The complex heterogeneity of immune cell signatures across wasting tissues with C26 and 5-fluorouracil-induced cachexia.

Immune cell-driven pathways are linked to cancer cachexia. Tumor presence is associated with immune cell infiltration whereas cytotoxic chemotherapies reduce immune cell counts. Despite these paradoxical effects, both cancer and chemotherapy can cause cachexia; however, our understanding of immune responses in the cachexia condition with cancer and chemotherapy is largely unknown. We sought to advance our understanding of the immunology underlying cancer and cancer with chemotherapy-induced cachexia. CD2F1 mice were given 106 C26 cells, followed by five doses of 5-fluorouracil (5FU; 30 mg/kg LM, ip) or PBS. Indices of cachexia and tumor (TUM), skeletal muscle (SKM), and adipose tissue (AT) immune cell populations were examined using high-parameter flow cytometry. Although 5FU was able to stunt tumor growth, % body weight loss and muscle mass were not different between C26 and C26 + 5FU. C26 increased CD11b+Ly6g+ and CD11b+Ly6cInt inflammatory myeloid cells in SKM and AT; however, both populations were reduced with C26 + 5FU. tSNE analysis revealed 24 SKM macrophage subsets wherein 8 were changed with C26 or C26 + 5FU. C26 + 5FU increased SKM CD11b-CD11c+ dendritic cells, CD11b-NK1.1+ NK-cells, and CD11b-B220+ B-cells, and reduced Ly6cHiCX3CR1+CD206+CD163IntCD11c-MHCII- infiltrated macrophages and other CD11b+Ly6cHi myeloid cells compared with C26. Both C26 and C26 + 5FU had elevated CD11b+F480+CD206+MHCII- or more specifically Ly6cLoCX3CR1+CD206+CD163IntCD11c-MHCII- profibrotic macrophages. 5FU suppressed tumor growth and decreased SKM and AT inflammatory immune cells without protecting against cachexia suggesting that these cells are not required for wasting. However, profibrotic cells and muscle inflammatory/atrophic signaling appear consistent with cancer- and cancer with chemotherapy-induced wasting and remain potential therapeutic targets.NEW & NOTEWORTHY Despite being an immune-driven condition, our understanding of skeletal muscle and adipose tissue immune cells with cachexia is limited. Here, we identified immune cell populations in tumors, skeletal muscle, and adipose tissue in C26 tumor-bearing mice with/without 5-fluorouracil (5FU). C26 and C26 + 5FU had increased skeletal muscle profibrotic macrophages, but 5FU reduced inflammatory myeloid cells without sparing mass. Tumor presence and chemotherapy have contrasting effects on certain immune cells, which appeared not necessary for wasting.

Panaxynol improves crypt and mucosal architecture, suppresses colitis-enriched microbes, and alters the immune response to mitigate colitis.

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents.

An efficient synthesis of 3-amino-2-formyl-functionalized benzothiophenes by a domino reaction protocol and their use to synthesize a library of novel scaffolds have been reported. Reactions of ketones and 1,3-diones with these amino aldehyde derivatives formed a series of benzothieno[3,2-b]pyridine and 3,4-dihydro-2H-benzothiopheno[3,2-b]quinolin-1-one, respectively. A plausible mechanism for the formation of fused pyridine derivatives by the Friedlander reaction has been elucidated by density functional theory (DFT) calculations. Furthermore, hydrazones were obtained by reacting the aldehyde functional group of benzothiophenes with different hydrazine derivatives. Preliminary screening of these compounds against several bacterial strains and cancer cell lines led to the discovery of several hit molecules. Hydrazone and benzothieno[3,2-b]pyridine derivatives are potent cytotoxic and antibacterial agents, respectively. One of the potent compounds effected ∼97% growth inhibition of the LOX IMVI cell line at 10 µM concentration.

An artificial intelligence approach for predicting death or organ failure after hospitalization for COVID-19: development of a novel risk prediction tool and comparisons with ISARIC-4C, CURB-65, qSOFA, and MEWS scoring systems.

