (2006): 845-852.

Kritz-Silverstein, D., et al. “Effects of Dehydroepiandrosterone Supplementation on Cognitive Function and Quality of Life.” Journal of the American Geriatrics Society 56 (2008): 1292-1298.

McNeill, G., et al. “Effect of Multivitamin and Multimineral Supplementation on Cognitive Function in Men and Women Aged Sixty-Five Years and Over.” Nutrition Journal 6 (2007): 10.

Malaguarnera, M., et al. “L-carnitine Treatment Reduces Severity of Physical and Mental Fatigue and Increases Cognitive Functions in Centenarians.” American Journal of Clinical Nutrition 86 (2007): 1738-1744.

Markus, C. R., et al. “Evening Intake of Alpha-lactalbumin Increases Plasma Tryptophan Availability and Improves Morning Alertness and Brain Measures of Attention.” American Journal of Clinical Nutrition 81 (2005): 1026-1033.

Maylor, E. A., et al. “Effects of Zinc Supplementation on Cognitive Function in Healthy Middle-aged and Older Adults.” British Journal of Nutrition 96 (2006): 752-760.

Murray-Kolb, L. E., and J. L. Beard. “Iron Treatment Normalizes Cognitive Functioning in Young Women.” American Journal of Clinical Nutrition 85 (2007): 778-787.

The NEMO Study Group. “Effect of a Twelve-mo Micronutrient Intervention on Learning and Memory in Well-Nourished and Marginally Nourished School-Aged Children.” American Journal of Clinical Nutrition 86 (2007): 1082-1093.

Rawson, E. S., et al. “Creatine Supplementation Does Not Improve Cognitive Function in Young Adults.” Physiology and Behavior 95 (2008): 130-134.

Van Uffelen, J. G., et al. “Walking or Vitamin B for Cognition in Older Adults with Mild Cognitive Impairment?” British Journal of Sports Medicine 42 (2008): 344-351.

What are biopharmaceuticals?

History of Biopharmaceuticals

Drugs have been used by humans for thousands of years. More than three thousand years ago, the Sumerians were the first culture to compile written medical information that outlined symptoms and treatments for disease. Most ancient cultures used medicines derived from plants and animals. These drugs were different from modern biopharmaceuticals in many ways, but the most significant difference is that the drugs were not engineered to treat a particular disease. Since there was no real understanding of the underlying problem, a rational approach to drug selection and design was difficult, if not impossible. One philosophy of medicine that developed to address this problem was called the doctrine of similitudes, in which treatments were based on similarities of structure with disease manifestation. For example, the leaves of St. John’s wort looked similar to damaged skin, so it was thought this plant extract could effectively treat cuts and burns.

It was not until the twentieth century that the underlying genetic basis for disease was discovered. The discovery that DNA is the genetic material that provides instructions to make proteins was revolutionary. In the mid-1900s, sickle-cell disease
was shown to be caused by a single nucleotide mutation from an A (adenine) to a T (thymine) in the hemoglobin beta-chain gene. This small change alters the shape of a red blood cell from a biconcave disc to a sharply pointed crescent. Although it was now possible to identify genetic mutations, there was still no way to manipulate or make changes to genetic information.

The advent of recombinant DNA
technology in the 1970s provided the first chance to engineer, or manipulate, genes. Restriction enzymes
became an important tool in this new technology. Restriction enzymes were first found in bacteria, where they function to protect the cell from foreign DNA by cutting it up at specific sequences. These sequences are usually palindromes of the letters that signify the four nucleotides that make up DNA: guanine (G), adenine (A), thymine (T), and cytosine (C). Most restriction enzymes cut the DNA in such a way that an overhang, called a sticky end, is created. Since excess unbound DNA, provided by the scientist, will readily bind its complementary base, these engineered sticky ends can be used to splice different pieces of DNA together in a laboratory. The resulting sequence is called recombinant DNA.

With the ability to engineer DNA now possible with restriction-enzyme technology, scientists looked again to use bacteria as a host “factory” in order to convert known DNA sequences into protein. Bacteria are ideal for protein production because they reproduce quickly, are easy to genetically manipulate, and can be grown in large quantities. Many bacteria contain circular pieces of DNA that are separate from their genome, called plasmids. Plasmids can be readily transferred between bacteria and are also inherited by daughter cells when a bacterium divides. With the use of restriction enzymes, plasmids are isolated from bacteria and engineered to contain a foreign gene. The recombinant plasmid is reinserted back into bacteria, which work nonstop to transcribe and translate the recombinant gene. The gene is then expressed as a fully functional protein. The first biopharmaceutical produced in bacteria was recombinant human insulin, which was marketed in 1982.

The future for biopharmaceuticals looks bright. In 1991, there were only fourteen biopharmaceuticals approved for use by the US Food and Drug Administration (FDA). By 2014, approximately 375 had been approved for use in the United States, and more than 580 major US companies were working to produce and develop biopharmaceuticals.

Design of Biopharmaceuticals

A popular method for the identification of disease-related genes is called genomics. Gene chip analysis is used to screen thousands of genes in a single experiment. This approach is drastically faster and more efficient than traditional methods and can be used for any disease, even those that are not hereditary.

Once the genomic information is obtained, it is used to build a broad understanding of how a disease gene functions and what role the gene plays in the cell. This information is gathered through the use of experimental models, genetic analysis, biochemical analysis, and structural analysis. Experimental models can range from cell culture to transgenic mice and can provide physiological information about the disease. Genetic analysis can provide information about where and when the gene is expressed. Biochemical analysis can provide information about protein-protein interactions, posttranslational modifications of the protein, and its enzymatic activity. Structural analysis can yield extremely detailed information about the physical arrangement of the atoms that make up the protein. All these approaches can identify important potential targets for treatment of the disease. A better understanding of the disease at the genetic and molecular levels facilitates the design of a biopharmaceutical.

Once a disease is better understood, it becomes possible to target a key pathway or protein for biopharmaceutical intervention. The resultant drug and the way that it is used clinically will vary from disease to disease. For example, type I diabetes
is caused by a deficiency in the hormone insulin. Without insulin, the body is not able to regulate the level of glucose in the blood. Lack of insulin was first corrected by an injection of the first biopharmaceutical, recombinant human insulin. It was developed by Genentech and marketed as Humulin by Eli Lilly & Company in 1982.

Another example of a biopharmaceutical is the enzyme tissue plasminogen activator (tPA). Most heart attacks are caused by a blood clot blocking the flow of blood through a coronary artery. Formation and removal of blood clots is a highly regulated and well-understood process. Tissue plasminogen activator is one of the key players in blood-clot removal. This knowledge led to the development of recombinant tPA, which can be provided by injection or infusion to heart attack patients. Once in the bloodstream, tPA breaks up coronary artery clots and restores blood flow to the heart, preventing any further muscle damage.

Clinical Trials

Before a biopharmaceutical can be used to treat disease, it must undergo rigorous clinical trials that test its safety and effectiveness in humans. There are four phases of clinical trials. Phase I trials involve studies on a small number of patients (fewer than one hundred) in order to determine drug safety and dosage. Phase II trials involve more patients (up to five hundred) in order to determine effectiveness and additional safety information, such as side effects. Phase III trials are the most extensive and involve large numbers of people (between one thousand and three thousand). These trials establish risk-benefit information and are compared with other currently used treatments. Phase IV trials determine the drug’s optimal use in a clinical setting.

In 2011, the entire process of drug design—from discovery to clinical trials—cost an estimated $1.5 billion and took an average of ten to fifteen years. Many years of research and millions of dollars are expended in an extraordinary effort that yields little success; only one in five thousand drugs makes it to market.

