Intermittent social isolation during adolescence increases ethanol preference in males and females and alters irritability-like behaviors and synaptic transmission in the CeA of adult males

Chronic stress during adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents faced prolonged periods of isolation. However, preclinical rodent models of adolescent social stress have produced mixed results that are often sex, species and strain-dependent. Here we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND28-56) and its long-term effects and alcohol drinking on anxiety, irritability, and synaptic transmission in both male and female Wistar rats. To this goal, we developed and utilized a new model of social isolation and alcohol exposure whereby adolescent (PND28) male and female rats were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20% v/v, 2h/session, Tues/Thur/Sat) vs. water, for 4 weeks. Two weeks later (young adults), all rats were tested for anxiety in the novelty induced hypophagia test and irritability-like behavior in the bottle brush test, and a subset was used to record spontaneous inhibitory GABAergic postsynaptic currents (sIPSCs) in the central nucleus of the amygdala (CeA). Additionally, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased alcohol preference vulnerability and high sensitivity to anxiety. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed controls, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Baseline frequency of sIPSCs was decreased in socially isolated male Wistar and msP adult rats vs. group-housed, while rise times, amplitudes, and decay times remained unchanged, indicating reduced basal presynaptic GABA release in the CeA. Together, these findings suggest that an intermittent social isolation produces increased alcohol preference in Wistar rats of both sexes and in male msPs, as well as synaptic changes in the CeA.Copyright © 2023

Pulmonary telerehabilitation in patients with chronic respiratory diseases during the pandemic by COVID-19 in Argentina. A multicenter observational study

Introduction: To our knowledge, there are no published studies on the implementation and results of Pulmonary telerehabilitation (PTR) in Argentina. Our objective was to describe PTR strategies used during the COVID-19 pandemic, the results of the different PTR modalities and the patient satisfaction. Method(s): A prospective study was carried out between April and August 2020. Patients who switched to different PTR modalities participated: synchronous (SPTR) or asynchronous (APTR). The level of satisfaction, quality of life with the St. George's Respiratory Questionnaire (SGRQ) and anxiety and depression with the Hospital Anxiety and Depression Scale (HADS) at baseline, 6 and 12 weeks were evaluated. Result(s): 20 centers participated. 299 patients were included (55.9% female), with a median (P25-75) age of 68 (62- 72) years, 184/249 (73.9%) diagnosed with COPD, 37 (14.9%) interstitial lung diseases, 12 (4.8%) asthma and 16 (6.4%) other CRD. 110 (36.8%) patients underwent SPTR and 189 (63.2%) with APTR. No differences were observed in the SGRQ and HADS except in the activities subscale of the SGRQ that increased significantly (p<0.05) in both groups, the impact subscale and the total that increased significantly in the SPTR group at 12 weeks (p<0.01). Both groups reported being satisfied with the PTR, 5.9 (5.4-6.3) in SPTR and 5 (4.6-5.4) in APTR, being significantly higher in SPTR (p=0.004) Conclusion(s): We observed significant satisfaction with PRT during the pandemic. No improvements were seen in quality of life, anxiety, or depression.

INTERMITTENT SOCIAL ISOLATION STRESS IN ADOLESCENCE INCREASES ETHANOL PREFERENCE IN JUVENILE MALES AND FEMALES AND ALTERS IRRITABILITY-LIKE BEHAVIORS IN MALE ADULTS

Chronic stress during the developmental period of adolescence increases the susceptibility to many neuropsychiatric diseases in adulthood, including anxiety-like and alcohol drinking behaviors. Social isolation is a particularly profound stressor with increasing human relevance, especially during the COVID-19 pandemic, when millions of adolescents have faced prolonged periods of isolation. Preclinical rodent models of adolescent isolation stress have produced mixed results that are often sex, species, and strain dependent. Here, we examined the effect of intermittent social isolation on alcohol intake and preference during adolescence (PND 28-56) in male and female Wistar rats and the long-term effects of juvenile social isolation and alcohol drinking on anxiety-and irritability-like behaviors. Furthermore, we studied genetically selected Marchigian Sardinian alcohol-preferring (msP) rats to compare the effects of social isolation in a rat strain of increased innate alcohol preference and high sensitivity to stress and anxiety. We developed and utilized a new model of social isolation and alcohol exposure whereby male and female rats beginning at PND28 were intermittently socially isolated for 24h prior to 2-bottle choice (2BC) access to ethanol (20%v/v, 2h/session) vs. water. After each session, the rats were regrouped until the next day when they were isolated again. This procedure was repeated for 3 days/week across 4 weeks. Two weeks later, as young adults (PND 80), all rats were tested for anxiety in the novelty induced hypophagia test and irritability in the bottle brush test. Social isolation increased alcohol preference in both male and female Wistars when compared to the group-housed control group, starting from week 1 and throughout adolescence. All msP rats displayed escalation of drinking during week 1 and 2 and the effect of the isolation was observed starting from week 3 in males only. No isolation effects were observed in female msPs throughout the 4 weeks. Social isolation and alcohol drinking during adolescence increased aggressive-like behavior in male adult Wistar rats, but not females, and did not alter anxiety measures. Together, these findings suggest that an intermittent social isolation followed by re-grouping produces increased alcohol preference in Wistar rats of both sexes and, with a different trend, in male msPs. Ongoing studies are elucidating the underlying physiological mechanisms.

