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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
October 13, 2012

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As Always, Asymptomatic Bacteriuria Is Best Ignored
Proton-Pump Inhibitors Often Are Prescribed Inappropriately at U.S. Teaching Hospitals
Celebrate Global Handwashing Day with a Trip to the Sink
Flu Vaccine Benefit Is "Modest"
Metabolic Syndrome Linked with Brain Abnormalities in Adolescents
Midlife Cardiovascular Fitness Predicts Healthy Aging
Chlorhexidine (CHG) Bathing Decreases Nosocomial Clostridium Difficile Infections (CDIs)
Sarcopenia During Androgen Deprivation Therapy
New Data Suggest Safety of Hormone Therapy in Early Menopause
Free Highly Effective Reversible Contraception: Conquering a Barrier
The Sex Difference in Depression and Anxiety Explained?
Apple a Day Cut Harmful Cholesterol

MM: In general I agree with the conclusions of this article with the addendum that if intervention is desired, the first step should be D-mannose powder or capsules. D-Mannose is generally effective for e.coli infections that tend to make up 75-80% of most common or uncomplicated urinary tract infections. Bacteria do not become resistant to it and super-infections are not created. For more information, dosing or guidelines of use of D-Mannose for UTI’s, please contact Mark Drugs Pharmacy.
Clin Infect Dis 2012 Sep 15; 55:771
As Always, Asymptomatic Bacteriuria Is Best Ignored
A study in healthy young women confirms that treatment leads to trouble.
Many clinicians treat patients who have asymptomatic bacteriuria (AB), but studies have confirmed that AB treatment provides no benefit in many groups, including older people, diabetic patients, and those with spinal cord injuries. Similar evidence now is provided for healthy young women with recurrent urinary tract infections (UTIs).
Almost 700 sexually active premenopausal women with AB who presented to a single Italian clinic were randomized to receive unblinded treatment or to be followed without treatment. All participants had experienced at least one UTI in the previous year. Those who were treated received oral antibiotics, to which their microbial isolates were confirmed to be sensitive.
After 3 months, 3.5% of untreated women and 8.8% of treated women experienced new symptomatic UTIs. The curves continued to diverge: By 1 year of follow-up, UTI recurrence rates were dramatically higher in the treated group (by our calculations from the data provided, cumulative UTI recurrence rates were 24% in the untreated group and 83% in the treated group). Rates of pyelonephritis were similar between groups.
At the beginning of the study, most bacterial isolates wereEscherichia coli (39%) or Enterococcus faecalis (33%). One year later, urine samples from most recurrence-free patients in the nontreatment group grew E. faecalis, whereas most samples from the few treated patients who were recurrence free grew E. coli.
Comment: This study adds sexually active young women to the list of those in whom asymptomatic bacteriuria should not be treated — in fact, treatment was harmful in this study. Treatment now is endorsed only during pregnancy and before urinary instrumentation. Editorialists link this insight to the developing understanding of the human microbiome and bacterial interference, in which colonizing nonpathogenic bacteria often defend against local infection far better than antibiotics do. Is E. faecalis a colonizer to be valued? Further studies will tell us.
— Abigail Zuger, MD Published in Journal Watch General Medicine October 11, 2012
Citation(s): Cai T et al. The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: To treat or not to treat? Clin Infect Dis 2012 Sep 15; 55:771.
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J Hosp Med 2012 May/Jun; 7:421
Proton-Pump Inhibitors Often Are Prescribed Inappropriately at U.S. Teaching Hospitals
Most prescriptions for PPIs lacked a valid indication.
Stress ulcer prophylaxis has demonstrated efficacy in critically ill patients who are at high risk for gastrointestinal bleeding (e.g., mechanical ventilation >48 hours, coagulopathy). Prophylaxis in general ward patients also has become common, despite the lack of evidence to support this practice.
Researchers performed a retrospective review of administrative data for hospitalized adult patients discharged from the internal medicine service at one hospital in Colorado and from hundreds of academic health centers and their affiliated hospitals that participate in the University HealthSystem Consortium (UHC). In 2008 and 2009, more than 6.5 million patients in the UHC met inclusion criteria. Among those who were prescribed proton-pump inhibitors (PPIs) at discharge, 73% had no valid indication. Results were similar for the 9875 patients discharged from the Colorado hospital — detailed chart reviews of >100 patients revealed that the main justification for prescribing PPIs at discharge was prophylaxis (56%). Moreover, Clostridium difficile–associated diarrhea (CDAD) occurred significantly more often in patients who received PPIs than in other patients.
Comment: This study reinforces that inpatient providers overprescribe PPIs without relevant indications. These relatively recent data, largely from academic teaching hospitals, imply that this practice persists among providers after training. Recent literature suggests substantial untoward effects of PPIs, including demonstrated association with CDAD, nosocomial pneumonia, electrolyte abnormalities, drug interactions, and fractures. Furthermore, once started, PPIs frequently are continued indefinitely. Healthcare providers and healthcare systems must take steps to prescribe PPIs according to guidelines (Am J Health Syst Pharm 1999; 56:347) and put systems in place to discontinue them when no longer indicated. Doing so would prevent unnecessary morbidity and healthcare costs.
