Characteristics and outcomes of patients undergoing second-trimester dilation and evacuation for intrauterine fetal demise vs induced abortion.

Objectives: Patients with intrauterine fetal demise (IUFD) are at higher risk of complications when undergoing dilation and evacuation (D&E) compared to patients undergoing abortion for other indications. We aimed to compare baseline characteristics and describe outcomes, including frequencies of complications such as disseminated intravascular coagulation (DIC) and hemorrhage, in patients undergoing D&E for IUFD vs induced abortion, with a goal of identifying associated risk factors for complications.

Study Design: We conducted a retrospective matched cohort study of patients undergoing nonemergent D&Es for singleton ≥14-0/7-week IUFD January 1, 2019 to May 31, 2021, matched with two patients undergoing induced second-trimester D&Es by cesarean delivery history, patient age, and gestational age (GA).

Roadmap for Trauma-Informed Medical Education: Introducing an Essential Competency Set.

Research has established that trauma is nearly universal and a root cause of numerous health and social problems, including 6 of the 10 leading causes of death, with devastating consequences across the life course. Scientific evidence now recognizes the complex injurious nature of structural and historical trauma (i.e.

Clinical experience with frontline Hyper-CVAD-based regimens, including Hyper-CVAD plus ponatinib, in patients with acute lymphoblastic leukemia treated at a comprehensive cancer center.

Background: Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated.

Vomiting and risk of endotracheal intubation related to preoperative doxycycline use for dilation and evacuation.

Objective: To describe the rate of vomiting from oral doxycycline 200 mg given the night before second trimester dilation and evacuation (D&E), proportion of anesthesia modalities, and anesthetic complications.

Study Design: We conducted a single-institution retrospective cohort study of patients presenting for second trimester D&E (14-0/7 to 23-6/7 weeks gestation) July 1, 2019-June30, 2020 following their scheduled preoperative visit as identified by billing codes. We recorded vomiting within 30 minutes of ingestion, anesthetic modality, and anesthetic complications.

Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001.

Introduction: Immune checkpoint inhibitor (ICI) therapy has been found to increase the risk/severity of immune-mediated adverse events with subsequent kinase inhibitor treatment in oncogenically driven cancers. We explored the risk for hypersensitivity with selpercatinib, a first-in-class highly selective and potent, central nervous system-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive NSCLC compared with their ICI-naive counterparts.

Methods: Data from patients enrolled by December 16, 2019, in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms of hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by greater than or equal to 1 of the following signs/symptoms: thrombocytopenia, increased aspartate aminotransferase or alanine aminotransferase, hypotension, tachycardia, or increased creatinine.

Evidence for genetic isolation and local adaptation in the field cricket Gryllus campestris.

Understanding how species can thrive in a range of environments is a central challenge for evolutionary ecology. There is strong evidence for local adaptation along large-scale ecological clines in insects. However, potential adaptation among neighbouring populations differing in their environment has been studied much less.

Review of Autism Profiles and Response to Sertraline in Fragile X Syndrome-Associated Autism vs. Non-syndromic Autism; Next Steps for Targeted Treatment.

Given significant genetic, molecular, and phenotypic overlaps, researchers have begun to investigate whether targeted treatments for Fragile X Syndrome (FXS) could also be beneficial for patients with Autism Spectrum Disorder (ASD). For example, low-dose sertraline, an SSRI, was used in two recent controlled trials in children with FXS and ASD. The first trial recruited 52 children with FXS, 32 of which were also diagnosed with ASD; the second trial recruited 58 children with non-syndromic ASD.

Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome.

Background: The purpose of this study was to conduct a 20-week controlled trial of lovastatin (10 to 40 mg/day) in youth with fragile X syndrome (FXS) ages 10 to 17 years, combined with an open-label treatment of a parent-implemented language intervention (PILI), delivered via distance video teleconferencing to both treatment groups, lovastatin and placebo.

Method: A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen participants were assigned to the lovastatin group; two participants terminated early from the study.

A Randomized Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder.

Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as measured by the Mullen Scales of Early Learning (MSEL) among those with comorbid autism spectrum disorder (ASD) in analysis, prompting the authors to probe whether sertraline is also indicated in nonsyndromic ASD. The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 58 children with ASD aged 24 to 72 months.

Xanthogranulomatous pyelonephritis with associated renal cell carcinoma.

Xanthogranulomatous pyelonephritis is associated with obstruction, stones and infection. CT is the mainstay of diagnosis, but appearances can mimic other conditions, including renal cell carcinoma. Nephrectomy is commonly recommended, but conservative treatment with antibiotics has been described after tissue diagnosis.

Metformin treatment in young children with fragile X syndrome.

Background: Metformin is a drug commonly used in individuals with type 2 diabetes, obesity, and impaired glucose tolerance. It has a strong safety profile in both children and adults. Studies utilizing the Drosophila model and knock out mouse model of fragile X syndrome (FXS) have found metformin to rescue memory, social novelty deficits, and neuroanatomical abnormalities.

