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1.
Br J Radiol ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254598

ABSTRACT

INTRODUCTION: Fluoroscopic guided procedures are a mainstay for Interventional Radiology (IR) procedures. Practice is needed for the novice to interpret fluoroscopic images and simultaneously perform the procedure hands-on as well as control the foot pedal to screen. We describe the development of a training simulation model which simulates the human kidney, ureter and bladder. METHOD: Stereolithography (SLA) 3D Print technology using SLA resin and Anycubic SLA printer were employed. A plastic tubing was used to connect the 3D printed kidney and bladder as the ureter. This simulation model permits fluoroscopic guided filling of "pelvicalyceal system" with contrast as well as ureteric stenting, guidewire and drainage catheter manipulation. Effectiveness of the model to attain skills for nephrostomy exchange and ureteric stenting was obtained via questionnaire from trainees prior to and after utilising the model. RESULT: The 3D printing simulation model of the kidney, ureter and bladder system enable trainees to perform nephrostomy exchange, nephrostogram and antegrade stenting. Participants felt more confident to perform the procedures as they were more familiar with the procedure. Besides that, participants felt their wire and catheter manipulation skills have improved after using the simulation model. CONCLUSION: Neph-ex simulation model is safe and effective for hands-on training in improving proficiency of fluoroscopy-guided nephrostomy exchange and antegrade ureteric stenting.

2.
Front Chem ; 12: 1358353, 2024.
Article in English | MEDLINE | ID: mdl-39165336

ABSTRACT

An electrochemical nitrite sensor probe is introduced herein using a modified flat glassy carbon electrode (GCE) and SrTiO3 material doped with spherical-shaped gold nanoparticles (Au-NPs) and polypyrrole carbon (PPyC) at a pH of 7.0 in a phosphate buffer solution. The nanocomposites (NCs) containing Au-NPs, PPyC, and SrTiO3 were synthesized by ultrasonication, and their properties were thoroughly characterized through structural, elemental, optical, and morphological analyses with various conventional spectroscopic methods, such as field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller method. The peak currents due to nitrite oxidation were characterized in detail and analyzed using conventional cyclic voltammetry (CV) as well as differential pulse voltammetry (DPV) under ambient conditions. The sensor response increased significantly from 0.15 to 1.5 mM of nitrite ions, and the sensor was fabricated by coating a conducting agent (PEDOT:PSS) on the GCE to obtain the Au-NPs/PPyC/SrTiO3 NCs/PEDOT:PSS/GCE probe. The sensor's sensitivity was determined as 0.5 µA/µM∙cm2 from the ratio of the slope of the linear detection range by considering the active surface area (0.0316 cm2) of the flat GCE. In addition, the limit of detection was determined as 20.00 ± 1.00 µM, which was found to be satisfactory. The sensor's stability, pH optimization, and reliability were also evaluated in these analyses. Overall, the sensor results were found to be satisfactory. Real environmental samples were then analyzed to evaluate the sensor's reliability through DPV, and the results showed that the proposed novel electrochemical sensor holds great promise for mitigating water contamination in the real samples with the lab-made Au-NPs/PPyC/SrTiO3 NC. Thus, this study provides valuable insights for improving sensors for broad environmental monitoring applications using the electrochemical approach.

