Microcirculatory dysfunction in hypertrophic cardiomyopathy with chest pain assessed by angiography-derived microcirculatory resistance.

Chest pain, a common initial symptom in hypertrophic cardiomyopathy (HCM) patients, is closely linked to myocardial ischemia, despite the absence of significant coronary artery stenosis. This study explored microvascular dysfunction in HCM patients by employing angiography-derived microcirculatory resistance (AMR) as a novel tool for comprehensive assessment. This retrospective analysis included HCM patients with chest pain as the primary symptom and control patients without cardiac hypertrophy during the same period. The AMR was computed through angiography, providing a wire-free and adenosine-free index for evaluating microcirculatory function. Propensity score matching ensured balanced demographics between groups. This study also investigated the correlation between the AMR and clinical outcomes by utilizing echocardiography and follow-up data. After matching, 76 HCM patients and 152 controls were analyzed. While there was no significant difference in the incidence of epicardial coronary stenosis, the AMR of three epicardial coronary arteries was markedly greater in HCM patients. The criterion of an AMR ≥ 250 mmHg*s/m was that 65.7% of HCM patients experienced coronary microvascular dysfunction (CMD). Independent risk factors for CMD included increased left ventricular (LV) wall thickness (OR = 1.209, 95% CI 1.013-1.443, p = 0.036). Furthermore, an AMR_LAD ≥ 250 mmHg*s/m had an increased cumulative risk of the endpoint (log-rank p = 0.023) and was an independent risk factor for the endpoint (HR = 11.64, 95% CI 1.13-120.03, p = 0.039), providing valuable prognostic insights.

Up-regulation of non-photochemical quenching improves water use efficiency and reduces whole-plant water consumption under drought in Nicotiana tabacum.

Water supply limitations will likely impose increasing restrictions on future crop production, underlining a need for crops that use less water per mass of yield. Water use efficiency (WUE) therefore becomes a key consideration in developing resilient and productive crops. In this study, we hypothesized that it is possible to improve WUE under drought conditions via modulation of chloroplast signals for stomatal opening by up-regulation of non-photochemical quenching (NPQ). Nicotiana tabacum plants with strong overexpression of the PsbS gene encoding PHOTOSYSTEM II SUBUNIT S, a key protein in NPQ, were grown under differing levels of drought. The PsbS-overexpressing lines lost 11% less water per unit CO2 fixed under drought and this did not have a significant effect on plant size. Depending on growth conditions, the PsbS-overexpressing lines consumed from 4-30% less water at the whole-plant level than the corresponding wild type. Leaf water and chlorophyll contents showed a positive relation with the level of NPQ. This study therefore provides proof of concept that up-regulation of NPQ can increase WUE, and as such is an important step towards future engineering of crops with improved performance under drought.

Complexities of Coexisting Cardiac Amyloidosis and Coronary Artery Disease: A Contemporary Review of Diagnostic and Treatment Approaches.

Cardiac amyloidosis (CA) represents an emerging challenge in cardiovascular medicine, with notable clinical overlaps and diagnostic complexities when coexisting with coronary artery disease (CAD). This integrative review navigates the intricate terrain of CA and CAD, elucidating epidemiology, clinical presentations, and diagnostic considerations. Examining both immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis, we underscore their shared demographic associations, diagnostic intricacies, and potential diagnostic confounders with CAD. Notably, we emphasize the impact of CA on epicardial coronary arteries and the consequential implications for coronary microcirculation. Further exploration reveals the connection between CA and acute myocardial infarction, emphasizing early recognition as pivotal. In terms of differential diagnosis, we underscore the significance of clinical symptoms, electrocardiography, echocardiography, cardiac magnetic resonance, and bone scintigraphy. Additionally, we scrutinize the intricate realm of treatment, encompassing medication selection, antithrombotic strategies, and revascularization modalities. Our review addresses the distinctive challenges posed by CA patients' limited tolerance for conventional therapies. This comprehensive synthesis serves as an invaluable resource for clinicians confronting the intricate intersection of CA and CAD. By offering insights into diagnostic refinement and innovative therapeutic avenues, we aim to enhance patient outcomes and quality of life within this complex clinical landscape.

Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.

A High-Reliability 12T SRAM Radiation-Hardened Cell for Aerospace Applications.

The static random-access memory (SRAM) cells used in the high radiation environment of aerospace have become highly vulnerable to single-event effects (SEE). Therefore, a 12T SRAM-hardened circuit (RHB-12T cell) for the soft error recovery is proposed using the radiation hardening design (RHBD) concept. To verify the performance of the RHB-12T, the proposed cell is simulated by the 28 nm CMOS process and compared with other hardened cells (Quatro-10T, WE-Quatro-12T, RHM-12T, RHD-12T, and RSP-14T). The simulation results show that the RHB-12T cell can recover not only from single-event upset caused by their sensitive nodes but also from single-event multi-node upset caused by their storage node pairs. The proposed cell exhibits 1.14×/1.23×/1.06× shorter read delay than Quatro-10T/WE-Quatro-12T/RSP-14T and 1.31×/1.11×/1.18×/1.37× shorter write delay than WE-Quatro-12T/RHM-12T/RHD-12T/RSP-14T. It also shows 1.35×/1.11×/1.04× higher read stability than Quatro-10T/RHM-12T/RHD-12T and 1.12×/1.04×/1.09× higher write ability than RHM-12T/RHD-12T/RSP-14T. All these improvements are achieved at the cost of a slightly larger area and power consumption.

Fascia defect closure versus non-closure in minimal invasive direct inguinal hernia mesh repair: a systematic review and meta-analysis of real-world evidence.

