Which blood tests are most helpful in evaluating pelvic inflammatory disease?

No individual or combination of blood tests can reliably diagnose pelvic inflammatory disease (PID)(strength of recommendation [SOR]: A, metaanalysis). The combination of white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and vaginal white blood cells can reliably exclude PID if results for all 4 tests are normal (sensitivity=100%) (SOR: B, cohort study, reference standard not uniformly applied)

In menopausal women, does fatigue indicate disease?

Though fatigue is a commonly reported symptom, high-quality studies evaluating it as a marker for diseases among menopausal women are lacking. Middle-aged women who report fatigue are more apt to screen positive for clinical depression or anxiety (strength of recommendation [SOR]: B, case series). Fatigue may signal obstructive sleep apnea (SOR: B, retrospective cohort). For menopausal women with cardiac risk factors, extreme fatigue may be a sign of coronary artery disease (SOR: C, review without critical appraisal)

Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity

Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is MMAIII, an intermediate in the generation of DMAV, a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination

Do dietary interventions improve ADHD symptoms in children?

Insufficient evidence exists to suggest that dietary interventions improve the symptoms of attention deficit hyperactivity disorder (ADHD) in children (strength of recommendation: B, extrapolation from randomized controlled trials [RCTs]). Interventions that have been investigated include removal of sugar and artificial food colorings from the diet and supplementation with fatty acids

Evaluation of hip pain in older adults

The evaluation of hip pain in patients 65 years and older should include a history and physical examination, followed by pertinent imaging studies. (Strength of Recommendation [SOR]: C, based on expert opinion.) Patients who have hip pain for more than four weeks or who have concerning historical features, signs, or symptoms require hip imaging with radiography. There are no trials comparing the accuracy of magnetic resonance imaging (MRI), computed tomography (CT), and bone scintigraphy. MRI should be used in patients with suspected acute fracture in whom plain radiography does not yield a definitive diagnosis. (SOR: C, based on one small case series.) If MRI is contraindicated or unavailable, CT or bone scintigraphy can be substituted. (SOR: C, based on expert opinion.

What is the best way to evaluate secondary infertility?

The work-up for secondary infertility--the inability to conceive after 1 year of regular unprotected intercourse for a couple who have previously had a child--should include a history and physical exam for both patients, plus evaluation of ovulation, semen analysis, and imaging of the uterus and fallopian tubes (strength of recommendation [SOR]: B, based on cohort studies)

Prompt neutrino fluxes from atmospheric charm

We calculate the prompt neutrino flux from atmospheric charm production by cosmic rays, using the dipole picture in a perturbative QCD framework, which incorporates the parton saturation effects present at high energies. We compare our results with the next-to-leading order perturbative QCD result and find that saturation effects are large for neutrino energies above 10^6 GeV, leading to a substantial suppression of the prompt neutrino flux. We comment on the range of prompt neutrino fluxes due to theoretical uncertainties.Comment: 13 pages with 11 figures; expanded discussion, added references, version to be published in Phys. Rev.

Mathematical modeling of the effects of glutathione on arsenic methylation

Background: Arsenic is a major environmental toxin that is detoxified in the liver by biochemical mechanisms that are still under study. In the traditional metabolic pathway, arsenic undergoes two methylation reactions, each followed by a reduction, after which it is exported and released in the urine. Recent experiments show that glutathione plays an important role in arsenic detoxification and an alternative biochemical pathway has been proposed in which arsenic is first conjugated by glutathione after which the conjugates are methylated. In addition, in rats arsenic-glutathione conjugates can be exported into the plasma and removed by the liver in the bile. Methods: We have developed a mathematical model for arsenic biochemistry that includes three mechanisms by which glutathione affects arsenic methylation: glutathione increases the speed of the reduction steps; glutathione affects the activity of arsenic methyltranferase; glutathione sequesters inorganic arsenic and its methylated downstream products. The model is based as much as possible on the known biochemistry of arsenic methylation derived from cellular and experimental studies. Results: We show that the model predicts and helps explain recent experimental data on the effects of glutathione on arsenic methylation. We explain why the experimental data imply that monomethyl arsonic acid inhibits the second methylation step. The model predicts time course data from recent experimental studies. We explain why increasing glutathione when it is low increases arsenic methylation and that at very high concentrations increasing glutathione decreases methylation. We explain why the possible temporal variation of the glutathione concentration affects the interpretation of experimental studies that last hours. Conclusions: The mathematical model aids in the interpretation of data from recent experimental studies and shows that the Challenger pathway of arsenic methylation, supplemented by the glutathione effects described above, is sufficient to understand and predict recent experimental data. More experimental studies are needed to explicate the detailed mechanisms of action of glutathione on arsenic methylation. Recent experimental work on the effects of glutathione on arsenic methylation and our modeling study suggest that supplements that increase hepatic glutathione production should be considered as strategies to reduce adverse health effects in affected populations

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Background: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. Objectives: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment). Methods: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: & 10 (n = 76), 10–100 (n = 104), 101–200 (n = 86), 201–300 (n = 67), and < 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. Results: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, –25.4 µmol/L; 95% CI: –45.3, –5.31) and plasma CySS (mean change, –3.00 µmol/L; 95% CI: –4.61, –1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. Conclusions: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine