Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study.

Objectives: High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria. Methods: We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria. Results: Length of stay linearly correlated with bacteriuria (R2 = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus. Conclusion: Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

Function and regulation of cGAS-STING signaling in infectious diseases.

The efficacious detection of pathogens and prompt induction of innate immune signaling serve as a crucial component of immune defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have emerged as key mediators of type I interferon (IFN) and nuclear factor-κB (NF-κB) responses in health and infection diseases. Moreover, both cGAS-STING pathway and pathogens have developed delicate strategies to resist each other for their survival. The mechanistic and functional comprehension of the interplay between cGAS-STING pathway and pathogens is opening the way for the development and application of pharmacological agonists and antagonists in the treatment of infectious diseases. Here, we briefly review the current knowledge of DNA sensing through the cGAS-STING pathway, and emphatically highlight the potent undertaking of cGAS-STING signaling pathway in the host against infectious pathogenic organisms.

Emotional Function, Negative Thoughts about the Pandemic, and Adaptability Skills among Dementia Caregivers during the COVID-19 Pandemic.

Background: It can be easily inferred that dementia caregivers were severely affected by the general home confinement, or 'lockdown', due to their caregiving roles. Aim: The aim of the current study is to investigate how the quarantine measures applied during the COVID-19 pandemic affected the emotional function (specifically the emotional management, emotional experience, and stress symptoms) and the negative thoughts, as well as the adaptability skills, of Greek dementia caregivers. Materials andMethods: In total, 303 participants (138 in the non-caregiving adults-control group; 165 in the dementia caregivers-experimental group) were recruited from the day centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD) from June 2020 to January 2021 in Thessaloniki, Greece. The caregiving population was split into group 1 (those who participated in support groups) and group 2 (those who did not participate in support groups). A self-reported questionnaire was created for research purposes and was digitally administered to participants via Google forms. Results: During the quarantine period, dementia caregivers had more difficulties in emotional management, especially in regards to stress symptoms, which was measured via the Beck Anxiety Inventory (BAI), in comparison to the control group. In regards to the caregiving populations, caregivers from group 1 were more able to manage their emotions according to their self-reports, but had increased agony and loneliness. Moreover, statistical significance was found between emotional management, negative feelings, and stress symptoms in those from group 2 who self-reported that the PwD deteriorated. This evidence was not found in group 1. Finally, there were no differences in the means of negative thoughts about the pandemic, as well as in the adaptation skills, both in dementia caregivers and in the control group, according to their self-reports. Discussion: It seems that different emotional aspects were affected in the dementia caregivers' population, and, therefore, future psychotherapeutic interventions should focus on those most severely affected by the restrictive measures imposed.

Emotional Function, Negative Thoughts about the Pandemic, and Adaptability Skills among Dementia Caregivers during the COVID-19 Pandemic

Background: It can be easily inferred that dementia caregivers were severely affected by the general home confinement, or 'lockdown', due to their caregiving roles. Aim: The aim of the current study is to investigate how the quarantine measures applied during the COVID-19 pandemic affected the emotional function (specifically the emotional management, emotional experience, and stress symptoms) and the negative thoughts, as well as the adaptability skills, of Greek dementia caregivers. Materials andMethods: In total, 303 participants (138 in the non-caregiving adults-control group;165 in the dementia caregivers-experimental group) were recruited from the day centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD) from June 2020 to January 2021 in Thessaloniki, Greece. The caregiving population was split into group 1 (those who participated in support groups) and group 2 (those who did not participate in support groups). A self-reported questionnaire was created for research purposes and was digitally administered to participants via Google forms. Results: During the quarantine period, dementia caregivers had more difficulties in emotional management, especially in regards to stress symptoms, which was measured via the Beck Anxiety Inventory (BAI), in comparison to the control group. In regards to the caregiving populations, caregivers from group 1 were more able to manage their emotions according to their self-reports, but had increased agony and loneliness. Moreover, statistical significance was found between emotional management, negative feelings, and stress symptoms in those from group 2 who self-reported that the PwD deteriorated. This evidence was not found in group 1. Finally, there were no differences in the means of negative thoughts about the pandemic, as well as in the adaptation skills, both in dementia caregivers and in the control group, according to their self-reports. Discussion: It seems that different emotional aspects were affected in the dementia caregivers' population, and, therefore, future psychotherapeutic interventions should focus on those most severely affected by the restrictive measures imposed.

Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN, which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathology and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clinical trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans.

Ebselen, a multi-target compound: its effects on biological processes and diseases

Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.