Notes

Phase shifts inside 1-bromoadamantane when compared with 1-chloroadamantane: similarities and different capabilities.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Many studies have shown a significant increase in the marker signal of the receptor for advanced glycation end-products (RAGE) with the malignant progression of tumor growth, metastasis and recurrence of breast cancer, including TNBC of primary tumors and lymph node metastases. Azeliragon is a RAGE inhibitor and it has been shown to actively inhibit the TNBC cell line, SUM149 (IC50 = 5.292 ± 0.310 μM). CI-1040 In order to develop a new anti-TNBC agent, we designed, synthesized and screened 26 Azeliragon triazole analogues to determine their anti-TNBC activities in vitro. The most active compound was KC-10 with an IC50 value of 0.220 ± 0.034 μM.Here we report the first small-molecule inhibitors of human sulfidequinone oxidoreductase (SQOR) that decrease the rate of breakdown of hydrogen sulfide (H2S), a potent cardioprotective signaling molecule. SQOR is a mitochondrial membrane-bound protein that catalyzes a two-electron oxidation of H2S to sulfane sulfur (S0), using glutathione (or sulfite) and coenzyme Q (CoQ) as S0 and electron acceptor, respectively. Inhibition of SQOR may constitute a new approach for the treatment of heart failure with reduced ejection fraction. Starting from top hits identified in a high-throughput screen, we conducted SAR development guided by docking of lead candidates into our crystal structure of SQOR. We identified potent SQOR inhibitors such as 19 which has an IC50 of 29 nM for SQOR inhibition and favorable pharmacokinetic and ADME properties required for in vivo efficacy testing.
The objective of this 3-arm randomized controlled trial was to evaluate efficacy of computerized cognitive training (CCT) to improve primary outcomes of delayed recall memory and serum brain-derived neurotrophic factor (BDNF) levels and secondary outcomes of working memory, instrumental activities of daily living (IADL), and health-related quality of life (HRQL) among patients with heart failure (HF).

Patients (N = 256) were randomly assigned to 8 weeks of CCT using BrainHQ, computerized crossword puzzles active control intervention, and usual care. All patients received weekly nurse enhancement interventions. Data were collected at enrollment and baseline visits and at 10 weeks and 4 and 8 months. In mixed effects models, there were no statistically significant group or group by time differences in outcomes. There were statistically significant differences over time in all outcomes in all groups. Patients improved over time on measures of delayed recall memory, working memory, IADL, and HRQL and had decrxplain improved outcomes. Future studies are needed.
In 256 patients with heart failure, 8 weeks of computerized cognitive training, computerized crossword puzzles, or usual care were studied for effects on (1st) recall memory and serum brain-derived neurotrophic factor (BDNF) and (2nd) working memory, instrumental activities of daily living (IADL), and health-related quality of life (HRQL). Measurements were at baseline, 10 weeks, 4- and 8-months. Nurse enhancement interventions (e.g., support, assessment) were provided. Recall memory, working memory, IADL, and HRQL improved over time. There were no statistically significant differences among treatment groups over time. BDNF unexpectedly decreased. Nurse enhancement interventions may explain improved outcomes. Future studies are needed.
In advanced heart failure (HF), Levosimendan increases peak oxygen uptake (peakVO
). We investigated whether peakVO
increase is linked to cardiovascular, respiratory or muscular performance changes.

Twenty patients hospitalized for advanced HF underwent, before and shortly after Levosimendan infusion, two different cardiopulmonary exercise tests (CPET) a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar-capillary gas diffusion measurements at rest and at peak exercise, and b) a step incremental workload CPET with continuous near-infrared spectroscopy analysis and cardiac output (CO) assessment by bioelectrical impedance analysis. Levosimendan significantly reduced natriuretic peptides, improved peakVO
(11.3 [IQR 10.1-12.8] to 12.6 [10.2-14.4] ml/Kg/min, p<0.01) and reduced VE/VCO
slope (47.7±10.7 to 43.4±8.1, p<0.01). In parallel, spirometry showed only a minor increase in forced expiratory volume, while peak exercise dead spaceery and extraction.
Heart failure (HF) is a leading contributor of cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. HF risk prediction tools that utilize readily available clinical parameters to risk stratify individuals with CKD are needed.

