Abstract Objective To determine the characteristics which lead individuals to get a flu shot. Study Design Two countries are examined using sample survey data to compare the relative contribution of education and self-perceived health in the flu shot decision. Methods Logit probability models are fitted to explain the binary decision to have a flu shot using the Canadian Covid-19 Antibody Survey for 2020 and the American National Health Interview Survey for 2022. Regressors included age gender, self reported health status and educational attainment. Results Educational attainment was shown to be the main driver of this decision in the US whereas self reported health explained most of the variation in the Canadian data. The difference in the results was attributed to differences in the health care systems. Conclusions Both countries have unacceptably low vaccination rates for influenza. For the US public policies should do a better job in addressing this problem by concentrating efforts on getting more low income or poorly educated respondents to get vaccinated. For Canada, the un-vaxinated are less visible but public education programs could be improved.
Bumpy and irritated skin can be brought on by tomato flu.The centre asserts that there is no connection between tomato flu and coronavirus, dengue, chikungunya, or monkeypox. According to reports, tomato flu is a self-limiting illness that primarily affects young children between the ages of 1 and 10 and people with weakened immune systems. In India, there have been over 100 instances of tomato flu reported in four distinct states: Tamil Nadu, Kerala, Odisha, and Haryana. Kids between the ages of 1 and 9 account for the majority of instances. However, all areas save the aforementioned four states remain unaffected. According to reports, it may be a clinical subtype of hand, foot, and mouth disease (HFMD).
Alcohol use disorder is complex and multifaceted, involving the coordination of multiple signaling systems across numerous brain regions. Previous work has indicated that both the insular cortex and dynorphin (DYN)/kappa opioid receptor (KOR) systems contribute to excessive alcohol use. More recently, we identified a microcircuit in the medial aspect of the insular cortex that signals through DYN/KOR. Here, we explored the role of insula DYN/KOR circuit components on alcohol intake in a long-term intermittent access (IA) procedure. Using a combination of conditional knock-out strategies and site-directed pharmacology, we discovered distinct and sex-specific roles for insula DYN and KOR in alcohol drinking and related behavior. Our findings show that insula DYN deletion blocked escalated consumption and decreased the overall intake of and preference for alcohol in male and female mice. This effect was specific to alcohol in male mice, as DYN deletion did not impact sucrose intake. Further, insula KOR antagonism reduced alcohol intake and preference during the early phase of IA in male mice only. Alcohol consumption was not affected by insula KOR knockout in either sex. In addition, we found that long-term IA decreased the intrinsic excitability of DYN and deep layer pyramidal neurons (DLPNs) in the insula of male mice. Excitatory synaptic transmission was also impacted by IA, as it drove an increase in excitatory synaptic drive in both DYN neurons and DLPNs. Combined, our findings suggest there is a dynamic interplay between excessive alcohol consumption and insula DYN/KOR microcircuitry. SIGNIFICANCE STATEMENT The insular cortex is a complex region that serves as an integratory hub for sensory inputs. In our previous work, we identified a microcircuit in the insula that signals through the kappa opioid receptor (KOR) and its endogenous ligand dynorphin (DYN). Both the insula and DYN/KOR systems have been implicated in excessive alcohol use and alcohol use disorder (AUD). Here, we use converging approaches to determine how insula DYN/KOR microcircuit components contribute to escalated alcohol consumption. Our findings show that insula DYN/KOR systems regulate distinct phases of alcohol consumption in a sex-specific manner, which may contribute to the progression to AUD.
BACKGROUND Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).
