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Cardio-oncology is a rapidly growing field in cardiology that focuses on the management of cardiovascular toxicities associated with cancer-directed therapies. Tumor hypoxia is a central driver of pathologic tumor growth, metastasis, and chemo-resistance. In addition, conditions that mimic hypoxia (pseudo-hypoxia) play a causal role in the pathogenesis of numerous types of cancer, including renal cell carcinoma. Therefore, therapies targeted at hypoxia signaling pathways have emerged over the past several years. Though efficacious, these therapies are associated with significant cardiovascular toxicities, ranging from hypertension to cardiomyopathy. This review focuses on oxygen metabolism in tumorigenesis, the role of targeting hypoxia signaling in cancer therapy, and the relevance of oxygen metabolism in cardio-oncology. This review will specifically focus on hypoxia signaling mediated by hypoxia-inducible factors and the prolyl hydroxylase oxygen-sensing enzymes, the cardiovascular effects of specific cancer targeted therapies mediated on VEGF and HIF signaling, hypoxic signaling in cardiovascular disease, and the role of oxygen in anthracycline cardiotoxicity. The implications of these therapies on myocardial biology and cardiac function are discussed, underlining the fine balance of hypoxia signaling in cardiac homeostasis. Understanding these cardiovascular toxicities will be important to optimize treatment for cancer patients while mitigating potentially severe cardiovascular side effects.

Epidemiological studies suggest that increases in red blood cell distribution width (RDW) and decreases in albumin level can independently predict adverse cardiovascular outcomes. The prognostic value of RDW-albumin ratio (RAR), an innovate biomarker of inflammation, in heart failure (HF) patients has not been assessed. This study aimed to explore the association between RAR and mortality of HF patients.

Data on patients diagnosed with HF were extracted from MIMIC-III database version 1.4. Cox proportional hazards models were used to investigate the associations between RAR and mortality of HF patients. HF patients admitted to the Second Affiliated Hospital of Wenzhou Medical University were also enrolled to explore the relationship between RAR and existing indicators of HF.

