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Objectives: To compare the cut scores and pass/fail rates achieved by arbitrary 60% method and Hofstee method in an undergraduate year 4 end semester objective structured clinical examination (OSCE) and check the possibility of using Hofstee method of standard setting in future exams. Method: 102 medical students of year 4 underwent a 10 station OSCE exam conducted in a state of art simulation lab in 3 cycles. The cut scores were calculated using arbitrary method aiming at 60% of task achievement and by Hofstee method. The student’s obtained scores were compared for cut scores and pass rates for individual stations and the entire exam. Results: The arbitrary and Hofstee methods of standard setting leads to different cut scores. For the individual stations it was 60% vs 65-70% and for the overall score it was 60% vs 70%. The percentage of students failing the exam is 13.7% based on arbitrary scores and is 29.4% when Hofstee cut score is applied. Conclusions: The two methods lead to different cut scores and students’ failure rates. Overall, Hofstee method is more appropriate for assessing competencies in an OSCE exam in medical schools as it leads to calculation of cut scores based on the difficulty level of the station/exam and the examiners expected level of performance by the students.

Abstract Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI

BackgroundGlobally, 36.5% of pregnancies are affected by anemia, particularly in low-and middle-income countries, posing significant risks to maternal and perinatal health. In rural Pakistan, 44.3% of pregnant women suffer from iron deficiency, contributing to the high prevalence of anemia. Limited accessibility to antenatal care exacerbates the challenge, necessitating innovative solutions. This study assessed a midwife-led continuity of care model, utilizing intravenous (IV) iron therapy for the management of anemia in Karachi, Pakistan.MethodsWe performed a retrospective analysis of data from a prospective cohort study conducted in two primary healthcare facilities, which employed a community midwife (CMW)-led continuity of care model for antenatal care, including IV iron therapy. We extracted data from February 2021 to March 2022 for women who were diagnosed with anemia based on hemoglobin (Hb) levels, categorized as mild (10.0 to 10.9 g/dL), moderate (7.0 to 9.9 g/dL), or severe (less than 7.0 g/dL). Assessment occurred at the initial antenatal care (ANC) visit to establish baseline anemia severity, and approximately 2 weeks after intravenous (IV) iron therapy administration to evaluate post-treatment changes were considered.ResultsWe enrolled 114 pregnant women, where the majority presented with moderate (88.6%) anemia. After IV iron treatment, 48.5% improved to normal-mild levels, while 50% remained unchanged. Severe anemia affected 10.5% at baseline; 42% shifted to moderate and 50% to normal-mild post-treatment, with one remaining unchanged (p

Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission.

IntroductionNeonatal deaths and stillbirths are significant public health concerns in Pakistan, with an estimated stillbirth rate of 43 per 1,000 births and a neonatal mortality rate of 46 deaths per 1,000 live births. Limited access to obstetric care, poor health seeking behaviors and lack of quality healthcare are the leading root causes for stillbirths and neonatal deaths. Rehri Goth, a coastal slum in Karachi, faces even greater challenges due to extreme poverty, and inadequate infrastructure. This study aims to investigate the causes and pathways leading to stillbirths and neonatal deaths in Rehri Goth to develop effective maternal and child health interventions.MethodsA mixed-method cohort study was nested with the implementation of large maternal, neonatal and child health program, captured all stillbirths and neonatal death during the period of May 2014 till June 2018. The Verbal and Social Autopsy (VASA) tool (WHO 2016) was used to collect primary data from all death events to determine the causes as well as the pathways. Interviews were conducted both retrospectively and prospectively with mothers and caregivers. Two trained physicians reviewed the VASA form and the medical records (if available) and coded the cause of death blinded to each other. Descriptive analysis was used to categorize stillbirth and neonatal mortality data into high- and low-mortality clusters, followed by chi-square tests to explore associations between categories, and concluded with a qualitative analysis.ResultsOut of 421 events captured, complete VASA interviews were conducted for 317 cases. The leading causes of antepartum stillbirths were pregnancy-induced hypertension (22.4%) and maternal infections (13.4%), while obstructed labor was the primary cause of intrapartum stillbirths (38.3%). Neonatal deaths were primarily caused by perinatal asphyxia (36.1%) and preterm birth complications (27.8%). The qualitative analysis on a subset of 40 death events showed that health system (62.5%) and community factors (37.5%) contributing to adverse outcomes, such as delayed referrals, poor triage systems, suboptimal quality of care, and delayed care-seeking behaviors.ConclusionThe study provides an opportunity to understand the causes of stillbirths and neonatal deaths in one of the impoverished slums of Karachi. The data segregation by clusters as well as triangulation with qualitative analysis highlight the needs of evidence-based strategies for maternal and child health interventions in disadvantaged communities.

This study is an initial attempt to examine the correlation between energy consumption and economic growth in Saudi Arabia's carbon emissions from 1985 to 2021. Notably, despite the prominence of low-carbon economic growth in the Paris Agreement and the Sustainable Development Goals, this specific link has yet to be previously investigated. The study used an autoregressive distributed lag (ARDL) approach to analyse the relationship between carbon emissions from energy consumption and economic development in Saudi Arabia. The bound test shows that the relationship has been going on for a long time, and the error correction equation shows that the endogenous and exogenous variables are negatively related by 0.58. This indicates that the system adjusts its previous period's imbalance by 58% within a single period. The Granger causality test reveals a one-way causal relationship between energy use and carbon dioxide emissions, economic growth, and oil consumption. Additionally, the generation of energy through oil-based power plants is known to result in the release of carbon emissions, although in a unidirectional manner. It is necessary to prioritize exploring alternate methods for power generation, particularly those that rely on non-conventional or renewable energy sources.

