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Peer reviewed data describing SARS-CoV-2 Omicron variant symptoms and clinical outcomes as compared to prior surges in the United States is thus far limited. We sought to determine disease severity, presenting features, and epidemiologic factors of the SARS-CoV-2 Omicron variant compared to prior surges. Retrospective cohort analysis was performed on patients admitted during five surges in Louisiana between March 2020 and January 2022. Patient data was pulled from the medical record and a subset of patients during Surge 5 were manually abstracted. Patients who were admitted to one of six Louisiana hospitals with a positive SARS-CoV-2 test during the 5 defined surge periods were included. Surges were compared using chi-squared tests and one way ANOVA for age, sex, vaccination status, length of stay, ICU status, ventilation requirement, and disposition at discharge. The records of patients admitted during the omicron surge were analyzed for presenting symptoms and incidental SARS-CoV-2 diagnosis. With each subsequent surge, a smaller proportion of patients presenting to the emergency department were admitted. Patients admitted during surge 5 had shorter lengths of stay and fewer comorbidities than prior surges. Fewer patients in surge 5 presented with a respiratory condition and fewer required ICU admission. In surges 4 and 5, fewer vaccinated patients were admitted compared to their unvaccinated counterparts. Overall mortality was lower in surge 5 (9%) than in surge 4 (15%) p < .0005. Of the SARS-Cov-2 admissions in surge 5, 22.3% were felt to be incidental diagnoses. As the COVID-19 pandemic progressed, a younger and less vaccinated population was associated with higher risk for severe disease, fewer patients required ICU admission and overall mortality decreased. Vaccinations seemed to be protective for overall risk of hospitalization but once admitted did not seem to confer additional protection against severe illness during the omicron surge. Age also contributed to patient outcomes.

Patients with diabetes and recent worsening heart failure that had led to hospitalization were randomly assigned to receive sotagliflozin or placebo. At a median of 9 months, the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure was significantly lower with sotagliflozin than with placebo.

In this randomized trial, patients with type 2 diabetes and atherosclerotic cardiovascular disease received 5 mg or 15 mg of ertugliflozin or placebo once daily. At a mean of 3.5 years, ertugliflozin (pooled data from the two doses) was noninferior to placebo with respect to the composite outcome of cardiovascular death, myocardial infarction, or stroke.

LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.

Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic disease that is characterised by fibrosis of the skin and internal organs and vasculopathy. Although systemic sclerosis is uncommon, it has a high morbidity and mortality. Improved understanding of systemic sclerosis has allowed better management of the disease, including improved classification and more systematic assessment and follow-up. Additionally, treatments for specific complications have emerged and a growing evidence base supports the use of immune suppression for the treatment of skin and lung fibrosis. Some manifestations of the disease, such as scleroderma renal crisis, pulmonary arterial hypertension, digital ulceration, and gastro-oesophageal reflux, are now treatable. However, the burden of non-lethal complications associated with systemic sclerosis is substantial and is likely to become more of a challenge. Here, we review the clinical features of systemic sclerosis and describe the best practice approaches for its management. Furthermore, we identify future areas for development.

Extracorporeal shockwave therapy (ESWT) is a non-invasive physical therapy intervention that has emerged in the recent past to address the upswing of osteoarthritis (OA). However, insufficient evidence is present to prove the efficacy of ESWT on grade IV knee osteoarthritis (KOA). The present study aimed to examine the effects of ESWT on functional ability in patients suffering from grade IV KOA. Thirty volunteers aged 45–60 years with grade IV primary KOA diagnosed by an orthopaedic surgeon based on the Kellgren-Lawrence score participated in the study. The participants were equally and randomly divided into two groups (i.e. experimental and control), with 15 participants in each group. The participants in the control group performed conventional physiotherapy (CPT) that included ultrasound therapy, isometric quadriceps, SLR and isometric hip adductor strengthening exercises. The participants in the experimental group received ESWT in addition to CPT. Lower extremity functional scale (LEFS) score was measured before and after the four weeks of intervention. In both groups, a statistically significant (p = 0.001) improvement in LEFS was observed. In the experimental groups, it improved by 81.92% and in the control groups by 48.15%. A statistically significant (p < 0.001) difference was observed in LEFS post-intervention values between both groups. As demonstrated by our trial results, the addition of ESWT to the CPT program will yield beneficial results in ameliorating the functional disability in patients with primary KOA (grade IV). Further studies are needed to confirm and apply these findings to a larger cohort.

