Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and Conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.

Feline ophthalmomyiasis externa caused by Cuterebra larvae: four cases (2005-2020).

CASE SERIES SUMMARY: Described are four cats diagnosed with ophthalmomyiasis externa caused by Cuterebra larvae. Medical records were retrospectively reviewed to identify cats with ophthalmomyiasis externa between 2005 and 2020 at Cornell University Hospital for Animals. Signalment, history, clinical and diagnostic findings, treatment and outcome were recorded. All cats were young (< 3 years of age), had outdoor access and were initially examined during the summer months. All cases had unilateral disease with the right eye affected. Two cases had nictitating membrane lesions and two had orbital disease. Concurrent superficial corneal ulceration was present in three cats. Two cats suffered from pyrexia, suspected secondary to inflammation from the larval infestation. Successful larval removal was performed in all cats, which resulted in improvement of discomfort and clinical signs. A corneal ulcer persisted in one cat, which was lost to follow-up prior to ulcer resolution. Parasite identification confirmed Cuterebra species infestation in all cases. RELEVANCE AND NOVEL INFORMATION: To the authors' knowledge, this is the first report of feline ophthalmomyiasis externa caused by Cuterebra species. Parasite removal was successful in restoring comfort and resolving clinical signs in all cats with adequate follow-up information.

A Qualitative Examination of Work, Families, and Schools in Low-Income Latinx Communities During Strict Immigration Enforcement.

Education policy and the role of schools are a neglected part of the welfare state. Yet schools may be important sites for understanding how policy, work, and families intersect in immigrant households. Drawing on thirty interviews from seventeen households, this article highlights the experiences of families with young children during a time of increased national hostility toward immigrants. Given that immigrant families are often excluded from more traditional forms of social insurance, findings reveal the central role of fathers both inside and outside the home. Parental involvement, defined as parents' interactions with their children's education both inside and outside the home, was structured by English-dominant schooling environments. In Phoenix, parental involvement was uniquely shaped by a punitive immigration context at father's work and in children's schools. We discuss the implications of our findings on the intergenerational transmission of disadvantage and advance policy recommendations to support foreign- and U.S.-born children's educational success.

A Masquerader of Disease: An Incomplete Presentation of Kawasaki Disease.

Kawasaki disease (KD) is a systemic pediatric vasculitis that most commonly affects children between the ages of 6 months and 4 years. The diagnosis of KD requires a high degree of clinical suspicion. In younger patients (less than 6 months) the diagnosis is exceedingly difficult as these patients typically do not meet the criteria to diagnosis KD clinically. Oftentimes, these younger patients do not meet enough of the criteria to warrant ordering an echocardiogram. We report a case of a 6-month-old Caucasian female who presented with high fevers originally thought to be due to a urinary tract infection. The patient required multiple echocardiograms in order to be diagnosed with incomplete KD. The patient was treated with IVIG and aspirin per standard of care, and experienced resolution of fevers and illness.

What the Joint Admission Medical Program (JAMP) can do for Texas physicians; what Texas physicians can do for JAMP.

Texas faces health challenges requiring a physician workforce with understanding of a broad range of issues -- including the role of culture, income level, and health beliefs -- that affect the health of individuals and communities. Building on previous successful physician workforce "pipeline" efforts, Texas established the Joint Admission Medical Program (JAMP), a first-of-its-kind program to encourage access to medical education by Texans who are economically disadvantaged. The program benefits those from racial and ethnic minority groups and involves all 31 public and 34 private Texas undergraduate colleges and universities offering life science degrees, as well as all 9 medical schools. Available program data indicate that JAMP has broadened enrollment diversity in Texas' medical schools. However, greater progress requires strengthened partnerships with professional colleagues practicing medicine in communities across Texas. This article explores how JAMP can help Texas physicians and how Texas physicians can help JAMP.

Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity.

OBJECTIVE: To evaluate disease-specific cardiovascular reactivity patterns in patients with fibromyalgia (FM) using a recently described method called fractal and recurrence analysis score (FRAS). METHODS: The study group included 30 women with FM, average age 46.7 years (SD 7.03). An age matched group of 30 women with other rheumatic disorders or having a dysautonomic background [chronic fatigue syndrome (CFS), non-CFS fatigue, neurally mediated syncope, and psoriatic arthritis (PsA)] served as controls. Subjects were evaluated with a head-up tilt test with beat-to-beat recording of the heart rate (HR) and pulse transit time. A 10-minute supine phase was followed by 600 cardiac cycles recorded on tilt. Data were processed by recurrence plot and fractal analysis. Variables acting as independent predictors of the cardiovascular reactivity were identified in FM patients versus controls. RESULTS: No statistically significant differences were found between the groups by univariate analysis comparing 92 variables of cardiovascular reactivity in FM patients compared to controls. CONCLUSION: Study of cardiovascular reactivity utilizing a head-up tilt test and processing the data using the FRAS method did not reveal a specific FM-associated abnormality. Our data confirm studies that utilized other methodologies and reached similar conclusions. Patients with FM represent a heterogenous group with respect to their pattern of cardiovascular reactivity.