Purpose Pakistan has disproportionately high maternal and neonatal morbidity and mortality. There is a lack of detailed, population-representative data to provide evidence for risk factors, morbidities and mortality among pregnant women and their newborns. The Pregnancy Risk, Infant Surveillance and Measurement Alliance (PRISMA) is a multicountry open cohort that aims to collect high-dimensional, standardised data across five South Asian and African countries for estimating risk and developing innovative strategies to optimise pregnancy outcomes for mothers and their newborns. This study presents the baseline maternal and neonatal characteristics of the Pakistan site occurring prior to the launch of a multisite, harmonised protocol.Participants PRISMA Pakistan study is being conducted at two periurban field sites in Karachi, Pakistan. These sites have primary healthcare clinics where pregnant women and their newborns are followed during the antenatal, intrapartum and postnatal periods up to 1 year after delivery. All encounters are captured electronically through a custom-built Android application. A total of 3731 pregnant women with a mean age of 26.6±5.8 years at the time of pregnancy with neonatal outcomes between January 2021 and August 2022 serve as a baseline for the PRISMA Pakistan study.Findings to date In this cohort, live births accounted for the majority of pregnancy outcomes (92%, n=3478), followed by miscarriages/abortions (5.5%, n=205) and stillbirths (2.6%, n=98). Twenty-two per cent of women (n=786) delivered at home. One out of every four neonates was low birth weight (

AbstractEven though the Paris Agreement and the Sustainable Development Goals say that low-carbon economic growth is essential, more research must be done to determine how the tourism sector affects carbon productivity. So, to see if increased energy usage, tourism, and economic growth jointly raise carbon productivity in Kuwait, this study uses a vector error correction strategy to look at the years 1995–2020. Predictions about how sustainable tourism will affect energy efficiency, and carbon productivity improvements are also an excellent way to learn more about this subject. As the amount of carbon dioxide in the air increases, tourism will go down by 0.13 percent. Inverse cointegration is the term for this phenomenon. However, the vector error correction model showed that carbon emissions go down as the economy grows and people pay more attention to how much energy they use. Nevertheless, Granger’s theory of cause and effect says that carbon emissions, energy use, and economic growth can only lead to more tourism in one way.

Abstract Background Helicobacter pylori is a key agent for causing gastric complications linked with gastric disorders. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the host’s autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented during infection and gastric cancer. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. Main methods Human gastric cancer (AGS) cells were infected with the H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression of autophagy proteins. Autophagy and lysosomal activity were monitored by fluorescence assays. A knockdown of HMGB1 was performed to verify the effect of glycyrrhizin. H. pylori infection in in vivo mice model was established and the effect of glycyrrhizin treatment was studied. Results The autophagy-lysosomal pathway was impaired due to an increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damage in mice. Conclusion This study showed that inhibiting HMGB1 restored lysosomal activity to ameliorate H. pylori infection. It also demonstrated the potential of glycyrrhizin as an antibacterial agent to address the problem of antimicrobial resistance.

As the world’s largest oil exporter, Saudi Arabia faces the same pressures as any other government to expand its economy. Saudi Vision 2030 is to reduce the country’s reliance on oil exports and revenues. One of the main goals of Saudi Vision 2030 is to increase the share of GDP that does not come from oil. Dynamic autoregressive distributed lag (ARDL) cointegration is used to look at how oil exports and exports of goods other than oil affect GDP growth. The results of the dynamic ARDL simulation show that there is both long-term and short-term cointegration between the variables. The dynamic ARDL simulation tests rely on the presence of cointegration to show that a 1% increase in oil exports will boost Saudi Arabia’s economic growth by about 0.48% in the long run and 0.18% in the short run, depending on the type of time frame. In the same way, the results about non-oil exports showed that an increase in non-oil exports would boost Saudi Arabia’s economic growth by 0.26 percentage points in the long run and by 0.16 percentage points in the short run. This is a good sign of Saudi Arabia’s efforts to diversify its economy away from oil exports and make room for international investors to help the country reach its Vision 2030 goals. AcknowledgmentThis study is supported via funding from Prince Sattam bin Abdulaziz University project number (PSAU/2023/R/1444).

This study determines Oman’s most important macroeconomic factors between 1990 and 2019. The ARDL bound test findings for co-integration show that both long and short runs exist. The error-correcting mechanism further states that when the divergence from long-run equilibrium is rectified at an adaptation speed of 78.9%, it signals an inversion to a long-run stable state. In response to a change in the previous year’s economic growth, the final consumption expenditure indicates a rise of 0.472; the gross fixed capital formation and export indicate hikes of 0.149 and 0.358 at a 1% significance level. Additionally, the findings of co-integration regression using fully modified ordinary least square (FMOLS), dynamic ordinary least square (DOLS), and canonical co-integration regression (CCR) were used to strengthen and validate the results that export ranks first in Oman, followed by final consumption spending. Therefore, export, gross fixed capital formation, and final consumption expenditure are vital macroeconomic elements supporting Oman’s economic development.

The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs—Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam—to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services.

Although low-carbon economic growth has been emphasized in both the Paris Agreement and the Sustainable Development Goals, this is the first study to examine the interplay between oil consumption, urbanization, and economic growth in India's GHG emissions from 1965 to 2021. A quantile regression analysis found that a one percent rise in greenhouse gas emissions is linked to a 0.34 percent rise in economic growth, a 0.599 percent rise in oil consumption, and a 0.28 percent drop in urbanization. Using the Granger causality technique, researchers found that CO2 emissions cause economic development and urbanization in only one direction. On the other hand, oil consumption only has a one-way influence on carbon emissions and urbanization, and economic expansion only has a one-way effect on urbanization.

Oil is among the enormously vital and most traded commodities globally, involving many forex transactions in the face of various types of shocks attributable to geopolitics, supply, demand, market crisis, etc. This study uses a systematic literature review approach to explore the Literature from the SCOPUS database considering the relationship between oil prices and exchange rates by analyzing the papers from 1998 to 2022 and includes the final 123 papers. This study emphasizes three objectives; Literature developed so far, standard methodologies and findings, and the research gaps which can be pursued in further studies. Findings show that vast literature is developed around these variables and sub-topics in various dimensions, such as the stock market, gold prices, economic growth, etc. Research around the variables has increased in the recent past, indicating the continued relevancy of the relationship. However, it can be due to increased access to higher education and research. This study also finds the gap in the literature and has implications for the policymakers in monetary and fiscal policy planning, as well as investors across the globe in making portfolio management strategies.

