Bilharzia in a small irrigation community: an assessment of water and toilet usage

A study on the hygienic usage of pit- latrines to avert bilharziasis in rural Zimbabwe.A questionnaire study was conducted in the Mushandike small scale irrigation schemes in Zimbabwe to investigate the following: 1) to establish whether field latrines are used or not; 2) to find out why people visit natural water bodies for bathing and laundry instead of using water from boreholes for these purposes; 3) to assess people’s knowledge on the transmission and control of schistosomiasis. Results of the study indicated that die field latrines tire utilized and that the borehole water is not preferred for bathing and laundry because of its hardness and oily nature. The results further indicated that the community was aware of schistosomiasis but their knowledge on transmission and control of the disease was limited. Possible reasons for tire observations made tire discussed in die paper and recommendations emanating from the study are stated

Synthesis of Some New Isoxazoline Derivatives of Chalconised Indoline 2-one as a Potential Analgesic, Antibacterial and Anthelmimtic Agents

A series of novel 1[5”-(2”’-substituted phenyl)-4”,5”’-dihydro isoxazole-3”-yl]-3-[(4 substituted phenyl)imino]1-3-dihydro-2H-indole-2-one were synthesized from different substituted chalconised indole-2,3-dione was prepared from the different chalconised Isatin. The structures of the compounds were elucidated by elemental and spectral (IR, 1H NMR, and MS) analysis. The synthesized compounds were screened for their analgesic activity by the acetic acid induced Writhing method and in vitro antimicrobial activity against the Gram-positive bacteria—Staphylococcus aureus and the Gram-negative bacteria—Pseudomonas auroginosa, Pseudomonas mirabilis, and E. coli by the cup plate agar diffusion method. Compounds 6a1, 6a3, 6b3, and 6b2 were found to be active against bacteria. The compounds 6a1, 6b3, and 6a3 show a significant analgesic activity. Synthesized compounds also screened for anthelmintic activity against Pheretima posthuma. Compounds 6a1, 6b1, and 6b3 show significant anthelmintic activity

Infant growth and body composition from birth to 24 months: Are infants developing the same?

Background: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries.Methods: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (-0.25 \u3e HAZ \u3c +0.25), below-average (≤-0.25) and above-average (≥+0.25) HAZ.Results: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ.Conclusion: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity

Current socio-economic measures, and not those measured during infancy, affect bone mass in poor urban South african children.

Understanding the impact of socio-economic status (SES) on physical development in children is important, especially in developing countries where considerable inequalities persist. This is the first study to examine the association between SES on bone development at the whole body, femoral neck, and lumbar spine in black children living in Soweto and Johannesburg, South Africa. Linear regression models were used to study associations between SES during infancy and current SES, anthropometric, and DXA-derived bone mass in 9/10-yr-old children (n = 309). Findings suggest that current SES measures, rather than SES during infancy, are stronger predictors of current whole body bone area (BA) and whole body BMC after adjusting for body size, pubertal development, physical activity, habitual dietary calcium intake, and body composition. SES had no significant effect on either hip or spine bone mass. Caregiver's marital/cohabiting status (indicator of social support) and whether there was a television in the home (indicator of greater income) at age 9/10 yr were the most important socio-economic determinants of whole body BA and BMC. SES has a significant independent effect on whole body BMC through its impact on BA. This suggests that poverty alleviation policies in South Africa could have a positive effect on bone health

Recent Advances in Combined Modality Therapy

This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy

Stunting in infancy, pubertal trajectories and adult body composition: the Birth to Twenty Plus cohort, South Africa.

BACKGROUND/OBJECTIVES: Childhood rapid growth and earlier puberty onset have been associated with adult obesity. However, the association between childhood stunting, pubertal timing and adult obesity is unclear. We examined whether the relationship between stunting at age 2 years (y) and body composition at 23 years is mediated by adolescent body mass index, and pubertal development, using the Birth-to-Twenty Plus cohort (South Africa). SUBJECTS/METHODS: For 1036 participants, data on anthropometrics between birth and 23 years, maternal factors, and pubertal development (Tanner scale at 9-16 years) were collected. Stunting at 2 years (height-for-age z-score < -2), 5-18 years BMI-for-age trajectories, pubertal development trajectories, and DXA-derived fat mass (FM) and fat free mass (FFM) at 23 years were determined. Data were analysed using hierarchical regressions and structural equation models. RESULTS: Stunting was directly associated with slower pubertal development and with shorter adult stature, but was not associated with adolescent BMI trajectories, adult FM or FFM. However, stunting was indirectly associated with adult FM and FFM through the direct associations between slower pubertal development and lower FM and between shorter height and lower FFM. BMI trajectories were independently associated with FM and FFM. CONCLUSIONS: Being stunted in this population predicted adult body composition through slower pubertal development and shorter adult stature

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable FoundationWe thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pd

Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma

Distinct oncogenic signalling cascades have been associated with non-Hodgkin lymphoma. ERK1/2 signalling elicits both transcriptional and post-transcriptional effects through phosphorylation of numerous substrates. Here we report a novel molecular relationship between ERK1/2 and CHK2, a protein kinase that is a key mediator of the DNA damage checkpoint that responds to DNA double-strand breaks. Our studies are the first to demonstrate the co-localization and overexpression of ERK1/2 and CHK2 in diffuse large B-cell lymphoma (DLBCL). The physical interaction between ERK and CHK2 was highly dependent on phosphorylated Thr 68 of CHK2. Concurrent administration of an ERK inhibitor enhances the antitumour activity of CHK2 inhibition in both a human DLBCL xenograft model as well as primary human DLBCL cells. Our data suggest a functional interaction between ERK and CHK2 and support the potential combined therapeutic targeting of ERK and CHK2 in human DLBCL

P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation

BACKGROUND: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. CONCLUSIONS/SIGNIFICANCE: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis