The COVID-19 pandemic placed unprecedented strain on the medical supply chain. Early in the pandemic, uncertainty regarding personal protective equipment (PPE) was high. Protecting health care workers from contracting illness is critical to preserve trust and workforce capacity.

We describe an initiative to design and manufacture a novel, re-usable, half-face respirator in case conventional medical supply chain failed to meet demand. It required new collaboration between the hospital, physicians, the medical school, and the school of engineering. We describe organizational priorities, constraints, and process of design, testing and approval as the health system engaged for the first time directly with the design and manufacturing process for PPE.

An original mask design was developed, and the University Hospital had an initial batch of this novel mask manufactured during the first wave of the SARS-COV-2 pandemic. Wnt antagonist These masks, and the die necessary to produce more, are in reserve in case of depletion of stores of conventionally sourced PPE.

The COVID-19 pandemic demonstrated fragility of medical supply chain. Organizations considering similar efforts should anticipate constraints on raw material supply chain and be flexible, adaptive, and fast. The incident command structure was vital to identifying priority areas needing alternative approaches, creating connections, and providing rapid approvals. We found organizational value in demonstrating commitment to assuring PPE supplies for health care worker safety.

The COVID-19 pandemic demonstrated fragility of medical supply chain. Organizations considering similar efforts should anticipate constraints on raw material supply chain and be flexible, adaptive, and fast. The incident command structure was vital to identifying priority areas needing alternative approaches, creating connections, and providing rapid approvals. We found organizational value in demonstrating commitment to assuring PPE supplies for health care worker safety.

Coronavirus disease 2019 (COVID-19) outbreaks often occur in nursing homes and prompt frequent surveillance testing for SARS-CoV-2. A single dose of the BNT162b2 vaccine reduces viral load and transmission. In this study, we describe the real-world efficacy of BNT162b2 single-dose vaccination during a COVID-19 outbreak at a Veterans Affairs Community Living Center (CLC).

From 12/2/20 to 5/14/21, twice weekly antigen testing was used to detect COVID-19 among 146 residents at the CLC. Residents without a prior history of COVID-19 who agreed to immunization were vaccinated with the BNT162b2 vaccine on 12/16/20 and 1/6/21. Single-dose vaccine efficacy was determined for days 1-21 and days 14-21 after the first vaccine dose.

The outbreak occurred from 12/2/20 to 1/7/21 with an attack rate of 30.8% (45/146); 46.7% (21/45) of the cases were due to asymptomatic COVID-19. One unit accounted for 77.8% (35/45) of the cases. In the vaccine analysis, 116 residents were a median age of 74.5 years and 93.1% (108/116) had ≥ 1 comorbid condition. Between the first and second dose, 15.5% (15/97) of vaccinated residents, and 21.2% (4/19) of unvaccinated residents developed COVID-19 (P=.81). One week after the second dose, no cases of COVID-19 occurred.

Albeit limited by the small numbers, a single dose of the BNT162b2 vaccine was not efficacious at preventing COVID-19 during this nursing home outbreak.

Albeit limited by the small numbers, a single dose of the BNT162b2 vaccine was not efficacious at preventing COVID-19 during this nursing home outbreak.Psychological resilience is always portrayed as the ability to rebound from adversity, which is essential for human mental health. Whereas thought control ability (TCA) is a reliable indicator of perceptual cognitive control and has a predictive effect on psychopathology. Whether and how resilience correlates with thought control are still unclear. The current study explored the whole-brain functional connectivity underlying resilience and its role in the association between resilience and TCA using resting-state fMRI. Results reveled a significant positive correlation between resilience and the functional connectivity of temporal cortex-insula, suggesting that individuals with high resilient ability exhibit flexible interaction between these two regions to facilitate emotional information processing. More importantly, a significant positive correlation between TCA and resilience was observed, and the functional connectivity of temporal cortex-insula has a significant mediation effect on the association between TCA and psychological resilience, revealing that individuals with high TCA show high levels of resilience ability through robust cognitive control on unwanted thoughts. In short, these results extended previous findings by shedding novel insights into the close relationship between resilience and TCA and the underlying neural mechanism.Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease for which effective treatment options are still lacking. ALS occurs in sporadic and familial forms which are clinically indistinguishable; about 20% of familial ALS cases are linked to mutations of the superoxide dismutase 1 (SOD1) gene. Fenretinide (FEN), a cancer chemopreventive and antiproliferative agent currently used in several clinical trials, is a multi-target drug which also exhibits redox regulation activities. We analyzed the effects of FEN on mutant SOD1 (mSOD1) toxicity in motoneuronal (NSC34) and a muscle (C2C12) cell lines and evaluated the impacts of chronic administration of a new nanomicellar fenretinide formulation (NanoMFen) on ALS disease progression in the SOD1G93A mouse model. The results showed that FEN significantly prevents the toxicity of mSOD1 expression in NSC34 motor neuron; furthermore, FEN is able to partially overcome the toxic effect of mSOD1 on the myogenic program of C2C12 muscle cells. Administration of NanoMFen ameliorates the disease progression and increases median survival of mSOD1G93A ALS mice, even when given after disease onset; beneficial effects in ALS mice, however, is restricted to female sex. Our data support the therapeutic potential of FEN against ALS-associated SOD1G93A mutant protein toxicity and promote further studies to elucidate specific cellular targets of the drug in ALS. Furthermore, the sex-related efficacy of NanoMFen in mSOD1G93A ALS mice strengthens the importance, in the perspective of a precision medicine approach, of gender pharmacology in ALS research.