Objective: To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. Method: The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. Results: There were 51 male patients with a mean age of 33.10+8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p>0.05). Conclusion: Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications was rare and there was no mortality. Key Words: Chlorine gas, HAZMAT incident, Emergency department.

Objective This study aimed to estimate the burden of unintentional poisoning in South Asian countries from 1999 to 2019.Design An ecological study conducted at the regional level for South Asian countries, based on data from the Global Burden of Disease Study 2019.Setting We extracted unintentional poisoning data from the Global Burden of Disease Study data set from 1990 to 2019 to assess trends in mortality, disability-adjusted life-years (DALYs), years of life lost, years lived with disability (YLDs) and causative agents in South Asian countries (Bangladesh, Bhutan, India, Nepal and Pakistan).Outcome measures We determined the per cent change and 95% CI for the period between 1990 and 2019 by age, gender and country. We also conducted Poisson regression to measure the percentage change in the rate per year.Results The absolute number of deaths due to unintentional poisoning in South Asia decreased (−32.6%) from 10 558 deaths in 1990 to 7112 deaths in 2019. The age standardised death rate from unintentional poisoning in South Asia has seen a downward trend (−55.88%), declining from 0.87 (0.67–1.01) age-standardised per 100 000 population in 1990 to 0.41 (0.34–0.47) in 2019. Among age groups, under 9 years and 10–19 years have seen downward trends for death and DALYs, accounting for −93.5% and −38.3%, respectively. YLDs have seen an upward trend (5.9%), increasing from 10 461.7 per 100 000 in 1990 to 11 084 per 100 000 in 2019. YLDs in women increased by 7.4%, from 11 558.2 per 100 000 to 12 418.3 per 100 000. The incidence rate ratios (IRRs) adjusted by all age groups and gender for DALYs in all South Asian countries has reduced significantly (IRR 0.97, 95% CI 0.96 to 0.97) from 1990 to 2019.Conclusion This study showed reduction in death and DALYs due to unintentional poisoning in South Asia except YLDs which is showing an increasing trend. Public health systems should continue efforts to minimise and prevent disabilities arising from unintentional poisoning in South Asia.

Aims: The increased risk of suicide among individuals with diabetes is a significant public health concern. However, few studies have focused on understanding the relationship between suicide attempts and diabetes. Association rule mining (ARM) is a data mining technique to discover a set of high-risk factors of a given disease. Therefore, this study aimed to utilize ARM to identify a high-risk group of suicide attempts among patients with diabetes using Cerner Real-World Data™ (CRWD). Methods: The study analyzed a large multicenter electronic health records data of 3,265,041 patients with diabetes from 2010 to 2020. The Least Absolute Shrinkage and Selection Operator regression with ten-fold cross-validation and the Apriori algorithm with ARM were used to uncover groups of high-risk suicide attempts. Results: Of the 52,217,517 unique patients in the CRWD, 3,266,856 were diagnosed with diabetes. There were 7764 (0.2%) patients with diabetes who had a history of suicide attempts. The study revealed that patients with diabetes who were never married and had average blood glucose levels below 150 mg/dl were more likely to attempt suicide. In contrast, patients with diabetes aged 60 and older who had diabetes for less than five years and A1C levels between 6.5 and 8.9% were less likely to attempt suicide. Risk factors were strongly associated with suicide attempts, including never married, White, blood glucose levels below 150 mg/dl, and LDL levels below 100 mg/dl. Conclusions: This is the first study utilizing ARM to discover the risk patterns for suicide attempts in individuals with diabetes. ARM showed the potential for knowledge discovery in large multi-center electronic health records data. The results are explainable and could be practically used by providers during outpatient clinic visits. Further studies are needed to validate the results and investigate the cause-and-effect relationship of suicide attempts among individuals with diabetes.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.

This paper applies a novel Bootstrap Autoregressive Distributed Lag (BARDL) approach to investigate the relationship between green innovation (GI), economic growth (GDP), drama and film (D&F) industry, and environmental sustainability in India for the 1995 to 2020 period. The data has been checked for its stationarity by applying the Zivot and Andrews (ZA) unit root test, and the cointegration test results suggest a long-run equilibrium relationship between the variables. The empirical finding of long-run estimates reveals that 1% augments of GI, GDP, and D&F industry increase CO2 emissions by −0.079, 0.566%, and 0.143%, respectively. Furthermore, the main results indicate that GDP and the D&F industry have statistically significant positive effects on CO2 emissions, and GI has statistically significant negative effects on CO2 emissions. The GI leads to lower environmental damage by reducing carbon emissions. Regarding causal relationships, bidirectional causality is found between D&F and CO2 emissions, GI and CO2 emissions. In addition, a unidirectional causality is also revealed from GDP to CO2 emissions. Based on the finding of this study, policy implications are suggested for India.

Local government innovation support (LGIS) is an exogenous pulling force for high-quality economic development. Accurately identifying the mechanism by which LGIS affects green development remains practically and theoretically significant for building a long-term framework for driving green development. Based on provincial panel data (2010–2019), this paper uses the Super-SBM model to measure the green development efficiency (GDE) of different provinces in China. A dynamic panel GMM model is constructed to evaluate the significant relationship between LGIS and GDE and to explore the potential impact mechanism of other key factors such as fixed asset investment (FAI), environmental regulation (ER), industrial structure (IS), and foreign direct investment (FDI) on GDE. The estimation showed that LGIS had a positive impact on GDE. The data analysis indicated that GDE in the lag period significantly affected the GDE in the current period. More so, as per the results, the promoting effect of GDE in the second lag period gradually weakened due to the decline of LGIS and ER restrictions. The current model also revealed that FAI and ER inhibited the GDE progress, while IS and FAI had improved the state of GDE in the region. The research findings imply that China should further increase the government innovation expenditure, FDI utilization, and IS upgrade to promote high-quality economic development.