3.
Braz J Biol ; 84: e284361, 2024.
Article in English | MEDLINE | ID: mdl-39140507

ABSTRACT

Coronary Artery Disease (CAD) is a global health concern, with diagnostic modalities and risk factors that exhibit regional variations. This study, conducted at the Islamabad Diagnostic Center, Pakistan, aimed to provide a comprehensive assessment of CAD prevalence, severity, and associated risk factors, while also evaluating the diagnostic accuracy of Computed Tomography Coronary Test (CTT) and Exercise Treadmill Test (ETT) in a cohort of 2909 patients. Among the patients assessed via CT Coronary scans, CAD was universally observed, presenting with varying degrees of severity. Our findings indicated that 24.5% of patients had mild CAD, 28.6% exhibited mild to moderate CAD, 16.3% were diagnosed with moderate CAD, 18.4% demonstrated moderate to severe CAD, and 20.4% displayed severe CAD. This spectrum underscores the diverse nature of CAD within the study population. In addition to CTT, we conducted a detailed evaluation of ETT results in 49 patients. These results revealed that 55.1% of patients tested positive for ischemia during the exercise test, emphasizing the prevalence of cardiac stress and underlying CAD. Conversely, 32.7% of patients exhibited negative ETT results, indicating favorable cardiac tolerance during physical activity. A subset of patients yielded non-diagnostic or inconclusive results, necessitating further clinical assessment. Disease history analysis showed a dichotomy within the cohort, with 20.4% having a known medical history and 79.6% possessing an unknown disease history, highlighting the importance of comprehensive medical records in clinical practice. Hypertension, a critical cardiovascular risk factor, was identified in 87.8% of patients, underscoring its significance. Smoking history displayed notable variation, with 69.4% categorized as smokers, 14.3% as ex-smokers, and 10.2% as non-smokers. Lipid profile analysis indicated that 69.4% of patients had abnormal lipid levels. To assess the diagnostic accuracy of CTT and ETT, we calculated Positive Predictive Values (PPV) and Negative Predictive Values (NPV). CTT exhibited a PPV of approximately 5.99% and an NPV of approximately 4.40%, whereas ETT displayed a higher PPV of around 26.44% and a substantially higher NPV of about 49.24%. This study offers valuable insights into CAD prevalence, severity, and associated risk factors in a Pakistani cohort, emphasizing the importance of holistic risk assessment and tailored interventions in clinical practice. Our findings also highlight the diagnostic utility of ETT in CAD assessment.


Subject(s)
Coronary Artery Disease , Exercise Test , Humans , Exercise Test/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Pakistan/epidemiology , Male , Female , Middle Aged , Adult , Risk Factors , Aged , Prevalence , Severity of Illness Index , Tomography, X-Ray Computed , Coronary Angiography
4.
J Biopharm Stat ; : 1-26, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38984691

ABSTRACT

Recently, interest has grown in the development of dose-finding methods that consider both toxicity and efficacy as endpoints. Along with responses on these, the incorporation of pharmacokinetic (PK) data can be beneficial in terms of patients' safety and can also increase the efficiency of the design for finding the best dose for the next phase. In this paper, the maximum concentration (Cmax) is used as the PK measure guiding the dose selection. The ethically attractive approach, which is based on the probability of efficacy, is used as a dose optimisation criterion. At each stage of an adaptive trial, that dose is selected for which the criterion is maximised, subject to the constraints imposed on the Cmax and the probability of toxicity. The inter-patient variability of the PK model parameters is considered, and population D-optimal sampling time points for measuring the concentration of a drug in the blood are calculated. The method is illustrated with a one-compartment PK model with first-order absorption, with the parameters being assumed to be random. The Cox model for bivariate binary responses is employed to model the dose-response outcomes. The results of a simulation study for several plausible dose-response scenarios show a significant gain in the efficiency of the design, as well as a reduction in the proportion of toxic responses.

