Prevalence and risk factors for chronic kidney disease of unknown cause in Malawi: a cross-sectional analysis in a rural and urban population.

BACKGROUND: An epidemic of chronic kidney disease of unknown cause (CKDu) is occurring in rural communities in tropical regions of low-and middle-income countries in South America and India. Little information is available from Southern African countries which have similar climatic and occupational characteristics to CKDu-endemic countries. We investigated whether CKDu is prevalent in Malawi and identified its potential risk factors in this setting. METHODS: We conducted a cross-sectional study from January-August 2018 collecting bio samples and anthropometric data in two Malawian populations. The sample comprised adults > 18 years (n = 821) without diabetes, hypertension, and proteinuria. Estimates of glomerular filtration rate (eGFR) were calculated using the CKD-EPI equation. Linear and logistic regression models were applied with potential risk factors, to estimate risk of reduced eGFR. RESULTS: The mean eGFR was 117.1 ± 16.0 ml/min per 1.73m2 and the mean participant age was 33.5 ± 12.7 years. The prevalence of eGFR< 60 was 0.2% (95% confidence interval (95% CI) 0.1, 0.9); the prevalence of eGFR< 90 was 5% (95% CI =3.2, 6.3). We observed a higher prevalence in the rural population (5% (3.6, 7.8)), versus urban (3% (1.4, 6.7)). Age and BMI were associated with reduced eGFR< 90 [Odds ratio (OR) (95%CI) =3.59 (2.58, 5.21) per ten-year increment]; [OR (95%CI) =2.01 (1.27, 3.43) per 5 kg/m2 increment] respectively. No increased risk of eGFR < 90 was observed for rural participants [OR (95%CI) =1.75 (0.50, 6.30)]. CONCLUSIONS: Reduced kidney function consistent with the definition of CKDu is not common in the areas of Malawi sampled, compared to that observed in other tropical or sub-tropical countries in Central America and South Asia. Reduced eGFR< 90 was related to age, BMI, and was more common in rural areas. These findings are important as they contradict some current hypothesis that CKDu is endemic across tropical and sub-tropical countries. This study has enabled standardized comparisons of impaired kidney function between and within tropical/subtropical regions of the world and will help form the basis for further etiological research, surveillance strategies, and the implementation and evaluation of interventions.

Coordination Chemistry and Structural Dynamics of a Long and Flexible Piperazine-Derived Ligand.

A long and highly flexible internally functionalized dipyridyl ligand α,α'-p-xylylenebis(1-(4-pyridylmethylene)-piper-4-azine), L, has been employed in the synthesis of a series of coordination polymer materials with Co(II), Cd(II), and Ag(I) ions. In poly-[Cd(L)(TPA)] 1 and poly-[Co(L)(IPA)], 2, (TPA = terephthalate, IPA = isophthalate) the ligand adopts a similar linear conformation to that seen in the structure of the unbound molecule and provides a long (2.6 nm) metal-metal bridging distance. Due to the mismatch of edge lengths with that provided by the carboxylate coligands, geometric distortions from the regular dia and (4,4) network geometries for 1 and 2, respectively, are observed. In poly-[Ag2(CF3SO3)2(L)], 3, the ligand coordinates through both pyridine groups and two of the four piperazine nitrogen donors, forming a high-connectivity 2-dimensional network. The compound poly-[Ag2(L)](BF4)2·2MeCN, 4, a porous 3-dimensional cds network, undergoes a fascinating and rapid single-crystal-to-single-crystal rearrangement on exchange of the acetonitrile guests for water in ambient air, forming a nonporous hydrated network poly-[Ag2(L)](BF4)2·2H2O, 5, in which the well-ordered guest water molecules mediate the rearrangement of the tetrafluoroborate anions and the framework itself through hydrogen bonding. The dynamics of the system are examined in greater detail through the preparation of a kinetic product, the dioxane-solvated species poly-[Ag2(L)](BF4)2·2C4H8O2, 6, which undergoes a slow conversion to 5 over the course of approximately 16 h, a transition which can be monitored in real time. The reverse transformation can also be observed on immersing the hydrate 5 in dioxane. The structural features and physical properties of each of the materials can be rationalized based on the flexible and multifunctional nature of the ligand molecule, as well as the coordination behavior of the chosen metal ions.