New Targeted Treatments for Fragile X Syndrome.

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated to be 1:5,000 in males and 1:8,000 in females. The increase of >200 Cytosine Guanine Guanine (CGG) repeats in the 5' untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with a subsequent reduction or absence of fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features.

Strategies and tools to improve crop productivity by targeting photosynthesis.

Crop productivity needs to substantially increase to meet global food and feed demand for a rapidly growing world population. Agricultural technology developers are pursuing a variety of approaches based on both traditional technologies such as genetic improvement, pest control and mechanization as well as new technologies such as genomics, gene manipulation and environmental modelling to develop crops that are capable of meeting growing demand. Photosynthesis is a key biochemical process that, many suggest, is not yet optimized for industrial agriculture or the modern global environment.

Teaching Medical Students How to Ask Patients Questions About Identity, Intersectionality, and Resilience.

Introduction: Medical education addressing people with sexual and gender minority (SGM) identities often focuses on sexual risk, is delivered in silos, and overlooks intersecting identities. SGM individuals-particularly those with coexisting stigmatized identities-experience a disproportionate burden of discrimination, which increases vulnerability to adverse health outcomes, especially when maladaptive coping behaviors are used to manage stress. Adaptive coping and resilience can develop in the context of identity affirmation and social support, for which sensitive clinician-patient interactions provide a crucial foundation.

Mechanism of inhibition defines CETP activity: a mathematical model for CETP in vitro.

Because cholesteryl ester transfer protein (CETP) inhibition is a potential HDL-raising therapy, interest has been raised in the mechanisms and consequences of CETP activity. To explore these mechanisms and the dynamics of CETP in vitro, a mechanistic mathematical model was developed based upon the shuttle mechanism for lipid transfer. Model parameters were estimated from eight published experimental datasets, and the resulting model captures observed dynamics of CETP in vitro.

Perspectives on mathematical modeling for receptor-mediated processes.

Mathematical modeling is a potent in silico tool that can help investigate, interpret, and predict the behavior of biological systems. The first step is to develop a working hypothesis of the biology. Then by "translating" the biological phenomena into equations, models can harness the power of mathematical analysis techniques to explore the dynamics and interactions of the biological components.

Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats.

The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. Understanding these regulatory mechanisms is important for assessing the reproductive effects of environmental and pharmaceutical androgenic and antiandrogenic compounds. A mathematical model for the dynamics of androgenic synthesis, transport, metabolism, and regulation of the adult rodent ventral prostate was developed on the basis of a model by Barton and Anderson (1997).

Neisseria gonorrhoeae FitA interacts with FitB to bind DNA through its ribbon-helix-helix motif.

The fit locus, encoding two proteins, FitA and FitB, was identified in a genetic screen for Neisseria gonorrhoeae determinants that affect trafficking across polarized epithelial cells. To better understand how the locus may control these activities, we have undertaken a biochemical analysis of FitA and FitB. FitA is a DNA-binding protein with a putative ribbon-helix-helix (RHH) motif.

Expression capable library for studies of Neisseria gonorrhoeae, version 1.0.

Background: The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system.

PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells.

The retractile type IV pilus participates in a number of fundamental bacterial processes, including motility, DNA transformation, fruiting body formation and attachment to host cells. Retraction of the N. gonorrhoeae type IV pilus requires a functional pilT.

Response to continuous and pulsatile PTH dosing: a mathematical model for parathyroid hormone receptor kinetics.

In this paper, we propose a mathematical model for parathyroid hormone receptor (PTH1R) kinetics, focusing on the receptor's response to PTH dosing to discern bone formation responses from bone resorption. The PTH1R is a major target for new osteoporosis treatments, as pulsatile PTH dosing has been shown to induce net bone formation in both animals and humans, and PTH(1-34) was recently FDA approved for the treatment of post-menopausal osteoporosis. PTH has also been shown to cause net bone loss when given continuously, so that the net action of PTH on bone is dependent on the dosing pattern.

Probabilistic methods for addressing uncertainty and variability in biological models: application to a toxicokinetic model.

Population variability and uncertainty are important features of biological systems that must be considered when developing mathematical models for these systems. In this paper we present probability-based parameter estimation methods that account for such variability and uncertainty. Theoretical results that establish well-posedness and stability for these methods are discussed.

Single pilus motor forces exceed 100 pN.

Force production by type IV pilus retraction is critical for infectivity of Neisseria gonorrhoeae and DNA transfer. We investigated the roles of pilus number and the retraction motor, PilT, in force generation in vivo at the single-molecule level and found that individual retraction events are generated by a single pilus fiber, and only one PilT complex powers retraction. Retraction velocity is constant at low forces but decreases at forces greater than 40 pN, giving a remarkably high average stall force of 110 +/- 30 pN.