Tag: nevin manimala

J Med Life. 2023 Apr;16(4):623-630. doi: 10.25122/jml-2022-0280.

ABSTRACT

Ischemia/reperfusion injury (IRI) is a common cause of kidney damage, characterized by oxidative stress and inflammation. In this study, we investigated the potential protective effects of IAXO-102, a chemical compound, on experimentally induced IRI in male rats. The bilateral renal IRI model was used, with 24 adult male rats randomly divided into four groups (N=6): sham group (laparotomy without IRI induction), control group (laparotomy plus bilateral IRI for 30 minutes followed by 2 hours of reperfusion), vehicle group (same as control but pre-injected with the vehicle), and treatment group (similar to control but pre-injected with IAXO-102). We measured several biomarkers involved in IRI pathophysiology using enzyme-linked immunosorbent assay (ELISA), including High mobility group box1 (HMGB1), nuclear factor kappa b-p65 (NF-κB p65), interleukin beta-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-isoprostane, Bcl-2 associated X protein (BAX), heat shock protein 27 (HSP27), and Bcl-2. Statistical analysis was performed using one-way ANOVA and Tukey post hoc tests. Our results showed that IAXO-102 significantly improved kidney function, reduced histological alterations, and decreased the inflammatory response (IL-1, IL-6, and TNF) caused by IRI. IAXO-102 also decreased apoptosis by reducing pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 without impacting HSP27. In conclusion, our findings suggest that IAXO-102 had a significant protective effect against IRI damage in the kidneys.

PMID:37305825 | PMC:PMC10251395 | DOI:10.25122/jml-2022-0280

J Med Life. 2023 Apr;16(4):599-609. doi: 10.25122/jml-2023-0019.

ABSTRACT

Classical Hodgkin lymphoma represents a paradigm of tumor cell-microenvironment interactions as the neoplastic Hodgkin Reed-Sternberg (HRS) cells typically constitute less than 1% of the total tumor volume. CTLA-4, a member of the CD28/B7 immunoglobulin superfamily, and CD28 and their ligands B7-1 and B7-2 are critically important for the initial activation of naive T cells. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of the HL microenvironment. The study included 50 histopathological confirmed cases of Hodgkin lymphoma. IHC staining for CTLA-4 and B7-1 was performed on archival paraffin-embedded biopsy. SPSS version 17 was used for statistical analysis. CTLA-4 IHC expression in HRS cells was negative in all cases, while in immune cells, CTLA-4 expression was observed in 45 (90%) cases. CD80 expression was present in all cases, both in HRS and immune cells. There was a significant association between HRS cell percentage and IPS score (p-value=0.001). Mean survival duration was longer in <50% immune cells compared to >50% groups, with an overall mean survival of 67.633 months. Considering the CTLA4 expression in immune cells within the microenvironment and the availability of targeted drugs like Iplimumab, which act through CTLA4 blockade, it may be appropriate to use this as targeted therapy in HL cases, particularly in those with refractory disease who are unable to achieve cure prior to ASCT.

PMID:37305822 | PMC:PMC10251379 | DOI:10.25122/jml-2023-0019

Geosci Lett. 2023;10(1):26. doi: 10.1186/s40562-023-00280-z. Epub 2023 Jun 6.

ABSTRACT

Despite Bangladesh being vulnerable to cyclones, there is a dearth of research on cyclone vulnerability assessment. Assessing a household’s vulnerability is considered a crucial step in avoiding the adverse effects of catastrophe risks. This research was conducted in the cyclone-prone district of Barguna, Bangladesh. This study’s purpose is to evaluate this region’s vulnerability. A questionnaire survey was conducted using a convenience sample technique. A door-to-door survey of 388 households in two Unions of Patharghata Upazila, Barguna district, was conducted. Forty-three indicators were selected to assess cyclone vulnerability. The results were quantified using an index-based methodology with a standardized scoring method. Where applicable, descriptive statistics have been obtained. In terms of vulnerability indicators, we also utilized the chi-square test to compare Kalmegha and Patharghata Union. When appropriate, the non-parametric Mann-Whitney U test was employed to evaluate the relationship between the Vulnerability Index Score (VIS) and the union. According to the results, the environmental vulnerability (0.53 ± 0.17) and the composite vulnerability index (0.50 ± 0.08) were significantly greater in Kalmegha Union than in Patharghata Union. They faced inequity in government assistance (71%) and humanitarian aid (45%) from national and international organizations. However, 83% of them underwent evacuation practices. 39% were satisfied with the WASH conditions at the cyclone shelter, whereas around half were dissatisfied with the status of the medical facilities. Most of them (96%) rely only on surface water for drinking. National and international organizations should have a comprehensive plan for disaster risk reduction that encompasses all individuals, regardless of race, geography, or ethnicity.

