Efficacy and safety of dapagliflozin add-on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled study.

AIM: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. PATIENTS AND METHODS: In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. RESULTS: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. CONCLUSION: Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.

Embedded-deep-learning-based sample-to-answer device for on-site malaria diagnosis.

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

Serial Vascular Responses of Balloon-Expandable Stent With Biodegradable Film-Type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study).

BACKGROUND AND OBJECTIVES: Arterial dissection during endovascular therapy rarely occurs but can be lethal. A fabric-based covered graft stents yield poor clinical outcomes. A novel balloon-expandable stent with biodegradable film graft for overcoming these issues was evaluated in a rabbit iliac artery model. METHOD: Eighteen rabbits with iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0×24 mm). Subsequently, survived twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year. RESULTS: There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2 weeks, 26.1 at 1 month, 29.7 at 3 months, 49.2 at 9 months, and 51.0 at 1 year), along with mild peri-strut inflammatory response (Grade: 1-2 at mid-term and 0-1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2 weeks, 12.3 at 1 month, 14.2 at 3 months, 25.1 at 9 months, and 26.6 at 1 year). CONCLUSIONS: The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model.

[What is the Impact of Early Rehabilitation and Rehabilitation Management on Outcome after Polytrauma?] / Welchen Einfluss haben Frührehabilitation und Reha-Management auf das Outcome nach Polytrauma?

Patients with polytrauma and other severe musculoskeletal injuries often suffer from permanently impaired functionality and quality of life. This results in long-term damage with high costs for the social system. A narrative review will show the impact of targeted coordination in the rehabilitation process from early rehabilitation to long-term case management on patients with severe musculoskeletal injuries. A systematic database search of MEDLINE and the Cochrane Library identified studies of multiple injuries that compared the outcome of early rehabilitation and rehabilitation management with other types of care. Studies of predominantly neurologic injury types, soldiers, and mild injury types with an ISS less than 9 or AIS less than 3 were excluded. Four studies were included and analyzed. They looked at functionality, quality of life, psychological impairment, and costs. While treatment and total costs were higher for early rehabilitation and rehabilitation management, no better results for improved function, psychological condition and quality of life could be demonstrated in the group comparison. An effect estimate is possible due to small group differences and the small number of individual studies included. There are insufficient studies to draw conclusions about the effectiveness of the early interventions. Future studies are needed that take into greater account structures of standard care and national differences in social security systems, as well as the chosen rehabilitation management interventions.

Cancer Incidence Among Residents Near Coal-Fired Power Plants Based on the Korean National Health Insurance System Data.

BACKGROUND: Cancer is a leading cause of death worldwide, posing a significant threat to human health and life expectancy. Numerous existing studies explored the correlation between coal-fired power plants and cancer development. Currently, Chungcheongnam-do Province hosts 29 coal-fired power plants, constituting half of the total 58 plants across South Korea. METHODS: This study assessed the cancer incidence by proximity to coal-fired power plants in Chungcheongnam-do Province, Korea. In this study, the exposed group comprised individuals residing within a 2-km radius of the coal-fired power plants, whereas the control group comprised individuals who had no prior residency within the 2-km radius of such plants or elsewhere in the province. Standardized incidence ratios were calculated using the cancer incidence cases retrieved from the National Health Insurance System data from 2007 to 2017. RESULTS: The study found that exposed men had a 1.11 (95% confidence interval [CI], 1.09-1.21) times higher risk of developing all cancer types and a 1.15 (95% CI, 1.09-1.22) times higher risk of developing cancers excluding thyroid cancer compared with control men. Exposed women had a 1.05 (95% CI, 1.00-1.14) times higher risk of developing all cancer types and a 1.06 (95% CI, 0.98-1.13) times higher risk of developing cancers excluding thyroid cancer than did control women. The colorectal, liver, prostate, and bladder cancer incidence rates were significantly higher in exposed men than that in all control groups. The incidence of esophageal, stomach, liver, and lung cancers were significantly higher in exposed women compared with all control groups. CONCLUSION: The residents near coal-fired power plants had a higher risk of developing cancer than did those living in other areas. In the future, long-term follow-up investigations in residents living in the vicinity of power plants are warranted.

Shaping future practices: German-speaking medical and dental students' perceptions of artificial intelligence in healthcare.