6.
Mymensingh Med J ; 33(3): 840-847, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38944730

ABSTRACT

Multiple myeloma (MM), mature B-cell lineage neoplasm, is characterized by abnormal clonal proliferation of plasma cells and presence of monoclonal protein (M protein). The study was conducted to reveal presenting features, laboratory findings, Eastern Cooperative Oncology Group (ECOG) performance status and skeletal survey on patients with multiple myeloma. This descriptive, cross-sectional study was carried out in the Department of Haematology, Dhaka Medical College Hospital, Dhaka, Bangladesh from January 2019 to July 2020 with a sample size of 81. Data were collected in a case record form after obtaining informed verbal consent from patients and /or their legal guardians. Relevant ethical issues and data quality assurance were taken into consideration. Data were analyzed with SPSS, Version 25.0 with presentation in figures and tables with frequency, percentage, mean and standard deviation based on data nature. Statistical tests were carried out as appropriate with 5.0% level of significance for assessing statistical association. Mean age of the patients was 58.9±12.0 years. Male female ratio was 2:1. 35(43.2%) patients were smokers with only 2(2.5%) had family history of haematological malignancies. Bone pain (72.8%) was the most common presenting feature, while hypertension (59.1%), diabetes mellitus (29.5%), respiratory illness (11.3%) and cardiac disease (11.4%) were the common co-morbidities. Most common ECOG performance status was ECOG-1(48.1%). Mean haemoglobin (Hb) was 9.4±2.3gm/dl and mean erythrocyte sedimentation rate (ESR) was 89.5±42.1 mm in 1st hour. Mean serum creatinine level was 2.0±1.85 mg/dl and ≥2.0mg/dl in 42(34.2%). Among 50 documentation serum lactate dehydrogenase (LDH) was raised in 18(36.0%). Mean serum calcium level was 9.6±1.8mg/dl >11.0mg/dL in 10(14.5%) cases. Serum albumin <3.5gm/dl in 37(49.3%), ß2-microglobulin >5.5mg/dl in 37(57.8%) cases, International staging system (ISS) stage III was in 59.4% and Bence Jones Protein (BJP) was present in 46.7% cases. Lytic lesions were present in 75.0%, In 38(74.5%) patients vertebrae were involved, while in 18(35.2%) ribs were involved, in 14(27.5%) patients skull was involved and in 3(5.9%) patients involved bones were femur, humerus, sternum and scapula. Mean plasma cells percentage was 62.1±24.9%. Immuno-Fixation Electrophoresis (IFE) revealed IgG (72.7%), IgA (18.2%), Free light chain (FLC) (9.1%). FLC ratio was ≥100 in 29.0% cases. Significant statistical association was observed between serum creatinine with Hb concentration (p<0.05), serum creatinine level with ISS staging (p<0.05) and serum calcium level (p<0/05), while insignificant association was revealed between BJP present status and serum creatinine level (p>0.05). Bone pain, fatigue, fever and neurological impairment were the common presenting features. Anaemia, renal impairment and skeletal lytic events were the prominent physical findings. ISS staging was statistically associated with serum creatinine level, while serum calcium level was associated with serum creatinine and lytic lesions.


Subject(s)
Multiple Myeloma , Tertiary Care Centers , Humans , Multiple Myeloma/complications , Multiple Myeloma/blood , Multiple Myeloma/pathology , Multiple Myeloma/epidemiology , Male , Female , Middle Aged , Cross-Sectional Studies , Aged , Bangladesh/epidemiology , Adult
7.
Mymensingh Med J ; 33(3): 671-676, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38944705

ABSTRACT

In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.


Subject(s)
Antifungal Agents , Candida , Candidemia , Intensive Care Units , Microbial Sensitivity Tests , Humans , Bangladesh/epidemiology , Candidemia/epidemiology , Candidemia/microbiology , Candidemia/drug therapy , Cross-Sectional Studies , Female , Male , Candida/isolation & purification , Candida/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Infant, Newborn , Adult , Drug Resistance, Fungal
8.
Int J Biol Macromol ; 273(Pt 1): 133030, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38857730

ABSTRACT

Skin wound healing and regeneration is very challenging across the world as simple or acute wounds can be transformed into chronic wounds or ulcers due to foreign body invasion, or diseases like diabetes or cancer. The study was designed to develop a novel bioactive scaffold, by loading aloesin to chitosan-coated cellulose scaffold, to cure full-thickness skin wounds. The physiochemical characterization of the scaffold was carried out using scanning electron microscopy (SEM) facilitated by energy-dispersive spectrophotometer (EDS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The results indicated the successful coating of chitosan and aloesin on cellulose without any physical damage. The drug release kinetics confirmed the sustained release of aloesin by showing a cumulative release of up to 88 % over 24 h. The biocompatibility of the aloesin-loaded chitosan/cellulose (AlCsCFp) scaffold was evaluated by the WST-8 assay that confirmed the significantly increased adherence and proliferation of fibroblasts on the AlCsCFp scaffold. The in vivo wound healing study showed that both 0.05 % and 0.025 % AlCsCFp scaffolds have significantly higher wound closure rates (i.e. 88.2 % and 95.6 % approximately) as compared to other groups. This showed that novel composite scaffold has a wound healing ability. Furthermore, histological and gene expression analysis demonstrated that the scaffold also induced cell migration, angiogenesis, re-epithelialization, collagen deposition, and tissue granulation formation. Thus, it is concluded that the aloesin-loaded chitosan/cellulose-based scaffold has great therapeutic potential for being used in wound healing applications in the clinical setting in the future.


