Identification of ABHD6 as a lysophosphatidylserine lipase in the mammalian liver and kidneys.

Lysophosphatidylserine (lyso-PS) is a potent hormone-like signaling lysophospholipid, which regulates many facets of mammalian biology and dysregulation in its metabolism is associated with several human neurological and autoimmune diseases. Despite the physiological importance and causal relation with human pathophysiology, little is known about the metabolism of lyso-PS in tissues other than the nervous and immune systems. To address this problem, here, we attempted to identify one (or more) lipase(s) capable of degrading lyso-PS in different mammalian tissues.

Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear.

ACSL4-mediated H3K9 and H3K27 hyperacetylation upregulates SNAIL to drive TNBC metastasis.

Triple-negative breast cancer (TNBC) has profound unmet medical need globally for its devastating clinical outcome associated with rapid metastasis and lack of targeted therapies. Recently, lipid metabolic reprogramming especially fatty acid oxidation (FAO) has emerged as a major driver of breast cancer metastasis. Analyzing the expression of major FAO regulatory genes in breast cancer, we found selective overexpression of acyl-CoA synthetase 4 (ACSL4) in TNBC, which is primarily attributed to the absence of progesterone receptor.

Modeling severe uncontrolled asthma: Transitioning away from health states.

Background: Models developed to date to simulate long-term outcomes of asthma have been criticized for lacking granularity and ignoring disease heterogeneity.

Objective: To propose an alternative approach to modeling asthma and apply it to model long-term outcomes in a population with moderate-to-severe type 2 asthma (patients with raised fractional exhaled nitric oxide or eosinophils) and treated with conventional therapy.

Methods: A discretely integrated condition event (DICE) approach was adopted, simulating individual profiles with asthma over patients' lifetime in terms of exacerbations, asthma-related death, and death unrelated to asthma.

Dupilumab improves sense of smell and clinical outcomes in patients with severe chronic rhinosinusitis with nasal polyps with anosmia.

Objective: Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP.

Implementing and Evaluating Face-to-Face Near-Peer Teaching in Response to the Absence of Objective Structured Clinical Examinations (OSCEs) for Junior Medical Students Following the COVID-19 Pandemic.

Introduction The COVID-19 pandemic resulted in the suspension of formative Objective Structured Clinical Examinations (OSCEs) at numerous institutions. This resulted in a significant gap in OSCE exposure for junior medical students, including those at our university. Drawing upon our prior experiences with OSCEs, we created a program to evaluate the effectiveness of near-peer teaching (NPT) in preparing third-year medical students to experience and succeed in OSCEs.

Lost in translation: Threonine dictates aggregation of CAT tails.

In this issue of Molecular Cell, Chang et al. elaborate on the mechanisms by which CAT tail aggregation is mediated through threonine residues and how it contributes to the perturbation of proteostasis.

UK Foot and Ankle Thromboembolism (UK-FATE).

Aims: Venous thromboembolism (VTE) is a potential complication of foot and ankle surgery. There is a lack of agreement on contributing risk factors and chemical prophylaxis requirements. The primary outcome of this study was to analyze the 90-day incidence of symptomatic VTE and VTE-related mortality in patients undergoing foot and ankle surgery and Achilles tendon (TA) rupture.

Real-World Evidence on Use of Ceftazidime-Avibactam in the Management of Gram-Negative Infections: A Retrospective Analysis.

There is limited real-world data from India examining the treatment characteristics, safety, and efficacy of ceftazidime-avibactam against Gram-negative organisms especially multidrug-resistant pathogens including carbapenem-resistant  and carbapenem-resistant . In this retrospective study, the real-world treatment patterns, effectiveness, and safety of ceftazidime-avibactam in treating Gram-negative infections were assessed. Data was extracted from electronic health records of adult patients admitted to the hospital with documented Gram-negative infection who had received treatment for at least 48 hours with ceftazidime-avibactam as a part of routine clinical management.

Ethical Issues Regarding Dermatopathology Care for Service-Members: A Review.

Dermatologic care within the military faces unique ethical challenges. Service members are stationed across nationally and globally diverse settings, and therefore, dermatologic care rendered ranges from within resource-rich, advanced military medical treatment facilities to austere, resource-limited, deployed field environments. Additionally, military service members are often at unique risk for dermatologic disease, given occupational, environmental, and geographic exposures not commonly faced by their civilian counterparts.

