Different COVID-19 treatments' impact on hospital length of stay.

Importance: COVID-19 has adversely affected global healthcare infrastructure since 2019. Currently, there are no large-scale published reports on the efficacy of combination therapy of dexamethasone, remdesivir, and tocilizumab on COVID-19 patients.

Objectives: Is the combination therapy of dexamethasone, remdesivir, and tocilizumab superior to other treatments on hospitalized COVID-19 patients?

Design: This is a retrospective, comparative effectiveness study.

TCR-independent Activation in Presence of a Src-family Kinase Inhibitor Improves CAR-T Cell Product Attributes.

Chimeric antigen receptor expressing T cells (CAR-T cells) have shown remarkable efficacy against some blood cancers and have potential to treat many other human diseases. During CAR-T cell manufacturing, T cells are activated via engagement of the T-cell receptor (TCR); however, persistent TCR engagement can induce unchecked activation, differentiation, and exhaustion, which can negatively affect CAR-T cell product quality and in vivo potency. In addition, T cells may not uniformly respond to TCR-dependent activation (TCRD) contributing to lot-to-lot variability, poor expansion, and manufacturing failures.

A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity.

Viral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy.

CAR-T Cell Therapy: Mechanism, Management, and Mitigation of Inflammatory Toxicities.

Engineered T cell therapies such as chimeric antigen receptor (CAR) expressing T cells (CAR-T cells) have great potential to treat many human diseases; however, inflammatory toxicities associated with these therapies present safety risks and can greatly limit its widespread use. This article briefly reviews our current understanding of mechanisms for inflammatory toxicities during CAR T-cell therapy, current strategies for management and mitigation of these risks and highlights key areas of knowledge gap for future research.

Structure-Mediated RNA Decay by UPF1 and G3BP1.

Post-transcriptional mechanisms regulate the stability and, hence, expression of coding and noncoding RNAs. Sequence-specific features within the 3' untranslated region (3' UTR) often direct mRNAs for decay. Here, we characterize a genome-wide RNA decay pathway that reduces the half-lives of mRNAs based on overall 3' UTR structure formed by base pairing.

Hyperoxia and Hypoxic Hypoxia Effects on Simple and Choice Reaction Times.

Introduction: Effects of exposure to hyperoxia (PiO2 > 105 mmHg), normoxia (PiO2 95-105 mmHg) and hypoxia (PiO2 < 95 mmHg) on simple and choice reaction performance tasks were evaluated.

Methods: Ten subjects performed simple and choice reaction time tests (SRT and CRT, respectively) at ground level for 40 min (20 min normoxic, 20 min hyperoxic, randomly assigned), 3048 m (10,000 ft) for 75 min (15 min hyperoxic, 60 min hypoxic), 4572 m (15,000 ft) for 60 min (15 min hyperoxic, 45 min hypoxic), and 6096 m (20,000 ft) for 35 min (15 min hyperoxic, 20 min hypoxic). SRT and CRT tests were also conducted at ground level 1 h after normoxic rest (recovery) to assess any recovery time effect on these psychomotor tasks.

Pulmonary Effects from a Simulated Long-Duration Mission in a Confined Cockpit.

Introduction: A recent U-2 fatigue study, in which 10 subjects completed 2 simulated long-duration missions breathing either 100% oxygen or air in a hypobaric chamber, offered an opportunity to compare subjects' pulmonary function before and after remaining seated in a confined cockpit for 12 h.

Methods: In one U-2 mission configuration, the subject wore a full pressure suit and breathed aviator's breathing oxygen while chamber pressure was maintained at 4572 m (15,000 ft) above mean sea level. In the second mission configuration, subjects wore standard aircrew flight equipment and breathed air while chamber pressure was maintained at 2438 m (8000 ft) above mean sea level.

Cognitive Deterioration in Moderate and Severe Hypobaric Hypoxia Conditions.

Background: Hypoxia continues to present risks in military aviation. Hypoxia symptoms include sensory and cognitive effects; of these, it is important to identify which components of operator performance are most vulnerable to hypoxia-induced decline in order to determine which sensory modality is most effective for alerting an impaired aviator of an imminent hypoxic episode.

Methods: A study was performed in a hypobaric chamber to characterize deterioration of cognitive performance under moderate (MH) and severe (SH) hypoxia conditions, culminating in subjects' inability to perform tasks.

CircRNAs: a regulator of cellular stress.

Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation.

Cognition Effects of Low-Grade Hypoxia.

Introduction: The effects of low-grade hypoxia on cognitive function are reported in this paper. The study compared cognitive function during short exposures at four different altitudes.

