Development of a Buchwald-Hartwig Amination for an Accelerated Library Synthesis of Cereblon Binders.

In recent years, targeted protein degradation (TPD) has emerged as a powerful therapeutic modality utilizing both heterobifunctional ligand-directed degraders (LDDs) and molecular glues (e.g., CELMoDs) to recruit E3 ligases for inducing polyubiquitination and subsequent proteasomal degradation of target proteins.

The Immediate and Delayed Maximal Nonirritating Skin Testing Concentrations of β-Lactam Antibiotics.

Background: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin among guidelines. However, there is variability among guidelines for maximal ST NICs of cephalosporins.

Objective: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants.

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen.

Invasive Nocardia Infections across Distinct Geographic Regions, United States.

We reviewed invasive infections in 3 noncontiguous geographic areas in the United States during 2011–2018. Among 268 patients with invasive nocardiosis, 48.2% were from Minnesota, 32.

Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels.

Development and validation of a purification system for functional full-length human SR-B1 and CD36.

Scavenger receptor class B type 1 (SR-B1) and CD36 are both members of the class B scavenger receptor family that play important roles in lipoprotein metabolism and atherosclerotic disease. SR-B1 is the primary receptor for high-density lipoproteins, while CD36 is the receptor responsible for the internalization of oxidized low-density lipoproteins. Despite their importance, class B scavenger receptor structure has only been studied by functional domain or peptide fragments-there are currently no reports of utilizing purified full-length protein.

Neurophenotypes of COVID-19: Risk factors and recovery outcomes.

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications. It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features.

Severe Mpox Proctitis Complicated by Bowel Obstruction.

Mpox is a rare infection caused by the zoonotic orthopoxvirus. We present the case of a 44-year-old man with HIV and a history of kidney transplant who presented with mpox and developed proctitis-associated bowel obstruction, urinary retention, and eosinophilia. Our case highlights potential gastrointestinal manifestations of severe mpox infection.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

Objective: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA.

Methods: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate).

Disseminated mycobacterial infections after tumor necrosis factor inhibitor use, revealing inborn errors of immunity.

Tumor necrosis factor-a inhibitors can be associated with increased risk of infections, particularly reactivation of latent tuberculosis or nontuberculous mycobacterium (NTM). However, because disseminated NTM is rare, inborn errors of immunity should be considered. We present three patients with disseminated NTM after tumor necrosis factor-a inhibitor use who were found to have inborn errors of immunity.

Neurophenotypes of COVID-19: risk factors and recovery outcomes.

Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications, termed "long COVID". It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features.

Neurocognitive screening in patients following SARS-CoV-2 infection: tools for triage.

Background: Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery.

Methods: In this cross-sectional study, participants were prospectively recruited from a hospital-wide registry.

Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage.

Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery. Participants were prospectively recruited from a hospital-wide registry.

SR-B1's Next Top Model: Structural Perspectives on the Functions of the HDL Receptor.

Purpose Of Review: The binding of high-density lipoprotein (HDL) to its primary receptor, scavenger receptor class B type 1 (SR-B1), is critical for lowering plasma cholesterol levels and reducing cardiovascular disease risk. This review provides novel insights into how the structural elements of SR-B1 drive efficient function with an emphasis on bidirectional cholesterol transport.

Recent Findings: We have generated a new homology model of full-length human SR-B1 based on the recent resolution of the partial structures of other class B scavenger receptors.

Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss.

Background: Histologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known.

Methods: We performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution.

Reduction in Health Care Facility-Onset Infection: A Quality Improvement Initiative.

Objective: To reduce health care facility-onset (HCFO) infection (CDI) incidence by improving diagnostic stewardship and reducing the inappropriate testing of assays.

Patients And Methods: A multidisciplinary team conducted a quality improvement initiative from January 1, 2020, through March 31, 2021. infection and inappropriate testing were identified via electronic health records using predefined criteria related to stool quantity/caliber, confounding medications, and laboratory data.

Antibiotic stewardship: Early discontinuation of antibiotics based on procalcitonin level in COVID-19 pneumonia.

What Is Known And Objective: Procalcitonin (PCT) levels rise in systemic inflammation, especially if bacterial in origin. COVID-19, caused by the novel coronavirus SARS-CoV-2, presents with acute respiratory distress syndrome. Elevated procalcitonin in COVID-19 is considered as a marker for severity of disease.

Foliar respiration is related to photosynthetic, growth and carbohydrate response to experimental drought and elevated temperature.

Short-term plant respiration (R) increases exponentially with rising temperature, but drought could reduce respiration by reducing growth and metabolism. Acclimation may alter these responses. We examined if species with different drought responses would differ in foliar R response to +4.

Approaches to setting dietary reference values for micronutrients, and translation into recommendations.

Dietary reference values (DRV) are estimates of the daily amounts of nutrients or food energy that meet the needs of healthy people. In the UK, three terms are used to express these estimates, assuming a normal distribution of requirements in a population. These are the estimated average requirement, the lower reference nutrient intake and the reference nutrient intake.

Disseminated cryptococcosis in a patient with newly diagnosed HTLV-1 infection.

Infection by human T-lymphotropic virus 1 (HTLV-1) is often seen as the cause of chronic infection or lymphoproliferative disorders, but many clinicians do not recognise its association with severe immunosuppression. We report the case of a woman in her 70s from the Caribbean who sought care at the emergency department for weakness, fatigue and weight loss. Further work-up showed atypical lymphocytosis with floral lymphocytes and smudge cells in the peripheral blood smear and hypercalcaemia.

Neurobrucellosis associated with feral swine hunting in the southern United States.

Although uncommon, infection can occur outside the areas of high endemicity, such as the USA. In the southern USA, hunters of wild swine are at risk for brucellosis. We present a case of a patient with fever, headache and constitutional symptoms that were ongoing for 11 months.

Nutritional and social contribution of meat in diets: Interplays among young urban and rural men.

Considering the recent increase in the demand for meat and its subsequent implications for health and food security, there is an increasing need to explore its nutritional and social importance among young men in settings experiencing nutrition transition. A better understanding of meat in the diets of this group could contribute to the design of socio-culturally appropriate interventions to improve healthy eating, as these men are key decision makers in family food choices. This mixed-methods study aimed to assess the nutritional and social contribution of meat in the diet of young adult men in urban and rural Zambia.

Tuberculosis presenting as dacryoadenitis in the USA.

A 25-year-old Filipino woman living in the USA was evaluated for a 5-month history of left eye pain and a subsequent orbital mass. Histopathological analysis of the lacrimal mass showed a mixed inflammatory process with necrotising granulomas and positive cultures for She was treated with antituberculosis therapy, with resolution of symptoms. Tuberculosis dacryoadenitis is extremely rare in the USA and other developed countries.

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages.

While increased levels of high-density lipoprotein (HDL)-cholesterol correlate with protection against cardiovascular disease, recent findings demonstrate that HDL function, rather than HDL-cholesterol levels, may be a better indicator of cardiovascular risk. One mechanism by which HDL function can be compromised is through modification by reactive aldehydes such as acrolein (Acro), 4-hydroxynonenal, and malondialdehyde (MDA). In this study, we tested the hypothesis that modification of HDL with reactive aldehydes would impair HDL's athero-protective functions in macrophages.