STRENGTHS AND WEAKNESSES IN EMERGENCY PUBLIC PROCUREMENT CAUSED BY THE COVID-19 HEALTH CRISIS. A COMPARATIVE STUDY BETWEEN SPAIN AND MEXICO

Emergency public procurement during the COVID-19 health crisis has been a resourceful instrument to provide an immediate response to public needs by the public administrations. The States have developed different emergency legislation and measures to resolve a crisis, as both the Spanish and Mexican cases demonstrate. The implementation of an emergency public contract shows some risks such as weakness in the legal bases and emergency reasoning, a disproportionate use or a deficiency in the administrative control that can affect the legal principles related to procurement. This article demonstrates the existence of different meanings of the concept, nature, and requirements of emergency public procurement. Based on anticipatory governance, Public Administrations must be prepared to use strategic public procurement to contribute to strengthening the Rule of Law within times a context of crisis.

Resolutive results with oral corticosteroids for patients with COVID-19 in pulmonary inflammatory phase. successful outpatient experience during the collapse of Belem do Para health system-Brazil

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well-known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem (Para, Brazil) Health System. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of 40 mg prednisolone, 40 mg enoxaparin and macrolides (500 mg clarithromycin, 500 mg axetylcefuroxime) associated and followed in outpatient facilities. Two hundred and eight patients had an excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

Clinical effectiveness and bacteriological eradication of three different Short-COurse antibiotic regimens and single-dose fosfomycin for uncomplicated lower Urinary Tract infections in adult women (SCOUT study): study protocol for a randomised clinical trial.

INTRODUCTION: Uncomplicated lower urinary tract infections (uLUTI) are a common problem in primary care. Current local guidelines recommend the use of a single 3 g dose of fosfomycin. However, most general practitioners (GP) prefer short-course therapies to single-dose therapy. No study has compared head-to-head short-course antimicrobial agents for uLUTIs. Therefore, the aim of this randomised clinical trial is to compare three different short-course antibiotic therapies with a single-dose of fosfomycin for these infections. METHODS AND ANALYSIS: This will be a pragmatic, multicentre, parallel group, open trial. Women aged 18 or older and with symptoms of uLUTI and a positive urine dipstick analysis will be randomised to one of the following four groups: a single dose of 3 g of fosfomycin, 2 days of 3 g of fosfomycin o.d., 3 days of pivmecillinam 400 mg three times per day (t.i.d) or 5 days of nitrofurantoin 100 mg t.i.d. A total sample of 1120 patients was calculated. The primary endpoint is clinical effectiveness at day 7, defined as cure of symptoms reported by the patients in a diary including four symptoms: dysuria, urgency, frequency and suprapubic pain, which will be scored on a 4-point severity scale (not present/mild/moderate/severe). Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed. If positive, antibiograms for the three antibiotics studied will be performed. Bacterial eradication will be measured at days 14 and 28. ETHICS AND DISSEMINATION: The study was approved by the Ethical Board of IDIAP Jordi Gol (reference number: 21/173-AC) and Spanish Agency of Medicines and Medical Devices. The findings of this trial will be disseminated through research conferences and peer-review journals. TRIAL REGISTRATION NUMBER: NCT04959331; EudraCT Number: 2021-001332-26. TIME SCHEDULE: January 2022 to April 2023.

