Lindbergfanning6937
The previously broad classification of CRS with or without nasal polyps is no longer sufficient at driving these treatment decisions.
Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly become a great public health hazard globally. Nasal epithelial cells are an important site for SARS-CoV-2 infection and replication. The purpose of this review is to summarize recent findings on the endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) and the potential impact of SARS-CoV-2 infection.
Endotypes of CRSwNP are characterized by type 1, type 2 and type 3 inflammation according to patterns of inflammatory cells and the cytokines expressed in nasal tissue. Nasal epithelial cells show the highest expression of angiotensin-converting enzyme 2 (ACE2), the receptor for attachment and entry of SARS-CoV-2 into host cells, among all investigated cells in the respiratory tree. SARS-CoV-2 infection likely leads to increased activation of T-helper-1 (Th1) cell responses. Recent studies further suggest that ACE2 may be upregulated by type 1 and downregulated by type 2 inflammatory cytokines in nasal epithelial cells.
Expression of ACE2 in nasal epithelial cells is influenced by inflammatory endotypes of CRSwNP. Type 1 inflammation in nasal tissue may increase the risk of SARS-CoV-2 infection by upregulating ACE2 expression. However, clinical association between CRSwNP and COVID-19 is still unclear.
Expression of ACE2 in nasal epithelial cells is influenced by inflammatory endotypes of CRSwNP. Type 1 inflammation in nasal tissue may increase the risk of SARS-CoV-2 infection by upregulating ACE2 expression. However, clinical association between CRSwNP and COVID-19 is still unclear.Hyperactivity of amygdala is observed in patients with major depressive disorder. Although the role of α1-adrenoceptor in amygdala on fear memory has been well studied, the role of α1-adrenoceptor in amygdala on depression-like behaviors remains unclear. Therefore, we investigated the effect of α1A-adrenoreceptor in amygdala on despair behavior, evaluated by the immobility time during tail suspension test (TST), pharmacological intervention, and immunohistological methods. C57BL6/J mice given a bilateral intra-amygdala injection of artificial cerebrospinal fluid exhibited an increased duration of immobility in the latter half of both trials of TST with a 24-h interval, a phenomenon known as learned despair. Intra-amygdala injection of WB4101 (1.7 nmol/0.1 µl), an α1 adrenoreceptor antagonist, but not propranolol (250 pmol/0.1 µl), a β-adrenoreceptor antagonist, blocked the induction of learned despair during TST. Immunostaining experiments revealed that ~61-75% of α1A-adrenoreceptor-positive neurons were colocalized with GAD65/67 in amygdala, implying that the α1-adrenoceptors in amygdala may enormously regulate the GABA release. Protein kinase C-beta (PKCβ) was predominantly expressed in the α1A-adrenoreceptor-positive neurons in the BLA, whereas protein kinase C-epsilon (PKCε) was highly expressed with the α1A-adrenoreceptor in the Central nucleus of amygdala. Intra-amygdala injection of ruboxistaurin (10 pmol/0.1 µl), a PKCβ inhibitor, blocked the induction of learned despair during TST, whereas neither TAT-εV1-2 (500 ng/0.1 μl), a cell-permeant PKCε inhibitory peptide, nor HBDDE (50 pmol/0.1 µl), an inhibitor of PKCα and -γ, affected the duration of immobility during TST. These data suggest that the α1-adrenoreceptor in amygdala regulates the induction of learned despair via PKCβ.
Clinical practice guidelines provide reliable, vetted, and critical information to bring research to practice. Some medical specialties (e.g., physical medicine and rehabilitation) provide multidomain treatment for various conditions. This presents challenges because physical medicine and rehabilitation is a small specialty, a diverse patient base in terms sociodemographics and diagnosis, treatments are difficult to standardize, and rehabilitation research is underfunded. We wished to identify quality and applicability of clinical practice guidelines and searched "Spinal Cord Injury AND Clinical Practice Guidelines AND Rehabilitation" and vetting process.Three hundred fifty-nine articles were identified of which 58 met all criteria for full-text review of which 13 were included in the final selection. Additional publications were accessed from a nondatabase search. Five articles addressed postacute care, community treatment. Nine articles had no recorded vetting process but addressed rehabilitation as an ouce guidelines and searched "Spinal Cord Injury AND Clinical Practice Guidelines AND Rehabilitation" and vetting process.Three hundred fifty-nine articles were identified of which 58 met all criteria for full-text review of which 13 were included in the final selection. Additional publications were accessed from a nondatabase search. Five articles addressed postacute care, community treatment. Nine articles had no recorded vetting process but addressed rehabilitation as an outcome and were included separately. Many of the clinical practice guidelines were developed without evidence from randomized controlled trials, one had input from stakeholders, and some are out of date and do not address important aspects of changes in demographics of the affected population and the use of newer technologies such as sensors and robotics and devices. Identification of these gaps may help stimulate treatment that is clinically relevant, accessible, and current.