Abstract Background Great disparities in immunization coverage exist in Pakistan between urban and rural areas. However, coverage estimates for large peri-urban slums in Sindh are largely unknown and implementation challenges remain unexplored. This study explores key supply- and demand-side immunization barriers in peri-urban slums, as well as strategies to address them. It also assesses immunization coverage in the target slums. Methods Conducted in four peri-urban slums in Karachi, this mixed-methods study consists of a baseline cross-sectional coverage survey of a representative sample of 840 caregivers of children aged 12–23 months, and 155 in-depth interviews (IDIs) through purposive sampling of respondents (caregivers, community influencers and immunization staff). After identifying the barriers, a further six IDIs were then conducted with immunization policy-makers and policy influencers to determine strategies to address these barriers, resulting in the development of an original validated implementation framework for immunization in peri-urban slums. A thematic analysis approach was applied to qualitative data. Results The survey revealed 49% of children were fully vaccinated, 43% were partially vaccinated and 8% were unvaccinated. Demand-side immunization barriers included household barriers, lack of knowledge and awareness, misconceptions and fears regarding vaccines and social and religious barriers. Supply-side barriers included underperformance of staff, inefficient utilization of funds, unreliable immunization and household data and interference of polio campaigns with immunization. The implementation framework’s policy recommendations to address these barriers include: (1) improved human resource management; (2) staff training on counselling; (3) re-allocation of funds towards incentives, outreach, salaries and infrastructure; (4) a digital platform integrating birth registry and vaccination tracking systems for monitoring and reporting by frontline staff; (5) use of digital platform for immunization targets and generating dose reminders; and (6) mutual sharing of resources and data between the immunization, Lady Health Worker and polio programmes for improved coverage. Conclusions The implementation framework is underpinned by the study of uncharted immunization barriers in complex peri-urban slums, and can be used by implementers in Pakistan and other developing countries to improve immunization programmes in limited-resource settings, with possible application at a larger scale. In particular, a digital platform integrating vaccination tracking and birth registry data can be expanded for nationwide use.

We presented the late magnetic resonance imaging characteristics in a 47-year-old male who diagnosed with a permanent trauma-induced diabetes insipidus. The patient developed polyuria following a deceleration injury which has been diagnosed as central diabetes insipidus based on the water deprivation test. Computed tomography or magnetic resonance evaluation of the pituitary gland is usually normal in such cases. Therefore, negative imaging studies do not exclude the diagnosis. However, MRI is more sensitive and can depict subtle injuries of the hypothalamus-pituitary axis in acute and late phases. The late MR imaging findings are not well established. To the best of our knowledge, this will be the first report to describe the late MR imaging features in a permanent case of trauma-induced diabetes insipidus.

Angiomyofibroblastoma (AMF) is a rare benign soft-tissue tumor that most frequently affects the lower genital tract of young to middle-aged women. It mainly consists of two components: stromal cells and prominent vasculature. Clinically, it is usually asymptomatic and resembles Bartholin's cyst. Although it is a benign tumor, cases with recurrence and sarcomatous transformation have been reported. Due to the overlapping of histopathological picture, diagnostic perplexity often arises between AMF and aggressive angiomyxoma (AAM). AMF being benign in nature is treated by local excision, whereas AAM is a more infiltrative lesion that has a higher tendency for local recurrence.

Travel and tourism have glimpsed a significant and promising implication for economic development. Despite the commendatory implication of tourism, it levies a stringent environmental cost such as environmental degeneration. Hence, this study will incorporate the 18 countries out of the top 20 travel and tourism contributors to economic growth to assess the progressive correlation between tourist arrival, economic growth, energy consumption, and oil consumption on carbon emission by applying panel ARDL spanning from 1995 to 2019. The outcome of the panel ARDL reveals that both periods have witnessed that the endogenous variables have a substantial and positive impact on environmental degradation except for tourism as it indicates −0.22 and −0.48% in the long and short run, having a rate of adjustment as −0.52 toward the equilibrium. The simultaneous quantile regression reveals that in the 50 and 75 percentiles, the effect of tourism has a negative impact, which contradicts the PMG findings. These determinations suggest that the policymakers look for more manageable and environmentally sound tourism and economic growth procedures to safeguard the sustainable environment in the studied countries.

Antibiotic treatment plays an essential role in preventing Shigella infection. However, incidences of global rise in antibiotic resistance create a major challenge to treat bacterial infection. In this context, there is an urgent need for newer approaches to reduce S. flexneri burden. This study largely focuses on the role of the herbal compound capsaicin (Caps) in inhibiting S. flexneri growth and evaluating the molecular mechanism behind bacterial clearance. Here, we show for the first time that Caps inhibits intracellular S. flexneri growth by inducing autophagy. Activation of autophagy by Caps is mediated through transcription factor TFEB, a master regulator of autophagosome biogenesis. Caps induced the nuclear localization of TFEB. Activation of TFEB further induces the gene transcription of autophagosomal genes. Our findings revealed that the inhibition of autophagy by silencing TFEB and Atg5 induces bacterial growth. Hence, Caps-induced autophagy is one of the key factors responsible for bacterial clearance. Moreover, Caps restricted the intracellular proliferation of S. flexneri-resistant strain. The efficacy of Caps in reducing S. flexneri growth was confirmed by an animal model. This study showed for the first time that S. flexneri infection can be inhibited by inducing autophagy. Overall observations suggest that Caps activates TFEB to induce autophagy and thereby combat S. flexneri infection.

Background: A Medical Acute Care Unit (MACU) was established at Chris Hani Baragwanath Academic Hospital (CHBAH) to provide comprehensive medical specialist care to the patients presenting with acute medical emergencies. Improved healthcare delivery systems at the MACU may result in shorter hospital stays, better outcomes, and less mortality. Objectives: The study's objective was to describe the demographics, diagnoses, disease patterns, and outcomes, including patient's mortality, admitted to the MACU at CHBAH. Methods: Records of 200 patients admitted, between March 2015 to August 2015, to the MACU at CHBAH were reviewed. Patient demographics, diagnosis at admission, duration of stay, and outcomes were documented. Patients transferred to the medical ward, the Intensive Care Unit (ICU), or discharge. The leading causes of mortality were documented. Results: Of the 200 patients, 59% were females. The patients' mean age was 46 (17.2) years, and the mean duration of stay at the MACU was 1.45 (1.25) days. Non-communicable diseases accounted for 76% of admissions. The most frequently diagnosed conditions included: diabetic ketoacidosis acidosis (DKA) and hyperosmolar non-ketotic (HONK) (17.5%), non-accidental self-poisoning (16%), hypertensive emergencies (9.5%), decompensated cardiac failure (8%) and ischemic heart disease (7%). Infectious diseases comprised 14% of the diagnoses, of which cases of pneumonia were the most common (5%). Most patients (77.5%) were transferred to medical wards, 12% to ICU, while 10% demised at the MACU. The leading causes of death included sepsis (25%), DKA/HONK (20%), non-accidental self-poisoning (10%), and cardiac failure (10%). Conclusion: Non-communicable diseases, particularly diabetic emergencies, were the leading causes of admission to the MACU at CHBAH. During the study period, high rates of case improvement, patient discharge, shorter hospital stay, and less mortality were observed. The leading cause of mortality was sepsis related.

Abstract Objective To assess knowledge and practice trends in managing acute pain in patients infected with human immunodeficiency virus (HIV+) or having acquired immunodeficiency syndrome (AIDS) among emergency physicians of four tertiary care hospitals. Acute pain management in such patients is complex because of multiple concomitant painful conditions related to their disease. After obtaining ethical approval and written informed consent, emergency physicians were requested to fill out a questionnaire. Results Out of 84 physicians who participated, 49 had managed HIV+/AIDS patients during the preceding year. Out of the 49, 30 (61.2%) physicians stated that they used a combination of analgesics for acute pain in these patients. Forty-two (50%) out of the 84 participants believed that routine doses of opioids were adequate for pain relief, while 42 (50%) agreed that pain management was more complex in these patients mainly due to presence of multiple coexisting problems and psychological issues. Only 26 (31%) respondents considered that pain was under-reported and under-treated in these patients, mainly because physicians were more focused on patients’ other disease related complications and issues. Formulation of guidelines are recommended for effective acute pain management in these patients encompassing associated issues, including concomitant painful conditions, opioid dependence, psychiatric problems, etc.

BackgroundConversion of sputum culture from positive to negative for M. tuberculosis is a key indicator of treatment response. An initial positive culture is a pre-requisite to observe conversion. Consequently, patients with a missing or negative initial culture are excluded from analyses of conversion outcomes. To identify the initial, or "baseline" culture, researchers must define a sample collection interval. An interval extending past treatment initiation can increase sample size but may introduce selection bias because patients without a positive pre-treatment culture must survive and remain in care to have a culture in the post-treatment interval.MethodsWe used simulated data and data from the endTB observational cohort to investigate the potential for bias when extending baseline culture intervals past treatment initiation. We evaluated bias in the proportion with six-month conversion.ResultsIn simulation studies, the potential for bias depended on the proportion of patients missing a pre-treatment culture, proportion with conversion, proportion culture positive at treatment initiation, and proportion of patients missing a pre-treatment culture who would have been observed to be culture positive, had they had a culture. In observational data, the maximum potential for bias when reporting the proportion with conversion reached five percentage points in some sites.ConclusionExtending the allowable baseline interval past treatment initiation may introduce selection bias. If investigators choose to extend the baseline collection interval past treatment initiation, the proportion missing a pre-treatment culture and the number of deaths and losses to follow up during the post-treatment allowable interval should be clearly enumerated.

Non-Hodgkin lymphomas of the hypothalamus and pituitary are rare. They usually remain clinically silent until onset of compressive features affecting surrounding structures. When symptomatic, patients most commonly present with diabetes insipidus, headaches, ophthalmoplegia and/or bilateral hemianopia. We report a case of a 67-year-old Caucasian female with a history of B-cell lymphoma in complete remission. She presented with left oculomotor nerve palsy and was subsequently found to have a sellar/suprasellar mass lesion on MRI. Alongside hypocortisolism and hypogonadotropic hypogonadism, she developed transient diabetes insipidus during her illness. Her clinical course was characterized by rapid intracranial progression of the sellar mass. MR spectroscopy suggested a diagnosis of lymphoma. Diagnostic biopsy confirmed high-grade diffuse large B-cell CNS lymphoma; this changed the definitive management from surgical excision to chemotherapy. Despite treatment, she succumbed to her illness within 7 months of initial presentation. This case highlights the aggressive nature of CNS lymphomas and the need for a high index of suspicion in an unusual presentation of sellar/suprasellar mass lesions.

Background: Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan. Methods: We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services. A physician assessed all children and adolescents (0–19 years) with presumptive DR-TB, including details of exposure to DR-TB, medical history, radiology, and laboratory results. All patients received treatment as per national DR-TB management guidelines based on WHO recommendations. Results: There were 262 treatment episodes for 247 patients enrolled during the study period. The median age of the cohort was 16 years (IQR: 13–18 years) with 16 (6.1%) children being under 5 years; 237 (90.5%) patients had pulmonary TB. The majority of the patients (194 or 74.1%) experienced a favourable treatment outcome and 26 (9.9%) died while on treatment. Female patients (78.5%) were more likely to experience favourable outcomes compared to males (64.7%; chi-sqr p-value = 0.02). Conclusions: We found high rates of favourable outcomes in children and adolescents treated for DR-TB. However, there were few young children in our cohort and there was a considerable gender gap that enhanced efforts to diagnose DR-TB in young children and to elucidate and mitigate the reasons for poor outcomes amongst males.

