Blood pressure in adults with short stature skeletal dysplasias

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.     

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.      

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

Projections from primary somatosensory cortex to the neostriatum: the role of somatotopic continuity in corticostriatal convergence

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.     

Relationships of sleep duration with sociodemographic and health‐related factors,psychiatric disorders and sleep disturbances in a community sample of Korean adults

The aim of this study is to examine relationships of sleep duration with sociodemographic and health‐related factors, psychiatric disorders and sleep disturbances in a nationwide sample in Korea. A total of 6510 subjects aged 18–64 years participated in this study. Logistic regression was used to calculate the odd ratios and 95% confidence intervals of the covariates, psychiatric disorders and sleep disturbances across the following sleep duration categories: 5 h or less, 6, 7, 8 and 9 h or more per day. Low levels of education, unemployment and physical illness were associated with sleeping for 5 h or less and 9 h or more. Being older and widowed/divorced/separated, high levels of physical activity, pain/discomfort, obesity and high scores on the General Health Questionnaires were associated with sleeping for 5 h or less. Female, being younger and underweight were associated with sleeping for 9 h or more. Alcohol dependence, anxiety disorder and social phobia were associated significantly with sleeping for 5 h or less and 9 h or more. Other psychiatric disorders were more common in subjects who slept for 5 h or less (e.g. alcohol use disorder, mood disorder, major depressive disorder, dysthymic disorder, obsessive‐compulsive disorder and specific phobia) or 9 h or more (e.g. post‐traumatic stress disorder). In addition, subjects who slept for 5 h or less reported more sleep disturbances than did subjects who slept for 7 h. Short or long sleep is associated with psychiatric disorders and/or sleep disturbance, therefore attention to the mental health of short or long sleepers is needed.     

Phosphorylation of yellow fever virus NS5 alters methyltransferase activity

Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (YFV) NS5 expressed in mammalian cells. Multiple different phosphopeptides were detected. Mutational and additional mass spectrometry data implicated serine 56 (S56), a conserved residue near the active site in the NS5 methyltransferase domain, as one of the phosphorylation sites. Methyltransferase activity is required to form a methylated RNA cap structure and for translation of the YFV polyprotein. We show the 2′-O methylation reaction requires the hydroxyl side chain of S56, and replacement with a negative charge inhibits enzymatic activity. Furthermore mutational alteration of S56, S56A or S56D, prevents amplification in a viral replicon system. Collectively our data suggest phosphorylation of NS5 S56 may act to shut down capping in the viral life cycle.     

Influence of artificial gastric juice composition on bioaccessibility of cobalt- and tungsten-containing powders

The dissolution of metal-containing particles in the gastric compartment is poorly understood. The purpose of this study was to elucidate the influence of artificial gastric juice chemical composition on bioaccessibility of metals associated with ingestion-based health concerns. Dissolution rates were evaluated for well-characterized feedstock cobalt, tungsten metal, and tungsten carbide powders, chemically bonded pre-sintered (spray dryer material) and post-sintered (chamfer grinder) cemented tungsten carbide materials, and an admixture of pure cobalt and pure tungsten carbide, prepared by mechanically blending the two feedstock powders. Dissolution of each study material was evaluated in three different formulations of artificial gastric juice (from simplest to most chemically complex): American Society of Testing Materials (ASTM), U.S. Pharmacopoeia (USP), and National Institute for Occupational Safety and Health (NIOSH). Approximately 20% of cobalt dissolved in the first dissolution phase (t_1/2 = 0.02 days) and the remaining 80% was released in the second long-term dissolution phase (t_1/2 = 0.5 to 1 days). Artificial gastric juice chemical composition did not influence dissolution rate constant values (k, g/cm² day) of cobalt powder, either alone or as an admixture. Approximately 100% of the tungsten and tungsten carbide that dissolved was released in a single dissolution phase; k-values of each material differed significantly in the solvents: NIOSH > ASTM > USP (p<0.05). The k-values of cobalt and tungsten carbide in pre- and post-sintered cemented tungsten carbide powders were significantly different from values for the pure feedstock powders. Solvent composition had little influence on oral bioaccessibility of highly soluble cobalt and our data support consideration of the oral exposure route as a contributing pathway to total-body exposure. Solvent composition appeared to influence bioaccessibility of the low soluble tungsten compounds, though differences may be due to variability in the data associated with the small masses of materials that dissolved. Nonetheless, ingestion exposure may not contribute appreciably to total body burden given the short residence time of material in the stomach and relatively long dissolution half-times of these materials (t_1/2 = 60 to 380 days).     

Identification of a CD4 homologue in the cat

Monoclonal antibody, Fel 7, produced against cat T cells, was found to react with a single-chain glycoprotein of Mr 65,000 present on a majority of the thymocytes, 40% of lymph node cells, 15% of splenocytes and 25% of blood mononuclear cells. Using a previously reported antibody that recognizes the feline CD8 antigen, approximately 65% of cat thymocytes were shown to express both the Fel 7 and fCD8 antigens, while 14% and 6% expressed either the Fel 7 or the fCD8 determinant respectively. The Fel 7 and fCD8 antigens were expressed by mutually-exclusive subpopulations of peripheral T cells, and not by B cells, macrophages or other types of blood cells. Expression of the Fel 7 antigen was down-regulated and the molecule was phosphorylated when T cells were stimulated with phorbol ester, while the expression of the fCD8 antigen was unaffected by this treatment. The addition of soluble Fel 7 antibodies efficiently blocked Con A-induced proliferation of T cells in a dose-dependent manner. The data suggest that the mAb Fel 7 identifies a feline CD4 homologue, providing an important reagent for the study of normal and abnormal T cell development in cats.