Biopharmaceuticals Today

Biopharmaceuticals are classified into several categories, including blood factors, thrombolytic agents, hormones, hematopoietic growth factors, interferons, interleukin-based products, vaccines, monoclonal antibodies, and other products. Some FDA-approved biopharmaceuticals of particular interest include Aralast, Gardasil, and ATryn. Aralast is marketed by Baxter and was approved for use by the FDA in 2003. Aralast is the trade name for the recombinant human protein known as alpha-1 proteinase inhibitor (A1PI). A1PI deficiency, also called alpha-1-antitrypsin deficiency, results in the destruction of lung tissue, which can lead to emphysema. Aralast is given to patients intravenously each week, protecting against future lung damage.

The popular vaccine Gardasil was designed to prevent genital human papillomavirus (HPV)
infection. Gardasil is marketed by Merck & Company and was approved by the FDA for use in young women in 2006. HPV is the most commonly sexually transmitted disease in the United States and has been shown to cause cervical cancer, the second leading cause of cancer deaths among women worldwide. Gardasil vaccinates against the four most common strains of HPV. It is a quadrivalent vaccine that stimulates the immune system to make antibodies that recognize and destroy HPV 6, 11, 16, and 18, protecting against future infection.

ATryn is the trade name for recombinant antithrombin III, an anticoagulant manufactured by GTC Biotherapeutics and sold by Ovation Pharmaceuticals. It is produced from the milk of transgenic goats that have been genetically modified to produce human antithrombin. In 2009, the FDA approved the use of ATryn to treat patients with hereditary antithrombin deficiency who need an anticlotting agent to undergo procedures that involve blood loss, such as surgery and childbirth. It was the first biopharmaceutical to be produced from genetically engineered animals, goats being chosen for their high reproduction rate.

A 1998 study found that more than 100,000 people in the United States die each year because of adverse drug reactions. Similarly, in 2013, the European Medicines Agency reported that adverse reactions caused approximately 197,000 deaths in the European Union annually. One trend in pharmaceutical research is the production of designer drugs through the new field of pharmacogenomics. These drugs are specifically matched to an individual patient’s genetic profile and their particular form of disease. Pharmacogenomics would make it possible to avoid adverse drug reactions. Research in pharmacogenomics will also increase the pool of drugs available to treat disease. While many drugs never make it to market because they work for only a small subset of patients, pharmacogenomic research will identify these specific patients as treatment successes.

Key Terms




clinical trial


:

an experimental research study that determines the safety and effectiveness of a medical treatment or drug




humanized antibody

:

a human antibody that has been engineered to contain a portion of a nonhuman variable region with known therapeutic activity




pharmacogenomics

:

the field of science that examines how variations in genes alter the metabolism and effectiveness of drugs





Bibliography

Barr, Eliav, and Heather L. Sings. “Prophylactic HPV Vaccines: New Interventions for Cancer Control.” Vaccine 26.49 (2008): 6244–57. Print.

Collins, Francis S., and Victor A. McKusick. “Implications of the Human Genome Project for Medical Science.” JAMA 285.5 (2001): 540–41. Print.

Nagle, Paul C., et al. “Characteristics of and Trends in the Late-Stage Biopharmaceutical Pipeline.” American Journal of Managed Care 14.4 (2008): 226–29. Print.

Ho, Rodney J. Y. Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs. 2nd ed. Hoboken: Wiley, 2013. Print.

Niemann, Heiner, and Wilfried A. Kues. “Transgenic Farm Animals: An Update.” Reproduction, Fertility and Development 19.6 (2007): 762–70. Print.

Shargel, Leon, Susanna Wu-Pong, and Andrew Yu. Applied Biopharmaceutics & Pharmacokinetics. 6th ed. New York: McGraw, 2012. Print.

Subramanian, Ganapathy, ed. Biopharmaceutical Production Technology. 2 vols. Weinheim: Wiley, 2012. Print.

Wu-Pong, Susanna, and Yon Rojanasakul, eds. Biopharmaceutical Drug Design and Development. 2nd ed. Totowa: Humana, 2008. Print.

How do you say "Hoodhood"? I am reading The Wednesday Wars and my reading group is having a dispute about how to say it.

That's an interesting debate! Since "Hoodhood" is the main character's last name as well as part of his father's company's name, I agree that it's important to know how to pronounce it correctly. 

Sources like this one suggest that you say "HOOD hood," putting the emphasis on the first syllable (like you do when you say "Johnson" and "Summers") and pronouncing both syllables just like the word "hood," as in the hood of a sweatshirt. (Just rhyme it with "could" and "should.") If you visit that link, you can play the audio pronunciation of the name.

Joel Johnstone, the voice actor who reads this novel in the widely available audio version, also pronounces "Hoodhood" as I just described. That's a good indication that we've found the right way to say this name.

The best way to be sure, though, would be to ask someone named Hoodhood! Now, you might wonder if this is impossible if you suspect that the author made up the name "Hoodhood" as a way of characterizing Holling as a bit quirky. But it's a real name. According to Forbears.io, the surname "Hoodhood" is the 1,999,413th most common in the world (compared to, for example, "Smith," the 117th most common). The site estimates that only about 35 people bear "Hoodhood" as a last name. Like I said, the best way to figure out how to pronounce this name is to ask someone who has it. But unfortunately for us, the statistics I just mentioned make it very unlikely that we know a Hoodhood personally.

Who helps Ms. Gruwell get permission to teach the seniors?

In the book The Freedom Writers Diary, Ms. Gruwell desired to teach her students during their senior year.

Unfortunately, it was challenging for Ms. Gruwell to receive permission to teach the seniors. Ms. Gruwell had little seniority at her school. At her school, it was unusual for teachers with little seniority to choose the classes and grades they wanted to teach. As Ms. Gruwell explained:

“Things are based on seniority around here.”

However, Ms. Gruwell received help from her superintendent (Dr. Cohn) and the president of the board of education (Karin Polachek). These two individuals accompanied the class on their trip to Washington D.C. Furthermore, these two individuals sympathized with Ms. Gruwell’s cause and helped Ms. Gruwell overcome this barrier.

Thus, although it was challenging to achieve this goal, influential leaders helped Ms. Gruwell obtain permission to teach the seniors. 

How does Harper Lee present inequality in the novel To Kill a Mockingbird, and how does it affect Scout, Jem and Dill?

Harper Lee presents inequality to Scout, Jem, and Dill in the novel by exposing them to the wrongful conviction of Tom Robinson. Prior to the trial, Scout, Jem, and Dill had never witnessed racial injustice. Because Tom Robinson is a black man living in the prejudiced community of Maycomb, he is found guilty of assaulting and raping Mayella Ewell. During the trial, Jem feels that Atticus is clearly winning the case based on the conflicting testimonies of the Ewells and the lack of evidence presented against Tom. When the prosecutor, Mr. Gilmer, questions Tom, Dill begins to cry uncontrollably, and Scout is forced to take him outside of the courtroom. Dill mentions to Scout that he couldn't stand the way Mr. Gilmer was talking down to Tom and treating him disrespectfully. When the final verdict is read, Jem is shocked and deeply upset. All three characters lose their childhood innocence by witnessing Tom's conviction.

As the novel progresses, Jem becomes jaded about his community and its widespread inequality and prejudice. Jem begins to understand the class divisions of Maycomb while Scout remains positive about their environment. Dill is so upset after witnessing the trial that he says he wants to become a clown. Dill's wish to become a clown is a naive expression of how he wishes to protect himself from further heartache. Scout, like her father, recognizes inequality and stands up for the oppressed and innocent. When Alexandra tells her that she can't play with Walter because he is "trash," Scout becomes upset and discusses her feelings with Jem. She also becomes cognizant of the overwhelming hypocrisy in her community regarding inequality, race, and religion. Despite Scout's loss of innocence, she is hopeful and tolerant of her community members. Scout does not become bitter like her brother or repress her feelings like Dill, instead, she chooses to follow Atticus' lead and view the town Maycomb for what it is.