BACKGROUND: The growing use of artificial intelligence (AI) in healthcare necessitates understanding the perspectives of future practitioners. This study investigated the perceptions of German-speaking medical and dental students regarding the role of artificial intelligence (AI) in their future practices. METHODS: A 28-item survey adapted from the AI in Healthcare Education Questionnaire (AIHEQ) and the Medical Student's Attitude Toward AI in Medicine (MSATAIM) scale was administered to students in Austria, Germany, and Switzerland from April to July 2023. Participants were recruited through targeted advertisements on Facebook and Instagram and were required to be proficient in German and enrolled in medical or dental programs. The data analysis included descriptive statistics, correlations, t tests, and thematic analysis of the open-ended responses. RESULTS: Of the 409 valid responses (mean age = 23.13 years), only 18.2% of the participants reported receiving formal training in AI. Significant positive correlations were found between self-reported tech-savviness and AI familiarity (r = 0.67) and between confidence in finding reliable AI information and positive attitudes toward AI (r = 0.72). While no significant difference in AI familiarity was found between medical and dental students, dental students exhibited slightly more positive attitudes toward the integration of AI into their future practices. CONCLUSION: This study underscores the need for comprehensive AI education in medical and dental curricula to address knowledge gaps and prepare future healthcare professionals for the ethical and effective integration of AI in practice.

A Fungicide, Fludioxonil, Formed the Polyploid Giant Cancer Cells and Induced Metastasis and Stemness in MDA-MB-231 Triple-Negative Breast Cancer Cells.

Fludioxonil, an antifungal agent used as a pesticide, leaves a measurable residue in fruits and vegetables. It has been identified to cause endocrine disruption, interrupt normal development, and cause various diseases such as cancers. In this study, fludioxonil was examined for its effects on the development and metastasis of breast cancer cells. On fludioxonil exposure (10-5 M) for 72 h, mutant p53 (mutp53) MDA-MB-231 triple-negative breast cancer (TNBC) cells significantly inhibited cell viability and developed into polyploid giant cancer cells (PGCCs), with an increase in the number of nuclei and expansion in the cell body size. Fludioxonil exposure disrupted the normal cell cycle phase ratio, resulting in a new peak. In addition, PGCCs showed greater motility than the control and were resistant to anticancer drugs, i.e., doxorubicin, cisplatin, and 5-fluorouracil. Cyclin E1, nuclear factor kappa B (NF-κB), and p53 expressions were remarkably increased, and the expression of cell cycle-, epithelial-mesenchymal-transition (EMT)-, and cancer stemness-related proteins were increased in the PGCCs. The daughter cells obtained from PGCCs had the single nucleus but maintained their enlarged cell size and showed greater cell migration ability and resistance to the anticancer agents. Consequently, fludioxonil accumulated Cyclin E1 and promoted the inflammatory cytokine-enriched microenvironment through the up-regulation of TNF and NF-κB which led to the transformation to PGCCs via abnormal cell cycles such as mitotic delay and mitotic slippage in mutp53 TNBC MDA-MB-231 cells. PGCCs and their daughter cells exhibited significant migration ability, chemo-resistance, and cancer stemness. These results strongly suggest that fludioxonil, as an inducer of potential genotoxicity, may induce the formation of PGCCs, leading to the formation of metastatic and stem cell-like breast cancer cells.

Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

Efficacy of Intensive Lifestyle Education and Forest-Based Exercise for the Primary Prevention of the Risk of Coronary Artery Disease.

Introduction: Despite its efficacy, conventional center-based cardiac rehabilitation has several limitations which have led to the emergence of home-based programs and intensive cardiac rehabilitation as alternative methods for overcoming these limitations. Alternative methods for primary prevention have been recommended for similar reasons. Lifestyle modification is considered key to success in both primary and secondary prevention. Therefore, this primary prevention study aimed to investigate the efficiency of intensive lifestyle education and home-based programs involving unstructured exercise in urban forests to prevent coronary artery disease (CAD). The availability of urban forests as preventive exercise environments was also examined. Methods: Patients with risk factors for CAD participated in primary prevention using either FBEG (forest-based exercise group (FBEG, n = 11) or CBEG (center-based exercise group (CBEG, n = 17) for 12 weeks. The FBEG was provided with intensive residential lifestyle education and followed a home program that included performing exercise in an urban forest. The CBEG followed a conventional supervised exercise program at a fitness facility. Changes in body composition, cardiometabolic variables, and functional capacity were tested using a 2-way repeated ANOVA measurement. An independent t-test was used to examine the differences in weekly energy expenditure between the two groups. Results: Significant within-group differences were identified in body composition, cardiometabolic variables, and the 10-yr probability of CAD in both groups. However, the functional capacity, weekly energy expenditure, and attendance rate showed between-group differences, with superiority in the FBEG. Conclusion: Intensive lifestyle education and subsequent home-based programs with unstructured exercise in the forest were as effective as a conventional center-based program, with superiority in terms of the change of some variables. Intensive education on experiencing and habituating a healthy lifestyle seemed to play an important role in improving motivation.

