IL-33 Induces Cellular and Exosomal miR-146a Expression as a Feedback Inhibitor of Mast Cell Function.

IL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood. Because the IL-33 receptor, ST2, acts via cascades used by the TLR family, similar feedback mechanisms may exist. MicroRNA (miR)-146a is induced by LPS-mediated TLR4 signaling and serves as a feedback inhibitor. Therefore, we explored whether miR-146a has a role in IL-33 signaling. IL-33 induced cellular and exosomal miR-146a expression in mouse bone marrow-derived mast cells (BMMCs). BMMCs transfected with a miR-146a antagonist or derived from miR-146a knockout mice showed enhanced cytokine expression in response to IL-33, suggesting that miR-146a is a negative regulator of IL-33-ST2 signaling. In vivo, miR-146a expression in plasma exosomes was elevated after i.p. injection of IL-33 in wild-type but not mast cell-deficient KitW-sh/W-sh mice. Finally, KitW-sh/W-sh mice acutely reconstituted with miR-146a knockout BMMCs prior to IL-33 challenge had elevated plasma IL-6 levels compared with littermates receiving wild-type BMMCs. These results support the hypothesis that miR-146a is a feedback regulator of IL-33-mediated mast cell functions associated with allergic disease.

Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen.

Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE-allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.

The Il9 CNS-25 Regulatory Element Controls Mast Cell and Basophil IL-9 Production.

IL-9 is an important mediator of allergic disease that is critical for mast cell-driven diseases. IL-9 is produced by many cell types, including T cells, basophils, and mast cells. Yet, how IL-9 is regulated in mast cells or basophils is not well characterized. In this report, we tested the effects of deficiency of a mouse Il9 gene regulatory element (Il9 CNS-25) in these cells in vivo and in vitro. In mast cells stimulated with IL-3 and IL-33, the Il9 CNS-25 enhancer is a potent regulator of mast cell Il9 gene transcription and epigenetic modification at the Il9 locus. Our data show preferential binding of STAT5 and GATA1 to CNS-25 over the Il9 promoter in mast cells and that T cells and mast cells have differing requirements for the induction of IL-9 production. Il9 CNS-25 is required for IL-9 production from T cells, basophils, and mast cells in a food allergy model, and deficiency in IL-9 expression results in decreased mast cell expansion. In a Nippostrongylus brasiliensis infection model, we observed a similar decrease in mast cell accumulation. Although decreased mast cells correlated with higher parasite egg burden and delayed clearance in vivo, T cell deficiency in IL-9 also likely contributes to the phenotype. Thus, our data demonstrate IL-9 production in mast cells and basophils in vivo requires Il9 CNS-25, and that Il9 CNS-25-dependent IL-9 production is required for mast cell expansion during allergic intestinal inflammation.

Lactic Acid Inhibits Lipopolysaccharide-Induced Mast Cell Function by Limiting Glycolysis and ATP Availability.

Sepsis has a well-studied inflammatory phase, with a less-understood secondary immunosuppressive phase. Elevated blood lactate and slow lactate clearance are associated with mortality; however, regulatory roles are unknown. We hypothesized that lactic acid (LA) contributes to the late phase and is not solely a consequence of bacterial infection. No studies have examined LA effects in sepsis models in vivo or a mechanism by which it suppresses LPS-induced activation in vitro. Because mast cells can be activated systemically and contribute to sepsis, we examined LA effects on the mast cell response to LPS. LA significantly suppressed LPS-induced cytokine production and NF-κB transcriptional activity in mouse bone marrow-derived mast cells and cytokine production in peritoneal mast cells. Suppression was MCT-1 dependent and reproducible with sodium lactate or formic acid. Further, LA significantly suppressed cytokine induction following LPS-induced endotoxemia in mice. Because glycolysis is linked to inflammation and LA is a byproduct of this process, we examined changes in glucose metabolism. LA treatment reduced glucose uptake and lactate export during LPS stimulation. LA effects were mimicked by glycolytic inhibitors and reversed by increasing ATP availability. These results indicate that glycolytic suppression and ATP production are necessary and sufficient for LA effects. Our work suggests that enhancing glycolysis and ATP production could improve immune function, counteracting LA suppressive effects in the immunosuppressive phase of sepsis.

