Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Long-Term Outcomes of Laparoscopic Gastric Plication for Treatment of Morbid Obesity: a Single-Center Experience.

BACKGROUND: Although laparoscopic gastric plication (LGP) has been mentioned in many studies, its practice has not yet been standardized. In addition, the outcomes remain conflicting, especially long-term ones. This study was conducted to elucidate the long-term consequences of LGP. METHODS: Retrospective analysis of patients with obesity underwent LGP at our institution between March 2010 and September 2014. Data were prospectively collected from our database. RESULTS: Of the 88 consecutive patients in the study period between 2010 and 2014, follow-up data out to 6 years was available in 60 LGP patients (68.18%). The mean age of the included patients was 41.3 ± 10 years. A total of 81.7% were females. We observed a significant BMI reduction out to 2 years (p < 0.001), a plateau at 3 and 4 years, and a significant BMI increase at 6 years (p < 0.01). %TWL at 2 years was 21.14% and 12.08% at 6 years. Weight regain was observed in 35 patients at 6 years to reach a rate of 58.3%. Predictors for weight regain at 6 years were disrupted plication fold, increased hunger, and non-adherence to regular exercise. The diabetes improvement rate was 66.6% at 6 years. There were 14 re-operations (23.3%): 1 emergency (1.6%) and 13 (21.6%) elective. There was no mortality. CONCLUSION: At the 6-year follow-up visit, LGP has a much less durable effect on weight loss with a % EWL of 32% and a weight regain of 58.3% resulting in a high rate of revisions.

A leadless pacemaker matched with a vasovagal syncope: how long can it last?

BACKGROUND: Guidelines recommend that cardiac pacing should be considered in patients suffering from frequent vasovagal syncopal (VVS) episodes. Studies have demonstrated the safety and efficacy of leadless pacemakers (LP) in cardioinhibitory vasovagal populations specifically, rendering them a reasonable alternative to transvenous pacing in these patients. However, due to the paucity of data on extraction and the number of concomitant LPs that can be safely implanted, there are concerns regarding LPs' battery longevity, especially in younger patients who may require decades of pacing therapy. METHODS: This is a retrospective analysis of the first 100 LPs implanted at a tertiary cardiac centre in the UK. Demographical data and device parameters at implant and follow-ups were obtained from the hospital's medical records. The battery life of the LPs in the VVS patients was compared to that of patients with other pacing indications. RESULTS: Ninety patients were included in the analysis. 14 patients (15.6%) had VVS, and 76 patients (84.4%) had other indications for pacing. Mean ages were 34 ± 13 years and 62 ± 20 years for the VVS and the other group, respectively. The estimated total battery life was 15.22 ± 0.35 and 13.65 ± 2.97 years in the VVS and the other indications group respectively (p = .04). There were no complications in the VVS group. CONCLUSION: LPs provide a promising treatment for patients with vasovagal syncope with reassuring battery performance at the short/intermediate term. Further longer-term follow-up data are needed to identify the true battery potential in this patient cohort.

Development and Validation of an Artificial Intelligence-Based Model to Predict Gastroesophageal Reflux Disease After Sleeve Gastrectomy.

PURPOSE: Prediction of the onset of de novo gastroesophageal reflux disease (GERD) after sleeve gastrectomy (SG) would be helpful in decision-making and selection of the optimal bariatric procedure for every patient. The present study aimed to develop an artificial intelligence (AI)-based model to predict the onset of GERD after SG to help clinicians and surgeons in decision-making. MATERIALS AND METHODS: A prospectively maintained database of patients with severe obesity who underwent SG was used for the development of the AI model using all the available data points. The dataset was arbitrarily split into two parts: 70% for training and 30% for testing. Then ranking of the variables was performed in two steps. Different learning algorithms were used, and the best model that showed maximum performance was selected for the further steps of machine learning. A multitask AI platform was used to determine the cutoff points for the top numerical predictors of GERD. RESULTS: In total, 441 patients (76.2% female) of a mean age of 43.7 ± 10 years were included. The ensemble model outperformed the other models. The model achieved an AUC of 0.93 (95%CI 0.88-0.99), sensitivity of 79.2% (95% CI 57.9-92.9%), and specificity of 86.1% (95%CI 70.5-95.3%). The top five ranked predictors were age, weight, preoperative GERD, size of orogastric tube, and distance of first stapler firing from the pylorus. CONCLUSION: An AI-based model for the prediction of GERD after SG was developed. The model had excellent accuracy, yet a moderate sensitivity and specificity. Further prospective multicenter trials are needed to externally validate the model developed.

S-ICD screening revisited: do passing vectors sometimes fail?

INTRODUCTION: Pre-implant ECG screening is performed to ensure that S-ICD recipients have at least one suitable sensing vector, yet cardiac over-sensing remains the commonest cause of inappropriate shock therapy in the S-ICD population. One explanation would be the presence of dynamic variations in ECG morphology that result in variations in vector eligibility. METHODS: Adult ICD patients had a 24-h ambulatory ECG performed using a digital Holter positioned to record all three S-ICD vectors. Using an S-ICD simulator, automated screening was then performed at one-minute intervals. In vectors with a mean vector score > 100 (the accepted value for a passing vector when screened on a single occasion), the percentage of all screening assessments that passed, eligible vector time (EVT), was calculated. EVT was compared statistically to QRS duration, corrected time to peak T (pTc) and mean vector score. RESULTS: Ambulatory monitoring was performed in 14 patients (mean age 63.7 ± 5.2 years, 71.4% male) with 42 vectors analysed. In 19 vectors the mean vector score was > 100. Within this "passing" cohort EVT varied between 42.7% and 100%. In 7/19 (37%) the EVT was <75%. A negative correlation was found between QRS duration and EVT (Pearson correlation -.60, p = .007). No correlation was found between EVT and mean vector score or pTc. CONCLUSION: Vector eligibility is dynamic. When "passing" vectors are subjected to repeated screening, 37% are found to be ineligible, more than a quarter of the time. Further investigation is required to determine the clinical significance of these findings.

