Possible association between the lrrk2 gene and anxiety behavior: a systematic literature review.

Alterations to the LRRK2 gene have been associated with Parkinson's disease and alcohol consumption in animals and humans. Furthermore, these disorders are strongly related to anxiety disorders (ADs). Thus, we investigated how the LRRK2 gene might influence anxiety in humans and mice. We elaborated a systematic review based on the PRISMA Statement of studies that investigated levels of anxiety in animal or human models with alterations in the LRRK2 gene. The search was conducted in the PubMed, Scopus, and Web of Science databases, and in reference lists with descriptors related to ADs and the LRRK2. From the 62 articles assessed for eligibility, 16 were included: 11 conducted in humans and seven, in mice. Lrrk2 KO mice and the LRRK2 G2019S, LRRK2 R1441G, and LRRK2 R1441C variants were addressed. Five articles reported an increase in anxiety levels concerning the LRRK2 variants. Decreased anxiety levels were observed in two articles, one focusing on the LRRK2 G2019S and the other, on the Lrrk2 KO mice. Eight other articles reported no differences in anxiety levels in individuals with Lrrk2 alterations compared to their healthy controls. This study discusses a possible influence between the LRRK2 gene and anxiety, adding information to the existing knowledge respecting the influence of genetics on anxiety.

Self-Assembly of Phosphocholine Derivatives Using the ELBA Coarse-Grained Model: Micelles, Bicelles, and Reverse Micelles.

The ELBA coarse-grained force field was originally developed for lipids, and its water model is described as a single-site Lennard-Jones particle with electrostatics modeled by an embedded point-dipole, while other molecules in this force field have a three (or four)-to-one mapping scheme. Here, ELBA was applied to investigate the self-assembly processes of dodecyl-phosphocholine (DPC) micelle, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dihexaoyl-sn-glycero-3-phosphocholine (DPPC/DHPC) bicelles, and DPPC/cyclohexane/water reverse micelles through coarse-grained molecular dynamics (MD) simulations. New parameters were obtained using a simplex algorithm-based calibration procedure to determine the Lennard-Jones parameters for cyclohexane, dodecane, and cyclohexane-dodecane cross-interactions. Density, self-diffusion coefficient, surface tension, and mixture excess volume were found to be in fair agreement with experimental data. These new parameters were used in the simulations, and the obtained structures were analyzed for shape, size, volume, and surface area. Except for the shape of DPC micelles, all other properties match well with available experimental data and all-atom simulations. Remarkably, in agreement with experiments the rodlike shape of the DPPC reverse micelle is well described by ELBA, while all-atom data in the literature predicts a disclike shape. To further check the consistency of the force field in reproducing the correct shapes of reverse micelles, additional simulations were performed doubling the system size. Two distinct reverse micelles were obtained both presenting the rodlike shape and correct aggregation number.

An overview of molecular dynamics simulations of oxidized lipid systems, with a comparison of ELBA and MARTINI force fields for coarse grained lipid simulations.

Biological membranes and model lipid systems containing high amounts of unsaturated lipids and sterols are subject to chemical and/or photo-induced lipid oxidation, which leads to the creation of exotic oxidized lipid products (OxPLs). OxPLs are known to have significant physiological impact in cellular systems and also affect physical properties of both biological and model lipid bilayers. In this paper we (i) provide a perspective on the existing literature on simulations of lipid bilayer systems containing oxidized lipid species as well as the main related experimental results, (ii) describe our new data of all-atom and coarse-grained simulations of hydroperoxidized lipid monolayer and bilayer systems and (iii) provide a comparison of the MARTINI and ELBA coarse grained force fields for lipid bilayer systems. We show that the better electrostatic treatment of interactions in ELBA is able to resolve previous conflicts between experiments and simulations. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

Serotypes, virulence markers and cell invasion ability of Shiga toxin-producing Escherichia coli strains isolated from healthy dairy cattle.

