Sensorimotor and Executive Functioning Differences between High-Functioning Individuals with Autism and Typically-Developing Individuals

Autism is a life-long neurodevelopment disorder affecting 1 in every 150 children in the United States. Along with the three major hallmarks of autism; impairments in social interaction, impairments in communication, and repetitive and restricted stereotypes of behavior, individuals with autism face a variety of impairments that affect their everyday functioning. These impairments include, but are not limited to, impairments in motor skills, impairments in sensory-perceptual skills, and impairments in executive functioning (EF) skills. This dissertation explored these aforementioned impairments in individuals with high-functioning autism (IHFA) in three studies. The first study explored simple and complex motor and simple and complex sensory-perceptual skills differences between IHFA and typically-developing individuals (TDI) for different age groups extending from childhood to early adulthood. The study found IHFA to be impaired compared to TDI on simple and complex motor skills across the continuum of age. However, for sensory-perceptual skills IHFA impairments were found only for complex sensory-perceptual skills for an older group of IHFA. The second study explored factors that were associated with good and poor complex fine-motor skills for IHFA and TDI. Two models were generated utilizing Exhaustive Chi-Square Automatic Interaction Detection (CHAID). In this study, we found different factors to be associated with complex fine-motor skills for IHFA versus TDI. The patterns of association for IHFA were also different from TDI. In the third study, we explored the factors that were associated with good and poor EF skills by generating two models, one for IHFA and one for TDI, utilizing Exhaustive CHAID. In this study, we found similar factors to be associated with EF skills for both IHFA and TDI, however, the factors held different levels of association with EF in each group. Findings from the first study suggest the importance of early assessment and continuous re-assessment of simple and complex motor skills and complex sensory-perceptual skills for IHFA. Findings from the second and third study offer models that have the potential to establish priorities for assessment and intervention for IHFA

An in vitro based investigation into the cytotoxic effects of D-amino acids

In the present study, cytotoxic effects of D-Ala, D-Pro and D-Lys are demonstrated. In an effort to study possible mechanisms of the observed cytotoxicity, catalase activity, H2O2 generation, and apoptotic activity were measured in HeLa and MCF-7 cell lines. Although D-Lys is a poor substrate for DAO and therefore low H2O2 has been detected, it was shown to provoke severe impairment of cellular integrity and survival. Interestingly, a very good substrate for DAO, such as D-Pro, did not substantially reduce cell viability. On the other hand, a moderate substrate for DAO, represented by D-Ala, was shown to moderately trigger toxicity in the tested cell lines. Although a correlation between the in vitro cytotoxicity of D-amino acids and the amount of H2O2 produced was absent, there was a good agreement between the ability of D-amino acids to trigger apoptosis and to provoke toxicity. Our results indicate that the toxicity of D-amino acids does not appear to be solely mediated by H2O2. Therefore, we hypothesize that other possible contributing apoptosis-mediated pathways might cause the observed toxicity

Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium

Purpose: To study the interaction between ciprofloxacin hydrochloride (Cipro) and diclofenac sodium (DS) in the presence and absence of metal ions.Methods: Complexes were prepared in the aqueous phase at different molar ratios (r) of Cipro:DS (ranged from 0.2 – 2.0). The complexes were characterized by Fourier transform-infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high pressure liquid chromatography (HPLC). Their properties, i.e., solubility, dissolution and partition coefficient (log P), were studied along with their permeability across Caco-2 cells. Furthermore, the antimicrobial activity of Cipro and its complexes was determined using standard broth dilution method and expressed as minimum inhibitory concentration (MIC).Results: Cipro formed an ion pair with DS. The product was confirmed to be a combination of the two drugs, DS and Cipro, but in a ratio that is dependent on the added amounts of each component (r = 1:1 or 1:2). The 1:1 product was more lipophilic than the individual components leading to a lower aqueous solubility and a higher octanol/water partition coefficient log P (6.7 vs. 0.77). The presence of DS within the dissolution medium appeared to modify the dissolution of Cipro depending on the concentration. Moreover, ternary complexes involving Cipro, DS and metal ions (iron and/or calcium) exhibited improved antimicrobial effect (MIC, 0.016 μg/ml compared to 0.258 μg/ml for Cipro). Caco-2 cell permeation data indicate that the presence of DS significantly improved the apparent permeability coefficient (Papp) of Cipro (20.6 × 10-6 cm/s) which was three times higher than that of free Cipro (p < 0.05). DS also appeared to counteract the well-known negative effect of metal ions on the bioavailability of Cipro.Conclusion: There is a clinically relevant interaction between DS and Cipro at the absorption level as a result of ion pair formation, which might even counteract the negative effect of metals on the absorption of Cipro. These findings should aid the design of new Cipro ion pairs that provide higher bioavailability than free Cipro.Keywords: Ciprofloxacin, Diclofenac, Interaction, Ion pair, Permeability coefficient, Bioavailability, Absorptio

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

Funder: Oxford Martin School, University of OxfordThe response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages

CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

Funder: Wellcome TrustIn response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially