Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

BACKGROUND: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. METHODS: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models. RESULTS: Between 2005 and 2018 in 2 302 260 screening episodes among 2 107 016 migrants to four countries, the programmes identified 1658 TB cases (yield 72.0 (95% CI 68.6-75.6) per 100 000). In logistic regression analysis, we found associations between TB screening yield and age (≥55 years: OR 2.91 (95% CI 2.24-3.78)), being an asylum seeker (OR 3.19 (95% CI 1.03-9.83)) or on a settlement visa (OR 1.78 (95% CI 1.57-2.01)), close TB contact (OR 12.25 (95% CI 11.73-12.79)) and higher TB incidence in the country of origin. We demonstrated interactions between migrant typology and age, as well as country of origin. For asylum seekers, the elevated TB risk remained similar above country of origin incidence thresholds of 100 per 100 000. CONCLUSIONS: Key determinants of TB yield included close contact, increasing age, incidence in country of origin and specific migrant groups, including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in the country of origin. The high, country of origin-independent TB risk in asylum seekers above a 100 per 100 000 threshold could reflect higher transmission and re-activation risk of migration routes, with implications for selecting populations for TB screening.

An insight into the mechanisms of action of selected bioactive compounds against epigenetic targets of prostate cancer: implications on histones modifications.

Prostate cancer is a leading cause of morbidity and mortality among men globally. In this study, we employed an in silico approach to predict the possible mechanisms of action of selected novel compounds reported against prostate cancer epigenetic targets and their derivatives, exhausting through ADMET profiling, drug-likeness, and molecular docking analyses. The selected compounds: sulforaphane, silibinin, 3, 3'-diindolylmethane (DIM), and genistein largely conformed to ADMET and drug-likeness rules including Lipinski's. Docking studies revealed strong binding energy of sulforaphane with HDAC6 (- 4.2 kcal/ mol), DIM versus HDAC2 (- 5.2 kcal/mol), genistein versus HDAC6 (- 4.1 kcal/mol), and silibinin against HDAC1 (- 7.0 kcal/mol) coupled with improved binding affinities and biochemical stabilities after derivatization. Findings from this study may provide insight into the potential epigenetic reprogramming mechanisms of these compounds against prostate cancer and could pave the way toward more success in prostate cancer phytotherapy.

Mitracarpus hirtus (L.) DC.: is a potential source for the exploitation of anticancer agents.

Mitracarpus hirtus (L.) DC. is a weed plant commonly used for the treatment of eczema. The potential of the plant to treat cancer has not been emphasized, hence the need to explore its anticancer potential. M. hirtus was extracted and subjected to petition with solvents of increasing polarity. Its cytotoxic potential was evaluated against MCF-7, HepG2, and HeLa cells using the Neutral red assay and further verified through morphological assessment and DNA fragmentation assay. Crude chloroform fraction (CCF) displayed a cytotoxic effect on all the cell lines with low IC50 concentrations ranging from 11-17.87 µg/mL. Morphological assessment of MCF-7 exposed to CCF indicates apoptotic cell death and is further confirmed by its DNA fragmentation. Our data suggest that M. hirtus is a potential source for mining anticancer agents.

Sub-acute toxicity study on hydromethanolic leaves extract of Combretum hypopilinum (Combretaceae) Diels in Wistar rats.

The plant Combretum hypopilinum Diels (Combretaceae) has been utilized in Nigeria and other African nations to treat many diseases including liver, inflammatory, gastrointestinal, respiratory, infectious diseases, epilepsy and many more. Pharmacological investigations have shown that the plant possesses anti-infective, antidiarrhoeal, hepatoprotective, anti-inflammatory, anticancer, sedative, antioxidant, and antiepileptic potentials. However, information on its toxicity profile is unavailable despite the plant's therapeutic potential. As such, this work aimed to determine the acute and sub-acute oral toxic effects of the hydromethanolic leaves extract of C. hypopilinum. The preliminary phytochemical evaluation was carried out based on standard procedures. The acute toxicity evaluation was conducted by oral administration of the extract at the dose of 5000 mg/kg based on the guideline of the Organization of Economic Co-operation and Development (OECD) 423. To investigate the sub-acute toxicity effects, the extract was administered orally to the animals daily for 28-consecutive days at the doses of 250, 500, and 1000 mg/kg. Mortality, body weight and relative organ weight were observed. The hepatic, renal, haematological, and lipid profile parameters were investigated. The liver, kidney, heart, lung, small intestine, and stomach were checked for any histopathological alterations. The results of the phytochemical investigation showed cardiac glycosides, tannins, steroids, flavonoids, alkaloids, saponins, and triterpenes. Based on the acute toxicity investigation outcome, no death and signs of toxic effects were observed. The result showed that the oral median lethal dose (LD50) of the extract was more than the 5000 mg/kg. The extract remarkably reduced the weekly body weight of the animals at 500 mg/kg in the first and second weeks. It also significantly decreased the relative kidney weight, alkaline phosphatase, glucose, potassium, and low-density lipoprotein. There was a remarkable elevation in the percentage of eosinophils, basophils, monocytes, and granulocyte. There were histopathological abnormalities on the kidney, lung, stomach, and small intestine. The extract is relatively safe on acute exposure but moderately toxic at higher doses on sub-acute administration, particularly to the kidney.

