Clinical Outcomes of Zinc Supplementation Among COVID-19 Patients.

Background: Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed.

Objective: Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness.

Targeting Replication Protein A for Cancer Therapy.

Replication protein A (RPA) plays essential roles in DNA replication, repair, recombination, and the DNA damage response (DDR). Retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy.

Antibiotic Prophylaxis and Incidence of Infection with External Ventricular Drains and Intra-Cranial Pressure Monitors.

Guidelines do not recommend extended antibiotic prophylaxis for external ventricular drains (EVD) or intra-cranial pressure (ICP) monitors. The study objective was to determine if infection rates are different for patients receiving antibiotic prophylaxis for EVD or ICP monitors. This single-center retrospective cohort reviewed intensive care unit patients who had an EVD or ICP monitor placed.

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole.

Design, synthesis, biological evaluation of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehydes as non-purine xanthine oxidase inhibitors: Tracing the anticancer mechanism via xanthine oxidase inhibition.

Xanthine oxidase (XO) has been primarily targeted for the development of anti-hyperuriciemic /anti-gout agents as it catalyzes the conversion of xanthine and hypoxanthine into uric acid. XO overexpression in various cancer is very well correlated due to reactive oxygen species (ROS) production and metabolic activation of carcinogenic substances during the catalysis. Herein, we report the design and synthesis of a series of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehyde derivatives (2a-2x) as xanthine oxidase inhibitors (XOIs).

Distinct Effectiveness of Oritavancin against Tolerance-Induced .

Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic "tolerant" subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant bacteria.

Discovery and development of novel DNA-PK inhibitors by targeting the unique Ku-DNA interaction.

DNA-dependent protein kinase (DNA-PK) plays a critical role in the non-homologous end joining (NHEJ) repair pathway and the DNA damage response (DDR). DNA-PK has therefore been pursued for the development of anti-cancer therapeutics in combination with ionizing radiation (IR). We report the discovery of a new class of DNA-PK inhibitors that act via a novel mechanism of action, inhibition of the Ku-DNA interaction.

Antibiotics and Innate Immunity: A Cooperative Effort Toward the Successful Treatment of Infections.

Despite the common ancestry of antimicrobial and immunological science, a divergence driven by artificially construed paradigms in microbiology has placed limits on how we understand the mechanisms of antibiotics in vivo. We summarize recent updates on data that shed light on how antibiotics interact with components of innate immunity.

Structure-Guided Optimization of Replication Protein A (RPA)-DNA Interaction Inhibitors.

Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA-DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 () compound were designed to improve potency and physicochemical properties.

Adolescent substance use and functional connectivity between the ventral striatum and hippocampus.

Neurodevelopmental explanations for adolescent substance use have focused on heightened sensitivity of mesolimbic circuitry, centered on the ventral striatum (VS). Recent evidence suggests that, relative to adults, adolescents show a stronger link between reinforcement learning and episodic memory for rewarding outcomes and greater functional connectivity between the VS and hippocampus, which may reflect a heightened reward modulation of memory. However, a link between VS-hippocampal circuitry and adolescent substance use has yet to be established.

Distinct Subpopulations of Intravalvular Methicillin-Resistant Staphylococcus aureus with Variable Susceptibility to Daptomycin in Tricuspid Valve Endocarditis.

We present a case of endocarditis wherein organisms cultured from different valve leaflets yielded different daptomycin susceptibilities from each other and from organisms obtained from peripheral blood culture. Genomic analyses showed mutations in , and Pharmacokinetic simulations showed consistent activity of daptomycin plus beta-lactam against all subpopulations. This represents an opportunity to understand evolution and fitness on daptomycin therapy and the role of beta-lactams to prevent the selection of daptomycin-resistant subpopulations.

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Bacteremia.

Immune biomarkers can stratify mortality risk in staphylococcal bacteremia. Microbial biomarkers may provide more consistent signals during early infection. We demonstrate that in ST45/USA600 bacteremia, bacterial membrane vesicle production in vitro predicts clinical mortality (773 vs.

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

Background: In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g.

A novel paradigm to study interpersonal threat-related learning and extinction in children using virtual reality.

Disruptions in fear-extinction learning are centrally implicated in a range of stress-related disorders, including anxiety and posttraumatic stress disorder. Given that these disorders frequently begin in childhood/adolescence, an understanding of fear-extinction learning in children is essential for (1) detecting the source of developmental susceptibility, (2) identifying mechanisms leading to pathology, and (3) informing the development and/or more judicious application of treatments for youth. Here, we offer and validate a novel virtual reality paradigm to study threat-related learning and extinction in children that models real-world cues, environments, and fear-inducing events that children are likely to experience, and are linked to the development of fear- and stress-related pathologies.

Mindfulness and dynamic functional neural connectivity in children and adolescents.

Background: Interventions that promote mindfulness consistently show salutary effects on cognition and emotional wellbeing in adults, and more recently, in children and adolescents. However, we lack understanding of the neurobiological mechanisms underlying mindfulness in youth that should allow for more judicious application of these interventions in clinical and educational settings.

Methods: Using multi-echo multi-band fMRI, we examined dynamic (i.

Implementation and Use of the Pharmacy Curriculum Outcomes Assessment at US Schools of Pharmacy.

Objective: To describe how schools and colleges of pharmacy use the Pharmacy Curriculum Outcomes Assessment (PCOA) in relation to student assessment and curricular feedback.

Methods: A survey was distributed to all programs that have implemented the PCOA. The survey was designed to assess 3 domains regarding the use of the PCOA: rationale for use, logistics of administration, and performance data review and distribution.

Significant weight loss may delay or eliminate the need for total knee replacement.

A 48-year-old morbidly obese woman with a left medial meniscal tear and moderately severe degenerative joint disease (DJD) reported for 14-month follow-up visit from arthroscopic surgery. She reported a resolution of pain, swelling and an improved range of motion (ROM). The patient was first evaluated 14 months ago, and at that time was considered a strong candidate for total knee replacement due to her limited (ROM), knee pain, swelling and functional impairment.

The AANA Foundation closed malpractice claims study: obstetric anesthesia.

The purpose of this study was to evaluate the anesthesia care provided during obstetric adverse events. Malpractice claims filed against nurse anesthetists for care involving obstetric anesthesia (n = 41) were extracted from the American Association of Nurse Anesthetists Foundation Closed Claim database. The events represented in the claims occurred from 1990 to 1996 and represented anesthetics provided by both anesthetists and anesthesiologists.