What is the lymphatic system?

Structure and Functions

The lymphatic system is a complex of capillaries, ducts, nodes, and organs that filters and maintains interstitial fluid—that is, fluid from body tissues. Fluid is collected from body tissues and returned to the bloodstream. In addition, the system functions as a site of the immune response, primarily in the spleen and the lymph nodes, and transports fat and protein to the bloodstream.

The organs of the lymphatic system are divided into primary lymphoid organs and secondary organs. The primary organs include the thymus and the bone marrow, which are sites where lymphocytes are produced and mature. Secondary lymphoid organs are those in which the immune response is carried out. These include both encapsulated organs such as the spleen and lymph nodes and unencapsulated organs such as the mucosal associated lymphoid tissue, which includes Peyer’s patches in the intestine and Waldeyer’s ring in the throat (the tonsils and adenoids), which encircles the pharnyx. Lymph nodes are found throughout the body, but they occur in large numbers in the head, neck, armpits (the axillary nodes), and abdomen and groin (the inguinal nodes).

The lymphatic vessels essentially parallel those of the bloodstream. The system originates in peripheral tissue as small openings, or sinuses, within the tissue. Fluid that drains from the tissue collects in these sinuses and forms lymph. In addition, a significant amount of liquid (1 to 2 liters) that is lost from blood capillaries each day also collects in the interstitial fluid. The lymph is physiologically similar to blood plasma in that it is a balanced solution of
electrolytes containing some carbohydrates, lipids, and proteins. In general, the protein level is about half that found in blood, since most blood proteins are too large to pass through the endothelial walls of blood capillaries. Arguably, the major function of the lymphatic system is the return of this fluid, and its constituent materials, to the blood. The buildup of abnormal amounts of fluid in tissue results in swelling, or edema. Approximately 60 percent of lost fluid is returned to the blood through the lymphatics, and the remainder is collected directly into small blood capillaries.

Generally speaking, the peripheral portion of the lymphatic system is completely separate from that of the blood. Once the interstitial fluid is collected, it begins to move toward the thoracic duct. Since the duct is found in the neck region, this movement is primarily in an upward direction. The fluid moves through regional lymph nodes, such as those found in the groin or armpits, and gradually collects in the larger ducts of the major lymphatics. Though an extensive system of valves is found in the lymphatic system to prevent the movement of lymph in the wrong direction, no internal pumping mechanism analogous to the heart exists. The movement of the lymph is mediated by the musculature of the body: respiratory pressure, muscular movement, and the pulsing or motion of nearby organs. Lymphatic fluids from all portions of the body, except for the upper-right quadrant, eventually collect in the thoracic duct. Lymph from the upper-right quadrant of the body collects in the right lymphatic duct. The endothelia of these major lymphatic ducts are contiguous with those of the veins in the neck, and it is here that the fluid is returned to the bloodstream. Valves present in the lymphatic ducts serve to prevent the backup of blood from the bloodstream into the lymphatic system.

In addition to the electrolytes and proteins that collect in lymph, foreign materials such as infectious agents may also penetrate the skin or internal surfaces of the body. These materials pass into tissue fluids and also collect in the lymphatic system. From here, they travel to regional lymph nodes, where they are filtered out by phagocytic cells such as macrophages. In addition, antigen-collecting cells in the skin, including dendritic cells, may transport foreign materials such as bacteria to these regional nodes. These cells may intercalate, or interdigitate, among the lymphocytes of the lymph nodes and, along with the macrophages, “present” antigen to B and T cells. In this manner, the immune response is initiated.

An analogous situation exists in the blood system. In this case, however, it is the macrophages of the spleen that serve to filter foreign material, such as infectious agents, from the blood. Damaged or old red blood cells are removed in a similar manner. The macrophages then degrade the foreign material and “present” it to B and T lymphocytes in the spleen.

Most of the immune response occurs in the lymph nodes and the spleen. Once the interaction has occurred between the APCs and the lymphocytes, differentiation of the B and T cells begins. The B cells develop into plasma cells, which are essentially antibody-producing factories, while T cells may undergo proliferation. Within the nodes, B and T cells are generally confined to specific areas: the outer cortex for B cells and the underlying paracortex for T cells. Embedded within the cortex are collections of primary nodules, which consist primarily of B cells. Once antigenic stimulation occurs, the cells within the nodules enlarge and proliferate, forming secondary follicles that surround germinal centers. These germinal centers enlarge as B lymphocytes mature and proliferate, and they account for the enlargement of regional lymph nodes in the event of infection. In addition, blood vessels within the node may become enlarged, increasing blood flow. Though some of the activated lymphocytes eventually find their way to the bloodstream, most remain within the lymphatic system. Antibodies produced in response to an infection, however, are transported to the blood.

Since lymph nodes serve as regions of drainage for local tissue, they also represent a route through the body for cancer cells that break away from a tumor. For example, cells from a breast cancer may lodge in regional lymph nodes of the neck or armpit and travel from there to other areas of the body. Although specialized types of lymphocytes capable of killing tumor cells are found in the nodes, some cancer cells may survive. It is for this reason that, during the removal of tumors, localized nodes are examined for evidence of metastasis. If no cancer cells are observed in the nodes, the chances are high that the cancer has not spread.

Mucosal associated lymphatic tissue (MALT) is found along mucosal membranes in regions of the intestines (Peyer’s patches and the appendix) and the throat (tonsils). The tonsils actually consist of a network of three groups of tissues that are located at the base of the tongue, at the back of the throat, and at the roof of the nasopharynx (adenoids). Like the spleen and the lymph nodes, MALT tissues may be sites of germinal centers. Unlike the spleen and lymph nodes, however, these tissues are not enclosed by defined capsules of connective tissue. They may be loosely organized, like the mucosa of the intestinal villi, or they may form organized regions like those of the tonsils and adenoids.

MALT appears to function to protect the body against respiratory or gastrointestinal agents. For example, agents such as bacteria or viruses that enter through the oral or respiratory route may stimulate an immune response by the tonsils. The swelling of the tonsils, tonsillitis, is the result of a localized immune response much like that found in the spleen or the lymph nodes. Germinal centers within the tissue represent areas of B cell maturation and proliferation. In the same way, the Peyer’s patches consist of approximately thirty to forty nodules along the wall of the intestines. Gastrointestinal antigens that penetrate the intestinal wall stimulate germinal centers in these regions.

Digestion products of carbohydrates and proteins are actively transported into the villi of the small intestine and enter the bloodstream directly. Fats, however, enter the blood in a more roundabout way through the lymphatic system. Fats are digested in the small intestine and diffuse into underlying cells. There they are assembled into triglycerides and, along with cholesterol, are enclosed in protein envelopes; the resulting bodies are called chylomicrons. Once these bodies pass into the lacteals of the lymphatic system, the whitish fluid, chyle, is transported to a region at the beginning of the thoracic duct called the cisterna chyli. It is here that the fat enters the bloodstream.

Disorders and Diseases

If the interstitial fluid—that is, the fluid in the tissues—increases beyond the capacity of the lymphatic system to handle the situation, an abnormal accumulation of fluid will build up in the tissue. This creates a situation known as edema. A variety of etiological factors can cause edema. For example, burns, inflammation, and certain allergic reactions may increase the level of capillary permeability. This is particularly true if a large amount of protein is lost as the result of a serious burn.

