The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.diuretics | kidney tubules | nephrogenic diabetes insipidus T he thiazide-sensitive Na-Cl cotransporter (NCC) (SLC12A3) and the Cl − /HCO 3 − exchanger pendrin (SLC26A4) are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na channel and NCC working by itself (1-6). Pendrin is expressed on the apical membrane of intercalated cells in late distal convoluted tubule (DCT), connecting tubule (CNT), and the cortical collecting duct (CCD) (7-9). The thiazide-sensitive NCC is primarily expressed on the apical membrane of DCT cells (10,11).Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions (5,(12)(13)(14)(15). Indeed, even a mild degree of salt wasting has not been demonstrated in these two genetically engineered mouse models at steady state. Kidney functions, including sodium and chloride excretion, urine output, and blood urea nitrogen (BUN) levels in mutant mice are comparable to wild-type (WT) animals (12-15). Both pendrin KO and NCC KO mice, however, show signs of volume depletion or develop hypotension during salt restriction (12,14). These findings have led investigators to conclude that pendrin and NCC are predominantly active during salt depletion (and or in response to increased aldosterone levels), and their contribution to salt reabsorption at baseline conditions is small.We hypothesized that NCC and pendrin may compensate for loss of the other under basal conditions, thereby masking the role that each plays in salt reabsorption. To test this hypothesis, we generated double knockout of pendrin and NCC mice by crossing animals with single deletion for NCC and pendrin. The double KO mice show significant salt and flui...

Introduction We investigated the influence of COVID-19 on smoking patterns in Pakistan. Methods In a longitudinal survey, we asked cigarette smokers in Pakistan about their smoking behaviours before and since COVID-19. Smokers were recruited before COVID-19 using two-stage random probability sampling. Since COVID-19, three subsequent waves were conducted over the telephone, asking additional questions on social determinants, mental health and wellbeing. Based on the first two waves, we estimated the proportion of smokers who stopped, decreased, maintained, or increased smoking. We also explored any factors associated with the change in smoking patterns. In those who stopped smoking soon after COVID-19, we estimated the proportion relapsed in subsequent waves. We estimated all proportions based on complete-case analysis. Results We recruited 6,014 smokers between September 2019 and February 2020; of these, 2,087 (2,062 reported smoking outcomes) were followed up in May 2020 after COVID-19. Since COVID-19, 14% (290/2,062) smokers reported quitting. Among those who continued smoking: 68% (1210/1772) reduced, 14% (239/1772) maintained, and 18% (323/1772) increased cigarette consumption; 37% (351/938) reported at least one quit attempt; 41% (669/1619) were more motivated while 21% (333/1619) were less motivated to quit. Changes in smoking patterns varied with nicotine dependence, motivation to quit, and financial stability since COVID-19. Among those reporting quitting soon after COVID-19, 39% (81/206) relapsed in the subsequent months (June-July 2020). Conclusions There have been significant bidirectional changes in smoking patterns since COVID-19 in Pakistan. While many people stopped, reduced, or tried quitting smoking, some increased smoking, and some relapsed after quitting. Implications We observed significant and complex changes in people’s smoking patterns, which are likely to be attributable to the COVID-19 pandemic and replicated in similar events in the future. Assessing these changes are essential for most low- and middle-income countries like Pakistan, where the vast majority of tobacco users live, but cessation support is still rudimentary. If provided routinely, smoking cessation interventions can potentially support millions of highly motivated individuals in quitting successfully both in general as well as in global events like COVID-19, in particular.

Background Tobacco uptake in adolescents is associated with a range of predictors. We examined the predictors of cigarette smoking, smokeless tobacco (ST) consumption and use of both ST and cigarettes among adolescents in four South Asian countries. Methods We analysed the Global Youth Tobacco Surveys (GYTS) data for Bangladesh (2013), India (2009), Pakistan (2013), and Sri-Lanka (2015), using multinomial regression to examine associations between several predictors and tobacco use. Results Data from 23,681 adolescents were analyzed. Overall, 82.8% of the study population were between 13 and 15 years and 52.7% were girls, 2% were cigarette smokers, 6.5% were ST users and 1.1% used both ST and cigarettes, in the past 30-days. Exposure to smoking in public places was associated with past 30-days smoking (RRR 5.59, 95%CI 4.28-7.28), ST use (RRR 2.07, 95%CI 1.84-2.32) and use of both ST and cigarettes (RRR 11.42, 95%CI 7.44-17.54). Exposure to tobacco use in electronic media and being offered free tobacco products were associated with all forms of tobacco use. Shopkeepers’ refusal to sell cigarettes protected adolescents from smoking (RRR 0.47, 95%CI 0.36-0.63) and ST use (RRR 0.65, 95%CI 0.45-0.95). However, exposure to anti-tobacco mass media messages was not protective for any form of tobacco use. Adolescents taught at school about harmful effects of tobacco were less likely to use ST; no evidence of this association was observed for smoking. Conclusion The associations between tobacco use and pro-tobacco factors were strong but the associations with anti-tobacco factors lacked strength and consistency in this study population.

The results of the study indicate a high prevalence of bullying in the participating dental institutions. Our results indicate a clear need to implement antiviolence regulations, anti-bullying educational programs and advocate further research on interventions to minimize bullying, enhance learning and professional engagement of interns in dental institutions.