Integrated ML-Based Strategy Identifies Drug Repurposing for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) affects an estimated global population of around 3 million individuals. IPF is a medical condition with an unknown cause characterized by the formation of scar tissue in the lungs, leading to progressive respiratory disease. Currently, there are only two FDA-approved small molecule drugs specifically for the treatment of IPF and this has created a demand for the rapid development of drugs for IPF treatment. Moreover, denovo drug development is time and cost-intensive with less than a 10% success rate. Drug repurposing currently is the most feasible option for rapidly making the drugs to market for a rare and sporadic disease. Normally, the repurposing of drugs begins with a screening of FDA-approved drugs using computational tools, which results in a low hit rate. Here, an integrated machine learning-based drug repurposing strategy is developed to significantly reduce the false positive outcomes by introducing the predock machine-learning-based predictions followed by literature and GSEA-assisted validation and drug pathway prediction. The developed strategy is deployed to 1480 FDA-approved drugs and to drugs currently in a clinical trial for IPF to screen them against "TGFB1", "TGFB2", "PDGFR-a", "SMAD-2/3", "FGF-2", and more proteins resulting in 247 total and 27 potentially repurposable drugs. The literature and GSEA validation suggested that 72 of 247 (29.14%) drugs have been tried for IPF, 13 of 247 (5.2%) drugs have already been used for lung fibrosis, and 20 of 247 (8%) drugs have been tested for other fibrotic conditions such as cystic fibrosis and renal fibrosis. Pathway prediction of the remaining 142 drugs was carried out resulting in 118 distinct pathways. Furthermore, the analysis revealed that 29 of 118 pathways were directly or indirectly involved in IPF and 11 of 29 pathways were directly involved. Moreover, 15 potential drug combinations are suggested for showing a strong synergistic effect in IPF. The drug repurposing strategy reported here will be useful for rapidly developing drugs for treating IPF and other related conditions.

Scalable Fabrication of Quasi-One-Dimensional van der Waals Ta2Pt3Se8 Nanowire Thin Films via Solution Processing for NO2 Gas Sensing over Large Areas.

Solution-based processing of van der Waals (vdW) one- (1D) and two-dimensional (2D) materials is an effective strategy to obtain high-quality molecular chains or atomic sheets in a large area with scalability. In this work, quasi-1D vdW Ta2Pt3Se8 was exfoliated via liquid phase exfoliation (LPE) to produce a stably dispersed Ta2Pt3Se8 nanowire solution. In order to screen the optimal exfoliation solvent, nine different solvents were employed with different total surface tensions and polar/dispersive (P/D) component (P/D) ratios. The LPE behavior of Ta2Pt3Se8 was elucidated by matching the P/D ratios between Ta2Pt3Se8 and the applied solvent, resulting in N-methyl-2-pyrrolidone (NMP) as an optimal solvent owing to the well-matched total surface tension and P/D ratio. Subsequently, Ta2Pt3Se8 nanowire thin films are manufactured via vacuum filtration using a Ta2Pt3Se8/NMP dispersion. Then, gas sensing devices are fabricated onto the Ta2Pt3Se8 nanowire thin films, and gas sensing property toward NO2 is evaluated at various thin-film thicknesses. A 50 nm thick Ta2Pt3Se8 thin-film device exhibited a percent response of 25.9% at room temperature and 32.4% at 100 °C, respectively. In addition, the device showed complete recovery within 14.1 min at room temperature and 3.5 min at 100 °C, respectively.

Biomedical Dogmas Still Influence the Delivery of Exercise Therapy in Chronic Low Back Pain Management: Mixed-Methods Study.

Purpose: Non-specific, chronic low back pain (NSCLBP) is a leading cause of disability, prompting long-term rehabilitation. Positive patient beliefs and expectations towards lasting exercise engagement play a crucial role for a successful management of this condition. The aim was to investigate beliefs, unmet needs and expectations of NSCLBP patients for exercise-related health behaviour change in the context of rehabilitative care. Patients and Methods: In a mono-centric mixed-methods study, we conducted semi-structured interviews with NSCLBP patients and care providers. We recruited in a rehabilitation clinic which is specialized in orthopaedics and internal medicine. Interviews were analysed deductively by combining health behaviour change theories with Donabedian's quality model of care. In a patient survey, disability (RMDQ), exercise behaviours, fear avoidance beliefs (FABQ), self-efficacy in chronic disease management (SES6G), process- and outcome-expectations (OEE-2) were queried and analysed descriptively. Results: Twenty-two interviews were conducted and 40 questionnaires completed. Qualitative results revealed that NSCLBP patients had persistent biomedical perspectives on their health condition, marked by strong preferences for biomedical diagnostics and beliefs in the superiority of specific exercise regimes. Based on met expectations and positive movement experiences, patients' motivation was successfully fostered in the motivational phase of health behavior change. In the volitional phase, the postulated desire to receive self-management strategies was largely unmet. Psychosocial aspects of care were not widely accepted. The survey study sample showed a disability score (RMDQ) of M = 6.8 (±4.6). Mean scores of validated scales reflecting on attitudes, beliefs and expectations of chronic NSCLBP management were at FABQ-pa M = 15.4 (±6.0), FABQ-w M = 24.0 (±12.1), SES6G M = 6.4 (±2.3), and OEE-2 M = 2.7 (±0.5). Conclusion: In this sample, patients' understanding of NSCLBP was still dominated by biomedical dogmas and perspectives. Inpatient rehabilitation predominantly addressed expectations towards the motivational phase of exercise-related health behaviour change.

Exploring Oxygen Vacancy Effect in 1D Structural SnIP for CO2 Electro-Reduction to Formate.

1D nanostructures exhibit a large surface area and a short network distance, facilitating electron and ion transport. In this study, a 1D van der Waals material, tin iodide phosphide (SnIP), is synthesized and used as an electrocatalyst for the conversion of CO2 to formate. The electrochemical treatment of SnIP reconstructs it into a web-like structure, dissolves the I and P components, and increases the number of oxygen vacancies. The resulting oxygen vacancies promote the activity of the CO2 reduction reaction (CO2RR), increasing the local pH of the electrode surface and maintaining the oxidative metal site of the catalyst despite the electrochemically reducing environment. This strategy, which stabilizes the oxidation state of the catalyst, also helps to improve the durability of CO2RR. In practice, 1D structured SnIP catalyst exhibits outstanding performance with >92% formate faradaic efficiency (FEformate) at 300 mA cm-2, a maximum partial current density for formate of 343 mA cm-2, and excellent long-term stability (>100 h at 100 mA cm-2 with >86% FEformate). This study introduced a method to easily generate oxygen vacancies on the catalyst surface by utilizing 1D materials and a strategy to improve the durability of CO2RR by stabilizing the oxidation state of the catalyst.

Quantum-Dot Light-Emitting Fiber Toward All-In-One Clothing-Type Health Monitoring.

In the Fourth Industrial Revolution, as the connection between objects and people becomes increasingly important, interest in wearable optoelectronic device-based medical diagnosis is on the rise. Pulse oximetry sensors based on a fiber platform, which is the smallest unit of clothing, could be considered an attractive candidate for this application. In this study, red and green quantum-dot light-emitting fibers (QDLEFs) based on a 250 µm-diameter 1-dimensional fiber were successfully implemented, achieving high current efficiencies of approximately 22.46 mW/sr/A and 23.6 mW/sr/A and narrow full-width at half-maximum (FWHM) of about 33 nm, respectively. In addition, its omnidirectional flexibility was confirmed through a vertical and lateral bending test with 0.92% strain. By employing a transparent and flexible elastomer, a wearable pulse oximeter incorporating QDLEFs was successfully demonstrated for oxygen saturation level (SpO2) monitoring on finger and wrist. It was demonstrated to be washable, and could be operated for up to about 18 h. Due to the elastomer and bottom emission, it exhibited excellent wear resistance characteristics in a 50 cycle reciprocating test conducted at about 2180.43 kPa with 220-grit abrasive paper sheet. A theoretical investigation based on modified photon diffusion analysis (MPDA) modeling also determined that using narrow FWHM light sources, such as QDLEFs, improves the resolution and accuracy of SpO2 monitoring. Accordingly, the proposed QDLEF showed distinguished potential as an all-in-one clothing type pulse oximetry.

Introduction to the Forensic Research via Omics Markers in Environmental Health Vulnerable Areas (FROM) study.

This research group (FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas­including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter­along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.

Rethinking food loss and waste to promote sustainable resource use and climate change mitigation in agri-food systems: A review.