The freedom-government relationship in times of pandemic in Brazil and Argentina

This article aims to analyse the freedom-government relationship through the discourses and governmental measures implemented in Brazil and Argentina on the occasion of COVID-19. It considers two variables that became relevant as the pandemic developed: 1) the dichotomy between"economy"and "health': and 2) the national/federal, provincial/state and municipal levels of government as scenarios in the fight against the pandemic -analyzing the specific cases of Sao Paulo and Buenos Aires. The objective is to understand the experiences of Brazil and Argentina based on the knowledge, calculations and government techniques implemented to guarantee the difficult and fragile balance between individual freedom and common security. The period of study is focused on the year of 2020. In this way, it is expected that it will contribute to the analysis of the responses that both countries have given during the first year of the pandemic from the perspective of governmental practices and discourses.

EXERCISE CAPACITY AND HEALTH-RELATED QUALITY OF LIFE IN SURVIVORS OF COVID-19 PNEUMONIA

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: To determine the effect of COVID-19 pneumonia on exercise capacity and quality of life among healthcare workers of the Philippine Heart Center who survived the disease. METHODS: This was a prospective cohort study conducted at the Philippine Heart Center (PHC) from September 2020 to January 2021. PHC Healthcare workers aged =/> 19 years old, discharged from PHC as a case of recovered COVID-19 Pneumonia were included. Those with signs and symptoms of possible COVID-19 reinfection, history of pulmonary resection, neurological or psychiatric disease, COPD, lung malignancies, or fulfilled any of the contraindications for a 6-Minute walk test (6MWT) were excluded. Participants were evaluated at the research site at 3 and 6 months from onset of illness (+/-2 weeks). During each visit, they were assessed for signs and symptoms of possible COVID-19 reinfection, vital signs were taken, 6MWT and the RAND free version of the Medical Outcomes Study 36-item Short Form General Health Survey (SF-36) questionnaires were completed. One-way ANOVA, Kruskal-Wallis test and Fisher's exact test were used to determine the difference of mean, rank and frequency within the three different COVID-19 severities. Paired Sample T-test or Wilcoxon Sign rank test was used to determine the difference of mean or rank from 3rd month to 6th month. Shapiro-Wilk was used to test the normality of the continuous variables. Null hypotheses was rejected at 0.05α-level of significance. RESULTS: Our study revealed that 3 months from illness-onset, COVID-19 survivors had lower average 6MWD (374 meters;326-404) compared to the general Filipino population. The 6MWD was also proportional to the severity of the disease, mild: 393;369-426 vs moderate: 318;304-326, vs severe:147;129-167, p=0.001.Those who had mild (p=0.000) and moderate disease (p= 0.0076) had significant improvements in the 6MWD six months from the onset of illness, in contrast to those who had severe COVID-19 disease (p=0.431). Although there was appreciable improvement in the 6MWD for mild and moderate disease, the actual 6MWD achieved was still subpar with the reference values for the general Filipino population. Majority of the domains of the SF-36 where all lower compared with the general Filipino population. Among these, physical functioning, social functioning, role limitations due to physical problems and general health scored the lowest in our study. CONCLUSIONS: We have demonstrated that statistically significant, but not clinically relevant improvements on exercise capacity may be observed on healthcare workers who survived COVID-19 pneumonia. Furthermore, impairment on exercise capacity and health-related quality of life still persists in patients with COVID-19 pneumonia even after 6 months. CLINICAL IMPLICATIONS: This finding underscores the need for large-scale follow up and early intervention to improve residual impairments in patients who had COVID-19. DISCLOSURES: No relevant relationships by Jamaica Ross David, source=Web Response No relevant relationships by Maria Encarnita Limpin, source=Web Response no disclosure on file for Bernice Ong-Dela Cruz;

Molecular diagnosis of SARS-CoV-2

ABSTRACT COVID-19 diagnosis is based on both clinical aspects and screening tests. However, clinical symptoms and signs in infected patients are highly atypical;hence, molecular tests are essential for diagnosis. RT-qPCR is carried out at BSL II level laboratories;the main molecular targets for viral detection are E gene (envelope), and RdRP gene (RNA-dependent RNA polymerase). False negatives in this diagnosis are due to sample quality and quantity, transport conditions, storage and handling before and after extraction (RNA is heat-labile and RNases are abundant);infection phase;virus mutations and presence of CRP inhibitors. Taking into account analytical sensitivity of RT-qPCR (5.2 copies of RNA / reaction) and the fact that once RNA it is extracted, it progressively degrades and affects test diagnostic sensitivity, a new sample -specifically taken from the lower respiratory tract in order to increase viral load- is recommended in the abovementioned cases. Timely diagnosis allows optimizing management (isolation and treatment), patient monitoring, implementing prevention and control measures as well as epidemiological surveillance of the disease.