Survival Outcomes in Stage IV Gastric Cancer Patients with Krukenberg Tumors: A Systematic Review and Meta Analysis.

BACKGROUND: Stage IV gastric cancer patients with Krukenberg tumors typically exhibit poor survival outcomes, often less than 2 years. The management of this tumor subgroup remains non-standardized, and the impact of oophorectomy on survival remains uncertain. In this study, we systematically analyzed survival outcomes among gastric cancer patients with ovarian metastases who underwent standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies retrieved from MEDLINE (PubMed), Embase, and the Cochrane Library until January 25, 2024, applying the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were performed using R (v.4.3.2., Vienna). The study was registered with PROSPERO (ID-CRD42023488373). RESULTS: A total of 1502 patients from 17 retrospective studies were pooled for analysis of overall survival (OS) outcomes. The OS in the standard chemotherapy cohort, as determined by the random effects model, was 6.708 months (95% CI 3.867 to 9.548; P<0.0001), with non-significant heterogeneity (I2 = 5.5%). In the surgical resection cohort, OS was 12.786 months (95% CI 6.9 to 18.671; P<0.0001), with low heterogeneity (I2 = 0%). In the combined chemotherapy and surgical resection cohort, OS was 16.228 months (95% CI 12.254 to 20.202), with insignificant heterogeneity (I2 = 0%). CONCLUSION: This meta-analysis offers key insights into survival outcomes associated with different therapeutic modalities in gastric cancer with Krukenberg metastases. It provides valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, careful consideration of patient-centric approaches is essential in the oncological care landscape.

Iatrogenic Bladder Injury During Laparoscopic Hysterectomy: A Case Report and Discussion of Anatomic Variations.

Hysterectomy, one of the most common surgical procedures performed in women worldwide, assumes a very important role in the definitive management of diverse gynecologic conditions. This case report presents a compelling instance of an iatrogenic bladder perforation that occurred during laparoscopically assisted vaginal hysterectomy in a 47-year-old woman with a high body mass index, extensive surgical history, and postural orthostatic tachycardia syndrome. Despite considerable preoperative planning and the use of minimally invasive techniques, the occurrence of physician-induced bladder perforation highlights the significance of understanding anatomical relationships and variations. The patient's previous abdominal surgeries including two cesarean sections, appendectomy, and cholecystectomy likely contributed to scar formation and adhesions, making dissection challenging. The case report and following discussion delve into anatomical variations, as well as the diagnosis and management of iatrogenic bladder injuries. The presented case serves as a valuable addition to the literature, contributing insights into the challenges and considerations surrounding urinary tract injuries during hysterectomy. This paper aims to review current research and guide practicing obstetricians and gynecologists in the management of intraoperative bladder injuries.

Synthesis and molecular docking of some new thiazolidinone and thiadiazole derivatives as anticancer agents.

New sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF-7, HTC-116, and WI38 cells. The synthetic approach is based on the preparation of 4-(4-acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5a-e, which are converted to the corresponding thiazoldin-4-one compounds 6a-e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4-(4-acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2-cyano-3,3-bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6c and 6e exhibited strong cytotoxicity against breast cancer cells, with an IC50 (6.70±0.5 µM) and IC50 (7.51±0.8 µM), respectively, very close to that of doxorubicin (IC50: 4.17±0.2 µM). In addition, the anti-cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)-(PDB Code-1DLS). Compounds 5d, 5e, 6d, 6e, and 7 have the best binding affinity, ranging from -8.5386 kcal.mol-1 to -8.2830 kcal.mol-1.

Retrospective analysis of pediatric sepsis and the burden of antimicrobial resistance in Duhok, Kurdistan Region of Iraq.