BACKGROUND: We applied machine learning (ML) algorithms to generate a risk prediction tool [Collaboration for Risk Evaluation in COVID-19 (CORE-COVID-19)] for predicting the composite of 30-day endotracheal intubation, intravenous administration of vasopressors, or death after COVID-19 hospitalization and compared it with the existing risk scores. METHODS: This is a retrospective study of adults hospitalized with COVID-19 from March 2020 to February 2021. Patients, each with 92 variables, and one composite outcome underwent feature selection process to identify the most predictive variables. Selected variables were modeled to build four ML algorithms (artificial neural network, support vector machine, gradient boosting machine, and Logistic regression) and an ensemble model to generate a CORE-COVID-19 model to predict the composite outcome and compared with existing risk prediction scores. The net benefit for clinical use of each model was assessed by decision curve analysis. RESULTS: Of 1796 patients, 278 (15%) patients reached primary outcome. Six most predictive features were identified. Four ML algorithms achieved comparable discrimination (P > 0.827) with c-statistics ranged 0.849-0.856, calibration slopes 0.911-1.173, and Hosmer-Lemeshow P > 0.141 in validation dataset. These 6-variable fitted CORE-COVID-19 model revealed a c-statistic of 0.880, which was significantly (P < 0.04) higher than ISARIC-4C (0.751), CURB-65 (0.735), qSOFA (0.676), and MEWS (0.674) for outcome prediction. The net benefit of the CORE-COVID-19 model was greater than that of the existing risk scores. CONCLUSION: The CORE-COVID-19 model accurately assigned 88% of patients who potentially progressed to 30-day composite events and revealed improved performance over existing risk scores, indicating its potential utility in clinical practice.

Impact of Preoperative Echocardiograms on In-Hospital Outcomes of Patients Undergoing Surgical Hip Fracture Repair and Their Clinical Appropriateness.

OBJECTIVES: Preoperative transthoracic echocardiograms (TTE) before hip fracture repairs are controversial. This study aimed to quantify the frequency of ordering TTE, the appropriateness of testing based on current guidelines, and the impact of TTE on in-hospital morbidity and mortality outcomes. METHODS: This retrospective chart review of adult patients admitted with hip fracture compared the length of stay (LOS), time to surgery, in-hospital mortality, and postoperative complications between TTE and non-TTE groups. TTE patients were risk stratified using the Revised Cardiac Risk Index (RCRI) to compare TTE indication according to current guidelines. RESULTS: Of the 490 patients included in this study, 15% received preoperative TTE. The median LOS of the TTE and non-TTE groups was 7.0 and 5.0 d, respectively, whereas the median time to surgery was 34 and 14 h, respectively. The odds of in-hospital mortality remained significantly higher in the TTE group after adjusting for RCRI but not when adjusted for the Charlson Comorbidity Index. Significantly more patients in the TTE groups had postoperative heart failure and up triage in the intensive care unit. Furthermore, 48% of patients with an RCRI score of 0 received preoperative TTE, with cardiac history as the most typical indication. TTE changed perioperative management in 9% of patients. CONCLUSIONS: Patients subjected to TTE before hip fracture surgery had a longer LOS and time to surgery, with higher mortality and intensive care unit up triage rates. TTE evaluations were typically conducted for inappropriate indications, which rarely made meaningful changes to patient management.

Optimum heparin dose in off-pump coronary artery bypass grafting: A systematic review and meta-analysis.

INTRODUCTION: Off-pump coronary artery bypass grafting (OPCABG) was introduced many years ago aiming to reduce the known complications of conventional on-pump coronary surgeries. Heparin is required during the procedures, but the available protocols have diverse dosage regimens. The primary objective of this systematic review is to examine the effect of different heparin doses on the outcomes of OPCABG. EVIDENCE ACQUISITION: MEDLINE and EMBASE were searched. Four reviewers identified eligible clinical trials. Two reviewers extracted data and independently assessed the risk of bias using Cochrane tool. The primary outcome was the activated clotting time (ACT) at three minutes. The secondary outcomes were proportion of patients requiring blood products and the length of hospital stay. An aggregate data approach was used. EVIDENCE SYNTHESIS: Three single-center randomized studies recruiting 256 patients were included. The studies compared low-dose (1.5-2 mg/kg) and high-dose (3 mg/kg) heparin boluses. The overall mean difference for ACT after three minutes between low- and high-dose heparin is - 126.16 (95% CI: - 142.19, - 110.14). The proportion of patients requiring blood products after surgery [odd ratio 1.27 (95% CI: 0.69, 2.32)] or the overall length of stay [mean difference -0.15 (95% CI: -0.84, 0.53)] did not differ between the heparin doses. CONCLUSIONS: In OPCABG, high-dose compared with low-dose heparin did not affect the utilization of more blood products or increased the overall length of stay. Unsurprisingly, ACT values were higher in the high-dose heparin group. Larger and adequately powered randomized clinical trials are indicated to resolve the uncertainty.