For 90-day mortality, the HR (95% CI) for the second (4.33＜RAR＜5.44) and the third (RAR＞5.44) tertiles were 2.00 (1.58, 2.54) and 3.63 (2.91, 4.53), respectively, compared to the first tertile (RAR＜4.33). When adjusted for age, gend in heart failure patients.Glaucoma, characterized by ocular hypertension, is the second most common cause of vision loss worldwide. The potential mechanism, however, has yet to be elucidated. This study aimed to assess the proteomic changes in the trabecular meshwork (TM) in an observational animal model of Dexamethasone (DEX)-induced OHT. OHT was induced in Wistar rats by applying DEX topically to both eyes for 28 days. Intraocular pressure (IOP) was evaluated and TM protein expressions and protein identification were performed by a TMT-based method for comparing the changes in proteins between DEX-induced OHT and the control group. The results showed that average IOP was elevated significantly in rats of the DEX-induced OHT group compared to controls. Further, a total of 4,804 proteins in the control and DEX-induced OHT group were determined and 4,064 proteins were quantified via TMT proteomics. In total, 292 significantly abundant proteins (173 downregulated and 119 upregulated) were identified between the two groups. Proteins associated with vision, including Crystallin related proteins, filensin, rhodopsin, recoverin, phosducin were lowered in the DEX-induced OHT group relative to the control group. In summary, DEX induced extensive changes in the protein expression of TM tissue. Sapanisertib ic50 These proteins were found to be candidate biomarkers for personalized treatment and diagnostic research in the future for improving visual health.Microglial cells are the main immune cells of the retina. The primary culture of the retinal microglia is critically important in investigating the cells’ properties and behaviors in neurodegenerative and inflammatory retinal disease. Here, we described a modified protocol of a microglial cell culture from the neonatal rat retina. In our culture protocol, the retina was isolated from the neonatal rat eye from postnatal day 1 to day 3 and trypsinized into a single-cell suspension. The cells were seeded into a T75 flask, which was pre-coated with poly-D-lysine (PDL) and cultured with dulbecco’s modified eagle medium-F12 (DMEM/F12) that contained 10% fetal bovine serum (FBS) with different concentrations. Small bright rounded cells were observed on the top of mixed glial cells on the seventh day, and attained the maximum cell number on the 14th day. Then, the isolation was performed by a shaking method and isolated cells were identified with microglia markers ionized calcium-binding adaptor molecule 1 (IBA1), trary retinal-microglial cells, with no need of an additional purification procedure. In conclusion, we provided a high-producing protocol for the primary culture of purified rat retinal-microglial cells.Spermatogonial stem cells (SSCs) are able to undergo both self-renewal and differentiation. Unlike self-renewal, which replenishes the SSC and progenitor pool, differentiation is an irreversible process committing cells to meiosis. Although the preparations for meiotic events in differentiating spermatogonia (Di-SG) are likely to be accompanied by alterations in chromatin structure, the three-dimensional chromatin architectural differences between SSCs and Di-SG, and the higher-order chromatin dynamics during spermatogonial differentiation, have not been systematically investigated. Here, we performed in situ high-throughput chromosome conformation capture, RNA-seq, and chromatin immunoprecipitation-sequencing analyses on porcine undifferentiated spermatogonia (which consist of SSCs and progenitors) and Di-SG. We identified that Di-SG exhibited less compact chromatin structural organization, weakened compartmentalization, and diminished topologically associating domains in comparison with undifferentiated spermatogonia, suggesting that diminished higher-order chromatin architecture in meiotic cells, as shown by recent reports, might be preprogrammed in Di-SG. Our data also revealed that A/B compartments, representing open or closed chromatin regions respectively, and topologically associating domains were related to dynamic gene expression during spermatogonial differentiation. Furthermore, we unraveled the contribution of promoter-enhancer interactions to premeiotic transcriptional regulation, which has not been accomplished in previous studies due to limited cell input and resolution. Together, our study uncovered the three-dimensional chromatin structure of SSCs/progenitors and Di-SG, as well as the interplay between higher-order chromatin architecture and dynamic gene expression during spermatogonial differentiation. These findings provide novel insights into the mechanisms for SSC self-renewal and differentiation and have implications for diagnosis and treatment of male sub-/infertility.Chromatin-modifying complexes containing histone deacetylase (HDAC) activities play critical roles in the regulation of gene transcription in eukaryotes. These complexes are thought to lack intrinsic DNA-binding activity, but according to a well-established paradigm, they are recruited via protein-protein interactions by gene-specific transcription factors and posttranslational histone modifications to their sites of action on the genome. The mammalian Sin3L/Rpd3L complex, comprising more than a dozen different polypeptides, is an ancient HDAC complex found in diverse eukaryotes. The subunits of this complex harbor conserved domains and motifs of unknown structure and function. Here, we show that Sds3, a constitutively-associated subunit critical for the proper functioning of the Sin3L/Rpd3L complex, harbors a type of Tudor domain that we designate the capped Tudor domain. Unlike canonical Tudor domains that bind modified histones, the Sds3 capped Tudor domain binds to nucleic acids that can form higher-order structures such as G-quadruplexes and shares similarities with the knotted Tudor domain of the Esa1 histone acetyltransferase that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draw attention to potentially new biological roles for this HDAC complex.Chronic kidney disease affects approximately 10% of the population or 800 million people globally, with diabetes being the leading cause. The presence of chronic kidney disease with impaired kidney function or with albuminuria is associated with an increased risk of a progressive loss of renal function and increased risk of cardiovascular disease and excess mortality. Screening for chronic kidney disease is critically important because during the initial stages patients often have no symptoms and because we now have available recently approved multiple interventions that can reduce the high risks dramatically. Screening should be performed with regular measurement of albumin in the urine and creatinine or cystatin C in blood for estimation of kidney function. Regretfully recent data indicates that screening for albuminuria is conducted in only 20%-50% of people at risk depending on the setting. Clinicians need to perform regular screening and concomitant management of risk factors. Recent therapeutic options must be implemented to improve outcomes. Finally, a reduction in albuminuria after initiation of intervention constitutes a treatment target because it indicates improved prognosis.

The purpose of this research was to use direct observation of the physical examination to elucidate the role physical examination technique plays in diagnostic accuracy. Physical examination is important for quality clinical care and requires multiple interrelated skills. The relationship of physical examination technique to related skills is poorly understood. Current methods of teaching and assessing physical examination skills provide few opportunities to evaluate physical examination technique and accuracy.

The authors developed a clinical examination assessment using volunteer patients and direct observation. Trained faculty preceptors rated resident performance in 7 domains 1) physical examination technique, 2) identification of physical signs, 3) clinical communication, 4) differential diagnosis, 5) clinical judgment, 6) managing patient concerns, and 7) maintaining patient welfare. The Pearson correlation coefficient was used to determine relationships between performance in each of these domains.s.

Our findings emphasize the necessity of multi-dimensional physical examination assessment. Observed deterioration of physical examination skill during internship may reflect contemporary practice patterns, which deprioritize the physical examination. Future research on physical examination education should focus on the interface between physical examination technique and related clinical skills.