Introduction: Sepsis is a life-threatening complication in pediatric patients. This study primarily aimed to investigate sepsis-causing bacteria and their antimicrobial resistance profile and check the change in the antimicrobial resistance trend for some selected bacteria. In addition, we evaluated the incidence of sepsis, the related mortality rate, and the effectiveness and outcome of the treatment regimes in sepsis pediatric patients. Methods: A retrospective analysis was conducted on 4-year data (2018-2021) collected from three intensive care units at the Hevi Pediatric Teaching Hospital. Sepsis screening involved clinical detection and confirmation by blood culture. Results: A total of 520 out of 1,098 (47.35%) blood samples showed positive microbial growth. A decrease in sepsis rate was observed during the COVID-19 pandemic. Coagulase-negative Staphylococci (CoNS) and Klebsiella pneumonia were the most commonly isolated bacteria. A notable variation in the antimicrobial resistance trend was observed among sepsis-causing bacteria. The empirical sepsis treatment recommended by the WHO was ineffective, as certain bacteria exhibited 100% resistance to every antibiotic tested. The mortality rate significantly increased from 1.3% in 2018 to 16.5% in 2021. Discussion: The antimicrobial resistance profile of sepsis causing bacteria is of concerns, indicating a potentially serious situation. Thus, to avoid treatment failure, the monitoring of antimicrobial resistance in pediatric patients is essential.

Capsaicin ameliorate pulmonary fibrosis via antioxidant Nrf-2/ PPAR- γ pathway activation and inflammatory TGF-ß1/ NF-κB/COX II pathway inhibition.

Bleomycin is an effective antibiotic with a significant anticancer properties, but its use is limited due to its potential to induce dose-dependent pulmonary fibrosis. Therefore, this study aimed to assess the therapeutic potential of Capsaicin as an additional treatment to enhance patient tolerance to Bleomycin compared to the antifibrotic drug Pirfenidone. Pulmonary fibrosis was induced in rats through by a single intratracheal Bleomycin administration in day zero, followed by either Capsaicin or Pirfenidone treatment for 7 days. After the animals were sacrificed, their lungs were dissected and examined using various stains for macroscopic and histopathological evaluation. Additionally, the study assessed various antioxidant, anti-inflammatory, and antifibrotic parameters were assessed. Rats exposed to Bleomycin exhibited visible signs of fibrosis, histopathological alterations, increased collagen deposition, and elevated mucin content. Bleomycin also led to heightened increased inflammatory cells infiltration in the bronchoalveolar lavage, elevated fibrosis biomarkers such as hydroxyproline, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-ß1), increased inflammatory markers including tumor necrosis factor-alpha (TNF-α), interlukine-6 (Il-6), interlukine-1ß (Il-1ß) nuclear factor-kappa B (NF-κB), and Cyclooxygenase-2 (COX-2), and transforming growth factor-beta (TGF-ß1),. Furthermore, it reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), increased oxidative stress biomarkers like nitric oxide (NO), malondialdehyde (MDA), myeloperoxidase (MPO) and protein carbonyl. Bleomycin also decreased the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), reduced glutathione (GSH), total antioxidant capacity, and the activities of catalase and superoxide dismutase (SOD). Treating the animals with Capsaicin and Pirfenidone following Bleomycin exposure resulted in improved lung macroscopic and microscopic characteristics, reduced collagen deposition (collagen I and collagen III) and mucin content, decreased inflammatory cell infiltration, lowered levels of hydroxyproline, α-SMA, and TGF-ß1, decreased TNF-α, Il-6, Il-1ß, NF-κB, and COX-2, increased PPAR-γ and Nrf-2 expression, and improvement improved in all oxidative stress biomarkers. In summary, Capsaicin demonstrates significant antifibrotic activity against Bleomycin-induced lung injury that may be attributed, at least in part, to the antioxidant and anti-inflammatory activities of Capsaicin mediated by upregulation of PPAR-γ and Nrf-2 expression and decreasing. TGF-ß1, NF-κB and COX II proteins concentrations.

SYNTHESIS OF SOME NOVEL THIOPHENE ANALOGUES AS POTENTIAL ANTICANCER AGENTS.

