Autism, surge in the prevalence and linkage with childhood vaccination - A Review

Autism a neurodegenerative disorder characterised by an abnormal child behaviour likeisolation, learning difficulties, general abnormality in communication and social reciprocity, inability to maintain eye contact or point at something, looking at thing with the peripheral vision and many other neurological disorders, the aetiology of autism is multifactorial including among other social, environmental, genetics, epigenetics andneurological factors, in recent years vaccines have drawn large interest of scientific community for its asserted role in the development of autism, this is largely due to the presence in higher concentration of a mercury containing compound thimerosal in many vaccines, and due to some evidence which link some vaccines including measles, mumps and rubella vaccines with autism, moreover several authentic scientific studies wereundertaken to falsified those findings. Here we critically review those assertion, examined some implicating component of vaccine and relate them with neurobiology of autism

Discordant transmission of bacteria and viruses from mothers to babies at birth

BACKGROUND: The earliest microbial colonizers of the human gut can have life-long consequences for their hosts. Precisely how the neonatal gut bacterial microbiome and virome are initially populated is not well understood. To better understand how the maternal gut microbiome influences acquisition of the infant gut microbiome, we studied the early life bacterial microbiomes and viromes of 28 infant twin pairs and their mothers. RESULTS: Infant bacterial and viral communities more closely resemble those of their related co-twin than unrelated infants. We found that 63% of an infant\u27s bacterial microbiome can be traced to their mother\u27s gut microbiota. In contrast, only 15% of their viral communities are acquired from their mother. Delivery route did not determine how much of the bacterial microbiome or virome was shared from mother to infant. However, bacteria-bacteriophage interactions were altered by delivery route. CONCLUSIONS: The maternal gut microbiome significantly influences infant gut microbiome acquisition. Vertical transmission of the bacterial microbiome is substantially higher compared to vertical transmission of the virome. However, the degree of similarity between the maternal and infant gut bacterial microbiome and virome did not vary by delivery route. The greater similarity of the bacterial microbiome and virome between twin pairs than unrelated twins may reflect a shared environmental exposure. Thus, differences of the inter-generation transmissibility at birth between the major kingdoms of microbes indicate that the foundation of these microbial communities are shaped by different rules. Video Abstract

Discipline in Sri Lanka, punish in Pakistan: neoliberalism, governance and housing compared

In discussions of urban infrastructure and land, neoliberalism is often presented as a hegemonic economic model with, seemingly, identical outcomes across a range of historical and political circumstances. For instance, in large cities of the Global South, a combination of speculative capitalism, and increased privatisation in the provision of public services, has been blamed for structural dispossession and the pushing out of working-class and vulnerable groups from urban centres. However, little has been said about how these processes interact with more contextual specificities—longer histories of state provision, existing inequalities, local political dynamics and legislative structures. Through comparative work on urban infrastructure projects in Lahore and Colombo, this article tells a story in which historical differences in state policy on housing and governance have impacted the ways in which dispossession is meted out, experienced and contested. Contributing to calls for studies of ‘actually existing neoliberalism’ (Wacquant 2012), we illustrate the importance of closely examining the relationship between neoliberal policies and dispossession on the ground through a historical perspective

Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is a respiratory condition causing accumulation of mucus in the airways, cough, and breathlessness; the disease is progressive and is the fourth most common cause of death worldwide. Current treatment strategies for COPD are multi-modal and aim to reduce morbidity and mortality and increase patients’ quality of life by slowing disease progression and preventing exacerbations. Fixed-dose combinations (FDCs) of a long-acting beta 2 -agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) delivered via a single inhaler are approved by regulatory authorities in the USA, Europe, and Japan for the treatment of COPD. Several LABA/LAMA FDCs are available and recent meta-analyses have clarified their utility versus their mono-components in COPD. Evaluation of the efficacy and safety of once-daily LABA/LAMA FDCs versus placebo will facilitate the comparison of different FDCs in future network meta-analyses. Objectives We assessed the evidence for once-daily LABA/LAMA combinations (delivered in a single inhaler) versus placebo on clinically meaningful outcomes in patients with stable COPD. Search methods We identified trials from Cochrane Airways’ Specialised Register (CASR) and also conducted a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch). We searched CASR and trial registries from their inception to 3 December 2018; we imposed no restriction on language of publication. Selection criteria We included parallel-group and cross-over randomised controlled trials (RCTs) comparing once-daily LABA/LAMA FDC versus placebo. We included studies reported as full-text, those published as abstract only, and unpublished data. We excluded very short-term trials with a duration of less than 3 weeks. We included adults (≥ 40 years old) with a diagnosis of stable COPD. We included studies that allowed participants to continue using their ICS during the trial as long as the ICS was not part of the randomised treatment. Data collection and analysis Two review authors independently screened the search results to determine included studies, extracted data on prespecified outcomes of interest, and assessed the risk of bias of included studies; we resolved disagreements by discussion with a third review author. Where possible, we used a random-effects model to meta-analyse extracted data. We rated all outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system and presented results in’Summary of findings’ tables. Main results We identified and included 22 RCTs randomly assigning 8641 people with COPD to either once-daily LABA/LAMA FDC (6252 participants) or placebo (3819 participants); nine studies had a cross-over design. Studies had a duration of between three and 52 weeks (median 12 weeks). The mean age of participants across the included studies ranged from 59 to 65 years and in 21 of 22 studies, participants had GOLD stage II or III COPD. Concomitant inhaled corticosteroid (ICS) use was permitted in all of the included studies (where stated); across the included studies, between 28% to 58% of participants were using ICS at baseline. Six studies evaluated the once-daily combination of IND/GLY (110/50 µg), seven studies evaluated TIO/OLO (2.5/5 or 5/5 µg), eight studies evaluated UMEC/VI (62.5/5, 125/25 or 500/25 µg) and one study evaluated ACD/FOR (200/6, 200/12 or 200/18 µg); all LABA/LAMA combinations were compared with placebo. The risk of bias was generally considered to be low or unknown (insufficient detail provided), with only one study per domain considered to have a high risk of bias except for the domain’other bias’ which was determined to be at high risk of bias in four studies (in three studies, disease severity was greater at baseline in participants receiving LABA/LAMA compared with participants receiving placebo, which would be expected to shift the treatment effect in favour of placebo). Compared to the placebo, the pooled results for the primary outcomes for the once-daily LABA/LAMA arm were as follows: all-cause mortality, OR 1.88 (95% CI 0.81 to 4.36, low-certainty evidence); all-cause serious adverse events (SAEs), OR 1.06 (95% CI 0.88 to 1.28, high-certainty evidence); acute exacerbations of COPD (AECOPD), OR 0.53 (95% CI 0.36 to 0.78, moderate-certainty evidence); adjusted St George’s Respiratory Questionnaire (SGRQ) score, MD -4.08 (95% CI -4.80 to -3.36, high-certainty evidence); proportion of SGRQ responders, OR 1.75 (95% CI 1.54 to 1.99). Compared with placebo, the pooled results for the secondary outcomes for the once-daily LABA/LAMA arm were as follows: adjusted trough forced expiratory volume in one second (FEV1), MD 0.20 L (95% CI 0.19 to 0.21, moderate-certainty evidence); adjusted peak FEV1, MD 0.31 L (95% CI 0.29 to 0.32, moderate-certainty evidence); and all-cause AEs, OR 0.95 (95% CI 0.86 to 1.04; high-certainty evidence). No studies reported data for the 6-minute walk test. The results were generally consistent across subgroups for different LABA/LAMA combinations and doses. Authors’ conclusions Compared with placebo, once-daily LABA/LAMA (either IND/GLY, UMEC/VI or TIO/OLO) via a combination inhaler is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild-to-moderate COPD; UMEC/VI appears to reduce the rate of exacerbations in this population. These conclusions are supported by moderate or high certainty evidence based on studies with an observation period of up to one year. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Guidelines for the empirical vulnerability assessment

