Effect of Hypoglycemia on QT Interval in Individuals with and without Type 2 Diabetes: A Randomized Crossover Trial.

Background: Our goal was to determine in healthy individuals and individuals with type 2 diabetes the impact of repeated episodes of hypoglycemia on the corrected QT (QTc) interval and the time course for QTc recovery. Further, since hypoglycemia increases aldosterone and patients with primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced QTc alterations.

Methods: Twenty-seven healthy participants completed a double-blinded crossover trial contrasting 3 experimental conditions: 1) euglycemia, 2) hypoglycemia, and 3) hypoglycemia with mineralocorticoid receptor blockade pretreatment.

Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia.

Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genetic and pharmacological approaches, we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in MLL-FP leukaemia. Whilst inhibition of KAT6A/B is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, increases the therapeutic efficacy.

SBS suppression in fiber amplifiers with a broadband seed.

We present a scalar, time-dependent, plane-wave model for stimulated Brillouin scattering (SBS) within a fiber amplifier having a seed linewidth comparable to, or greater than, the Brillouin frequency shift. The broadband model introduces the existence of a backward anti-Stokes wave, in addition to the Stokes wave present in the narrowband model. The model also incorporates a Fresnel reflection within the fiber or at the exit face.

Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy.

Lysine acetyltransferases (KATs) are a family of epigenetic enzymes involved in the regulation of gene expression; they represent a promising class of emerging drug targets. The frequent molecular dysregulation of these enzymes, as well as their mechanistic links to biological functions that are crucial to cancer, have led to exploration around the development of small-molecule inhibitors against KATs. Despite early challenges, recent advances have led to the development of potent and selective enzymatic and bromodomain (BRD) KAT inhibitors.

Common Sense (Radiation) Oncology: Redefining targets in radiotherapy.

In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.

Selection for oligotrophy among bacteria inhabiting host microbiomes.

Understanding how natural selection has historically shaped the traits of microbial populations comprising host microbiomes would help predict how the functions of these microbes may continue to evolve over space and time. Numerous host-associated microbes have been found to adapt to their host, sometimes becoming obligate symbionts, whereas free-living microbes are best known to adapt to their surrounding environment. Our study assessed the selective pressures of both the host environment and the surrounding external environment in shaping the functional potential of host-associated bacteria.

Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase Activity, While Driving Potency and Aqueous Solubility.

An unmet medical need remains for patients suffering from dry eye disease (DED). A fast-acting, better-tolerated noncorticosteroid anti-inflammatory eye drop could improve patient outcomes and quality of life. Herein, we describe a small-molecule drug discovery effort to identify novel, potent, and water-soluble JAK inhibitors as immunomodulating agents for topical ocular disposition.

Discovery and Preclinical Development of Novel Intraocular Pressure-Lowering Rho Kinase Inhibitor: Corticosteroid Conjugates.

A new class of ocular steroids designed to mitigate steroid-induced intraocular pressure (IOP) elevation while maintaining anti-inflammatory activity was developed. Herein is described the discovery and preclinical characterization of ROCK'Ster compound . Codrugs consisting of a Rho kinase inhibitor (ROCKi) and a corticosteroid were synthesized.

Gas Pressure From the Endoscope: An Unexplored Contributor to Morbidity and Mortality?

Background It has been shown that the incidence of venous air embolism and venous carbon dioxide (CO) embolism is high during endoscopic retrograde cholangiopancreatography (ERCP). We examined insufflating gas flow and maximum pressure produced by three types of commonly used endoscopes because we could not readily locate technical data for endoscope gas flow and maximum emitted pressure in the manufacturer's manuals. Methods We tested the Olympus GIF-Q180 used for esophagogastroduodenoscopy, the CF-Q180 used for colonoscopy, and the TJF-Q180 used for ERCP (Olympus America Inc.

OPA1 Regulates Lipid Metabolism and Cold-Induced Browning of White Adipose Tissue in Mice.

Mitochondria play a vital role in white adipose tissue (WAT) homeostasis including adipogenesis, fatty acid synthesis, and lipolysis. We recently reported that the mitochondrial fusion protein optic atrophy 1 (OPA1) is required for induction of fatty acid oxidation and thermogenic activation in brown adipocytes. In the current study we investigated the role of OPA1 in WAT function in vivo.

Communication Between Cancer Patients and Physicians About Complementary and Alternative Medicine: A Systematic Review.

Complementary and alternative medicine (CAM) has become increasingly popular among cancer patients and is often used concomitantly with standard cancer therapies. Nonetheless, disclosure of CAM utilization by cancer patients to physicians, along with the provision of information on CAM therapies by physicians, is poor. This review explores the literature to synthesize existing information on communication about CAM usage, reasons for nondisclosure, and the clinical implications thereof.

Survey of Lifestyle, Past Medical History and Complementary and Alternative Medicine Use Among Adult Patients Participating in the National Cancer Institute's Exceptional Responders Initiative.

Introduction: The Exceptional Responders Initiative (ERI) at the National Cancer Institute attempts to correlate unusually good outcomes in patients with cancer with genetic targets in tumors and the therapies the patients received. It is not known if other factors might contribute to exceptional responses or outcomes. We explored aspects of the medical history, lifestyle changes, complementary and alternative medicine (CAM) use and communication between health care practitioners and patients who experienced an exceptional response following cancer treatment.