BackgroundEntamoeba infections have major impact on millions of the people worldwide. Entamoeba histolytica has long been accepted as the only pathogenic species. However, recent reports of other Entamoeba spp. in symptomatic cases have raised questions on their pathogenicity.Methodology/principal findingsTotal 474 stool samples and 125 liver aspirates from patients with intestinal and extra intestinal manifestations and from community were included. Sewage samples from the hospital and the city were also included. Microscopic examination and molecular detection were performed to detect presence of E. histolytica/ dispar/ moshkovskii/ bangladeshi. The associated demographic and socioeconomic factors were statistically analyzed with the presence of Entamoeba. Microscopy detected Entamoeba spp. in 5.4% stool and 6.4% liver aspirate samples. Through nested multiplex PCR, prevalence of Entamoeba spp. in intestinal and extra-intestinal cases was 6.6% (20/301) and 86.4% (108/125) respectively and in asymptomatic population was 10.5% (13/123). Sewage samples did not show presence of any Entamoeba spp. Uneducated subjects, low economic conditions, untreated drinking water, consumption of raw vegetables and habit of not washing hands before meals were significantly associated with presence of Entamoeba spp.ConclusionsE. histolytica still remains the only Entamoeba spp. in invasive extra intestinal infections. E. dispar was detected in both asymptomatic and symptomatic intestinal infections. Routine identification of Entamoeba spp. should incorporate PCR based detection methods.

Abstract Background At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens. Methods This is a protocol for a multi-center prospective cohort study to enroll 2600 patients from April 2015 through September 2018 in 17 countries. The protocol describes inclusion of patients started on treatment with bedaquiline- or delamanid- containing regimens under routine care, who consented to participate in the endTB observational study. Patient follow-up was according to routine monitoring schedules recommended for patients receiving bedaquiline or delamanid as implemented at each endTB site. Therefore, no additional tests were performed as a part of the study. Data were to be collected in a customized, open-source electronic medical record (EMR) system developed as a part of the endTB Project across all 17 countries. Discussion The endTB observational study will generate evidence on safety and efficacy of bedaquiline- and delamanid-containing regimens in a large, extremely heterogeneous group of MDR-TB patients, from 17 epidemiologically diverse countries. The systematic, prospective data collection of repeated effectiveness and safety measures, and analyses performed on these data, will improve the quality of evidence available to inform MDR-TB treatment and policy decisions. Further, the resources available to countries through implementation of the endTB project will have permitted countries to: gain experience with the use of these drugs in MDR-TB regimens, improve local capacity to record and report adverse events (pharmacovigilance), and enhance significantly the body of data available for safety evaluation of these drugs and other novel treatments. Trial registration This study was registered on 24 August 2017 at clincaltrials.gov (Registration number: NCT03259269).

Background: A growing body of evidence suggests that nonfunctioning and subclinical cortisol secreting adrenal incidentalomas (AIs) are associated with several components of metabolic syndrome resulting in increased cardiometabolic risk. The long-term metabolic outcome of these AIs is largely unknown and their most appropriate management remains controversial. Objectives: To undertake a systematic review of the prevalence of cardiometabolic abnormalities in nonfunctioning and subclinical cortisol secreting AIs and long-term outcome of conservative treatment and adrenalectomy. Methods: MEDLINE, Cochrane Controlled Trials Register, and EMBASE were searched for relevant studies and systematic review was performed. National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies was used to assess the risk of bias in the studies. Results: Of the 65 studies screened, 18 (10 retrospective, 5 prospective, 2 cross-sectional studies, and 1 randomized controlled trial) were included in the systematic review. Prevalence of hypertension (HTN), impaired glucose metabolism, dyslipidaemia, and raised body mass index (BMI) was higher in subclinical cortisol secreting AIs as compared with nonfunctioning AIs. Surgical intervention had a beneficial effect on blood pressure, glucometabolic control, and obesity in patients with subclinical Cushing's syndrome. The results for lipid metabolism were equivocal. There was no significant improvement in cardiometabolic risk factors after adrenalectomy in nonfunctioning AIs. The quality of evidence was found to be low to moderate. Conclusions: The systematic review demonstrated increased prevalence of components of metabolic syndrome in patients with subclinical cortisol secreting and nonfunctioning AIs. A beneficial role of adrenalectomy on HTN, glucometabolic control, and BMI was observed in patients with subclinical cortisol secreting AIs.

Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the pro-inflammatory cytokines during infection. It also regulates the transcriptional network of several inflammatory cytokine genes. Hence, targeting NF-kB could be an important strategy to reduce pathogenesis. Moreover, treatment of H. pylori needs attention as current therapeutics lack efficacy due to antibiotic resistance, highlighting the need for alternative therapeutic approaches. In this study, we investigated the effects of capsaicin, a known NF-kB inhibitor in reducing inflammation and gastric complications during H. pylori infection. We observed that capsaicin reduced NF-kB activation and upregulation of cytokine genes in an in vivo mice model. Moreover, it affected NF-kB–miRNA interplay to repress inflammation and gastric damages. Capsaicin reduced the expression level of mir21 and mir223 along with the pro-inflammatory cytokines. The repression of miRNA further affected downstream targets such as e-cadherin and Akt. Our data represent the first evidence that treatment with capsaicin inhibits inflammation and induces antimicrobial activity during H. pylori infection. This alternative approach might open a new avenue in treating H. pylori infection, thus reducing gastric problems.

