A Clinical Study of Anterior Abdominal Wall Hernias and Its Management: A Medical College Experience.

Objective We aim to evaluate the various risk factors contributing to the occurrence of anterior abdominal wall hernias and assess the various surgical modalities. Materials and methods This prospective observational research was conducted between 2022 and 2024 at a tertiary care health center, involving 100 participants with an anterior abdominal wall hernia diagnosis aged over 14 years. The study excluded patients under 14 years with bleeding diathesis, inherited coagulopathies, inguinal or femoral hernias, or recurrent ventral hernias. Participants underwent detailed clinical examinations and biochemical evaluations and underwent a primary ultrasonography (USG)/contrast-enhanced computed tomography (CECT) to determine defect size. Risk factors were documented, including age, gender, occupation, body mass index (BMI), comorbidities, previous surgery history, multiparity, smoking, chronic straining due to constipation or benign prostatic hyperplasia (BPH), malnutrition, chronic steroid use, chronic renal failure, and chronic liver disease. The surgical procedure was determined by the same surgical team for all cases. Standard antibiotic prophylaxis and preoperative painting/draping protocols were followed in all cases. Intraoperatively, intraoperative time (in hours) was documented. Postoperative parameters included pain, hematoma formation, seroma formation, surgical site infections (SSIs), and early recurrence. These intra- and postoperative findings constituted the primary outcome parameters. Secondary outcome parameters included hospital stay duration and time taken to return to work. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 16 (IBM SPSS Statistics, Armonk, NY) software. Results The study analyzed the occurrence of ventral hernias in 100 patients, with the fourth decade having the highest occurrence (n=42 (42%)). The majority of the participants were male (female: n=47 (47%), male: n=53 (53%)). The majority of the participants were laborers, and 24% (n=24) were office workers. The study found that hypertension, diabetes mellitus, and chronic obstructive pulmonary disease were risk factors for hernias. Other risk factors included obesity, previous history of surgery, multiparity, smoking, chronic straining, malnutrition, and chronic steroid use. The most common type of ventral hernia was umbilical hernia (n=33 (33%)), followed by paraumbilical hernias (n=30 (30%)), and incisional hernias (n=20 (20%)). Of the 100 patients, 74% underwent open hernia repair, with the mean operation time being minimal in cases managed with laparoscopic repair (2.5±0.67 hours). Postoperative pain was highest with the Rives-Stoppa (RS) repair with component separation group. The incidence of surgical site infection was the maximum among cases of open anatomical repair (41.7%), followed by RS repair (31.3%), while it was the minimum in laparoscopic repair (3.7%). Early recurrence was lower in the laparoscopic group (n=1 (3.7%)). Conclusion The study highlights risk factors for abdominal wall hernia and management approaches. Understanding these is crucial for identifying and preventing recurrence. Surgeons must choose the right surgical approach based on patient health and symptoms to achieve desired outcomes and minimize complications. In addition, surgical expertise, availability of resources, and knowledge of what works best for the surgeon constitute important determinants of surgical outcomes.

Lateral cephalometric parameters among Arab skeletal classes II and III patients and applying machine learning models.

BACKGROUND: The World Health Organization considers malocclusion one of the most essential oral health problems. This disease influences various aspects of patients' health and well-being. Therefore, making it easier and more accurate to understand and diagnose patients with skeletal malocclusions is necessary. OBJECTIVES: The main aim of this research was the establishment of machine learning models to correctly classify individual Arab patients, being citizens of Israel, as skeletal class II or III. Secondary outcomes of the study included comparing cephalometric parameters between patients with skeletal class II and III and between age and gender-specific subgroups, an analysis of the correlation of various cephalometric variables, and principal component analysis in skeletal class diagnosis. METHODS: This quantitative, observational study is based on data from the Orthodontic Center, Jatt, Israel. The experimental data consisted of the coded records of 502 Arab patients diagnosed as Class II or III according to the Calculated_ANB. This parameter was defined as the difference between the measured ANB angle and the individualized ANB of Panagiotidis and Witt. In this observational study, we focused on the primary aim, i.e., the establishment of machine learning models for the correct classification of skeletal class II and III in a group of Arab orthodontic patients. For this purpose, various ML models and input data was tested after identifying the most relevant parameters by conducting a principal component analysis. As secondary outcomes this study compared the cephalometric parameters and analyzed their correlations between skeletal class II and III as well as between gender and age specific subgroups. RESULTS: Comparison of the two groups demonstrated significant differences between skeletal class II and class III patients. This was shown for the parameters NL-NSL angle, PFH/AFH ratio, SNA angle, SNB angle, SN-Ba angle. SN-Pg angle, and ML-NSL angle in skeletal class III patients, and for S-N (mm) in skeletal class II patients. In skeletal class II and skeletal class III patients, the results showed that the Calculated_ANB correlated well with many other cephalometric parameters. With the help of the Principal Component Analysis (PCA), it was possible to explain about 71% of the variation between the first two PCs. Finally, applying the stepwise forward Machine Learning models, it could be demonstrated that the model works only with the parameters Wits appraisal and SNB angle was able to predict the allocation of patients to either skeletal class II or III with an accuracy of 0.95, compared to a value of 0.99 when all parameters were used ("general model"). CONCLUSION: There is a significant relationship between many cephalometric parameters within the different groups of gender and age. This study highlights the high accuracy and power of Wits appraisal and the SNB angle in evaluating the classification of orthodontic malocclusion.

