Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe ...OSA phenotype.
Is NIV effective in OHS without severe OSA phenotype?
In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients’ enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups.
Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms.
In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS.
ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov ;
The impact of disasters on the population does not discriminate on grounds of sex, age or socioeconomic status. However, some populations show higher vulnerability than others in emergency or ...disaster situations. The aim of this article is to present the frequency and distribution of some of the vulnerable populations in Puerto Rico, whose fragility increases during and after disasters. In turn, the findings are discussed to provide a look at possible strategies to address the needs of these populations and thus safeguard their welfare in disaster situations. Secondary data from the Hazard and Vulnerability Assessment (HVA) of the Puerto Rico public health systems was used to identify vulnerable populations. Results showed that in Puerto Rico almost half of the population (48%) is under poverty level and 20.4% has at least one disability. Furthermore, 21% of the population is considered vulnerable because of their age group: 6% are children under five years old, and 15% have at least 65 years old, which indicates an aging population. According to these findings, Puerto Rico presents great challenges due to the large number of vulnerable populations, especially in disaster response. El impacto de los desastres no discrimina por razón de sexo, edad, condición socioeconómica ni estatus social. Sin embargo, algunas poblaciones pueden ser más vulnerables que otras en situaciones de desastres. El objetivo de este artículo es describir las poblaciones vulnerables en Puerto Rico que puedan verse afectadas al momento de un desastre. Utilizando bases de datos secundarias del Estudio de Vulnerabilidad y Riesgo para Puerto Rico, se adquirió información sobre poblaciones vulnerables. Se encontró que en Puerto Rico, aproximadamente, la mitad de la población (48%) está bajo el nivel de pobreza. Un 15% de la población de Puerto Rico son personas mayores de 65 an̄os, además, un 20.4% de la población posee alguna discapacidad. Resulta importante para Puerto Rico, que las necesidades especiales de las poblaciones vulnerables sean incluidas dentro de los procesos de planificación, preparatión y notificatión ante desastres. Les catastrophes climatiques ne font aucune distinction entre sexe, âge, statut économique ou social. Tbutefois, certaines populations restent plus vulnérables que d'autres face aux catastrophes naturelles. Cet article se donne pour objectif de décrire ces populations plus vulnérables à Porto Rico, des populations qui se considèrent elles-mêmes particulièrement affectées en cas de catastrophe. Les bases de données secondaires de l'Etude de Risques et de Vulnérabilités (Estudio de Vulnerabilidad y Riesgo) de Porto Rico, ont permis de recueillir des informations sur ces populations. II apparaît ainsi que près de la moitiéde la population (48%) vit en dessous du seuil de pauvreté. Or, 15% de la population de Porto Rico se compose de personnes âgées et 20,4% de cette même population aurait un handicap de quelque forme qu'il soit. Il semble done important pour Porto Rico que les besoins spécifiques de ces populations dites vulnérables soient pris en compte dans les mesures de planification, de préparation mais aussi d'annonce de catastrophes naturelles.
The indoor environment contributes considerably to human exposure to poly- and perfluoroalkyl substances (PFASs). This study estimated the human exposure to PFASs from the indoor environment through ...hand-to-mouth and dermal contacts using hand wipes. An analytical method was developed to determine 25 PFASs in hand wipe samples collected as a composite sample from both hands of 60 adults. Polyfluoroalkyl phosphate esters (PAPs) were the predominant PFASs in the hand wipe samples (medians between 0.21 and 0.54 ng per sample). Positive and significant correlations were observed between PAPs, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA) in hand wipes. Low frequency of daily hand washing (≤8 times day–1) was associated with 30–50% higher concentrations of PFOS, PFOA, and 8:2diPAP in hand wipes. Further, significant correlations between paired hand wipes and house dust samples were observed for PFOS, PFOA, and 6:2diPAP. Also, a significant correlation between PFOS in hand wipes and EtFOSE in indoor air was found. This finding indicates either a common source of exposure or a transformation of EtFOSE to PFOS in the environment or on the hands. The contributions of direct and indirect exposure to perfluoroalkyl acids (PFAAs) showed that PFOA contributed the highest exposure to adults via hand-to-mouth and dermal contacts, followed by PFOS. The median of estimated daily intakes via hand-to-mouth and dermal contacts (for hands only) for PFOA were 0.83 and 0.50 pg·kg bw–1·day–1, respectively. This study gives a first indication that PFAS concentrations in hand wipes can be used as a proxy for the exposure to PFASs from indoor environments, but further studies are needed to confirm this.
Aeromonas caviae is an emerging human pathogen. Here, we report the draft genome sequence of Aeromonas caviae strain 429865 INP which shows the presence of various putative virulence-related genes.
•This study contributed to the field of human exposure to poly- and perfluoroalkyl substances.•Dietary exposure from the ingestion of food and drinks was the predominant exposure pathway.•Measured ...and modelled serum concentrations were in the same order of magnitude.•The estimated daily intakes of PFASs in this study were lower than the health-based guidance values.
