Mutations to the sarcomere-localized co-chaperone protein Bcl2-associated athanogene 3 (BAG3) are associated with dilated cardiomyopathy (DCM) and display greater penetrance in male patients. Decreased protein expression of BAG3 is also associated with non-genetic heart failure, however, the factors regulating cardiac BAG3 expression are unknown. Using left ventricular (LV) tissue from non-failing and DCM human samples we found that whole LV BAG3 expression was not significantly impacted by DCM or sex, however, myofilament localized BAG3 was significantly decreased in males with DCM. DCM females displayed no changes in BAG3 compared with non-failing. This sex-difference appears to be estrogen independent as estrogen treatment in ovariectomized female rats had no impact on BAG3 expression. BAG3 gene expression is primarily regulated by heat shock transcription factor-1 (HSF-1). Thus, we next assessed the relationship between HSF-1 and BAG3 localization/expression. Whole LV HSF-1 expression and nuclear localized/active HSF-1 each displayed a striking positive correlation with whole LV BAG3 expression. We further show that HSF-1 localizes to the sarcomere Z-disc in cardiomyocytes and that this myofilament-associated HSF-1 pool decreases in heart failure. The decrease of HSF-1 was more pronounced in male patients and tightly correlated with myofilament BAG3 expression. Together our findings indicate that cardiac BAG3 expression and myofilament localization are differentially impacted by sex and disease and are linked to HSF-1. Our findings implicate decreased BAG3 expression in DCM pathogenesis for male, but not female patients, and suggest heart failure therapies targeting HSF-1 may be efficacious.

Ultrasound-guided vacuum-assisted breast biopsy had a lower mean cost per cancer diagnosis than 14-gauge spring-loaded core-needle biopsy. This advantage was only seen in tethered vacuum-assisted instruments. Within device families, larger instruments tended to outperform smaller instruments.

Background The third epidemic of retinopathy of prematurity (ROP) has majorly involved middle income countries in which tailored screening and local guidelines require development. The data regarding ROP prevalence and cutoff numbers for screening in Egypt are lacking. Methods Retrospective analysis of an independent screening effort spanning 2 years (February 2019 to February 2021) and involving 32 neonatal care units within Sharkia governorate, Egypt. Infants of gestational age (GA) ≤ 34 weeks and/or birth weight (BW) ≤ 2000 g were included, as well as those with unstable clinical course. Two eyecare centers located in Sharkia and Cairo governorates served as referral centers for any required interventions. Results Of the 276 screened infants, 133 (48.2%) had some form of ROP that was bilateral in 127 (95.5%) of them. Aggressive posterior ROP (AP-ROP) was detected in both eyes of 24 infants (8.7%). The median (IQR) GA of infants with ROP was 32 (30–34) weeks, and the median (IQR) BW was 1600 (1350–2000) g. Sixty-three infants (47.4%) required treatment. Of the total 84 eyes that primarily were treated, 73 (86.9%) received intravitreal ranibizumab, 8 (9.5%) underwent laser ablation therapy, and 3 eyes (3.6%) underwent surgery. Recurrence rate was 16.7% (14 eyes). Final outcome was favorable in 83 eyes (98.8%). Applying the American Academy criteria would have led to the missing of 36.8% of infants with ROP and 28.6% of those requiring treatment in our sample. Conclusion The incidence of both ROP and AP-ROP in the Egyptian rural setting appears to be in the high end of global reported rates. Prevention measures should urgently be planned and implemented.

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