Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Genome-Wide Linkage Analysis of Global Gene Expression in Loin Muscle Tissue Identifies Candidate Genes in Pigs

BACKGROUND: Nearly 6,000 QTL have been reported for 588 different traits in pigs, more than in any other livestock species. However, this effort has translated into only a few confirmed causative variants. A powerful strategy for revealing candidate genes involves expression QTL (eQTL) mapping, where the mRNA abundance of a set of transcripts is used as the response variable for a QTL scan. METHODOLOGY/PRINCIPAL FINDINGS: We utilized a whole genome expression microarray and an F(2) pig resource population to conduct a global eQTL analysis in loin muscle tissue, and compared results to previously inferred phenotypic QTL (pQTL) from the same experimental cross. We found 62 unique eQTL (FDR <10%) and identified 3 gene networks enriched with genes subject to genetic control involved in lipid metabolism, DNA replication, and cell cycle regulation. We observed strong evidence of local regulation (40 out of 59 eQTL with known genomic position) and compared these eQTL to pQTL to help identify potential candidate genes. Among the interesting associations, we found aldo-keto reductase 7A2 (AKR7A2) and thioredoxin domain containing 12 (TXNDC12) eQTL that are part of a network associated with lipid metabolism and in turn overlap with pQTL regions for marbling, % intramuscular fat (% fat) and loin muscle area on Sus scrofa (SSC) chromosome 6. Additionally, we report 13 genomic regions with overlapping eQTL and pQTL involving 14 local eQTL. CONCLUSIONS/SIGNIFICANCE: Results of this analysis provide novel candidate genes for important complex pig phenotypes

Preconditioning with Physiological Levels of Ethanol Protect Kidney against Ischemia/Reperfusion Injury by Modulating Oxidative Stress

Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress.Bilateral renal warm IR was induced in male C57BL/6 mice after ethanol or saline administration. Blood ethanol concentration, kidney function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity and Aldehyde dehydrogenase (ALDH) enzymatic activity were assessed to evaluate the impact of antecedent ethanol exposure on IR-induced renal injury.After bilateral kidney ischemia, mice preconditioned with physiological levels of ethanol displayed significantly preserved renal function along with less histological tubular damage as manifested by the reduced inflammatory infiltration and cytokine production. Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities. Our studies further demonstrated that ethanol pretreatment specifically increased ALDH2 activity, which then suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE).Our results provide first line of evidence indicating that antecedent ethanol exposure can provide protection for kidneys against IR-induced injury by enhancing antioxidant capacity and preventing lipid peroxidation. Therefore, ethanol precondition and ectopic ALDH2 activation could be potential therapeutic approaches to prevent renal IR injury relevant to various clinical conditions

A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis

Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from “authentic” telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words

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Not AvailableBovine mastitis is one of economically important disease affecting livestock and causing economic losses to dairy farmers in India. Coagulase Negative Staphylococcus (CNS) species also infects the mammary glands of animals and leads to persistent or subclinical mastitis. The prevalence of CNS mastitis in various parts of the world were 6-72 and 6-30% in subclinical and clinical mastitis cases, respectively. Epidemiology of CNS species causing mastitis in animals gives the newer approaches for preventing the occurrence of CNS species mastitis. The CNS species predominantly isolated from milk were S. chromogenes, S. epidermidis, S. haemolyticus, S. simulans, S. warneri, S. hominis, S. saprophyticus, S. xylosus, S. hyicus, S. sciuri and S. intermedius. The S. epidermidis intramammary infections were found in multiparous cow and S. chromogenes in primiparous cows. The CNS mastitis shows only mild clinical signs and cause persistent infections, resulting in increased milk SCC, which affects milk quality and may be related to decreased milk production. The clinical signs, diagnosis and treatment of CNS mastitis are necessary for effective control and prevention. There was emergence of CNS species as an important mastitis causing pathogen in subclinical mastitis and persistence infection of udder in dairy animals of India and world. In conclusion, there is need to further identify the CNS at species level and also systematic experimental study of various CNS species in dairy animals is required for better understanding the occurrence of CNS mastitis in livestock of India. Further, comparative study of CNS mastitis with organisms causing severe mastitis in various animal models to know the basic mechanisms of host pathogen interaction using advance molecular biology tools is necessary.Not Availabl

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Not AvailableIntroduction: Mastitis is caused by different Staphylococcus species, produce great economic loss to farmers. Present study was conducted to know pathological changes in mice inoculated with Staphylococcus epidermidis, S. chromogenes, S. haemolyticus and S. aureus isolated from bovine milk. Materials and Methods: Mice were inoculated with 50 μl (2x104 cfu organisms) per mammary gland and euthanized at 6, 12, 24, 48, 72 and 96 h. Mammary gland weight, gross and histopathological changes of mammary gland, liver, kidney, spleen, heart, lung and inguinal lymph node were studied. Results: Mammary gland weight and percentage of body weight increased at 6 and 96 h in S. aureus and S. haemolyticus infected mice. Gross changes were observed in mammary gland but not in other organs. Mammary gland revealed gross changes from 24 to 72 h in three Coagulase negative staphylococcal (CNS) species and persisted up to 96 h in S. aureus infected mice. Histopathological changes in mammary glands was severe in S. aureus and moderate in CNS species. S. aureus infected mice revealed severe damage to alveoli and loss of alveolar architecture at 96 h but three CNS species infection was overcome by host factors which was evident by proliferation of alveolar epithelial cells. No histological changes were observed in kidney, spleen, lung, heart and inguinal lymph nodes. Conclusions: S. aureus caused severe mastitis in mice when compared to CNS species. Further, it is first report of mice to study CNS mastitis, and in future it can be used as model for CNS mastitis.Not Availabl

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