Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2.

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has been no scientific evidence to recommend mouth rinses with an anti-SARS-CoV-2 effect to control the viral load in the oral cavity. This critical review indicates that current knowledge of these reagents would likely improve trends in salivary viral load status. This finding is a strong sign to encourage clinical research for which quality protocols are already available in the literature

Effects of lockdown on emergency room admissions for psychiatric evaluation: an observational study from the AUSL Romagna, Italy

Objectives: An observation of the admissions to the emergency room (ER) requiring psychiatric evaluation during the lockdown and investigation of the demographic and clinical variables. Methods: Retrospective longitudinal observational study of ER accesses for psychiatric evaluation was performed, comparing two periods (9 March–3 May 2020 vs. 9 March–3 May 2019). Data (number of admissions, key baseline demographic and clinical variables) were extracted from the ER databases of referral centres in a well-defined geographic area of North-Eastern Italy (Cesena, Ravenna, Forlì, and Rimini). Results: A 15% reduction of psychiatric referrals was observed, together with a 17% reduction in the total number of patients referring to the ER. This reduction was most evident in the first month of the lockdown period (almost 25% reduction of both referrals and patients). Female gender (OR: 1.52: 95%, CI: 1.12–2.06) and being a local resident (OR: 1.54: 95%CI: 1.02–2.34) were factors associated with the decrease. Conclusions: Lockdown changed dramatically health priorities in the local population, including people with mental health. We speculate that our observations do not only refer to the confinement due to the lockdown regime but also to fear of contagion and adoption of different coping strategies, especially in women.Key-points During lockdown 15% reduction of psychiatric visits and >17% reduction in the number of psychiatric patients referring to the ER was observed. in the first four weeks of the lockdown almost 25% reduction of both visits and patients was observed Female gender and being a local resident were factors associated with the decrease

Na+/K+-ATPase is a new interacting partner for the neuronal glycine transporter GlyT2 that downregulates its expression in vitro and in vivo

The neuronal glycine transporter GlyT2 plays a fundamental role in the glycinergic neurotransmission by recycling the neurotransmitter to the presynaptic terminal. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is absolutely necessary to preserve quantal glycine content in synaptic vesicles. Alterations in GlyT2 activity modify glycinergic neurotransmission and may underlie several neuromuscular disorders, such as hyperekplexia, myoclonus, dystonia, and epilepsy. Indeed, mutations in the gene encoding GlyT2 are the main presynaptic cause of hyperekplexia in humans and produce congenital muscular dystonia type 2 (CMD2) in Belgian Blue cattle. GlyT2 function is strictly coupled to the sodium electrochemical gradient actively generated by the Na+/K+-ATPase (NKA). GlyT2 cotransports 3Na+/Cl-/glycine generating large rises of Na+ inside the presynaptic terminal that must be efficiently reduced by the NKA to preserve Na+ homeostasis. In this work, we have used high-throughput mass spectrometry to identify proteins interacting with GlyT2 in the CNS. NKA was detected as a putative candidate and through reciprocal coimmunoprecipitations and immunocytochemistry analyses the association between GlyT2 and NKA was confirmed. NKA mainly interacts with the raft-associated active pool of GlyT2, and low and high levels of the specific NKA ligand ouabain modulate the endocytosis and total expression of GlyT2 in neurons. The ouabain-mediated downregulation of GlyT2 also occurs in vivo in two different systems: zebrafish embryos and adult rats, indicating that this NKA-mediated regulatory mechanism is evolutionarily conserved and may play a relevant role in the physiological control of inhibitory glycinergic neurotransmission

Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs

© 2015 Macmillan Publishers Limited. Epithelial organs develop through tightly coordinated events of cell proliferation and differentiation in which endocytosis plays a major role. Despite recent advances, how endocytosis regulates the development of vertebrate organs is still unknown. Here we describe a mechanism that facilitates the apical availability of endosomal SNARE receptors for epithelial morphogenesis through the developmental upregulation of plasmolipin (pllp) in a highly endocytic segment of the zebrafish posterior midgut. The protein PLLP (Pllp in fish) recruits the clathrin adaptor EpsinR to sort the SNARE machinery of the endolysosomal pathway into the subapical compartment, which is a switch for polarized endocytosis. Furthermore, PLLP expression induces apical Crumbs internalization and the activation of the Notch signalling pathway, both crucial steps in the acquisition of cell polarity and differentiation of epithelial cells. We thus postulate that differential apical endosomal SNARE sorting is a mechanism that regulates epithelial patterning.MINECO (BFU2011-22622) and CONSOLIDER (CSD2009-00016); Fundación Obra Social `La Caixa' PhD fellowship. G.A. was supported by the Amarouto Program for senior researchers from the Comunidad Autónoma de Madrid.Peer Reviewe

Mid-term psychiatric consequences of the COVID-19 pandemic: a 4 months observational study on emergency room admissions for psychiatric evaluation after the (first) lockdown period in Italy

Purpose: The aim of our study is to evaluate the number and the features of admissions to the emergency room (ER) requiring psychiatric consultation, in the period between May 4th and August 31st 2020. Methods: We carried out a retrospective longitudinal observational study examining the 4 months following the initial lockdown imposed during the COVID-19 outbreak (May 4th and August 31st 2020). More specifically, the ER admissions leading to psychiatric referral were reviewed at all seven public hospitals of AUSL Romagna (Emilia Romagna region, Italy). Socio-demographic variables, history of medical comorbidities or psychiatric disorders, reason for ER admission, psychiatric diagnosis at discharge, and actions taken by the psychiatrist were collected. Results: An 11.3% (p = 0.007) increase in psychiatric assessments was observed when compared with the same period of the previous year (2019). A positive personal history of psychiatric disorders (OR:0.68, CI: 0.53–0.87) and assessments leading to no indication for follow-up (OR: 0.22, CI: 0.13–0.39) were significantly less frequent, while there was a significant increase of cases featuring organic comorbidities (OR: 1.24, CI: 1.00–1.52) and suicidal ideation/self-harm/suicide attempt (OR: 1,71, CI: 1.19–2.45) or psychomotor agitation (OR: 1.46, CI: 1.02–2.07) as reason for admission. Conclusions: Our results showed an increase in ER psychiatric consultations compared to the previous year, underlying the increased psychological distress caused by the lockdown

Smoothelin-like 2 Inhibits Coronin-1B to Stabilize the Apical Actin Cortex during Epithelial Morphogenesis

The actin cortex is involved in many biological processes and needs to be significantly remodeled during cell differentiation. Developing epithelial cells construct a dense apical actin cortex to carry out their barrier and exchange functions. The apical cortex assembles in response to three-dimensional (3D) extracellular cues, but the regulation of this process during epithelial morphogenesis remains unknown. Here, we describe Smoothelin-like 2 (SMTNL2) function, a member of the smooth-muscle related Smoothelin protein family, in apical cortex maturation. SMTNL2 is induced during the development of multiple epithelial tissues and localizes to the apical and junctional actin cortex in intestinal and kidney epithelial cells. SMTNL2 deficiency leads to membrane herniations in the apical domain of epithelial cells, indicative of cortex abnormalities. We find that SMTNL2 binds to actin filaments and is required to slow down the turnover of apical actin. We also characterize the SMTNL2 proximal interactome and find that SMTNL2 executes its functions partly through inhibition of Coronin-1B. While Coronin-1B-mediated actin dynamics are required for early morphogenesis, its sustained activity is detrimental for the mature apical shape. SMTNL2 binds to Coronin-1B through its N-terminal coiled-coil region and negates its function to stabilize the apical cortex. In sum, our results unveil a mechanism for regulating actin dynamics during epithelial morphogenesis, providing critical insights on the developmental control of the cellular corte

The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2

Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation. © 2010 Elsevier Inc.This work was supported by grants (BFU2006-01925, BFU2009-07886, and CONSOLIDER COAT CSD2009-00016) to M.A.A. from the Ministerio de Ciencia e Innovación (MICINN), Spain. R.M. is the holder of a contract from the Ramón y Cajal Program of the MICINN. The authors declare no competing financial interests

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity