Is disruption of sleep quality a consequence of severe Covid-19 infection? A case-series examination

ABSTRACT

The Covid-19 outbreak put enormous stress on the health system worldwide, and objective data to handle the emergency are still needed. We aimed to objectively assess the consequence of severe symptoms of Covid-19 infection on sleep quality through wrist actigraphy monitoring of four patients during the sub-acute recovery stage of the disease. The sleep of those patients who had experienced the most severe respiratory symptoms and who had needed prolonged intensive care unit (ICU) stay showed lower Sleep Efficiency and Immobility Time and higher Fragmentation Index compared to those patients who had experienced only mild respiratory symptoms and not requiring ICU stay. Wrist actigraphy assessment provided important clinical information about the sleep and activity levels of Covid-19 patients during the post-acute rehabilitation management.     

Chromosomal studies in <Emphasis Type="Italic">Crenicichla lepidota</Emphasis> and <Emphasis Type="Italic">Australoheros facetus</Emphasis> (Cichlidae,Perciformes) from extreme Southern Brazil

Fishes of the family Cichlidae generally show low karyotype variability. Nevertheless, karyotype variants have been identified within some genera, providing information about their evolutionary history. In the present study, karyotype characteristics of Crenicichla lepidota and Australoheros facetus, two sympatric species found in the São Gonçalo-Mangueira basin, were studied. Besides conventional procedures, double fluorochromes staining chromomycin A₃/DAPI and fluorescent in situ hybridization (FISH) with rDNA probes were also used. Both species presented 2n = 48 chromosomes, but karyotypes were differentiated by fundamental number, which was equal to 70 in A. facetus and 56 in C. lepidota. Similar heterochromatin distribution patterns were also observed on the pericentromeric region of most chromosomes, although C. lepidota presented an additional heterochromatic block in the first pair. The Ag-NORs, 18S rDNA probe and CMA₃/DAPI were coincident in location on the first and second pairs of C. lepidota and A. facetus, respectively. The minor rDNA loci (5S rDNA) were found in four sites located on two distinct chromosomal pairs in C. lepidota. Although the data obtained here to C. lepidota and to A. facetus show chromosomal characteristics considered ancestral to the family, new data are presented to both species. Additionally, this study corroborates the hypothesis in which evolutionary processes like non-Robertsonian rearrangements are involved in the diversification of the major groups of Neotropical Cichlidae. Thus, the karyotype diversification observed in A. facetus have the high fundamental number pathway while C. lepidota has others evolutionary chromosomal mechanisms.     

Endothelins participate in the central and peripheral regulation of submandibular gland secretion in the rat

We previously reported that endothelins (ETs) are involved in the rat central and peripheral regulation of bile secretion. In this study we sought to establish whether ET-1 and ET-3 modulated submandibular gland secretion when locally or centrally applied. Animals were prepared with gland duct cannulation to collect saliva samples and jugular cannulation to administer sialogogues. ETs were given either into the submandibular gland or brain lateral ventricle. Intraglandularly administered ETs failed to elicit salivation per se. However, ET-1, but not ET-3, potentiated both cholinergic- and adrenergic-evoked salivation through ET(A) receptors. ET-1 decreased cAMP content but increased phosphoinositide hydrolysis, whereas ET-3 attenuated both intracellular pathways. The expression of ET(A) and ET(B) receptor mRNAs as well as that of ETs was revealed in the submandibular gland by RT-PCR. Immunohistochemical studies showed that ET(A) receptor staining was localized around the interlobular ducts and acini, compatible with the myoepithelial cells' location, whereas ET(B) receptor staining was restricted to small blood vessels. When applied to the brain, both ETs induced no salivation but enhanced cholinergic- and adrenergic-evoked salivary secretion through parasympathetic pathways. ET-1 response was mediated by brain ET(A) receptors, whereas that of ET-3 was presumably through nonconventional ET receptors. Present findings show that ETs are involved in the brain regulation of cholinergic- and adrenergic-stimulated submandibular gland secretion through the activation of distinct brain ET receptors and parasympathetic pathways. However, when ETs were administered into the gland, only ET-1 enhanced cholinergic and adrenergic salivation likely through myopithelial cell contraction by activating ET(A) receptors coupled to phospholipase C. The presence of ETs and ET receptors suggests the existence of an endothelinergic system in the submandibular gland.     