Exposure to PFASs may result in adverse health effects. This study aimed to characterise the exposure to PFASs from diet, house dust, indoor air, and dermal contact and the relative contribution from different external exposure pathways to human serum concentrations. Daily intakes of 18 perfluoroalkyl acids (PFAAs) and 12 PFAA precursors from diet, dust ingestion, inhalation of indoor air and dermal absorption were estimated using a comprehensive dataset comprising 61 adults from the Oslo area, Norway. Concentrations of PFAAs and PFAA precursors in house dust, indoor air, hand wipes, foods and drinks were utilised to estimate the daily intakes. Perfluorooctanesulfonate (PFOS) was the predominant PFAS in serum for this study group. On a median level, perfluorooctanoate (PFOA) contributed most to the total estimated daily intake of PFAAs, with a median intake of 280 (range: 72–1810) pg·kg bw−1·day−1, covering both direct and indirect (precursors) exposure. Out of this, only 3% (range: <1–48%) of the total PFOA intake came from indirect exposure. Dietary exposure from ingestion of food and drinks was in general the predominant exposure pathway, followed by exposure from ingestion of house dust, inhalation of indoor air, and dermal absorption, but considerable variations were observed among individuals. House dust ingestion and indoor air inhalation contributed most to the total intakes for some participants, for which most of them were among the 20% participants with the highest total estimated intakes. Some statistical significant associations between concentrations of PFASs measured in serum and estimated intakes were observed. Measured serum concentrations and modelled serum concentrations based on external exposure estimates were in the same order of magnitude for PFOS, PFHxS, PFOA, and PFNA, but only PFOA concentrations were comparable, 1.9 and 2.0 ng mL−1 for observed and modelled serum concentrations, respectively. The estimated daily intakes of PFASs in this study were lower than the health-based guidance values, e.g. the tolerable weekly intakes derived by EFSA. This study underlines the importance of performing studies considering multiple exposure pathways on an individual basis.
Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory ...response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients.
This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification.
HDCPT showed a statistically significant decrease in mortality (HR = 0.087 95% CI 0.021-0.36; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L).
HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.
Very-short- (vSCCPs, C6–9), short- (SCCPs, C10–13), medium- (MCCPs, C14–17), and long-chain chlorinated paraffins (LCCPs, C>17) were analyzed in indoor air and dust collected from the living rooms ...and personal 24 h air of 61 adults from a Norwegian cohort. Relatively volatile CPs, i.e., vSCCPs and SCCPs, showed a greater tendency to partition from settled indoor dust to paired stationary indoor air from the same living rooms than MCCPs and LCCPs, with median logarithmic dust–air partition ratios of 1.3, 2.9, 4.1, and 5.4, respectively. Using the stationary indoor air and settled indoor dust concentrations, the combined median daily exposures to vSCCPs, SCCPs, MCCPs, and LCCPs were estimated to be 0.074, 2.7, 0.93, and 0.095 ng/kg bw/d, respectively. Inhalation was the predominant exposure pathway for vSCCPs (median 99%) and SCCPs (59%), while dust ingestion was the predominant exposure pathway for MCCPs (75%) and LCCPs (95%). The estimated inhalation exposure to total CPs was ∼ 5 times higher when the personal 24 h air results were used rather than the corresponding stationary indoor air results in 13 paired samples, indicating that exposure situations other than living rooms contributed significantly to the overall personal exposure. The 95th percentile exposure for CPs did not exceed the reference dose.
Post-translational modifications (PTMs) mediated by nitric oxide (NO)-derived molecules have become a new area of research, as they can modulate the function of target proteins. Proteomic data have ...shown that ascorbate peroxidase (APX) is one of the potential targets of PTMs mediated by NO-derived molecules. Using recombinant pea cytosolic APX, the impact of peroxynitrite (ONOO–) and S-nitrosoglutathione (GSNO), which are known to mediate protein nitration and S-nitrosylation processes, respectively, was analysed. While peroxynitrite inhibits APX activity, GSNO enhances its enzymatic activity. Mass spectrometric analysis of the nitrated APX enabled the determination that Tyr5 and Tyr235 were exclusively nitrated to 3-nitrotyrosine by peroxynitrite. Residue Cys32 was identified by the biotin switch method as S-nitrosylated. The location of these residues on the structure of pea APX reveals that Tyr235 is found at the bottom of the pocket where the haem group is enclosed, whereas Cys32 is at the ascorbate binding site. Pea plants grown under saline (150mM NaCl) stress showed an enhancement of both APX activity and S-nitrosylated APX, as well as an increase of H2O2, NO, and S-nitrosothiol (SNO) content that can justify the induction of the APX activity. The results provide new insight into the molecular mechanism of the regulation of APX which can be both inactivated by irreversible nitration and activated by reversible S-nitrosylation.
The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease ...(COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.
•Metformin glycinate inhibits SARS-CoV-2 viral replication after 48 h of exposure.•MG increased survival in cells exposed to VOI (alpha, delta, and epsilon).•Patients treated with metformin glycinate reduces SARS-CoV2 viral load in 3.3 days.
Overview of the GSNO turnover mechanisms and especially the role of GSNO as a modulator of NO-dependent signalling under physiological and stress conditions in plants.
Abstract
Nitric oxide (NO) has ...emerged as an essential biological messenger in plant biology that usually transmits its bioactivity by post-translational modifications such as S-nitrosylation, the reversible addition of an NO group to a protein cysteine residue leading to S-nitrosothiols (SNOs). In recent years, SNOs have risen as key signalling molecules mainly involved in plant response to stress. Chief among SNOs is S-nitrosoglutathione (GSNO), generated by S-nitrosylation of the key antioxidant glutathione (GSH). GSNO is considered the major NO reservoir and a phloem mobile signal that confers to NO the capacity to be a long-distance signalling molecule. GSNO is able to regulate protein function and gene expression, resulting in a key role for GSNO in fundamental processes in plants, such as development and response to a wide range of environmental stresses. In addition, GSNO is also able to regulate the total SNO pool and, consequently, it could be considered the storage of NO in cells that may control NO signalling under basal and stress-related responses. Thus, GSNO function could be crucial during plant response to environmental stresses. Besides the importance of GSNO in plant biology, its mode of action has not been widely discussed in the literature. In this review, we will first discuss the GSNO turnover in cells and secondly the role of GSNO as a mediator of physiological and stress-related processes in plants, highlighting those aspects for which there is still some controversy.
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