In this trial involving patients with atherosclerotic disease who were receiving effective statin therapy, those who were assigned to receive anacetrapib, a CETP inhibitor, had a lower risk of major coronary events than did those in the placebo group.

In this trial, patients with an acute coronary syndrome within the previous 10 days were randomly assigned to simvastatin plus either ezetimibe or placebo. At a median of 6 years, the rate of cardiovascular events was modestly but significantly lower with simvastatin–ezetimibe. The use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces both low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events in patients with and those without cardiovascular disease. 1 – 4 Intensive statin therapy, as compared with moderate-dose statin therapy, incrementally lowers LDL cholesterol levels and rates of nonfatal cardiovascular events. 5 – 9 Because of the residual risk of recurrent cardiovascular events and safety concerns associated with high-dose statin therapy, 10 additional lipid-modifying therapies have been sought. 11 – 14 Ezetimibe targets the Niemann–Pick C1–like 1 (NPC1L1) protein, thereby reducing absorption of cholesterol from the intestine. 15 , 16 When added to statins, ezetimibe reduces LDL cholesterol . . .

Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or doubling of serum creatinine from baseline. Patients ≥40 years old with T2DM (HbA1c 7.0–10.5%) and established atherosclerotic cardiovascular disease (ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind placebo, ertugliflozin 5 mg or 15 mg added to existing therapy. 8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was 64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry, coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8% of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients. The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients with T2DM and ASCVD.

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system’s versatility. Every experience – be it a sight, a sound or a memorable event – activates a unique set of neurons within the brain that together are known as a neuronal ensemble. Identifying these ensembles is key to deciphering how the brain represents experiences and stores them in memory. The most commonly used method for doing so at present relies upon a class of genes called immediate early genes (or IEGs for short). Whenever a neuron becomes active, it switches on its IEGs. By genetically modifying animals to use this mechanism to drive the production of protein markers – such as a fluorescent protein – it is possible to visualize and control the neurons that become activated in response to a stimulus. However, existing IEG-based systems for detecting neuronal activity are not ideal. In particular, these systems could be made more sensitive (so that they are more likely to respond to neuronal activity) and more specific (so that they are more likely to respond only to relevant neuronal activity). Sørensen, Cooper et al. have now developed a new system for tagging recently activated neurons that offers a number of advantages over its predecessors. Known as Robust Activity Marking (RAM), the new system consists of a specially designed DNA sequence that is switched on by neuronal activity. Compared with currently existing systems, the RAM system has low levels of background activity, meaning that it only becomes active in actively firing neurons. It is also extremely sensitive and gives a robust signal. An additional advantage of the RAM system is that the timing of its activation can be precisely controlled. This is useful for identifying those neurons that become active in response to one particular sensory stimulus. The DNA elements in the RAM system that respond to neuronal activity are conserved, which means it could be used in a variety of species, from fruit flies to primates. The relatively small size of the RAM system means that, in contrast to other IEG-based systems, it can be introduced into brains by packaging the entire DNA sequence inside a virus particle that can infect a wide range of experimental species. Finally, the design of the RAM system allows it to be targeted to specific subtypes of neurons and to cells that are connected in particular ways. Together, the multiple advantages of the RAM system over traditional IEG-based systems should make it possible for neuroscientists from many different fields to explore how the brain stores experiences in patterns of neuronal activity.