Objectives Blended learning (BL) combines conventional face to face (F2F) sessions with online educational resources. This method includes the advantages of online course delivery without the omission of conventional F2F interaction. The purpose of the present study was to evaluate students' satisfaction and educational outcomes in a BL course compared to traditionally administered dental anatomy course. Methods A prospective non‐randomized study was conducted to compare the outcomes and perception of BL for teaching dental anatomy to dental students. First year dental anatomy students (n = 98) were included (48 in the conventional F2F learning and 50 in the BL group). Multiple choice questions were used to assess the achievement of learning outcomes and the Dundee Ready Education Environment Measure (DREEM) to determine the educational environment during the course. Results There was no significant difference in the pre‐test scores of both groups; however the mean post‐test score for the BL group (31.5 ± 4.5) was significantly higher than the F2F group (27.2 ± 4.9). The post‐test scores were comparable across both genders in the BL group while females secured significantly higher scores than males in the F2F group. The DREEM scores were also significantly higher in the BL group (147.3 ± 15.5) than the F2F group (134.5 ± 15.1) (p < 0.002). A similar pattern was observed in DREEM subscales. Conclusions The BL course is associated with improved students’ satisfaction and learner achievement compared to a conventionally administered dental anatomy course. In addition, BL enhanced students’ accessibility, self‐assessment, and higher level of engagement compared to F2F delivery of the course.

ObjectiveThe manufacturers of electronic cigarettes (e-cigarettes) are actively marketing their product through electronic and social media. Undergraduate medical students are expected to have better knowledge and awareness as they directly interact with patients in their training, The purpose of this study is therefore, to determine knowledge, use and perception regarding e-cigarettes among medical students from Sindh, Pakistan.ResultsA cross-sectional study was conducted between 1st July and 30th September 2016 at five different medical colleges situated in the second largest province of Sindh, Pakistan. The data was collected through a structured, self-administered questionnaire. Of the 500 students, the mean age was 21.5 ± 1.7 years and 58% were females. Over (65.6%) students were aware of e-cigarettes, 31 (6.2%) reported having used e-cigarettes, of whom 6 (1.2%) self-reported daily use. Users of conventional tobacco products were significantly more likely to have heard of e-cigarettes (87.6% vs 51.6%, p < 0.001) and having used them (13.9% vs 1.3%, p < 0.001). On multivariable logistic regression analysis we found a strong association of e-cigarette use with consumption of conventional cigarettes [OR: 10.6, 95% CI 3.6–30.8, p < 0.001], use of smokeless tobacco products [OR: 7.9, 95% CI 2.7–23.4, p < 0.001] however a weak association was observed for Shisha use [OR: 3.05, 95% CI 0.9–9.6, p = 0.05].

Introduction We assessed the magnitude of smokeless tobacco (ST) use in Pakistan and identified policy gaps to help ascertain short-, medium- and long-term priorities. We then elicited stakeholders’ views as to which of these identified priorities are most important. Methods In a multi-method study, we: analysed Global Tobacco Surveillance System datasets to estimate ST consumption and disease burden; conducted a documentary review to identify gaps in policies to control ST in comparison with smoking; elicited stakeholders’ views in an interactive workshop, to identify a set of policy options available to address ST burden in Pakistan; and ranked policy priorities using a post-event survey. Results Among all tobacco users in Pakistan (n=24million), one-third of men and two-thirds of women consume ST. In 2017, its use led to an estimated 18,711 deaths due to cancer and ischemic heart disease. Compared to smoking, policies to control ST lag behind significantly. Priority areas for ST policies included: banning ST sale to and by minors, advocacy campaigns, introduction of licensing, levying taxes on ST and standardising ST packaging. A clear commitment to close cooperation between state actors and stakeholder groups is needed to create a climate of support and information for effective policy making. Conclusions Smokeless tobacco control in Pakistan should focus on four key policy instruments: legislation, education, fiscal policies and quit support. More research into the effectiveness of such policies is also needed. Implications A number of opportunities to improve ST regulation in Pakistan were identified. Among these, immediate priorities include banning ST sale to and by minors, mobilising advocacy campaign, introduction of licensing through the 1958 Tobacco Vendors Act, levying taxes on ST and standardising ST packaging.

Primary effusion lymphoma (PEL) or body cavity lymphoma is a rare type of extra nodal lymphoma of B-cell origin that presents as lymphomatous effusion(s) without any nodal enlargement or tumor masses. It belongs to the group of AIDS related non-Hodgkin's lymphomas. First described in 1996 in HIV infected individuals who were coinfected with Kaposi's sarcoma-associated herpesvirus (KSHV) or HHV-8 virus, it was included as a separate entity in WHO classification of tumors of hematopoietic and lymphoid tissue in the year 2001. The definition included association with HHV-8 virus as a mandatory diagnostic criterion. However, cases were later reported where PEL-like disease process was diagnosed in HHV-8 negative patients. This was eventually recognized as a rare but distinct entity termed as “HHV-8-unrelated PEL-like lymphoma”. Herein, we are reporting a case of an elderly patient who presented with a large pleuropericardial effusion and was eventually diagnosed with this entity. Till date, only around 50 cases of HHV-8-unrelated PEL-like lymphoma have been reported and our case being EBV, HIV, and Hepatitis C negative makes it very unique and rare occurrence. We are also presenting a review of relevant literature focused mainly on comparing outcomes in patients treated with and without chemotherapy.