Refractory fungal infection: Three case reports highlighting good practice.

Refractory invasive fungal disease is a significant clinical problem, with high morbidity, mortality and costs. The complex causes of refractory infection include breakthrough infection due to antifungal resistance (both innate and acquired), suboptimal therapy and impaired immune responses in critically ill or immunocompromised patients. This case series details three reports on the identification and management of refractory fungal infections, two cases of azole resistance and one case of resistant candidiasis, highlighting the importance of accurate diagnosis, monitoring, implementation of biomarkers (serological markers, PCR), antifungal susceptibility testing and antifungal stewardship to optimise management and minimise risks of emergence of drug resistance.

Determination of residual alkyl iodides and alkyl bromides as their corresponding alkyl chlorides in drug substances by headspace GC-FID.

Primary and secondary alkyl iodides and primary alkyl bromides were quickly and conveniently converted into their corresponding alkyl chlorides via S2 halide-halide substitution. The resultant alkyl chlorides simultaneously demonstrated increased volatility and stability paired with standard headspace GC-FID methodology. The derivatization was performed on both standard and sample alike and occurred during the headspace oven equilibration phase, eliminating the extra reaction step traditionally performed during many derivatization analyses.

Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults.

In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup.

Employer Perspective on Pain Fellowship Education: A Survey to Understand the Current State of Pain Medicine Training.

Background: Pain medicine care has expanded to encompass a wider range of conditions, necessitating updated education and training for pain specialists to utilize emerging technologies effectively. A national survey was conducted through several verified Pain organizations regarding pain physician employers' perspectives on pain medicine fellowship training and education. The survey aimed to gather insights from a diverse range of geographic locations, practice types (academic and private practice), and practice settings.

Identification of a new spliceogenic variant causing severe primary coenzyme Q deficiency.

Background And Aims: Primary Coenzyme Q (CoQ) deficiency caused by defects is a clinically heterogeneous mitochondrial condition characterized by reduced levels of CoQ in tissues. Next-generation sequencing has lately boosted the genetic diagnosis of an increasing number of patients. Still, functional validation of new variants of uncertain significance is essential for an adequate diagnosis, proper clinical management, treatment, and genetic counseling.

The economic consequences of local gas leaks with evidence from Massachusetts housing market.

This study provides the first empirical evidence of the impact of leaks in natural gas distribution pipelines on nearby home prices. Using high-resolution property transaction data in Massachusetts and a difference-in-differences approach, we find that gas leaks significantly reduce nearby home prices by 2.61% ($11,700) on average.

Joint tensor modeling of single cell 3D genome and epigenetic data with Muscle.

Emerging single cell technologies that simultaneously capture long-range interactions of genomic loci together with their DNA methylation levels are advancing our understanding of three-dimensional genome structure and its interplay with the epigenome at the single cell level. While methods to analyze data from single cell high throughput chromatin conformation capture (scHi-C) experiments are maturing, methods that can jointly analyze multiple single cell modalities with scHi-C data are lacking. Here, we introduce Muscle, a semi-nonnegative joint decomposition of Multiple single cell tensors, to jointly analyze 3D conformation and DNA methylation data at the single cell level.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

RSV immunization uptake among infants and pregnant persons - Wisconsin, October 1, 2023-March 31, 2024.

Respiratory syncytial virus (RSV) is the leading cause of hospitalizations among infants in the United States. New strategies to prevent RSV among infants and high-risk young children include the maternal RSVpreF vaccine (Abrysvo, Pfizer Inc.) and nirsevimab (Beyfortus, Sanofi and AstraZeneca), a long-acting monoclonal antibody.

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

Intrathecal Drug Delivery for Intractable Pain: Identified Patient Satisfaction Survey Study Comparing Intrathecal Dose With Satisfaction, Pain Relief, and Side Effects.

Objectives: Past studies have shown the efficacy of spinal targeted drug delivery (TDD) in pain relief, reduction in opioid use, and cost-effectiveness in long-term management of complex chronic pain. We conducted a survey to determine treatment variables associated with patient satisfaction.

Materials And Methods: Patients in a single pain clinic who were implanted with Medtronic pain pumps to relieve intractable pain were identified from our electronic health record.

Reversal of neuronal tau pathology via adiponectin receptor activation.