An increase in capillary hydrostatic pressure may also increase the rate of fluid buildup in the tissues. This may be a by-product of several conditions: congestive heart failure, renal failure, or the use of a variety of drugs (estrogen, phenylbutazone). For example, an increase in the sodium concentration of the blood caused by retention resulting from
renal failure or simply an excess of salt in the diet may cause water retention and increased blood volume. The sequelae include increased fluid leakage and edema. It is for this reason that a reduction in sodium intake is often recommended for those who suffer from this problem. Diuretics may be prescribed to promote the excretion of sodium and water. Similarly, venous obstruction as serious as phlebitis or as minor as the pressure from a tight bandage or clothing may increase hydrostatic pressure and lead to edema.

A buildup of fluid in the lungs, or
pulmonary edema, may occur as a result of congestive heart failure. Hydrostatic pressure in the capillaries of the lungs is relatively low when compared with that of the circulation elsewhere. As a result, the “wetness” of lung tissue is minimal. In patients with serious congestive heart disease, capillary fluid is backed up into the lung (and, indeed, in tissues of the extremities). The result is fluid leakage into the alveoli and bronchioles. Though the lymphatics are capable of removing small amounts of excess fluids, at some point the leakage of plasma and dissolved proteins exceeds the capacity of the lymphatic system to handle the problem. The result is a vicious circle. Since less oxygen is taken up through the lungs, capillary permeability increases. More fluid and protein are then lost. Unless intervention is carried out, the patient may eventually drown in his or her own fluids.

Intervention for pulmonary edema generally involves elevating the head and knees of the patient (Fowler’s position) and the administration of diuretics. A low-sodium diet, allowing for decreased fluid retention, may also relieve some of the stress on the lymphatic system. With time, the number of lymphatic vessels in the lungs may increase, allowing for a greater capacity to remove fluids.

A variety of disorders may directly involve the lymphatic system itself. Lymphedema, or the accumulation of lymph in tissue with subsequent swelling, may result from the absence of lymphatic vessels or from obstructions within the vessels. The symptoms of lymphedema, particularly in the lower extremities, include mild swelling that becomes increasingly severe with time. The problem may be exacerbated by menstruation or pregnancy. In some instances, lymphatic vessels may be absent, either congenitally or because of surgical removal. Diagnosis of the problem often requires the use of lymphangiography (lymphography). In this procedure, a contrast medium is injected, and the lymphatic vessels are examined by means of x-rays.

The etiologic factors associated with lymphatic obstruction may either be congenital or have external causes. Milroy disease is a hereditary lymphedema characterized by chronic obstructions. The obstruction of lymphatic vessels may also be caused by the presence of tumor cells or the infiltration of parasites. For example,
elephantiasis is caused by an infestation of a parasitic worm that obstructs the flow of fluid. The affected limb or region of the body may swell to an astounding degree.

The treatment of most of these disorders is essentially symptomatic. An obstruction may be treated or removed. Often, lymphedema may be treated by having the patient sleep with the feet elevated. A low-salt diet or diuretics may be indicated, and a light massage in the direction of lymph flow may also be helpful.

As is true for all tissues in the body, the cells and organs of the lymphatic system may also undergo malignant transformation. Any neoplasm of lymphoid tissue is referred to as a lymphoma. In general, these are malignant. Though lymphomas may be of different forms and involve different types of cells, they are characterized by enlarged lymph nodes (generally in the neck), fever, and weight loss. Among the more common forms of lymphomas are Hodgkin’s disease and non-Hodgkin lymphomas, a mixed collection of malignant solid tumors originating among the secondary lymphoid tissues of the lymph nodes. Hodgkin disease generally appears first among the cervical or axillary lymph nodes. Its manner of presentation usually allows for early diagnosis and treatment. As a result, the prognosis with early intervention has significantly improved since the 1960s.

Non-Hodgkin lymphomas often develop in less obvious areas of the lymphatic system, such as the gastrointestinal tract, the central nervous system, and the oral and nasal pharynx. The result is that diagnosis is often delayed until the disease has spread, and therefore the prognosis is less optimistic. According to the Lymphoma Research Foundation, 85 percent of non-Hodgkin lymphomas are of B-lymphocyte origin; they often arise within the follicles of the lymph node. There is some evidence that neoplastic transformation may be related to antigen exposure. In some instances, molecular defects of the cell DNA may result in the neoplastic event. Non-Hodgkin lymphomas may also be of T-lymphocyte or, less commonly, macrophage origin. Most treatments of lymphomas include both radiation therapy and chemotherapy.

Perspective and Prospects

The first description of the lymphatic system was made by the Italian anatomist Gasparo Aselli in 1622. Aselli observed the lacteals in the intestinal walls of dogs that he had dissected, and he included diagrams of the lacteals in his text De Lactibus (1627), the first anatomical medical text with color plates.

The role of the lymphatic system in maintaining the fluid dynamics of the body was understood by the beginning of the twentieth century. Much of this knowledge resulted from the early work of the British physiologist Ernest Henry Starling.

Beginning about 1900, Starling’s research centered on the secretion and circulation of lymph. It was known that the lymphatic system as a parallel to blood circulation was found only among the higher vertebrates. This indicated that it had developed relatively late during the course of evolution. There occurred, along with the increasing development of the body’s circulatory system as organisms evolved, an increase in the hydrostatic pressure within the system—that is, as the circulatory system became more complex, blood vessels branched into smaller and thinner capillaries. The pressure within those capillaries became higher. Starling pointed out the significance of the hydrostatic pressures within the capillaries: Fluids and dissolved materials leak out of the capillaries into the tissues.

Starling did not believe, however, that protein was able to leak through the capillary walls. In the 1930s, Cecil Drinker demonstrated that protein is a major constituent of dissolved material in lymph and suggested that an important role of the lymphatic system is the return of this protein to the bloodstream. Drinker was unable to prove definitively that the protein in lymph originated with the blood, and it remained for H. S. Mayerson to confirm this point in the 1940s.

Lymphocytes had been observed in the blood as early as the nineteenth century. Their role in the immune process was not readily apparent, however, and various functions were assigned to them. In 1948, Astrid Fagraeus demonstrated that lymphocytes mature into antibody-producing plasma cells. It remained unclear whether this was the sole purpose of these cells.

In 1956, Bruce Glick and Timothy Chang, working with chickens, discovered that an organ called the bursa, found near the cloaca in the region of the tail, was the site of the production of antibody-producing cells. Their discovery, along with those of Robert Good and Jacques Miller some years later, showed that lymphocytes are not all identical; at least two distinct populations exist. It remained for Henry Claman and his coworkers, in 1966, to demonstrate that these two populations of lymphocytes act cooperatively in the production of antibodies.

In 1969, Ivan Roitt called those lymphocytes that mature in the thymus gland T cells. The lymphocytes that mature in the bursa, an organ found only in birds, were called B cells. Since mammals lack the bursa, B cells in these organisms mature within the bone marrow (considered a bursa equivalent). Once the cells are released from the marrow, they migrate into both the lymphatic system and the bloodstream.

Bibliography

Delves, Peter J., et al. Roitt’s Essential Immunology. 12th ed. Malden, Mass.: Blackwell, 2011.

Dwyer, John M. The Body at War: The Story of Our Immune System. 2d ed. London: J. M. Dent, 1993.

Eales, Lesley-Jane. Immunology for Life Scientists. Hoboken, N.J.: John Wiley & Sons, 2003.

Gold, John C. Learning About the Circulatory and Lymphatic Systems. Berkeley Heights, N.J.: Enslow, 2013.