Ran GTPase in nuclear envelope formation and cancer metastasis.

Ran is a small ras-related GTPase that controls the nucleocytoplasmic exchange of macromolecules across the nuclear envelope. It binds to chromatin early during nuclear formation and has important roles during the eukaryotic cell cycle, where it regulates mitotic spindle assembly, nuclear envelope formation and cell cycle checkpoint control. Like other GTPases, Ran relies on the cycling between GTP-bound and GDP-bound conformations to interact with effector proteins and regulate these processes. In nucleocytoplasmic transport, Ran shuttles across the nuclear envelope through nuclear pores. It is concentrated in the nucleus by an active import mechanism where it generates a high concentration of RanGTP by nucleotide exchange. It controls the assembly and disassembly of a range of complexes that are formed between Ran-binding proteins and cellular cargo to maintain rapid nuclear transport. Ran also has been identified as an essential protein in nuclear envelope formation in eukaryotes. This mechanism is dependent on importin-ß, which regulates the assembly of further complexes important in this process, such as Nup107-Nup160. A strong body of evidence is emerging implicating Ran as a key protein in the metastatic progression of cancer. Ran is overexpressed in a range of tumors, such as breast and renal, and these perturbed levels are associated with local invasion, metastasis and reduced patient survival. Furthermore, tumors with oncogenic KRAS or PIK3CA mutations are addicted to Ran expression, which yields exciting future therapeutic opportunities.

Environmental risk factors for reduced kidney function due to undetermined cause in India: an environmental epidemiologic analysis.

BACKGROUND: An epidemic of chronic kidney disease is occurring in rural communities in low-income and middle-income countries that do not share common kidney disease risk factors such as diabetes and hypertension. This chronic kidney disease of unknown etiology occurs primarily in agricultural communities in Central America and South Asia. Consequently, environmental risk factors including heat stress, heavy metals exposure, and low altitude have been hypothesized as risk factors. We conducted an environmental epidemiological analysis investigating these exposures in India which reports the disease. METHODS: We used a random sample population in rural and urban sites in Northern and Southern India in 2010, 2011, and 2014 (n = 11,119). We investigated associations of the heat index, altitude, and vicinity to cropland with estimated glomerular filtration rate (eGFR) using satellite-derived data assigned to residential coordinates. We modeled these exposures with eGFR using logistic regression to estimate the risk of low eGFR, and linear mixed models (LMMs) to analyze site-specific eGFR-environment associations. RESULTS: Being over 55 years of age, male, and living in proximity to cropland was associated with increased risk of low eGFR [odds ratio (OR) (95% confidence interval (CI) = 2.24 (1.43, 3.56), 2.32 (1.39, 3.88), and 1.47 (1.16, 2.36)], respectively. In LMMs, vicinity to cropland was associated with low eGFR [-0.80 (-0.44, -0.14)]. No associations were observed with temperature or altitude. CONCLUSIONS: Older age, being male, and living in proximity to cropland were negatively associated with eGFR. These analyses are important in identifying subcommunities at higher risk and can help direct future environmental investigations.

Effectiveness of the Communities Care programme on change in social norms associated with gender-based violence (GBV) with residents in intervention compared with control districts in Mogadishu, Somalia.

OBJECTIVE: Determine the effectiveness of the Communities Care programme (CCP) on change in harmful social norms associated with gender-based violence (GBV) and confidence in provision of services with residents in intervention compared with control district. We hypothesised that residents in the intervention district would report a decrease in support for harmful social norms and increase in confidence in services in comparison with control district. SETTING: The study was conducted in Mogadishu, Somalia. PARTICIPANTS: In the intervention district, 192 community members (50% women) completed baseline surveys with 163 (84.9%) retained at endline. In the control district, 195 community members (50% women) completed baseline surveys with 167 (85.6%) retained at endline. INTERVENTION: CCP uses facilitated dialogues with community members to catalyse GBV prevention actions and provides training to diverse sectors to strengthen response services for GBV survivors. RESULTS: Residents in the intervention district had significantly greater improvement in change in social norms: (1) response to sexual violence (b=-0.214, p=0.041); (2) protecting family honour (b=-0.558, p<0.001); and (3) husband's right to use violence (b=-0.309, p=0.003) compared with control district participants. The greatest change was seen in the norm of 'protecting family honour' with a Cohen's d effect size (ES) of 0.70, followed by the norm 'husband's right to use violence' (ES=0.38), and then the norm of 'response to sexual violence' (ES=0.28). Residents in intervention district had a significantly greater increase in confidence in provision of GBV services across diverse sectors than the control district (b=0.318, p<0.001) with an associated effect size of 0.67. There were no significant differences between residents in intervention and control districts on change in personal beliefs on the norms. CONCLUSION: The evaluation showed the promise of CCP in changing harmful social norms associated with GBV and increasing confidence in provision of services in a complex humanitarian setting.