Inter-rater and intrarater reliability of the South African Triage Scale in low-resource settings of Haiti and Afghanistan.

OBJECTIVE: The South African Triage Scale (SATS) has demonstrated good validity in the EDs of Médecins Sans Frontières (MSF)-supported sites in Afghanistan and Haiti; however, corresponding reliability in these settings has not yet been reported on. This study set out to assess the inter-rater and intrarater reliability of the SATS in four MSF-supported EDs in Afghanistan and Haiti (two trauma-only EDs and two mixed (including both medical and trauma cases) EDs). METHODS: Under classroom conditions between December 2013 and February 2014, ED nurses at each site assigned triage ratings to a set of context-specific vignettes (written case reports of ED patients). Inter-rater reliability was assessed by comparing triage ratings among nurses; intrarater reliability was assessed by asking the nurses to retriage 10 random vignettes from the original set and comparing these duplicate ratings. Inter-rater reliability was calculated using the unweighted kappa, linearly weighted kappa and quadratically weighted kappa (QWK) statistics, and the intraclass correlation coefficient (ICC). Intrarater reliability was calculated according to the percentage of exact agreement and the percentage of agreement allowing for one level of discrepancy in triage ratings. The correlation between years of nursing experience and reliability of the SATS was assessed based on comparison of ICCs and the respective 95% CIs. RESULTS: A total of 67 nurses agreed to participate in the study: In Afghanistan there were 19 nurses from Kunduz Trauma Centre and nine from Ahmed Shah Baba; in Haiti, there were 20 nurses from Martissant Emergency Centre and 19 from Tabarre Surgical and Trauma Centre. Inter-rater agreement was moderate across all sites (ICC range: 0.50-0.60; QWK range: 0.50-0.59) apart from the trauma ED in Haiti where it was moderate to substantial (ICC: 0.58; QWK: 0.61). Intrarater agreement was similar across the four sites (68%-74% exact agreement); when allowing for a one-level discrepancy in triage ratings, intrarater reliability was near perfect across all sites (96%-99%). No significant correlation was found between years of nursing experience and reliability. CONCLUSION: The SATS has moderate reliability in different EDs in Afghanistan and Haiti. These findings, together with concurrent findings showing that the SATS has good validity in the same settings, provide evidence to suggest that SATS is suitable in trauma-only and mixed EDs in low-resource settings.

PHYTOCHEMICAL ANALYSIS AND CARDIOTONIC ACTIVITY OF METHANOLIC EXTRACT OF RANUNCULUS MURICATUS LINN. IN ISOLATED RABBIT HEART.

Ranunculus muricatus Linn. (RML) have been traditionally used for the treatment of various cardiovascular disorders. The aim of present study was to evaluate their cardiovascular effects in isolated perfused rabbit heart. The methanolic extract of RML was prepared by cold maceration process. The methanolic extract of RML (1 ng to 10 mg) was used to determine the percentage change in force of contraction (FC), heart rate (HR) and perfusion pressure (PP) by using Langendorff's Perfused Heart Apparatus. The PP, FC and HR of isolated rabbit heart were measured by power lab data acquisition system. Moreover, phytochemical analysis and acute toxicity study were also performed. The methanolic extract at the doses from I ng to 10 mg exhibited a significant increase in perfusion pressure and force of contraction. Moreover, the crude extract of RML revealed a significant increase in heart rate at doses from 1 ng to µg. The maximum rise in all the thee parameters was observed at 1 µg and 1 ng, respectively In another study, the melhanoliC extract was tested in the presence of propranolol and verapamil on isolated perfused rabbit heart. The study shown that the increase in HR and FC produced by the plant extracts was significantly reduced in the presence of propranolol whereas PP remained significantly raised even in the presence of propranolol. However, in the presence of verapamil, this increased PP was significantly reversed to a decrease while a significant positive inotropic and chronotropic effects were observed. It is concluded that the cardiotonic activity of methanolic extract of RML might be due certain cardio active chemical compounds. Further studies are needed to isolate these pharmacologically active phytochemical constituents and elucidate their exact mechanism of action.

Preparation technology and preservation mechanism of γ-CD-MOFs biaological packaging film loaded with curcumin.

To prevent food spoilage caused by microbial infection, the development of an environmentally friendly antimicrobial preservation material is crucial. Here, the microporous γ-CD-MOFs was utilized to encapsulate the hydrophobic active substance curcumin, resulting in the preparation of a non-toxic antimicrobial material (Cur-CD-MOFs). The results revealed that curcumin encapsulation in Cur-CD-MOFs occurred primarily in the carbonyl group, benzene ring, and enolic side ring of curcumin. The Cur-CD-MOFs had a 100% bactericidal effect on Escherichia coli and Staphylococcus aureus at 4 h and 8 h, and a strong inhibitory effect on aerial mycelium of Penicillium expansum and Botrytis cinerea. Furthermore, the incorporation of Cur-CD-MOFs improved the Pul/Tre film barrier and mechanical properties. The effectiveness of Cur-CD-MOFs-Pul/Tre in retaining fruit freshness was validated using Centennial Seedless grapes. This study confirmed that Cur-CD-MOFs is a promising antibacterial material, and Cur-CD-MOFs-Pul/Tre will be a potent candidate for food preservation.

Comparison Of Efficacy Of Miltefosine Versus Meglumine Antimonate In The Treatment Of Cutaneous Leishmaniasis.

BACKGROUND: Cutaneous Leishmaniasis is a morbid condition that generates stigmatization and disfiguring scars. Pakistan is among the ninety-eight countries where cutaneous Leishmaniasis is endemic. Purpose of study was to compare the efficacy of miltefosine and meglumine antimoniate in the treatment of cutaneous Leishmaniasis. METHODS: All patients with cutaneous Leishmaniasis (CL) who met the inclusion criteria were divided into two groups using the envelop method. Capsule Miltefosine 50 mg (2.5 mg/ kg) was given to group A, while intralesional Glucantime injection was given to group B. The treatment's efficacy was evaluated after four weeks and again after eight weeks. RESULTS: Out of 74 patients, 37 patients were included in each group. In group A (miltefosine group), 56.75% were males, and 43.25% were females. In group B (meglumine antimoniate group), 62% were males, while 38% were females (p=0.63). The mean age was 32.81 years±12.09 SD, the mean duration of the disease was 5.4 months±2.3 SD and the mean number of lesions was 2.56±1.33 SD. The efficacy of Miltefosine and meglumine antimoniate (I/L) was 91.9% and 56.75%, respectively (p<0.001). CONCLUSIONS: Miltefosine was more effective than intralesional meglumine antimoniate in the treatment of cutaneous Leishmaniasis (p<0.001).

Efficacy Of Methotrexate Versus Azathioprine In The Treatment Of Chronic Actinic Dermatitis: A Randomized Control Trial.

Background: Azathioprine is first line immunosuppressive agent in treatment of chronic actinic dermatitis. The role of methotrexate has been effective in different dermatosis and it seems reasonable to use it in the treatment of chronic actinic dermatitis. Aims: We sought to compare the efficacy of methotrexate versus azathioprine in treatment of chronic actinic dermatitis. Methods: Patients with chronic actinic dermatitis were randomized to receive methotrexate in group A and azathioprine in group B. The response to treatment in terms of percentage PASI reduction and side effects of medications were assessed 12 weeks follow-up. Results: In group A, the percentage PASI reduction was <25% in 2 (1.19%) patients, 25-49% in 47 (27.9%) patients, 50-74% was achieved by 35 (20.8%) patients while in group B, the percentage PASI reduction of 25% was achieved by 2 (1.19%) patients, 25-49% in 45 (26.7%) patients, 50-74% in 37 (22.0%) patients. More than or equal to 75 percentage PASI reduction was not achieved by any patient in the study. Both drugs were found efficacious in treatment of CAD. A total of 23 (27.38%) patients in group A and 22 (26.19%) patients in group B showed derangement in laboratory investigations during 12 weeks treatment. The limitation of study was inability to do photo-patch test, so patients were diagnosed clinically and biopsy was done in clinically challenging cases. Conclusion: : This study shows that methotrexate is equally effective as azathioprine in the treatment of chronic actinic dermatitis with its added benefits of being cost effective and better safety profile.