Subject(s)
Cellulose , Chitosan , Regeneration , Skin , Tissue Scaffolds , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Cellulose/chemistry , Cellulose/pharmacology , Wound Healing/drug effects , Skin/drug effects , Animals , Tissue Scaffolds/chemistry , Regeneration/drug effects , Rats , Fibroblasts/drug effects , Mice , Cell Proliferation/drug effects , Drug Liberation , Male , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
9.
Des Monomers Polym ; 27(1): 35-50, 2024.
Article in English | MEDLINE | ID: mdl-38903406

ABSTRACT

The C3-symmetry ionic polymer PPyTri has been designed with multi-walled carbon nanotubes (MWCNTs) or graphene nanoplatelets (GNPs) and studied as an ultrasensitive electrochemical sensor for trace Hg(II) detection. The synthesis approach incorporated attaching three pyridinium cationic components with chloride anions to the triazine core. The precursors, BPy, were synthesized using a condensation process involving 4-pyridine carboxaldehyde and focused nicotinic hydrazide. The polymer PPyTri was further modified with either MWCNTs or GNPs. The resulting ionic polymer PPyTri and its fabricated nanocomposites were characterized using infrared (IR), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and powder X-ray diffraction (XRD). The analysis revealed that both the polymer and its nanocomposites have semi-crystalline structures. The electroactivity of the designed nanocomposites toward Hg + 2 ions revealed that among the nanocomposites and bare copolymer, the glassy carbon electrode (GCE) adapted with the PPyTri GNPs-5% exhibited the greatest current response over a wide range of Hg + 2 concentrations. The nanocomposite-modified electrode presented an excellent sensitivity of 83.33 µAµM - 1 cm - 2, a low detection limit of 0.033 nM, and a linear dynamic range of 0.1 nM to 0.01 mM (R2 = 0.9945).

11.
J Contam Hydrol ; 265: 104379, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38851130

ABSTRACT

During the past decades, microplastics (MPs) have become an emerging concern due to their persistence and potential environmental threat. MP pollution has become so drastic that it has been found in the human food chain, breast milk, polar regions, and even the Himalayan basin, lake, etc. Inflammation, pulmonary hypertension, vascular occlusions, increased coagulability and blood cell cytotoxicity, disruption of immune function, neurotoxicity, and neurodegenerative diseases can all be brought on by severe microplastic exposure. Although many MPs studies have been performed on single environmental compartments, MPs in multi-environmental compartments have yet to be explored fully. This review aims to summarize the muti-environmental media, detection tools, and global management scenarios of MPs. The study revealed that MPs could significantly alter C flow through the soil-plant system, the structure and metabolic status of the microbial community, soil pH value, biomass of plant shoots and roots, chlorophyll, leaf C and N contents, and root N contents. This review reveals that MPs may negatively affect many C-dependent soil functions. Different methods have been developed to detect the MPs from these various environmental sources, including microscopic observation, density separation, Raman, and FT-IR analysis. Several articles have focused on MPs in individual environmental sources with a developed evaluation technique. This review revealed the extensive impacts of MPs on soil-plant systems, microbial communities, and soil functions, especially on water, suggesting possible disturbances to vital ecological processes. Furthermore, the broad range of detection methods explored emphasizes the significance of reliable analytical techniques in precisely evaluating levels of MP contamination in various environmental media. This paper critically discusses MPs' sources, occurrences, and global management scenarios in all possible environmental media and ecological health impacts. Future research opportunities and required sustainable strategies have also been suggested from Bangladesh and international perspectives based on challenges faced due to MP's pollution.


Subject(s)
Environmental Monitoring , Microplastics , Microplastics/analysis , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Soil Pollutants/analysis
12.
Anal Methods ; 16(26): 4333-4346, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38888440

ABSTRACT

A poly(luminol-o-anisidine-o-toluidine) terpolymer was synthesized, characterized, and modified with GNPs and ZnO NPs. The nanocomposites were then examined for their electroactivity and potential use as cationic electrochemical sensors for detecting Sb3+ ions in phosphate buffer on the surface of a glassy carbon electrode (GCE). Among the different compositions and the terpolymer, the GCE adapted with the PLAT/ZnO/GNPs-5% nanocomposite displayed the highest current response. The fabricated nanocomposite sensor exhibited high sensitivity, with a value of 21.4177 µA µM-1 cm-2, and a low detection limit of 95.42 pM. The analytical performance of the sensor was evaluated over the linear dynamic range (LDR) of 0.1 nM to 0.01 mM. The proposed sensor is effective in detecting and measuring carcinogenic Sb3+ ions in real environmental samples using an electrochemical approach, making it a promising tool for environmental monitoring.