AIM: The occurrence of virulence markers, serotypes and invasive ability were investigated in Shiga toxin-producing Escherichia coli (STEC) isolated from faecal samples of healthy dairy cattle at Rio de Janeiro State, Brazil. METHODS AND RESULTS: From 1562 stx-positive faecal samples, 105 STEC strains were isolated by immuno-magnetic separation (IMS) or plating onto MacConkey agar (MC) followed by colony hybridisation. Fifty (47·6%) strains belonged to nine serotypes (O8:H19, O22:H8, O22:H16, O74:H42, O113:H21, O141:H21, O157:H7, O171:H2 and ONT:H21). The prevalent serotypes were O157:H7 (12·4%), O113:H21 (6·7%) and O8:H19 (5·7%). Virulence genes were identified by polymerase chain reaction (PCR). E-hlyA (77·1%) was the more prevalent virulence marker, followed by espP (64·8%), saa (39%), eae (24·8%) and astA (21·9%). All O157:H7 strains carried the γ (gamma) variant of the locus of enterocyte effacement (LEE) genes and the stx2c gene, while the stx1/stx2 genotype prevailed among the eae-negative strains. None of the eae-positive STEC produced the localized adherence (LA) phenotype in HEp-2 or Caco-2 cells. However, intimate attachment (judged by the fluorescent actin staining test) was detected in some eae-positive strains, both in HEp-2 (23·1%) and in Caco-2 cells (11·5%). Most strains (87·5%) showed 'peripheral association' (PA) adherence phenotype to undifferentiated Caco-2 cells. Twenty-five (92·6%) of 27 strains invaded Caco-2 cells. The highest average value of invasion (9·6%) was observed among the eae-negative bovine strains from serotypes described in human disease. CONCLUSION: Healthy dairy cattle is a reservoir of STEC carrying virulence genes and properties associated with human disease. SIGNIFICANCE AND IMPACT OF THE STUDY: Although reports of human disease associated with STEC are scarce in Brazil, the colonization of the animal reservoir by potentially pathogenic strains offers a significant risk to our population.

Salt intake during pregnancy alters offspring's myocardial structure.

BACKGROUND AND AIM: To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. METHODS AND RESULTS: Low- (LS, 0.15%), normal- (NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. CONCLUSIONS: HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake.

Bacterial Leaf Spot of Radicchio (Cichorium intybus) is caused by Xanthomonas hortorum.

Radicchio (Cichorium intybus) is ranked 22 among crops in Monterey County, California, with a farm gate value of $19,531,000 (3). Beginning in 2002, a leaf spot disease of radicchio was observed in Monterey County. The disease began as small lesions and in some cases coalesced into larger, irregular spots. Lesions were maroon to dark brown; in some cases, the margins of brown lesions became dark maroon with aging. Each leaf spot was observable from both adaxial and abaxial leaf surfaces. Symptoms primarily occurred on the outer foliage of the heads, though on occasion the head cap leaf could develop lesions. Disease incidence in the first year resulted in up to 10% unharvested radicchio because of cap leaf infections or reduced head size if outer wrapper leaves were all removed; outbreaks in subsequent seasons were more limited. Bacteria forming yellow mucoid colonies were isolated from surface disinfested symptomatic tissue that was macerated and streaked onto sucrose peptone agar medium. Bacteria were gram negative, did not fluoresce on King's Medium B, and used esculin as a carbon source but used none of the other 48 carbon sources tested using the API 50 CH test strip. Nine isolates from symptomatic radicchio had the same DNA fragment banding pattern generated by repetitive extragenic palindromic sequence polymerase chain reactions (rep-PCR) using the BOXA1R primer. Amplicons of rpoD, dnaK, fyuA, and gyrB for multilocus sequence typing (MLST) were generated using a modification of the scheme developed by Young et al. (4) and sequenced by a commercial laboratory. Concatenated sequences of the four genes from the radicchio isolates were compared to the sequences available in the Plant Associated and Environmental Microbes Database (1). The genetic distance between the nine isolates from radicchio and pathotypes of Xanthomonas hortorum were 0.03 or less and MLST analysis indicated that radicchio isolates were members of the species X. hortorum (2). To complete Koch's postulates, freshly grown cultures were suspended in phosphate buffer and adjusted to approximately 5 × 108 CFU/ml. The inoculum was sprayed onto the undersides of leaves of 40-day-old radicchio plants (C. intybus cv. Leonardo). Plants were incubated at 100% humidity for 48 h and then moved to a greenhouse. Plants sprayed with buffer served as negative controls. For each of the two experiments conducted, there were three and six single-plant replicates per treatment. The buffer treated plants did not develop symptoms but the plants treated with isolates from radicchio developed leaf spots similar to those observed in the field with symptoms beginning to be visible after 5 days. The bacteria isolated from symptomatic tissue on inoculated plants were identical to the original strains when compared with rep-PCR, thus completing Koch's postulates. Results from the two experiments were similar. To our knowledge, this is the first report of X. hortorum causing a leaf spot disease on radicchio. The disease continues to occur sporadically on radicchio grown in coastal California. References: (1) Almeida et al. Phytopathology 100:208, 2010. (2) Bull et al. Phytopathology 101:847, 2011. (3) Lauritzen, Monterey County Crop Report, 2010; (4) Young et al. Syst. Appl. Microbiol. 31:366, 2008.

The environmental dimensions of the HIV/AIDS pandemic: a call for scholarship and evidence-based intervention.

The HIV/AIDS pandemic has had dramatic influence on the demographic dynamics of many of the world's less economically developed regions. Today, an estimated 33 million individuals are living with HIV, and recent data suggest that, every day, over 6800 persons become HIV-infected and over 5700 persons die from AIDS (UNAIDS 2006). The age profile of HIV infection is well known, with new cases impacting primarily prime-age adults. Sub-Saharan Africa remains the world's most affected region with recent population-based surveys suggesting that adult prevalence rates (age 15-49) reaches as high as 25% in Botswana and over 23% in Lesotho (UNAIDS 2006). Still, HIV/AIDS also impacts children, with over 2 million HIV+ individuals under age 15 in sub-Saharan Africa; And the disease profile now includes many individuals over age 50 due to the positive impact on life expectancy of recent treatment advances (UNAIDS 2006).Of course, HIV/AIDS' impacts at the individual and household levels are difficult to discern from aggregate data although ethnographic research provides insights into nuanced household survival strategies (e.g., Evans 2005; Schatz and Ogunmefun 2007). Such work reveals household efforts to maintain a sense of "normality" in response to the impacts of HIV/AIDS, otherwise known as "the disease" (Bohman et al. 2007).

WITHDRAWN: Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. AUTHORS' CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Effect of Entomopathogenic Nematodes (Rhabditida: Steinernematidae and Heterorhabditidae) on Meloidogyne mayaguensis Rammah and Hirschmann (Tylenchida: Meloidoginidae) Infection in Tomato Plants.

Some studies suggest that entomopathogenic nematodes (EPN) affect plant-parasitic nematode populations. Here, the effects of live and dead IJ of Heterorhabditis bacteriophora JPM4, H. baujardi LPP7, Steinernema feltiae SN and S. carpocapsae All were evaluated against eggs and J2 of the plant-parasitic nematode Meloidogyne mayaguensis. According to treatment, 100 IJ were applied with 350 eggs, 350 J2 or 175 eggs + 175 J2 to tomato plants. Bioassays were conducted in March to May and repeated in September to November 2005. Both experiments lasted 9 weeks, and the variable evaluated was number of galls per plant. When eggs were used for infections in the first trial, plants exhibited lower gall number compared to control when live and dead H. baujardi IJ and live S. feltiae IJ were added (9.7, 4.5, 7.3 and 85.7 galls, respectively). In the second trial, live S. feltiae and S. carpocapasae IJ influenced gall formation compared to control (14.33, 14.57 and 168.02 galls, respectively). When J2 were used for infections, plants with live H. baujardi IJ presented less galls when compared to control in both trials (38.3 and 355.7 galls in the first trial and 145.2 and 326.2 in the second one, respectively). Infection with a mixture of J2 and eggs resulted in fewer galls than when live S. feltiae IJ were present in both trials, compared to control (38.3 and 44.2 galls vs. 275.3 and 192.2 galls, respectively). We conclude that H. baujardi and S. feltiae apparently may be inhibiting egg hatching and J2 infection.

Methylene Blue Location in (Hydroperoxized) Cardiolipin Monolayer: Implication in Membrane Photodegradation.