The current research was carried out to characterize the phytosociology of the forests of one of Pakistan’s most valuable tree species (Deodar) across its native range. In this context, our main hypothesis was that, along the altitudinal gradient, we would find different plant communities that would be driven by different environmental variables (climatic, edaphic, and physiographic). Therefore, to assess the vegetation structure of the pure Deodar forests of the unexplored Manoor Valley (Northwestern Himalaya), Pakistan, frequent field visits were carried out during different seasons of 2015–2018. Ecological methods: Line transects sampling (23 stands) and phytosociological attributes were evaluated in relation to geographical and environmental variables. Various statistical software applications (i.e., PCORD, RStudio 4.0, and R 3.6.1) were used to examine all of the gathered data of plant species and environmental variables. A total of three different plant communities (Cedrus–Isodon–Cynodon, Cedrus–Cynodon–Dryopteris, and Sambucus–Cedrus–Desmodium) were identified by grouping 162 species and 23 stands in pure Deodar forests under the influence of geographic, slope, edaphic, and climatic variables, ranging from 1580.8 to 2373.8 m. The altitude (1936–2373 m), slope angle (25–85°), sandy (29–48%) and loamy soil texture, wind speed (1.45 ms−1), and temperature (25.8 °C) all had a strong influence on the Sambucus–Cedrus–Desmodium community. In contrast with this, the Cedrus–Cynodon–Dryopteris community showed a positively significant relationship with the northeastern slope, silty (32–58%) and sandy (15.8–55%) loamy soil texture, and barometric pressure (814.3 pa). Nonetheless, the Cedrus–Isodon–Cynodon community revealed a significant positive association with the northeastern to southwestern slope, pH (6.3), wet bulb (19.7), and dew point (17.7). We found significant differences (p < 0.001) among the three communities found in the pure Deodar forests in the four diversity indexes. The Sambucus–Cedrus–Desmodium community has the maximum number of plants (129 species), Shannon’s diversity (H’ = 3.7), and Simpson’s dominance (0.98) values among the recorded communities. The Pielou’s evenness index value was led by the Cedrus–Isodon–Cynodon community (0.97). Beta diversity showed a dissimilarity lower than 50% among the three communities. Simple term effects in the canonical correspondence analysis model revealed significant (p < 0.05) differences in altitude, slope angle, slope (southeastern), and wind speed variables. The present investigation sheds light on vegetation pattern and species contribution as a function of environmental gradients and provides a baseline for future studies.

Objective: To describe the characteristics of people with Parkinson disease and movement disorders (PDMDs) referred by neurologist to a physiatrist-led interdisciplinary rehabilitation screening program. Design: Retrospective data analysis of electronic health records (EMRs). Setting: Outpatient PDMD neurology clinic and an interdisciplinary rehabilitation hospital’s PDMD screening program. Participants: People with PDMDs referred by neurologists to the interdisciplinary rehabilitation screening program from 2009-2017 (n=934), with early referrals from 2009-2015 (n=449) and recently referred from 2015-2017 (n=485), and patients who had new interdisciplinary rehabilitation screening program evaluations from 2015-2017 (n=183). Intervention: Participation in the physiatrist-led PDMD screening clinic. Main Outcome Measures: Demographics, disease-related features, timed Up and Go, conversational voice volume, recommended therapy services, and number of therapies completed 90 days following interdisciplinary rehabilitation screening program. Results: People referred from the neurologists to the interdisciplinary rehabilitation screening program from 2009-2017 were 72±12.9 years old, male (56%), white (65%), and with 1 or more comorbidities (62%). Compared with early referrals from 2009-2015, more recently referred participants from 2015-2017 were younger (P

Background: Assessment of the effectiveness of tuberculosis control strategies requires the periodic measurement of M. tuberculosis transmission in populations, which is notoriously difficult. One well-established method is to measure the prevalence of infectious pulmonary tuberculosis in the population which is then repeated at a second time point after a period of ‘intervention’, such as scale up of the Search-Treat-Prevent strategy of the Zero TB Cities initiative, allowing for a ‘before and after’ comparison. Protocol: The concurrent adult pulmonary tuberculosis prevalence survey (using digital radiography and Xpert MTB/RIF Ultra) and child M. tuberculosis infection survey (using QuantiFERON-TB® Gold Plus) will primarily provide a baseline measure of the burden of adult infectious tuberculosis in Karachi and assess whether a large-scale interferon gamma release assay survey in children aged 2 to 4 years is feasible. The target population for the prevalence survey is comprised of a stratified random sample of all adults aged 15 years and above and all children aged 2 to 4 years resident in four districts in Karachi. The survey procedures and analyses to estimate pulmonary tuberculosis prevalence are based on the World Health Organization methodology for tuberculosis prevalence surveys. Ethics and dissemination: The study protocol has been approved by the Interactive Research Development / The Indus Hospital Research Centre Research Ethics Committee in Karachi, Pakistan and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Due to non-representative sampling in this setting, where a large proportion of the population are illiterate and are reluctant to provide fingerprints due to concerns about personal security, verbal informed consent will be obtained from each eligible participant or guardian. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and with the Provincial and National TB programme.

This present study was an evaluation of the antioxidant and cytotoxic activities of Incarvillea emodi (Bignoniaceae). The aqueous extracts of different parts of Incarvillea emodi, collected from different places in Pakistan, were tested for radical scavenging effects on 2,2-diphenyl-1-picrylhydrazil (DPPH), nitric oxide (NO), superoxide (SO) and [2,2"-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] (ABTS•+) radicals. DPPH radical scavenging effects of three polyamide column fractions of one extract were also tested. The cytotoxicity of the extracts were tested against Hep-2 (human larynx epidermoid carcinoma) cancer cell line by MTT [3-(4,5- dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide] method. In addition, an HPLC-DAD system was used to show the presence of phenylethanoid glycosides in the most active polyamide column fraction. The free radical scavenging effects of the extracts were found comparable to that of reference antioxidants, 3-t-butyl-4-hydroxyanizole (BHA), quercetin and ascorbic acid (AA). Concentration dependent cytotoxic activity was observed against Hep-2 cancer cell line. Two phenylethanoid glycosides, acteoside and leucosceptoside A, were identified in the active polyamide column fraction at HPLC-DAD system. The presence of phenylethanoid glycosides in Incarvillea emodi was shown for the first time with this study. Antioxidant and cytotoxic activity researches are important for developing new drugs. Our results supported to use of Incarvillea emodi as folk medicine due to several biological effects in Pakistan. Moreover, the use of Incarvillea genus as a traditional ethnoveterinary medicine in dyspepsia and internal diseases were reported in previous studies.