The sustainable agri-food system is an important sector recognized for promoting the United Nations' Sustainable Development Goals on food security, resource conservation and climate change mitigation. However, the increasing food loss and waste (FLW) along the supply chains has continued to hinder these goals. This study evaluates the trend of FLW research from 1975 to 2022 and how it promotes the achievement of resource and environmental sustainability in agri-food systems. The salient research themes and hotspots that are of interest to researchers were identified. Bibliometric and network analyses were carried out on scholarly research articles from the Scopus database using bibliometrix and VOSviewer. Furthermore, the content analysis was conducted on the selected highly influential articles containing relevant data to understand the role of FLW in promoting sustainable agri-food systems. The results showed disaggregate and unbalanced research distribution on the impacts of FLW among the countries, with China and the United States having the highest contributions. The identified major research themes relating to sustainable agri-food systems are food waste and sustainable systems, food waste management and food waste impact assessment. Moreover, the circular economy was found to be a relatively new approach being explored in agri-food systems to promote FLW reduction and ensure sustainability of resource use. This study highlights the critical role of the impact of FLW in addressing the grand challenge of food security, resource use efficiency and environmental sustainability.

Linking the 1940 US Census to the NSHAP: Novel Opportunity to Understand the Effects of Childhood Residential Environment on Cognitive Aging.

OBJECTIVE: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition. METHOD: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function. DISCUSSION: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.

Bidirectional crosstalk between bone and muscle: the role of RANKL pathway in osteosarcopenia.

Osteosarcopenia, which refers to the concomitant presence of osteoporosis and sarcopenia, is expected to increase in the rapidly progressive aging world, with serious clinical implications. However, the pathophysiology of osteosarcopenia has not been fully elucidated, and no optimal treatment specific to osteosarcopenia is available. The RANKL-RANK pathway is widely used as a therapeutic target for osteoporosis. Growing evidence supports the importance of the RANKL-RANK pathway, not only in bone, but also in muscle, and the therapeutic potential of targeting this pathway in muscle diseases has been noted. The muscles and bones closely communicate with each other through various secretory factors called myokines and osteokines. This review covers the roles of the RANKL-RANK pathway in the bone and muscle and their reciprocal interactions. Moreover, we will suggest future directions to move forward for the treatment of osteosarcopenia to prepare for an upcoming aging society.

Low Inter-Rater Reliability and Reproducibility of Neck Reflex/"Adler-Langer" Points in Neural Therapy Diagnostics but Increased Pressure Pain Threshold after Therapy: Results of a Randomized Controlled Observer-Blind Trial.

BACKGROUND: Neck reflex points or Adler-Langer points are commonly used in neural therapy to detect so-called interference fields. Chronic irritations or inflammations in the sinuses, teeth, tonsils, or ears are supposed to induce tension and tenderness of the soft tissues and short muscles in the upper cervical spine. The individual treatment strategy is based on the results of diagnostic Adler-Langer point palpation. This study investigated the inter- and intra-rater reliability and explored treatment effects. METHODS: We performed a randomized controlled trial with 104 inpatients (80.8% female, 51.8 ± 12.74 years) of a German department for internal and integrative medicine. Patients were randomized to individual neural therapy according to the pathological findings (n = 48) or no treatment (n = 56). In each patient, three experienced raters (20-45 years of experience in neural therapy) and two novice raters (medical students) rated Adler-Langer points rigidity on a standardized rating scale ("strong," "weak," "none"). The patients independently evaluated the tenderness on palpation of the eight points using the same scale. Pressure pain thresholds were assessed at the eight Adler-Langer points. All patients were retested after 30 min. The five raters were blinded to treatment allocation and assessments of the other raters. Video recordings were obtained to assess the consistency of the areas tested by the different raters. RESULTS: Agreement between patients and raters (Cohen's kappa = 0.161-0.400) and inter-rater reliability were low (Fleiss kappa = 0.132-0.150). Moreover, the individual agreement (pre-post comparisons in untreated patients) was similarly low even in experienced raters (Cohen's kappa = 0.099-0.173). Video documentation suggests that raters do not place their fingers in the correct segments (percentage of correct position: 42.0-60.6%). Pressure pain thresholds at five of the eight Adler-Langer points showed significant changes after treatment compared to none in the control group. CONCLUSION: Under this artificial experimental setting, this method of Adler-Langer point palpation has not proven to be a reliable diagnostic tool. But it could be shown that, as claimed by the method, the tenderness in five of eight Adler-Langer points decreased after neural therapy.

Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site.

During HIV infection, specific RNA-protein interaction between the Rev response element (RRE) and viral Rev protein is required for nuclear export of intron-containing viral mRNA transcripts. Rev initially binds the high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. Here, we present the crystal structure of RRE stem-loop II in distinct closed and open conformations. The high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, and only the open conformation has the widened major groove conducive to initial Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. We propose a binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.