A multi-centre observational study of HIV, tuberculosis and risk of chronic lung disease in urban West Africa.

OBJECTIVE: HIV and tuberculosis (TB) are risk factors for non-communicable chronic lung disease (CLD). Despite the high prevalence of these infections in West Africa, there are no studies that compare CLD between people with HIV and HIV-negative populations in this setting. This study sought to quantify the contribution of HIV and TB infection in addition to conventional CLD risk factors, such as tobacco and biofuel exposure, to CLD in urban West Africa. DESIGN: A multi-centre cross-sectional study was conducted in three community clinics in Lagos, Nigeria between 2018 and 2019. METHODS: Spirometry, questionnaires and clinical records were used to estimate prevalence of CLD and association with risk factors. RESULTS: In total, 148 HIV-negative individuals and 170 HIV-positive individuals completed the study. Current cigarette (11 of 318, 3.5%) and lifetime domestic biofuel (6 of 318, 1.8%) exposures were low. Airway obstruction (33 of 170, 19.4% vs. 12 of 148, 8.1%, P  = 0.004) and CLD (73 of 170, 42.9% vs. 34 of 148, 23%, P  < 0.0001) were more prevalent in people with HIV compared with the HIV-negative group. HIV infection [odds ratio 2.35 (1.33, 4.17), P  = 0.003] and history of TB [odds ratio 2.09 (1.04, 4.20), P  = 0.038] were independently associated with increased risk of CLD. CONCLUSION: HIV and TB far outweigh conventional risk factors, including tobacco and domestic biofuel exposure, as drivers of non-communicable CLD in urban West Africa. Current global policy for CLD may have limited impact on CLD in this setting. Enhanced prevention, diagnosis and management strategies for incident HIV and TB infections are likely to have a significant impact on long-term lung health in sub-Saharan Africa.

Improving Knowledge and Early Detection of Atrial Fibrillation through a Community-Based Opportunistic Screening Program: What's Your Beat?

A community-based opportunistic screening program was implemented to (i) improve atrial fibrillation (AF) awareness and detection and (ii) assess the performance of the Microlife WatchBP Home A for detecting AF when used in community screening. Screening sessions were conducted among people aged ≥ 65 years with no history of AF at public events across Tasmania, Australia. Participants with positive screening results were referred to their general medical practitioner for assessment. The device's performance was assessed using the positive predictive value. A total of 1704 eligible participants were screened at 79 sessions. Of these people, 50 (2.9%) had a positive screening result. The device correctly identified AF in 22 (46.8%) participants with positive results. Among those with subsequently confirmed AF, 6 (27.3%) had a history of AF but were not aware of the diagnosis, and 16 (72.7%) were identified to have previously undiagnosed AF, with an overall prevalence of 0.9% (95% CI, 0.58 to 1.52). Oral anticoagulation therapy was initiated in 12 (87.5%) eligible participants. The positive predictive value of the device was 46.8% (95% CI, 33.3 to 60.7). Given the relatively low performance of the device, its application in community-based opportunistic screening programs for AF is unlikely to be cost-effective.

Potential epigenetic modifications implicated in triple- to quadruple-negative breast cancer transition: a review.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Revisiting oil rents-output growth nexus in Nigeria: evidence from dynamic autoregressive distributive lag model and kernel-based regularized least squares approach.