We present molecular dynamics simulations of cardiolipin (CL) and CL monohydroperoxized derivative (CLOOH) monolayers to investigate the initial steps of phospholipid oxidation induced by methylene blue (MB) photoexcitation under continuous illumination. We considered different MB atomic charge distributions to simulate the MB electronic distribution in the singlet ground and triplet excited states. Simulation results allied to experimental data revealed that initial CL photooxidation probably occurs via a type II mechanism, to produce lipid hydroperoxide by singlet oxygen attack to the alkyl chain unsaturations. The resulting hydroperoxide group prefers to reside near the aqueous interface, to increase the membrane surface area and to decrease lipid packing. Interestingly, MB orientation changes from nearly parallel to the water-monolayer interface in the ground state to normal to the interface in its triplet excited state. The latter orientation favors oxidative chain reaction continuity via a type I mechanism, during which the hydrogen atom must be transferred from the hydroperoxide group to triplet MB. Taken together, the present results can be extrapolated to improve our understanding of how oxidation progresses in lipidic biomembrane, which will lead to the formation of oxidized species with shortened chains and will cause severe photodamage to self-organized systems.

Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection.

The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6%) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01%) were genotype 1 and 20 (28.99%) genotype non-1. Iron overload was detected in 14 (28.6%) patients with genotype 1 and in 6 (30%) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8%) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70% of group I patients compared to 46.2% of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1%) had a sustained virologic response and 8 (27.6%) of them had hepatic iron overload. Iron overload was detected in 18 (32.1%) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

First record of Neobenedenia melleni (Monogenea: Capsalidae) in dog snapper (Lutjanus jocu) in the western South Atlantic / Primeiro registro de Neobenedenia melleni (Monogenea: Capsalidae) em dentão (Lutjanus jocu) no oeste do Atlântico Sul

Neobenedenia melleni (MacCallum, 1927) (Monogenea) é um patógeno amplamente distribuído em cultivo de teleósteos marinhos no mundo. Com o crescimento da piscicultura marinha no Brasil, faz-se necessário um maior cuidado em relação à identificação e ao tratamento das principais patologias nesse tipo de cultivo. Este estudo relata a primeira ocorrência de Neobenedenia melleni em dentão (Lutjanus jocu) no oeste do Atlântico Sul. Também são sugeridos procedimentos adotados para eliminação desse parasito em peixes cultivados em laboratório.(AU)

Investigation of urban ethnoveterinary in three veterinary clinics at east zone of São Paulo city, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Urban Ethnoveterinary should be further explored because of its value as it resists conventional medical care. In addition, the comparison between the resources used by Ethnoveterinary and Ethnopharmacology should be investigated in depth, increasing the availability of new bioactive potential in human and veterinary medicines. This project aimed to determine whether plants are used in the health care of dogs and/or cats in urban area and to compare its uses with other ethnoveterinary and ethnopharmacological data. MATERIALS AND METHODS: Three veterinary clinics from east area of São Paulo city were selected, in order to record the offering of plants to pets by their owners. Individual interviews were conducted from May to November 2012 and consisted of application of semi-structured interviews and questionnaires. A literature search was performed to compare our findings with other ethnopharmacological and ethnoveterinarian data from the literature. RESULTS: A total of 273 people were interviewed and 46 (16.84%) of them utilize medicinal plants for their pets. Most plant species are exclusively home grown (57.9%). The plants most cited were Plectranthus barbatus Andrews, Matricaria chamomilla L. and Foeniculum vulgare Mill. The most frequent route of administration, part utilized and mode of preparation was oral (80.35%), leaves (89.47%) and infusion (61.90%), respectively. From 19 cited plants, 14 (73.7%) are mentioned in ethnoveterinary literature, whereas 11 (57.9%) are used for the same purposes. All plants reported in our study have at least one common use with ethnopharmacology. CONCLUSION: The survey provided evidence of ethnoveterinary use of medicinal plants for dogs and/or cats in urban area of São Paulo, complementarily with the official veterinary, and showed that the plants used in pets are also used in humans with the same purposes and routes of administration, as well as in other animals.

Work and health in a contemporary society: demands, control, and insecurity.

