Neuroprotection is a proactive approach to safeguarding the nervous system, including the brain, spinal cord, and peripheral nerves, by preventing or limiting damage to nerve cells and other components. It primarily defends the central nervous system against injury from acute and progressive neurodegenerative disorders. Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Due to its high metabolic rate and oxygen consumption, the brain is particularly vulnerable to oxidative stress. Excessive ROS damages the essential biomolecules, leading to cellular malfunction and neurodegeneration. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Understanding the impact of oxidative stress in these conditions is crucial for developing new treatment methods. Researchers are exploring using antioxidants and other molecules to mitigate oxidative stress, aiming to prevent or slow down the progression of brain diseases. By understanding the intricate interplay between oxidative stress and neurological disorders, scientists hope to pave the way for innovative therapeutic and preventive approaches, ultimately improving individuals' living standards.

Background: Opioids administered as bolus doses or continuous infusions are widely used by anesthesiologists worldwide for major and day care surgeries. Opioid-free anesthesia is a multimodal anesthesia and analgesia technique that does not use opioid drugs, thereby benefitting patients from opioid-related adverse effects. In this study, we compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. Methods: This study included 88 patients aged 18–60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with forty-four participants in each group. The opioid-free anesthesia group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas the opioid-based group was administered fentanyl with conventional general anesthesia. The primary outcome was to compare the total amount of fentanyl consumed by both groups during the 6 h postoperative period following extubation. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. Results: Both the groups had similar demographic characteristics. The opioid-free group required less postoperative analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at the sixth postoperative hour (opioid-free group 152 ± 28.2 vs. opioid group 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. Conclusions The opioid-free anesthesia technique in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in the first two hours of the postoperative period and was associated with decreased PONV.

Recurrent anterior shoulder dislocation (RASD) in cases of seizure disorders (SDs) total 50%–80% of all SD-associated shoulder instabilities. Based on the extent of bone loss, treatment options include bony and soft-tissue reconstructions, arthroplasty, and arthrodesis. The primary objective of this paper was to review the treatment options for RASD in SDs. Methods: Several bibliographic databases were searched for RASD treatment options in SD patients. The demographic outcome measures, the failure rate (defined as the relative risk of recurrence of dislocation postoperation), and the postoperative seizure recurrence rate were recorded. Results: We pooled 171 cases (187 shoulders) from 11 studies. Of these, one, five, two, two, and one reports studied Bankart’s operation with remplissage (27 cases/29 shoulders), the Latarjet procedure (106/118), bone block operation (21/23), arthroplasty (11/11), and arthrodesis (6/6), respectively, in treating SD-associated RASD. The relative risk of failure between SD and non-SD patients was 3.76 (1.3610.38) after the Latarjet operation. The failure rates were 17% and 13% for Bankart’s operation with remplissage and the Latarjet procedure in SD patients, respectively, but 0% each for bone block operation, arthroplasty, and arthrodesis. The total rate of seizure recurrence after operation was 33% of the pooled cases. Conclusions: SD recurrence in the postoperative period, the size of the bone block, and the muscular attachments to a small coracoid autograft are the determinants of failure among various reconstructive operations in SD-associated RASD. Level of evidence: III.

Introduction: Increase in the number of primary shoulder arthroplasty has led to an increase in the number of revisions which presents many complex challenges and often has inferior outcomes. Materials and methods: Data was collected retrospectively, and patients were classified using Dines classification. Comprehensive case reviews were done to identify preoperative and intra-operative challenges. The primary outcome measure was Oxford shoulder score (OSS). The secondary measures were range of motion (ROM) and patient satisfaction (very satisfied, satisfied, not satisfied or worse). Results: A total of 32 patients were identified with a mean age of 67.64 years and the most common cause of revision was a combination of bone and soft tissue failure (39.3%). All patients (n=8) with hemiarthroplasty had rotator cuff deficiency while patients with resurfacing had both rotator cuff failure and bony erosion. Four patients needed a proximal humeral osteotomy and six patients needed allograft reconstruction of the glenoid for bone loss. Twentyone shoulders were revised to reverse total shoulder arthroplasty (TSA), 2 to anatomical TSA and 5 were left with cement spacer in situ. Mean duration of follow-up was 41.6 months. Mean OSS at the last follow-up was 26.88 with statistically significant improvement in ROM. There was no statistical difference in clinical outcomes (p>0.05) based on the type of primary prosthesis or cause of revision. A total of 70% patients were pain free. Patients with infection had inferior outcomes with a mean OSS of 17. Conclusion: Management of patients with failed shoulder arthroplasty is often challenging but has good clinical outcome except in infections.