— Aaron J. Calderon, MD, FACP Published in Journal Watch Hospital Medicine October 5, 2012
Citation(s): Reid M et al. Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med 2012 May/Jun; 7:421
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Celebrate Global Handwashing Day with a Trip to the Sink
Break out the soap. MMWR is reminding readers that October 15 is Global Handwashing Day. It was first observed 5 years ago to raise awareness of how good hand hygiene can prevent disease.
The fifth annual Global Handwashing Day will be observed on October 15, 2012. This observance increases awareness and understanding of handwashing with soap as an effective and affordable method of preventing disease around the world.
Handwashing with soap has an important role to play in child survival and health. About 2.2 million children aged <5 years die each year from diarrheal diseases or pneumonia, the top two killers of young children worldwide (1). Handwashing is not only simple and inexpensive, but handwashing with soap can reduce the incidence of diarrhea by 30% (2) and respiratory infections by 21% (3) among children aged <5 years.
Although persons around the world clean their hands with water, very few use soap to wash their hands. Washing hands with soap removes bacteria much more effectively (4).
Additional information on Global Handwashing Day is available from CDC at 
References: 1.) Liu L, Johnson HL, Cousens S, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012;379:2151–61.  2.)  Ejemot RI, Ehiri JE, Meremikwu MM, Critchley JA.  Hand washing for preventing diarrhoea. Cochrane Database Syst Rev 2008;(1):CD004265.  3.)  Aiello AE, Coulborn RM, Perez V, Larson EL. Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis. Am J Public Health 2008;98:1372–81.  4.) Burton M, Cobb E, Donachie P, Judah G, Curtis V, Schmidt WP. The effect of handwashing with water or soap on bacterial contamination of hands. Int J Environ Res Public Health 2011;8:97–104.
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Clin Infect Dis 2012 Oct 1; 55:951
Flu Vaccine Benefit Is "Modest"
The antigenically well-matched influenza vaccine from the 2010–2011 season was about 60% protective.
Formulation of the seasonal influenza vaccine is a bit of a guessing game, and sometimes antigenic mismatch between vaccine and circulating flu strains is cited to explain suboptimal vaccine performance. But the vaccine used during the 2010–2011 season was well matched to circulating strains: So how did it perform?
Researchers at four large U.S. medical centers ascertained vaccine status among almost 5000 infants, children, and adults who presented with flu-like illness during the 2010–2011 flu season; they used standard polymerase chain reaction techniques to diagnose acute influenza A or B. Overall, about 30% of flu cases occurred in vaccinated people. The overall age-adjusted efficacy of either inactivated or live-attenuated vaccine was estimated to be 60% (with use of a standard case-control strategy). All age groups showed roughly similar efficacy except for older people (age, ≥65), in whom the vaccine essentially was ineffective. However, the paucity of patients in this age group (<5% of the whole cohort) might have influenced this finding.
Comment: These results are similar to efficacy results during other well-matched flu vaccine seasons (and contrast with studies of poorly matched vaccines, which have an estimated efficacy <30%). However, the researchers concede that the overall "level of benefit could be described as modest" and note that the consistent finding of poor efficacy among older adults is concerning.
— Abigail Zuger, MD Published in Journal Watch General Medicine October 11, 2012
Citation(s): Treanor JJ et al. Effectiveness of seasonal influenza vaccines in the United States during a season with circulation of all three vaccine strains. Clin Infect Dis 2012 Oct 1; 55:951.
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MM: A frequent mantra of educators is that standard test performance is directly related to zip code and socio-economic status. With the striking conclusions that may potentially be drawn from this study, one must question to see what the demographics of the study are and if there is such a cross reference.
Pediatrics 2012 Oct; 130:e856.
Metabolic Syndrome Linked with Brain Abnormalities in Adolescents
Adolescents with metabolic syndrome had lower cognitive performance and reductions in brain structural integrity compared with matched controls.
Metabolic syndrome is associated with cognitive dysfunction in middle-age and older adults, but the association has not been studied in children. Investigators compared brain structure and cognitive performance in 49 adolescents with metabolic syndrome (age range, 14–20 years; 63% female; 84% Hispanic) and 62 matched controls without metabolic syndrome. Metabolic syndrome was defined as at least three of the following five criteria: waist circumference ≥90th percentile for age and gender; HDL level <50 mg/dL (girls) or <40 mg/dL (boys); serum triglyceride levels >110 mg/dL; blood pressure (BP) ≥90th percentile for age, gender, and height (for age <18 years) or BP ≥130 mm Hg systolic, BP ≥85 mmHg diastolic, or the use of antihypertensive medication (for age ≥18 years); and insulin resistance. Adolescents with other medical problems, Tanner stage <4, history of depression, or learning disabilities were excluded.
Mean body-mass index (BMI) was 38.4 kg/m2 in the metabolic syndrome group and 27 kg/m2 in controls. Adolescents with metabolic syndrome scored significantly lower on measures of math and spelling achievement and on measures of attention and mental flexibility (components of executive functioning). Mean estimated full-scale IQ was 106 in the control group and 102 in the metabolic syndrome group (a nonsignficant difference). On magnetic resonance imaging scans, adolescents with metabolic syndrome had significantly smaller hippocampal volumes, larger CSF volumes, and diminished fiber organization in such white matter fiber tracts as the corpus callosum, optic radiations, and medial longitudinal fasciculi. Differences remained after controlling for blood pressure and self-reported sleep apnea symptoms. In linear regression, abnormalities in structure and function were even more pronounced in adolescents who met four or five metabolic syndrome criteria.
Comment: On the basis of additional analyses, the authors speculate that obesity or hypertension may be sufficient to affect cognitive performance, whereas some degree of metabolic dysregulation is necessary to result in structural changes. If confirmed, these findings add more urgency to prevent and treat obesity. From a behavior-change perspective, these results may provide powerful motivation for some obese adolescents (and their families) to make necessary lifestyle changes.
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine
October 10, 2012
Citation(s): Yau PL et al. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics 2012 Oct; 130:e856.
(http://pediatrics.aappublications.org/content/130/4/e856 )
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MM: Apparently, it’s almost never too late to benefit from healthier activities and lifestyles. Remember, skinny on the outside does not necessarily mean that the inside is not fat. If a person fails to exercise, at least moderately, irrespective of how thin they are, they run the risk of diminishing their health and increasing their risk of chronic disease. This study indicates that exercise may serve to improve the quality of life even more that we realize.
Arch Intern Med Sep 24; 172:1333.
Midlife Cardiovascular Fitness Predicts Healthy Aging
Better fitness was associated with lower risk for chronic conditions during the next 26 years.
Robust midlife cardiovascular (CV) fitness is associated with lower cardiovascular-related mortality, but what about morbidity? Researchers assessed relations between fitness and several chronic conditions (ischemic heart disease, congestive heart failure, stroke, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, Alzheimer disease, and lung or colon cancer) in older individuals by linking a preventive medicine registry to Medicare data. About 19,000 participants (mean age at entry, 49; 79% men) received full baseline fitness and medical assessments and were stratified into five quintiles of fitness. Most participants had relatively favorable CV risk profiles at entry.
During a median 26-year follow-up, participants in the highest fitness quintile had about half the prevalence of chronic conditions than did those in the lowest quintile. In adjusted analyses, each metabolic equivalent increase in baseline fitness was associated with roughly 6% reduction in risk for developing a chronic condition.
Comment: Although these results are not surprising, they add another motivation for encouraging midlife cardiovascular fitness: This approach can lower risk for frailty and comorbidities while improving quality of life in older people.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine October 4, 2012
Citation(s): Willis BL et al. Midlife fitness and the development of chronic conditions in later life. Arch Intern Med 2012 Sep 24; 172:1333.
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MM: It would be interesting to see if the results of this study could be reproduced in other institutions and furthermore to see if the results could be maintained longitudinally or if micro-organism resistance would develop as it tends to do with other agents.
Infect Control Hosp Epidemiol 2012 Nov; 33:1094.
Chlorhexidine (CHG) Bathing Decreases Nosocomial Clostridium Difficile Infections (CDIs)
Institution-wide chlorhexidine bathing of patients daily or three times weekly was associated with a significant decrease in hospital-acquired Clostridium difficile infections.
The use of daily bed baths with chlorhexidine gluconate (CHG) in the intensive care unit (ICU) has been found to decrease the incidence of central line–associated bloodstream infections, as well as infections caused by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (VRE).
In a recent study partially funded by the manufacturer of CHG, researchers at the University of Nebraska Medical Center extended CHG patient bathing across their entire 689-bed institution. Using a quasi-experimental, dose-ranging, staged-introduction study design, they evaluated the effect of either daily or three-times-weekly CHG bathing on the incidence of healthcare-acquired infections.
From February 2009 through August 2010, 68,302 CHG baths were administered, with a 60.6% adherence rate. During this period, the incidence of Clostridium difficile infections (CDIs) decreased significantly with bathing either daily (relative risk, 0.41; 95% confidence interval, 0.29–0.59) or three times weekly (RR, 0.71; 95% CI, 0.57–0.89), compared with a 1-year baseline observation period. The rate rose again during a 3-month postintervention washout period (RR [compared with the daily bathing period], 1.85; 95% CI, 1.38–2.53). Decreases were also noted in rates of VRE (Vancomycin Resistant Enterococci) colonization and infection throughout the hospital, central line–associated bloodstream infections in ICU patients, and catheter-associated urinary tract infections in non-ICU patients, but the incidence of these infections did not rebound during the washout period. No adverse effects were identified with CHG bathing.
Comment: The authors note that the significant decrease in CDI incidence was not expected, but is biologically plausible. If such a decrease is confirmed in additional studies, CHG bathing would be an attractive approach to controlling this problematic pathogen.
— Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases October 10, 2012
Citation(s): Rupp ME et al. Effect of hospital-wide chlorhexidine patient bathing on healthcare-associated infections. Infect Control Hosp Epidemiol 2012 Nov; 33:1094.
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MM: In light of all the negative health effects associated with ADT, I have to ask is this approach to treatment smart? Is the potential benefit worth the almost certain risk of the significant diminished Quality of Life (QOL)? How much added life are we typically able to provide to these patients and how much are they losing from the treatment? Risk vs. benefit is a question that must always be asked for any treatment. Non-metastatic Prostate cancer is no exception.
J Clin Oncol 2012 Sep 10; 30:3271
Sarcopenia During Androgen Deprivation Therapy
Lean body mass decreased significantly after 1 to 3 years of ADT in men with nonmetastatic prostate cancer.
In a prior randomized, placebo-controlled trial, investigators assessed whether denosumab prevents fractures in men undergoing androgen deprivation therapy (ADT) for nonmetastatic prostate cancer (N Engl J Med 2009; 361:745). Now, these investigators have conducted a prespecified substudy of patients in the trial to assess long-term changes in lean body mass (LBM) in response to ADT.
The analysis included 252 men (age ≥70, or <70 with history of osteoporotic fracture or baseline T-score <–1.0; more than 75% were overweight or obese) with biopsy-proven adenocarcinoma of the prostate and performance status 0 to 2; exclusion criteria included prostate-specific antigen (PSA) level ≥5 ng/mL after 1 month of ADT. Patients underwent total-body, dual-energy x-ray absorptiometry scanning at baseline and at 12, 24, and 36 months. The primary outcome was change in LBM from baseline to 12, 24, and 36 months.
Overall, LBM decreased 1.0% at 12 months, 2.1% at 24 months, and 3.2% at 36 months. LBM loss was greater in men ≥70 and was most significant for patients with body-mass index ≤25 kg/m2 and for those who had been on ADT for ≥6 months at the time of study entry.
CommentIt has been well established that ADT for adenocarcinoma of the prostate is associated with substantial long-term adverse effects, including osteoporosis, altered body composition, sexual dysfunction, diabetes, metabolic syndrome, and decreased quality of life. It is now evident that ADT results in a decrease in LBM due to the loss of androgen stimulus. This effect is clinically important because loss of LBM has been associated with decreased physical function, increased morbidity, and reduced quality of life, particularly in elderly patients. Moreover, some clinically significant sarcopenia might have been masked in this study given that more than three quarters of patients were overweight or obese. It is critical that clinicians monitor for acute and late effects of ADT. Because urologists are often unprepared to take on this task burden, the treatment team and patient must establish at ADT initiation who will be responsible for toxicity monitoring and management. Decisions about the start time and course of ADT must also be considered carefully for each patient.
— Barbara A. Murphy, MD: Published in Journal Watch Oncology and Hematology October 9, 2012
Citation(s): Smith MR et al. Sarcopenia during androgen-deprivation therapy for prostate cancer. J Clin Oncol 2012 Sep 10; 30:3271.
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MM: One tends to wonder about data interpretation that is so different from analyst to analyst. In earlier analysis the synthetic progestin reviewed was typically medroxyprogesterone, aka Provera®. Bio-Identical Progesterone was not included in the studies and was not shown to have any detrimental effect. It is possible that other synthetic progestin analogs may not represent a significant health issue but we must still ask why introduce a synthetic progestin when we see the long established benefits and safety of Bio-identical Progesterone?
New Data Suggest Safety of Hormone Therapy in Early Menopause
In early menopause, 10 years of hormone therapy might lower the risk for cardiac events without raising the risk for cancer, thrombosis, or stroke, according to an open-label study in BMJ.
Roughly 1000 newly menopausal women (mean age, 50) in Denmark were randomized to hormone therapy (estradiol plus norethisterone acetate for those with an intact uterus, estradiol alone for those posthysterectomy) or to no treatment. The intervention was stopped at 10 years, after the Women's Health Initiative reported HT-associated harms.
At the end of treatment, the primary outcome — a composite of death, MI, or heart failure — was less common among women on HT; this significant benefit persisted through 16 years' total follow-up. Risks for thrombosis, stroke, and cancer did not differ between the groups. Speculating on why these results differ from the WHI's findings, the researchers point to the younger age of the current cohort and the different hormones used.
Andrew Kaunitz of Journal Watch Women's Health said: "Taken together with findings from a subanalysis of younger women from the WHI, these data should reassure clinicians and women that use of hormone therapy in recently menopausal women is safe."
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MM: The question must be asked as it always is. Which is more objectionable? Preventing unwanted pregnancies that lead to abortions or endorsing contraception? The ideal situation would be less promiscuity, sound judgement and no unwanted pregnancies that force a decision. Unfortunately, this is not reality. The statistics of this study merely indicate the results of the program and the demographics associated with the data.
Obstet Gynecol 2012 Oct 3
Free Highly Effective Reversible Contraception: Conquering a Barrier
