Natural infection and diversity of hemotropic mycoplasmas in free-ranging Geoffroy's cat (Leopardus geoffroyi) and margay cat (Leopardus wiedii) populations in Southern Brazil.

Hemoplasma infection significantly impacts felines health, yet there is a research gap regarding free-ranging wild small felids. Therefore, this study aimed to investigate the occurrence of hemoplasma in Leopardus geoffroyi and Leopardus wiedii in southern Brazil. For this purpose, we conducted molecular research for Mycoplasma spp.

US Real-World Effectiveness Study of Nirmatrelvir/Ritonavir in Preventing Hospitalization of High-Risk COVID-19 Patients.

Purpose: We describe nirmatrelvir/ritonavir (NMV/r) effectiveness in preventing hospitalization among COVID-19 patients at high risk of severe disease.

Methods: An ongoing US population-based observational cohort study with retrospective and prospective collection of national electronic healthcare data collected from the US Optum® deidentified COVID-19 Electronic Health Record dataset during December 22, 2021-July 20, 2022. Participants were ≥12 years old; had a positive SARS-CoV-2 test, COVID-19 diagnosis, or NMV/r prescription; and were at high risk of severe COVID-19 based on demographic/clinical characteristics.

Cytotoxic properties of hydroalcoholic extract on androgen unresponsive prostate cancer cells.

Androgen independent phase in prostate cancer (PCa) commonly limits the therapeutic efficacy. through its main active compound, α-thujone, appears to be an option, considering its anti-proliferative, anti-metastatic and pro-apoptotic effects on hepatocellular carcinoma. However, studies on PCa are limited.

A Randomized, Open-Label, Phase I, Single-Dose Study of Antisense Oligonucleotide, Vupanorsen, in Chinese Adults with Elevated Triglycerides.

Background: Vupanorsen is a GalNAc-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.

Objectives: The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).

Methods: In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg.

Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial.

Aims: Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.

Methods And Results: TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150-500 mg/dL.

Clinicopathologic and Molecular Characteristics of Resected Thoracic Mass Lesions in the Pediatric Population: A 25-Year Institutional Experience From a Tertiary Care Center.

Context.—: Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data.

Objective.

Development of a tool to calculate the probability of hypocalcemia after total thyroidectomy: a prospective study.

Purpose: This study aimed to evaluate the ability of the percentage of decrease in serum PTH level in the first 8 h after total thyroidectomy (TT) to predict hypocalcemia requiring Ca supplementation and develop a tool to predict it.

Methods: 97 patients who underwent TT with measurement of preoperative parathyroid hormone (PTH) levels were prospectively evaluated 1 and 8 h after TT; postoperative magnesium (Mg2PO) and phosphorus levels were evaluated on the 2nd day after surgery. The percentage of decrease in PTH level 1 h (%dPTH1h) and 8 h (%dPTH8h) postoperatively and predictors of hypocalcemia requiring Ca supplementation were evaluated and an equation was developed to predict this outcome.

Hepatic fat changes with antisense oligonucleotide therapy targeting ANGPTL3.

Background: Angiopoietin-like protein 3 (ANGPTL3) is a novel therapeutic target for hyperlipidemia. Vupanorsen, an antisense oligonucleotide targeting ANGPTL3, reduced triglycerides up to 57% in a phase 2b trial, but caused dose-dependent increases in hepatic fat fraction (HFF).

Objective: To determine the degree of HFF progression with escalating doses of vupanorsen, differential HFF increases in key patient subgroups, and the correlation between changes in HFF and liver enzymes.

Basal or stimulated thyroglobulin in evaluating response to treatment in papillary thyroid carcinoma? A retrospective cohort study.

Objective: It is not clear whether response to initial treatment in papillary thyroid carcinoma (PTC) patients is best evaluated by measuring thyroglobulin (Tg) in the presence of levothyroxine (BTg) or when stimulated by elevated TSH (STg). The aim of this study was to evaluate whether response to therapy 1 year after initial treatment changes with the use of STg in relation to BTg in PTC patients treated with total thyroidectomy (TT) and radioiodine (I), and, if observed, to assess which response is better associated with clinical course.

Subjects And Methods: This is a retrospective study of 148 PTC patients submitted to TT and I.

Association between Clinical and Histopathological Findings in Intestinal Neuronal Dysplasia Type B: An Advance towards Its Definition as a Disease.

Introduction: Intestinal neuronal dysplasia type B (IND-B) is a controversial entity that affects the submucosal nerve plexus of the distal intestine. The lack of definition of the causal relationship between histological findings and clinical symptoms has been identified as the primary point to be elucidated in the scientific investigation related to IND-B, which is essential for it to be considered a disease.

Objective: To investigate the relationship between histopathological findings and symptoms in a series of patients with IND-B.

A population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis of vupanorsen from phase I and phase II studies.

