OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.

Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women’s well-being and ensure healthcare system preparedness during future public health crises.

This work reports on the development and numerical implementation of the linear electromagnetic gyrokinetic (GK) model in a tokamak flux-tube geometry using a moment approach based on the expansion of the perturbed distribution function on a velocity-space Hermite–Laguerre polynomials basis. A hierarchy of equations of the expansion coefficients, referred to as the gyro-moments (GMs), is derived. We verify the numerical implementation of the GM hierarchy in the collisionless limit by performing a comparison with the continuum GK code GENE, recovering the linear properties of the ion temperature gradient, trapped electron, kinetic ballooning and microtearing modes, as well as the collisionless damping of zonal flows. An analysis of the distribution functions and ballooning eigenmode structures is performed. The present investigation reveals the ability of the GM approach to describe fine velocity-space-scale structures appearing near the trapped and passing boundary and kinetic effects associated with parallel and perpendicular particle drifts. In addition, the effects of collisions are studied using advanced collision operators, including the GK Coulomb collision operator. The main findings are that the number of GMs necessary for convergence decreases with plasma collisionality and is lower for pressure gradient-driven modes, such as in H-mode pedestal regions, compared with instabilities driven by trapped particles and magnetic gradient drifts often found in the core. The accuracy of approximations often used to model collisions (relative to the GK Coulomb operator) is studied in the case of trapped electron modes, showing differences between collision operator models that increase with collisionality and electron temperature gradient, consistent with the results of Pan et al. (Phys. Rev. E, vol. 103, 2021, L051202). Such differences are not observed in other edge microinstabilities, such as microtearing modes. The importance of a proper collision operator model is also confirmed by analysing the collisional damping of geodesic acoustic modes and zonal flows.

Active galactic nuclei (AGN) have been observed as far as redshift $z \sim 7$. They are crucial in investigating the early Universe as well as the growth of supermassive black holes at their centres. Radio-loud AGN with their jets seen at a small viewing angle are called blazars and show relativistic boosting of their emission. Thus, their apparently brighter jets are easier to detect in the high-redshift Universe. DES J014132.4–542749.9 is a radio-luminous but X-ray weak blazar candidate at $z = 5$. We conducted high-resolution radio interferometric observations of this source with the Australian Long Baseline Array at $1.7$ and $8.5$ GHz. A single, compact radio-emitting feature was detected at both frequencies with a flat radio spectrum. We derived the milliarcsecond-level accurate position of the object. The frequency dependence of its brightness temperature is similar to that of blazar sources observed at lower redshifts. Based on our observations, we can confirm its blazar nature. We compared its radio properties with those of two other similarly X-ray-weak and radio-bright AGN, and found that they show very different relativistic boosting characteristics.

Abstract

There have been a number of recent findings that elucidate the ways repeated episodes relate to cognitive impairment and poor functioning in Bipolar Disorder. While available treatments are undoubtedly helpful, many patients are still lacking improvement and adequate prophylaxis even when adherence to treatment is accomplished. New research point to neural glial cells resilience and connectivity as major contributors to the pathophysiology of the disorder. In this context, growth factors such as the brain-derived neurotrophic factor (BDNF) have been pointed out as potential targets for the development of new treatments. In the psychological domain, better assessment of the cognitive decline associated with the disorder is a major issue. Once cognitive disability is present, interventions with the potential to recover functioning have been put forward. In the biological domain, strategies aiming at reducing neural damage and with the potential to regenerate connectivity among brain cell are promising avenues for the development of new treatments. Another important development would be the incorporation of biological markers as a means to help staging the degree of severity of the disorder and guide the pharmacological treatment. These topics and their relationship to the clinical context will be discussed in this session.

Psychiatric intensive care is supposed to offer treatment and to hold patients with psychiatric illness, if they pose a threat to themselves or to others. Besides treating the underlying psychiatric diagnoses, it is also necessary to take care of severe somatic comorbidity, which is often impeded by patients’ limited ability to cooperate. Treatment often requires the administration of sedative medication and occasionally the use of medical restraints. Involuntary commitment, involuntary treatment and the usage of physical restraints is regulated by national mental health laws. Medical professionals working in the field of psychiatric intensive care must have expert knowledge in the fields of psychopharmacology and intensive care medicine. Treatment concepts should be aimed to provide optimized care for psychiatric inpatients in a potentially life-threatening phase of their illness. This article outlines current clinical practice at the psychiatric intensive care unit of the Medical University of Vienna (Austria). Furthermore, we present diagnoses, diagnostic procedures and specific treatments of a sample of 100 consecutive inpatients treated in the years 2008 and 2009 at this ward.

Psychiatric disorders per se or treatment resistance can cause life-threatening conditions. More than 25 years have passed since the term “psychiatric intensive care unit” (PICU) was introduced in the United Kingdom. This system is comprised of security units for psychiatric patients with suicidal or violent behaviour, providing a locked environment with more resources regarding personnel and care. The PICU concept at the Department of Psychiatry and Psychotherapy in Vienna, Austria, represents a progress towards optimal care of patients with serious psychiatric illnesses who also have critical somatic illnesses. One third of the patients are transferred from inpatient facilities of medical departments such as internal medicine, emergency medicine, trauma surgery or anesthesiology. Our PICU is dedicated to somatically, critically ill patients who have psychiatric symptoms (e.g., agition, aggression, impulsivity, delusions, catatonia, confusion, reduced consciousness, impaired self-reliance) complicating recovery from their critical, somatic condition. Generally, the dosages for antipsychotics are not higher than those at normal psychiatric wards. Benzodiazepine dosages of about 30mg diazepam equivalents per day are frequently used. In the years 2008 and 2009, 10% of all patients at the Viennese PICU were treated with electroconvulsive therapy. Delirium requires immediate therapy of underlying intracerebral pathologies, extracerebral illnesses or toxic features. Involuntary commitment, physical restraints and urinary catheterization were applied in approximately 50% of the patients, nasogastric tube or central venous catheter in 20%. In every case, intensive care nursing, monitoring of vital functions and specific experience at the interface between psychiatry and somatic medicine are required.