Roles of myosin 1e and the actin cytoskeleton in kidney functions and familial kidney disease.

Mammalian kidneys are responsible for removing metabolic waste and maintaining fluid and electrolyte homeostasis via selective filtration. One of the proteins closely linked to selective renal filtration is myosin 1e (Myo1e), an actin-dependent molecular motor found in the specialized kidney epithelial cells involved in the assembly and maintenance of the renal filter. Point mutations in the gene encoding Myo1e, MYO1E, have been linked to familial kidney disease, and Myo1e knockout in mice leads to the disruption of selective filtration. In this review, we discuss the role of the actin cytoskeleton in renal filtration, the known and hypothesized functions of Myo1e, and the possible explanations for the impact of MYO1E mutations on renal function.

Integrative approach for women with fibromyalgia in a Veterans Affairs Medical Center: An observational study.

Fibromyalgia, a complex condition characterized by widespread musculoskeletal pain, presents a significant burden on individuals and healthcare systems. This observational study aims to explore the potential of an outpatient integrative care model for the management of fibromyalgia in women, focusing on personalized goals, patient education, non-pharmaceutical treatments, and lifestyle modifications. The primary objective is to assess patient satisfaction and its correlation with pain, quality of life, depression, and post-traumatic stress disorder (PTSD) symptoms. This pilot study seeks to determine the effectiveness of this model in the alleviation of fibromyalgia-related pain and the improvement of overall well-being. Twenty-five women diagnosed with fibromyalgia participated in a 14-week outpatient treatment program at a Veterans Affairs Medical Center, involving weekly patient-directed, integrative group visits and health coaching. Pre- and post-evaluation questionnaires were administered to assess patient satisfaction, patients' subjective sense of empowerment in the management of fibromyalgia, and symptom improvement (i.e., pain, quality of life, depression, and PTSD). In addition, the study evaluated the correlation of patient empowerment with symptom improvement. The integrative care model received high patient satisfaction, with a mean score of 8.04 out of 10. Significant pain reduction was observed based on the Numeric Rating Scale (n = 22, P < .001). Quality of life showed significant improvement according to the Fibromyalgia Impact Questionnaire (n = 24, P = .01). Furthermore, depression symptoms improved significantly, as assessed by Patient Health Questionnaire (n = 24, P = .04). However, there was no statistically significant change in PTSD scores (n = 22, P = .3). Patient empowerment was strongly correlated with pain reduction (n = 25, r = .78, P < .001), quality of life (n = 25, r = .57, P < .001), and improvement in depression symptoms (n = 22, r = .50, P = .004). Pairwise deletion was used for each outcome. This integrative care model demonstrated promising results in effectively managing fibromyalgia-related pain and enhancing quality of life and depression symptoms in women. This model presents a feasible and potentially effective treatment approach for fibromyalgia. Further research with larger sample sizes and control groups is warranted to validate these findings and encourage broader implementation.

A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium.

BACKGROUND: Recent data show survival after matched unrelated donor (MUD) bone marrow transplantation (BMT) is similar to matched sibling procedures for young patients with severe aplastic anemia (SAA). Donor delays, risk of transplant-related mortality (TRM), and concern about chronic graft versus host disease raise questions about whether MUD BMT or immune suppression therapy (IST) should be preferred initial therapy for young patients lacking matched sibling donors. PROCEDURE: We performed a pilot trial to assess the feasibility of randomizing patients under age 26 with newly diagnosed SAA to receive IST versus MUD BMT. Primary aims assessed the acceptability of randomization and timing of BMT. Secondary aims measured toxicities, response, and survival. RESULTS: Sixty-seven patients with possible SAA were screened at nine centers. Of 57 with confirmed SAA, 23 underwent randomization and received therapy with a median follow-up of 18 months. Of 12 randomized to BMT, 10 started BMT as initial therapy at a median of 36 days after randomization. One BMT recipient experienced secondary graft failure, requiring a second procedure. Six of 11 randomized to IST responded, whereas five with refractory disease underwent successful salvage BMT. One patient achieving complete response relapsed after discontinuation of immune suppression and died of infection after salvage BMT. CONCLUSIONS: This feasibility study showed that a high percentage of patients underwent randomization and received up-front MUD BMT. Our study lays the groundwork for a larger randomized trial that will define best initial therapy for young patients with SAA who have an available MUD.