Intrabiliary rupture of hepatic hydatid cyst: multidetector-row CT demonstration.

Rupture of a hydatid cyst into the biliary tract, also known as cystobiliary communication, is the most common complication of hepatic hydatid cyst. This may lead to obstructive jaundice, pancreatitis, cholangitis, and sepsis with high mortality. Imaging plays an important role in the preoperative diagnosis of this condition which facilitates its management. We studied six patients with rupture of hepatic hydatid cyst into a large bile duct in whom multidetector-row CT (MDCT) suggested the diagnosis. The imaging findings included a single hepatic cyst less than 10 cm in diameter in all the cases; interruption of the cyst wall adjacent to a bile duct signifying cyst-bile duct communication was seen in five patients. The common bile duct was dilated in all the patients, with linear membranes in four and diffuse irregular high dense intrabiliary material observed within the common bile duct in two of them. Intrahepatic ducts were dilated in all the six cases and two patients showed linear dense contents within distended gallbladder. Subcapsular and intrathoracic rupture was associated in one patient each. MDCT demonstration of hydatid cyst in the liver together with a dilated common bile duct and distended gallbladder containing high density hydatid material suggest rupture of the cyst into biliary tree. MDCT enhances demonstration of the dilated common bile duct with hydatid material inside. The diagnosis is reinforced by the demonstration of the cystobiliary communication itself.

Bidirectional relationship between diabetes and periodontal disease: review of evidence.

Presently there are 170 million diabetic patients worldwide. Pakistan ranks sixth in the world with approximately 6.2 million in the 20-79 year age affected by the diabetes. 6-10% of the 35-44year old diabetic patients have been reported to be affected by moderate form of periodontal disease in Pakistan. Periodontal disease is referred to as sixth complication of diabetes. The association between diabetes and periodontal disease has been reported for more than 40 years but reverse has not been the focus of researchers until recently. Studies have suggested a bidirectional relationship between periodontal disease and glycaemic control with each disease having a potential impact on the other.

Foreign body within sphenoid sinus: multidetector-row computed tomography (MDCT) demonstration.

Trans-nasal sphenoid sinus foreign body is a rare condition. We report a case of trans-nasal gun bullet within the sphenoid sinus with breach of the floor of the sella turcica. A 42-year-old soldier presented a few weeks after a gun battle with a history of headache. The skull x-ray demonstrated a foreign body in the region of sphenoid sinus and sella. Multidetector-row CT with multiplanar reformats demonstrated a bullet within the sphenoid sinus with its tip penetrating into the sella turcica. A few days later the patient coughed up the bullet as it came out spontaneously without any intervention. This is perhaps the unique occurrence of such a foreign body.

Comparison of interaction between three similar chalconoids and α-lactalbumin: Impact on structure and functionality of α-lactalbumin.

Interaction between α-lactalbumin (α-LA) and three similar chalconoids was compared using a combination of multi-spectral analysis and molecular docking, and their influence on structure and functional properties of α-LA was also investigated. Chalconoids strongly quenched α-LA fluorescence in a static mode and their binding constants to α-LA were declined in the order of hydroxy safflower yellow A (SYA), neohesperidin dihydrochalcone (NHDC) and naringin dihydrochalcone (NGDC). The main interaction forces involved in the binding of SYA, NHDC and NGDC to α-LA included hydrophobic forces and hydrogen bonds. There was non-radiative energy transfer between α-LA and three chalconoids, as indicated by the estimated by Förster's distance. The vicinity of SYA to tryptophan residues of α-LA showed the minimum value. Based on Fourier transform infrared spectroscopy (FTIR) spectra, SYA induced the conversion of more α-LA from α-helix into its ß-structures than NHDC and NGDC. Also, although the addition of three chalconoids had no significant effect on the emulsifying activity of α-LA, it slightly improved the emulsion stability of α-LA. In addition, SYA showed the maximum decrease on surface hydrophobicity of α-LA. Antioxidant capacity of SYA was also decreased more than that of NHDC and NGDC after the binding to α-LA. Additionally, docking studies indicated that SYA, NHDC and NGDC bound to the cleft between α-domains and ß-domains by three, two and two hydrogen bonds, respectively. Therefore, these findings suggest that there are significant differences among the effects of three similar chalconoids on structure and functionality of α-LA.