OBJECTIVE: To examine independent associations of job strain (high demands and low control) and job insecurity with mental and physical health outcomes. DESIGN: Cross sectional general population study conducted in 2000 using a self completed questionnaire. SETTING: Two adjoining cities in south east Australia. SUBJECTS: 1188 employed professionals, aged 40-44 years, 55% (n = 655) male. MAIN OUTCOME MEASURES: Depression, anxiety, physical, and self rated health (SRH). RESULTS: Adverse job conditions were relatively prevalent as 23% of the sample reported high job strain, while 7.3% and 23% reported high and moderate job insecurity respectively. Associations between job conditions and health persisted after adjustment for gender, education, marital status, employment status, major life events, and negative affectivity (personality). When adjusted for job strain, high job insecurity was independently associated with a greater than threefold increase in odds for poor SRH, depression and anxiety (OR (95% confidence intervals) poor SRH: 3.72 (1.97 to 7.04) depression: 3.49 (1.90 to 6.41), anxiety: 3.29 (1.71 to 6.33)), and a twofold increase for physical health 2.19 (1.21 to 3.95). High job strain also showed significant independent associations with depression: 2.54 (1.34 to.4.75) and anxiety: 3.15 (1.48 to 6.70). CONCLUSION: In this relatively privileged socioeconomic group, insecure employment and high job strain showed independent, consistent, and strong associations with physical and mental health. These adverse job conditions are on the increase, particularly insecure employment, and the influence of these two work conditions are an important focus for future public health research and their prevalence and impact should be examined in other occupations.

Vitamin A for treating measles in children.

BACKGROUND: Measles is a leading cause of childhood morbidity and mortality. Vitamin A deficiency is a recognised risk factor for severe measles. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. OBJECTIVES: The purpose of this review is to determine whether vitamin A when commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other complications in children. SEARCH STRATEGY: MEDLINE and the Cochrane Library, Issue 4, 1999 were searched. SELECTION CRITERIA: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two reviewers. The analysis of dichotomous outcomes was done using the StatXact software package. Sub-group analyses were done for dose, formulation, age, hospitalisation and pneumonia specific mortality. Weighted mean difference with 95% CI were calculated for continuous outcomes. MAIN RESULTS: The relative risks (RR) and 95% Confidence Intervals (CI) are based on the estimates from the StatXact software package. There was no significant reduction in mortality in the vitamin A group when all the studies were pooled together (RR 0.60; 95% CI 0.32 to 1.12)(StatXact estimate). There was a 64% reduction in the risk of mortality in children who were given two doses of 200,000 IU of vitamin A (RR=0.36; 95% CI 0.14 to 0.82) as compared to placebo. Two doses of water based vitamin A were associated with a 81% reduction in risk of mortality (RR=0.19; 95% CI 0.02 to 0.85) as compared to 48% seen in two doses of oil based preparation (RR=0.52; 95% CI 0.16 to 1.40). Two doses of oil and water based vitamin A were associated with a 82% reduction in the risk of mortality in children under the age of 2 years (RR=0.18; 95% CI 0.03 to 0.61) and a 67% reduction in the risk of pneumonia specific mortality (RR=0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose of 200,000 IU was associated with a reduced risk of mortality among children with measles (RR=0.77; 95% CI 0.34 to 1.78). Sub-groups like age, dose, formulation, hospitalisation and case fatality in the study area were highly correlated and there were not enough studies to separate out the individual effects of these factors. There was a 47% reduction in the incidence of croup (RR=0.53; 95% CI 0.29 to 0.89), while there was no significant reduction in the incidence of pneumonia (RR=0.92; 95% CI 0.69 to 1.22) or of diarrhoea (RR=0.80; 95% CI 0.27 to 2.34). Duration of diarrhoea was measured in days and there was a reduction in its duration of almost two days WMD -1.92, 95% CI -3.40 to -0.44. Only one study evaluated otitis media and found a 74% reduction in its incidence (RR=0.26, 95% CI, 0.05 to 0.92). We did not find evidence that a single dose of 200,000 IU of vitamin A per day, given in oil-based formulation in areas with low case fatality, was associated with reduced mortality among children with measles. However, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. REVIEWER'S CONCLUSIONS: Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. The effect was greater in children under the age of two years. There were no trials that compared a single dose with two doses, although the precision of the estimates of trials that used a single dose were similar to the trials that used two doses.

Vitamin A for treating measles in children.