Providing such contraception at no cost significantly reduced abortion rates.
The Institute of Medicine recently recommended that, in keeping with the Patient Protection and Affordable Care Act of 2010, reliable contraception be provided at no charge. The Contraceptive CHOICE Project was designed in part to provide insight into how such an objective could change the face of U.S. family planning services. The goal of this prospective cohort study was to promote use of effective contraceptives (with emphasis on highly effective reversible contraceptive methods) by providing them for free to women at high risk for unintended pregnancy in greater metropolitan St. Louis (JW Womens Health May 24 2012). Teen births and repeat abortions were selected as surrogates for unintended pregnancies. Between August 2007 and September 2011, 9256 participants (age range, 14–45; 51% black; 35% with high school education or less; 37% on public assistance) were enrolled. Highly effective reversible contraceptive methods were chosen by 75% of women (most commonly the levonorgestrel intrauterine device).
Between 2008 and 2010, the number of abortions in the St. Louis area fell by 20.6% (P<0.001) but did not change in the rest of Missouri. Among CHOICE participants during this period, abortion rates did not exceed 7.5/1000, whereas the national rate was 19.6/1000 women aged 15 to 44. The proportion of repeat abortions in the St. Louis area also declined (P=0.002). The teen birth rate among CHOICE participants aged 15 to 19 was 6.3/1000 versus the national rate of 34.3/1000.
CommentThe authors' calculations based on number needed to treat indicate that, if the CHOICE paradigm were available nationally, one abortion could be prevented for every 79 to 137 women and teens (equivalent to averting 62% to 78% of U.S. abortions annually). These findings from St. Louis demonstrate that we have the tools to forestall unintended pregnancy and induced abortion. The remaining question is whether or not our ever-evolving, politically influenced healthcare system will make highly effective reversible contraception broadly available.
— Anne A. Moore, DNP, APRN, FAANP Published in Journal Watch Women's Health October 11, 2012
Citation(s): Peipert JF et al. Preventing unintended pregnancies by providing no-cost contraception. Obstet Gynecol 2012 Oct 3; [e-pub ahead of print].
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MM: This study indicates that estrogen sensitivity and depression or anxiety associated with it may have a significant genetic predisposition and that genetic mapping may lead to better ways to diagnose and potentially treat both of these conditions. Although this seems to have a greater significance with women, estrogen sensitivity can also have varying effects on males. With the increased prevalence of testosterone replacement therapy in men and the subsequent partial conversion of testosterone to estrogen, this may show greater significance in male diagnoses in the not too distant future. I recommend that physicians check testostyerone and estradiol levels in men before and after initiating testosterone tha=erapy. At Mark Drugs we have been directing clinicians in this area for more than a decade and are happy to provide guidance to practitioners who are working in this challenging field.
Biol Psychiatry 2012 Sep 15; 72:499
The Sex Difference in Depression and Anxiety Explained?
An animal study suggests that a genetic variant of brain-derived neurotrophic factor could play an important role.
A single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) has been implicated in the development of anxiety (JW Psychiatry Dec 11 2006). The SNP, which causes methionine (met) to be substituted for valine (val) at position 66, results in a reduction of BDNF expression. Moreover, the SNP, carried by about 30% of the white population, may attenuate the ability of estrogen to induce BDNF. Investigators explored the possible role of this SNP in the relatively higher prevalence of anxiety and depression in women after menarche and in the recurrence of depression in association with reproductive events. After inserting the human SNP into mice, they measured performance on several behavioral tests that model anxiety- and depression-like behavior in met/met female mice versus wild-type val/val females throughout the life span and the reproductive cycle.
Consistent with previous findings, met/met mice were more likely than val/val mice to exhibit anxious and depressive responses in behavioral tests. However, met/met animals exhibited higher levels of anxiety only after the mouse equivalent of puberty. Met/met (but not val/val) females exhibited more anxiety during a low-estrogen phase (estrus) of the ovarian cycle.
Comment: These animal results may be applicable to humans. Low BDNF levels, which are associated with anxiety, depression, and other abnormal stress responses, might be less effectively counteracted by estrogen in women who are heterozygous or homozygous for this single nucleotide polymorphism. As a result, phases of the menstrual cycle (and age-related changes in the reproductive cycle) associated with decreased estrogen levels might trigger greater vulnerability to these syndromes in women who carry the SNP. Editorialists suggest that BDNFgenotyping could ultimately facilitate identification of women who are susceptible to postpartum, premenstrual, and menopausal mood and anxiety disorders.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry October 5, 2012
Citation(s): Bath KG et al. Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice. Biol Psychiatry 2012 Sep 15; 72:499.
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Apple a Day Cut Harmful Cholesterol
Daily apple habit lowered oxidized LDL cholesterol levels by 40 percent in one month; supplemental apple polyphenols also worked, but less well
By Craig Weatherby

