Urinary cortisol and depression in early pregnancy: Role of adiposity and race

Background: Depression before and during pregnancy is associated with adverse birth outcomes including low birth weight and preterm birth. Abnormal maternal cortisol has been hypothesized as one mediator between depression and adverse birth outcomes. The relationship between cortisol and depression in pregnancy is exhibited most strongly in the African American population, and most studies have focused either on circulating or placental levels of cortisol. The utility of urinary cortisol in early pregnancy related to depression and adiposity has not been investigated. Methods: Twenty-five pregnant African American women identified by the Edinburgh Depression Scale as having depression were investigated and matched by body mass index (BMI), age, race, and infant birth weight centile to non-depressed subjects. Maternal urine and plasma cortisol in early pregnancy were quantified and investigated in relation to depression and adiposity. Results: Morning urine cortisol levels tracked positively with plasma cortisol (r2=0.25, p<0.001). However, no differences were observed in either urinary or plasma cortisol between depressed and non-depressed pregnant women. Plasma cortisol was significantly negatively associated with several measures of maternal adiposity including percent body fat (r2=-0.10, p <0.05), however this relationship was present only in the non-depressed women. In a post-hoc analysis, non-depressed non-obese women were found to have significantly higher cortisol levels compared to women with depression, obesity or both (p < 0.05). Conclusions: Depressed pregnant women and non-depressed obese pregnant women evidence atypical cortisol levels compared to non-depressed non-obese pregnant women. Plasma cortisol in early pregnancy is negatively associated with measures of maternal adiposity. Atypical low circulating maternal cortisol among depressed (lean and obese) and non-depressed obese pregnant African American women may indicate hypothalamic-pituitary axis dysfunction in early pregnancy

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure

Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): A case-control study

BACKGROUND: In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. METHODS: Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4(+ )T lymphocyte count, date of CD4(+ )count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. RESULTS: The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37–33.5, and outside the home: OR 3.16; 95% CI 1.23–8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%. CONCLUSIONS: Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water

Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

<p>Abstract</p> <p>Background</p> <p>Interleukin-12 (IL-12) is a cytokine well known for its role in immunity. A lesser known function of IL-12 is its role in hematopoiesis. The promising data obtained in the preclinical models of antitumor immunotherapy raised hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity, largely due to repeat dose regimens, and modest clinical response observed in the clinical trials have pointed to the necessity to design protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. We have focused on the lesser known role of IL-12 in hematopoiesis and hypothesized that an important clinical role for IL-12 in cancer may be as an adjuvant hematological cancer therapy. In this putative clinical function, IL-12 is utilized for the prevention of cancer therapy-related cytopenias, while providing concomitant anti-tumor responses over and above responses observed with the primary therapy alone. This putative clinical function of IL-12 focuses on the dual role of IL-12 in hematopoiesis and immunity.</p> <p>Methods</p> <p>We assessed the ability of IL-12 to facilitate hematopoietic recovery from radiation (625 rad) and chemotherapy (cyclophosphamide) in two tumor-bearing murine models, namely the EL4 lymphoma and the Lewis lung cancer models. Antitumor effects and changes in bone marrow cellularity were also assessed.</p> <p>Results</p> <p>We show herein that carefully designed protocols, in mice, utilizing IL-12 as an adjuvant to radiation or chemotherapy yield facile and consistent, multilineage hematopoietic recovery from cancer therapy-induced cytopenias, as compared to vehicle and the clinically-utilized cytokine granulocyte colony-stimulating factor (G-CSF) (positive control), while still providing concomitant antitumor responses over and above the effects of the primary therapy alone. Moreover, our protocol design utilizes single, low doses of IL-12 that did not yield any apparent toxicity.</p> <p>Conclusion</p> <p>Our results portend that despite its past failure, IL-12 appears to have significant clinical potential as a hematological adjuvant cancer therapy.</p

HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8–9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit–expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD50/30) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12–14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting hematopoiesis and recovery of immune functions and possibly gastrointestinal functions, likely through a network of interactions involving dendritic cells, osteoblasts, and soluble factors such as IL-12, IFN-γ, and cytoprotectant erythropoietin

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Trends and connections across the Antarctic cryosphere

Satellite observations have transformed our understanding of the Antarctic cryosphere. The continent holds the vast majority of Earth’s fresh water, and blankets swathes of the Southern Hemisphere in ice. Reductions in the thickness and extent of floating ice shelves have disturbed inland ice, triggering retreat, acceleration and drawdown of marine-terminating glaciers. The waxing and waning of Antarctic sea ice is one of Earth’s greatest seasonal habitat changes, and although the maximum extent of the sea ice has increased modestly since the 1970s, inter-annual variability is high, and there is evidence of longer-term decline in its extent

The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor.

BackgroundRecent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (HIV-1), and Ebola virus have shown, first with molecular modeling, and then X-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein.ResultsStructural models of the transmembrane glycoproteins (GP-2) of the Arenaviruses, lymphochoriomeningitis virus (LCMV) and Lassa fever virus, are presented, based on consistent structural propensities despite variation in the amino acid sequence. The principal features of the model, a hydrophobic amino terminus, and two antiparallel helices separated by a glycosylated, antigenic apex, are common to a number of otherwise disparate families of enveloped RNA viruses. Within the first amphipathic helix, demonstrable by circular dichroism of a peptide fragment, there is a highly conserved heptad repeat pattern proposed to mediate multimerization by coiled-coil interactions. The amino terminal 18 amino acids are 28% identical and 50% highly similar to the corresponding region of Ebola, a member of the Filovirus family. Within the second, charged helix just prior to membrane insertion there is also high similarity over the central 18 amino acids in corresponding regions of Lassa and Ebola, which may be further related to the similar region of HIV-1 defining a potent antiviral peptide analogue.ConclusionsThese findings indicate a common pattern of structure and function among viral transmembrane fusion proteins from a number of virus families. Such a pattern may define a viral transmembrane superfamily that evolved from a common precursor eons ago