Catalytic Framework: Intersectional Analysis for Community Engagement

The Community Engagement Centre (CEC) has been active across a range of diverse urban and rural populations throughout Pakistan and works closely with marginalised communities. The collective nature of Pakistani culture and its social inequities has required the CEC to recognize the intersections that shape contexts and situations, to promote local ownership, empower communities to identify and utilize existing resources for sustainable change, and improve health outcomes. Through an immersive community engagement (CE) strategy, CEC utilises participatory tools to collect stories from communities to understand their lived experiences, barriers and enablers to access, and the dynamics of power that influence these. To understand this complex relationship, a Catalytic Framework that examined the intersections within communities’ narratives was developed. Preliminary review of community narratives collected as part of programmatic operations yielded four significant elements: (1) unique, individual circumstances, (2) aspects of identity, (3) types of discrimination (if present), and (4) larger structures that reinforce exclusion (or enforce inclusion). A unique feature identified within the process of CE was the role of ‘catalysts’ – one or many people who may have transformative potential at any of these levels due to their influence, active facilitation, or agency. This novel framework enables an understanding of the threads of experience and identifying the elements and structures that impact lives of Pakistan’s diverse population. It works by recognizing the visible intersections of class, identity, gender, and power, as well as questioning what remains unarticulated, and thus promotes meaningful community engagement across different cultures and fields

Catalytic Framework: Intersectional Analysis for Community Engagement

The Community Engagement Centre (CEC) has been active across a range of diverse urban and rural populations throughout Pakistan and works closely with marginalised communities. The collective nature of Pakistani culture and its social inequities has required the CEC to recognize the intersections that shape contexts and situations, to promote local ownership, empower communities to identify and utilize existing resources for sustainable change, and improve health outcomes. Through an immersive community engagement (CE) strategy, CEC utilises participatory tools to collect stories from communities to understand their lived experiences, barriers and enablers to access, and the dynamics of power that influence these. To understand this complex relationship, a Catalytic Framework that examined the intersections within communities’ narratives was developed. Preliminary review of community narratives collected as part of programmatic operations yielded four significant elements: (1) unique, individual circumstances, (2) aspects of identity, (3) types of discrimination (if present), and (4) larger structures that reinforce exclusion (or enforce inclusion). A unique feature identified within the process of CE was the role of ‘catalysts’ – one or many people who may have transformative potential at any of these levels due to their influence, active facilitation, or agency. This novel framework enables an understanding of the threads of experience and identifying the elements and structures that impact lives of Pakistan’s diverse population. It works by recognizing the visible intersections of class, identity, gender, and power, as well as questioning what remains unarticulated, and thus promotes meaningful community engagement across different cultures and fields

Exploring Celiac Disease: A Case Analysis of Multi-Systemic Symptoms and Effective Dietary Intervention in a Young Female

This study presents the case of a 23-year-old woman diagnosed with celiac disease (CD), a condition triggered by an immune response to gluten, leading to inflammation in the small intestine. The patient manifested typical gastrointestinal symptoms, including diarrhea, abdominal pain, and vomiting, complemented by extra-intestinal signs such as fatigue and skin rashes. Diagnosis was corroborated through the presence of tTG-IgA antibodies and distinct histological changes in the duodenum. A notable finding was the patient\u27s iron deficiency anemia, directly linked to the duodenal damage caused by CD. Effective management, encompassing a strict gluten-free diet and iron supplementation, resulted in marked improvement in her condition. This case accentuates the significance of early CD detection, especially in patients exhibiting a combination of gastrointestinal and extra-intestinal symptoms. Emphasis is placed on the pivotal role of timely diagnosis, adherence to a gluten-free regimen, and sustained monitoring to ensure patient well-being and prevent complications

The characteristics of appendicoliths associated with acute appendicitis

Introduction: Differences between appendicoliths associated with appendicitis and those found incidentally have not been studied. The objective of this study was to determine the characteristics of appendicoliths that are associated with acute appendicitis. Methods: A cross-sectional study of patients with appendicoliths identified on computed tomographic (CT) scan from January 2008 till December 2014 was conducted. Patients were divided into two group: appendicitis and appendicoliths (AA) and incidentally discovered appendicoliths (IA). Results: Overall, 321 patients were included in the study. Of these, 103 (32%) patients were in the AA group while 218 (68%) patients were in the IA group. Both groups were similar in age and gender distribution. Significantly greater proportion of patients in the AA group had more than one appendicolith [AA vs. IA: 63 (62%) vs. 82 (38%), p \u3c 0.001], appendicolith location at the base [AA vs. IA: 34 (33%) vs. 33 (15%), p \u3c 0.001] and appendicolith diameter of 5 mm or more [AA vs. IA: 71 (69%) vs. 28 (13%), p \u3c 0.001]. On multivariate analysis, more than one appendicolith [Odds ratio (OR): 1.9, 95% CI: 1.1-3.4; p = 0.02] and diameter of 5 mm or more (OR: 13, 95% CI: 7.1-23.6; p \u3c 0.001) were independently associated with acute appendicitis. Conclusion: Multiple appendicoliths and appendicoliths larger than 5 mm are associated with acute appendicitis

Current Management Strategies in Breast Cancer by Targeting Key Altered Molecular Players

Breast Cancer is second largest disease affecting women worldwide. It remains the most frequently reported and leading cause of death among women in both developed and developing countries. Chemoprevention is one the promising approaches which reduces breast cancer. Tamoxifen and raloxifene are commonly used for treatment of breast cancer in women with high risk, although resistance occurs by tamoxifen after five years of therapy and both drugs cause uterine cancer and thromboembolic events. Aromatase inhibitors are coming up as potential option for prevention in treatment with adjuvant trials in practice. The combination of aromatase inhibitors along with tamoxifen can also be beneficial. For this, clinical trials based on large number of patients with optimal dose and lesser side effects have to be more in practice. Despite the clinical trials going on, there is need of better molecular models which can identify high risk population and new agents with better benefit having less side effects and improved biomarkers for treating breast cancer

Whole exome sequence of Pakistani acute lymphocytic leukemia patient from Pakhtuns ancestry reveal the novel genetic variant characterization in the GLDC gene

Background: Acute Lymphoblastic Leukemia (ALL) is the most common malignant disease in children and often involves numerical chromosomal abnormalities, fusion genes, or minor localized deletions that are significant in the development of leukemia. Glycine Decarboxylase (GLDC) gene overexpression and mutation is associated with oncogenic activity in various cancers. However, the pathophysiological roles and structural consequences of GLDC in acute lymphocytic leukemia have not been investigated. Objective: We aimed to identify novel variant in acute lymphocytic leukemia through whole exome sequencing. Methods: This study employs whole exome sequencing to examine seven pediatric patients with Acute Lymphoblastic Leukemia (ALL) in Pakistan. The patients under investigation are of Pakistani origin. The deleterious effect was predicted by SIFT, PolyPhen2, CADD, FATHMM, HOPE, and Mutation Assessors. Structure stability assessment was performed using the I-Mutant-3.0server. The atomic structure of the Single Nucleotide Polymorphism (SNP) was analyzed utilizing the Molecular Dynamics (MD) with WEBGRO server. Results: The present study identified a novel pathogenic heterozygous variant NM_000170.2:p.Ser551Cys/c.1651A>T in GLDC gene of early stage diagnose ALL patient the variant was not present in the dbSNP & 1000Genome Project databases. Structural instability, disrupted function, and altered 3D structure were observed in the mutant GLDC protein model compared to the wild-type structure. Conclusion: The novel SNP was found in a highly conserved region of the GLDC protein and is predicted to be a high-risk candidate for leukemia. This variant greatly affects the stability of the protein

Characterization of rare spontaneous Human Immunodeficiency Virus viral controllers attending a national United Kingdom clinical service using a combination of serology and molecular diagnostic assays

Background We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805–1336), and normal CD4/CD8 ratio (median 1.8, range 1.2–1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4–14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation

Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human

Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation

The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017 : a systematic analysis for the Global Burden of Disease study 2017

Background: Stomach cancer is a major health problem in many countries. Understanding the current burden of stomach cancer and the differential trends across various locations is essential for formulating effective preventive strategies. We report on the incidence, mortality, and disability-adjusted life-years (DALYs) due to stomach cancer in 195 countries and territories from 21 regions between 1990 and 2017. Methods: Estimates from GBD 2017 were used to analyse the incidence, mortality, and DALYs due to stomach cancer at the global, regional, and national levels. The rates were standardised to the GBD world population and reported per 100 000 population as age-standardised incidence rates, age-standardised death rates, and age-standardised DALY rates. All estimates were generated with 95% uncertainty intervals (UIs). Findings: In 2017, more than 1·22 million (95% UI 1·19–1·25) incident cases of stomach cancer occurred worldwide, and nearly 865 000 people (848 000–885 000) died of stomach cancer, contributing to 19·1 million (18·7–19·6) DALYs. The highest age-standardised incidence rates in 2017 were seen in the high-income Asia Pacific (29·5, 28·2–31·0 per 100 000 population) and east Asia (28·6, 27·3–30·0 per 100 000 population) regions, with nearly half of the global incident cases occurring in China. Compared with 1990, in 2017 more than 356 000 more incident cases of stomach cancer were estimated, leading to nearly 96 000 more deaths. Despite the increase in absolute numbers, the worldwide age-standardised rates of stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with improved Socio-demographic Index. Globally, 38·2% (21·1–57·8) of the age-standardised DALYs were attributable to high-sodium diet in both sexes combined, and 24·5% (20·0–28·9) of the age-standardised DALYs were attributable to smoking in males. Interpretation: Our findings provide insight into the changing burden of stomach cancer, which is useful in planning local strategies and monitoring their progress. To this end, specific local strategies should be tailored to each country's risk factor profile. Beyond the current decline in age-standardised incidence and death rates, a decrease in the absolute number of cases and deaths will be possible if the burden in east Asia, where currently almost half of the incident cases and deaths occur, is further reduced. Funding: Bill & Melinda Gates Foundation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London