Relative contributions of adiposity and muscularity to physical function in community-dwelling older adults

Objective: To determine the relative contributions of adiposity and muscularity to multi‐dimensional performance‐based and perceived physical function in older adults living independently. Methods and Procedures: Data from 109 women and men, aged 60 or older, with low serum dehydroepiandrosterone (DHEA) sulfate levels were included in this cross‐sectional analysis of baseline measures from a single‐site, randomized, controlled trial of DHEA replacement therapy. Physical function was determined by means of performance on the 100‐point Continuous Scale‐Physical Functional Performance (CS‐PFP) test and by self‐reporting using the physical function subscale of the Medical Outcomes Short Form‐36 (SF36_PF). Body composition was measured by dual‐energy X‐ray absorptiometry (DXA). Linear regression analyses were used to determine the contributions of body mass index (BMI; kg body mass/m²), fat index (FI; kg fat/m²), and appendicular skeletal muscle index (ASMI; kg muscle/m²) to the CS‐PFP and SF36_PF scores, adjusted for age and sex. Results: Age‐adjusted regression analyses indicated that FI, but not ASMI, was a significant (P < 0.001) determinant of CS‐PFP (R ² = 0.54) and SF36_PF (R ² = 0.37). When adjusted for age and sex, BMI was nearly as good a predictor of CS‐PFP (R ² = 0.50) and SF36_PF (R ² = 0.34) as FI. Discussion: Adiposity was a stronger predictor of measured and self‐reported physical function than was muscularity in older adults living independently. BMI, adjusted for sex, is a reasonable substitute for adiposity in the prediction of physical function.     

Microsatellite evolution in congeneric mammals: domestic and bighorn sheep

We compared genotypes at eight (AC)n microsatellite loci in domestic sheep (Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The domestic sheep had greater genetic variation, higher allele-size variances, and larger allele sizes than the wild sheep. Accumulating evidence from higher taxonomic comparisons shows that these parameters are biased if microsatellite loci are selected in one taxon and used in another. Our results demonstrate similar biases between congeneric species. We compared standard measures of genetic variation, differentiation, and distance within and between species (H, D, FST) to newer measures based on allele-size variance (SW, SB, RST). The size-based distances better detected species-level divergence, but standard measures better distinguished allopatric populations. Empirical calibration of these measures at the subspecies level is needed to establish their useful ranges.      

Early events in the cellular formation of proparathyroid hormone

Early events in the cellular synthesis and subsequent transfer into membrane-limited compartments of pre-proparathyroid hormone (pre-proPTH) and proparathyroid hormone (proPTH) were investigated by electrophoretic analyses of newly synthesized proteins in subcellular fractions of parthyroid gland slices pulse-labeled for 0.5-5 min with [(35)S] methionine. During these short times of incubation, both pre-proPTH and proPTH were confined to the microsomal fraction. Labeled pre-proPTH and proPTH were detected in a 30-s interval between 0.5 and 1.0 min of incubation. The radioactivity in proPTH became relatively constant between 3 and 5 min, whereas the radioactivity in ProPTH increased markedly over this period. When corrected for the known content of methionine in the prohormone and the prohormone, we found four times as much radiolabeled prohormone as prehormone between 0.5 and 1.0 min of synthesis. Sequestration of labeled prohomrone into endoplasmic reticulum compartments was shown by treatment of the microsomal fraction with chymotrypsin and trypsin, which resulted in the degradation of the prehormone but not of the prohormones. Approximately 50 percent of pre-prohormone and 25 percent of prohormone were released from the microsomes by their extraction with 1.0 M KCl, whereas 80-90 percent of both was released by treatment with Triton X-100. These results in intact cells support the signal hypothesis proposed by Blobel and his co-workers in studies utilizing cell-free systems, inasmuch as the results indicate transfer of prohormone into the cisternal space of the rough endoplasmic reticulum concomitant with the growth of the nascent polypeptide chain. Appearance of membrane-sequestered proPTH takes place without entry of pre-proPTH into the cisternal space, suggesting that proteolytic removal of the leader peptide occurs during transfer of the polypeptide through the lipid bilayer. Further evidence in support of this process is that pre-proPTH is only partly extracted from the microsomes by treatment with 1.0 M KCl, suggesting that a substantial fraction of the nascent pre-proPTH is integrally inserted into the membranes before it is cleaved to form proPTH.     

Evidence that androgenic and estrogenic metabolites contribute to the effects of dehydroepiandrosterone on cognition in postmenopausal women

Prior studies of the effects of dehydroepiandrosterone (DHEA) on cognition have produced complex and inconsistent results. We hypothesize that these results may arise, in part, because of DHEA's metabolism into estrogens and androgens that produce opposing effects on cognition. Our study administered 50 mg of oral DHEA daily for 4 weeks in a placebo-controlled crossover design to six postmenopausal women. We measured blood levels of androgens (total testosterone, free testosterone, DHEA, DHEAS), estrogens (estradiol, estrone), and cognitive performance on recognition memory, perceptual identification, digit span memory, and visual attentional vigilance under both drug and placebo conditions. Multiple regression models incorporating the factors of age and body mass index (BMI) were used to ascertain the relation between sex steroids and cognitive performance. Our results demonstrated that estrogens produced a positive effect on recognition memory, while androgens produced a negative effect. This pattern reversed in perceptual identification with estrogens producing a negative effect and androgens producing a positive effect. In addition, BMI produced a negative effect on digit span memory, age produced a negative effect on perceptual identification, and androgens produced a negative effect on visual attentional vigilance. These results help, in part, to explain DHEA's complex effects on cognition. The diverse effects of sex steroids across tasks underscore the importance of identifying the specific cognitive mechanisms influenced by sex steroids and emphasizes that one should not expect sex steroids to produce homogeneous effects across cognitive tasks.     