The aim of this study involves the synthesis novel thiophene analogues that can be used as anticancer medications through a strategic multicomponent reaction connecting ethyl 4-chloroacetoacetate (1), phenyl isothiocyanate, and a series of active methylene reagents, including ethyl acetoacetate (2), malononitrile, ethyl cyanoacetate, cyanoacetamide 6a-c, N-phenyl cyanoacetamide derivatives 13a-c, and acetoacetanilide derivatives 18. This reaction was facilitated by dry dimethylformamide with a catalytic quantity of K2CO3. The resultant thiophene derivatives were identified as 4, 8a-b, 9, 12a-d, 15a-c, and 20a-b. Further reaction of compound 4 with hydrazine hydrate yielded derivative 5, respectively. When compound 1 was refluxed with ethyl 3-mercapto-3-(phenylamino)-2-(p-substituted phenyldiazenyl)acrylate 10a-e in the presence of sodium ethoxide, it produced thiophene derivatives 12a-d. Comprehensive structural elucidation of these newly synthesized thiophene-analogues was accomplished via elemental and spectral analysis data. Furthermore, the study delves into the cytotoxicity of the newly synthesized thiophenes was evaluated using the HepG2, A2780, and A2780CP cell lines. The amino-thiophene derivative 15b exhibited an increased growth inhibition of A2780, and A2780CP with IC50 values 12±0.17, and 10±0.15 µM, respectively compared to Sorafenib with IC50 values 7.5±0.54 and 9.4±0.14. This research opens new avenues for developing thiophene-based anticancer agents.

Systematic review and pooled analysis of the impact of treatment-induced lymphopenia on survival of glioblastoma patients.

PURPOSE/OBJECTIVE(S): Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT). MATERIALS/METHODS: Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS. RESULTS: Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies. CONCLUSION: These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions.

BACKGROUND: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion. OBJECTIVE: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions. METHODS: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways. RESULTS: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments. CONCLUSION: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.

Classification of cancer types based on microRNA expression using a hybrid radial basis function and particle swarm optimization algorithm.

The diagnosis and treatment of cancer is one of the most challenging aspects of the medical profession, despite advances in disease diagnosis. MicroRNAs are small noncoding RNA molecules involved in regulating gene expression and are associated with several cancer types. Therefore, the analysis of microRNA data has become one of the most important areas of cancer research in recent years. This paper presents an improved method for cancer-type classification based on microRNA expression data using a hybrid radial basis function (RBF) and particle swarm optimization (PSO) algorithm. Two datasets containing microRNA information were used, and preprocessing and normalization operations were performed on the raw data. Feature selection was carried out by using the PSO algorithm, which can identify the most relevant and informative features in the data along with helping to prioritize them. Using a PSO algorithm for feature selection is an effective approach to microRNA analysis. This enhances the accuracy and reliability of cancer-type classifications based on microRNA expression data. In the proposed method, we, respectively, achieved an accuracy of 0.95% and 0.91% on both datasets, with an average of 0.93%, using an improved RBF neural network classifier. These results demonstrate that the proposed method outperforms previous works. RESEARCH HIGHLIGHTS: To enhance the accuracy of cancer-type classifications based on microRNA expression data. We present a minimal feature selection method using particle swarm optimization to reduce computational load & radial basis function to improve accuracy.

Evaluation of pharmacokinetic pharmacodynamic target attainment of meropenem in pediatric patients.

BACKGROUND: Meropenem is a widely used carbapenem for treating severe pediatric infections. However, few studies have assessed its pharmacokinetics/pharmacodynamics (PK/PD) in pediatric patients. This study aimed to evaluate the proportion of Saudi pediatric patients achieving the PK/PD target of meropenem. METHODS: A prospective observational study was conducted at King Saud University Medical City from July to September 2022. Pediatric patients receiving meropenem for suspected or proven infections were included in the study. The primary outcome was the percentage of patients achieving the recommended PK/PD target for critically ill or non-critically ill pediatric patients. RESULTS: The study included 30 patients (nine neonates and 21 older pediatric patients). All neonates were critically ill. Among them, 55 % achieved the PK/PD target of 100 % free time above the MIC. In older ICU pediatric patients, only 11 % attained this target, whereas 58 % of older pediatrics in the general wards achieved the PK/PD target of 50 % free time above the MIC. Augmented renal clearance (ARC) was identified in 57 % of our pediatric patient population, none of whom achieved the recommended PK/PD targets. The median trough concentrations in patients with and without ARC were 0.75 and 1.3 µg/mL, respectively (P < 0.05). CONCLUSIONS: The majority of patients in our cohort did not achieve the PK/PD target for meropenem. ARC emerged as a major risk factor for target attainment failure in both critically ill and non-critically ill pediatric patients.