Changes in CNS cells in Hyperammonemic portal hypertensive rats

Rats with pre‐hepatic portal hypertension because of partial portal vein ligation develop minimal hepatic encephalopathy (MHE) with hyperammonemia, impaired blood–brain barrier, mild brain edema, and severe mitochondrial changes in the hippocampus. The aim of this study was to evaluate changes of different neural cells in the cerebral cortex and the hippocampus. Animals were divided into two groups, MHE and sham. Astrocytes were studied by immunostaining with glial fibrillary acidic protein and S100β protein; neurons were immunostained with neuronal nuclear marker, microtubule associated protein‐2, and NF‐200 and capillaries with Nestin. The hypoxia‐inducible factor 1α (HIF‐1α) and its downstream proteins, P‐glycoprotein (P‐gp) and erythropoietin receptor (Epo‐R), were also evaluated. Astrocytes were increased in area and number only in the hippocampus, while S100β increased in both brain areas in MHE animals. Microtubule associated protein‐2 and NF‐200 immunoreactivities (‐ir) were significantly reduced in both areas. Hippocampal Nestin‐ir was increased in MHE animals. These cellular changes were similar to those described in ischemic conditions, thus HIF‐1α, P‐gp, and Epo‐R were also evaluated. A high expression of HIF‐1α in cortical neurons was observed in the MHE group. It is likely that this hypoxia‐like state is triggered via ammonia occupying the binding domain of HIF‐1α and thereby preventing its degradation and inducing its stabilization, leading to the over‐expression of P‐gp and the Epo‐R.

     

Real Time Identification of Drug-Induced Liver Injury (DILI) through Daily Screening of ALT Results: A Prospective Pilot Cohort Study

Objective

Identification of drug-induced liver disease (DILI) is difficult, even among hospitalized patients. The aim of this pilot study was to assess the impact of a specific strategy for DILI screening.

Design

We prospectively compared the number of acute DILI cases identified in one week of a proactive strategy based on centralized elevated ALT values to those identified with a standard of care strategy for 24-week period based on referral cases to the hepatology unit. In the centralized strategy, a designated study biochemist identified patients with ALT greater than 3 times the upper limit of normal values (ULN) and notified the designated hepatologists, who then went to the patients'' wards, analyzed the charts, and if necessary, interviewed the identified patients. During these two periods, patients with possible DILI were included after signing an informed consent in an ongoing European diagnostic study (SAFE-T consortium).

Results

During the 24-week period of the standard strategy, 12 (0.04%) patients out of a total of 28,145 were identified as having possible DILI, and 11 of these accepted to be included in the protocol. During the one-week proactive period, 7 patients out of a total of 1407 inpatients (0.498%) [odds ratio vs. standard = 12.1 (95% CI, 3.9–32.3); P<0.0001] were identified with possible DILI, and 5 were included in the protocol.

Conclusion

A simple strategy based on the daily analysis of cases with ALT >3 ULN by designated biochemists and hepatologists identified 12 times more acute cases of drug-induced liver disease than the standard strategy.This pilot cohort is registered on the number AP-HP P110201/1/08-03-2011 and AFSSAPS B110346-70.     

Expression of major capsid protein VP-1 in the absence of viral particles in thymomas induced by murine polyomavirus

Thymomas induced by polyomavirus strain PTA in mice are known to express the major capsid protein VP-1. Since the expression of a late structural protein such as VP-1 is considered a sign of virus replication, the present work attempted to clarify the implication of the presence of this protein in tumor cells. Electron microscopy of tumors showed a striking absence of viral particles in the vast majority of the cells. However, immunoelectron microscopy of the same samples demonstrated intranuclear VP-1 in most cells despite the absence of viral particles. Very little infectious virus was recovered from tumors. A change in the electrophoretic mobility of VP-1 from thymomas was detected compared with VP-1 from productively infected cells. The data presented in this work prove that the expression of VP-1 in polyomavirus-induced tumors is not synonymous with the presence of infectious virus, suggesting a possible defect in viral encapsidation.     