Introduction: Despite recent advances, management of distal tibial fractures is challenging, with high rate of complications. Fibula pro tibia plating technique fixes fibula and tibia together, via laterally placed fibular plate without disturbing the tibial soft tissue sleeve. We contemplated this pilot study to assess effectiveness of fibula pro tibia plating in management of distal tibia fibula fractures. Materials and methods: A total of 30 patients with distal tibia fibula fractures with fracture line extending within 5cm from tibial plafond were managed with fibula pro tibia plating, with or without minimal articular fixation. Outcome evaluation was done by union, union time, alignment and functional outcome as assessed by AOFAS score. Results: Mean age in the series was 39.4 years with male to female ratio of 3:2. Mean duration of surgery, blood loss and C arm exposure were 79 minutes (range 52 to 98min), 80ml (range 62 to 102ml) and 48 shoots (range 36 to 81 shoots), respectively. All fractures united in mean union time of 10.2 weeks (range 9 to 14 weeks) with acceptable alignment in all the patients except one. Mean AOFAS score was 86.3 (range 70 to 93) with 29 patients having good to excellent outcome. One patient had varus malunion and in one case infection was seen. Conclusion: Fibula pro tibia plating can be successfully used to manage complex distal tibia fractures which leaves the soft tissue and periosteal sleeve undisturbed, thus avoiding wound related problems and leading to early union.

Background/Aims: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. Results: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively. Conclusions Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Background: Accessory infraorbital foramen (AIOF) can change the normal course of emerging branches of the infraorbital nerve and blood vessels exiting the infraorbital foramen (IOF). This study aimed to examine the AIOF, number of foramina, and their position in relation to IOF using cone-beam computed tomography (CBCT). Methods: We performed a retrospective CBCT assessment of hospital records between January 2018 and August 2022. The CBCT of 507 patients were examined to extract information on the prevalence, number, position, linear distance from the IOF, and diameter of AIOF in relation to demographic factors. Descriptive statistics were used to evaluate the prevalence of AIOF. Mean and standard deviation were used to calculate the linear distance and diameter of the AIOF, respectively. The AIOFs, its distribution, and number were compared between sexes and sides using the chi-square test. The independent t-test and Mann–Mann-Whitney test were used to compare the mean difference between the sexes and sides. Statistical significance was set at P < 0.05. Results: In this current study, the prevalence of AIOF was 7.1% (36 of the 507 patients). Additionally, the current study examined the number of foramina using a single foramen on each side and double foramina located bilaterally at a distance from the AIOF to the IOF. The mean AIOF diameter was also studied, and the AIOF position with respect to the IOF on CBCT was superomedial or inferomedial. There were no statistically significant associations between any of the parameters assessed in this study when comparing sex and sides. Conclusions A greater number of patients with AIOF presented with a single foramen and unilateral occurrence, without a statistically significant difference. The AIOF was most commonly located superomedial to the IOF.

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established.It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction.Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.

An undifferentiated carcinoma (UC) of the gall bladder behaves aggressively and has a grave prognosis. Small cell type undifferentiated carcinoma of the gall bladder is a rare variant. This paper reports a case of UC of gall bladder with PAS-positive diastase-resistant eosinophilic hyaline globules present as liver mass (on imaging) in a male patient. The microscopic findings of the liver and gall bladder after a right tri-segmentectomy showed an un-differentiated malignant neoplasm composed of cells with round to oval nuclei, prominent nucleoli, and scanty neoplasm. No definite cell pattern was identified with these neoplastic cells. A section from the gall bladder revealed a tumor arising from the lining epithelium and infiltrating through the muscularis. This tumor was infiltrating the adherent liver tissue directly and forming a mass of undifferentiated malignant cells. The focal area within the tumor mass showed the presence of PAS-positive, diastase-resistant, eosinophilic hyaline globules within the neoplastic cells. The immunohistochemistry test was diffusely positive for perinuclear anti-neutrophil cytoplasmic antibodies and negative for chromogranin, vimentin, Desmin, alpha-fetoprotein, leukocyte common antigen, CD34, and bcl2. When the clinical and radiological data are inconclusive, careful analysis of the histological and immunophenotypic features is needed to make the final diagnosis of UC of the gall bladder. The biological behavior and prognosis of this tumor remain unclear because of its rarity. Further studies will be needed to understand the characteristics of this deadly tumor and to establish an effective therapy for it.

OBJECTIVE: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells. METHODS: Sulforhodamine B (SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide (IIIM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4',6-diamidino-2-phenylindole (DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma (EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice. RESULTS: IIIM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of IIIM-067 toward A549 cells was higher among other cancer cell lines, with a selectivity index (SI) value of 2.28. IIIM-067 demonstrated concentration- and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and 0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells (SI > 1) than the parent compound colchicine (SI = 1). IIIM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. IIIM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP (100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated 78% apoptosis at 0.4 μmol/L. IIIM-067 significantly (P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore, IIIM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition (TGI) of 67.0% at a dose of 6 mg/kg (i.p.) and a reduced mortality compared to colchicine. IIIM-067 also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68% and 44.00% at doses of 5 mg/kg (i.p.), 6 mg/kg (i.p.) and 7 mg/kg (p.o.), respectively. CONCLUSION IIIM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.
Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Reactive Oxygen Species/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Colchicine/pharmacology* ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Mammals/metabolism*