Synthesis biological evaluation and molecular docking of isatin hybrids as anti-cancer and anti-microbial agents.

Isatin, known as 1H-indole-2,3-dione, was originally recognised as a synthetic molecule until its discovery in the fruits of the cannonball tree, Couroupita guianensis. It is naturally occurring in plants of the genus Isatis and serves as a metabolic derivative of adrenaline in humans. Isatin possesses significant pharmacological importance, and its synthetic versatility has prompted extensive interest in its derivative compounds due to their diverse biological and pharmacological properties. These derivatives represent a valuable class of heterocyclic compounds with potential applications as precursors for synthesizing numerous valuable drugs. In the pursuit of advancing our research on isatin hybrids, we investigate the utilisation of readily available hydrazonoindolin-2-one and isatin as starting materials for the synthesis of a wide range of analogues. Characterisation of the synthesized compounds was carried out through various analytical techniques. Furthermore, the obtained compounds were subjected to extensive testing to evaluate their anticancer and antimicrobial activities. Specifically, their efficacy against key proteins, namely Staphylococcus aureus protein (PDB ID: 1JIJ), Escherichia coli protein (PDB ID: 1T9U), Pseudomonas aeruginosa protein (PDB ID: 2UV0), and Acinetobacter baumannii protein (PDB ID: 4HKG), was examined through molecular docking calculations. Several molecules, such as 3, 4, 6, 16, and 19, displayed remarkable activity against the renal cancer cell line UO-31. Additionally, the results of antimicrobial activity testing revealed that compound 16 exhibited significant cytotoxicity against Candida albicans and Cryptococcus neoformans. Subsequently, ADME/T calculations were performed to gain insights into the potential effects and reactions of these molecules within human metabolism. This comprehensive study provides valuable insights into the potential pharmacological applications of isatin derivatives and underscores their significance in drug development.

Investigating the association between asthma and opioid use disorder with interactions of anxiety and depression among a national sample of the US population.

INTRODUCTION: Previous studies have not examined the association between asthma and opioid use disorder (OUD) in a comprehensive national sample of the U.S. population. This study aims to investigate such an association. METHODS: This is a matched retrospective cohort study, with a follow-up period of two years, utilizing longitudinal electronic medical records of a comprehensive national healthcare database in the U.S.-Cerner-Real World DataTM. Patients selected for analysis were ≥12 years old with a hospital encounter between January 2000 and June 2020. Adjusted risk ratios (aRRs) of incident OUD for those with asthma compared to those without asthma were calculated using a modified Poisson regressions with robust standard errors via the Huber-White sandwich estimator, and results were stratified by comorbid mental illnesses. RESULTS: Individuals with asthma had a greater risk of OUD compared to those without asthma (aRR = 2.12; 95% CI 2.03-2.23). When stratified by anxiety and depression status, individuals with asthma and no anxiety or depression had a greater risk of incident OUD compared to individuals with asthma and either anxiety, depression, or both. Additionally, individuals with asthma medication had 1.29 (95% CI: 1.24, 1.35) greater overall risk for incident OUD compared to those without medication. Independent of comorbid mental illnesses, individuals with asthma medication had greater risk for incident OUD compared to those without medication among individuals without severe/obstructive asthma. CONCLUSIONS: Individuals with asthma face a higher OUD risk compared to those without asthma. Comorbid mental illnesses modulate this risk. Caution is advised in opioid prescribing for asthma patients.

