Notes

Present along with Story Alkylators inside Several Myeloma.
Diabetic retinopathy (DR) is a vision-loss complication caused by diabetes with high prevalence. During DR, the retinal microvascular injury and neurodegeneration derived from chronic hyperglycemia have attracted global attention to retinal Müller cells (RMCs), the major macroglia in the retina contributes to neuroprotection. Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA) dephosphorylates the transcriptional coactivator Yes-associated protein (YAP) to promote the transcription of glutamine synthetase (GS). GS catalyzes the transformation of neurotoxic glutamate (Glu) into nontoxic glutamine (Gln) to activate the mammalian target of rapamycin complex 1 (mTORC1), which promotes the activation of RMCs. In this study, in vitro MIO-M1 cell and in vivo mouse high-fat diet and streptozotocin (STZ)-induced diabetic model to explore the role of the PPP1CA/YAP/GS/Gln/mTORC1 pathway on the activation of MRCs during DR. Results showed that PPP1CA promoted the dephosphorylation and nuclear translocation of YAP in high glucose (HG)-exposed MIO-M1 cells. YAP transcribed GS in HG-exposed MIO-M1 cells in a TEAD1-dependent and PPP1CA-dependent way. GS promoted the biosynthesis of Gln in HG-exposed MIO-M1 cells. Gln activated mTORC1 instead of mTORC2 in HG-exposed MIO-M1 cells. The proliferation and activation of HG-exposed MIO-M1 cells were PPP1CA/YAP/GS/Gln/mTORC1-dependent. Finally, RMC proliferation and activation during DR were inhibited by the PPP1CA/YAP/GS/Gln/mTORC1 blockade. The findings supplied a potential idea to protect RMCs and alleviate the development of DR.
Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation.

This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes.

This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits between 6 and 14 weeks' gestation and between 22 and 30 weeks' gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. Ters, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10-2.57).

Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.
Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.
Early diagnosis is fundamental to reducing breast cancer (BC) mortality, and understanding potential barriers from initial screening to confirmed diagnosis is essential. The aim of this study was to evaluate patient characteristics that contribute to delay in diagnosis of screen-detected cancers and the contribution of delay to tumor characteristics and BC mortality.

Three hundred sixty-two White and 368 Black women were identified who were screened and received subsequent BC diagnoses within Emory Healthcare, a part of Emory University health care system (2010-2014). Cyclopamine molecular weight Multivariable-adjusted logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associating patient characteristics with delay to diagnostic evaluation (≥30 versus <30 days), delay to biopsy (≥15 versus <15 days), and total delay (≥45 versus <45 days). Additionally, the ORs and 95% CIs associating delay with tumor characteristics and BC mortality were computed.

Black women and women diagnosed at later stages, with larger tumor sizes, and with triple-negative tumors were more likely to experience ≥45 days to diagnosis. In multivariable-adjusted models, Black women had at least a two-fold increase in the odds of delay to diagnostic evaluation (OR, 1.98; 95% CI, 1.45-2.71), biopsy delays (OR, 2.41; 95% CI, 1.67-3.41), and total delays ≥45 days (OR, 2.22; 95% CI, 1.63-3.02) compared with White women. A 1.6-fold increased odds of BC mortality was observed among women who experienced total delays ≥45 days compared with women without delays in diagnosis (OR, 1.57, 95% CI, 0.96-2.58).

The study demonstrated racial disparities in delays in the diagnostic process for screen-detected malignancies. Total delay in diagnosis was associated with an increase in BC mortality.
The study demonstrated racial disparities in delays in the diagnostic process for screen-detected malignancies. Total delay in diagnosis was associated with an increase in BC mortality.
Females with coronary artery disease (CAD) have inferior outcomes compared with males, including higher mortality following coronary artery bypass grafting (CABG). We aimed to evaluate the association of female sex with the use of guideline-concordant CABG revascularization techniques.

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was queried for adult patients who underwent first-time isolated CABG in the US from 2011-2019. The association between female sex and the odds of (1) receiving a left internal mammary artery (LIMA) graft for revascularization of the left anterior descending (LAD) artery, (2) undergoing complete revascularization, and (3) undergoing multi-arterial grafting was assessed, adjusting for procedural anatomy.

Among 1,212,487 patients meeting inclusion criteria, 75% were male (n=911,178) and 25% were female (n=301,309). Female sex was associated with lower unadjusted rates of revascularization with an IMA (93.9% vs 95.9%, P<.001), bilateral IMA (2.9% vs 5.6%, P<.
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