Rationale and population-based prospective cohort protocol for the disadvantaged populations at risk of decline in eGFR (CO-DEGREE).

INTRODUCTION: A recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction. METHODS AND ANALYSIS: This generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR<60 mL/min/1.73m2), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline. ETHICS AND DISSEMINATION: Ethical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate.

Social norms and beliefs about gender based violence scale: a measure for use with gender based violence prevention programs in low-resource and humanitarian settings.

BACKGROUND: Gender-based violence (GBV) primary prevention programs seek to facilitate change by addressing the underlying causes and drivers of violence against women and girls at a population level. Social norms are contextually and socially derived collective expectations of appropriate behaviors. Harmful social norms that sustain GBV include women's sexual purity, protecting family honor over women's safety, and men's authority to discipline women and children. To evaluate the impact of GBV prevention programs, our team sought to develop a brief, valid, and reliable measure to examine change over time in harmful social norms and personal beliefs that maintain and tolerate sexual violence and other forms of GBV against women and girls in low resource and complex humanitarian settings. METHODS: The development and testing of the scale was conducted in two phases: 1) formative phase of qualitative inquiry to identify social norms and personal beliefs that sustain and justify GBV perpetration against women and girls; and 2) testing phase using quantitative methods to conduct a psychometric evaluation of the new scale in targeted areas of Somalia and South Sudan. RESULTS: The Social Norms and Beliefs about GBV Scale was administered to 602 randomly selected men (N = 301) and women (N = 301) community members age 15 years and older across Mogadishu, Somalia and Yei and Warrup, South Sudan. The psychometric properties of the 30-item scale are strong. Each of the three subscales, "Response to Sexual Violence," "Protecting Family Honor," and "Husband's Right to Use Violence" within the two domains, personal beliefs and injunctive social norms, illustrate good factor structure, acceptable internal consistency, reliability, and are supported by the significance of the hypothesized group differences. CONCLUSIONS: We encourage and recommend that researchers and practitioners apply the Social Norms and Beliefs about GBV Scale in different humanitarian and global LMIC settings and collect parallel data on a range of GBV outcomes. This will allow us to further validate the scale by triangulating its findings with GBV experiences and perpetration and assess its generalizability across diverse settings.

Erythrocyte folate and 5-methyltetrahydrofolate levels decline during 6 months of oral anticoagulation with warfarin.

Dietary fluctuations of vitamin K are detrimental to oral anticoagulant control. Attempts to improve control through the avoidance of vitamin K-rich foods (mainly green vegetables) may inadvertently compromise folate status, itself a risk factor for thromboembolism. We evaluated the effect of a 6-month period of warfarin therapy on folate status in 114 patients using measurements of red-cell folate and 5-methyltetrahydrofolate and plasma folate and total homocysteine. Circulatory levels of phylloquinone, vitamin B12 and methylmalonic acid were also determined. A subset of 45 patients completed 7-day food diaries at the beginning and end of their treatment. There was a significant decrease in total erythrocyte folate (P = 0.005) and 5-methyltetrahydrofolate (P = 0.002) during the study. A concurrent increase in plasma phylloquinone (P = 0.003) was attributed to warfarin-induced perturbation of vitamin K metabolism. No other longitudinal changes were observed. Folate and phylloquinone intakes correlated with each other at baseline (P = 0.024) and after treatment (P = 0.011). Based on robust measurements of erythrocyte folates, patients showed a significant impairment in folate status after 6-month therapy with warfarin. The majority of patients had intakes of folate and phylloquinone below the national average or UK guidelines. The study highlights the need for improved dietary management of patients taking oral anticoagulants.