Outcomes of Arthroscopic Joint Preservation Techniques for Chondral Lesions in the Hip: An Updated Systematic Review.

PURPOSE: To systematically review outcomes of joint preservation procedures for chondral lesions of the hip through analysis of survival rates and patient-reported outcomes (PROs). METHODS: A literature search from 2018 to May 2023 was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in 3 databases: PubMed, Embase, and Google Scholar. Studies were included if they reported on outcomes of patients undergoing hip arthroscopy for the treatment of chondral lesions of the hip joint and if there were quantifiable postoperative outcome measures. Quality assessment was completed using the Methodological Index for Non-Randomized Studies criteria. RESULTS: Twenty-seven studies were included, with 20 noncomparative and 7 comparative studies. Microfracture (MFx) was the most common procedure, reported in 17 studies. Other procedures include autologous chondrocyte transplantation (ACT) (5 studies), autologous matrix-induced chondrogenesis (AMIC) (3 studies), and MFx in conjunction with CarGel (3 studies). Seven other novel procedures were reported in individual separate studies. Survival rates, defined by no revision surgery or conversion to total hip arthroscopy (THA) at latest follow-up, for MFx (14 studies), AMIC (3 studies), and MFx in conjunction with CarGel (3 studies) ranged from 59.1% to 100%, 92.9% to 100%, and 94.4% to 95.7%, respectively. Survival rates of ACT, biological reconstruction, debridement and abrasion, microfragmented autologous adipose tissue transplantation, and ChondroFiller gel were all reported once in separate studies with rates of 100%, 100%, 85.4%, 100%, and 92.3%, respectively. All studies included PROs, most reporting statistically significant improvements (P < .05) at the latest follow-up. CONCLUSIONS: Isolated MFx remained the most commonly performed technique, but with lower survival and higher conversion to THA rates than in studies before 2018. Novel techniques that were performed in conjunction with MFx or that avoided MFx altogether had higher overall survival rates despite being minimally performed. Most patients across all techniques demonstrated significant improvements in PROs. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

The flavonoid luteolin reduces mutant huntingtin aggregation and cytotoxicity in huntingtin-mutated neuroblastoma cells.

Background: Huntington's disease is an inherited progressive neurodegenerative disorder caused by an expansion of the polyglutamine tract leading to malformation and aggregation of the mutant huntingtin protein in the cell cytoplasm and nucleus of affected brain regions. The development of neuroprotective agents from plants has received considerable research attention. Objective: Our study aims to investigate the neuroprotective effects of luteolin and the mechanisms that underline its potential mediated protection in the mutant htt neuroblastoma cells. Methods: The mutant htt neuroblastoma cells were transfected with 160Q, and the control wild-type neuroblastoma cells were transfected with 20Q htt for 24 h and later treated with luteolin. Cell viability was determined by MTT and PI staining in both groups, while western blotting was used to evaluate caspase 3 protein expression. Aggregation formation was assessed via immunofluorescence microscopy. Also, western blotting was utilized to measure the protein expression of mutant htt aggregated and soluble protein, Nrf2 and HO-1. The impact of Nrf2 on luteolin-treated neuroblastoma cells was assessed using small interfering RNAs. Results: Our study reports that luteolin can protect cultured cells from mutant huntingtin cytotoxicity, evidenced by increased viability and decreased apoptosis. Also, luteolin reduced the accumulation of soluble and insoluble mutant huntingtin aggregates in mutant htt neuroblastoma cells transfected with 160Q compared to the control wild-type. The mutant htt aggregate reduction mediated by luteolin appeared to be independent of the Nrf2 -HO-1 antioxidant pathway. Conclusion: Luteolin presents a new potential therapeutic and protective agent for the treatment and decreasing the cytotoxicity in neurodegenerative diseases such as Huntington's disease.

Detection of Clostridium difficile among diarrheic children using cultural and polymerase chain reaction technique.