The main transport channel of the global economy is represented by shipping. Engineers and hull designers are more preoccupied in ensuring fleet safety, the proper operation of the ships, and, more recently, compliance with International Maritime Organization (IMO) regulatory incentives. Considerable efforts have been devoted to in-depth understanding of the hydrodynamics mechanism and prediction of ship behavior in waves. Prediction of seakeeping performances with a certain degree of accuracy is a demanding task for naval architects and researchers. In this paper, a fully numerical approach of the seakeeping performance of a KRISO (Korea Research Institute of Ships and Ocean Engineering, Daejeon, South Korea) container ship (KCS) container vessel is presented. Several hydrodynamic methods have been employed in order to obtain accurate results of ship hydrodynamic response in regular waves. First, an in-house code DYN (Dynamic Ship Analysis, “Dunarea de Jos” University of Galati, Romania), based on linear strip theory (ST) was used. Then, a 3D fully nonlinear time-domain Boundary Element Method (BEM) was implemented, using the commercial code SHIPFLOW (FLOWTECH International AB, Gothenburg, Sweden). Finally, the commercial software NUMECA (NUMECA International, Brussels, Belgium) was used in order to solve the incompressible unsteady Reynolds-averaged Navier–Stokes equation (RANSE) flow at ship motions in head waves. The results obtained using these methods are represented and discussed, in order to establish a methodology for estimating the ship response in regular waves with accurate results and the sensitivity of hydrodynamical models.
B. Molins, Adriana Mora, Sara Romero-Vázquez
et al.
The vascular endothelium responds to the shear stress generated by blood flow and changes function to maintain tissue homeostasis and adapt to injury in pathological conditions. Shear stress in the retinal circulation is altered in patients with retinal vascular diseases, such as diabetic retinopathy. Therefore, we aimed to study the effect of laminar shear stress on barrier properties and on the release of proinflammatory cytokines in human retinal microvascular endothelial cells (HRMEC). HRMEC were cultured in Ibidi flow chambers and exposed to laminar shear stress (0-50 dyn/cm2) for 24-48 h. Tight junction distribution (ZO-1 and claudin-5) and cytokine production were determined by immunofluorescence and ELISA, respectively. The chemotactic effect of conditioned media exposed to shear stress was determined by measuring lymphocyte transmigration in Transwells. We found that cells exposed to moderately low shear stress (1.5 and 5 dyn/cm2) showed enhanced distribution of membrane ZO-1 and claudin-5 and decreased production of the proinflammatory cytokines IL-8, CCL2, and IL-6 compared to static conditions and high shear stress values. Moreover, conditioned media from cells exposed to low shear stress, had the lowest chemotactic effect to recruit lymphocytes compared to conditioned media from cells exposed to static and high shear stress conditions. In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC.
Abstract Background Alinity hq (Abbott) is a new high-throughput hematology analyzer that exclusively employs optical principles for detecting and enumerating blood cells. It reports 29 parameters, including a six-part white blood cell (WBC) differential. The aim of this multicenter study was to evaluate the analytical and clinical performance of the Alinity hq. Methods Complete blood count (CBC) results and morphological flagging were compared to that of CELL-DYN Sapphire (Abbott) and 2 × 200-cell manual differential results, on 1473 whole-blood samples from a well-defined patient population from three different clinical laboratories in the Netherlands. In addition, within-run and within-laboratory precision, linearity, limit of quantitation, carryover and sample stability were assessed. External quality assessment samples were also evaluated. Results Data analysis demonstrated strong concordance of Alinity hq results with those of CELL-DYN Sapphire for all CBC parameters, except for basophil granulocytes. Alinity hq WBC differential showed high level of agreement with manual differential results and exhibited a better agreement with manual basophil results than CELL-DYN Sapphire. The sensitivity of the Alinity hq Blast flag was 57.6%, equal to the 57.6% sensitivity of the CELL-DYN Sapphire’s Blast Alert. When considering samples with ≥5% blasts, the sensitivity of the Alinity hq Blast flag was 70.0%. Analytical performance of Alinity hq was shown to be consistent with state-of-the-art (SOTA) performance characteristics. Conclusions Alinity hq CBC measurands demonstrated good overall agreement with results obtained with CELL-DYN Sapphire, as well as manual WBC differential. The analytical and clinical performance characteristics of Alinity hq make it well suited for clinical laboratories.
Abstract We describe mathematical model to study bird flu transmission in bird system and human system. The behaviour of this model was analyzed through stability of constant solutions. Our result shows that these stabilities depend on values of some parameters. Furthermore, the model of bird system is reformulated by adding diffusive term. Traveling wave solutions of the diffusive model were investigated. The positive solutions are numerically illustrated with homogeneous Neumann boundary conditions. The result shows that transmission progress can be expressed in form of a traveling wave solutions.
