Subcellular Feature-Based Classification of α and ß Cells Using Soft X-ray Tomography.

The dysfunction of α and ß cells in pancreatic islets can lead to diabetes. Many questions remain on the subcellular organization of islet cells during the progression of disease. Existing three-dimensional cellular mapping approaches face challenges such as time-intensive sample sectioning and subjective cellular identification. To address these challenges, we have developed a subcellular feature-based classification approach, which allows us to identify α and ß cells and quantify their subcellular structural characteristics using soft X-ray tomography (SXT). We observed significant differences in whole-cell morphological and organelle statistics between the two cell types. Additionally, we characterize subtle biophysical differences between individual insulin and glucagon vesicles by analyzing vesicle size and molecular density distributions, which were not previously possible using other methods. These sub-vesicular parameters enable us to predict cell types systematically using supervised machine learning. We also visualize distinct vesicle and cell subtypes using Uniform Manifold Approximation and Projection (UMAP) embeddings, which provides us with an innovative approach to explore structural heterogeneity in islet cells. This methodology presents an innovative approach for tracking biologically meaningful heterogeneity in cells that can be applied to any cellular system.

Comparative Effectiveness of Different Exercises for Reducing Pain Intensity in Primary Dysmenorrhea: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Studies have demonstrated that exercise can mitigate the intensity of menstrual pain in primary dysmenorrhea, but the most effective type of exercise remains unclear. The objective of this systematic review and network meta-analysis was to evaluate the effectiveness of different exercise regimens in reducing pain associated with primary dysmenorrhoea. METHODS: Randomized controlled trials investigating the relationship between menstrual pain and exercise were selected from major electronic databases until February 2, 2024. The primary outcome was the effect of exercise on pain intensity measured by the mean difference on a 10-cm visual analogue scale at 4 and 8 weeks after intervention. The secondary outcome was the difference in risk of dropout at 8 weeks. The study protocol was registered as INPLASY202330050. RESULTS: This systematic review and network meta-analysis included 29 randomized controlled trials, which involved 1808 participants with primary dysmenorrhea. Exercise interventions included relaxation exercise, strength training, aerobic activity, yoga, mixed exercise, and the Kegel maneuver. Relaxation exercise was the most effective in reducing menstrual pain in 4 weeks (- 3.56; 95% confidence interval: - 5.03 to - 2.08). All exercise interventions were effective in reducing menstrual pain at 8 weeks, with reductions ranging from - 3.87 (95% CI - 5.51 to - 2.22) for relaxation exercise to - 2.75 (95% CI - 4.00 to - 1.51) for yoga, compared to the control group. Relaxation exercises were found to have a significantly lower dropout risk (- 0.11; 95% CI - 0.20 to 0.02), while none of the exercise types was associated with a higher dropout risk than the control group. CONCLUSION: All exercise interventions were effective in reducing menstrual pain in primary dysmenorrhea after 8 weeks of intervention. However, relaxation exercise was found to be the most effective intervention at 4 and 8 weeks and had the lowest risk of dropout.

This analysis aimed to see how effective different types of exercise are in reducing pain in women with primary dysmenorrhea. The researchers looked at 29 studies involving 1808 participants and evaluated six different types of exercise. The main outcome was the effect of pain reduction after 4 and 8 weeks of exercise. The researchers found that all types of exercise were effective in reducing menstrual pain after 8 weeks, with relaxation exercises being the most effective at both 4 and 8 weeks. None of the exercise types were associated with higher dropout risks than the control group, and relaxation exercise had a lower dropout risk than the other types of exercise.

Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. METHODS: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. RESULTS: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group. CONCLUSION: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Polylactic acid micro/nanoplastic-induced hepatotoxicity: Investigating food and air sources via multi-omics.

Micro/nanoplastics (MNPs) are detected in human liver, and pose significant risks to human health. Oral exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse liver. Similarly, nasal exposure to non-biodegradable plastics can cause airway dysbiosis in mice. However, the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly understood. Here we show the hepatotoxic effects of biodegradable polylactic acid (PLA) MNPs through multi-omics analysis of various biological samples from mice, including gut, fecal, nasal, lung, liver, and blood samples. Our results show that both foodborne and airborne PLA MNPs compromise liver function, disrupt serum antioxidant activity, and cause liver pathology. Specifically, foodborne MNPs lead to gut microbial dysbiosis, metabolic alterations in the gut and serum, and liver transcriptomic changes. Airborne MNPs affect nasal and lung microbiota, alter lung and serum metabolites, and disrupt liver transcriptomics. The gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure, while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP exposure. The relevant results suggest that foodborne PLA MNPs could affect the "gut microbiota-gut-liver" axis and induce hepatoxicity, while airborne PLA MNPs could disrupt the "airway microbiota-lung-liver" axis and cause hepatoxicity. These findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the environment. Our current study could be a starting point for biodegradable MNPs-induced hepatotoxicity. More research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

The cost implications of Wilson disease among hospitalized patients: analysis of USA hospitals.

