Cardioprotective effects of l-glutamine in an ischemic rat heart model.

Introduction: l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied.

Methods: This study hypothesized that l-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only.

Effect of intranasal insulin administration on postoperative delirium prevention in elderly cardiac surgery patients: study protocol for a multicenter, double-blind, randomized, controlled trial.

Background: Postoperative delirium (POD) is a complication after surgery which leads to worse outcomes. The frequency of this syndrome is increasing as more elderly patients undergo major surgery. The frequency is around 10-25% but reaches as high as 50% for cardiac surgery.

The Quality of Preoperative Glycemic Control Predicts Insulin Sensitivity During Major Upper Abdominal Surgery: A Case-Control Study.

Objective: To examine the association of the quality of preoperative glycemic control and insulin sensitivity during major upper abdominal surgery.

Background: In cardiac surgery, glycated hemoglobin A (HbA), an indicator of glycemic control during the preceding 3 months, correlated with intraoperative insulin sensitivity. Furthermore, insulin resistance showed a significant association with adverse clinical outcomes.

Role of the protein kinase A signaling pathway and identification of mediators in the cardioprotective effects of enteral lactoferrin for ischemia-reperfusion injury in an isolated rat heart model.

Objective: Lactoferrin is an iron-binding glycoprotein. Enteral lactoferrin attenuates myocardial ischemia-reperfusion (IR) injury, but the underlying mechanism remains unknown. The aim of this study was to investigate protein kinase A (PKA) signaling pathway activation and levels of serum glucagonlike peptide-1 (GLP-1), secreted by intestinal endocrine L cells, and adiponectin, secreted by adipose tissue, after enteral lactoferrin administration.

Senescence markers in subcutaneous preadipocytes differ in childhood- versus adult-onset obesity before and after weight loss.

Objective: The aim of this study was to determine the effect of age of obesity onset on senescence-related markers in abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) before and after moderate (~10%) weight loss.

Methods: AB and FEM SAT were collected from human females with childhood-onset obesity (CO) or adult-onset obesity (AO) before and after diet- and exercise-induced weight loss. Immunofluorescence analysis of γH2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated β-galactosidase (SA-β-gal) activity was measured in SAT.

Randomized controlled trial of the effect of hyperinsulinemic normoglycemia during liver resection on postoperative hepatic function and surgical site infection.

Background: While avoidance of preoperative fasting followed by hyperinsulinemic-normoglycemic clamp (HNC) reduced postoperative hepatic dysfunction and surgical site infection (SSI), the effect of HNC restricted to the intraoperative period is unknown. This study examined whether HNC restricted to the intraoperative period has similar effects in patients undergoing elective liver resections.

Methods: This study is a post hoc exploratory analysis of a randomized-controlled trial in patients undergoing hepatobiliary surgery and receiving the HNC as a potential preventative intervention to reduce infectious morbidity postoperatively.

Improved platform for breast cancer circulating tumor cell enrichment and characterization with next-generation sequencing technology.

Circulating tumor cells (CTCs) represent cells shed from the primary tumor or metastatic sites and can be used to monitor treatment response and tumor recurrence. However, CTCs circulate in extremely low numbers making in-depth analysis beyond simple enumeration challenging when collected from peripheral blood. Furthermore, tumor heterogeneity, a hallmark of many tumors, especially breast cancer, further complicates CTC characterization.

Quantitative proteomics and biological activity of extracellular vesicles engineered to express SARS-CoV-2 spike protein.

SARS-CoV-2 viral infection led to the devastating COVID-19 pandemic, where illness stemmed from interactions between virions and recipient host cells resulting in multi-layered pathological consequences. The role of the infection portal is now understood to be the cellular angiotensin converting enzyme-2 (ACE2) receptor, which binds to viral spike (S) protein initiating virion internalisation process. Since SARS-CoV-2 virions bear some resemblance to endogenously produced small extracellular vesicles (sEVs) we reasoned that EVs engineered to express S protein (viral mimics) may interfere with viral infection.

Cardioprotective effects of enteral vs. parenteral lactoferrin administration on myocardial ischemia-reperfusion injury in a rat model of stunned myocardium.

Background: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium.

Methods: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series.

Background: Patients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions.

Materials And Methods: This study is a retrospective analysis of SRS for brain metastasis using VMAT.

PI3K/Akt pathway mediates the positive inotropic effects of insulin in Langendorff-perfused rat hearts.

Insulin exerts positive inotropic effects on cardiac muscle; however, the relationship between cardiac contractility and phosphoinositol-3-kinase/Akt (PI3K/Akt) activation remains unclear. We hypothesized that the positive inotropic effects of insulin are dose-dependent and mediated via the PI3K/Akt pathway in isolated normal rat hearts. The Institutional Animal Investigation Committee approved the use of hearts excised from rats under pentobarbital anesthesia.

