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microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects. Resumo Os microRNAs (miRNAs) são reconhecidos como biomarcadores do diabetes mellitus tipo 2 (DM2), úteis para a compreensão do metabolismo da doença, e possuem grande potencial como alvos terapêuticos. O aumento da expressão de BDNF e IGF1 está altamente envolvido nos benefícios as vias de insulina e glicose, porém, são regulados negativamente em condições de resistência à insulina, enquanto seu aumento de expressão está correlacionado com a melhora do metabolismo da glicose e da insulina. Estudos sugerem a regulação desses genes por microRNA em vários contextos diferentes, proporcionando uma nova abordagem de investigação para compreender o metabolismo do DM2 e revelar potenciais alvos terapêuticos. No presente estudo, investigamos em diferentes modelos animais (humanos, ratos e camundongos) miRNAs que têm como alvo BDNF e IGF1 em tecido muscular esquelético com condições fisiológicas de DM2. As análises foram realizadas utilizando ferramentas de bioinformática e bancos de dados para predição de miRNA, homologia molecular, validação experimental de interações, expressão na condição fisiológica estudada e interação em rede. Os resultados mostraram três candidatos a miRNAs para IGF1 (miR-29a, miR-29b e miR-29c) e um para BDNF (miR-206). As avaliações experimentais e a busca pela expressão no músculo esquelético de indivíduos com DM2 confirmaram a interação prevista entre miRNA-mRNA para miR-29b e miR-206 através de modelos humanos, ratos e camundongos. Essa interação foi reafirmada em múltiplas análises de rede. Em conclusão, nossos resultados mostram a relação de regulação entre miR-29b e miR-206 com os genes investigados, em diversos tecidos, sugerindo um padrão de inibição. Contudo, esses dados mostram um grande número de possíveis processos fisiológicos de interação para perspectivas biotecnológicas.

The Hamilton Anxiety Inventory (HAM-A) is one of the oldest and most commonly used anxiety rating scales in clinical research. Despite its ubiquity, no studies have examined the scale's underlying factor structure and criterion validity among Black and African American adults with psychopathology (Mage = 42.25, SD = 11.44). Therefore, we estimated a confirmatory factor analysis of the commercially available Structured Interview Guide for the Hamilton Anxiety scale (SIGH-A; Williams, 1996) among African American adults (n = 88; 43% female) with co-occurring heavy alcohol use and trauma-related symptoms. Next, we examined the criterion validity of its Psychic and Somatic factors and overall anxiety severity score from participants who completed a single screening session (i.e., cross-sectional analysis) for a larger study. Results indicated that a two-factor solution provided an adequate fit to the data. Regression analyses indicated that the total SIGH-A score, but not its subscales, significantly predicted posttraumatic stress disorder (PTSD) severity. Neither the SIGH-A subscales nor total scores were significant predictors of alcohol consumption. The current findings suggest that the SIGH-A factor structure among African American adults with alcohol and trauma-related conditions is similar to previous reports that have tested largely White samples but highlight potential shortcomings when its subscales are used independently. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Disease can be spread through contact with contaminated surfaces (fomites). For example, fomites have been implicated in the spread of meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Antimicrobial surface treatments are a potential method of reducing disease transmission from fomites, and broad-spectrum activity is desirable.To test cuprous oxide (CuWe fabricated two surface coatings. The CuThe coatings rapidly killed nine different micro-organisms, including Gram-negative and Gram-positive bacteria, mycobacteria and fungi. For example, the CuThe combination of broad-spectrum antimicrobial activity, abrasion resistance, and low toxicity of the Cu

