Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 μg/mL, n = 9 vs. 1.4 ± 0.3 μg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity

Expression of B-cell Lymphoma 2 (BCL-2) in Breast Cancer

Introduction: Immunohistochemical expression of B-cell lymphoma 2 (BCL-2) is seen variably in invasive ductal carcinoma. This study was conducted to determine the frequency of BCL-2 expression in different histologic grades of invasive ductal carcinoma. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan, on subjects with invasive ductal carcinoma of various histologic grades. Immunohistochemistry was done using the BCL-2 antibody in all cases. The frequency of BCL-2 positive cases in different histologic grades was noted. Post-stratification, the chi-square test was applied. A p-value ≤ 0.05 was considered significant. Results: All 52 subjects were females (100%) with a mean age of 47.58 ± 1.43 years. BCL-2 expression was observed in 28 (53.85 %) subjects with breast cancer. Out of 33 participants with grade III, 13 (39.39 %) participants were positive for BCL-2 expression. Among 18 subjects with grade II, 14 (77.78 %) subjects were positive for BCL-2 expression. Reduced frequency of BCL-2 expression was observed with increasing histologic grade (i.e., more in low-grade tumors and less in grade III), but the difference was statistically not significant. Conclusion: A differential expression of BCL-2 was observed across different grades of invasive ductal carcinoma. However, the difference was not statistically significant

Technical and Economic Evaluation of a 50 MW Solar Power Plant in Quetta

Pakistan is a developing country that is facing its worst energy crisis in two decades. In recent years, the gap between demand and supply has multiplied. With increasing demand, this situation has triggered a complete power shutdown in urban areas for 10&ndash;12 h and rural areas for 16&ndash;18 h. The prime objective of this study is to evaluate the techno-economic feasibility of a 50 MW solar farm in Quetta, Pakistan. Solar radiation data are collected from radiation devices, i.e., a tier two weather station with a rotating shadow band irradiometer. The devices collected data every 10 min. The data were gathered for one year, and a techno-economic evaluation of the information has been carried out. For the proposed plant&rsquo;s economic feasibility evaluation, the levelized cost of electricity (LCOE) model is used and estimates that the energy produced by the proposed power plant will cost 6 Pkr/kWh. Technical evaluation of the power plant reveals that 91.980 GWh of electricity can be produced per year at the capital cost of 59.689 million USD, with an O and M cost of 0.9 million USD/year and a 10.5498 discount rate (%). An economic evaluation of the proposed PV plant produces electricity at 0.0385 USD/kWh. The results of this study depict that a 50 MW PV plant will be feasible for Quetta

Recent developments in catalyst synthesis using DBD plasma for reforming applications

The catalyst has a significant role in gas processing applications such as reforming technologies for H2 and syngas production. The stable catalyst is requisite for any industrial catalysis application to make it commercially viable. Several methods are employed to synthesize the catalysts. However, there is still a challenge to achieve a controlled morphology and pure catalyst which majorly influences the catalytic activity in reforming applications. The conventional methods are expansive, and the removal of the impurities are major challenges. Nevertheless, it is not straightforward to achieve the desired structure and stability. Therefore, significant interest has been developed on the advanced techniques to take control of the physicochemical properties of the catalyst through non-thermal plasma (NTP) techniques. In this review, the systematic evolution of the catalyst synthesis using NTP technique is elucidated. The emerging DBD plasma to synthesized and effective surface treatment is reviewed. DBD plasma synthesized catalyst performance in reforming application for H2 and syngas production is summarised. Furthermore, the status of DBD plasma for catalyst synthesis and proposed future avenues to design environmentally suitable and cost-effective synthesis techniques are discussed

National cervical cancer burden estimation through systematic review and analysis of publicly available data in Pakistan

Abstract Background Cervical cancer is a major cause of cancer-related deaths among women worldwide. Paucity of data on cervical cancer burden in countries like Pakistan hamper requisite resource allocation. Objective To estimate the burden of cervical cancer in Pakistan using available data sources. Methods We performed a systematic review to identify relevant data on Pakistan between 1995 to 2022. Study data identified through the systematic review that provided enough information to allow age specific incidence rates and age standardized incidence rates (ASIR) calculations for cervical cancer were merged. Population at risk estimates were derived and adjusted for important variables in the care-seeking pathway. The calculated ASIRs were applied to 2020 population estimates to estimate the number of cervical cancer cases in Pakistan. Results A total of 13 studies reported ASIRs for cervical cancer for Pakistan. Among the studies selected, the Karachi Cancer Registry reported the highest disease burden estimates for all reported time periods: 1995–1997 ASIR = 6.81, 1998–2002 ASIR = 7.47, and 2017–2019 ASIR = 6.02 per 100,000 women. Using data from Karachi, Punjab and Pakistan Atomic Energy Cancer Registries from 2015–2019, we derived an unadjusted ASIR for cervical cancer of 4.16 per 100,000 women (95% UI 3.28, 5.28). Varying model assumptions produced adjusted ASIRs ranging from 5.2 to 8.4 per 100,000 women. We derived an adjusted ASIR of 7.60, (95% UI 5.98, 10.01) and estimated 6166 (95% UI 4833, 8305) new cases of cervical cancer per year. Conclusion The estimated cervical cancer burden in Pakistan is higher than the WHO target. Estimates are sensitive to health seeking behavior, and appropriate physician diagnostic intervention, factors that are relevant to the case of cervical cancer, a stigmatized disease in a low-lower middle income country setting. These estimates make the case for approaching cervical cancer elimination through a multi-pronged strategy

Observation of four top quark production in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe observation of the production of four top quarks in proton-proton collisions is reported, based on a data sample collected by the CMS experiment at a center-of-mass energy of 13 TeV in 2016-2018 at the CERN LHC and corresponding to an integrated luminosity of 138 fb$^{-1}$. Events with two same-sign, three, or four charged leptons (electrons and muons) and additional jets are analyzed. Compared to previous results in these channels, updated identification techniques for charged leptons and jets originating from the hadronization of b quarks, as well as a revised multivariate analysis strategy to distinguish the signal process from the main backgrounds, lead to an improved expected signal significance of 4.9 standard deviations above the background-only hypothesis. Four top quark production is observed with a significance of 5.6 standard deviations, and its cross section is measured to be 17.7$^{+3.7}_{-3.5}$ (stat) $^{+2.3}_{-1.9}$ (syst) fb, in agreement with the available standard model predictions