Prevention of pulmonary complications in sedated patients undergoing interventional procedures in the nonoperating room anesthesia setting.

Purpose Of Review: Nonoperating room anesthesia (NORA) procedures have expanded in number, variety, and complexity. NORA involves all age groups, including frail older adults and patients often considered too sick to tolerate traditional surgical interventions. Postoperative pulmonary complications are a significant source of adverse events in the perioperative setting.

Qualitative fit test outcomes for N95 filtering facepiece respirators in health care workers.

Background: We analyzed the qualitative fit test results of the filtering facepiece respirators (FFRs) used at our institution to determine their performance and utility.

Methods: We retrospectively analyzed 12,582 qualitative fit testing results for several FFR models among 8,809 health care workers (HCWs).

Results: The overall failure rate for HCWs was 15.

Genome Wide Association Study Uncovers the QTLome for Osmotic Adjustment and Related Drought Adaptive Traits in Durum Wheat.

Osmotic adjustment (OA) is a major component of drought resistance in crops. The genetic basis of OA in wheat and other crops remains largely unknown. In this study, 248 field-grown durum wheat elite accessions grown under well-watered conditions, underwent a progressively severe drought treatment started at heading.

Quality Assessment of Online Complementary and Alternative Medicine Information Resources Relevant to Cancer.

Background: Complementary and alternative medicine (CAM) is often used by cancer patients and survivors in the US. Many people turn to the internet as their first source of information. Health information seeking through the internet can be useful for patients to gain a better understanding of specific CAM treatments to discuss with their healthcare team, but only if the information is comprehensive, high quality, and reliable.

The National Cancer Institute and Cannabis and Cannabinoids Research.

The landscape of both recreational and medicinal cannabis use has changed dramatically over the past decade; however, research examining the risks and benefits of cannabis and cannabinoid use has lagged significantly behind the increased media promotion and their use by the general public and cancer patients. The National Cancer Institute (NCI) has supported cannabis-related research projects and funding opportunity announcements. In addition, NCI organized a virtual symposium on December 15-18, 2020, to discuss recent research findings on the use of cannabis and cannabinoids in relationship to cancer risk, prevention, and care.

Case Report: Novel Copy Number Variant 16p11.2 Duplication Associated With Prune Belly Syndrome.

Prune belly syndrome (PBS) is a rare congenital disease that predominantly occurs in males and is identified by its classic triad of abdominal wall musculature deficiencies, cryptorchidism, and urinary tract abnormalities. However, numerous anomalies involving the kidneys, heart, lungs, and muscles have also been reported. A multitude of chromosomal abnormalities have been implicated in its pathogenesis.

Case Report: Rare Presentation of Mixed Germ Cell Tumor in an Infant.

The estimated incidence of pediatric testis tumor is 0.5-2.0 per 100,000 children, accounting for 1-2% of all pediatric tumors.

A Comparison of Group Anger Management Treatments for Combat Veterans With PTSD: Results From a Quasi-Experimental Trial.

Difficulty controlling anger is a significant concern among combat veterans with posttraumatic stress disorder (PTSD), yet few controlled studies have examined the efficacy of anger treatments for this population. This study examined the effects of a group cognitive behavioral therapy (CBT) intervention compared with a group present-centered therapy (PCT) control condition in male and female combat veterans with PTSD. Thirty-six combat veterans with PTSD and anger difficulties began group treatment (CBT, = 19; PCT, = 17).

Effects of a Single Rapid Infusion System on Platelet Function in Stored Whole Blood: An Ex Vivo Study.

Introduction Rapid infusion systems (RIS) are used to warm and rapidly infuse crystalloids and blood products. Current guidelines do not approve of platelet transfusion through a RIS, but data supporting these guidelines are scarce. Our hypothesis was that an infusion of whole blood through a RIS would degrade platelet quantity, impede viscoelastic clot strength, and inhibit platelet aggregation response to adenosine diphosphate pathway (ADP) activation.

Surge in testicular torsion in pediatric patients during the COVID-19 pandemic.

Background: Testicular torsion is a pediatric surgical emergency, and prompt diagnosis and treatment is imperative. During the COVID-19 pandemic, pediatric patients with symptoms of testicular torsion may be reluctant to seek medical care which increases the likelihood of delayed presentation and the need for an orchiectomy. This observational study sought to determine whether there was a higher number of testicular torsion cases during COVID-19.

Quantile regression illuminates the successes and shortcomings of long-term eutrophication remediation efforts in an urban river system.

Despite massive financial investment in mitigation, eutrophication remains a major water quality problem and management priority. Eutrophication science-well established for lakes-is not as well developed for rivers, and scientific understanding of how rivers respond to eutrophication management is far more limited. Long-term data are required to evaluate progress, but such datasets are relatively rare for rivers.

Conservative Management for Urethral Foreign Body: A Case Report of an Adolescent Boy With Repeated Events.

Placing foreign bodies into the urethra is not a common occurrence in the general population. Patients self-insert foreign bodies for a multitude of reasons such as sexual gratification, secondary gain, and psychiatric illness. From our own experience and what has been reported in the literature, there is a wide variability in the type of objects that patients place into the urethra.