14.
Bioorg Chem ; 147: 107336, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636431

ABSTRACT

In this series we report the structure-based design, synthesis and anticancer activity evaluation of a series of eighteen cyclopropylamine containing cyanopyrimidine derivatives. The computational predictions of ADMET properties revealed appropriate aqueous solubility, high GI absorption, no BBB permeability, no Lipinski rule violations, medium total clearance and no mutagenic, tumorigenic, irritant and reproductive toxic risks for most of the compounds. Compounds VIIb, VIIi and VIIm emerged as the most potent anticancer agents among all compounds evaluated against 60 cancer cell lines through the one-dose (10 µM) sulforhodamine B assay. Further, the multiple dose cell viability studies against cancer cell lines MOLT-4, A549 and HCT-116 revealed results consistent with the one-dose assay, besides sparing normal cell line HEK-293. The three potent compounds also displayed potent LSD1 inhibitory activity with IC50 values of 2.25, 1.80 and 6.08 µM. The n-propyl-thio/isopropyl-thio group bonded to the pyrimidine ring and unsubstituted/ electron donating group (at the para- position) attached to the phenyl ring resulted in enhanced anticancer activity. However, against leukemia cancer, the electron donating isopropyl group remarkably enhanced anti-cancer activity. Our findings provide important leads, which merit further optimization to result in better cancer therapeutics.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Dose-Response Relationship, Drug , Drug Design , Drug Screening Assays, Antitumor , Histone Demethylases , Pyrimidines , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Histone Demethylases/antagonists & inhibitors , Histone Demethylases/metabolism , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Cell Line, Tumor , Molecular Dynamics Simulation , Molecular Docking Simulation , Cell Survival/drug effects
15.
PLoS One ; 19(4): e0302059, 2024.
Article in English | MEDLINE | ID: mdl-38683800

ABSTRACT

This study aimed to explore the prevalence and determinants of discrimination against or harassment among Bangladeshi women. The nationally representative cross-sectional data of the Multiple Indicator Cluster Survey 2019 were employed in the study. Women aged 15-49 were asked whether they felt discrimination or harassment due to seven potential reasons in the last twelve months before the survey. The outcome was a binary variable indicating whether a woman has experienced discrimination or harassment for any of the seven reasons. Responses were obtained from 64378 women and analysed through bivariate and multivariate procedures. The data had a hierarchical structure since women were nested within the clusters. A mixed-effects logistic regression model was used to analyse the data appropriately. A strong association between discrimination or harassment was seen with the functional difficulties of women. Notably, women with functional difficulties were 1.629 times more likely to experience discrimination or harassment than women without such difficulties. Other significant factors were the respondents' area, age, education, current marital status, wealth index quintile and ethnicity. The study concludes that education, marital status, functional difficulties and wealth index are the most important determinants of discrimination or harassment of women.


Subject(s)
Sexual Harassment , Humans , Female , Bangladesh/epidemiology , Adult , Cross-Sectional Studies , Adolescent , Middle Aged , Young Adult , Prevalence , Sexual Harassment/statistics & numerical data , Surveys and Questionnaires , Socioeconomic Factors
16.
Mar Pollut Bull ; 202: 116349, 2024 May.
Article in English | MEDLINE | ID: mdl-38604081

ABSTRACT

Coastal Mangroves are facing growing threats due to the harmful consequences of human activities. This first-ever detailed study of natural radioactivity in soil samples collected from seven tourist destinations within the Sundarbans, the world's largest mangrove forest, was conducted using HPGe gamma-ray spectrometry. Although the activity levels of 226Ra (11 ± 1-44 ± 4 Bq/kg) and 232Th (13 ± 1-68 ± 6 Bq/kg) generally align with global averages, the concentration of 40K (250 ± 20-630 ± 55 Bq/kg) was observed to surpass the worldwide average primarily due to factors like salinity intrusion, fertilizer application, agricultural runoff, which suggests the potential existence of potassium-rich mineral resources near the study sites. The assessment of the hazard parameters indicates that the majority of these parameters are within the recommended limits. The soil samples do not pose a significant radiological risk to the nearby population. The results of this study can establish important radiological baseline data before the Rooppur Nuclear Power Plant begins operating in Bangladesh.