Income inequality and depression: a systematic review and meta‐analysis of the association and a scoping review of mechanisms

Most countries have witnessed a dramatic increase of income inequality in the past three decades. This paper addresses the question of whether income inequality is associated with the population prevalence of depression and, if so, the potential mechanisms and pathways which may explain this association. Our systematic review included 26 studies, mostly from high‐income countries. Nearly two‐thirds of all studies and five out of six longitudinal studies reported a statistically significant positive relationship between income inequality and risk of depression; only one study reported a statistically significant negative relationship. Twelve studies were included in a meta‐analysis with dichotomized inequality groupings. The pooled risk ratio was 1.19 (95% CI: 1.07‐1.31), demonstrating greater risk of depression in populations with higher income inequality relative to populations with lower inequality. Multiple studies reported subgroup effects, including greater impacts of income inequality among women and low‐income populations. We propose an ecological framework, with mechanisms operating at the national level (the neo‐material hypothesis), neighbourhood level (the social capital and the social comparison hypotheses) and individual level (psychological stress and social defeat hypotheses) to explain this association. We conclude that policy makers should actively promote actions to reduce income inequality, such as progressive taxation policies and a basic universal income. Mental health professionals should champion such policies, as well as promote the delivery of interventions which target the pathways and proximal determinants, such as building life skills in adolescents and provision of psychological therapies and packages of care with demonstrated effectiveness for settings of poverty and high income inequality.     

Inhibition of crossed caudal interneurons by lateral interneurons in lamprey spinal cord during fictive locomotion

Templates of the membrane potential profiles from lateral (LI) interneurons and motoneurons during glutamate- and N-methyl-D-aspartate (NMDA)-induced fictive locomotion showed pronounced plateau phases. In contrast, crossed caudal (CC) interneurons had a less obvious and steeper plateau region that was followed by a clear notch coinciding with the end of the lateral interneuron plateau phase. These results indicate a significant inhibitory input from LI to CC interneurons.     

Reflechi twòp—Thinking Too Much: Description of a Cultural Syndrome in Haiti’s Central Plateau

A rich Haitian ethnopsychology has been described, detailing concepts of personhood, explanatory models of illness, and links between mind and body. However, little research has engaged explicitly with mental illness, and that which does focuses on the Kreyòl term fou (madness), a term that psychiatrists associate with schizophrenia and other psychoses. More work is needed to characterize potential forms of mild-to-moderate mental illness. Idioms of distress provide a promising avenue for exploring common mental disorders. Working in Haiti’s Central Plateau, we aimed to identify idioms of distress that represent cultural syndromes. We used ethnographic and epidemiologic methods to explore the idiom of distress reflechi twòp (thinking too much). This syndrome is characterized by troubled rumination at the intersection of sadness, severe mental disorder, suicide, and social and structural hardship. Persons with “thinking too much” have greater scores on the Beck Depression Inventory and Beck Anxiety Inventory. “Thinking too much” is associated with 8 times greater odds of suicidal ideation. Untreated “thinking too much” is sometimes perceived to lead to psychosis. Recognizing and understanding “thinking too much” may allow early clinical recognition and interventions to reduce long-term psychosocial suffering in Haiti’s Central Plateau.     

Delineation of amplification,hybridization and location effects in microarray data yields better-quality normalization

Background  

Oligonucleotide arrays have become one of the most widely used high-throughput tools in biology. Due to their sensitivity to experimental conditions, normalization is a crucial step when comparing measurements from these arrays. Normalization is, however, far from a solved problem. Frequently, we encounter datasets with significant technical effects that currently available methods are not able to correct.     

Quantitative,Architectural Analysis of Immune Cell Subsets in Tumor-Draining Lymph Nodes from Breast Cancer Patients and Healthy Lymph Nodes

Background

To date, pathological examination of specimens remains largely qualitative. Quantitative measures of tissue spatial features are generally not captured. To gain additional mechanistic and prognostic insights, a need for quantitative architectural analysis arises in studying immune cell-cancer interactions within the tumor microenvironment and tumor-draining lymph nodes (TDLNs).

Methodology/Principal Findings

We present a novel, quantitative image analysis approach incorporating 1) multi-color tissue staining, 2) high-resolution, automated whole-section imaging, 3) custom image analysis software that identifies cell types and locations, and 4) spatial statistical analysis. As a proof of concept, we applied this approach to study the architectural patterns of T and B cells within tumor-draining lymph nodes from breast cancer patients versus healthy lymph nodes. We found that the spatial grouping patterns of T and B cells differed between healthy and breast cancer lymph nodes, and this could be attributed to the lack of B cell localization in the extrafollicular region of the TDLNs.

Conclusions/Significance

Our integrative approach has made quantitative analysis of complex visual data possible. Our results highlight spatial alterations of immune cells within lymph nodes from breast cancer patients as an independent variable from numerical changes. This opens up new areas of investigations in research and medicine. Future application of this approach will lead to a better understanding of immune changes in the tumor microenvironment and TDLNs, and how they affect clinical outcomes.     

Erratum

Neurotransmitter receptor trafficking and the regulation of synaptic strength. Traffic 2001:2(7):437–448.