Vupanorsen (PF-07285557) is a second-generation ligand-conjugated 2'O-methoxyethyl modified antisense oligonucleotide designed to target angiopoietin-like 3 (ANGPTL3) mRNA expressed by the liver, shown to reduce lipids and apolipoproteins in subjects with dyslipidemia. Using pooled data from two phase I studies of participants with elevated triglycerides (Western: n = 48 and Japanese: n = 12), and two phase II studies of patients with hypertriglyceridemia, diabetes, and nonalcoholic fatty liver disease (n = 105), and statin-treated patients with dyslipidemia (n = 286), we developed population pharmacokinetic (PK) and PK/pharmacodynamic (PK/PD) models. Efficacy target values were set a priori to -75%, -60%, and -35% for ANGPTL3, triglyceride (TG), and non-high-density lipoprotein-cholesterol (non-HDL-C), respectively.

A multi-purpose Japanese phase I study in the global development of vupanorsen: Randomized, placebo-controlled, single-ascending dose study in adults.

Vupanorsen (PF-07285557) is a second-generation tri-N-acetyl galactosamine (GalNAc )-antisense oligonucleotide targeted to angiopoietin-like 3 (ANGPTL3) mRNA, shown to reduce lipids and apolipoproteins in subjects with dyslipidemia. To aid bringing innovative drugs to global patients efficiently, a multi-purpose Japanese phase I study was conducted, with integrated development approaches agreed by the Pharmaceuticals and Medical Devices Agency (PMDA). This randomized, double-blind, placebo-controlled, single-ascending dose (SAD) study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of vupanorsen administered subcutaneously to Japanese adults (20-65 years) with elevated triglycerides (TG).

Effects of coconut oil long-term supplementation in Wistar rats during metabolic syndrome - regulation of metabolic conditions involving glucose homeostasis, inflammatory signals, and oxidative stress.

This study was designed to evaluate the long-term effects of Fructose (20%) feeding in rats, simulating metabolic syndrome (MetS), and the effects of coconut oil (C.O.) supplementation when administered in a MetS context.

Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study.

Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT).

Subjects And Methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve.

Burnout and network centrality as proxies for assessing the human cost of resilient performance.

The extra effort of healthcare professionals to provide care is a manifestation of resilient performance (RP), usually going unnoticed due to successful outcomes. However, it is not clear how the human cost of RP can be assessed. This study addresses this gap by investigating the relationships between proxies of RP and its human cost.

Agreement between histopathological and intraoperative classifications for pediatric appendicitis and its relationship with the post-operative clinical outcome.

Introduction: Some studies have shown poor agreement between intraoperative and histopathological classifications for appendicitis, despite their routine use in clinical practice.

Objective: To investigate the agreement between histopathological and intraoperative classifications for pediatric appendicitis and evaluate the predictive potential of these classifications for the post-operative outcome.

Methods: A retrospective, longitudinal, observational single-center study, carried out with 485 patients up to15 years of age, with a confirmed diagnosis of acute appendicitis by histopathological evaluation.

PTEN Immunohistochemistry.

Context.—: Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has been established by histopathologic analysis of rectal biopsies.

Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70.

Background: Genetic loss-of-function variants in are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.

Methods: Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks).

Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells.

Intestinal neuronal dysplasia type B (IND-B) is a controversial condition among gastrointestinal neuromuscular disorders. Constipation is its most common clinical manifestation in patients. Despite intense scientific research, there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies.

Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

Objectives: Differentiating malignant pleural mesothelioma from benign reactive mesothelial processes can be quite challenging. Ancillary tests such as BRCA1-associated protein 1 (BAP1) immunohistochemistry and p16 fluorescence in situ hybridization (FISH) are helpful tools to aid in this distinction. Immunohistochemistry for methylthioadenosine phosphorylase (MTAP) has recently been proposed as an effective surrogate marker for p16 FISH and is an attractive alternative test due to shorter turnaround time.

SATB2 Is Expressed in a Subset of Pulmonary and Thymic Neuroendocrine Tumors.

Objectives: To evaluate SATB2 expression and prognostic implications in a large cohort of thoracic neuroendocrine tumors.

Methods: Surgical pathology files (1995-2017) and an institutional thymic epithelial tumor database (2010-2020) were searched for resected neuroendocrine tumors. Cases were stained with SATB2 (clone EP281).

Treatment with isolated gold nanoparticles reverses brain damage caused by obesity.

In this study, we performed two experiments. In the first experiment, the objective was to link gold nanoparticles (GNPs) with sodium diclofenac and/or soy lecithin and to determine their concentration in tissues and their toxicity using hepatic and renal analyzes in mice to evaluate their safety as therapeutic agents in the subsequent treatment of obesity. In the second experiment, we evaluated the effect of GNPs on inflammatory and biochemical parameters in obese mice.

Utility of Immunohistochemistry for MUC4 and GATA3 to Aid in the Distinction of Pleural Sarcomatoid Mesothelioma From Pulmonary Sarcomatoid Carcinoma.

Context.—: Distinguishing pulmonary sarcomatoid carcinoma from pleural sarcomatoid mesothelioma is challenging because of overlapping histology, immunophenotype, and clinical features. Reliable immunohistochemical markers to aid in this distinction would be very valuable.