Subject(s)
Radiation Monitoring , Wetlands , Soil Pollutants, Radioactive/analysis , Radium/analysis , Thorium/analysis , Spectrometry, Gamma , Soil/chemistry , Bangladesh , Potassium Radioisotopes/analysis , Forests
17.
bioRxiv ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38559035

ABSTRACT

Background: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism. Methods: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient). Results: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1ß,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine). Conclusion: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.

18.
Mymensingh Med J ; 33(2): 461-465, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38557526

ABSTRACT

Urothelial carcinoma (UC) is the most common malignancy of urinary bladder. It is the 9th leading cause of death worldwide and second most common genitourinary malignancy among male. Incidence is increasing in developing countries like Bangladesh. About 80% of patients are found between 50 to 80 years of age. It is 3-4 times more common in male than in female. Determination of therapeutic strategy and prediction of progression of urothelial carcinoma is a major clinical challenge. Treatment of urothelial carcinoma still now mostly depends on pathological stages. Amplification or genomic alteration of Cyclin D1 (a proto-oncogene) may cause protein overexpression which is frequently realized as a clonal pathology in various human neoplasms including bladder cancer. Evaluation of Cyclin D1 expression is promising for guiding therapeutic strategies, risk stratification and prediction of tumor progression. The aim of the study was to determine the expression of Cyclin D1 in urothelial carcinoma of urinary bladder and its association with tumour grade. This cross-sectional observational study was conducted in Department of Pathology, Dhaka Medical College, Dhaka, Bangladesh from July 2019 to June 2021. Histomorphologically diagnosed 51 urothelial carcinomas were included. Sections were stained with hematoxylin and eosin. Immunostaining with Cyclin D1 antibody was also done. Relevant information was collected and recorded in a predesigned data sheet. Statistical analysis was carried out as required. Mean age ±SD was 57.8±10.55 years. Male female ratio was 4.6:1. In this study 39(76.5%) patients were smoker. Regarding clinical presentations 36(70.6%) patients presented with painless hematuria alone. Lateral wall (64.7%) was the most frequent tumor location. Among 51 cases, 38(74.5%) cases were high grade urothelial carcinoma (HGUC) and 13(25.5%) cases were low grade urothelial carcinoma (LGUC). Considering Cyclin D1 expression, most of the LGUC cases showed high level of expression by both percentage (84.6%) and intensity (84.6%). Most of the HGUC cases showed low level of expression by both percentage (63.2%) and intensity (60.5%). Cyclin D1 showed significant inverse association with HGUC (p<0.05). In urothelial carcinoma of urinary bladder, Cyclin D1 expression was decreased with increasing grade of the tumor. Cyclin D1 expression was inversely associated with tumour grade.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Female , Humans , Male , Bangladesh/epidemiology , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/pathology , Cross-Sectional Studies , Cyclin D1/metabolism , Urinary Bladder/metabolism , Urinary Bladder/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
19.
Mymensingh Med J ; 33(2): 393-401, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38557517