Given the dominant role of oil in terms of foreign exchange earnings in Nigeria, this study revisits the oil rents and output growth nexus, using the novel dynamic autoregressive distributive lag (DYNARDL) model and kernel-based regularized least squares (KRLS) approach over the period 1973-2020. The major finding from this study is that oil rents are less significant for output and also exhibit decreasing marginal effect on output growth in Nigeria. However, our robustness result shows that oil revenue is positive and significantly affects output growth, while corruption dampens output growth. Result from the oil revenue model with a minimum root square mean error, when compared with the oil rents model, corroborate the finding. We are thus of the opinion that oil revenue is more important for output growth in Nigeria than oil rents. Having established this fact, it is recommended that policymakers and the government should accord utmost attention to boosting oil revenue via transparency and accountability. They should also ensure a lasting solution to the nation's high dependency on refined crude oil products importation for a sustainable economic growth and development. Also, more efforts should be directed at developing the seven identified strategic solid minerals to further enhance the revenue base of the government.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID-19.

Cytokine storm is a phrase used to refer to an abrupt upsurge in the circulating levels of various pro-inflammatory cytokines, causing increased stimulation and activity of immune cells during disease conditions. The binding of pattern recognition receptors to pathogen-associated molecular patterns during COVID-19 infection recruits response machinery involving the activation of transcription factors and proteins required for a robust immune response by host cells. These immune responses could be influenced by epigenetic modifications as evidenced by significant variations in COVID-19 pathophysiology and response to therapy observed among patients across the globe. Considering that circulating levels of interleukin 1, tumor necrosis factor-α, and interleukin 6 are significantly elevated during cytokine storm in COVID-19 patients, genetic and epigenetic variations in the expression and function of these proteins could enhance our understanding of the disease pathogenesis. Treatment options that repress the transcription of specific cytokine genes during COVID-19 infection could serve as possible targets to counteract cytokine storm in COVID-19. Therefore, the present article reviews the roles of cytokines and associated genes in the COVID-19 cytokine storm, identifies epigenetic modifications associated with the disease progression, and possible ameliorative effects of some vitamins and minerals obtained as epigenetic modifiers for the control of cytokine storm and disease severity in COVID-19 patients. PRACTICAL APPLICATIONS: COVID-19 causes mortality and morbidity that adversely affect global economies. Despite a global vaccination campaign, side effects associated with vaccination, misconceptions, and a number of other factors have affected the expected successes. Cytokine storm in COVID-19 patients contributes to the disease pathogenesis and response to therapy. Epigenetic variations in the expression of various cytokines could be implicated in the different outcomes observed in COVID-19 patients. Certain vitamins and minerals have been shown to interfere with the expression and activity of cytokines implicated in cytokine storm, thereby counteracting observed pathologies. This review examines cytokines implicated in cytokine storm in COVID-19, epigenetic modifications that contribute to increased expression of identified cytokines, specific foods rich in the identified vitamins and minerals, and suggests their possible ameliorative benefits. The article will be beneficial to both scientists and the general public who are interested in the role of vitamins and minerals in ameliorating COVID-19.

Dihydroartemisinin as a potential drug candidate for cancer therapy: a structural-based virtual screening for multitarget profiling.

Cancer is a rapidly growing non-communicable disease worldwide that is responsible for high mortality rates, which account for 9.6 million death in 2018. Dihydroartemisinin (DHA) is an active metabolite of artemisinin, an active principle present in the Chinese medicinal plant Artemisia annua used for malaria treatment. Dihydroartemisinin possesses remarkable and selective anticancer properties however the underlying mechanism of the antitumor effects of DHA from the structural point of view is still not yet elucidated. In the present study, we employed molecular docking simulation techniques using Autodock suits to access the binding properties of dihydroartemisinin to multiple protein targets implicated in cancer pathogenesis. Its potential targets with comprehensive pharmacophore were predicted using a PharmMapper database. The co-crystallised structures of the protein were obtained from a Protein Data Bank and prepared for molecular docking simulation. Out of the 24 selected protein targets, DHA has shown about 29% excellent binding to the targets compared to their co-crystallised ligand. Additionally, 75% of the targets identified for dihydroartemisinin binding are protein kinases, and 25% are non-protein kinases. Hydroxyl functional group of dihydroartemisinin contributed to 58.5% of the total hydrogen interactions, while pyran (12.2%), endoperoxide (9.8%), and oxepane (19.5%) contributed to the remaining hydrogen bonding. The present findings have elucidated the possible antitumor properties of dihydroartemisinin through the structural-based virtual studies, which provides a lead to a safe and effective anticancer agent useful for cancer therapy.Communicated by Ramaswamy H. Sarma.