Gastrointestinal Stromal Tumor (GIST) Masquerading as a Pancreatic Pseudocyst: A Rare Case Report.

Despite their relative rarity, gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal tumor in the gastrointestinal (GI) tract. Here, we describe a rare case of a 62-year-old hypertensive female presenting with abdominal pain and a palpable mass, initially suspected to be a pancreatic pseudocyst based on radiological findings. Subsequent histopathological (HPE) examination following surgical resection revealed a large cystic lesion originating from the stomach, characterized as a malignant epithelioid GIST. Based on these findings and taking into consideration the symptomatology of the patient, the decision was made to post the patient for an upfront, open surgical exploration without pre-operative biopsy studies. Frozen section facilities were kept on standby considering the differential diagnosis. Since the frozen section revealed a gastric GIST, a decision was made to perform subtotal gastrectomy, followed by gastrojejunostomy (GJ) and jejunojejunostomy (JJ). In addition, the part of the cyst adherent to the left lobe of the liver was dealt with with a non-anatomical wedge resection. Immunohistochemical (IHC) analysis showed positivity for Cluster of Differentiation 117 (CD117) with negativity for Cluster of Differentiation 34 (CD34), Desmin, and Discovered On Gastrointestinal Stromal Tumors 1 (DOG-1). The tumor exhibited aggressive features, including high mitotic activity, i.e., >5/10 high power field (hpf), hemorrhagic areas, and infiltration into the liver parenchyma. The patient then received adjuvant imatinib-based chemotherapy and was maintained on strict follow-up.

Multiple Tubercular Intestinal Perforations: A Case Report.

Intestinal tuberculosis (TB) is a frequently encountered pathology by surgeons all over India. There exists a vast body of knowledge about this disease; however, a detailed understanding of its presentation as well as surgical management is essential for every Indian surgeon, given its rampant nature. This report discusses the case of a 28-year-old female presenting with severe left upper abdominal pain, non-bilious vomiting, and fever, who was ultimately diagnosed with small bowel TB leading to perforations. Despite a history of pulmonary TB treated a year prior, the patient exhibited significant clinical and imaging findings, including pneumoperitoneum and peritonitis. Exploratory laparotomy revealed multiple tubercular perforations in the mid-jejunum and a stricture causing proximal jejunal dilatation. Surgical intervention involved resection of the affected segment and end-to-end anastomosis. Histopathological analysis confirmed TB as the cause. This case underscores the importance of considering TB in the differential diagnosis of small bowel perforations and highlights the critical role of timely surgical intervention and comprehensive management in improving patient outcomes.

The Impact of Thyroid Surgery on Calcium and Magnesium Homeostasis: A Prospective Study.