INTRODUCTION: Clostridium difficile is the most common cause of antibiotic-associated diarrhea and colitis. Several methods are available for the detection of C. difficile in stool samples. This study aimed to use glutamate dehydrogenase (GDH), toxin detection, culture and polymerase chain reaction (PCR) techniques for the diagnosis of this pathogen. METHODOLOGY: A total of 300 stool samples were collected from children with hospital acquired diarrhea (HA-D), community acquired diarrhea (CA-D), and hospitalized non-diarrheic children as control with ages ranging from 6 months to 6 years (mean 3.7 ± 1.7). Each stool sample was divided into two parts; one part was tested for the enzyme GDH, toxin A and B and then cultured on selective media; and the other part for direct DNA extraction. RESULTS: From a total of 300 stool samples, 9 (3.0%) were positive for C. difficile by the PCR technique, 7 (7%) samples of which were from HA-D cases and 2 (2.0%) from CA-D cases; the control group samples were negative. The enzyme GDH was detected in 12 (12%) samples and toxins A and B in 8 (8%) samples from HA-D cases compared to 5 (5%) and 2 (2%), respectively from CA-D cases. Both GDH and the toxins were negative in control samples. Only 19 (19.0%) samples from HA-D cases gave suspected growth and all of these were negative by PCR. CONCLUSIONS: Based on the results of this study, we conclude that the PCR technique is the only reliable method for the diagnosis of this pathogen.

Early pigment spot segmentation and classification from iris cellular image analysis with explainable deep learning and multiclass support vector machine.

Globally, retinal disorders impact thousands of individuals. Early diagnosis and treatment of these anomalies might halt their development and prevent many people from developing preventable blindness. Iris spot segmentation is critical due to acquiring iris cellular images that suffer from the off-angle iris, noise, and specular reflection. Most currently used iris segmentation techniques are based on edge data and noncellular images. The size of the pigment patches on the surface of the iris increases with eye syndrome. In addition, iris images taken in uncooperative settings frequently have negative noise, making it difficult to segment them precisely. The traditional diagnosis processes are costly and time consuming since they require highly qualified personnel and have strict environments. This paper presents an explainable deep learning model integrated with a multiclass support vector machine to analyze iris cellular images for early pigment spot segmentation and classification. Three benchmark datasets MILE, UPOL, and Eyes SUB were used in the experiments to test the proposed methodology. The experimental results are compared on standard metrics, demonstrating that the proposed model outperformed the methods reported in the literature regarding classification errors. Additionally, it is observed that the proposed parameters are highly effective in locating the micro pigment spots on the iris surfaces.

Prevalence of GCKR rs1260326 Variant in Subjects with Obesity Associated NAFLD and T2DM: A Case-Control Study in South Punjab, Pakistan.

The glucokinase regulatory protein (GCKR) regulates glycogen metabolism and insulin secretion, and the GCKR rs1260326 is a putative single nucleotide polymorphism (SNP) associated with metabolic disorders including nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study was conducted to investigate the genetic association of the GCKR rs1260326 in NAFLD and T2DM in our population. NAFLD (n = 103), T2DM (n = 100), and control (n = 100) samples were collected and genotyped for GCKR rs1260326 by tetra-arm PCR. The genetic variant GCKR rs1260326 was significantly linked with NAFLD and T2DM, while the GCKR rs1260326 was significantly associated with the progression of obesity only in NAFLD subjects. The frequency of the C allele (mutant) was higher in both NAFLD (f = 0.69) and T2DM (f = 0.66) subjects as compared to healthy controls of NAFLD (0.52) and T2DM (f = 0.32). The frequency of the C allele was also positively linked with the progression of obesity in both diseases. The frequency of the C allele was 0.66, 0.67, and 0.74 in NAFLD normal weight, overweight, and obese subjects, respectively, while the frequency of the C allele was 0.60, 0.60, and 0.74 in T2DM in normal weight, overweight, and obese subjects, respectively. Homozygous mutant (CC) was 53% in both NAFLD and T2DM subjects, while heterozygous mutant (CT) was 15.53% in NAFLD and 22% in T2DM subjects. Wild-type allele (TT) was 31.06% in NAFLD and 25% in T2DM subjects. In conclusion, the GCKR rs1260326 is a highly prevalent SNP in NAFLD and T2DM subjects, which possibly contributed to obesity, insulin resistance, and metabolic disorders in our population.