We included Black and White participants aged 30 to 79 years with CKD stages 2-4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study and without self-reported cardiovascular disease. We assessed model performance of the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) to predict incident HF hospitalizations and refit the PCP-HF in the CKD population using CRIC data-derived coefficients and survival from CRIC Study participants in the CKD population (PCP-HF
). We investigated the improvement in HF prediction with inclusion of estimated glomerular filtration rate [eGFR] and urine albumin to creatinine ratio [UACR] into the PCP-HF
equations by change in C-statistic, net reclassification improvement (NRI) and integrated discriminaailure in patients with chronic kidney disease. This study investigated whether a previously developed tool that used routinely available clinical data could predict heart failure events in individuals with chronic kidney disease. Results demonstrated that this tool performed poorly in individuals with chronic kidney disease. However, when albuminuria, a measurement of protein in the urine that represents kidney dysfunction, was added to the risk prediction equation, the risk prediction tool was better able to predict heart failure events in this population. Implementation of this tool may be able to identify individuals with chronic kidney disease at high risk for heart failure hospitalization and improve clinical outcomes.MicroRNAs (miRNAs) contribute to gonadal development in animals. However, there is little information about miRNA regulation function involved in gonadal development in fish. Our group previously identified sex-related miRNAs of Chinese tongue sole (Cynoglossus semilaevis) during sex determination and differentiation by small RNA sequencing. In the present study, we characterized ssa-mir-196a-4 and its expression in testis and verified its interaction with lgr8. miRNA ssa-mir-196a-4 precursor was predicted to have a typical hairpin structure and highly conserved among various fish species. Fluorescence in situ hybridization (FISH) of ssa-mir-196a-4 in the testis of Chinese tongue sole showed that it is mainly expressed in the cytoplasm of Sertoli cells. We determined that ssa-mir-196a-4 interacted with lgr8 by bioinformatics analysis using miRanda software. According to the dual-luciferase gene reporter assay, lgr8 is a direct target of ssa-mir-196a-4. Overexpression of ssa-mir-196a-4 in the cells of the testis cell line of Chinese tongue sole decreased the expression levels of lgr8 messenger RNA (mRNA) and protein by targeting its coding sequence (CDS) region. These results suggest that ssa-mir-196a-4 acts as a post-transcriptional regulator of lgr8 and plays an important role in developing testes of Chinese tongue sole.
It has been recognized that psychological factors influence the return to sports after anterior cruciate ligament reconstruction (ACLR). The ACL-return to sports after injury (RSI) scale was developed based on subcategories of emotions, confidence in physical performance and risk appraisal. However, it has not been clarified describing which is the most influential psychological factor of the ACL-RSI scale.

Risk appraisal is the most influent for return to sports in the subcategories of the ACL-RSI scale.

A total of 85 competitive patients who had undergone ACLR were evaluated at 6, 12 and 24 months after surgery. They were classified the return to sports (RTS) group and non-return to sports (NRTS) group. Evaluations were several clinical and functional scores including Cincinnati knee rating system, Knee Osteoarthritis Outcome Score (KOOS), Lysholm score, limitation in activities of daily living (ADL) and sports which estimated by Visual Analog Scale (VAS) score, Isokinetic Muscle Strength (quadriceps e ACL-RSI scale, risk appraisal took the longest time to improve and strongly affected the return to sports. The KOOS-QOL and VAS score for sports were most strongly correlated with the ACL-RSI risk appraisal. It seems that it is important to reduce the psychological risk as soon as possible after ACL injury in ACLR patients.

II.
II.
Cemented femoral implants incur a serious risk of potentially fatal accidents in case of bone cement implantation syndrome (BCIS). As French data are sparse regarding this issue, Orthorisq, the official accreditation body for orthopedic surgeons, conducted an interprofessional survey 1) to assess the frequency of BCIS, 2) to analyze risk factors related to the patient and to professional practices, and 3) to set out guidelines to reduce frequency and/or severity.

French data on BCIS are underestimated and need updating to ease communication between colleagues.

In 2019, Orthorisq ran a survey of its members' practices and a "mirror" survey of anesthesiologists. In the decade from 2009 to 2018, the 775 respondent orthopedic surgeons, both occasional and systematic "cementers", reported their experience with a declared annual rate of 80,112 arthroplasties, including 63,799 (79.6%) in scheduled surgery. Some of the survey questions concerned cementing technique. With the help of the French College of Anesthcidents was 0.19% and mortality was 0.05%, for a cumulative probability of 0.24% per year. Extrapolated to the data of the ATIH Technical Agency of Hospitalization Information and subtracting arthroplasties by "never-cementers", these figures indicate 311 accidents with 65 deaths in femoral BCIS for 2018.

In scheduled surgery, BCIS was exceptional, but the rate in traumatology was much higher. Certain techniques intended to improve femoral cementing quality actually increased the risk of BCIS; in high-risk patients, especially in traumatology, non-cemented femoral implants or else a 1st-generation cementing technique should therefore be preferred. Prevention of BCIS and/or reduction of severity requires identification of at-risk patients and good communication between surgeons and anesthesiologists, especially at the various steps of the check-list.

IV; case series.
IV; case series.The ability to use symbols is a defining feature of human intelligence. However, neuroscience has yet to explain the fundamental neural circuit mechanisms for flexibly representing and manipulating abstract concepts. This article will review the research on neural models for symbolic processing. The review first focuses on the question of how symbols could possibly be represented in neural circuits. The review then addresses how neural symbolic representations could be flexibly combined to meet a wide range of reasoning demands. Finally, the review assesses the research on program synthesis and proposes that the most flexible neural representation of symbolic processing would involve the capacity to rapidly synthesize neural operations analogous to lambda calculus to solve complex cognitive tasks.
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