Appraisal of anti-inflammatory and immunomodulatory potential of ramipril against Freund's adjuvant-provoked arthritic rat model.

Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.

Three-dimensional random walk models of individual animal movement and their application to trap counts modelling.

BACKGROUND: Random walks (RWs) have proved to be a powerful modelling tool in ecology, particularly in the study of animal movement. An application of RW concerns trapping which is the predominant sampling method to date in insect ecology and agricultural pest management. A lot of research effort has been directed towards modelling ground-dwelling insects by simulating their movement in 2D, and computing pitfall trap counts, but comparatively very little for flying insects with 3D elevated traps. METHODS: We introduce the mathematics behind 3D RWs and present key metrics such as the mean squared displacement (MSD) and path sinuosity, which are already well known in 2D. We develop the mathematical theory behind the 3D correlated random walk (CRW) which involves short-term directional persistence and the 3D Biased random walk (BRW) which introduces a long-term directional bias in the movement so that there is an overall preferred movement direction. In this study, we focus on the geometrical aspects of the 3D trap and thus consider three types of shape; a spheroidal trap, a cylindrical trap and a rectangular cuboidal trap. By simulating movement in 3D space, we investigated the effect of 3D trap shapes and sizes and of movement diffusion on trapping efficiency. RESULTS: We found that there is a non-linear dependence of trap counts on the trap surface area or volume, but the effect of volume appeared to be a simple consequence of changes in area. Nevertheless, there is a slight but clear hierarchy of trap shapes in terms of capture efficiency, with the spheroidal trap retaining more counts than a cylinder, followed by the cuboidal type for a given area. We also showed that there is no effect of short-term persistence when diffusion is kept constant, but trap counts significantly decrease with increasing diffusion. CONCLUSION: Our results provide a better understanding of the interplay between the movement pattern, trap geometry and impacts on trapping efficiency, which leads to improved trap count interpretations, and more broadly, has implications for spatial ecology and population dynamics.

Correction to: Systematic review and meta-analysis of public hospital efficiency studies in Gulf region and selected countries in similar settings.

[This corrects the article DOI: 10.1186/s12962-019-0185-4.].

Case report: robotic thoracic surgery of posterior mediastinal mass.

We report a 39-year-old male with accidental findings of posterior mediastinum mass at right superior aspects, located at T2 with close proximity to trachea, superior vena cava, azygus vein, right subclavian artery and oesophagus. Apart from intermittent right shoulder pain, there was no other significant symptom. He opted for conservative management initially, given the benign nature and proximity to important structures. We postulated that robotic approach will be of advantage for this particular case which was successfully performed with uneventful recovery. This case illustrated the advantages of robotic-assisted surgery, compared to conventional VATS in otherwise potentially difficult case to undertake.

Characterization of oral mucosa lesions and prevalence of yeasts in diabetic patients: A comparative study.

BACKGROUND: There is no data available on the prevalence of oral mucosal lesion and candida infection among DM patients which necessitate conducting a local or nation-wide study to assess the oral mucosa lesions and candida prevalent in diabetic patients in Riyadh, Saudi Arabia. OBJECTIVES: The objective of the present study was to characterize oral mucosa lesions, and the prevalence of yeasts in diabetic patients and their association with the risk factors in comparison with a group of non-diabetic controls. METHODS: Study design: A cross-sectional comparative study was conducted assuming 50% of the diabetic patients have oral lesions compared to nondiabetic patients and a power of 80% with 5% level of significance, the minimum required sample size was estimated to be 115 in each group. The buccal swabs were collected to isolate Candida species from the individual patient with a current and former history of diabetes. The laboratory findings were collected and the clinical examination of the oral mucosa was processed at the department of microbiology. RESULTS: The results inferred a significant presence of oral mucosa alterations in the diabetic group. A majority of the patients were suffering from type 2 diabetes for the past 10 years. C. albicans was the predominant yeast, followed by. C. tropicalis and C. krusei nonalbicans species that were most frequently isolated. Diabetes and smoking habit were the two risk factors for oral mucosa alterations. CONCLUSIONS: The study found a significant presence of oral mucosa alterations in the diabetic group and the fungal infection tended to be more in the diabetic group with a high incidence of C. albicans. The presence of diabetes and smoking habit were two risk factors identified as significant for oral mucosa alterations. The significant variation in education level in groups indicates that education would help to enhance the prognosis in diabetic patients and healthcare behavior.