Cardiorespiratory fitness (CRF) varies with sex and is an independent predictor of mortality. We sought to investigate sex differences in the exercise protocol selected, CRF levels, and their relationships with long term all-cause mortality.

In a 25-year stress testing registry spanning from 1991 to 2014, consecutive all-comer patients who underwent exercise stress testing at Cleveland Clinic were categorized by sex, stress protocol and imaging modality. All tests were conducted by one or more of stress test technicians, sonographers and nuclear medicine technologists, and interpreted by cardiologists. The primary outcome all-cause mortality was analyzed in using multivariable Cox regression.

In 120,705 patients, the mean age was 53.3±12.5years, and 41% were female. Females were more commonly referred for non-Bruce exercise protocols (modified Bruce, Cornell 0, 5 and 10, Naughton and modified Naughton) with odds ratio of 2.62; 95% confidence interval (95%CI) (2.54-2.70) after adjusting for age and comorbidities. When also adjusting for the protocol chosen, females achieved lower CRF with beta -1.40, 95% CI (-1.43, -1.37). There were 8426 (6.9%) deaths during a mean follow-up of 8.7years. Both female sex and CRF were independently associated with lower all-cause mortality with hazards ratio (95%CI) of 0.44 (0.41-0.46) and 0.41 (0.39-0.42) respectively, after adjusting for age, co-morbidities and protocol chosen.

Women were more likely referred for less demanding exercise protocols, more imaging protocols and achieved lower CRF than men. Despite this, female sex was associated with significantly lower long term mortality for equivalent CRF level in adjusted analyses.

Women were more likely referred for less demanding exercise protocols, more imaging protocols and achieved lower CRF than men. Despite this, female sex was associated with significantly lower long term mortality for equivalent CRF level in adjusted analyses.In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = -0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = -0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95% 0.77-0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease.The accumulation of amyloid-β (Aβ) peptides in the brain is considered to be the initial event in the Alzheimer’s disease (AD). Neurotoxicity mediated by Aβ has been demonstrated to damage the cognitive function. In the present study, we sought to determine the effects of O-1602, a specific G-protein coupled receptor 55 (GPR55) agonist, on the impairment of learning and memory induced by intracerebroventricular (i.c.v.) of Aβ1-42 (400 pmol/mouse) in mice. Our results showed that i.c.v. injection of aggregated Aβ1-42 into the brain of mice resulted in cognitive impairment and neurotoxicity. In contrast, O-1602 (2.0 or 4.0 μg/mouse, i.c.v.) can improve memory impairment induced by Aβ1-42 in the Morris water maze (MWM), and novel object recognition (NOR) tests. Besides, we found that O-1602 reduced the activity of β-secretase 1 (BACE1) and the level of soluble Aβ1-42 in the hippocampus and frontal cortex. Importantly, O-1602 treatment reversed Aβ1-42-induced GPR55 down-regulation, decreased pro-inflammatory cytokines, and the level of malondialdehyde (MDA), increased the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as well as suppressed apoptosis as indicated by decreased TUNEL-positive cells, and increased the ratio of Bcl-2/Bax.