Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

Real-time PCR assays that detect genes for botulinum neurotoxin A-G subtypes.

The role of Real-Time PCR assays for surveillance and rapid screening for pathogens is garnering more and more attention because of its versatility and ease of adoption. The goal of this study was to design, test, and evaluate Real-Time TaqMan PCR assays for the detection of botulinum neurotoxin (/A-G) genes from currently recognized BoNT subtypes. Assays were computationally designed and then laboratory tested for sensitivity and specificity using DNA preparations containing genes from 82 target toxin subtypes, including nine bivalent toxin types; 31 strains representing other clostridial species; and an extensive panel that consisted of DNA from a diverse set of prokaryotic (bacterial) and eukaryotic (fungal, protozoan, plant, and animal) species.

Examining the Relationship Between Workplace Industry and COVID-19 Infection: A Cross-sectional Study of Canada's Largest Rapid Antigen Screening Program.

Objectives: To control virus spread while keeping the economy open, this study aimed to identify individuals at increased risk of COVID-19 transmission in the workplace using rapid antigen screening data.

Methods: Among adult participants in a large Canadian rapid antigen screening program (January 2021-March 2022), we examined screening, personal, and workplace characteristics and conducted logistic regressions, adjusted for COVID-19 wave, screening frequency and location, role, age group, and geography.

Results: Among 145,814 participants across 2707 worksites, 6209 screened positive at least once.

RGS1 Modulates Autophagic and Metabolic Programs and Is a Critical Mediator of Human Regulatory T Cell Function.

Regulatory T cells (Tregs) are critical mediators of immune tolerance and play a diametric role in cancer and autoimmunity. Tumor-infiltrating Tregs are often associated with poor prognosis in solid tumors because their enrichment in the tumor microenvironment contributes to immunosuppression. Conversely, dysregulation in the Treg compartment can disrupt self-tolerance, leading to autoimmunity.

The heme-responsive PrrH sRNA regulates pyochelin gene expression.

is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, expresses the PrrF1 and PrrF2 small RNAs (sRNAs), which post-transcriptionally repress expression of nonessential iron-containing proteins, thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH.

Do we want less automation?

AI may provide a path to decrease inequality.

Melville's "Bartleby, the Scrivener: A Story of Wall-Street": The Vicissitudes of Treating a Difficult Patient.

Taking the liberty of imagining the lawyer in Melville's "Bartleby, the Scrivener" as narrator/therapist and Bartleby as patient, this article, written with the therapist/reader in mind, traces the vicissitudes of countertransference and speculates on what constitutes a "good enough" therapeutic effort.

Internet-delivered cognitive behavioral therapy for tinnitus compared to Internet-delivered mindfulness for tinnitus: a study protocol of a randomized controlled trial.

Background: Tinnitus affects around 15% of the population and can be a debilitating condition for a sizeable part of them. However, effective evidence-based treatments are scarce. One recommended treatment for tinnitus is cognitive behavioral therapy which has been found to be effective when delivered online.

The heme-responsive PrrH sRNA regulates pyochelin gene expression.

is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, expresses the PrrF1 and PrrF2 small regulatory RNAs (sRNAs), which post-transcriptionally repress expression of non-essential iron-containing proteins thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH.

Healing From Home: Examination of an Online Mindfulness-Based Tinnitus Stress Reduction Course During the 2020 COVID Pandemic.

Purpose: The purpose of this study was to assess the effectiveness of an Internet delivered Mindfulness Based Tinnitus Stress Reduction (i-MBTSR) program during the COVID-19 pandemic. Tinnitus, often a chronic condition, is experienced by 15% of the population. For those with severe, bothersome tinnitus, quality of life is reduced and the treatment options are limited.

Cellular mechanisms and effects of IL-4 receptor blockade in experimental conjunctivitis evoked by skin inflammation.