Laparoscopic Ventral Rectopexy Versus Stapled Transanal Rectal Resection for Treatment of Obstructed Defecation in the Elderly: Long-term Results of a Prospective Randomized Study.

BACKGROUND: Obstructed defecation is a common complaint in coloproctology. Many anal, abdominal, and laparoscopic procedures are adopted to correct the underlying condition. OBJECTIVE: The purpose of this study was to compare long-term functional outcome, recurrence rate, and quality of life between laparoscopic ventral rectopexy and stapled transanal rectal resection in the treatment of obstructed defecation. DESIGN: This was a prospective randomized study. SETTING: This study was performed at academic medical centers. PATIENTS: Patients were included if they had obstructed defecation attributed to pelvic structural abnormalities that did not to respond to conservative measures. Exclusion criteria included nonrelaxing puborectalis, previous abdominal surgery, other anal pathology, and pudendal neuropathy. INTERVENTION: Patients were randomly allocated to either laparoscopic ventral rectopexy (group 1) or stapled transanal rectal resection (group 2). MAIN OUTCOME MEASURES: The primary outcome measures were improvement of modified obstructed defecation score and recurrences after ≥3 years of follow-up. Secondary outcomes were postoperative complications, continence status using Wexner incontinence score, and quality of life using Patient Assessment of Constipation-Quality of Life Questionnaire. RESULTS: The study included 112 patients (56 in each arm). ASA score II was reported in 32 patients (18 in group 1 and 14 in group 2; p = 0.12), whereas 3 patients in each group had ASA score III. Minor postoperative complications were seen in 11 patients (20%) of group 1 and 14 patients of group 2 (25%; p = 0.65). During follow-up, 3 patients had fecal urgency after stapled transanal rectal resection but no sexual dysfunction in either procedure. After 6 months, modified obstructed defecation score improvement >50% was reported in 73% versus 82% in groups 1 and 2 (p = 0.36). After a mean follow-up of 41 months, recurrences of symptoms were reported in 7% in group 1 versus 24% in group 2 (p = 0.04). Six months postoperation, perineal descent improved >50% in defecogram in 80% of group 1 versus no improvement in group 2. Quality of life significantly improved in both groups after 6 months; however a significant long-term drop (>36 months) was seen only in group 2. LIMITATIONS: Possible limitations of this study are the presence of a single operator and the absence of blindness of the technique for both patient and assessor. CONCLUSIONS: In elderly patients even with comorbidities, both laparoscopic ventral rectopexy and stapled transanal rectal resection are safe and can improve function of the anorectum in patients with obstructed defecation attributed to structural abnormalities. Laparoscopic ventral rectopexy has better long-term functional outcome, less complications, and less recurrences compared with stapled transanal rectal resection. Perineal descent only improves after laparoscopic ventral rectopexy. Stapled transanal rectal resection was shown not to be the first choice in elderly patients with obstructed defecation unless they had a medical contraindication to laparoscopic procedures. See Video Abstract at http://links.lww.com/DCR/A788.

Capsular genotype and lipooligosaccharide locus class distribution in Campylobacter jejuni from young children with diarrhea and asymptomatic carriers in Bangladesh.

Campylobacter jejuni-related diarrheal diseases is one of the major health issues among young children (0-59 months old) in low-income countries. Monitoring of the capsular (capsule polysaccharide, CPS) types of virulent C. jejuni strains in regions where the disease is endemic is of great importance for the development of a customized capsule-based multivalent vaccine. Therefore, we aimed to determine the prevalence of CPS genotypes among C. jejuni strains isolated from young children with enteritis (n = 152) and asymptomatic carriers matched by age, sex, and residence defined as the control group (n = 215) in Bangladesh. CPS genotyping was performed using a newly established multiplex polymerase chain reaction (PCR) method and lipooligosaccharide (LOS) locus classes (A-E) were characterized using PCR as well. We identified 24 different CPS genotypes among the 367 isolates. Four prevalent capsular types, HS5/31 complex (n = 27, 18%), HS3 (n = 26, 17%), HS4A (n = 10, 7%), and HS8/17 (n = 10, 7%) covered almost 50% of the strains from enteritis patients and 43% of the isolates from controls. In combination, the CPS genotype and LOS class was not discriminative between cases and controls. Dominant capsular types previously identified in C. jejuni strains isolated from patients with Guillain-Barré syndrome in Bangladesh were rarely detected in strains isolated from the young children. A similar distribution was evident among enteritis- and control-related strains when comparison was done between CPS types and LOS classes. This is the first systematic study presenting the distribution of CPS genotypes of C. jejuni strains isolated in Bangladesh from children with diarrhea and controls, with capsular genotypes HS5/31 complex, HS3, HS4A, and HS8/17 being prevalent in both. In conclusion, systematic studies are required to develop a multivalent capsule-based vaccine for children in low-income countries.