Vasculitides can affect small, medium and/or large vessels, leading to end-organ damage, decreased quality of life and death. Glucocorticoids remain the backbone of treatment for systemic vasculitis but are associated with numerous toxicities. In recent years, the efficacy of glucocorticoid-sparing biologic and novel small molecule therapies has been demonstrated.
In giant cell arteritis, tocilizumab was superior to glucocorticoid monotherapy in maintenance remission and cumulative glucocorticoid exposure and is now approved for the treatment of giant cell arteritis. In addition to the previously demonstrated efficacy of rituximab for remission induction in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, recent trials have also demonstrated its superiority for remission maintenance compared to alternative approaches. Mepolizumab is superior to standard of care alone with regard to remission rates and glucocorticoid-sparing effect in refractory eosinophilic granulomatosis with polyangiitis. Avacopan has shown significant promise in ANCA-associated vasculitis as part of a glucocorticoid-free induction regimen in a recently completed phase 3 trial. Use of biologics in rarer vasculitides remains guided by reports from small case series.
Biologics and other novel therapies have an increasingly important role in the management of systemic vasculitis. Additional studies are needed to define their optimal use and to guide their use in more rare forms of vasculitis.
Biologics and other novel therapies have an increasingly important role in the management of systemic vasculitis. Namodenoson Additional studies are needed to define their optimal use and to guide their use in more rare forms of vasculitis.
BMI and waist circumference (WC) have commonly been used to identify obesity in practice. The aim of the present study was to assess the blood pressure (BP) status among Chinese college students categorized by BMI and WC.
A total of 4226 college students (2107 males and 2119 females) aged 19-22 years included in the study. The WHO BMI cutoffs were used to define underweight, normal weight and overweight. The WC cutoffs (90 cm for man and 80 cm for woman) were used to define central obesity. High BP was defined as SBP/DBP ≥140/90 mmHg. The BP status of subjects within each category across BMI and WC were assessed.
When subjects were categorized by BMI, overweight males and females had a higher prevalence of high BP than their nonoverweight counterparts. When WC was used to diagnose central obesity, subjects with central obesity had a higher prevalence of high BP than those with normal WC. A positive association between BMI, WC and BP was also observed even in normal-weight subjects, with 'high normal BMI' subgroup (BMI = 23.7-24.9) had a higher BP level and prevalence of high BP than 'low normal BMI' subgroups (BMI = 18.5-19.7 and BMI = 19.8-21.0, P < 0.05).
Prevention of overweight/obesity in youth may be an effective approach for preventing the development of hypertension in the future; for normal-weight youth, it is essential to keep their BMI at a lower level within normal range.
Prevention of overweight/obesity in youth may be an effective approach for preventing the development of hypertension in the future; for normal-weight youth, it is essential to keep their BMI at a lower level within normal range.Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.Identifying genes that result in monogenic diabetes can provide insights that can build a scientific foundation for precision medicine. At present, nearly 20% of neonatal diabetes cases have unknown causes. In this issue of the JCI, De Franco and Lytrivi et al. sequenced the genome of two probands with a rare neonatal diabetes subtype that also associated with microcephaly and epilepsy. The authors revealed mutations in the YIPF5 gene. YIPF5 resides in the Golgi apparatus and is thought to play a critical role in vesicular trafficking. Notably, disrupting YIPF5 in β cell-based models induced ER stress signaling and resulted in the accumulation of intracellular proinsulin. We believe that utilizing registries and biobanks to reveal other monogenic atypical forms of diabetes is an important approach to gaining insight and suggest that an insulin sensitizer may alleviate ER stress associated with YIPF5 disruption by decreasing the demand for insulin secretion.