OBJECTIVE: Total thyroidectomy constitutes one of the bread-and-butter procedures of surgeons all over the world. Like with any surgical procedure, complications form a part and parcel of the postoperative course in the hospital. Hypocalcemia represents one such prevalent complication post-total thyroidectomy. This study aimed to evaluate the impact of total thyroidectomy on calcium and magnesium levels and to assess the role of magnesium in postoperative hypocalcemia. METHODS AND MATERIALS: This study was carried out at a tertiary health center over a two-year period from 2022 to 2024. It involved 100 participants with thyroid conditions (benign/malignant) who required total thyroidectomy. Patients with pre-existing conditions affecting calcium levels (e.g., chronic renal failure, medullary carcinoma thyroid, etc.) were expressly excluded. Preoperative calcium, magnesium, and parathyroid hormone (PTH) levels were recorded. Intraoperative parameters such as time and fluid volume were also measured. Postoperatively, serum calcium and magnesium levels, PTH levels, and complications like hypocalcemia and hypomagnesemia were monitored. The descriptive statistics were computed to delineate the study sample. After completion of data collection, data analysis was achieved using IBM SPSS Statistics for Windows, V. 16.0 (SPSS Inc., Chicago, IL). The chi-squared test of significance was utilized to establish statistical correlations between calcium and magnesium levels post-total thyroidectomy. A p-value of less than 0.05 was considered statistically significant. RESULTS: The study analyzed 100 total thyroidectomy patients. The mean age of patients in our study was 50.7±8.86 years, with 97 females and three males. The most common pathology indicating total thyroidectomy was diffuse colloid goiter (46%), followed by multinodular goiter (38%). Only a single patient had preoperative biochemical hypocalcemia or hypomagnesemia, but none exhibited symptoms. After total thyroidectomy, 15% (n=15) developed hypocalcemia, and 11% (n=11) developed hypomagnesemia. Postoperative mean PTH levels slightly decreased to 28.8±11.75 pg/dl, indicating similar variability to preoperative levels. Patients who underwent intra-capsular dissection had a mean postoperative ionic calcium level of 4.89±0.54 mg/dl, while those who underwent extra-capsular dissection had a slightly lower mean ionic calcium level of 4.72±0.76 mg/dl. CONCLUSION: Hypocalcemia is one of the most prevalent complications associated with total thyroidectomy. The role of magnesium in maintaining calcium homeostasis after thyroidectomy should be further explored to improve the management of hypocalcemia. Additionally, the type of capsular dissection performed during the surgery can impact the occurrence of hypocalcemia, and using intra-capsular dissection whenever possible may help reduce the incidence of hypocalcemia.

Fabrication, optimization, and in vitro validation of penicillin-loaded hydrogels for controlled drug delivery.

Bacterial infections present a major global challenge. Penicillin, a widely used antibiotic known for its effectiveness and safety, is frequently prescribed. However, its short half-life necessitates multiple high-dose daily administrations, leading to severe side-effects. Therefore, this study aims to address these issues by developing hydrogels which control the release of penicillin and alleviate its adverse effects. Various combinations of aspartic acid and acrylamide were crosslinked by N', N'-methylene bisacrylamide through a free radical polymerization process to prepare aspartic acid/acrylamide (Asp/Am) hydrogels. The fabricated hydrogels underwent comprehensive characterization to assess physical properties and thermal stability. The soluble and insoluble fractions and porosity of the synthesized matrix were evaluated by sol-gel and porosity studies. Gel fraction was estimated at 88-96%, whereas sol fraction was found 12-4% and porosity found within the 63-78% range for fabricated hydrogel formulations. Maximum swelling and drug release were seen at pH 7.4, demonstrating a controlled drug release from hydrogel networks. The results showed that swelling, porosity, gel fraction, and drug release increased with higher concentrations of aspartic acid and acrylamide. However, integration of N', N'-methylene bisacrylamide exhibited the opposite effect on swelling and porosity, while increasing gel fraction. All formulations followed the Korsymer-Peppas model of kinetics with 'r' values within the range of 0.9740-0.9980. Furthermore, the cytotoxicity study indicated an effective and safe use of hydrogel because the cell viability was higher than 70%. Therefore, these prepared hydrogels show promise candidates for controlled release of Penicillin and are anticipated to be valuable in clinical applications.

Hippophae Rhamnoides-derived Phytomedicine Nano-System Modulates Bax/Fas Pathways to Reduce Proliferation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn' extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy.

Lemmel Syndrome: A Surgical Enigma.

A periampullary diverticulum (PAD) is the most common type of duodenal diverticula found in patients undergoing upper gastrointestinal tract assessments. Even while PAD typically does not manifest any symptoms, it can nevertheless be a source of obstructive jaundice in the absence of a tumor or choledocholithiasis, a condition known as Lemmel's syndrome. We report a case of a 60-year-old woman who presented with abdominal discomfort and multiple episodes of vomiting. After comprehensive clinical examination and investigations, a provisional diagnosis of Lemmel's syndrome was made, leading to initial conservative management for diverticulitis, followed by an exploratory procedure. This case underscores the importance of recognizing Lemmel's syndrome as a differential diagnosis for obstructive jaundice when duodenal diverticula are present, to prevent misdiagnosis and ensure timely, appropriate treatment.

Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1 magnetic resonance imaging.

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care.

Long-range polymer ordering by directional coating to remarkably enhance the charge carrier mobility in PCDTPT-based organic field-effect transistors.

With the wide potential of organic field-effect transistors in all the modern electronic circuitries, researchers are grappling with the challenge of poor charge transport and hence lower mobility in organic polymers. Low-charge carrier mobility is mainly due to disorder in the molecular packing of organic semiconductors along with other factors, such as impurities, defects and interactions between molecules. The current research work has been conducted to align the molecular chains of poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-|||b:5,4-|b']|dithiophen-2-yl)-alt-[1,2,5]thiadiazolo-[3,4-c]pyridine] (PCDTPT) using directional coating techniques such as dip coating and brush coating on nano-grooved substrates. Long-range order of polymer chains was clearly observed along the direction of brush coating and nanogrooves in optical and atomic force microscope (AFM) images while transmission spectra confirmed decreased pi-pi stacking for the polymer films deposited by this technique. By comparing the mobility performance of brush-coated devices with other techniques, we found a remarkable mobility enhancement of 90 times that of conventional spin-coated device and 24 times enhancement compared with the dip-coated device for the case when the alignment of polymer chains was parallel to the channel. All the fabrication and characterizations were performed in the ambient environment. This study demonstrates a potential approach to align the polymers on long and short ranges hence providing a route for high-performing devices in ambient conditions.

Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18- to 87-Year-Old Men.

OBJECTIVES: Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown. METHODS: We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed. RESULTS: We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m2, 7.65 ± 0.92 kg/m2, 6.87 ± 0.93 kg/m2, for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men. CONCLUSION: Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing.

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.

Impact of Postprocedural Graft Flow on Outcomes Following Chronic Total Occlusion Intervention in Postcoronary Artery Bypass Graft Patients: A Detailed Angiographic Analysis.

Chronic total occlusions (CTOs) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes after CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 patients with previous CABG who underwent CTO-PCI in 12 international centers in 2019 to 2023 were categorized into "grafted" and "ungrafted" groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into "graft-occluded" and "graft-patent" groups, depending on graft patency. The primary end points were (1) technical success rate, (2) target vessel failure, and (3) CTO failure rates at 1 year. CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs 80%, p = 0.004) than nongrafted CTOs. Of the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs 81%, p = 0.022). An occluded graft was an independent predictor of technical failure (odds ratio 2.04, 95% confidence interval 1.03 to 4.76, p = 0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1 year (hazard ratio 5.6, 95% confidence interval 1.2 to 27.5, log-rank p = 0.033). In conclusion, in patients with previous CABG who underwent CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure.

Engineering Titanium-Hydroxyapatite Nanocomposite Hydrogels for Enhanced Antibacterial and Wound Healing Efficacy.

External factors often lead to predictable damage, such as chemical injuries, burns, incisions, and wounds. Bacterial resistance to antibiotics at wound sites underscores the importance of developing hydrogel composite systems with inorganic nanoparticles possessing antibacterial properties to treat infected wounds and expedite the skin regeneration process. In this study, a promising TiO2-HAp@PF-127@CBM inorganic and organic integrated hydrogel system was designed to address challenges associated with bacterial resistance and wound healing. The synthesized TiO2-hydroxyapatite (HAp) nanocomposites were coated with an FDA-approved PluronicF-127 polymer and combined with a carbomer hydrogel (CBM) to accomplish the final product. The synthesized nanoparticles exhibit enhanced biocompatibility against L929 and HUVECs and cell proliferation effects. To mitigate oxidative stress caused by TiO2-induced reactive oxygen species in dark environments for effective antibacterial effects, HAp promotes cell proliferation, expediting wound skin layer formation. CBM binds to inorganic nanoparticles, facilitating their gradual release and promoting wound healing. The reduced inflammation and enhanced tissue regeneration observed in the TiO2-HAp@PF-127@CBM group suggest a favorable environment for wound repair. These results align with prior findings highlighting the biocompatibility and wound-healing properties of titanium-HAp-based materials. The ability of the TiO2-HAp@PF-127@CBM hydrogel dressing to promote granulation tissue formation and facilitate epidermal regeneration underscores its potential for promoting antibacterial effects and wound healing applications.