PURPOSE: Laparoscopic and robotic inguinal hernia mesh repair are both common surgical procedures worldwide. Postoperative hernia recurrence and seroma formation are important concerns. In ventral hernia, primary defect closure in laparoscopic surgery reduces the recurrence rate. However, there is no synthetic evidence of direct inguinal hernia defect closure versus non-closure in minimal invasive surgery. Therefore, this study investigated the efficacy of defect closure in patients undergoing minimal invasive direct inguinal hernia mesh repair. METHODS: Eligible studies were identified through a search of PubMed, Embase, Cochrane Library, and CINAHL from their inception until March 2022. Studies examining defect closure in laparoscopic direct inguinal hernia repair were included, and a meta-analysis was performed using the random-effect model. Sensitivity analyses were performed by removing one study at a time. The primary outcomes were hernia recurrence and seroma formation. Acute and chronic postoperative pain, operation time, and length of hospital stay were the secondary outcomes. RESULTS: Five nonrandomized studies and one randomized controlled trial were included. Pooled analysis revealed defect closure might reduce the hernia recurrence rate (risk difference, - 0.02; 95% confidence interval [CI] - 0.04 to - 0.00; p = 0.02). The result of seroma formation (odds ratio, 0.49; 95% CI 0.17-1.46; p = 0.20) showed no significant difference. Moreover, no significant differences were observed in acute postoperative pain, chronic pain, length of hospital stay, and operation time. CONCLUSIONS: Our study indicated defect closure seems to be an option to reduce the direct inguinal hernia recurrence rate. No significant benefits were shown in seroma formation and other secondary outcomes. Our study was mostly based on nonrandomized studies and underestimated the effect of defect closure; thus, further high-quality studies are required to draw definitive conclusions.

Analgesic Effects of Regional Analgesic Techniques in Pediatric Inguinal Surgeries: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Various regional analgesic techniques have been used in pediatric inguinal surgery to facilitate postoperative recovery. However, each technique's relative performance was undetermined owing to the lack of quantitative analysis. METHODS: We systematically searched MEDLINE, Cochrane Library, EMBASE, and Web of Science for randomized controlled trials that compared regional analgesia in pediatric inguinal surgeries. After critical study screening and selection, a random-effects network meta-analysis was performed. The primary outcome was the time to the first rescue analgesic after surgery, and the secondary outcomes were the number of patients requiring rescue analgesics after surgery, postoperative pain scores, incidence of postoperative nausea and vomiting, and other adverse events. RESULTS: This network meta-analysis included 69 randomized controlled trials (4636 patients) that compared 10 regional analgesic techniques. Our study revealed that the quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic after pediatric inguinal surgeries, by 7.7 hours (95% confidence interval [CI], 5.0-10.3) and 6.0 hours (95% CI, 3.9-8.2) when compared with the control group, respectively. In the subgroup involving only inguinal hernia repair, the quadratus lumborum block significantly prolonged the time to the first rescue analgesic than all other regional analgesics. In contrast, in the subgroup involving orchidopexies, only the caudal block significantly prolonged the time to the first rescue analgesic when compared with the control group (4.1 hours; 95% CI, 0.7-7.5). Wound infiltration and landmark-based ilioinguinal-iliohypogastric block had relatively poor analgesic effects than other regional analgesics. No serious adverse effects related to the regional analgesic techniques were reported in any of the included studies. CONCLUSIONS: The quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic and the least rescue analgesic requirement for pediatric inguinal surgeries. Specifically, the quadratus lumborum block had the longest analgesic duration in inguinal hernia repair, and the caudal block was found to be the only regional analgesia that extended the time to the first rescue analgesic in pediatric orchidopexy. Most included randomized controlled trials had some concern or a high risk of bias, and future studies should focus on providing high-quality evidence to further clarify the analgesic effects of regional analgesia for pediatric inguinal surgeries.

Field-Based Scoring of Soybean Iron Deficiency Chlorosis Using RGB Imaging and Statistical Learning.

Iron deficiency chlorosis (IDC) is an abiotic stress in soybean that can cause significant biomass and yield reduction. IDC is characterized by stunted growth and yellowing and interveinal chlorosis of early trifoliate leaves. Scoring IDC severity in the field is conventionally done by visual assessment. The goal of this study was to investigate the usefulness of Red Green Blue (RGB) images of soybean plots captured under the field condition for IDC scoring. A total of 64 soybean lines with four replicates were planted in 6 fields over 2 years. Visual scoring (referred to as Field Score, or FS) was conducted at V3-V4 growth stage; and concurrently RGB images of the field plots were recorded with a high-throughput field phenotyping platform. A second set of IDC scores was done on the plot images (displayed on a computer screen) consistently by one person in the office (referred to as Office Score, or OS). Plot images were then processed to remove weeds and extract six color features, which were used to train computer-based IDC scoring models (referred to as Computer Score, or CS) using linear discriminant analysis (LDA) and support vector machine (SVM). The results showed that, in the fields where severe IDC symptoms were present, FS and OS were strongly positively correlated with each other, and both of them were strongly negatively correlated with yield. CS could satisfactorily predict IDC scores when evaluated using FS and OS as the reference (overall classification accuracy > 81%). SVM models appeared to outperform LDA models; and the SVM model trained to predict IDC OS gave the highest prediction accuracy. It was anticipated that coupling RGB imaging from the high-throughput field phenotyping platform with real-time image processing and IDC CS models would lead to a more rapid, cost-effective, and objective scoring pipeline for soybean IDC field screening and breeding.