Expression Efficiency of Multiple Il9 Reporter Alleles Is Determined by Cell Lineage.

Generation of allelic gene reporter mice has provided a powerful tool to study gene function in vivo. In conjunction with imaging technologies, reporter mouse models facilitate studies of cell lineage tracing, live cell imaging, and gene expression in the context of diseases. Although there are several advantages to using reporter mice, caution is important to ensure the fidelity of the reporter protein representing the gene of interest. In this study, we compared the efficiency of two Il9 reporter strains Il9citrine and Il9GFP in representing IL-9-producing CD4+ TH9 cells. Although both alleles show high specificity in IL-9-expressing populations, we observed that the Il9GFP allele visualized a much larger proportion of the IL-9-producing cells in culture than the Il9citrine reporter allele. In defining the mechanistic basis for these differences, chromatin immunoprecipitation and chromatin accessibility assay showed that the Il9citrine allele was transcriptionally less active in TH9 cells compared with the wild-type allele. The Il9citrine allele also only captured a fraction of IL-9-expressing bone marrow-derived mast cells. In contrast, the Il9 citrine reporter detected Il9 expression in type 2 innate lymphoid cells at a greater percentage than could be identified by IL-9 intracellular cytokine staining. Taken together, our findings demonstrate that the accuracy of IL-9 reporter mouse models may vary with the cell type being examined. These studies demonstrate the importance of choosing appropriate reporter mouse models that are optimal for detecting the cell type of interest as well as the accuracy of conclusions.

Characterization and Antioxidant Activity of Products Derived from Xylose-Bovine Casein Hydrolysate Maillard Reaction: Impact of Reaction Time.

The characterization and antioxidant activity on Maillard reaction products (MRPs) derived from xylose and bovine casein hydrolysate (BCH) was investigated at 100 °C and initial pH 8.0 as a function of reaction time. The pH values and free amino groups contents of xylose-BCH MRPs remarkably decreased with the reaction time up to 8 h, whereas their browning intensities significantly increased (p < 0.05). After 4 h of heat treatment, the fluorescence properties of xylose-BCH MRPs reached the maximum. There was a production of higher and smaller molecular substances in xylose-BCH MRPs with an increased reaction time, as analyzed by size exclusion chromatography. The 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging capacity and ferrous reducing activity of xylose-BCH MRPs gradually increased with the reaction time extended from 0 to 8 h.

A conserved enhancer regulates Il9 expression in multiple lineages.

Cytokine genes are regulated by multiple regulatory elements that confer tissue-specific and activation-dependent expression. The cis-regulatory elements of the gene encoding IL-9, a cytokine that promotes allergy, autoimmune inflammation and tumor immunity, have not been defined. Here we identify an enhancer (CNS-25) upstream of the Il9 gene that binds most transcription factors (TFs) that promote Il9 gene expression. Deletion of the enhancer in the mouse germline alters transcription factor binding to the remaining Il9 regulatory elements, and results in diminished IL-9 production in multiple cell types including Th9 cells, and attenuates IL-9-dependent immune responses. Moreover, deletion of the homologous enhancer (CNS-18) in primary human Th9 cultures results in significant decrease of IL-9 production. Thus, Il9 CNS-25/IL9 CNS-18 is a critical and conserved regulatory element for IL-9 production.

Malignant solid pseudopapillary tumor of pancreas causing sinistral portal hypertension.

Solid pseudopapillary tumor (SPT) of the pancreas is a rare benign or low-grade malignant epithelial tumor that occurs mainly in young females in second to fourth decades of life. Pathologic and imaging findings include a well-defined, encapsulated pancreatic mass with cystic and solid components with evidence of hemorrhage. We report a 23-year-old female who presented with upper abdominal pain of long duration and epigastric mass on palpation. Multidetector-row CT (MDCT) demonstrated a large well-defined heterogeneous attenuation mass, containing hyperdense areas of hemorrhage mixed with solid enhancing and cystic non-enhancing areas, arising from the pancreatic body and tail. Splenic vein thrombosis was present with dilated splenoportal collateral vessels between splenic hilum and portal/superior mesenteric veins, with dilated vessels seen in the gastric wall, with patent portal vein, compatible with sinistral portal hypertension. Typical imaging features and age and sex of the patient suggested a diagnosis of SPT of pancreas complicated by segmental portal hypertension due to splenic vein thrombosis. Histopathology of the biopsy material was confirmatory.