Near-infrared-II responsive ovalbumin functionalized gold-genipin nanosystem cascading photo-immunotherapy of cancer.

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.

Resistance Exercise Reduces Sarcopenia by Repairing Leaky Gut in Patients with Alzheimer's Disease.

PURPOSE: Sarcopenia or age-associated muscle loss is common in patients with Alzheimer's disease (AD). We have previously demonstrated the contribution of a leaky gut to sarcopenia in AD. Here, we asked whether resistant exercise (RE) reduces the sarcopenia phenotype by repairing intestinal leakage in patients with AD. METHOD: A prospective, single-center study of older adults, including healthy controls and patients with AD (n = 44-51/group), was conducted to measure plasma zonulin and claudin-3 (markers of intestinal leakage), handgrip strength (HGS), and short physical performance battery (SPPB) as a measure of functional capacity. Measurements in patients with AD were performed at baseline and after 12 weeks of RE. RESULTS: At baseline, patients with AD had higher plasma zonulin and claudin-3 and lower HGS, gait speed, and SPPB scores than controls. RE reduced plasma zonulin and claudin-3 levels and improved HGS, SPPB scores, and gait speed. Regression analysis revealed robust relationships between changes in plasma zonulin and claudin-3 with HGS. Plasma zonulin was also positively associated with SPPB scores. In addition, RE downregulated plasma markers of inflammation and oxidative stress. However, the prevalence of sarcopenia based on low HGS and muscle atrophy or low SPPB was not affected by RE. CONCLUSION: Taken together, disruption of the intestinal mucosal barrier may contribute to functional decline and sarcopenia in AD, which is incompletely recovered by RE. Circulating levels of zonulin and claudin-3 may be valuable in predicting sarcopenia and functional capacity in older adults with AD.

Studying the Effect of the Host Genetic Background of Juvenile Polyposis Development Using Collaborative Cross and Smad4 Knock-Out Mouse Models.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases.

Breathing new life into tissue engineering: exploring cutting-edge vascularization strategies for skin substitutes.

Tissue-engineered skin substitutes (TESS) emerged as a new therapeutic option to improve skin transplantation. However, establishing an adequate and rapid vascularization in TESS is a critical factor for their clinical application and successful engraftment in patients. Therefore, several methods have been applied to improve the vascularization of skin substitutes including (i) modifying the structural and physicochemical properties of dermal scaffolds; (ii) activating biological scaffolds with growth factor-releasing systems or gene vectors; and (iii) developing prevascularized skin substitutes by loading scaffolds with capillary-forming cells. This review provides a detailed overview of the most recent and important developments in the vascularization strategies for skin substitutes. On the one hand, we present cell-based approaches using stem cells, microvascular fragments, adipose tissue derived stromal vascular fraction, endothelial cells derived from blood and skin as well as other pro-angiogenic stimulation methods. On the other hand, we discuss how distinct 3D bioprinting techniques and microfluidics, miRNA manipulation, cell sheet engineering and photosynthetic scaffolds like GelMA, can enhance skin vascularization for clinical applications. Finally, we summarize and discuss the challenges and prospects of the currently available vascularization techniques that may serve as a steppingstone to a mainstream application of skin tissue engineering.

Study of half-metallic ferromagnetism and transport characteristics of double perovskites Sr2AIrO6 (A = Y, Lu, Sc) for spintronic applications.

The precise manipulation of electromagnetic and thermoelectric characteristics in the miniaturization of electronic devices offers a promising foundation for practical applications in quantum computing. Double perovskites characterized by stability, non-toxicity, and spin polarization, have emerged as appealing candidates for spintronic applications. This study explores the theoretical elucidation of the influence of iridium's 5d electrons on the magnetic characteristics of Sr2AIrO6 (A = Y, Lu, Sc) with WIEN2k code. The determined formation energies confirm the thermodynamic stability while an analysis of band structure and the density of states (DOS) reveals a half-metallic ferromagnetic character. This characteristic is comprehensible through the analysis of exchange constants and exchange energies. The current analysis suggests that crystal field effects, a fundamental hybridization process and exchange energies contribute to the emergence of ferromagnetism due to electron-spin interactions. Finally, assessments of electrical and thermal conductivities, Seebeck coefficient, power factor, figure of merit and magnetic susceptibility are conducted to assess the potential of the investigated materials for the applications in thermoelectric devices.