Molecular changes induced by excessive alcohol consumption may underlie formation of dysphoric state during acute and protracted alcohol withdrawal which leads to craving and relapse. A main molecular addiction hypothesis is that the upregulation of the dynorphin (DYN)/κ-opioid receptor (KOR) system in the nucleus accumbens (NAc) of alcohol-dependent individuals causes the imbalance in activity of D1- and D2 dopamine receptor (DR) expressing neural circuits that results in dysphoria. We here analyzed post-mortem NAc samples of human alcoholics to assess changes in prodynorphin (PDYN) and KOR (OPRK1) gene expression and co-expression (transcriptionally coordinated) patterns. To address alterations in D1- and D2-receptor circuits, we studied the regulatory interactions between these pathways and the DYN/KOR system. No significant differences in PDYN and OPRK1 gene expression levels between alcoholics and controls were evident. However, PDYN and OPRK1 showed transcriptionally coordinated pattern that was significantly different between alcoholics and controls. A downregulation of DRD1 but not DRD2 expression was seen in alcoholics. Expression of DRD1 and DRD2 strongly correlated with that of PDYN and OPRK1 suggesting high levels of transcriptional coordination between these gene clusters. The differences in expression and co-expression patterns were not due to the decline in neuronal proportion in alcoholic brain and thereby represent transcriptional phenomena. Dysregulation of DYN/KOR system and dopamine signaling through both alterations in co-expression patterns of opioid genes and decreased DRD1 gene expression may contribute to imbalance in the activity of D1- and D2-containing pathways which may lead to the negative affective state in human alcoholics.
The dynorphin/kappa opioid receptor (DYN/KOR) system appears to be a key mediator of the behavioral effects of chronic exposure to alcohol. Although KOR opioid receptor antagonists have been shown to decrease stress-related behaviors in animal models during acute ethanol withdrawal, the role of the DYN/KOR system in regulating long-term behavioral changes following protracted abstinence from ethanol is not well understood. The objective of the current study was to further explore the role of the DYN/KOR system in regulating stress-related behavioral changes associated with acute withdrawal and protracted abstinence from ethanol. More specifically, the present experiments sought to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI) to reverse depressive-like behavior in the forced swim test in rats exposed to chronic ethanol. In the first experiment, rats were fed an ethanol or control liquid diet for 28–30 days, and then 24 hours after removal of the diet, were exposed to inescapable swim stress. Immediately following this procedure, rats were injected with nor-BNI (20 mg/kg) or saline and then tested 24 hours later in the forced swim test. A second experiment used a similar procedure to examine the effects of nor-BNI on behavioral changes during protracted abstinence in rats tested in the forced swim test 3 weeks after exposure to the ethanol liquid diet procedure. Ethanol-dependent rats showed increased immobility, which is thought to indicate a depressive-like state, when examined during acute withdrawal and protracted abstinence compared to controls, an effect attenuated by nor-BNI. These results suggest that the DYN/KOR system plays role in mediating both short- and long-term behavioral changes associated with depression following chronic alcohol exposure.
The dynorphin/kappa (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adults, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.
The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3–4 days were exposed to a step increase (0 to 20 dyn/cm2) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction. The expressions of Rho kinase (ROCK) and its downstream signal molecules, the myosin-binding subunit of myosin phosphatase (MYPT) and the myosin light chain 2 (MLC2), were evaluated. Results showed that the exposure of HUVSMCs to shear stress for 30 min induced cell contraction significantly, which was accompanied by ROCK1 up-regulation, re-distribution, as well as MYPT1 and MLC activation. However, these shear induced phenomenon could be completely abolished by heparinase III or Y-27632 pre-treatment. These results indicate shear stress induced VSMC contraction was mediated by cell surface glycocalyx via a ROCK-MLC phosphatase (MLCP) pathway, providing evidence of the glycocalyx mechanotransduction in myogenic response.