DEPRESSION, ANXIETY, STRESS, AND THEIR ASSOCIATED FACTORS AMONG CORPS MEMBERS SERVING IN KEBBI STATE.

BACKGROUND: Depression, anxiety and stress, are not only health problems by themselves, but also associated with other negative health consequences. The national youth service is usually characterized by a number of new challenges and experiences which may require life style adjustments by the corps member. However, no previous study on psychological factors has been conducted among corps members. OBJECTIVE: This study was conducted to determine the prevalence of depression, anxiety and, stress and their associated factors among corps members serving in Kebbi state. METHODS: A cross-sectional study was conducted among 264 corps members from four local government areas of the state. Selection of the local government areas and the individual participants was by simple random sampling. Data was collected from May to June 2014 using a self-administered questionnaire. Data analysis used chi-square test to identify the relationship between categorical variables and multivariate logistic regression to identify the independent factors for depression, anxiety and stress each. RESULTS: The response rate was 97%. Most of the respondents were males (63.6%), single (85.5%), and above 20 years of age (71.6%). The overall prevalences of depression, anxiety and stress among the respondents were 36.4%, 54.5% and 18.2% respectively. The independent factors for depression were; being from the North central (OR = 5.99; 95% CI: 2.194-16.354) or South-south; and the perception of earning enough income (OR = 2.987; 95% CI: 1.062-8.400). For anxiety, male gender (OR = 0.411; 95% CI: 0.169-0.999); and being from the North central were significant risk factors (OR = 3.731; 95% CI: 1.450-9.599). Being above 26 years of age was an independent risk factor for stress (OR = 0.083; 95% CI: 0.018-0.381). Also, those who had ever schooled outside their towns of residence were less likely to be stressed compared to those who had never (OR = 0.30; 95% CI: 0.110-0.855). All other factors did not show any significant association with any of the outcome variables in multivariate analysis. CONCLUSION: In conclusion, the prevalences of depression, anxiety and stress are high among corps members serving in Kebbi state. There is need to expand the scope of this study to a national level so as to get a bigger picture of the problem.

Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional disorder characterized by chronic or recurrent abdominal pain or discomfort with bowel disturbances. This prospective, randomized clinical trial has been conducted on IBS patients, using trimebutine and Mebeverine in separate group in parallel design to compare the efficacy and safety of Trimebutine 100mg twice daily with mebeverine 135mg twice daily. Patients of 15 to 60 years old and both sexes were included from the out patient department (OPD) of gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from June 2010 to December 2011. A validated IBS-QOL instrument consisted of 34 questions used to assess improvement of quality of life before and after treatment. A total of 140 patients were enrolled in this study. Eighteen patients dropped out. One hundred twenty two patients completed the trial. In this study at the end of 6 weeks therapy, improvement of symptoms was statistically significant. However, differences of improvement between the two groups in relieving various symptoms were not statistically significant. Mean QOL score before treatment was 103 in Trimebutine group and 106 in Mebeverine group. After 6 weeks of treatment mean QOL score was 82 in Trimebutine group and 95 in Mebeverine group indicating improvement in both groups was statistically significant. The difference between the two groups was also significant. No worsening of symptoms and no side effects of the therapeutic agents was observed in any patient during the trial.

Peginterferon α-2a and rivabirin in the treatment of chronic hepatitis C.