Ocular surface diseases, including conjunctivitis, are recognized as common comorbidities in atopic dermatitis (AD) and occur at an increased frequency in patients with AD treated with biologics targeting IL-4 receptor α (IL-4Rα) or IL-13. However, the inflammatory mechanisms underlying this pathology are unknown. Here, we developed a potentially novel mouse model of skin inflammation-evoked conjunctivitis and showed that it is dependent on CD4+ T cells and basophils.

VACCINE HESITANCY, PASSPORTS, AND THE DEMAND FOR VACCINATION.

Vaccine hesitancy is modeled as an endogenous decision within a behavioral epidemiological model with endogenous agent activity. It is shown that policy interventions that directly target costs associated with vaccine adoption may counter vaccine hesitancy whereas those that manipulate the utility of unvaccinated agents will either lead to the same or lower rates of vaccine adoption. This latter effect arises with vaccine passports whose effects are mitigated in equilibrium by reductions in viral/disease prevalence that themselves reduce the demand for vaccination.

Large-scale implementation of rapid antigen testing system for COVID-19 in workplaces.

The transmission of coronavirus disease 2019 (COVID-19) in workplaces has been a persistent issue throughout the pandemic. In response, a not-for-profit initiative emerged to mitigate COVID-19 workplace transmission in Canada. We report the process for establishing a workplace frequent rapid antigen test (RAT) program.

False-Positive Results in Rapid Antigen Tests for SARS-CoV-2.

This study examines the incidence of false-positive results in a sample of rapid antigen tests used to serially screen asymptomatic workers throughout Canada.

Test sensitivity for infection versus infectiousness of SARS-CoV-2.

The most commonly used test for the presence of SARS-CoV-2 is a PCR test that is able to detect very low viral loads and inform on treatment decisions. Medical research has confirmed that many individuals might be infected with SARS-CoV-2 but not infectious. Knowing whether an individual is infectious is the critical piece of information for a decision to isolate an individual or not.

Contemplating Raising Fees: An Exercise in Therapist Disquiet.

This paper discusses the experience of psychodynamically oriented therapists in private practice as they contemplate raising their fees. Raising fees stirs up competing self-interest, transference-countertransference reverberations, financial fantasies and realities, ethical concerns, and uncomfortable as well as satisfied self-reflection. These dynamics are discussed under the following categories: exercise of power; incurring guilt; inappropriate entitlement; fear of loss; modeling of self-care; rapaciousness; unconscious factors; and self-esteem.

Blood phenylalanine reduction reverses gene expression changes observed in a mouse model of phenylketonuria.

Phenylketonuria (PKU) is a genetic deficiency of phenylalanine hydroxylase (PAH) in liver resulting in blood phenylalanine (Phe) elevation and neurotoxicity. A pegylated phenylalanine ammonia lyase (PEG-PAL) metabolizing Phe into cinnamic acid was recently approved as treatment for PKU patients. A potentially one-time rAAV-based delivery of PAH gene into liver to convert Phe into tyrosine (Tyr), a normal way of Phe metabolism, has now also entered the clinic.

Optical Biosensor Platforms Display Varying Sensitivity for the Direct Detection of Influenza RNA.

Detection methods that do not require nucleic acid amplification are advantageous for viral diagnostics due to their rapid results. These platforms could provide information for both accurate diagnoses and pandemic surveillance. Influenza virus is prone to pandemic-inducing genetic mutations, so there is a need to apply these detection platforms to influenza diagnostics.

A cross-study analysis of drug response prediction in cancer cell lines.

To enable personalized cancer treatment, machine learning models have been developed to predict drug response as a function of tumor and drug features. However, most algorithm development efforts have relied on cross-validation within a single study to assess model accuracy. While an essential first step, cross-validation within a biological data set typically provides an overly optimistic estimate of the prediction performance on independent test sets.

Erratum: Azimuthal Anisotropy of K_{S}^{0} and Λ+Λ[over ¯] Production at Midrapidity from Au+Au Collisions at sqrt[s]_{NN}=130 GeV [Phys. Rev. Lett. 89, 132301 (2002)].

This corrects the article DOI: 10.1103/PhysRevLett.89.