Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.

Caspases are a highly conserved family of cysteine-aspartyl proteases known for their essential roles in regulating apoptosis, inflammation, cell differentiation, and proliferation. Complementary to genetic approaches, small-molecule probes have emerged as useful tools for modulating caspase activity. However, due to the high sequence and structure homology of all 12 human caspases, achieving selectivity remains a central challenge for caspase-directed small-molecule inhibitor development efforts.

Chemoproteomics identifies proteoform-selective caspase-2 inhibitors.

Caspases are a highly conserved family of cysteine-aspartyl proteases known for their essential roles in regulating apoptosis, inflammation, cell differentiation, and proliferation. Complementary to genetic approaches, small-molecule probes have emerged as useful tools for modulating caspase activity. However, due to the high sequence and structure homology of all twelve human caspases, achieving selectivity remains a central challenge for caspase-directed small-molecule inhibitor development efforts.

20-Year Experience With Repair of Pulmonary Atresia or Stenosis and Major Aortopulmonary Collateral Arteries.

Background: We have followed a consistent, albeit evolving, strategy for the management of patients with pulmonary atresia or severe stenosis and major aortopulmonary collateral arteries (MAPCAs) that aims to achieve complete repair with low right ventricular pressure by completely incorporating blood supply and relieving stenoses to all lung segments.

Objectives: The purpose of this study was to characterize our 20-year institutional experience managing patients with MAPCAs.

Methods: We reviewed all patients who underwent surgery for MAPCAs and biventricular heart disease from November 2001 through December 2021.

Serial Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.

Background: In patients with tetralogy of Fallot and major aortopulmonary collaterals (MAPCAs), pulmonary blood supply is highly variable. Our approach to this condition emphasizes complete unifocalization of the pulmonary circulation, incorporating all lung segments and addressing stenoses out to the segmental level. Post-repair, we recommend serial lung perfusion scintigraphy (LPS) to assess short-term changes in pulmonary blood flow distribution.

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

'A life in a day' simulation experience: perceptions of oncology nurses and pharmacy staff.

Background: Due to an increase in patient numbers, more cancer patients are being reviewed by non-medical healthcare professionals (HCPs), and it is essential that they can empathise with patients and care for them holistically. 'A Life in a Day' is a role reversal simulation (RRS) which demonstrates the challenges, choices and impacts that cancer patients face every day, facilitated by a Smartphone application (app). This study focused on renal cell carcinoma (RCC) and was designed to evaluate the impact of RRS on participants from the British Oncology Pharmacy Association (BOPA) and the UK Oncology Nursing Society (UKONS), and identify any changes made to clinical practice as a result.

Differential and subtype-specific neuroimaging abnormalities in amnestic and nonamnestic mild cognitive impairment: A systematic review and meta-analysis.

While mild cognitive impairment (MCI) has been classified into amnestic MCI (aMCI) and nonamnestic MCI (naMCI), the neuropathological bases of these two subtypes remain elusive. Here, we performed a systematic review and meta-analysis to determine the subtype specificity of neuroimaging abnormalities in MCI and to identify neural features that may differ between aMCI and naMCI. We synthesized 50 studies that used common neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, to compare brain atrophy, white matter abnormalities, cortical thinning, cerebral hypometabolism, amyloid/tau deposition, or other features among aMCI, naMCI, and normal cognition.

An Unusual Case of Intramyocardial Dissecting Hematoma.

• IDH can occur after revascularizing a chronically infarcted myocardium. • Treatment of IDH should be individualized based on hemodynamics and hematoma size. • The potential role of IABP in hastening recovery after IDH in our case needs further study.

Airway Characteristics of Patients With 22q11 Deletion Undergoing Pulmonary Artery Reconstruction Surgery: Retrospective Cohort Study.

Objectives: We have previously shown that patients with a chromosome 22q11 microdeletion are at risk for prolonged respiratory failure after pulmonary artery reconstruction surgery compared with those with normal genotype. We sought to describe preexisting airway abnormalities in this patient population and examine relationships between airway abnormalities and outcomes.

Design: Single-center retrospective chart review from Society of Thoracic Surgery and Pediatric Cardiac Critical Care Consortium databases and the electronic medical record.

Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease.

Objective: To assess outcomes in a large cohort of patients with Alagille syndrome (ALGS) who underwent pulmonary artery reconstruction surgery for complex pulmonary artery disease.

Study Design: Patients with ALGS who underwent pulmonary artery reconstruction surgery at Lucile Packard Children's Hospital Stanford were reviewed. Patients were examined as an overall cohort and based on the primary cardiovascular diagnosis: severe isolated branch pulmonary artery stenosis, tetralogy of Fallot (TOF) without major aortopulmonary collateral arteries (MAPCAs), or TOF with MAPCAs.

Outcomes After Aortopulmonary Window for Hypoplastic Pulmonary Arteries and Dual-Supply Collaterals.

Background: Our institutional approach to tetralogy of Fallot with major aortopulmonary collateral arteries (MAPCAs) emphasizes early unifocalization and complete repair (CR). In the small subset of patients with dual-supply MAPCAs and confluent but hypoplastic central pulmonary arteries (PAs), our surgical approach is early creation of an aortopulmonary window (APW) to promote PA growth. Factors associated with successful progression to CR and mid-term outcomes have not been assessed.

Outcomes After Initial Unifocalization to a Shunt in Complex Tetralogy of Fallot With MAPCAs.

Background: Our approach to tetralogy of Fallot (TOF) with pulmonary atresia and major aortopulmonary collateral arteries (MAPCAs) emphasizes early single-stage unifocalization and intracardiac repair. However, a subset of patients with small native pulmonary arteries (PAs) and MAPCAs undergo unifocalization to a shunt rather than simultaneous intracardiac repair.

Methods: Patients with TOF/MAPCAs who underwent complete unifocalization to a systemic-to-PA shunt by a single surgeon were reviewed.

Immediately loaded implants in a patient with involuntary mandibular movements: a clinical report.

Immediately loaded implant prostheses have been used to successfully rehabilitate completely edentulous arches. Risk factors for successful treatment have not included involuntary mandibular movements. The treatment was completed on a patient with a history of neuroleptic medications who had remaining mandibular teeth extracted and then developed involuntary mandibular movements.

Prevention of pediatric graft coronary artery disease: atorvastatin.

Graft coronary artery disease is a significant cause of late graft failure and death after cardiac transplantation. HMG-coenzyme A reductase inhibitors have been used safely in children but their preventative effects against GCAD are not well known. We investigated whether atorvastatin when initiated early could prevent against the development of pediatric GCAD.

Aluminum neurotoxicity in mammals.

Although aluminum comprises a large percentage of the Earth's crust, it is excluded from body tissues, and especially from the central nervous system. When aluminum is experimentally introduced to the central nervous system, several neurotoxic effects are observed:i.e.

A comparative study of the tapetum, retina and skull of the ferret, dog and cat.

Results of this investigation indicate that the ferret (Mustela putorius) closely resembles the dog (Canis familiaris) and should be a useful research animal alternative. The tapetum lucidum is a common structure present in the eyes of dogs, cats (Felis catus) and other nocturnal animals. Our study showed that this structure was present in ferret eyes.

Aluminum-induced neurofibrillary changes in axons and dendrites.

We examined the chronic effect of aluminum on the rabbit central nervous system (CNS) and documented the occurrence of axonal swellings (spheroids) and dendritic thickening in spinal cord neurons in addition to the accumulation of neurofibrillary material in the perikaryon. The axonal swellings always occurred at the first heminode, and the neurofilaments appeared disorganized, whereas in dendrites the neurofilaments generally retained their longitudinal arrangements. Although neurofibrillary tangles were present in cortical neurons, no axonal swellings were observed.

Use of the enzyme-linked immunosorbent assay (ELISA) for detection of Entamoeba histolytica antigen in faecal samples.

A promising new ELISA method developed by Root et al. to diagnose amoebiasis by the detection of Entamoeba histolytica coproantigen was tested in Mexico City and was reported to be more than twice as sensitive as microscopy. In this study the same procedure was compared to microscopy for paired specimens from 107 patients in San Francisco.