Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats

Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 micrograms) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4 degrees C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with beta-adrenoceptor antagonist, propranolol (10 micrograms) but not with the alpha-adrenoceptor antagonist, prazosin (1 and 10 micrograms). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 microgram) and the neurotoxin DSP-4 (25 micrograms). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that beta-adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress.     

Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3)

X-linked progressive retinal atrophy (XLPRA) in the Siberian husky dog is a naturally occurring X-linked retinopathy closely resembling X-linked retinitis pigmentosa (XLRP) in humans. In affected males, initial degeneration of rods is followed by cone degeneration and complete retinal atrophy; carrier females have random patches of rod degeneration consistent with random X chromosome inactivation. By typing the XLPRA pedigree with five intragenic markers [dystrophin, retinitis pigmentosa GTPase regulator ( RPGR ), tissue inhibitor of metalloproteinases 1, androgen receptor and factor IX], we established a linkage map of the canine X chromosome, and confirmed that the order of these five genes is identical to that on the human X. XLPRA was tightly linked to an intragenic RPGR polymorphism (LOD 11.7, zero recombination), thus confirming locus homology with RP3. We cloned the full-length canine RPGR cDNA and three additional splice variants. No disease-causing mutation was found in the RPGR-coding sequence of the four splice variants characterized, a finding similar to approximately 80% of human XLRP patients whose disease maps to the RP3 locus. In addition, there were no significant differences in the proportional expression of each splice variant in normal and pre-degenerate XLPRA-affected retina. Expression of all RPGR splice variants increased later in the disease, when retinas were undergoing active degeneration. The results provide further evidence of cross-species retention of a complex splicing pattern in the 3' portion of RPGR, the functional significance of which is unknown. In addition, the possibility of another disease locus in the RP3 region is supported.     

Coordinated multivesicular release at a mammalian ribbon synapse

Traditional models of synaptic transmission hold that release sites within an active zone operate independently. Although the release of multiple vesicles (multivesicular release; MVR) from single active zones occurs at some central synapses, MVR is not thought to require coordination among release sites. Ribbon synapses seem to be optimized to release many vesicles over an extended period, but the dynamics of MVR at ribbon synapses is unknown. We examined MVR at a ribbon synapse in a retinal slice preparation using paired recordings from presynaptic rod bipolar and postsynaptic AII amacrine cells. When evoked release was highly desynchronized, discrete postsynaptic events were larger than quantal miniature excitatory postsynaptic currents (mEPSCs) but had the same time course. The amplitude of these multiquantal mEPSCs, which seem to arise from the essentially simultaneous release of multiple vesicles, was reduced by lowering release probability. The release synchrony reflected in these multivesicular events suggests that release within an active zone is coordinated during MVR.     

Benzoxazole-2-thiol/dibenzoyl peroxide combination as photoinitiator for methyl methacrylate polymerization

Benzoxazole-2-thiol ( 1 )/dibenzoyl peroxide (Bz₂O₂) was used as photoinitiator for the polymerization of methyl methacrylate (MMA) in bulk and in solution. The study of initiator decomposition was conducted spectrophotometrically. Kinetic studies of the photopolymerization indicated the formation of a complex between 1 and Bz₂O₂ in the stoichiometric ratio 2:1. The initiation is believed to occur via in situ formation of bis(benzoxazol-2-yl) disulfide in the presence of light.     

Chemical and biological characterization of volatile components of environmental samples after fractionation by vacuum line cryogenic distillation