These Guidelines provide state-of-the-art guidance on the construction of vulnerability relationships from post-earthquake survey data. The Guidelines build on and extend procedures for empirical fragility and vulnerability curve construction found in the literature, and present a flexible framework for the construction of these relationships that allows for a number of curve-fitting methods and ground motion intensity measure types (IMTs) to be adopted. The philosophy behind the design of the framework is that the characteristics of the data should determine the most appropriate statistical model and intensity measure type used to represent them. Hence, several combinations of these must be trialled in the determination of an optimum fragility or vulnerability curve, where the optimum curve is defined by the statistical model that provides the best fit to the data as determined by a number of goodness-of-fit tests. The Guidelines are essentially a roadmap for the process, providing recommendations and help in deciding which statistical model to attempt, and promote trialling of models and IMTs. The Guidelines are targeted at analysts with Master’s level training in a numerate subject that includes some level of statistics. The Authors recognise that the statistical analysis understanding of analysts varies. To accommodate for these differences, two levels of statistical approaches for constructing empirical fragility functions that include procedures of increasing complexity, are proposed. All stages of the fragility and vulnerability curve construction are reviewed and presented in the Guidelines with practical advice given for the preparation of empirical data for use in the construction of these curves, for the identification of sources of uncertainty in the data and in the chosen intensity measures, and where possible, for uncertainty quantification and modelling. To facilitate adoption of the Guidelines, the code and commands required for the implementation of the described statistical models are provided for the open source software R (2008). Appendices B to G also provide example applications of the guidelines, where each step of the guideline is illustrated for empirical datasets deriving from the 1980 Irpinia, Italy, earthquake, the 1978 Thessaloniki, Greece, Earthquake, the 1989 Newcastle and 2010 Kalgoorlie, Australia, earthquakes and for two earthquakes that affected the town of Christchurch New Zealand in 2010 and 2011. The fragility and vulnerability curves developed from these applications are all presented using a reporting template (presented in Appendix A) designed to facilitate the evaluation and inclusion of empirical fragility curves derived using these Guidelines into the Global Earthquake Model (GEM)

Autoantibodies against C1q as a diagnostic measure of lupus nephritis:systematic review and meta-analysis

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Objectives: To evaluate the diagnostic accuracy of C1q autoantibodies in identifying lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE). Data Sources and methods: Citation indexes were searched and 370 articles published from 1977 to 2013 were evaluated. The 31 selected studies included in the meta-analysis were cross-sectional in design. Among the 31 studies, 28 compared anti-C1q antibodies in 2769 SLE patients including those with (n = 1442) and without a history of LN (n = 1327). Nine studies examined anti-C1q in 517 SLE patients with active (n = 249) and inactive LN (n = 268). Hierarchical summary receiver operating characteristic (HSROC) random effects models were fitted to pool estimates of accuracy across the studies. Results: Anti-C1q antibodies discriminated between patients with and without a history of LN, with a median specificity of 73.5%. The HSROC model estimated the corresponding sensitivity to be 70.4%. A hypothetical patient with a 55% prior probability of having a history of LN as opposed to no history (the median prevalence across 28 eligible studies) would have a post-test probability of 76.4% following a positive test result (positive predictive value) or 33.0% following a negative test result (negative predictive value). For differentiating active from inactive LN the median specificity of anti-C1q antibodies was 80%, with a corresponding estimated sensitivity value 75.7% based on the HSROC model. A hypothetical patient with a 56% prior probability of active as opposed to inactive LN (the median prevalence across the 9 eligible studies) would have a post-test probability of 82.8% following a positive test result or 27.9% following a negative test result. Conclusions: Although C1q antibodies are associated with lupus nephritis the post-test probabilities are not sufficiently convincing to provide reasonable certainty of the presence or absence of history of disease/active disease.Arthritis Research UKPeninsula Collaboration for Leadership in Applied Health Research and Care (CLAHRC)National Health Service South West, funded by the National Institute for Health Research, U