Albumin and fibrinogen kinetics in sepsis: a prospective observational study.

Background: The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects.

Profound synchrony of age-specific incidence rates and tumor suppression for different cancer types as revealed by the multistage-senescence model of carcinogenesis.

The age-specific trend of cancer incidence rates, but not its magnitude, is well described employing the multistage theory of carcinogenesis by Armitage and Doll in combination with the senescence model of Pompei and Wilson. We derived empirical parameters of the multistage-senescence model from U.S.

Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain.

Background: Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology.  However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program.

Results: Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life.

The imperative for scientific societies to change the face of academia: Recommendations for immediate action.

As organizations that facilitate collaboration and communication, scientific societies have an opportunity, and a responsibility, to drive inclusion, diversity, equity, and accessibility in science in academia. The American Association for Anatomy (AAA), with its expressed and practiced culture of engagement, can serve as a model of best practice for other professional associations working to become more inclusive of individuals from historically underrepresented groups. In this publication, we acknowledge anatomy's exclusionary past, describe the present face of science in academia, and provide recommendations for societies, including the AAA, to accelerate change in academia.

IntraIndividual Variability in Serum Alpha-1 Antitrypsin Levels.

Background: Measuring alpha-1 antitrypsin (AAT) serum levels is often the first step when investigating for alpha-1 antitrypsin deficiency (AATD). The purpose of this study was to determine the test-retest reproducibility of AAT serum levels and to determine if between-measurements variability was associated with acute phase markers of inflammation.

Methods: We retrospectively analyzed a sample of 255 patients from a community respirology practice with chronic obstructive pulmonary disease (COPD) in whom AAT serum levels were measured twice, on separate visits.

Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1.

Long-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment.

Oncogenic RAS drives the CRAF-dependent extracellular vesicle uptake mechanism coupled with metastasis.

Oncogenic RAS impacts communication between cancer cells and their microenvironment, but it is unclear how this process influences cellular interactions with extracellular vesicles (EVs). This is important as intercellular EV trafficking plays a key role in cancer invasion and metastasis. Here we report that overexpression of mutant RAS drives the EV internalization switch from endocytosis (in non-transformed cells) to macropinocytosis (in cancer cells) resulting in enhanced EV uptake.

Radiofrequency Ablation as a Primary Therapy for Benign Functioning Insulinoma.

Objective: Insulinomas are rare, life-threatening pancreatic neuroendocrine tumors. Surgical removal continues to be the treatment of choice, yet it is associated with considerable risk of morbidity. Here, we describe our patient with insulinoma who was successfully treated with radiofrequency ablation.

Intranasal administration of 40 and 80 units of insulin does not cause hypoglycemia during cardiac surgery: a randomized controlled trial.

Purpose: Intranasal insulin administration may improve cognitive function in patients with dementia and may prevent cognitive problems after surgery. Although the metabolic effects of intranasal insulin in non-surgical patients have been studied, its influence on glucose concentration during surgery is unknown.

Methods: We conducted a randomized, double-blind, placebo-contolled trial in patients scheduled for elective cardiac surgery.

Pharmacological Inhibition of PPARy Boosts HIV Reactivation and Th17 Effector Functions, While Preventing Progeny Virion Release and de Infection.

The frequency and functions of Th17-polarized CCR6RORytCD4 T cells are rapidly compromised upon HIV infection and are not restored with long-term viral suppressive antiretroviral therapy (ART). In line with this, Th17 cells represent selective HIV-1 infection targets mainly at mucosal sites, with long-lived Th17 subsets carrying replication-competent HIV-DNA during ART. Therefore, novel Th17-specific therapeutic interventions are needed as a supplement of ART to reach the goal of HIV remission/cure.

Dual staining for p16/Ki-67 to detect high-grade cervical lesions: Results from the Screening Triage Ascertaining Intraepithelial Neoplasia by Immunostain Testing study.

We compared clinical performance of p16/Ki-67 dual-stained cytology and human papillomavirus (HPV) genotyping, via different algorithms-alone, or in combination with cytology-to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) in women referred to as colposcopy. We included 492 cervical specimens (134 normal, 130 CIN1, 99 CIN2, 121 CIN3, 8 cancers) randomly selected from 1158 specimens with valid conventional cytology, HPV (cobas 4800 HPV test) and biopsy results. Dual-stained cytology was retrospectively performed (CINtec PLUS assay) on PreservCyt material; slides were read by a cytologist and confirmed by two pathologists, blinded to cytology, biopsy and genotyping results.

International Pediatric Otolaryngology Group (IPOG) Consensus Recommendations: Congenital Cholesteatoma.

Objective: To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of children who present with signs and symptoms of congenital cholesteatoma.

Methods: A two-iterative Delphi method questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group, on the preoperative work-up, the perioperative considerations, and follow-up.

Results: Twenty-two members completed the survey, in 14 tertiary-care center departments representing 5 countries.