ABSTRACT

Hand Surgery is a specialized branch of Plastic and Reconstructive surgery. There are many conditions that require hand surgery, for example, congenital deformity, electric or flame burn, mechanical or road traffic injury, and post burn or post traumatic deformity. A retrospective observational study was conducted in the department of Burn and Plastic surgery, Mymensingh Medical College Hospital, Bangladesh during a 2 years period extending from 9th September 2021 to 8th September 2023. The objective of this study was to see the hand surgery status in a tertiary hospital of Bangladesh during the post Covid pandemic period. During this period 236 hand surgery procedures were performed in 176 patients. The age of the patients ranged from 02 to 78 years (Mean 31.14±1.52). One hundred and four (59.0%) were male and 72(41.0%) were female. Thirty-four (19.32%) patients had co-morbidities e.g., Epilepsy, Diabetes Mellitus, Chronic Kidney Diseases and HBsAg +ve. Causes of surgery included, wound due to electric burn 49(27.84%), flame burn 36(20.45%), post traumatic 24(13.64%), post infective 11(06.25%), tumor excision 02(2.24%), Dupuytren's contracture 03(1.70%), congenital anomalies 06(3.41%), post burn scar contractures 41(23.29%), nerve injury 01(00.57%) and carpal tunnel syndrome 01 (00.57%). Procedures were performed: post burn scar contracture release 41(17.37%), syndactly release 06(2.54%), release of post traumatic contracture 06(2.54%), carpal tunnel release 01(00.42%), release of Dupuytren's contracture 03(01.27%), nerve repair 01(00.42%), debridement, amputation and Fillet flap 29(12.29%), split thickness skin graft 46 (19.49%), V-Y advancement flap 06(2.54%), transposition flap 18(07.63%), cross finger flap 16 (06.78%), reverse cross finger flap 02 (00.85%), first dorsal metacarpal artery (FDMA) flap 05 (02.12%), reverse FDMA flap 01 (00.42%), metacarpal artery perforator flap 08(3.39%), radial artery perforator flap 04(01.69%), posterior interosseous artery flap 05(2.12%), abdominal flap 11(04.46%) and flap division and insetting 27(11.44%). Outcome of surgery was satisfactory in 225(95.34%) and 11(04.46%) cases had complications (p value 0.453), which was not significant. So, it can be concluded that the outcome of various types of hand surgery procedures in tertiary hospital of northern Bangladesh during the post Covid period was satisfactory overall.


Subject(s)
Dupuytren Contracture , Perforator Flap , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Bangladesh/epidemiology , Cicatrix , Perforator Flap/blood supply , Perforator Flap/transplantation , Tertiary Care Centers , Treatment Outcome , Retrospective Studies
20.
Mymensingh Med J ; 33(2): 426-432, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38557521

ABSTRACT

Functional dyspepsia (FD) is a common gastrointestinal problem in the world. The Rome III consensus subdivided functional dyspepsia into two groups: meal-related postprandial distress syndrome (PDS) and meal-unrelated epigastric pain syndrome (EPS). Limited data are available regarding FD in Bangladesh. The aim of this study was to investigate the demographic and clinical characteristics of FD and its sub-types. This cross-sectional study was conducted in which we recruited patients who attended the outpatient department of Gastroenterology of Bangabandhu Sheikh Mujib Medical University, Bangladesh from March 2017 to February 2018. Patients fulfilling Rome III FD criteria and a negative upper GIT endoscopy were included for this study. The patients were then subdivided into 'pure' PDS (i.e. meeting criteria for PDS without EPS symptoms), 'pure' EPS (i.e., meeting criteria for EPS without PDS symptoms), and overlapping PDS-EPS (i.e., symptoms of both PDS and EPS) groups. Total of 368 FD patients (56.0% females, mean age 32.8±8.6 years, BMI: 22.0±2.7), were included in this study. Out of them, 112(30.4%) patients (57.2% females, mean age 33.9±9.3 years, BMI: 22.0±2.7) fulfilled criteria of pure EPS and 64(17.4%) patients (68.8% females, mean age 33.2±7.8 years, BMI: 22.1±2.4) fulfilled criteria of pure PDS. However, the majority of patients [192(52.2%), 52.1% females, mean age 32.0±8.4 years, BMI: 21.9±2.8] had symptoms of overlapping EPS-PDS. More than 40% of patients in our study presented with 3 or more of the four key symptoms of FD. A longer duration of presenting symptoms was seen among patients with overlapping EPS-PDS in comparison to pure EPS and pure PDS (p<0.001). A significant overlap of symptoms of both EPS and PDS was noticed among patients with FD. The value of dividing functional dyspepsia into the subgroups of PDS and EPS is thus questionable. Further research and modification of the diagnostic criteria for FD subtypes are necessary.


Subject(s)
Dyspepsia , Adult , Female , Humans , Young Adult , Male , Dyspepsia/diagnosis , Dyspepsia/epidemiology , Abdominal Pain/epidemiology , Abdominal Pain/etiology , Bangladesh/epidemiology , Tertiary Care Centers , Cross-Sectional Studies , Demography
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