A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson's Disease.

In Parkinson's disease, dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability. However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype of Sox6+ DANs, Anxa1+, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice.

Chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.

The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood.

Progesterone treatment is not necessary for sexual experience-enhanced paced mating behavior in estradiol benzoate-primed female rats.

Sexual behavior in female rats varies depending on sexual history and the combination of ovarian hormones administered to induce receptivity. Experiment 1 tested whether paced mating behavior differed in sexually experienced rats when receptivity was induced with sequential estradiol benzoate (EB) and progesterone (P) or EB-Alone. Rats gained paced mating experience under EB/P (10 μg EB 48 hr + 1 mg P 4-6 hr before mating) and then were primed with EB-Alone (2 μg EB for 6 days).

Evaluating urine volume and host depletion methods to enable genome-resolved metagenomics of the urobiome.

Background: The gut microbiome has emerged as a clear player in health and disease, in part by mediating host response to environment and lifestyle. The urobiome (microbiota of the urinary tract) likely functions similarly. However, efforts to characterize the urobiome and assess its functional potential have been limited due to technical challenges including low microbial biomass and high host cell shedding in urine.

Behavioral and social drivers of COVID-19 vaccination initiation in the US: a longitudinal study March─ October 2021.

Many studies have examined behavioral and social drivers of COVID-19 vaccination initiation, but few have examined these drivers longitudinally. We sought to identify the drivers of COVID-19 vaccination initiation using the Behavioral and Social Drivers of Vaccination (BeSD) Framework. Participants were a nationally-representative sample of 1,563 US adults who had not received a COVID-19 vaccine by baseline.

A machine learning one-class logistic regression model to predict stemness for single cell transcriptomics and spatial omics.

Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets.

Droperidol undermining gastroparesis symptoms (DRUGS) in the emergency department.

Background/purpose: Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this chronic disease is difficult to treat which often leads to hospital admissions. This study aimed to evaluate the impact droperidol administration has on opioid therapy, symptom relief, co-administration of antiemetic and prokinetic medications, disposition, cost, and length of stay (LOS) of patients presenting to the ED.

Dectin-3-targeted antifungal liposomes efficiently bind and kill diverse fungal pathogens.

DectiSomes are anti-infective drug-loaded liposomes targeted to pathogenic cells by pathogen receptors including the Dectins. We have previously used C-type lectin (CTL) pathogen receptors Dectin-1, Dectin-2, and DC-SIGN to target DectiSomes to the extracellular oligoglycans surrounding diverse pathogenic fungi and kill them. Dectin-3 (also known as MCL, CLEC4D) is a CTL pathogen receptor whose known cognate ligands are partly distinct from other CTLs.

DectiSomes: C-type lectin receptor-targeted liposomes as pan-antifungal drugs.

Combatting the ever-increasing threat from invasive fungal pathogens faces numerous fundamental challenges, including constant human exposure to large reservoirs of species in the environment, the increasing population of immunocompromised or immunosuppressed individuals, the unsatisfactory efficacy of current antifungal drugs and their associated toxicity, and the scientific and economic barriers limiting a new antifungal pipeline. DectiSomes represent a new drug delivery platform that enhances antifungal efficacy for diverse fungal pathogens and reduces host toxicity for current and future antifungals. DectiSomes employ pathogen receptor proteins - C-type lectins - to target drug-loaded liposomes to conserved fungal cognate ligands and away from host cells.

A qualitative study of behavioral and social drivers of COVID-19 vaccine confidence and uptake among unvaccinated Americans in the US April-May 2021.

Introduction: Around one-third of Americans reported they were unwilling to get a COVID-19 vaccine in April 2021. This focus group study aimed to provide insights on the factors contributing to unvaccinated adults' hesitancy or refusal to get vaccinated with COVID-19 vaccines.

Method: Ipsos recruited 59 unvaccinated US adults who were vaccine hesitant (i.

Explaining demographic differences in COVID-19 vaccination stage in the United States - April-May 2021.

COVID-19 vaccine coverage in the US has marked demographic and geographical disparities, but few explanations exist for them. Our paper aimed to identify behavioral and social drivers that explain these vaccination disparities. Participants were a national probability sample of 3562 American adults, recruited from the Ipsos KnowledgePanel.

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.

The Chromatin Remodeler HELLS: A New Regulator in DNA Repair, Genome Maintenance, and Cancer.