CG17192 is a Phospholipase That Regulates Signaling Lipids in the Gut upon Infection.

The chemoproteomics technique, activity-based protein profiling (ABPP), has proven to be an invaluable tool in assigning functions to enzymes. The serine hydrolase (SH) enzyme superfamily, in particular, has served as an excellent example in displaying the versatility of various ABPP platforms and has resulted in a comprehensive cataloging of the biochemical activities associated within this superfamily. Besides SHs, in mammals, several other enzyme classes have been thoroughly investigated using ABPP platforms.

Three techniques for 360-degree gonioscopy-assisted transluminal trabeculotomy with iTrack advance.

Purpose: 360-degree gonioscopy-assisted transluminal trabeculotomy (GATT) is a safe and effective angle-based intervention to lower IOP. Use of the iTrack Advance allows the surgeon to efficiently advance the microcatheter in one continuous motion with a slider, an improvement upon previous techniques in which microcatheters or sutures which had to be manually threaded through Schlemm's canal with microforceps. This report demonstrates three variations in surgical technique for successful 360-degree GATT using the iTrack Advance.

Management implications of latent TB among under-five children at risk: Insights from a community study in Mumbai, India.

Background: Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown.

Mild and symptom-free months in patients with chronic rhinosinusitis with nasal polyps treated with dupilumab.

Background: Frequently reported outcomes of clinical trials in chronic rhinosinusitis with nasal polyps (CRSwNP) may have limited relatability for patients.

Objective: To enhance the patient relatability of outcomes in dupilumab clinical trials for CRSwNP, daily symptom scores were used to determine new patient‑centered end points: mild-to-no-symptom months (MSM) and symptom-free months (SFM).

Methods: This work is a post hoc analysis of patients receiving dupilumab 300 mg or placebo every 2 weeks for 24 weeks (SINUS-24 study; NCT02912468) or 52 weeks (SINUS‑52; NCT02898454).

Molecular characterization of clinically isolated with varying resistance to ceftazidime-avibactam and ceftolozane-tazobactam collected as a part of the ATLAS global surveillance program from 2020 to 2021.

Ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) are important agents for treating multidrug-resistant infections. In this study, we evaluated the molecular characteristics of 300 globally collected clinical isolates non-susceptible (NS) to CZA, C/T, or both agents. Isolates were CZA-NS and C/T-NS ( = 57), CZA-susceptible (S) and C/T-NS ( = 145), or CZA-NS and C/T-S ( = 98) selected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) surveillance program from 2020 to 2021.

Psychometric evaluation of the Dysphagia Symptom Questionnaire for adults and adolescents with eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus leading to symptoms of esophageal dysfunction; dysphagia is the most common symptom experienced by adults and adolescents.

Objective: We sought to perform a psychometric evaluation of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measure for patients with EoE.

Methods: Using baseline and week 24 data from the randomized, interventional, multinational phase 3 R668-EE-1774 trial (NCT03633617), the measurement properties of the DSQ-including reliability, construct and known-groups validity, responsiveness, and interpretation of change-were evaluated.

Effectiveness and cost-effectiveness of a community intervention in enhancing access to care and improving clinical outcomes for depression: a protocol for a cluster randomised controlled trial in India.

Background: Although depression is the leading cause of disability worldwide, treatment coverage for the condition is inadequate. Supply-side barriers (e.g.

A Facile LC-MS Method for Profiling Cholesterol and Cholesteryl Esters in Mammalian Cells and Tissues.

Cholesterol is central to mammalian lipid metabolism and serves many critical functions in the regulation of diverse physiological processes. Dysregulation in cholesterol metabolism is causally linked to numerous human diseases, and therefore, in vivo, the concentrations and flux of cholesterol and cholesteryl esters (fatty acid esters of cholesterol) are tightly regulated. While mass spectrometry has been an analytical method of choice for detecting cholesterol and cholesteryl esters in biological samples, the hydrophobicity, chemically inert nature, and poor ionization of these neutral lipids have often proved a challenge in developing lipidomics compatible liquid chromatography-mass spectrometry (LC-MS) methods to study them.

Schizodontic Molarization of Mandibular Premolars: A Case Report of Gemination.

Background: Tooth gemination is a single enlarged or joined tooth with a normal tooth count when the anomalous tooth is counted as one. Mandibular second premolars show an elevated variability of crown morphology. Only nine cases of isolated second premolar macrodontia have been reported in the literature.