Methods: Ninety-one subjects were exposed to simulated altitudes of ground level, 1524, 2438, and 3658 m (5000, 8000, and 12,000 ft) in the Brooks City-Base altitude pressure chamber in a balanced design.

G Protection When Adding Pressurized Sleeves and Gloves to a Representative G-Suit Ensemble.

Background: In a previous study, pressurized sleeves and gloves were found to substantially diminish or eliminate G-induced arm pain. Since this equipment presumably acts similarly to a G suit for the arms and hands, it was hypothesized that higher inflation pressures might provide an additional increment of G protection.

Methods: In a human-rated centrifuge, 15 well trained subjects using Combat Edge and ATAGS G-protective equipment were exposed to gradual and rapid onset relaxed G exposures as well as rapid onset straining and simulated aerial combat maneuver G exposures up to + 9 Gz with and without pressurized sleeves and gloves.

Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine nucleotides.

The metabolism of the nonessential amino acid proline contributes to tumor metabolic reprogramming. Previously we showed that MYC increases proline biosynthesis (PB) from glutamine. Here we show MYC increases the expression of the enzymes in PB at both protein and mRNA levels.

Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKCε, Stat3, and Epithelial-to-Mesenchymal Transition Markers.

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma.

Proline metabolism and cancer: emerging links to glutamine and collagen.

Purpose Of Review: Proline metabolism impacts a number of regulatory targets in both animals and plants and is especially important in cancer. Glutamine, a related amino acid, is considered second in importance only to glucose as a substrate for tumors. But proline and glutamine are interconvertible and linked in their metabolism.

α-Mangostin: a dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model.

Aims: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC.

Plumbagin, a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model.

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10(6)) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt.

Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKCε, Stat3 and neuroendocrine markers.

Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, is a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L. (also known as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans cinerea (whitenut) and Juglans nigra (blacknut).

Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways.

Pancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer-related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1).

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas.

Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P.

Acceleration tolerance after ingestion of a commercial energy drink.

Background: Caffeine ingestion has been demonstrated to increase physical performance in some situations. This study examined the ability of a commercial energy drink containing caffeine to enhance acceleration tolerance and strength under G load.

Methods: Eight experienced centrifuge subjects completed three separate experimental acceleration exposures following ingestion of 11.

The influence of 8 weeks of whey-protein and leucine supplementation on physical and cognitive performance.

The purpose of this study was to investigate the ability of whey-protein and leucine supplementation to enhance physical and cognitive performance and body composition. Thirty moderately fit participants completed a modified Air Force fitness test, a computer-based cognition test, and a dual-energy X-ray-absorptiometry scan for body composition before and after supplementing their daily diet for 8 wk with either 19.7 g of whey protein and 6.

Air break during preoxygenation and risk of altitude decompression sickness.

Introduction: To reduce the risk of decompression sickness (DCS), current USAF U-2 operations require a 1-h preoxygenation (PreOx). An interruption of oxygen breathing with air breathing currently requires significant extension of the PreOx time. The purpose of this study was to evaluate the relationship between air breaks during PreOx and subsequent DCS and venous gas emboli (VGE) incidence, and to determine safe air break limits for operational activities.

Acceleration tolerance at night with acute fatigue and stimulants.

Introduction: The impact of pharmacological agents on aviators concerns all flight surgeons. This study tested the related hypotheses that acute fatigue reduces +Gz tolerance and endurance, and that stimulants can partially reverse this impact. Additionally, the researchers attempted to develop a test battery sensitive enough to detect subtle differences in aviator cognition and performance among conditions.

Cognitive performance following premature awakening from zolpidem or melatonin induced daytime sleep.

Background: The hypnotic zolpidem and the hormone melatonin were evaluated and directly compared for their effects on performance when subjects sleeping under their influence were prematurely awakened from daytime sleep.

Method: Non-sleep deprived volunteers (eight men and five women) received single oral doses of 5 or 10 mg melatonin (Mel-5; Mel-10), 10 or 20 mg zolpidem (Zol-10; Zol-20), or placebo immediately before retiring at 13:00. Performance testing and subjective evaluations occurred prior to dosing and following forced awakening at 15:00, 2 h after dosing.

Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission.

Introduction: Interventions to maintain performance are necessary to meet demanding mission requirements during sustained and surge aviation operations. Tube foods are the only foods that can be consumed during a U-2 mission due to the confining and encapsulating nature of required support equipment. Caffeine is a safe and effective strategy to enhance cognitive performance and is an ingredient in some tube foods.