PMID:37305781 | PMC:PMC10243237 | DOI:10.1186/s40562-023-00280-z

J Hum Reprod Sci. 2023 Jan-Mar;16(1):22-28. doi: 10.4103/jhrs.jhrs_182_22.

ABSTRACT

BACKGROUND: Following microsurgical vaso-epididymal anastomosis (VEA), anastomotic patency with sperm returning to the ejaculate is not always present and may even be delayed. The presence of motile spermatozoa is highly suggestive of future patency following surgery.

AIMS: We prospectively analyse the factors that could predict motile spermatozoa at the epididymis intraoperatively and predictors of patency in patients with obstructive azoospermia (OA) undergoing microsurgical VEA.

SETTINGS AND DESIGN: Department of Urology of a tertiary care centre in Northern India. It is a prospective observational study.

MATERIALS AND METHODS: Over a 2-year period (July 2019 to June 2021), 26 patients with idiopathic OA were enrolled in the study. Twenty patients underwent microsurgical VEA. Patients were divided into two groups based on the presence/absence of intraoperative motile spermatozoa.

STATISTICAL ANALYSIS USED: Analysis of preoperative and intraoperative factors was done using the Mann-Whitney U-test, Chi-squared test and Fischer exact test.

RESULTS: Out of 20 patients, 5 (group 2) had intraoperative motile spermatozoa in the epididymal fluid and 15 (group 1) had nonmotile spermatozoa. Low luteinising hormone (LH) levels (P = 0.01) and high testosterone levels (P = 0.05) were the predictive of presence of motile spermatozoa in epididymal fluid. Mean follow-up was 9 months (6-18 months). Predictors of higher patency were grade 2 epididymis (firm, turgid and tense) (P = 0.003), low LH levels (P = 0.03), low sertoli cell index (P = 0.006), high sperm-Sertoli index (P = 0.002) and better surgeon satisfaction (P = 0.01).

CONCLUSION: Low LH levels and high testosterone levels may be predictive of the presence of motile spermatozoa in epididymal fluid. Firm, turgid and tense epididymis, low Sertoli cell index, high sperm-Sertoli index and surgeon satisfaction suggest a greater chance of success after VEA for idiopathic azoospermia.

PMID:37305778 | PMC:PMC10256949 | DOI:10.4103/jhrs.jhrs_182_22

J Hum Reprod Sci. 2023 Jan-Mar;16(1):64-69. doi: 10.4103/jhrs.jhrs_180_22.

ABSTRACT

BACKGROUND: Vitrification of embryos following a single-controlled ovarian stimulation has been the strategy practised now in many in vitro fertilisation clinics to minimise the risk of early ovarian hyper stimulation syndrome, to reduce multiple pregnancy rates and to improve cumulative pregnancy rates. In recent years, advances in vitrification techniques and improved culture conditions have led to good post-thaw embryo survival rates, thereby increasing pregnancy rates of frozen embryo transfer (FET) cycles.

AIM: The aim of this study was to analyse the effect of post-thaw incubation time of frozen embryos on the clinical pregnancy rates (CPRs) of frozen embryo transfer (FET) cycles.

SETTINGS AND DESIGN: This was a retrospective, comparative study done at a teaching hospital in assisted reproductive treatment.

MATERIALS AND METHODS: Three hundred and ten FET cycles were analysed, of which 125 had day 2 freezing and 185 had day 3 freezing. Depending upon the day of thawing and day of transfer, FET cycles were divided into six groups: Group 1 (day 2 thawing and day 3 transfer), Group 2 (day 2 thawing and day 4 transfer), Group 3 (day 2 thawing and day 5 transfer), Group 4 (day 3 thawing and day 3 transfer), Group 5 (day 3 thawing and day 4 transfer) and Group 6 (day 3 thawing and day 5 transfer).

STATISTICAL ANALYSIS USED: Statistical analysis was performed using version 14 R software version 4.0.1 (2020-06-06) (R foundation for Statistical Computing, Vienna, Austria). A P < 0.05 is taken as significant.

RESULTS: The CPR of Group 4 was 42.4% which was more than that of the other groups but it did not reach statistical significance.

CONCLUSIONS: Short incubation time of 2-4 h is as effective as an extended incubation time in terms of CPRs of FET cycles.

PMID:37305777 | PMC:PMC10256942 | DOI:10.4103/jhrs.jhrs_180_22

Chronobiol Int. 2023 Jun 11:1-7. doi: 10.1080/07420528.2023.2222816. Online ahead of print.

ABSTRACT

Since the use of light and electronic devices is inevitable, the use of blue light filters (in various light sources, electronic devices or optical devices including intraocular lenses) has been shown to improve sleep quality, especially in later hours of the day and during night time. In this study, we examine the effect of the blue light on sleep and wakefulness rhythms and positive and negative emotions. This randomized clinical trial was conducted with 80 AJA University of Medical Sciences employees who use computers at least 2 h a day. All subjects were employees of the discharge unit of Imam Reza Hospital, which is located next to AJA University. The subjects were divided into two groups of 40 people, blue light filter software intervention and sham treatment. Pittsburgh Sleep Quality Index (PSQI), Positive and Negative Affect Schedule (PANAS), Visual Function Questionnaire (VFQ), Epworth Sleepiness Scale (ESS) and salivary melatonin and cortisol levels were assessed for both groups before and 3 months after the intervention. Data analysis was performed using IBM SPSS statistics for windows, version 21.0 (Armonk, NY: IBM Corporation). P value ≤ 0.05 was considered as statistically significant. The results showed that the Pittsburgh sleep scale after the intervention was significantly lower in the intervention group than in the control group. After the intervention, the VFQ was significantly lower in the intervention group than in the control group (P = 0.018). There was no significant difference in the Epworth Sleepiness Scale (ESS) between the two study groups after the intervention (P = 0.370). There was no significant difference in Positive and Negative Affect Schedule (PANAS) in the two study groups after the intervention (P = 0.140). After the intervention, cortisol levels were significantly higher in the intervention group than in the control group (P = 0.006). Also, the amount of cortisol increased significantly in the intervention group (P = 0.028). The amount of melatonin decreased significantly in the intervention group (P = 0.034). The sleep quality score after the intervention was significantly lower in the intervention group than in the control group. This indicates better sleep quality in the intervention group. The results also show that the level of visual fatigue in the intervention group decreased significantly. However, no significant change was detected regarding positive and negative emotions. After the intervention, cortisol levels were significantly higher in the intervention group than the control group. In addition, cortisol levels increased significantly and melatonin levels decreased significantly in the intervention group during the course of study.

PMID:37302816 | DOI:10.1080/07420528.2023.2222816

Anal Biochem. 2023 Jun 9:115211. doi: 10.1016/j.ab.2023.115211. Online ahead of print.

ABSTRACT

LC-MS based multi-attribute methods (MAM) have drawn substantial attention due to their capability of simultaneously monitoring a large number of quality attributes of a biopharmaceutical product. For successful implementation of MAM, it is usually considered a requirement that the method is capable of detecting any new or missing peaks in the sample when compared to a control. Comparing a sample to a control for rare differences is also commonly practiced in many fields for investigational purpose. Because MS signal variability differs greatly between signals of different intensities, this type of comparison is often challenging, especially when the comparison is made without enough replicates. In this report we describe a statistical method for detecting rare differences between two very similar samples without replicate analyses. The method assumes that an overwhelming majority of components have equivalent abundance between the two samples, and signals with similar intensities have similar relative variability. By analyzing several monoclonal antibody peptide mapping datasets, we demonstrated that the method is suitable for new-peak detection for MAM as well as for other applications when rare differences between two samples need to be detected. The method greatly reduced false positive rate without a significant increase of false negative rate.