Janeway, Charles A., Jr., et al. Immunobiology: The Immune System in Health and Disease. 7th ed. New York: Garland Science, 2007.

Kindt, Thomas J., Richard A. Goldsby, and Barbara A. Osborne. Kuby Immunology. 6th ed. New York: W. H. Freeman, 2007.

Santambrogio, Laura. Immunology of the Lymphatic System. New York: Springer, 2013.

Venuta, Federico, and Erino A. Rendina. The Lymphatic System in Thoracic Oncology. Philadelphia: Saunders, 2012.

What was the effect of new technologies on warfare in World War I?

The development of new technologies affected the fighting in World War I. The Zeppelin airship allowed Germany to drop bombs on their enemies. The development of the machine gun gave more firepower to the soldiers fighting on the ground. With the use of trench warfare, the use of the machine gun had deadly consequences. Casualty rates were very high in some of the battles.

Other new technologies were also used. The use of chemical weapons, especially chlorine gas, had to be dealt with by the Allies. Gas masks were used to combat this weapon. Airplanes were used in World War I. The development of tracer ammunition allowed pilots to see where they were firing. This would help the pilots to be more accurate when shooting at their targets. Tanks were also used in World War I.

The Germans used the submarine in World War I. The submarine was designed to attack Allied ships without warning. This weapon struck fear into the hearts of the crews of the merchant marine. The Germans sunk several ships with their use of submarines.

What are Münchausen syndrome and Münchausen syndrome by proxy?

Introduction

Munchausen syndrome is often used interchangeably with factitious disorder; however, Munchausen syndrome describes a specific form of factitious disorder. Factitious disorders are characterized by the deliberate creation or simulation of physical or psychological symptoms.

In 1951, physician Richard Asher identified a pattern of patients who were fabricating medical histories and symptoms. He termed it Munchausen syndrome after Baron Münchhausen, an eighteenth-century Prussian cavalry officer who created fantastical stories about his exploits.

Munchausen syndrome represents one of the most severe form of factitious disorder, in which individuals complain of serious physical symptoms although they are aware that they are fabrications. It differs from malingering, in which patients deliberately report nonexisting symptoms, in its motivation. Malingerers seek specific rewards such as time off from work or monetary benefits; people with Munchausen syndrome are motivated by internal needs such as a desire for approval or attention.

The serious symptoms reported by those with Munchausen syndrome often result in multiple hospitalizations, and individuals may travel between hospitals or engage in “doctor shopping” to earn a desired diagnosis. Patients usually describe their symptoms in dramatic detail; they can be highly knowledgeable about symptoms, terminology, and procedures. However, they may become vague when questioned. They often eagerly accept recommendations for invasive procedures and may display multiple surgical scars. In extreme cases, individuals may sabotage their laboratory samples or aggravate existing symptoms. If they are hospitalized, few friends visit, and patients are reluctant to have medical professionals query prior medical providers. Tests often reveal no medical causes for the reported symptoms. After initial tests are negative, patients with Munchausen syndrome often will report that their previous symptoms are gone, but new ones have appeared. After medical professionals have failed to substantiate reported symptoms, patients are either released or diagnosed with Munchausen syndrome. If confronted, patients may deny the diagnosis of Munchausen syndrome or suddenly discharge themselves, only to seek another opinion.

Munchausen Syndrome by Proxy

In 1977, pediatrician Roy Meadow reported that one mother poisoned her child with salt and another injected her own blood into her baby’s urine. He termed this behavior Munchausen syndrome by proxy. Munchausen syndrome by proxy describes a condition in which caregivers create symptoms or actual illness in a person under their care. The caregiver is usually the mother, and the victim typically a child under the age of six; however, cases have occurred in which adults create or lie about illnesses in their elderly parents. The caregiver ensures that the child experiences afflictions that warrant medical attention and presents the child to medical authorities while claiming not to know how symptoms began. Rarely, those with Munchausen syndrome by proxy may be medical professionals who create symptoms in their patients.

Individuals with Munchausen syndrome by proxy may use their child’s illness as a way to gain sympathy. Their hospitalized child gets them attention from medical professionals, and they may use this as a way to earn praise for their devotion to the child’s care, often developing friendships with medical personnel. These caregivers may have previously experienced Munchausen syndrome themselves, but when they make their child ill, they learn that they can receive psychological rewards for playing the “hero” role.

Individuals with Munchausen syndrome by proxy may exacerbate a child’s condition by lying about symptoms, altering samples, feeding the child contaminated or poisoned food, or injecting the child with bacteria, causing symptoms such as gastrointestinal upset or infection. The child may improve while hospitalized but become ill again after discharge.

When confronted, individuals with Munchausen syndrome by proxy may become depressed and suicidal. Some respond with anger and hastily remove the child from medical care. Since Munchausen syndrome by proxy has a victim, it is considered a form of abuse and is a criminal offense. It is estimated that approximately 10 percent of victims of Munchausen syndrome by proxy die. In some cases, the child learns that sickness gains him or her attention and manifests Munchausen syndrome in adulthood. It has been recognized that children and adolescents may falsify their own illnesses and have Munchausen syndrome rather than be victims of Munchausen syndrome by proxy.

Possible Causes and Treatments

There are no reliable statistics on the prevalence of the disorders because of the inherent dishonesty involved. Individuals with these disorders may visit various hospitals, making any statistics suspect. The causes of both are also not known, but theories center on existing mental or personality disorders or a major life stress as possible origins. In some instances, the impulse to cause illness stems from rage, jealousy, or the desire to control others. Individuals with Munchausen syndrome may have had childhood illnesses that required extensive hospitalization or may have experienced family disturbances or abuse. Munchausen syndrome is associated with low self-esteem and severe emotional disturbances. It is very difficult to treat and often requires years of therapy. The patients’ first goal is to acknowledge that they are lying. Psychotherapy aids in working through underlying psychological issues. Family therapy might be indicated to teach family members not to reward “sick” behavior on the part of the patient. In Munchausen syndrome by proxy, the first concern is the victim’s safety. Psychotherapists, law enforcement, foster care organizations, and social workers all may be involved in treatment.

Bibliography

"Diseases and Conditions: An Overview of Factitious Disorders." Cleveland Clinic. Cleveland Clinic, 11 June 2013. Web. 3 Mar. 2014.

Doyle, Celia, and Charles Timms. Child Neglect and Emotional Abuse. London: Sage, 2014. Print.

Feldman, Marc. Playing Sick? Untangling the Web of Munchausen Syndrome, Münchhausen Syndrome by Proxy, Malingering, and Factitious Disorder. New York: Routledge, 2004. Print.

Gregory, Julie. Sickened: The True Story of a Lost Childhood. New York: Bantam Books, 2004. Print.

Kamm, F. M. Bioethical Prescriptions: To Treat, End, Choose, and Improve Lives. Oxford: Oxford UP, 2014. Print.

Lasher, Louisa J., and Mary S. Sheridan. Munchausen by Proxy: Identification, Intervention, and Case Management. New York: Haworth Maltreatment and Trauma Press, 2004. Print.

Olsen, Gregg. Cruel Deception: A Mother’s Deadly Game, a Prosecutor’s Crusade for Justice. New York: St. Martin’s True Crime, 2005. Account of a mother whose daughter died suddenly of suspected sudden infant death syndrome (SIDS) and whose newborn son then developed the same symptoms. Details the criminal aspects of Munchausen syndrome by proxy, including trial and aftermath.