Multidetector-row computed tomography in cerebral hydatid cyst.

Intracranial localization is a rare manifestation of hydatid cyst disease (Echinococcosis). It comprises only 2% of cases of Echinococcosis infection even in endemic areas and is predominantly seen in children. Clinical manifestations resulting from raised intracranial tension are nonspecific. Imaging with computed tomography (CT) may suggest the diagnosis preoperatively with reasonable accuracy. Multidetector-row CT (MDCT) with its high resolution multiplanar reformations can demonstrate the relationship of the cyst with adjacent brain structures and thus help in planning surgery. This has a practical utility in places where magnetic resonance imaging is not available. We describe a case of cerebral hydatid cyst in a 13-year-old boy who was diagnosed with MDCT, which helped in planning its surgical removal.

Prevalence and predictors of smoking in Pakistan: results of the National Health Survey of Pakistan.

OBJECTIVE: We analysed data collected during a nationwide cross-sectional household survey to estimate the prevalence of and identify factors associated with smoking in Pakistan. DESIGN: Population-based, cross-sectional survey [National Health Survey of Pakistan (NHSP) 1990-1994]. METHODS: A population-based survey was carried out in Pakistan during 1990-1994. A nationally representative sample of 18,135 individuals aged 6 months and older was surveyed. We restricted this analysis to individuals aged 15 years or older (n=9442). The main outcome measure was self-reported smoking. Smokers were defined as individuals who reported current smoking and having smoked at least 100 cigarettes or 'beddies' during their lifetime. RESULTS: Overall prevalence of smoking was 15.2% [95% confidence interval (CI), 14.5-15.9%]. It was 28.6% (27.3-29.9%) among men and 3.4% (2.9-3.9%) among women. The highest prevalence was reported in men aged 40-49 years (40.9%). The independent predictors of smoking identified in the multivariate logistic regression analysis included age, male gender, ethnicity and illiteracy. CONCLUSIONS: One out of every two to three middle-aged men in Pakistan smoke cigarettes. Our findings suggest that ethnically sensitive smoking control programmes that include measures for improving literacy rates are needed in Pakistan.

Proteinuria in South Asian children: prevalence and determinants.

Proteinuria in children is a marker of kidney disease and atherosclerosis, both which are known predictors of cardiovascular mortality. Recent evidence suggests that migrant South Asian populations living in the West may be at higher risk of kidney disease than native Caucasians. However, the determinants of proteinuria in South Asian children have not been explored. Previously, we reported ethnic variation in the prevalence of proteinuria in the adult population of Pakistan. However, it is not known whether ethnic predisposition to proteinuria appears during childhood or whether it is acquired later in life as a result of prolonged exposure to undiagnosed diabetes and hypertension. Analyses were based on a subset of data for 4977 children aged 5 to less than 15 years collected as part of the broad National Health Survey of Pakistan, conducted between 1990 and 1994. Proteinuria was defined as a dipstick positive for protein on a random urine sample. Ethnicity was reported as "mother-tongue", which is specific for each of the five major ethnic subgroups of Pakistan: Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi. The overall prevalence (95% CI) of proteinuria in the children was 3.3% (2.7-3.9%). It was 6.2% in Sindhis, 3.6% in Muhajirs, 2.8% in Punjabis, 2.8% in Baluchis, and 1.0% in Pashtuns (p<0.001). In multivariable analyses, proteinuria was associated with greater height (p=0.007), urban dwelling (p=0.03), lower socioeconomic status (p=0.02), and certain ethnicities (p=0.005). The ethnic variation in proteinuria in South Asian children mirrors variation among ethnic groups in adults. This suggests variations in susceptibility or early exposure to causes of chronic kidney disease, rather than long-term exposure to undiagnosed diabetes or hypertension. Further studies are needed to determine factors in early life that may differentially predispose certain ethnic groups to proteinuria.