Volatile components from diesel exhaust particles and coal gasifier process gas condensate were vacuum fractionated by cryogenic distillation and identified by infrared spectroscopy and gas chromatography/mass spectrometry. The vacuum distillation line consisted of a sample flask and nine traps cooled from 0°C to ?196°C in approximately 20°C steps. The pressure in the vacuum line of about 10^?2 Torr was maintained with a vacuum pump. Separated compounds were identified by comparison to reference infrared spectra and confirmed by comparison with standards when practical. Volatile compounds identified from the diesel exhaust particle sample included NO_x, carbon dioxide, sulfur dioxide, alkanes, aldehydes, and one and two ring aromatic hydrocarbons. Volatile compounds identified in process gas condensate from a coal gasifier were ammonia, carbonyl sulfide, carbon dioxide, C₃-C₇ hydrocarbons, one and two ring aromatic hydrocarbons, and phenols. Volatile components collected at either 0° or ?24°C were evaluated to determine their genotoxicity using the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) assay. Neither the gasifier condensate nor diesel particle samples produced mutations at the HGPRT locus. The diesel samples were not cytotoxic at the concentrations tested (100 μg/ml) but the gasifier samples resulted in 50% cell killing at concentrations between 25 and 100 μg/ml depending on the temperature of collection and the test conditions. Vacuum desorption with cryogenic distillation has provided a means to separate the volatile components in complex environmental samples to allow chemical and biological characterization of these components.     

Between a hygiene rock and a hygienic hard place: Avoiding SARS-CoV-2 while needing environmental exposures for immunity

Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers.Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene.     

Determinants and Consequences of Adolescent Fatherhood: A Longitudinal Study in Ethiopia,India, Peru,and Vietnam

PurposeAdolescent parenthood is a major challenge in low- and middle-income countries (LMICs). However, the vast majority of the evidence has focused on adolescent motherhood. Little is known about adolescent fatherhood in LMICs. The aim of this study was to examine the determinants of early fatherhood and its consequences on a range of outcomes among adolescent males.MethodsThis study used three waves of longitudinal data from the multicountry Young Lives cohort study, specifically following a sample of 1,779 adolescent boys at ages 15, 19, and 22 years in Ethiopia, India, Peru, and Vietnam. Individual fixed effects models were conducted to investigate the sociodemographic determinants of adolescent fatherhood and the consequences of adolescent fatherhood on males' education, health, psychosocial well-being, and time use outcomes.ResultsThe results indicated that lower educational attainment, absence of the adolescent's mother and father from the home, larger household size, and poverty increased the likelihood of becoming an adolescent father by age 22 years. The results revealed that becoming an adolescent father was associated with a higher likelihood of school dropout, being overweight, smoking, greater internalizing problems, and less time spent on leisure activities and more time spent on caregiving responsibilities.ConclusionsHighlighting the experiences of young men as adolescent parents in LMICs, findings underscore the importance of prevention strategies to delay early parenthood for adolescent boys and multicomponent interventions to support young fathers and their unique health, socioeconomic, psychosocial, and behavioral needs.     

Impact of Compensated Cirrhosis Etiology on Postoperative Outcomes Following Total Knee Arthroplasty

BackgroundCirrhotics often demonstrate worse outcomes than their non-cirrhotic counterparts following orthopedic surgery; however, there are limited arthroplasty-focused data on this occurrence. Additionally, variances in postoperative outcomes among the different etiologies of cirrhosis have not been well described. The aim of this study is to evaluate the effect compensated cirrhosis had on postoperative outcomes following elective total knee arthroplasty (TKA).MethodsIn total, 1,734,568 patients who underwent primary TKA from 2006 to 2013 were identified using the Medicare Claims Database. Patients were divided into those with a history of compensated cirrhosis and those with no history of liver disease. Subgroup analysis was performed based on the etiology of cirrhosis. Multivariate logistic regression was used to evaluate postsurgical outcomes of interest.ResultsCirrhotic patients had higher risk of developing disseminated intravascular coagulation (odds ratio [OR] 2.76, P = .003), encephalopathy (OR 3.00, P < .001), and periprosthetic infection (OR 1.79, P < .001) compared to controls. Following subgroup analysis, alcoholic cirrhotics had high risk of periprosthetic infection (OR 2.12, P < .001), fracture (OR 3.28, P < .001), transfusion (OR 2.45, P < .001), and encephalopathy (OR 7.34, P < .001) compared to controls. Viral cirrhosis was associated with an increase in 90-day charges ($14,941, P < .001) compared to controls, while cirrhosis secondary to other causes was associated with few adverse outcomes compared to controls.ConclusionLiver cirrhosis is an independent risk factor for increased perioperative morbidity and financial burden following TKA. Cirrhosis due to etiologies other than viral infections and alcoholism are associated with few adverse outcomes. Surgeons should be aware of these complications to properly optimize postoperative management.