Shaw, R., et al. “Factitious Disorder by Proxy: Pediatric Condition Falsification.” Harvard Review of Psychiatry 16 (July, 2008): 215-224. This comprehensive overview of Munchausen syndrome by proxy discusses definitions and causes, and gives information on assessment, legal issues, and treatment.

What happens at the end of Charles Dickens' Great Expectations?

Pip goes to Cairo and Estella marries someone else.

There are two endings of the book.  Charles Dickens was advised by a friend to make the ending a little happier, so he revised it.  However, in both endings Pip and Estella do not get together. 

In the revised ending, we are told that Pip has “no shadow of another parting from her” but this is not an indication that they get together.  The conversation between Pip and Estella indicates that.

“… I have been bent and broken, but—I hope—into a better shape. Be as considerate and good to me as you were, and tell me we are friends.”

“We are friends,” said I, rising and bending over her, as she rose from the bench.

“And will continue friends apart,” said Estella. (Ch. 59)

When Pip returns to Satis house, it is being demolished.  Estella is there overseeing it, and she will build on the site.  After Drummle died, Pip was aware that Estella had married again.

Pip tells Estella that he still lives abroad.  He never married.  Herbert married Clara, and Joe married Biddy.  Joe and Biddy had a son they named Pip.  Pip came back to visit them.

Pip and Estella agree to remain friends.  However, Pip will still live in Cairo and Estella has her own life.  It is a happy ending in that the two of them have settled into life and are doing well enough, even though they cannot be together.

Readers should appreciate that both Pip and Estella are broken psychologically.  They have done as well as could be expected as adults after their difficult childhoods.  An ending where Pip and Estella marry would not make sense.  Estella told Pip she could not love.  Pip loves her, but understands that he can’t have her.  He has to be content with them being friends apart.

How did the United states react to the Soviet Union exploding its first atomic bomb?

The first successful test of an atomic bomb in the Soviet Union occurred in 1949. This caused great fear and consternation in the United States, as most experts believed the Soviets lagged far behind the Americans in atomic expertise. Fears were intensified when it was discovered that spies within the Manhattan Project, notably Klaus Fuchs, had passed atomic secrets to the Soviets that greatly sped up their efforts. So the explosion of the bomb, along with the victory of Communist revolutionaries led by Mao Zedong in China in the same year, contributed to American fears that the nation was losing the global struggle against Communism. This gave rise to the Second Red Scare, a period of intense anti-Communist hysteria. But perhaps more importantly, it convinced American policy-makers that the nation needed to commit more resources to building a military that could counter the Soviet threat. This commitment was embodied by NSC-68, a memo from the National Security Council to President Truman emphasizing the threat posed by the Soviets, and recommending that the nation be placed, essentially, on a war footing. It began a nuclear "arms race" that would only intensify during the Eisenhower Administration. 

How does the novel introduce the conflict between the Socs and greasers in The Outsiders?

The conflict between the greasers and Socs is introduced when Johnny and Pony meet the Soc girls at the movie theater. 

Pony gives us some background about the differences between greasers and Socs before going to the movies.  He explains that greasers are in danger from Socs. For this reason, he is nervous about walking without his gang. 

Greasers can't walk alone too much or they'll get jumped, or someone will come by and scream "Greaser!" at them, which doesn't make you feel too hot, if you know what I mean. We get jumped by the Socs… the jet set, the West-side rich kids. (Ch. 1) 

At the movies, Pony and his friend Johnny, another greaser, meet two Soc girls named Cherry and Marcia.  The girls are kind to Johnny and Pony, but do not like Dally.  Dally behaves crudely toward them and Johnny stands up for them.  Cherry asks Pony why he is friends with someone like Dally. 

Cherry was looking at me. "What's a nice, smart kid like you running around with trash like that for?"

I felt myself stiffen. "I'm a grease, same as Dally. He's my buddy." (Ch. 2) 

Although Cherry apologizes, this incident helps the reader understand the Socs perception of greasers.  There are no physical fights here, but there is still a class conflict.  The girls are there without their boyfriends because their boyfriends were drunk.  They know that the boys would not approve of them hanging out with greasers, but they personally do not mind the greaser boys.  Cherry and Pony discuss what they have in common. 

The conflict comes to a head when they are leaving, and the Soc boys return.  The girls know that there will be a problem with them hanging around with greaser boys.  Johnny is also frightened because Bob and his group jumped him before and hurt him badly.  The girls avoid a fight by going with the Soc boys, but that is not the end of it.  Bob and Randy later fight Pony and Johnny in the park.

Why were women's roles so neatly contained to the domestic sphere in the 1950s?

The largely domestic role of married women in America in the 1950s was due in large part to the return to the home front of millions of men who had fought in World War Two, retaking the jobs that they had vacated in order to fight. In many ways, the role of American women in the workplace during both World War One and during World War Two was anomalous, and the relative prosperity that most Americans enjoyed during the 1950s made it possible for most families to live off of one income, the husband's.

Yet the notion that all women stayed at home is a false and misleading one. It is more accurate to say that most all married women were confined to raising their children and keeping up the house. Single women, unless they came from wealthy families, still worked outside of the house in various jobs, but they were paid badly and often treated worse, so even those who did not particularly want to get married and raise a family came under great societal pressure to do so, for economic reasons.

Additionally, the Cold War, which began right after World War Two, was a time characterized by intense pressure to conform to societal norms or face being ostracized and even punished. The role of the family and mother was elevated to an almost worshipful level, partly in order to differentiate the American, capitalist system from the Soviet system, in which the worker was deemed to be of paramount importance. The American propaganda machine that idealized family life in American was powerful and wide reaching. So was paranoia about possible Russian spies on the home front. Due to the fact that domestic politics revolved around anti-Soviet sentiment and fear of nuclear annihilation, the price of non-conformity was very high indeed. The U.S. government maintained that the nuclear family was the basic building block of American society, and that upholding "American family values" was essential to maintaining societal cohesion and defeating the Soviets.

Thus, many American women who tried to pursue careers outside of the home or to have relationships with men outside of marriage were not only shunned by their families and neighbors, but sometimes even institutionalized by their families for behavior that society and even the medical community considered pathological. In essence, women faced the proverbial carrot and stick: in order to partake of the economic boom that was taking place, women had to marry, and in order to avoid being marginalized by society, women had to marry. To do otherwise required financial independence and/or the courage to live a solitary, lonely existence.

What is the theme of Frindle with examples?

The primary theme of the book Frindle is that words have power.  Nick asks his teacher, Mrs. Granger, who invents words.  He asks who decided that the word "dog" referred to the pet.  Mrs. Granger tells him that she, him, and "'everyone in this class and this school and this town and this state and this country'" are the ones who decide what words mean.  She tells him that people "'decide what goes in that [dictionary].'"

With this information in mind, Nick invents a new word, frindle.  This word describes a pen.  He and his classmates start calling "pens" "frindles," much to the annoyance of their teacher.  The word becomes more and more popular.  Soon all the kids at school are using the word frindle.  Nick becomes famous.  He goes on the radio and television to talk about frindles.  There is frindle merchandise and a licensing deal.  Nick becomes wealthy from frindles.

Nick proves that words have power.  He starts with a simple word, but in the end he becomes a person of influence.  He becomes wealthy and powerful because of one word.

When dilute sulfuric acid reacts with marble, carbon dioxide gas is produced. Out of the choices below, which will increase the rate of reaction...

The rate of a chemical reaction is increased by factors that increase the rate of collisions between reactant particles or that result in higher energy collisions. Some examples are:

• Shaking or stirring the reaction mixutre


• increasing the temperature of the reaction mixture


• increasing the concentration of one or more reactants


• increasing the surface area of a solid reactant

Let's look at the possibilities given in the problem:

Using a larger or smaller open container for reactants in aqueous solution doesn't affect the frequency or energy of collisions between particles so neither of these will significantly affect the rate of the reaction. 