Changes in brain mitochondrial metabolism are coincident with functional decline; however, direct links between the two have not been established. Here, we show that mitochondrial targeting via the adiponectin receptor activator AdipoRon (AR) clears neurofibrillary tangles (NFTs) and rescues neuronal tauopathy-associated defects. AR reduced levels of phospho-tau and lowered NFT burden by a mechanism involving the energy-sensing kinase AMPK and the growth-sensing kinase GSK3b.

Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance.

Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood in Drosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA.

The utility of a sensitive genitourinary exam in the management of pediatric bowel and bladder dysfunction.

Introduction: Bladder and bowel dysfunction (BBD) is a commonly experienced disorder that can cause adverse physical and psychological impacts on a child and their family.

Objective: This study aimed to assess the yield of clinically significant sensitive genitourinary (GU) examination findings and whether findings influence BBD management.

Methods: A cross-sectional, descriptive, correlational research design was used to study the relationship between GU examination findings and management of pediatric BBD.

A foundation model with weak experiential guidance in detecting muscle invasive bladder cancer on MRI.

Preoperative detection of muscle-invasive bladder cancer (MIBC) remains a great challenge in practice. We aimed to develop and validate a deep Vesical Imaging Network (ViNet) model for the detection of MIBC using high-resolution Tweighted MR imaging (hrTWI) in a multicenter cohort. ViNet was designed using a modified 3D ResNet, in which, the encoder layers were pretrained using a self-supervised foundation model on over 40,000 cross-modal imaging datasets for transfer learning, and the classification modules were weakly supervised by an experiential knowledge-domain mask indicated by a nnUNet segmentation model.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Chemopreventive effect of Pistacia vera leaf extract against Mammary Carcinoma Induced by Dimethyl-Benz(a)anthracene in vivo and in vitro: potential role of antioxidant, antiinflammatory and immune mechanisms.

This study aimed to define the antitumor effect of ethanolic extract of Pistacia vera leaves (PEE) toward breast cancer both in vitro and in vivo using dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in adult female rats. PEE showed a potent antioxidant effect toward both DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radicals with IC values of 72.6 and 107.

Donor Type Does Not Impact Late Graft Failure Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Based Graft-Versus-Host Disease Prophylaxis.

Background: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12-20% in haplo-HCT recipients using PTCy. The objective of this study was to determine if donor type influenced the risk of late graft failure following RIC HCT using PTCy-based GVHD prophylaxis.

Rapid-onset cancer.

Human cancers are generally thought to develop over the course of decades. Such slow progression is well documented for a variety of cancers that we designate "slow-onset" cancers. "Rapid-onset" cancers, in contrast, can develop in a matter of months in humans or in as little as 9 days in mice.

Measurement of the Ge(d,n)As cross section from 2.1 MeV to 10 MeV.

This work reports experimental Ge(d,n)As cross sections producing Arsenic-71 (t = 65.3 h, 28% β), a potentially useful diagnostic radionuclide. Target stacks containing two Ge foils, a Ni monitor foil, and an Al degrader were irradiated with 5.

Role of Interferon Regulatory Factor 1 in acute and chronic virus infections.

Decades of research have defined the function of interferon regulatory factors (IRFs) in the antiviral immune response. Interferon regulatory factor-1 (IRF-1) is the founding member of the IRF family, with recognized antiviral effects across diverse virus infections. While most antiviral activities of IRF-1 were defined in vitro, fewer studies examined the role of IRF-1 during viral infection of an intact host.

Using language to evaluate curricular impact: a novel approach in assessing clinical reasoning curricula.

Objectives: Published clinical reasoning curricula are limited, and measuring curricular impact has proven difficult. This study aims to evaluate the impact of a broad-reaching, multi-level reasoning curricula by measuring utilization of clinical reasoning terminology in published abstracts.

Methods: In 2014, the University of Pittsburgh Medical Center (UPMC) created a clinical reasoning curriculum with interventions at the student, resident, and faculty levels with the goal of bringing reasoning education to the forefront.

Simultaneous Emergent Phenomena: Leadership and Team Synchrony.

Emergent phenomena exhibit interesting dynamics when considered individually. The present article examines two emergent processes that could be occurring simultaneously in an intense team interaction: the emergence of leaders and the emergence of autonomic synchrony within teams making dynamic decisions. In the framework of panarchy theory and related studies on complex systems, autonomic synchrony would be a fast dynamic that is shaped or controlled by leadership emergence, which is a slower dynamic.