Assessment of COVID-19 Information Overload Among the General Public.

BACKGROUND: A relentless flood of information accompanied the novel coronavirus 2019 (COVID-19) pandemic. False news, conspiracy theories, and magical cures were shared with the general public at an alarming rate, which may lead to increased anxiety and stress levels and associated debilitating consequences. OBJECTIVES: To measure the level of COVID-19 information overload (COVIO) and assess the association between COVIO and sociodemographic characteristics among the general public. METHODS: A cross-sectional online survey was conducted between April and May 2020 using a modified Cancer Information Overload scale. The survey was developed and posted on four social media platforms. The data were only collected from those who consented to participate. COVIO score was classified into high vs. low using the asymmetrical distribution as a guide and conducted a binary logistic regression to examine the factors associated with COVIO. RESULTS: A total number of 584 respondents participated in this study. The mean COVIO score of the respondents was 19.4 (± 4.0). Sources and frequency of receiving COVID-19 information were found to be significant predictors of COVIO. Participants who received information via the broadcast media were more likely to have high COVIO than those who received information via the social media (adjusted odds ratio ([aOR],14.599; 95% confidence interval [CI], 1.608-132.559; p = 0.017). Also, participants who received COVID-19 information every minute (aOR, 3.892; 95% CI, 1.124-13.480; p = 0.032) were more likely to have high COVIO than those who received information every week. CONCLUSION: The source of information and the frequency of receiving COVID-19 information were significantly associated with COVIO. The COVID-19 information is often conflicting, leading to confusion and overload of information in the general population. This can have unfavorable effects on the measures taken to control the transmission and management of COVID-19 infection.

Current Status of Endoplasmic Reticulum Stress in Type II Diabetes.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

COVID-19 lockdown may increase cardiovascular disease risk factors.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and was declared a worldwide pandemic by the World Health Organization (WHO) on 11 March 2020 which is leading to significant morbidity and mortality. In compliance with WHO recommendation of movement restrictions, many countries have imposed compulsory self-quarantine and restricted movements of their citizenries (lockdown/sit at home) and closure of businesses and borders as preventive measures to the fast-spreading virus. Consequently, this decision has made the emergence of behaviors that are detrimental to cardiovascular diseases (CVDs) which are the leading cause of the global mortality rate. MAIN BODY: The increase in sedentary lifestyles, alcohol consumption, and substance abuse during COVID-19 pandemic lockdown as a result of personal restrictions in COVID-19 lockdown is linked with the risk of death from chronic diseases such as cardiovascular diseases (CVDs). CONCLUSION: The lockdown has increased risk factors of CVDs, and as such, there might be an increase in the number of non-communicable disease (NCD)-related mortality rate. The effect does not end during the period of coronavirus pandemic but even after the pandemic.

The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study.

OBJECTIVE: To investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK). METHODS: This cross-sectional study used data collected in the UK Prognostic Evaluation of Diagnostic Interferon-Gamma Release Assays (IGRAs) Consortium Study which enrolled 9176 recent tuberculosis (TB) contacts and migrants at National Health Service (NHS) facilities and community settings in the UK. The study outcome was LTBI (positive IGRA test (QuantiFERON-TB Gold In-Tube or T-SPOT.TB)). The main exposures were history of smoking, history of substance misuse, homelessness, prison stay and socioeconomic deprivation. RESULTS: 4914 (56.2%) individuals resided in the most deprived areas and 2536 (27.6%) had LTBI. In the multivariable analysis (adjusting for age, gender, place of birth, ethnicity, HIV status, BCG vaccination and recent TB contact) living in the least deprived areas compared with living in the most deprived areas was associated with reduced odds of LTBI (odds ratio (OR)=0.68, 95% CI: 0.51 to 0.90) while ever been homeless (OR=1.50, 95% CI: 1.02 to 2.21) was associated with increased odds of LTBI. Smoking, homelessness and substance misuse were not associated with LTBI. CONCLUSION: Social deprivation could be an important risk factor for LTBI, highlighting the social inequality in the burden of TB infection in the UK. Migrants and TB contacts who were socially deprived or homeless were at a significantly higher risk for LTBI, thus tailored intense public health interventions to these groups may help to reduce the risk of future TB disease. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01162265).