Using powdered marble will increase the rate of the chemical reaction because it results in more surface area, increasing the number of collisions with the acid particles.

Using larger marble chunks will decrease the rate of the chemical reaction because it results in less surface area so the number of collisions between reactant particles will decrease.

Why is Fitzgerald's style in The Great Gatsby described as "lushly evocative"?

First of all, let's define lush and evocative; I Googled the words and found these definitions:

lush: "very rich and providing great sensory pleasure"

evocative: "bringing strong images, memories, or feelings to mind"

Clearly, the critic describing Fitzgerald's work was praising the author's ability to captivate his readers and transport them to the fictional world he creates, introducing them to characters richly drawn and easy to envision. In The Great Gatsby, he makes Tom Buchanan leap off the page with this description from chapter one:

"Now he was a sturdy straw-haired man of thirty with a rather hard mouth and a supercilious manner. Two shining arrogant eyes had established dominance over his face and gave him the appearance of always leaning aggressively forward. Not even the effeminate swank of his riding clothes could hide the enormous power of that body--he seemed to fill those glistening boots until he strained the top lacing, and you could see a great pack of muscle shifting when his shoulder moved under his thin coat. It was a body capable of enormous leverage--a cruel body."

Through superb diction, Fitzgerald is able to convey not only his commanding physical presence, but also his menacing personality and egotism without having Tom Buchanan utter a single word. Fitzgerald's description of Tom Buchanan's physique, the way his clothes fit his body, the arrangement of his facial features, his posture and movement--even the texture of his hair--"lushly evoke" the character rather than simply describing him.

Fitzgerald, F. Scott. The Great Gatsby. Charles Scribner's Sons, 1925.

In "The Lottery," how long had the people been using the box?

Nobody knows exactly how long the current box has been in use.  The only specific detail that the reader is told about the age of the box is that it has been in use for a long time.  The box has been in use since before Old Man Warner was born.  That is a significant amount of time, because Old Man Warner is the oldest man in the entire town.  

. . . and the black box now resting on the stool had been put into use even before Old Man Warner, the oldest man in town, was born.

Of course being the oldest man in a town that practices a raffle to stone people to death might mean Old Man Warner isn't that terribly old.  But in this case, Old Man Warner is indeed an old man.  While Old Man Warner's exact age isn't specifically stated, the reader is told that he is participating in his 77th lottery.  That means the box is at least 78 years old.

A bit later in that same paragraph, Jackson provides further evidence that the box is indeed quite old and well used.  The text explains that the wood is splintered badly and faded in odd locations, which is evidence of age and dry rot.  

The black box grew shabbier each year: by now it was no longer completely black but splintered badly along one side to show the original wood color, and in some places faded or stained.

In Harper Lee's To Kill a Mockingbird, how does Scout make Mr. Cunningham stand in Atticus' shoes?

In Chapter 15 of Lee's To Kill a Mockingbird, Jem, Scout and Dill discover Atticus sitting outside of the Maycomb jail on the Sunday night before the Robinson trial is to take place. When a group of Cunninghams show up, Scout runs to her father to check out the situation. Scout doesn't know that the Cunninghams are there to lynch Tom before the trial can even take place. Once she senses trouble, she becomes a chatterbox. She identifies Walter Cunningham in the crowd and tells him that she is friends at school with his son. The presence of children in an adult situation, plus the fact that Scout brings up Walter, Jr. in conversation, reminds Mr. Cunningham of what is most important in life--family and the fact that he is a father. 

Then, without much to say, Scout unleashes the ramblings of her mind and talks to Mr. Cunningham about his legal problems. Since Atticus has very kindly and patiently helped Mr. Cunningham in the past, Scout reminds him of what Atticus stands for. Atticus is a good father, a kind friend, and a fair and generous lawyer. This might bring to Mr. Cunningham's mind how Atticus has allowed him to pay his legal fees in-kind; that is to say, he is allowed to pay with goods and services rather than money. By reminding Mr. Cunningham first of his son and then of Atticus's goodness and quality of character, Scout helps to soften Mr. Cunningham's heart to the point that he calls off the mob. These topics of conversation help Mr. Cunningham to see Atticus as a father and good person rather than a lawyer standing in the way of him and his plan to lynch a black man. Of this experience Atticus says the following:

"So it took an eight-year-old child to bring 'em to their senses, didn't it? . . . That proves something--that a gang of wild animals can be stopped, simply because they're still human. Hmp, maybe we need a police force of children . . . you children last night made Walter Cunningham stand in my shoes for a minute. That was enough" (157).

What is a quote from Mark Twain's The Adventures of Tom Sawyer that shows that Tom is naïve?

Intriguing question! In the book The Adventures of Tom Sawyer by Mark Twain, numerous quotes throughout the book demonstrate Tom being naïve.

Foremost, Tom is shown as naïve when it relates to his superstitious beliefs. For example, Tom believes that actions must be done in certain ways or during certain times due to superstition. Tom fears that if he does not follow his superstitious beliefs that his plans will go awry. For example, while searching for buried treasure, Tom illustrates that his idea is not wrong, but that witches are interfering with his plan. As the text reveals:

“It is mighty curious, Huck. I don’t understand it. Sometimes witches interfere. I reckon maybe that’s what’s the trouble now.”

Furthermore, Tom is naïve about relationships, especially marital relationships. This is especially seen in his relationship with Becky Thatcher and his conversations with Huck. For example, Tom believes that he will find a girl that never argues with him. Furthermore, he illustrates that when he is married, Huck will simply come live with them. As Tom’s conversation with Huck reveals:

“'Only if you get married I’ll [Huck] be more lonesomer than ever.’

‘No you won’t. You’ll come and live with me [Tom].'”

Thus, Tom appears naïve throughout the story. Although Tom is quite clever, his naïve beliefs impact his actions. For example, Tom often blames supernatural forces for plans going awry, instead of realizing his own planning flaws. Furthermore, he appears naïve about marital relationships, perhaps due to his own lack of parents.

What are Malassezia?

Definition

Malassezia are lipophilic, dimorphic fungi that
are found as normal flora on the skin of humans and other mammals. These
fungi can cause a variety of skin conditions and systemic infections in special circumstances.

Natural Habitat and Features

Malassezia are lipophilic yeasts. Most species depend upon saturated fatty acids for growth.
They are found as part of the normal flora of the skin of humans and other mammals
in areas where sebaceous glands secreting sebum are located. Sebum is composed of
triglycerides and esters. Malassezia
lipases degrade triglycerides into both unsaturated and saturated fatty acids. The
Malassezia consume the specific saturated fatty acids and
leave the unsaturated fatty acids on the skin.

Since discovery of the fungi in 1874, thirteen Malassezia sp.
have been described. Four species, caprae,
equina, nana, and
pachydermatis, are associated with animals, and the other
species are found as human commensals and as opportunistic pathogens. Human colonization begins
shortly after birth and is maintained throughout adulthood. Certain diseases, such
as diabetes
mellitus or human immunodeficiency virus infection,
may encourage the yeasts to grow, as may treatment with drugs, such as
corticosteroids or cancer chemotherapy, that impair the
immune system. Systemic infection may occur in association with vascular
catheters, particularly when intravenous lipids are administered.