Peginterferon α-2a with ribavirin produces significantly higher sustained virological response (SVR) in comparison to conventional interferon monotherapy in patients with chronic hepatitis C virus (HCV) infection. We evaluated the efficacy and safety of peginterferon α-2a plus ribavirin combination in the treatment of chronic hepatitis C among Bangladeshi patients. A total of 64 patients were randomly selected in this study and were assigned for treatment with peginterferon α-2a 180µg once weekly plus ribavirin daily for 24 weeks in case of genotypes 2 and 3 infections and 48 weeks in case of genotypes 1 and 4 infections. Ribavirin was given 800mg in divided doses in case of genotypes 2 and 3 infections and 1000mg-1200 mg in case of genotypes 1 and 4 infections according to body weight daily(1000 mg in divided doses if body weight <75kg and 1200mg in divided doses if body weight >75kg). Efficacy was assessed by measurements of serum HCV-RNA and serum ALT. A higher proportion of patients (71.87%) who received peginterferon α-2a plus ribavirin had a sustained virological response. It is observed that genotype 3 (a and b) patients showed poor response (SVR-47.05%), where as genotypes 1(a,b), 3 and 4 mixed, 2b and 4 infections showed response rate of 100%. So it can be concluded that once weekly peginterferon α-2a plus daily ribavirin is effective in chronic HCV infection in Bangladesh and overall response rate is similar to that reported in other studies.

Impact of Eco-Friendly Plaster Using Epoxy Resin and Epoxy Hardener on Mechanical Properties under Compression and Tension.

BISCO plaster (BRP) is an environmentally friendly material with high mechanical properties and is considered a great elective to conventional materials such as gypsum and cement. Our investigation seeks to examine BISCO plaster (BRP) and a mixture of resin and hardener in three proportions (30%, 45%, and 60%) to achieve our ultimate goal, which is to preserve the environment and achieve the vision of the Kingdom of Saudi Arabia 2030 to reach zero carbon emissions by 2060? Emissions tests were performed, and although the CO2 level was zero, they emitted SO2 sulfur dioxide and NO2 nitrogen dioxide, and 60% was the lowest emission rate. We also used ANSYS 2023 R1 software to compare them with their mechanical properties resulting from tensile and compression testing. In this study, we looked closely at the mechanical characteristics of different materials designed for wall coverings, with particular emphasis on their environmental sustainability. We carried out experiments to gauge the tensile and compressive stress on samples with varying mixing ratios. Our main objective was on crucial mechanical properties such as the modulus of elasticity, ultimate tensile strength, yield strength, yield strain, modulus of resilience, and ductility. Through meticulous scrutiny, we determined that the amalgamation of these mechanical attributes at the 30% mixing ratio provides an optimal combination for attaining structural integrity, adaptability, and resilience in wall coverings. Significantly, this ratio also underscores a commitment to environmentally conscious material selection. Our study offers important new insights into the selection of wall covering materials by providing a detailed understanding of their mechanical behavior under various stress conditions. It aligns with the increasing significance of environmental responsibility in contemporary design and construction. By emphasizing the 30% mixing ratio, our findings establish a foundation for informed decision making, promoting the utilization of sustainable materials that achieve a balance between strength, flexibility, and longevity. This ensures optimal performance in practical applications while simultaneously minimizing the environmental impact.

Studying the cellular basis of small bowel enteropathy using high-parameter flow cytometry in mouse models of primary antibody deficiency.

Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined. Methods: In this study, several mouse strains reflecting a spectrum of primary antibody deficiency (IgA -/- , Aicda -/- , CD19 -/- and J H -/- ) were used to generate a functional small-bowel-specific cellular atlas using a novel high-parameter flow cytometry approach that allows for the enumeration of 59 unique cell subsets. Using this cellular atlas, we generated a direct and quantifiable estimate of immune dysregulation. This estimate was then used to identify specific immune factors most predictive of the severity of inflammatory disease of the small bowel (small bowel enteropathy). Results: Results from our experiments indicate that the severity of primary antibody deficiency positively correlates with the degree of immune dysregulation that can be expected to develop in an individual. In the SI of mice, immune dysregulation is primarily explained by defective homeostatic responses in T cell and invariant natural killer-like T (iNKT) cell subsets. These defects are strongly correlated with abnormalities in the balance between protein (MHCII-mediated) versus lipid (CD1d-mediated) antigen presentation by intestinal epithelial cells (IECs) and intestinal stem cells (ISCs), respectively. Conclusions: Multivariate statistical approaches can be used to obtain quantifiable estimates of immune dysregulation based on high-parameter flow cytometry readouts of immune function. Using one such estimate, we reveal a previously unrecognized tradeoff between iNKT cell activation and type 1 immunity that underlies disease in the small bowel. The balance between protein/lipid antigen presentation by ISCs may play a crucial role in regulating this balance and thereby suppressing inflammatory disease in the small bowel.