BACKGROUND: Measles is a leading cause of childhood morbidity and mortality. Vitamin A deficiency is a recognised risk factor for severe measles. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. OBJECTIVES: The purpose of this review is to determine whether vitamin A when commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other complications in children. SEARCH STRATEGY: MEDLINE and the Cochrane Library, Issue 4, 1999 were searched. SELECTION CRITERIA: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two reviewers. The analysis of dichotomous outcomes was done using the StatExact software package. Sub-group analyses were done for dose, formulation, age, hospitalisation and pneumonia specific mortality. Weighted mean difference with 95% CI were calculated for continuous outcomes. MAIN RESULTS: The relative risks (RR) and 95% Confidence Intervals (CI) are based on the estimates from the StatExact software package. There was no significant reduction in mortality in the vitamin A group when all the studies were pooled together (RR 0.60; 95% CI 0.32 to 1.12)(Statexact estimate). There was a 64% reduction in the risk of mortality in children who were given two doses of 200,000 IU of vitamin A (RR=0.36; 95% CI 0.14 to 0.82) as compared to placebo. Two doses of water based vitamin A were associated with a 81% reduction in risk of mortality (RR=0.19; 95% CI 0.02 to 0.85) as compared to 48% seen in two doses of oil based preparation (RR=0.52; 95% CI 0.16 to 1.40). Two doses of oil and water based vitamin A were associated with a 82% reduction in the risk of mortality in children under the age of 2 years (RR=0.18; 95% CI 0.03 to 0.61) and a 67% reduction in the risk of pneumonia specific mortality (RR=0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose of 200,000 IU was associated with a reduced risk of mortality among children with measles (RR=0.77; 95% CI 0.34 to 1.78). Sub-groups like age, dose, formulation, hospitalisation and case fatality in the study area were highly correlated and there were not enough studies to separate out the individual effects of these factors. There was a 47% reduction in the incidence of croup (RR=0.53; 95% CI 0.29 to 0.89), while there was no significant reduction in the incidence of pneumonia (RR=0.92; 95% CI 0.69 to 1.22) or of diarrhoea (RR=0.80; 95% CI 0.27 to 2.34). Duration of diarrhoea was measured in days and there was a reduction in its duration of almost two days WMD -1.92, 95% CI -3.40 to -0.44. Only one study evaluated otitis media and found a 74% reduction in its incidence (RR=0.26, 95% CI, 0.05 to 0.92). We did not find evidence that a single dose of 200,000 IU of vitamin A per day, given in oil-based formulation in areas with low case fatality, was associated with reduced mortality among children with measles. However, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. REVIEWER'S CONCLUSIONS: Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. The effect was greater in children under the age of two years. There were no trials that compared a single dose with two doses, although the precision of the estimates of trials that used a single dose were similar to the trials that used two doses.

Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Antibiotics for preventing pneumonia in children with measles.

BACKGROUND: Measles causes more than a million deaths a year, of which most are children under five years of age who die from pneumonia. OBJECTIVES: The objective of this review was to assess the effects of antibiotics given to children with measles on reducing pneumonia or mortality, and to assess whether antibiotics should be given to all children with measles in communities with a high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE (1980-1999) and the specialized trials register of the Acute Respiratory Infections Group in August 1999, and all relevant journals in the University of Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised or controlled trials of antibiotics for children with measles. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Six trials with 1304 children were included. All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor, and they provide very weak evidence for giving antibiotics to all children with measles. Available evidence suggests that antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Retrospective hospital-based searches for cases of acute flaccid paralysis.

OBJECTIVE: Australia had to demonstrate adequate acute flaccid paralysis (AFP) surveillance by achieving a rate of one per 100,000 in children under the age of 15 to fulfil one of the requirements of the Regional Commission for the Certification of Poliomyelitis Eradication to be declared polio free. To increase the ascertainment rate of AFP cases, a hospital search was conducted to identify cases not reported to the active AFP surveillance. METHODS: A computerised search of hospital admissions in New South Wales (NSW) and Western Australia (WA) on ICD-9 codes of Guillain Barré Syndrome (GBS), unspecified encephalitis, poliomyelitis, vaccine-associated paralytic polio (VAPP) and flaccid paralysis was conducted for the period 1995-98. Medical records of cases that were not reported to the active surveillance were reviewed in three hospitals of NSW and two hospitals in WA. RESULTS: Twenty additional cases recorded as GBS and five as transverse myelitis (TM) were identified through the searches, which increased the average four-year AFP rate from 1.0 to 1.4 per 100,000 in children under the age of 15 years in these two states and the overall AFP rate in Australia increased from 0.78 to 1.14. There were no cases of polio or VAPP found. Nine cases of GBS and five of TM reported to the active AFP surveillance were not found in the hospital searches. CONCLUSION: A combination of active surveillance and hospital-based searches increased the investigated AFP rate, which fulfilled one of the certification requirements for Australia to be certified polio free. IMPLICATIONS: Until global certification is achieved, AFP surveillance needs to be improved to identify cases of importation of wild poliovirus.