Altered expression of Alzheimer\u27s disease-related proteins in male hypogonadal mice

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer\u27s disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1β protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology

Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents

Objectives: Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity (SG) are better adjustments. Design and Methods: The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n=343) and first morning urine every three months (n=644). Unadjusted, creatinine and SG-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and SG adjusted were also compared. Results: Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or SG. Urine creatinine concentration increases with Tanner stages, age and male gender whereas, urine SG was not influenced by Tanner stage, age or gender. Adjustment by creatinine or SG of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Conclusions: Urine steroid and LH concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and SG adjustments are equally suitable

Blood testosterone threshold for androgen deficiency symptoms.

There are few systematic studies of the relationship between blood testosterone concentrations and the symptoms of overt androgen deficiency. Because most testosterone preparations are relatively short-term, the rapid changes in blood testosterone concentrations they cause make it difficult to define any testosterone threshold. By contrast, subdermal testosterone implants provide stable blood testosterone concentrations over days to weeks, while gradually declining to baseline over 5-7 months. Hence, this provides an opportunity to define a blood testosterone threshold for androgen deficiency symptoms by observing androgen-deficient men as their familiar androgen deficiency symptoms return as testosterone pellets slowly dissolve. Among 52 androgen-deficient men who underwent 260 implantations over 5 yr, at the time of return of androgen deficiency symptoms the blood total and free testosterone concentrations were highly reproducible within individuals (F ‫؍‬ 0.8, P ‫؍‬ 0.49 and F ‫؍‬ 1.4, 0.24, respectively) but varied markedly between men (F ‫؍‬ 167 and F ‫؍‬ 138, both P < 0.001), indicating that each person had a consistent testosterone threshold for androgen deficiency symptoms that differed markedly between individuals. The most reported symptoms of androgen deficiency were lack of energy, lack of motivation, and reduced libido. The symptomatic threshold was significantly lower in men with secondary hypogonadism compared with men with primary or mixed hypogonadism (total, 9.7 ؎ 0.5 nmol/liter vs. T HE EFFECTS OF androgen deficiency and replacement on objective endpoints, notably bone (1, 2) and muscle (3-7), are well known and increasingly studied. Yet, whereas symptoms of androgen deficiency are discussed in textbooks and form the basis for practical clinical monitoring of androgen replacement therapy (8), there is a paucity of systematic studies of the symptoms of, and symptomatic threshold for, androgen deficiency. The subjective effects of androgen deficiency and replacement have generally been studied as objectively recorded measures of mood, behavior and cognitive responses (9 -11), but symptoms themselves are more difficult to study objectively. As a result, subjective effects of androgens have received most attention in the psychology literature, where empirical studies are, however, largely observational and restricted to eugonadal men limiting the salience of any inferences regarding relationships of blood testosterone concentrations to symptoms of overt androgen deficiency. A major limitation of interventional clinical research on androgen deficiency symptoms is that the available relatively short-term testosterone preparations produce swings in blood testosterone levels over days to weeks, which make it difficult or impossible to distinguish reliably symptom resolution and reappearance from pharmacological effects. The present study overcomes this limitation by using a long-acting depot testosterone preparation, which maintains stable blood testosterone concentrations over days to weeks but, as the biodegradable implants erode, allows them to decline slowly back to baseline over 5-7 months (12-15). Because the treated men return for blood testosterone measurement and reimplantation when their familiar androgen deficiency symptoms return, this allows a prospective evaluation of the relationships between individual androgen deficiency symptoms and the blood testosterone concentrations that accompany them. Subjects and Methods Patients We reviewed prospectively collected data from patients having regular androgen replacement therapy with a standard dose (four 200-mg pellets) of subdermal testosterone implants for androgen deficiency as described previously Procedures Implantation procedure. Testosterone pellet implantation procedures are booked throughout the week. At visits, men have a blood sample drawn JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community

Reducing STEM gender bias with VIDS (video interventions for diversity in STEM)

Gender biases contribute to the underrepresentation of women in STEM. In response, the scientific community has called for methods to reduce bias, but few validated interventions exist. Thus, an interdisciplinary group of researchers and filmmakers partnered to create VIDS (Video Interventions for Diversity in STEM), which are short videos that expose participants to empirical findings from published gender bias research in 1 of 3 conditions. One condition illustrated findings using narratives (compelling stories), and the second condition presented the same results using expert interviews (straightforward facts). A hybrid condition included both narrative and expert interview videos. Results of two experiments revealed that relative to controls, VIDS successfully reduced gender bias and increased awareness of gender bias, positive attitudes toward women in STEM, anger, empathy, and intentions to engage in behaviors that promote gender parity in STEM. The narratives were particularly impactful for emotions, while the expert interviews most strongly impacted awareness and attitudes. The hybrid condition reflected the strengths of both the narratives and expert interviews (though effects were sometimes slightly weaker than the other conditions). VIDS produced substantial immediate effects among both men and women in the general population and STEM faculty, and effects largely persisted at follow-up. (PsycINFO Database Record (c) 2018 APA, all rights reserved

“Deconstructing” Scientific Research: A Practical and Scalable Pedagogical Tool to Provide Evidence-Based Science Instruction

Focused analysis of current research projects provides an effective platform for teaching early-stage undergraduates the logic of scientific inquiry

Effect of Angiogenesis-Related Cytokines on Rotator Cuff Disease: The Search for Sensitive Biomarkers of Early Tendon Degeneration

Background Hallmarks of the pathogenesis of rotator cuff disease (RCD) include an abnormal immune response, angiogenesis, and altered variables of vascularity. Degenerative changes enhance production of pro-inflammatory, anti-inflammatory, and vascular angiogenesis-related cytokines (ARC) that play a pivotal role in the immune response to arthroscopic surgery and participate in the pathogenesis of RCD. The purpose of this study was to evaluate the ARC profile, ie, interleukin (IL): IL-1β, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG), in human peripheral blood serum and correlate this with early degenerative changes in patients with RCD. Methods Blood specimens were obtained from 200 patients with RCD and 200 patients seen in the orthopedic clinic for nonrotator cuff disorders. Angiogenesis imaging assays was performed using power Doppler ultrasound to evaluate variables of vascularity in the rotator cuff tendons. Expression of ARC was measured by commercial Bio-Plex Precision Pro Human Cytokine Assays. Results Baseline concentrations of IL-1β, IL-8, and VEGF was significantly higher in RCD patients than in controls. Significantly higher serum VEGF levels were found in 85% of patients with RCD, and correlated with advanced stage of disease (r = 0.75; P < 0.0005), average microvascular density (r = 0.68, P < 0.005), and visual analog score (r = 0.75, P < 0.0002) in RCD patients. ANG and IL-10 levels were significantly lower in RCD patients versus controls. IL-1β and ANG levels were significantly correlated with degenerative tendon grade in RCD patients. No difference in IL-6 and bFGF levels was observed between RCD patients and controls. Patients with degenerative changes had markedly lower ANG levels compared with controls. Power Doppler ultrasound showed high blood vessel density in patients with tendon rupture. Conclusion The pathogenesis of RCD is associated with an imbalance between pro-inflammatory, anti-inflammatory, and vascular ARC

Evaluation of INSeq To Identify Genes Essential for

The reciprocal interaction between rhizosphere bacteria and their plant hosts results in a complex battery of genetic and physiological responses. In this study, we used insertion sequencing (INSeq) to reveal the genetic determinants responsible for the fitness of Pseudomonas aeruginosa PGPR2 during root colonization. We generated a random transposon mutant library of Pseudomonas aeruginosa PGPR2 comprising 39,500 unique insertions and identified genes required for growth in culture and on corn roots. A total of 108 genes were identified as contributing to the fitness of strain PGPR2 on roots. The importance in root colonization of four genes identified in the INSeq screen was verified by constructing deletion mutants in the genes and testing them for the ability to colonize corn roots singly or in competition with the wild type. All four mutants were affected in corn root colonization, displaying 5- to 100-fold reductions in populations in single inoculations, and all were outcompeted by the wild type by almost 100-fold after seven days on corn roots in mixed inoculations of the wild type and mutant. The genes identified in the screen had homology to genes involved in amino acid catabolism, stress adaptation, detoxification, signal transduction, and transport. INSeq technology proved a successful tool to identify fitness factors in P aeruginosa PGPR2 for root colonization

Frequency and type of adverse analytical findings in athletics: Differences among disciplines.

Athletics is a highly diverse sport that contains a set of disciplines grouped into jumps, throws, races of varying distances, and combined events. From a physiological standpoint, the physical capabilities linked to success are quite different among disciplines, with varying involvements of muscle strength, muscle power, and endurance. Thus, the use of banned substances in athletics might be dictated by physical dimensions of each discipline. Thus, the aim of this investigation was to analyse the number and distribution of adverse analytical findings per drug class in athletic disciplines. The data included in this investigation were gathered from the Anti-Doping Testing Figure Report made available by the World Anti-Doping Agency (from 2016 to 2018). Interestingly, there were no differences in the frequency of adverse findings (overall, 0.95%, range from 0.77 to 1.70%) among disciplines despite long distance runners having the highest number of samples analysed per year ( 9812 samples/year). Sprinters and throwers presented abnormally high proportions of adverse analytical findings within the group of anabolic agents (p < 0.01); middle- and long-distance runners presented atypically high proportions of findings related to peptide hormones and growth factors (p < 0.01); racewalkers presented atypically high proportions of banned diuretics and masking agents (p = 0.05). These results suggest that the proportion of athletes that are using banned substances is similar among the different disciplines of athletics. However, there are substantial differences in the class of drugs more commonly used in each discipline. This information can be used to effectively enhance anti-doping testing protocols in athletics.post-print1.911 K

Glycine methyl ester hydro­chloride

The title compound [systematic name: (methoxy­carbonyl­meth­yl)ammonium chloride], crystallizes as a salt, C3H8NO2 +·Cl−, with the charged species inter­acting mutually via strong and highly directional N+—H⋯Cl− hydrogen bonds which lead to the formation of a supra­molecular tape running parallel to the c axis. Tapes close pack in the solid state mediated by multipoint recognition synthons based on weak C—H⋯O inter­actions and van der Waals contacts between adjacent methyl groups