Eating an apple a day might help keep the cardiologist away. The news comes from Ohio State University, where scientists conducted a study in healthy, middle-aged adults. The participants who ate an apple a day for four weeks lowered their blood levels of oxidized LDL cholesterol by an average of 40 percent. When people took a daily capsule containing the amount of polyphenol “antioxidants” found in one apple, they showed a similar but smaller benefit.

Oxidation turns healthy cholesterol dangerous
Importantly, the effect exerted by apples was to lower levels of oxidized LDL. Despite opposing evidence, public health authorities long asserted that people’s total and LDL cholesterol levels largely determine their heart risk … but we now know that risk is much better gauged by the totality of your triglycerides and the amounts and relative proportions of various kinds or cholesterol). See “Cholesterol Fiasco Undermines Accepted Theory”, which links to several New York Times articles refuting the myth that people’s cholesterol profiles regulate cardiovascular risks. However, oxidized LDL cholesterol – which promotes artery clogging/hardening (atherosclerosis) – presents a very real cardiovascular risk.

When LDL cholesterol gets oxidized – often by the poorly controlled proliferation of free radicals promoted by unhealthful diets and lifestyles – it begins to promote inflammation and artery dysfunctions, leading to atherosclerosis. Fortunately, said lead researcher Robert DiSilvestrom “We got a tremendous effect against LDL being oxidized with just one apple a day for four weeks.” (OSU 2012) The difference was similar to that found between people with normal coronary arteries versus those with coronary artery disease, he said.

DiSilvestro described daily apple consumption as significantly more effective at lowering oxidized LDL than other antioxidants he has studied, including curcumin, green tea and tomato extract:
“Not all antioxidants are created equal when it comes to this particular effect,” he said (OSU 2012). (We should note that the curcumin in standard supplements – the orange pigment complex in turmeric – is poorly absorbed … unlike curcumin accompanied by the essential oils in turmeric. (However, apple polyphenols clearly excel at protecting LDL from oxidation.)

DiSilvestro became interested in studying the health effects of apples after reading a Turkish study that found this habit raised the amount of a specific antioxidant enzyme in the body. In the end, his team didn't find the same effect on the enzyme, but was surprised at the considerable influence the apples had on oxidized LDL.

Apple a day cut cholesterol oxidation
The OSU researchers recruited 51 non-smoking healthy adults between the ages of 40 and 60 who had a history of eating apples less than twice a month … and who didn't take supplements containing polyphenols or other plant-based concentrates.
They were divided into three groups, each assigned to a different daly regimen for four weeks:

The researchers found no effect on oxidized LDLs in the placebo group. But, as DiSilvestro said, “We got a tremendous effect against LDL being oxidized with just one apple a day for four weeks.” (OSU 2012) “We think the polyphenols account for a lot of the effect from apples, but we did try to isolate just the polyphenols, using about what you'd get from an apple a day,” DiSilvestro said. (OSU 2012) “We found the polyphenol extract did register a measurable effect, but not as strong as the straight apple. That could either be because there are other things in the apple that could contribute to the effect, or, in some cases, these bioactive compounds seem to get absorbed better when they're consumed in foods.” (OSU 2012) Still, DiSilvestro said polyphenol extracts could be useful in some situations, “perhaps in higher doses than we used in the study, or for people who just never eat apples.” (OSU 2012) The study also found eating apples raised those participants’ saliva levels of internal antioxidants, which has implications for dental health, DiSilvestro said.

Dr. DiSilvestro discusses his team’s findings in this video.

The study was funded by a grant from the U.S. Apple Association/Apple Product Research and Education Council and a donation from Futureceuticals Inc. of Momence, Ill.

Sources: Ohio State University (OSU). Study: An Apple a Day Lowers Level of Blood Chemical Linked to Hardening of the Arteries. October 2,2012. Accessed at
Disilvestro RA, Joseph E, Zhao S, Joshua B. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11(1):79. [Epub ahead of print] Nemzer BV, Rodriguez LC, Hammond L, Disilvestro R, Hunter JM, Pietrzkowski Z. Acute reduction of serum 8-iso-PGF2-alpha and advanced oxidation protein products in vivo by a polyphenol-rich beverage; a pilot clinical study with phytochemical and in vitro antioxidant characterization. Nutr J. 2011 Jun 15;10:67.

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