Effect of Altitude Level on Surgical Outcomes of Laparoscopic Sleeve Gastrectomy for Patients With Morbid Obesity: A Multicentre Prospective Study.

BACKGROUND: This study aimed to evaluate the impact of altitude level on surgical outcomes of laparoscopic sleeve gastrectomy (LSG) for patients with morbid obesity. METHODS: At the normal altitude level, 808 patients underwent LSG, and 467 patients underwent LSG in high-altitude regions. The primary outcome was evaluated based on the postoperative morbidity rate. Secondary outcomes were evaluated based on operating time, mortality, hospital stay, percentage of total weight loss (TWL), and comorbidities improvement. RESULTS: No significant differences were noted in-hospital stay, time to start oral intake, gastric leakage, overall complications, and hospital mortality between the 2 groups. Deep vein thrombosis, pulmonary embolism, and mesenteric vascular occlusion were significantly higher in high altitude [11 (1.3%) vs. 14 (3%), P=0.04; 8 (0.7%) vs. 11 (2.4%), P=0.01; 4 (0.5%) vs. 8 (1.7%), P=0.03, respectively]. Patients with normal altitude recorded a better %TWL than those at high altitude after 12 months (41±9 vs. 39±9.6, P=0.002) and after 24 months (41±8 vs. 40±9, P=0.009). In both groups, a significant improvement was noted in comorbidity after LSG. CONCLUSION: The %TWL significantly achieved with LSG in normal and high altitudes. After 12 and 24 months, the %TWL is significantly higher with LSG at normal altitudes. High altitude is associated with a high incidence of deep vein thrombosis, pulmonary embolism, and superior mesenteric vascular occlusion with LSG.

Deep learning methods for screening patients' S-ICD implantation eligibility.

Subcutaneous Implantable Cardioverter-Defibrillators (S-ICDs) are used for prevention of sudden cardiac death triggered by ventricular arrhythmias. T Wave Over Sensing (TWOS) is an inherent risk with S-ICDs which can lead to inappropriate shocks. A major predictor of TWOS is a high T:R ratio (the ratio between the amplitudes of the T and R waves). Currently, patients' Electrocardiograms (ECGs) are screened over 10 s to measure the T:R ratio to determine the patients' eligibility for S-ICD implantation. Due to temporal variations in the T:R ratio, 10 s is not a long enough window to reliably determine the normal values of a patient's T:R ratio. In this paper, we develop a convolutional neural network (CNN) based model utilising phase space reconstruction matrices to predict T:R ratios from 10-second ECG segments without explicitly locating the R or T waves, thus avoiding the issue of TWOS. This tool can be used to automatically screen patients over a much longer period and provide an in-depth description of the behavior of the T:R ratio over that period. The tool can also enable much more reliable and descriptive screenings to better assess patients' eligibility for S-ICD implantation.

Lateral Extracavitary Approach Versus Posterior Extensive Circumferential Decompression in the Treatment of Complicated Thoracic and Lumbar Tuberculous Spondylitis.

OBJECTIVES AND STUDY DESIGN: The aim of this study was to retrospectively evaluate 45 patients operated upon either by posterior extensive circumferential decompression (PECD) or by the lateral extracavitary (LEC) technique and compare the clinical, radiologic, laboratory, and functional outcomes. SUMMARY OF BACKGROUND: The debate continues on the best decompression-fusion technique for treating complicated spinal tuberculosis. In recent times, the advantages of combined surgery have been successfully achieved using the 1-stage salvage technique, with enough accessibility to all 3 spinal columns. MATERIALS AND METHODS: From January 2011 to December 2013, 51 patients with complicated spinal tuberculous were surgically treated at our department. After gaining the approval of the local ethics committee, 45 patients and their records were available for evaluation. The patients were divided into 2 groups. Group I included 23 patients treated with PECD and group II included 22 patients treated with LEC. Two authors and an independent observer performed the final clinical assessment by means of clinical examination and by using the Visual Analog Scale and Oswestery Disability Index for determining pain, disability, and quality of life. The radiographs were reviewed independently by 3 authors and a radiologist for fusion, kyphotic angle, and angle loss rate. Neurological assessment using the American Spinal Injury Association motor index was performed by 2 authors and a neurologist independently. RESULTS: The mean follow-up period was 36±5.5 months. In all patients, local symptoms were relieved significantly postoperatively. There were no major complications in this series. Three patients contracted superficial wound infection and 2 developed intercostal neuralgia. Both complications resolved uneventfully and did not influence the outcome. Solid interbody fusion was diagnosed in 43 cases (95.6%). Deformity correction and neurological recovery were significantly improved in both groups (P<0.001). PECD showed better results than LEC. CONCLUSIONS: Both procedures attained good results for maintained deformity correction, bony fusion, spinal cord decompression, and neurological improvement in complicated tuberculous spondylitis. However, PECD may be superior to LEC.