Influence of fasting on the effects of diazoxide in the ischemic-reperfused rat heart

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel opener diazoxide could reproduce the protection conferred by ischemic preconditioning and to ascertain whether its effects are associated with changes in glycogen breakdown and glycolytic activity. Hearts of fed and 24-h fasted rats were perfused with 10 mM glucose containing medium and exposed to 25 min no-flow ischemia plus 30 min reperfusion. Diazoxide (10 microM) perfusion was begun 10 min before ischemia and continued throughout the experiment. Fasting accelerated reperfusion recovery of contraction, reduced the post-ischemic contracture and decreased lactate accumulation during ischemia but had no effects on glycogen levels and cellular viability. Diazoxide, did not affect glycogen catabolism but improved reperfusion recovery of contraction. Furthermore, diazoxide reduced ischemic lactate accumulation and contracture amplitude only in the fed group whereas it improved cell viability in the fed and fasted groups. These data indicate that: 1) reduced lactate production which may attenuate myocyte acidification might explain, at least in part, the beneficial effects of diazoxide on mechanical function, although data obtained with the fasted rat hearts indicate that other mechanisms must be involved as well; 2) the reduction of lactate production occurring in the fed group, does not seem to be related to glycogenolysis; and 3) since diazoxide improved cell viability in the fasted rat group where it did not reduce glycolytic activity, other mechanisms may be responsible for this cytoprotective effect.     

Analysis and assembling of network structure in mutualistic systems

It has been observed that mutualistic bipartite networks have a nested structure of interactions. In addition, the degree distributions associated with the two guilds involved in such networks (e.g., plants and pollinators or plants and seed dispersers) approximately follow a truncated power law (TPL). We show that nestedness and TPL distributions are intimately linked, and that any biological reasons for such truncation are superimposed to finite size effects. We further explore the internal organization of bipartite networks by developing a self-organizing network model (SNM) that reproduces empirical observations of pollination systems of widely different sizes. Since the only inputs to the SNM are numbers of plant and animal species, and their interactions (i.e., no data on local abundance of the interacting species are needed), we suggest that the well-known association between species frequency of interaction and species degree is a consequence rather than a cause, of the observed network structure.     

Chemical Composition and Antimicrobial Activity of Essential Oils from Chromolaena laevigata during Flowering and Fruiting Stages

The chemical compositions and antimicrobial activities of essential oils from the leaves, stems, capitula, and cypselas of Chromolaena laevigata were evaluated at two different phenological stages, flowering and fruiting. Thirty‐eight compounds were identified in the crude oils by GC/MS. The sesquiterpene laevigatin was the major constituent of the leaf, capitulum, and cypsela oils, while the sesquiterpene spathulenol was the main component in the stem oils. The antimicrobial activities of the oils were evaluated against Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Stem oil obtained from Chromolaena laevigata during the fruiting stage generally showed the highest activity with minimum inhibitory concentration (MIC) values of 62.5 μg/ml against Candida albicans and S. aureus, and 500 μg/ml against P. aeruginosa and E. coli. Pure laevigatin exhibited MIC values of 500 and 125 μg/ml against C. albicans and S. aureus, respectively, indicating that this constituent could be responsible, at least in part, for the antimicrobial activities detected in the crude oils. More studies concerning the biological activities of isolated derivatives are required to improve our knowledge of the antimicrobial potential of volatile compounds present in native plants.     

Properties and Antioxidant Action of Actives Cassava Starch Films Incorporated with Green Tea and Palm Oil Extracts

There is an interest in the development of an antioxidant packaging fully biodegradable to increase the shelf life of food products. An active film from cassava starch bio-based, incorporated with aqueous green tea extract and oil palm colorant was developed packaging. The effects of additives on the film properties were determined by measuring mechanical, barrier and thermal properties using a response surface methodology design experiment. The bio-based films were used to pack butter (maintained for 45 days) under accelerated oxidation conditions. The antioxidant action of the active films was evaluated by analyzing the peroxide index, total carotenoids, and total polyphenol. The same analysis also evaluated unpacked butter, packed in films without additives and butter packed in LDPE films, as controls. The results suggested that incorporation of the antioxidants extracts tensile strength and water vapor barrier properties (15 times lower) compared to control without additives. A lower peroxide index (231.57%), which was significantly different from that of the control (p<0.05), was detected in products packed in film formulations containing average concentration of green tea extracts and high concentration of colorant. However, it was found that the high content of polyphenols in green tea extract can be acted as a pro-oxidant agent, which suggests that the use of high concentration should be avoided as additives for films. These results support the applicability of a green tea extract and oil palm carotenoics colorant in starch films totally biodegradable and the use of these materials in active packaging of the fatty products.