BACKGROUND AND AIM: In this study, we used a national cohort of patients with Wilson's disease (WD) to investigate the admissions, mortality rates, and costs over the captured period to assess specific subpopulations at higher burden. METHODS: Patients with WD were selected using 2016-2019 National Inpatient Sample (NIS). The weighted estimates and patient data were stratified using demographics and medical characteristics. Regression curves were graphed to derive goodness-of-fit for each trend from which R2 and P values were calculated. RESULTS: Annual total admissions per 100 000 hospitalizations due to WD were 1075, 1180, 1140, and 1330 ( R2  = 0.75; P  = 0.13) from 2016 to 2019. Within the demographics, there was an increase in admissions among patients greater than 65 years of age ( R2  = 0.90; P  = 0.05) and White patients ( R2  = 0.97; P  = 0.02). Assessing WD-related mortality rates, there was an increase in the mortality rate among those in the first quartile of income ( R2  = 1.00; P  < 0.001). The total cost for WD-related hospitalizations was $20.90, $27.23, $24.20, and $27.25 million US dollars for the years 2016, 2017, 2018, and 2019, respectively ( R2  = 0.47; P  = 0.32). There was an increasing total cost trend for Asian or Pacific Islander patients ( R2  = 0.90; P  = 0.05). Interestingly, patients with cirrhosis demonstrated a decreased trend in the total costs ( R2  = 0.97; P  = 0.02). CONCLUSION: Our study demonstrated that certain ethnicity groups, income classes and comorbidities had increased admissions or costs among patients admitted with WD.

Pictorial Essay on Ultrasound and Magnetic Resonance Imaging of Paraspinal Muscles for Myofascial Pain Syndrome.

The paraspinal muscles of the cervical, thoracic, and lumbar spine are important pain generators because muscle strains or myofascial pain syndrome caused by trigger points are common during clinical practice. Ultrasonography is the most convenient imaging tool for evaluating these muscles due to its advantages, such as providing good delineation of soft tissues, easy accessibility, and zero radiation. Additionally, ultrasound can serve as a useful guiding tool for paraspinal muscle intervention to prevent inadvertent injuries to vital axial neurovascular structures. This pictorial essay presents ultrasound scanning protocols for the paraspinal and other associated muscles as well as a discussion of their clinical relevance. Axial magnetic resonance imaging has also been used to elucidate reciprocal anatomy. In conclusion, ultrasound imaging proves to be a valuable tool that facilitates the differentiation of individual paraspinal muscles. This capability significantly enhances the precision of interventions designed to address myofascial pain syndrome.

Ultrasound imaging of the transversus nuchae muscle: a potential entrapment site for the lesser occipital nerve.

.

Enhancing Overhead Throwing Ball Velocity after Core Muscle Training in Athletes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the influence of core muscle training (CMT) on throwing ball velocity among overhead throwing athletes. DESIGN: A literature search was performed from inception to July 2023 for randomized controlled trials (RCTs) investigating the effects of CMT on overhead throwing ball velocity. The primary outcome was the change in standing throwing ball velocity. The secondary outcome focused on the enhancement of step/jump throwing ball velocity. RESULTS: Seven RCTs were included, revealing a significant improvement in standing throwing ball-velocity in the group undergoing CMT (Hedges' g = 0.701, 95% confidence interval [CI] = 0.339 to 1.063, p < 0.001). Longer treatment duration and a higher frequency of CMT sessions per week contributed to improved standing throwing ball velocity. However, CMT did not show significant benefits for step (Hedge's g = 0.463, 95% CI = -0.058 to 0.985, p = 0.082) and jump throwing ball-velocity (Hedges' g = 0.550, 95% CI = -0.051 to 1.152, p = 0.073). CONCLUSION: CMT significantly enhanced standing ball throwing velocity. However, its effect on step/jump-throwing ball velocity was less certain. Further research is needed to explore the impact of CMT (especially its long-term effects) on throwing ball velocity.

Effectiveness of Lumbar Segmental Stabilization Exercises in Managing Disability and Pain Intensity Among Patients with Lumbar Spondylolysis and Spondylolisthesis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: This study aims to assess the effectiveness of lumbar segmental stabilization exercises (LSSE) in managing spondylolysis and spondylolisthesis. SUMMARY OF BACKGROUND DATA: Spondylolysis and spondylolisthesis are spinal disorders associated with lumbar segmental instability. LSSE have shown positive effects in treating these conditions; however, systematic reviews and meta-analyses are lacking. METHODS: A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies from the inception of the databases used up to January 2024, was conducted. Disability improvement and pain intensity change were the primary and secondary outcomes, respectively, standardized using Hedges' g. Eligible articles underwent independent scrutiny by two authors, who also performed data extraction and quality assessment. Data pooling was accomplished using a random-effects model. RESULTS: In total, five randomized controlled trials comprising 198 participants were included, revealing a trend effect toward disability improvement in the LSSE group (Hedges' g=-0.598, 95% CI=-1.211 to 0.016, P=0.056, I2=75.447%). When the LSSE was administered as a single treatment, disability improvement became significant (Hedges' g=-1.325, 95% CI=-2.598 to -0.053, P=0.041, I2=80.020%). No significant effect of LSSE on pain reduction was observed (Hedges' g=-0.496, 95% CI=-1.082 to 0.090, P=0.097, I2=73.935%). CONCLUSION: In summary, our meta-analysis suggests that LSSE can potentially improve disability, especially when used as a single treatment. LSSE appears more beneficial in reducing disability than alleviating pain. Future research on different patient groups is needed to understand comprehensively LSSE's effects on other musculoskeletal disorders.

