We designed a prospective randomized clinical study to compare unilateral and bilateral antegrade cerebral perfusion (ACP) under moderate hypethermia in open distal aortic hemiarch replacement in ascending aortic aneurysm.

Forty-two patients were prospectively randomized into two groups; unilateral ACP to Group 1 and bilateral ACP to Group 2. Inclusion criteria were pathological aortic aneurysm in the ascending aorta and/or aortic arch, elective operation, normal preoperative carotid Doppler ultrasonography, and nonexistence of preoperative neurological event. Patients were evaluated with preoperative and postoperative biochemical blood analysis, magnetic resonance imaging (MRI), and neurological disorders. The primary endpoints were permanent neurological disorder and death.

There were 21 patients in each group. Mean age was 56.57 ± 10.06 years in Group 1 and 50.95 ± 15.64 years in Group 2 (p = .170). No significant difference was found according to demographic data. ACP times were significantly higher in bilateral ACP (Group 1 12.62 ± 5.04 min, Group 2 18.23 ± 9.04 min, p = .018) whereas cross-clamp time and cardiopulmonary bypass times were not (p = .693 and p = .584 sequentially). selleck products Transient neurological disorder was found in seven patients in Group 1 and in 4 patients in Group 2 (p = .484). Postoperative MRI revealed new milimetric ischemic zones in three patients in Group 1 but none in Group 2. No permanent neurological disorder or mortality was seen.

The present randomized clinical prospective study could not prove the superiority of one of the technique in cerebral protection probably because, our overall ACP time was too short.

The present randomized clinical prospective study could not prove the superiority of one of the technique in cerebral protection probably because, our overall ACP time was too short.The microencapsulation of spermatozoa offers potential benefits for maintaining sperm survival in vitro. The technique has also resulted in the production of offspring in several domestic animal species, but as yet, it has not been successfully applied in human reproductive medicine. This study examined the effect of alginic acid microencapsulation on human sperm membrane integrity (viability) and sperm DNA fragmentation (SDF) following storage for 24 hr at 37°C. The cumulative sperm viability (Log-rank, Mantel-Cox; Chi-square = 114.95, p = .000) and cumulative sperm DNA fragmentation (Log-rank, Mantel-Cox; Chi-square = 187.86, p = .000) of encapsulated spermatozoa were substantially improved when compared to control spermatozoa. Significant differences in the dynamic behaviour of different individuals were only apparent for sperm viability in microencapsulated samples (p = .021) while no significant differences were observed in control spermatozoa (p = .245); the equivalent comparison for SDF showed no differences (control p = .320; microencapsulated p = .432). We present potential scenarios for the use of microencapsulated human spermatozoa in reproductive medicine.Readmission or death soon after heart failure (HF) admission is a significant problem. Traditional analyses for predicting such events often fail to consider the gamut of characteristics that may contribute- tending to focus on 30-day outcomes even though the window of increased vulnerability may last up to 90 days. Risk assessments incorporating machine learning (ML) methods may be better suited than traditional statistical analyses alone to sort through multitude of data in the electronic health record (EHR) and identify patients at higher risk. HYPOTHESIS ML-based decision analysis may better identify patients at increased risk for 90-day acute HF readmission or death after incident HF admission. METHODS AND RESULTS Among 3189 patients who underwent index HF hospitalization, 15.2% experienced primary or acute HF readmission and 11.5% died within 90 days. For risk assessment models, 98 variables were considered across nine data categories. ML techniques were used to help select variables for a final logistic regression (LR) model. The final model’s AUC was 0.760 (95% CI 0.752 to 0.767), with sensitivity of 83%. This proved superior to an LR model alone [AUC 0.744 (95% CI 0.732 to 0.755)]. Eighteen variables were identified as risk factors including dilated inferior vena cava, elevated blood pressure, elevated BUN, reduced albumin, abnormal sodium or bicarbonate, and NT pro-BNP elevation. A risk prediction ML-based model developed from comprehensive characteristics within the EHR can efficiently identify patients at elevated risk of 90-day acute HF readmission or death for whom closer follow-up or further interventions may be considered.Modern drug design aims to discover novel lead compounds with attractable chemical profiles to enable further exploration of the intersection of chemical space and biological space. Identification of small molecules with good ligand efficiency, high activity, and selectivity is crucial toward developing effective and safe drugs. However, the intersection is one of the most challenging tasks in the pharmaceutical industry, as chemical space is almost infinity and continuous, whereas the biological space is very limited and discrete. This bottleneck potentially limits the discovery of molecules with desirable properties for lead optimization. Herein, we present a new direction leveraging posttranslational modification (PTM) protein isoforms target space to inspire drug design termed as “Post-translational Modification Inspired Drug Design (PTMI-DD).” PTMI-DD aims to extend the intersections of chemical space and biological space. We further rationalized and highlighted the importance of PTM protein isoforms and their roles in various diseases and biological functions. We then laid out a few directions to elaborate the PTMI-DD in drug design including discovering covalent binding inhibitors mimicking PTMs, targeting PTM protein isoforms with distinctive binding sites from that of wild-type counterpart, targeting protein-protein interactions involving PTMs, and hijacking protein degeneration by ubiquitination for PTM protein isoforms. These directions will lead to a significant expansion of the biological space and/or increase the tractability of compounds, primarily due to precisely targeting PTM protein isoforms or complexes which are highly relevant to biological functions. Importantly, this new avenue will further enrich the personalized treatment opportunity through precision medicine targeting PTM isoforms.