Goldsmith D

No abstract text is available yet for this article.

Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques...

The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulation, and thus impacts fetal growth and development. We have previously shown that nano-titanium dioxide (nano-TiO2 ) inhalation exposure during gestation decreased fetal female pup and placenta mass [1], which persists in the following generation [2]. In utero exposed females, once mated, their offspring's placentas had increased capacity for H2 O2 production. Generation of oxidants such as hydrogen peroxide (H2 O2 ), have been shown to impact cyclooxygenase activity, specifically metabolites such as prostacyclin (PGI2 ) or thromboxane (TXA2 )...

Low temperatures slow or halt undesired biological and chemical processes, protecting cells, tissues, and organs during storage. Cryopreservation techniques, including controlled media exchange and regulated freezing conditions, aim to mitigate the physical consequences of freezing. Dimethyl sulfoxide (DMSO), for example, is a penetrating cryoprotecting agent (CPA) that minimizes ice crystal growth by replacing intracellular water, while polyvinyl alcohol (PVA) is a nonpenetrating CPA that prevents recrystallization during thawing...

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends...

CONTEXT.—: In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered. Per the National Academy of Medicine standards for developing trustworthy guidelines, guidelines should be updated when new evidence suggests modifications. OBJECTIVE.—: To assess evidence published since the release of the original guideline and develop updated evidence-based recommendations...

OBJECTIVE: To describe the clinical, endoscopic, histologic, and treatment outcomes of Helicobacter heilmannii (H. heilmannii) associated gastritis in children in the New England region of the United States. METHODS: Retrospective study of children (1-18 years) with H. heilmannii identified on gastric mucosal biopsies from two pediatric centers over a 21-year period, January 2000-December 2021. Cases were identified by querying pathology databases at each institution...

A 72-Year-Old Woman with Fatigue and Shortness of BreathA 72-year-old woman presented for evaluation of fatigue, dyspnea on exertion, and weight loss. How do you approach the evaluation, and what is the most likely diagnosis?

Despite significant advancements in rare genetic disease diagnostics, many patients with rare genetic disease remain without a molecular diagnosis. Novel tools and methods are needed to improve the detection of disease-associated variants and understand the genetic basis of many rare diseases. Long-read genome sequencing provides improved sequencing in highly repetitive, homologous, and low-complexity regions, and improved assessment of structural variation and complex genomic rearrangements compared to short-read genome sequencing...

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide-a glucagon-like peptide 2 analog approved for pediatric use in 2019-stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration...

From lead 1, ( N -(4-((4-(3-(4-(3-methoxyphenyl)-1 H -1,2,3-triazol-1-yl)propyl)piperazin-1-yl)sulfonyl)-phenyl)acetamide), a S100A2-p53 protein-protein interaction inhibitor based on an in silico modelling driven hypothesis, four focused libraries were designed and synthesised. Growth inhibition screening was performed against 16 human cancer cell lines including the pancreatic cell lines MiaPaCa2, BxPC3, AsPC-1, Capan-2, HPAC, PANC-1 and the drug resistant CFPAC1. Modification of 1's phenylacetamide moiety, gave Library 1 with only modest pancreatic cancer activity...

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL128/130/131A and gO...

BACKGROUND: Managing acute pain is a common challenge in the emergency department (ED). Though widely used in perioperative settings, ED-based ultrasound-guided nerve blocks (UGNBs) have been slow to gain traction. Here, we develop a low-cost, low-fidelity, simulation-based training curriculum in UGNBs for emergency physicians to improve procedural competence and confidence. METHODS: In this pre-/postintervention study, ED physicians were enrolled to participate in a 2-h, in-person simulation training session composed of a didactic session followed by rotation through stations using handmade pork-based UGNB models...

No abstract text is available yet for this article.

OBJECTIVES: Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited, possibly because the full spectrum of biobehavioral systems is not addressed by diet and exercise alone. We propose a biobehavioral model detailing mechanisms of body composition decline among perimenopausal women and the associated components of Meditative Movement (ie, tai chi, qigong, yoga) that address each of these factors...

OBJECTIVES: To assess if the distribution of villous intraepithelial lymphocytes (IELs) in a pediatric cohort with Marsh I histopathology is specific to celiac disease (CeD). METHODS: Multicenter, retrospective case-control study between January 2001 and December 2019 in children (<18 years) with and without CeD with intraepithelial lymphocytosis and normal villous architecture. Pathology specimens were reviewed by 2 study pathologists who were blinded to the final diagnosis...

The tapeworm Echinococcus multilocularis is an emerging pathogen of significance to human and animal health in Canada, yet little is known about key rodent intermediate hosts in local urban ecosystems. In Europe, invasive muskrats (Ondatra zibethicus) are an important indicator intermediate host species; however, the role of this semiaquatic rodent in the ecology of E. multilocularis is undetermined in the North American context. We examined 93 muskrats that were livetrapped in the spring of 2017 within Calgary, Alberta, Canada, for the presence of E...

Previously, we found that linear quinol-containing ligands could allow manganese complexes to act as functional mimics of superoxide dismutase (SOD). The redox activity of the quinol enables even Zn(ii) complexes with these ligands to catalyze superoxide degradation. As we were investigating the abilities of manganese and iron complexes with 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane (H4 qp4) to act as redox-responsive contrast agents for magnetic resonance imaging (MRI), we found evidence that they could also catalyze the dismutation of H2 O2 ...

BACKGROUND & AIMS: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes...

Clostridioides difficile infection (CDI) is a major cause of healthcare-associated gastrointestinal infections1,2 . The exaggerated colonic inflammation caused by C. difficile toxins such as toxin B (TcdB) damages tissues and promotes C. difficile colonization3-6 , but how TcdB causes inflammation is unclear. Here we report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors, including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in pericytes...