Ultrasound imaging of the posterior lateral corner of the knee: a pictorial review of anatomy and pathologies.

Assessment of the posterior lateral knee pain poses diagnostic challenges, requiring accurate evaluation of various structures in light of the medical history and physical examination. Despite substantial progress in the ultrasonographic diagnosis of musculoskeletal disorders, the current protocol (EURO-MUSCULUS/USPRM. Basic scanning protocols for knee) fails to conduct a comprehensive investigation into the intricate, tendons, and ligaments of the posterior lateral knee. This pictorial review aims to bridge this gap by offering a systematic approach to utilize ultrasound examination of the less-discussed structures in this specific region. Providing cadaveric and magnetic resonance images, this essay demonstrates the efficacy of ultrasound in diagnosing posterior lateral knee pain. Notably, pathologies such as ligamentous sprains and tears are clearly discernible. Moreover, the integration of ultrasound guidance plays a vital role in reducing the risk of inadvertent neurovascular injury during injection, such as the common peroneal nerve and lateral genicular artery. This comprehensive approach will enhance clinicians' understanding and equip them with effective management strategies for posterior lateral knee pain.Critical relevance statement In this visual exposition, we delve into the intricacies of the posterior lateral corner of the knee. Offering a methodical approach to employ ultrasound for visualization of the less-explored structures within this region, the authors aim to enhance the diagnosis in posterior lateral knee pain.Key points1. Ultrasound excels at revealing intricate structures in the posterior lateral knee.2. Due to proximity of vital structures, extreme caution is crucial during injections.3. Employing dynamic scan and understanding ligaments enables a comprehensive exploration of pathologies.

Cysteine-binding adjuvant enhances survival and promotes immune function in a murine model of acute myeloid leukemia.

ABSTRACT: Therapeutic vaccination has long been a promising avenue for cancer immunotherapy but is often limited by tumor heterogeneity. The genetic and molecular diversity between patients often results in variation in the antigens present on cancer cell surfaces. As a result, recent research has focused on personalized cancer vaccines. Although promising, this strategy suffers from time-consuming production, high cost, inaccessibility, and targeting of a limited number of tumor antigens. Instead, we explore an antigen-agnostic polymeric in situ cancer vaccination platform for treating blood malignancies, in our model here with acute myeloid leukemia (AML). Rather than immunizing against specific antigens or targeting adjuvant to specific cell-surface markers, this platform leverages a characteristic metabolic and enzymatic dysregulation in cancer cells that produces an excess of free cysteine thiols on their surfaces. These thiols increase in abundance after treatment with cytotoxic agents such as cytarabine, the current standard of care in AML. The resulting free thiols can undergo efficient disulfide exchange with pyridyl disulfide (PDS) moieties on our construct and allow for in situ covalent attachment to cancer cell surfaces and debris. PDS-functionalized monomers are incorporated into a statistical copolymer with pendant mannose groups and TLR7 agonists to target covalently linked antigen and adjuvant to antigen-presenting cells in the liver and spleen after IV administration. There, the compound initiates an anticancer immune response, including T-cell activation and antibody generation, ultimately prolonging survival in cancer-bearing mice.

A systematic review on sonoelastography for rotator-cuff post-repair assessment.

Surgical repair of rotator cuff tears is performed routinely; however, the risks of re-tears and the associated consequences are significant. Sonoelastography, an imaging modality that evaluates the mechanical properties of tissues, can examine the dynamic transitions in rotator cuff stiffness following retear and investigate the relationship between these changes and the occurrences of retears. This systematic review aimed to summarize the role of perioperative sonoelastography in repaired rotator cuffs. A comprehensive search of the PubMed, Embase, and Cochrane databases was conducted, covering studies published until June 19, 2023. The Newcastle-Ottawa scale was used for quality assessment. The key information extracted from each study included the injury/surgery type, follow-up duration, sonoelastography mode, and main sonoelastographic findings. Eleven eligible studies comprising 355 patients were included. All studies focused on supraspinatus muscles and tendons with previous arthroscopic repairs. During the postoperative 1st - 6th months, muscle stiffness increased in the supraspinatus and decreased in the ipsilateral deltoid. Failure to recover supraspinatus muscle elasticity might be indicative of potential tendon re-tear; however, it is imperative to first establish correlations with other imaging modalities. Conflicting findings have been observed regarding stiffening or softening of the supraspinatus tendon after surgical repair. The preoperative stiffness of the supraspinatus tendon did not correlate with postoperative tendon integrity or function.