Plant species are distributed in different types of habitats, forming different communities driven by different sets of environmental variables. Here, we assessed potential plant communities along an altitudinal gradient and their associations with different environmental drivers in the unexplored Manoor Valley (Lesser Himalaya), Pakistan. We have implemented various ecological techniques and evaluated phytosociological attributes in three randomly selected 50 m-transects within each stand (a total of 133) during different seasons for four years (2015–2018). This phytosociological exploration reported 354 plant species representing 93 different families. The results revealed that the Therophytic life form class dominated the flora, whereas Nanophyll dominated the leaf size spectra. There were a total of twelve plant communities identified, ranging from the lowest elevations to the alpine meadows and cold deserts. The maximum number of species were found in Cedrus–Pinus–Parrotiopsis community (197 species), in the middle altitudinal ranges (2292–3168 m). Our results showed that at high altitudes, species richness was reduced, whereas an increase in soil nutrients was linked to progression in vegetation indicators. We also found different clusters of species with similar habitats. Our study clearly shows how altitudinal variables can cluster different plant communities according to different microclimates. Studies such as ours are paramount to better understanding how environmental factors influence ecological and evolutionary aspects.

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

Research on forecasting the seasonality and growth trend of natural gas (NG) production and consumption will help organize an analysis base for NG inspection and development, social issues, and allow industrials elements to operate effectively and reduce economic issues. In this situation, we handle a comparison structure on the application of different models in monthly NG production and consumption forecasting using the cross-correlation function and then analyze the association between exogenous variables. Moreover, the SARIMA-X model is tested for US monthly NG production and consumption prediction via the proposed method for the first time in the literature review in this study. The performance of that model has been compared with SARIMA (p, d, q) * (P, D, Q)s. The results from RMSE and MAPE indicate that the superiority of the best model. By applying this method, the US monthly NG production and consumption is forecast until 2025. The success of the proposed method allows the use of seasonality patterns. If this seasonal approach continues, the United States’ NG production (16%) and consumption (24%) are expected to increase by 2025. The results of this study provide effective information for decision-makers on NG production and consumption to be credible and to determine energy planning and future sustainable energy policies.

Treatment of primary adrenal insufficiency (PAI) requires lifelong hormone replacement with glucocorticoids (GCs) and mineralocorticoids. Impaired quality of life and increased standardized mortality ratio in these patients emphasize the importance of tailoring therapy to individual needs. Role of education is paramount in improving patient compliance and in anticipating and preventing adrenal crises. Although discovery of synthetic GCs was a major breakthrough in treatment of patients with this life-threatening condition, management of PAI continues to be challenging. The obstacles for clinicians appear to vary widely across the globe. While optimization and individualization of therapy after diagnosis of PAI remain the main challenges for clinicians in the developed world, doctors in a developing country face problems at almost every stage from the diagnosis to the treatment and follow-up of these patients; cost of therapy, lack of resources, and funding are the main hindrances. Adherence to therapy and patient education are found to be common issues in most parts of the world. This commentary highlights the challenges from both developed and developing country's perspective in treating PAI; it also provides an update on current management scenario and future treatment options.

Background: Chemical exposure is a major health problem globally. Poison control centers (PCCs) play a leading role both in developed and developing countries in the prevention and control of poisonous chemical exposures. In this study, we aimed to assess the current state of PCCs in Pakistan and highlight capacity building needs in these centers. Methods: A cross-sectional survey of the two registered PCCs was done during August – December 2011. Necessary services of the PCCs were evaluated and the data were recorded on a predesigned checklist. Results: Both PCCs are affiliated to a tertiary care hospital. Clinical services to poisoned patients were available 24 hours a day / 7 days a week. Information on common local products was available to poison center staff. Both centers were involved in undergraduate and post graduate teaching. Telephone poison information service was not available in either of centers. There was a limited capacity for qualitative and analytical toxicology. Common antidotes were available. There were limited surveillance activities to capture toxic risks existing in the community and also a deficiency was observed in chemical disaster planning. Conclusion: PCCs in Pakistan need capacity building for specialized training in toxicology, toxicovigilance, chemical disaster planning, analytical laboratory tests and telephone service for consultation in poisoning cases. How to cite this article: Khan NU, Mir MU, Khan UR, Khan AR, Ara J, Raja K, et al. The Current State of Poison Control Centers in Pakistan and the Need for Capacity Building. Asia Pac J Med Toxicol 2014;3:31-5.

Sleep apnea has been recognized as a factor predisposing to atrial fibrillation recurrence and progression. The effect of other sleep-disturbing conditions on atrial fibrillation progression is not known. We sought to determine whether frequent periodic leg movement during sleep is a risk factor for progression of atrial fibrillation. In this retrospective study, patients with atrial fibrillation and a clinical suspicion of restless legs syndrome who were referred for polysomnography were divided into two groups based on severity of periodic leg movement during sleep: frequent (periodic movement index >35/h) and infrequent (≤35/h). Progression of atrial fibrillation to persistent or permanent forms between the two groups was compared using Wilcoxon rank-sum test, chi-square tests and logistic regression analysis. Of 373 patients with atrial fibrillation (77% paroxysmal, 23% persistent), 108 (29%) progressed to persistent or permanent atrial fibrillation during follow-up (median, 33 months; interquartile range, 16-50). Compared to patients with infrequent periodic leg movement during sleep (n=168), patients with frequent periodic leg movement during sleep (n=205) had a higher rate of atrial fibrillation progression (23% vs. 34%; p=0.01). Patients with frequent periodic leg movement during sleep were older and predominantly male; however, there were no significant differences at baseline in clinical factors that promote atrial fibrillation progression between both groups. On multivariate analysis, independent predictors of atrial fibrillation progression were persistent atrial fibrillation at baseline, female gender, hypertension and frequent periodic leg movement during sleep. In patients with frequent periodic leg movement during sleep, dopaminergic therapy for control of leg movements in patients with restless legs syndrome reduced risk of atrial fibrillation progression. Frequent leg movement during sleep in patients with restless legs syndrome is associated with progression of atrial fibrillation to persistent and permanent forms.