Mutations in non-muscle myosin 2A disrupt the actomyosin cytoskeleton in Sertoli cells and cause male infertility.

Mutations in non-muscle myosin 2A (NM2A) encompass a wide spectrum of anomalies collectively known as MYH9-Related Disease (MYH9-RD) in humans that can include macrothrombocytopenia, glomerulosclerosis, deafness, and cataracts. We previously created mouse models of the three mutations most frequently found in humans: R702C, D1424N, and E1841K. While homozygous R702C and D1424N mutations are embryonic lethal, we found homozygous mutant E1841K mice to be viable. However the homozygous male, but not female, mice were infertile. Here, we report that these mice have reduced testis size and defects in actin-associated junctions in Sertoli cells, resulting in inability to form the blood-testis barrier and premature germ cell loss. Moreover, compound double heterozygous (R702C/E1841K and D1424/E1841K) males show the same abnormalities in testes as E1841K homozygous males. Conditional ablation of either NM2A or NM2B alone in Sertoli cells has no effect on fertility and testis size, however deletion of both NM2A and NM2B in Sertoli cells results in infertility. Isolation of mutant E1841K Sertoli cells reveals decreased NM2A and F-actin colocalization and thicker NM2A filaments. Furthermore, AE1841K/AE1841K and double knockout Sertoli cells demonstrate microtubule disorganization and increased tubulin acetylation, suggesting defects in the microtubule cytoskeleton. Together, these results demonstrate that NM2A and 2B paralogs play redundant roles in Sertoli cells and are essential for testes development and normal fertility.

Large Heterogeneity Among Minimal Clinically Important Differences for Hip Arthroscopy Outcomes: A Systematic Review of Reporting Trends and Quantification Methods.

PURPOSE: To perform a systematic review of reporting trends and quantification methods for the minimal clinically important difference (MCID) within the hip arthroscopy literature. METHODS: Cochrane, PubMed, and OVID/MEDLINE databases were queried for hip arthroscopy articles that reported the MCID. Studies were classified as (1) calculating new MCID values for their specific study-population or (2) referencing previously established MCID values. Data pertaining to patient demographics, study characteristics, outcome measures, method of MCID quantification, MCID value, anchor questions, measurement error, and study from which referenced MCID values were obtained were extracted. RESULTS: A total of 59 articles with 18,830 patients (19,867 hips) was included. A total of 19 unique outcome measures was reported. A total of 33 (n = 55.9%) studies (follow-up range 6-60 months) used previously established MCID values to assess their study population (MCID values established at a follow-up range 6-31 months). The remaining 26 studies (44.1%) performed new MCID calculations. The MCID values were inconsistent and varied widely (Hip Outcome Score-Activities of Daily Living: 5.0-15.4; Hip Outcome Score-Sports Subscale: 6-25; modified Harris hip score: 2.4-20.9). Among the 33 studies that used previously established MCID values, 10 different studies were cited as the reference. Among the remaining 26 studies that calculated a new MCID value, the most common method was 0.5 standard deviation method (n = 21, 80.8%). Only 3 of 26 (11.5%) studies reported a measurement of error in conjunction with their MCID values. CONCLUSIONS: Inconsistencies in MCID reporting and quantification methods led to a wide range of MCID values for commonly administered outcome measures within the hip arthroscopy literature-even for the same outcome measures. The majority of studies referenced previously established MCID values with variable ranges of follow-up and applied those values to assess their specific study population at varying follow-ups. LEVEL OF EVIDENCE: IV, systematic review.

Utilization of Implantable Cardioverter-Defibrillators in Patients With Heart Transplant (from National Inpatient Sample Database).

Heart transplant (HT) recipients represent a unique and vulnerable population in whom medium and long-term outcomes are significantly affected by the risk of arrhythmias and sudden cardiac death. The use of implantable cardioverter-defibrillators (ICDs) in this population remains debated. A retrospective analysis of the National Inpatient Sample data between 2009 and 2018 was conducted. Hospitalization data on patients who underwent HT, or who had a preexisting HT, and who received a new ICD were included (excluding the preexisting ICD). Outcomes assessed included inpatient mortality, length of stay, and inflation-adjusted costs. We explored temporal trends in ICD placement and mean length of stay, and predictors of ICD placement. Between 2009 and 2018, 22,673 hospitalizations were recorded for HT, during which patients either received a concurrent new ICD placement (n = 70 [0.31%]) or no new ICD placement (n = 22,603 [99.7%]). During the same period, 146,555 admissions were recorded in patients with a history of HT. ICD placement in patients with a preexisting HT was associated with significantly higher inflation-adjusted costs ($55,680.7 vs $17,219.2; p <0.001). Predictors of ICD placement in preexisting patients with HT included cardiac arrest during hospitalization (odds ratio [OR]:14.3 [3.5 to 58.6]), drug abuse (OR:6.0 [1.3 to 27.1]), and previous PCI (OR:6.0 [2.1 to 17.3]). In conclusion, ICD placement in patients with HT history was associated with significantly higher inflation-adjusted costs. In patients with HT history, factors predicting ICD placement included cardiac arrest at hospitalization, previous PCI, and drug abuse.

Association of Demographic Variables with the Awareness of Type 2 Diabetes Mellitus Patients (T2DM) among the Northwest Population in Saudi Arabia.

The chronic hyperglycemia in diabetes is associated with long-term damage, dysfunction, and failure of different organs. Lack of patient education and knowledge about these complications can worsen the quality of a patient's life. Hence, more efforts are needed to improve patient's education especially in rural areas. Aim. Our objective is to explore the association between demographic variables and the knowledge of self-care practices in type 2 diabetes mellitus. Methods. We used observational cross-sectional descriptive study using a validated self-administered questionnaire in both Arabic and English languages as well. A descriptive correlation design analyzed the questionnaire completed by a convenience sample meeting the inclusion criteria. Results. A total of 100 patients met the inclusion criteria for the analysis out of 3251 patients who completed the questionnaire. The study population has low moderate knowledge in diabetes, moderate knowledge in self-care practices, and good knowledge about complications of nephropathy and cardiovascular disease. No significant association between demographic variables. However, better knowledge observed in male (p = 0.028) and self-care practices with female (p = 0.020). Further, educational status is significantly influencing the knowledge of diabetic patients. Conclusion. The study emphasizing irrespective of demographic variable and the importance of patient education to achieve well glycemic control.