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Complexity of longitudinal data lies in the inherent dependence among measurements from same subject over different time points. For multiple longitudinal responses, the problem is challenging due to inter-trait and intra-trait dependence. While linear mixed models are popularly used for analysing such data, appropriate inference on the shape of the population cannot be drawn for non-normal data sets. We propose a linear mixed model for joint quantile regression of multiple longitudinal responses. We consider an asymmetric Laplace distribution for quantile regression and estimate model parameters by Monte Carlo EM algorithm. Nonparametric bootstrap resampling method is used for estimating confidence intervals of parameter estimates. Through extensive simulation studies, we investigate the operating characteristics of our proposed model and compare the performance to other traditional quantile regression models. We apply proposed model for analysing data from nutrition education programme on hypercholesterolemic children of the USA. [ABSTRACT FROM AUTHOR]

Purpose of Review: The entire gamut of changes in the lipid profile that precede, predict, and correlate with hypertension in metabolic syndrome is unknown. Recent Findings: The power, resolution, and accuracy of lipidomic assay technologies have brought us to the threshold of another information explosion. Understanding of hypertension and its pathophysiology especially within the setting of metabolic syndrome has been greatly improved by recent lipidomic studies. Hypertension in metabolic syndrome differs from other forms of hypertension, and recent studies have highlighted this difference in many interesting ways. Mounting evidence points towards a derangement of the sphingolipid pathway that may trigger the precursor clinical conditions of hypertension as well as hypertension itself. In this review, we summarize the available published literature in this field and propose a unifying hypothesis based on the published evidence. Summary: Recent studies have created substantial interest and advances in the understanding of hypertension in metabolic syndrome. Studies that directly test these concepts within a lipidomic framework are urgently needed. [ABSTRACT FROM AUTHOR]

Sex selection, a gender discrimination of the worst kind, is highly prevalent across all strata of Indian society. Physicians have a crucial role in this practice and implementation of the Indian Government's Pre-Natal Diagnostic Techniques Act in 1996 to prevent the misuse of ultrasound techniques for the purpose of prenatal sex determination. Little is known about family preferences, let alone preferences among families of physicians. We investigated the sex ratios in 946 nuclear families with 1,624 children, for which either one or both parents were physicians. The overall child sex ratio was more skewed than the national average of 914. The conditional sex ratios decreased with increasing number of previous female births, and a previous birth of a daughter in the family was associated with a 38 % reduced likelihood of a subsequent female birth. The heavily skewed sex ratios in the families of physicians are indicative of a deeply rooted social malady that could pose a critical challenge in correcting the sex ratios in India. [ABSTRACT FROM AUTHOR]

Purpose: The role of v-ATPases in cancer biology is being increasingly recognized. Yeast studies indicate that the tyrosine kinase inhibitor imatinib may interact with the v- ATPase genes and alter the course of cancer progression. Data from humans in this regard are lacking. Methods: We constructed 55 lymphoblastoid cell lines from pedigreed, cancer-free human subjects and treated them with IC20 concentration of imatinib mesylate. Using these cell lines, we (i) estimated the heritability and differential expression of 19 genes encoding several subunits of the v-ATPase protein in response to imatinib treatment; (ii) estimated the genetic similarity among these genes; and (iii) conducted a high-density scan to find cis-regulating genetic variation associated with differential expression of these genes. Results: We found that the imatinib response of the genes encoding v-ATPase subunits is significantly heritable and can be clustered to identify novel drug targets in imatinib therapy. Further, five of these genes were significantly cis-regulated and together represented nearly half-log fold change in response to imatinib ( p = 0.0107) that was homogenous ( p = 0.2598). Conclusions: Our results proffer support to the growing view that personalized regimens using proton pump inhibitors or v-ATPase inhibitors may improve outcomes of imatinib therapy in various cancers. [ABSTRACT FROM AUTHOR]

Zinc has caught wide scientific attention for the conceptual promise it has to offer for prevention, control and treatment of acute diarrhea. This review focuses on the mechanisms by which zinc might contribute to the pathogenesis of acute diarrhea and the degree of success achieved in diarrhea control and treatment by zinc supplementation. Animal and in vitro studies have continued to fascinate the scientific fraternity and form a solid basis for the potential use of zinc supplementation against diarrhea. However, emerging evidence in terms of controlled studies in humans beckons a more complete understanding of the mechanistic basis for zinc supplementation. Current evidence indicates that studies specifically addressing the variability in response to zinc supplementation need to be undertaken to better comprehend these mechanisms. [ABSTRACT FROM AUTHOR]

A response by Weijing He and colleagues to a letter to the editor on their articles regarding the methodological concerns of C-C chemokine ligand-3-like-1 (CCL3L1) gene quantitative Polymerase Chain Reaction (qPCR) assay is presented.

The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. [ABSTRACT FROM AUTHOR]

Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry–independent mechanisms. [ABSTRACT FROM AUTHOR]

To determine the prognostic value of indirect and direct hyperbilirubinemia in neonates with jaundice. A cohort of 92 consecutive neonates reporting with hyperbilirubinemia to a tertiary care center were followed up till well and discharged, or, till death to assess risk and rate of mortality. The baseline median values of total, direct and indirect bilirubin in the cohort of 21.8, 1.6 and 18.6 mg/dl, respectively, were used as cut-offs for high and low levels. Using survival analyses i.e. Kaplan-Meier plots, logrank tests and multivariate Cox proportional hazards regression models to adjust for other strong predictors such as receipt of breastfeeding, being small for gestational age (SGA) and exchange transfusion, high direct bilirubin (≥ median value of 1.6 mg/dl) was independently associated with a higher and faster mortality. This study showed that direct bilirubin has independent and additive prognostic value and due attention should be given to newborns with raised levels. [ABSTRACT FROM AUTHOR]

Considering the multigenic and multifactorial nature of the disease, we argue that a generalized bone marrow hyperplasia—and not merely erythroid hyperplasia—will occur in sickle cell disease. Consequently, we expect the hematological parameters to depict erythroid, myeloid as well as megakaryocyte hyperplasia. In the light of this expectation, we hypothesized that platelet distribution width (PDW) will increase in sickle cell disease. Here, we report the results from a cross-sectional study of 216 children admitted with complaints suggestive of vaso-occlusive crisis. We observed a strong association between PDW and sickle cell disease as compared to children who had HbAA genotype. Our findings bridge previous inconsistencies relating to the role of platelets in sickle cell disease. Implications of this finding are discussed. [ABSTRACT FROM AUTHOR]

Objective: There is limited data available on symptomatic leptospirosis in Indian children. We report an outbreak of leptospirosis that occurred in children living in slums following heavy rainfall and flooding. This hospital-based prospective study was conducted from July to August 2001.Methods: Diagnosis of acute leptospirosis was suspected by following the Indian Leptospirosis Society working definition for leptospirosis. Diagnosis was confirmed by detecting anti-Leptospira antibodies, using either a Leptospira genus-specific latex agglutination assay or a dipstick assay or by a macroscopic slide agglutination test.Result: Thirty (32%) out of 93 children admitted had acute leptospirosis. Fever, bodyache, chills, abdominal pain, headache, vomiting, cough, hepatosplenomegaly, edema and crepitations were the common presenting signs and symptoms. Twenty - two children had anicteric leptospirosis and 8 had Weil disease. Response to penicillin treatment was good in all except in one child with Weil disease who died of renal failure within 3 hours of admission.Conclusion: Leptospirosis has emerged as an infectious disease in Mumbai. During monsoon, parents should ensure that their child does not have contact with the contaminated flood water. [ABSTRACT FROM AUTHOR]

The Coffin-Lowry syndrome is an established syndrome of severe mental and growth retardation, characteristic dysmorphic features and skeletal anomalies. The authors report a one and half year old boy with classical features of this syndrome. Early recognition of this condition is important for genetic counseling and prevention of progressive skeletal deformities. [ABSTRACT FROM AUTHOR]

Bilateral anotia or microtia is known to be associated with multiple order malformations. The authors report a young infant who presented with failure to thrive and recurrent respiratory tract infections. The patient had bilaterally absent pinnae; instead small skin tags were present. He also had asymmetric crying facies and clinical evidence of hypothyroidism in the form of hoarse voice, constipation and generalized hypotonia. Thyroid function tests confirmed the diagnosis of hypothyroidism. [ABSTRACT FROM AUTHOR]