Heavy Metal Levels in Vegetables and Soil Cultivated with Industrial Wastewater from Different Sites of Chunian and Jamber, District, Kasur

In human diet, vegetables play important role to maintain the physiological conditions. Due to anthropogenic activities and pollution, the food items become contaminated. The present study was performed to evaluate the level of heavy metals in the vegetables irrigated with wastewater across Chunian and Jamber, district, Kasur. Level of heavy metals from the study area like Zinc, Lead and chromium in the soil, water and vegetables was compared. The four sites of each city and 10 vegetables e.g. potato, radish, carrot, fenugreek, spinach, tomato, Onion, Turnip, Cauliflower, Pangalo were selected to conduct the experiment. The vegetables were irrigated with industrial wastewater and the concentration of heavy metals was measured by the atomic absorption spectrophotometer (AAS). We concluded that the level of heavy metals was beyond the FAO limits in irrigated water due to industrial waste. In Jamber and Chunian, the level of Zn and Pb was high and beyond the FAO safe limits in the all water sample, the level of Cr was much higher only in the water sample of one site from Jamber. The concentration of zinc was higher in soil samples as compared to lead and chromium. Zn and Pb in vegetables of study area were labeled as priority pollutants but this concentration was within the safe limits set by FAO. However, constant inspection of heavy metals is recommended to avoid accumulation in the food chain and thus avoid human health risks. Keywords: Atomic absorption spectrophotometer, Heavy metals, Industrial wastewater, Vegetables

Inotropic and chronotropic effects of methanol extract of Aquilaria agallocha on rabbit heart

Aquilaria agallocha Roxb. (Thymelaeceae) heartwood is used in cardiac failure; however, its cardiotonic properties are poorly understood at a pharmacological level. This study investigated methanol extract of A. agallochafor presence of glycosides and its effects on force of contraction, heart rate and coronary flow on rabbit isolated heart. Furthermore, contribution of β1-adrenoceptors and/or L-type Ca2+ channels in A. agallocha-induced cardiac effects was explored. A. agallocha extract, digoxin, verapamil and metoprolol were administered in a retrograde manner. Force of contraction and heart rate were recorded with a force transducer attached to the heart. Coronary flow was measured from collected effluent. The extract induced a significant increase in force of contraction (p<0.001), decrease in heart rate (p<0.05) and coronary flow (p<0.001). Metoprolol (p<0.01) and verapamil (p<0.01) significantly inhibited the plant extract-induced effects. Thus, A. agallocha exhibited cardiotonic effects, most likely via cardiac glycosides, involving ?1-adrenoceptors and L-type Ca2+ channels

Iono- and chronotropic effects of aqueous extract of berberis lycium royle root bark and berberine on in situ frog-heart preparation

Berberis lycium Royle is used in folk medicines for treating various ailments however it has not been investigated in cardiac problems at pharmacological level. Here, iono- and chronotropic effects of B. lycium root bark’s aqueous extract and berberine were studied on frog-heart. Present data showed that aqueous extracts of B. lycium and berberine exhibited dose-dependent negative chronotropic and ionotropic effects and at higher doses both caused a heart block. Berberine also displayed a positive ionotropic effect but at very low doses. Diltiazem did not antagonize positive ionotropic effect of berberine indicating that this activity is independent of L-type calcium channels, while propranolol antagonized the positive ionotropic effect, suggesting involvement of β1 - adrenoceptors. It is concluded that ionotropic and chronotropic effects exerted by aqueous extract of B. lycium may be due to berberine while its negative ionotropic actions and heart block may attribute to other active principle(s) present in the extract.Colegio de Farmacéuticos de la Provincia de Buenos Aire