Mid- to Long-Term Outcomes of Arthroscopic Shoulder Stabilization in Athletes: A Systematic Review.

There exists a considerable amount of evidence regarding short-term outcomes of shoulder arthroscopy in athletes; however, mid- to long-term data are limited. Therefore, the purpose of this review is to evaluate studies assessing mid- to long-term outcomes and rates of return to sport in athletes undergoing primary shoulder arthroscopy. A search for the systematic review was performed in PubMed, Scopus, and Embase on 14 March 2023. Study parameters, as well as their respective outcomes, were described in detail and compiled into diagrams. Five studies were included, which contained data on a total of 307 shoulders in patients with mean ages ranging from 20.3 to 26.9 years and mean follow-up times ranging from 6.3 to 14 years. The arthroscopic Bankart repair was the primary surgical intervention performed in all five studies. The overall rate of return to sport was 84% (range, 70-100%) across the studies. The rate of return to sport at pre-injury level was 65.2% (range, 40-82.6%) across four studies. The overall rate of recurrent instability was 17.3%, with redislocation specifically occurring in 13.7% of patients across all studies. The overall rate of revision surgery was 11.1%. Athletes who underwent primary shoulder arthroscopy demonstrated favorable outcomes and a high rate of RTS at a minimum follow-up of 5 years. However, rates of recurrent instability, redislocation, and revision surgery occurred at less than favorable numbers, which emphasizes the importance of proper patient selection when considering candidates for arthroscopic versus open repairs.

Antimicrobial and antioxidant potential of the silver nanoparticles synthesized using aqueous extracts of coconut meat (Cocos nucifera L).

Human pathogenic fungi and bacteria pose a huge threat to human life, accounting for high rates of mortality every year. Unfortunately, the past few years have seen an upsurge in multidrug resistance pathogens. Consequently, finding an effective alternative antimicrobial agent is of utmost importance. Hence, this study aimed to phytofabricate silver nanoparticles (AgNPs) using aqueous extracts of the solid endosperm of Cocos nucifera L, also known as coconut meat (Cm). Green synthesis is a facile, cost-effective and eco-friendly methods which has several benefits over other physical and chemical methods. The synthesized nanoparticles were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Cm-AgNPs showed a UV-Vis peak at 435 nm and were crystalline and quasi-spherical, with an average size of 15 nm. The FTIR spectrum displayed functional groups of phenols, alkaloids, sugars, amines, and carbonyl compounds, which are vital in the reduction and capping of NPs. The antibacterial and anticandidal efficacy of the Cm-AgNPs was assessed by the agar-well diffusion method and expressed as a zone of inhibition (ZOI). Amongst all the test isolates, Staphylococcus epidermidis, Candida auris, and methicillin-resistant Staphylococcus epidermidis were more susceptible to the NPs with a ZOI of 26.33 ± 0.57 mm, 19.33 ± 0.57 mm, and 18 ± 0.76 mm. The MIC and MFC values for Candida spp. were higher than the bacterial test isolates. Scanning electron microscopic studies of all the test isolates at their MIC concentrations showed drastically altered cell morphology, indicating that the NPs could successfully cross the cell barrier and damage the cell integrity, causing cell death. This study reports the efficacy of Cm-AgNPs against several Candida and bacterial strains, which had not been reported in earlier studies. Furthermore, the synthesized AgNPs exhibited significant antioxidant activity. Thus, the findings of this study strongly imply that the Cm-AgNPs can serve as promising candidates for therapeutic applications, especially against multidrug-resistant isolates of Candida and bacteria. However, further investigation is needed to understand the mode of action and biosafety.