PMID:37302778 | DOI:10.1016/j.ab.2023.115211

Eur J Pharm Sci. 2023 Jun 9:106492. doi: 10.1016/j.ejps.2023.106492. Online ahead of print.

ABSTRACT

While many novel therapies have been approved in recent years for treating patients with multiple myeloma, there is still no established curative regimen, especially for patients with high-risk disease. In this work, we use a mathematical modeling approach to determine combination therapy regimens that maximize healthy lifespan for patients with multiple myeloma. We start with a mathematical model for the underlying disease and immune dynamics, which was presented and analyzed previously. We add the effects of three therapies to the model: pomalidomide, dexamethasone, and elotuzumab. We consider multiple approaches to optimizing combinations of these therapies. We find that optimal control combined with approximation outperforms other methods, in that it can quickly produce a combination regimen that is clinically-feasible and near-optimal. Implications of this work can be used to optimize doses and advance the scheduling of drugs.

PMID:37302768 | DOI:10.1016/j.ejps.2023.106492

Ann Oncol. 2023 Jun 9:S0923-7534(23)00721-4. doi: 10.1016/j.annonc.2023.05.012. Online ahead of print.

ABSTRACT

PURPOSE: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2+ breast cancer. Here, we evaluated the association of HER2DX scores with 1) pCR according to hormone receptor status and various treatment regimens, and 2) survival outcome according to pCR status.

METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n=765) in combination with pertuzumab (n=328), lapatinib (n=187) or without a second anti-HER2 drug (n=250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e., NEOHER and PAMELA) with a pCR (n=118) and without a pCR (n=150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low- or high-risk beyond pCR status.

RESULTS: HER2DX pCR score was significantly associated with pCR in all patients (odds-ratio [OR] per 10-unit increase=1.59, 95% CI 1.43-1.77; AUC=0.75), with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR=2.56, 1.29-5.20). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR=3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (p<0.001) and OS (p=0.006) compared to patients with HER2DX high-risk.

CONCLUSION: HER2DX pCR-score and risk-score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

PMID:37302750 | DOI:10.1016/j.annonc.2023.05.012

J Nutr. 2023 Jun 9:S0022-3166(23)72410-3. doi: 10.1016/j.tjnut.2023.05.031. Online ahead of print.

ABSTRACT

BACKGROUND: Vitamin B12 is involved in several physiological functions, and malabsorption is reported with medication use.

OBJECTIVE: Studies have reported an inverse association between use of metformin or acid lowering agents (ALAs) such as proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2RAs) and blood vitamin B12 concentration, due to malabsorption. The concomitant use of these medications is under reported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults.

METHODS: This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75y at baseline. Our study comprised 1428, 1155 and 782 participants at baseline, wave2 (2.2y from baseline) and wave3 (6.2y from baseline), respectively. Covariate-adjusted linear and logistic regression were used to examine association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 < 148 pmol/L or methylmalonic acid (MMA) > 271nmol/L), and long-term medication use (continuous use for ∼6.2y) and wave3 B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in B12 supplement users.

RESULTS: At baseline, we observed an association between metformin use (β = -0.069, P = 0.03) and concomitant ALA and metformin use (β = -0.112, P = 0.02) and vitamin B12 concentration, but not deficiency. We did not observe associations between ALA, PPI, or H2RA, individually, with vitamin B12 concentration or deficiency.

CONCLUSIONS: These results suggest an inverse relationship between metformin and concomitant ALA and metformin use and serum vitamin B12 concentration.

PMID:37302714 | DOI:10.1016/j.tjnut.2023.05.031