While Malassezia are classified as yeasts, they are dimorphic fungi occurring as both saprophytic yeasts and parasitic mycelia. The yeast forms vary from spherical to ovoid and reach diameters of 8 micrometers (m). The yeasts multiply by monopolar budding. The presence of a prominent collarette at the budding site helps to distinguish them from Candida glabrata, which is otherwise similar in appearance. The hyphae are short and septate with occasional branching and are 2.5 to 4 m in diameter. Parker’s ink, Gomori’s methenamine silver, or periodic acid-Schiff (PAS) stains can all be used to aid in microscopic visualization of the organisms from specimens such as skin scrapings or punch biopsies.

The fungi are difficult to culture; a source of lipid must be added to meet their growth requirements. Sabouraud’s dextrose agar can be overlaid with sterile olive oil or other media, including Leeming-Norman, Dixon agar; Littman oxgall may be employed. Colonies comprising budding yeasts grow slowly, maturing in five days at 86° to 98.6° Fahrenheit (30° to 37° Celsius). They initially appear as small, smooth, creamy colonies and later become dull and wrinkled with a tan or brownish coloration. Colonial and microscopic morphology, growth requirements, biochemical tests, and molecular tests have all been used for the identification of various species.

Pathogenicity and Clinical Significance

Sebaceous
glands cover the human body, with the exception of the palms
of the hands and the soles of the feet. The secretion of sebum is under glandular
control. Activity begins at birth under control of maternal androgens and then
declines until puberty. Secretion remains steady until middle age, when androgens
decrease and sebum production declines. In women, the decline is linked to
menopause, but in men the decline occurs somewhat later.

Dandruff and seborrheic dermatitis are superficial infections with Malassezia species that are associated with the hyperproliferation of the cells of the epidermis, which results in flaking of the skin. When Malassezia shift the composition of sebum to a preponderance of unsaturated fatty acids, these fatty acids alter the skin barrier and create inflammation and ultimately hyperproliferation and flaking of the skin. These two conditions affect up to 50 percent of the population at some time in their lives, and they are most common during those years of highest sebaceous gland activity. While dandruff affects only the scalp, seborrheic dermatitis can involve the scalp, eyebrows, nose, external ears, and even the trunk and groin areas. M. globosa and M. restricta are the most common species identified. The diagnosis may be confirmed by microscopic examination of skin scrapings that reveal the round yeasts.

Pityriasis versicolor is a superficial infection of the skin covering the trunk and proximal extremities in young adults. The infection is associated with transformation of the yeast to the mycelial phase, but the factor or factors inciting the change is unknown. A fatty acid metabolite of Malassezia, azeleic acid, is responsible for the depigmentation of the skin lesions. M. globosa is the species found in the majority of infected persons. In most cases the diagnosis is made clinically, but confirmation can be obtained by observing round yeast forms accompanied by short hyphae elements on microscopic examination of skin scrapings.

Neonatal cephalic pustulosis, or
neonatal acne, occurs in about 3 percent of hospitalized neonates. The condition is a pustular eruption involving the face, neck, and scalp. Maternal hormones stimulate neonatal sebum production, facilitating Malassezia growth after being introduced to the fetus during pregnancy or passed on by health care workers. The diagnosis is made on the basis of the clinical appearance of the skin lesions, smears showing yeasts on microscopic examination, and response to topical antifungal therapy. M. sympodialis has been the species associated with more severe cases, while M. furfur is found in mild cases or in asymptomatic infants.

Severely ill neonates or adults receiving infusions of intravenous lipids to provide parenteral nutrition are at risk for systemic infection through the bloodstream by Malassezia. While the lipid emulsions are not intrinsically contaminated, they do support the growth of Malassezia by providing them with fatty acids. The impaired immune systems of severely ill persons may allow systemic spread of the infection.

Most conventional blood culture systems have poor cultural yields for these organisms. Lysis-centrifugation with subsequent culture onto lipid supplemented media, or the addition of lipids to the broth used for blood culture, may provide a higher yield. Blood cultures obtained through the central venous catheter used for hyperalimentation are more likely to be positive than are peripheral vein samples. Additionally, buffy coat smears have revealed yeast forms in the blood of some infants. M. furfur is the species usually found.

Domestic pets, especially dogs, are colonized and sometimes infected with Malassezia. Canine ear and skin infections are commonly observed and treated by veterinarians. M. pachydermatis is the usual species, and because this species is uncommon in human infections, canine transmission is thought to be of minimal importance.

Drug Susceptibility

Malassezia are uniformly susceptible to the azole class of
antifungal agents. Ketoconazole is the most commonly used azole in the treatment
of the various types of infection caused by these organisms. Ketoconazole shampoo
and cream are employed for superficial infections such as dandruff,
seborrheic dermatitis, and neonatal cephalic pustulosis. Ketoconazole cream may
also be successfully used for the treatment of pityriasis versicolor, but more
extensive or persistent cases should be treated with oral itraconazole or
fluconazole. In cases of systemic infection associated with lipid infusions, the
contaminated central venous catheter should be removed and intravenous antifungal
therapy with an agent such as fluconazole commenced.

Bibliography

Hibbett, David S., et al. “A Higher-Level Phylogenetic Classification of the Fungi.” Mycological Research 111 (2007): 509-547. A complete classification of fungi.

Inamadar, A. C., and A. Palit. “The Genus Malassezia and Human Disease.” Indian Journal of Dermatology, Venereology, and Leprology 69 (2003): 265-270. A short general review of diseases caused by Malassezia.

Larone, Davise H. Medically Important Fungi: A Guide to Identification. 4th ed. Washington, D.C.: ASM Press, 2002. A standard guide with illustrations.

Naldi, Luigi, and Alfredo Rebora. “Seborrheic Dermatitis.” New England Journal of Medicine 360 (2009): 387-396. Comprehensive review of effective treatments for dandruff and seborrheic dermatitis.

Ro, Byung In, and Thomas L. Dawson. “The Role of Sebaceous Gland Activity and Scalp Microfloral Metabolism in the Etiology of Seborrheic Dermatitis and Dandruff.” Journal of Investigative Dermatology Symposium Proceedings 10 (2005): 194-197. An excellent scientific explanation of the metabolic relationship of Malassezia to the skin.

What are three things that Nicolaus Copernicus invented or discovered that impact our lives today?

Nicolaus Copernicus, who lived from 1473 to 1543, was quite the rebel in his day! Copernicus lived in a time when most people believed that the Earth was the center of the universe. As an astronomer who frequently watched the skies, he didn't think this theory held up. Instead, Copernicus proposed a heliocentric theory, which held that the Sun was the center of the universe and planets orbited around it. He was almost correct! Our planet (and the others in our solar system) do, in fact, orbit around the Sun. However, the Sun is not at the center of the universe. Copernicus was the first to propose this heliocentric theory, and it has lead directly to our understanding of our solar system and the universe today.

Copernicus' heliocentric theory was proposed in his book titled On the Revolutions of the Celestial Spheres. This book went beyond simply saying that the Sun was the center of the universe, and created and justified an entirely new system of understanding the layout of our solar system. He explained that the apparent movement of the Sun in its rise and fall is not a result of any motion of our star, but actually the result of Earth's movement. Copernicus described that we experience years as a result of Earth's revolution, and we experience days (and nights) as a result of Earth's rotation on its axis. 

Copernicus also described that the apparent motions of other planets are dependent upon Earth's own motions. When we keep track of planetary motions and find that a planet has gone into "retrograde," or appears to be moving backwards or falling behind, this is the result of our own planet overtaking another in orbit. The planets do not orbit at the same speed on their various tracks, so sometimes Earth passes by another planet from a distance, creating the illusion that the planet is moving backwards.

It may seem strange to us today that Copernicus introduced all of this as new information, because we have been taught all of this as truth! In his day, it was quite shocking information and even caused some amount of scandal among the Catholic Church.