Robust, tightly regulated DNA repair is critical to maintaining genome stability and preventing cancer. Eukaryotic DNA is packaged into chromatin, which has a profound, yet incompletely understood, regulatory influence on DNA repair and genome stability. The chromatin remodeler HELLS (helicase, lymphoid specific) has emerged as an important epigenetic regulator of DNA repair, genome stability, and multiple cancer-associated pathways.

Developmental basis of evolutionary lung loss in plethodontid salamanders.

One or more members of four living amphibian clades have independently dispensed with pulmonary respiration and lack lungs, but little is known of the developmental basis of lung loss in any taxon. We use morphological, molecular, and experimental approaches to examine the Plethodontidae, a dominant family of salamanders, all of which are lungless as adults. We confirm an early anecdotal report that plethodontids complete early stages of lung morphogenesis: Transient embryonic lung primordia form but regress by apoptosis before hatching.

A REVIEW OF LAWSUITS RELATED TO POINT-OF-CARE EMERGENCY ULTRASOUND APPLICATIONS.

Background: Previous investigators have assessed United States Case Law to evaluate the medicolegal risk surrounding point-of-care ultrasound applications. These studies have suggested that nonperformance is the primary source of an allegation of medical malpractice.

Objectives: The objective of this study is to update the literature regarding medical malpractice cases involving ultrasound applications that could be used at the point of care, and assess the risk conveyed to advanced practice providers and by application of emerging applications of ultrasound.

Targeted Delivery of Antifungal Liposomes to .

Mucormycosis (a.k.a.

Gene co-expression reveals the modularity and integration of C4 and CAM in Portulaca.

C4 photosynthesis and Crassulacean acid metabolism (CAM) have been considered as largely independent adaptations despite sharing key biochemical modules. Portulaca is a geographically widespread clade of over 100 annual and perennial angiosperm species that primarily use C4 but facultatively exhibit CAM when drought stressed, a photosynthetic system known as C4 + CAM. It has been hypothesized that C4 + CAM is rare because of pleiotropic constraints, but these have not been deeply explored.

Emergent and urgent ventral hernia repair: comparing recurrence rates amongst procedures utilizing mesh versus no mesh.

Background: The decision for emergent and urgent ventral hernia repair (VHR) is driven by acute symptomatology, concern for incarceration and strangulation, and perforation. Although mesh has been established to reduce hernia recurrences, the potential for mesh complications may impact the decision for utilization in emergent repairs. This study evaluates hernia repair outcomes in the emergent setting with/without mesh.

DC-SIGN targets amphotericin B-loaded liposomes to diverse pathogenic fungi.

Background: Life-threatening invasive fungal infections are treated with antifungal drugs such as Amphotericin B (AmB) loaded liposomes. Our goal herein was to show that targeting liposomal AmB to fungal cells with the C-type lectin pathogen recognition receptor DC-SIGN improves antifungal activity. DC-SIGN binds variously crosslinked mannose-rich and fucosylated glycans and lipomannans that are expressed by helminth, protist, fungal, bacterial and viral pathogens including three of the most life-threatening fungi, Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans.

DectiSomes: Glycan Targeting of Liposomal Drugs Improves the Treatment of Disseminated Candidiasis.

Candida albicans causes life-threatening disseminated candidiasis. Individuals at greatest risk have weakened immune systems. An outer cell wall, exopolysaccharide matrix, and biofilm rich in oligoglucans and oligomannans help spp.

Diagnoses of Exclusion in the Workup of Abdominal Complaints.

Abdominal pain is a common complaint in the emergency department, comprising 8.8% of all visits. Despite advances in medicine and imaging, 20% to 30% of patients still leave the department without a definitive diagnosis, whichhis can be both distressing for patients and unsatisfying for providers.

Versatile cell-based assay for measuring DNA alkylation damage and its repair.

DNA alkylation damage induced by environmental carcinogens, chemotherapy drugs, or endogenous metabolites plays a central role in mutagenesis, carcinogenesis, and cancer therapy. Base excision repair (BER) is a conserved, front line DNA repair pathway that removes alkylation damage from DNA. The capacity of BER to repair DNA alkylation varies markedly between different cell types and tissues, which correlates with cancer risk and cellular responses to alkylation chemotherapy.

Penile Extra-Tunical Graft Reconstruction of Peyronie's Disease Concavity Deformities.

Objectives: To report our initial experience with the extra-tunical grafting (ETG) procedure. This procedure was recently introduced by UCSF investigators as a tunica-sparing technique for management of penile concavity deformities.

Methods: We retrospectively reviewed records of patients who underwent ETG at our tertiary-care referral center between 2017 - 2020.