VK is funded by an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the UK Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). MB-N and VdAO are funded by the Fazer o Bem Faz Bem programme from JBS SA. MB-N is also funded by CNPQ and FAPESB (PNX0008/2014). EPS is funded by the Wellcome Trust (213589/Z/18/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. Background Little is known about vaccine effectiveness over time among adolescents, especially against the SARS-CoV-2 omicron (B.1.1.529) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. Methods We did test-negative, case-control studies in adolescents aged 12–17 years with COVID-19-related symptoms in Brazil and Scotland. We linked records of SARS-CoV-2 RT-PCR and antigen tests to national vaccination and clinical records. We excluded tests from individuals who did not have symptoms, were vaccinated before the start of the national vaccination programme, received vaccines other than BNT162b2 or a SARS-CoV-2 booster dose of any kind, or had an interval between their first and second dose of fewer than 21 days. Additionally, we excluded negative SARS-CoV-2 tests recorded within 14 days of a previous negative test, negative tests recorded within 7 days after a positive test, any test done within 90 days after a positive test, and tests with missing sex and location information. Cases (SARS-CoV-2 test-positive adolescents) and controls (test-negative adolescents) were drawn from a sample of individuals in whom tests were collected within 10 days of symptom onset. We estimated the adjusted odds ratio and vaccine effectiveness against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil across fortnightly periods. Findings We analysed 503 776 tests from 2 948 538 adolescents in Brazil between Sept 2, 2021, and April 19, 2022, and 127 168 tests from 404 673 adolescents in Scotland between Aug 6, 2021, and April 19, 2022. Vaccine effectiveness peaked at 14–27 days after the second dose in both countries during both waves, and was significantly lower against symptomatic infection during the omicron-dominant period in Brazil (64·7% [95% CI 63·0–66·3]) and in Scotland (82·6% [80·6–84·5]), than it was in the delta-dominant period (80·7% [95% CI 77·8–83·3] in Brazil and 92·8% [85·7–96·4] in Scotland). Vaccine efficacy started to decline from 27 days after the second dose for both countries, reducing to 5·9% (95% CI 2·2–9·4) in Brazil and 50·6% (42·7–57·4) in Scotland at 98 days or more during the omicron-dominant period. In Brazil, protection against severe disease remained above 80% from 28 days after the second dose and was 82·7% (95% CI 68·8–90·4) at 98 days or more after receiving the second dose. Interpretation We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in Brazil and Scotland from 27 days after the second dose. However, protection against severe COVID-19 outcomes remained high at 98 days or more after the second dose in the omicron-dominant period. Booster doses for adolescents need to be considered. Publisher PDF

The objective of this study is to assess the determinants of willingness to pay to enhance pandemic preparedness in Mauritius.A contingent valuation method is used to estimate willingness to pay to pay for enhancing pandemic preparedness using a sample of working people in Mauritius.A two-phase decision process analysis is carried out to model the willingness to pay to enhance pandemic preparedness. The first phase is to analyse the respondents' decision of whether or not to pay for enhancing pandemic preparedness using a Probit model. The second phase is to estimate the determinants of the amount of money respondents are willing to pay using a Tobit model.Income earners are willing to pay an average of Rs. 1,900 (approximately USD 50) per annum to enhance pandemic preparedness. 'Perceived Response Efficacy', 'Awareness of the Need and Responsibility for Paying', 'Subjective Obligation to Pay' and the 'Theory of Planned Behaviour' are found to affect both stages of of the decision-making process. Knowledge on COVID-19 is found to have a positive impact on the decision to pay and health responsibility attitude is found to have a negative impact on the amount people are willing to pay.On average, the government can potentially expect to mobilise an additional Rs. 1,047,470,000 (USD 27,565,000) from taxpayers to spend on enhancing pandemic preparedness in Mauritius. To increase willingness to pay for enhanced pandemic preparedness, the government can focus on improving knowledge on a pandemic, perceived response efficacy and awareness on need and responsibility of paying.

ObjectivesTo disseminate and assess the level of acceptability and applicability of the European Alliance of Associations for Rheumatology (EULAR) recommendations for patient education among professionals in rheumatology across Europe and three Asian countries and identify potential barriers and facilitators to their application.MethodsA parallel convergent mixed-methods design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0–10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes.ResultsA total of 1159 completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment and inviting patients to provide feedback on patient education delivery.ConclusionsThis project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools.

Scarring is a major clinical issue that affects a considerable number of patients. The associated problems go beyond the loss of skin functionality, as scars bring aesthetic, psychological, and social difficulties. Therefore, new strategies are required to improve the process of healing and minimize scar formation. Research has highlighted the important role of mechanical forces in the process of skin tissue repair and scar formation, in addition to the chemical signalling. A more complete understanding of how engineered biomaterials can modulate these mechanical stimuli and modify the mechanotransduction signals in the wound microenvironment is expected to enable scar tissue reduction. The present review aims to provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment. Furthermore, a broad overview of current challenges and future perspectives of promising mechanomodulatory biomaterials for this application are provided. STATEMENT OF SIGNIFICANCE: Scarring still is one of the biggest challenges in cutaneous wound healing. Beyond the loss of skin functionality, pathological scars, like keloids and hypertrophic, are associated to aesthetic, psychological, and social distress. Nonetheless, the understanding of the pathophysiology behind the formation of those scars remains elusive, which has in fact hindered the development of effective therapeutics. Therefore, in this review we provide an overview of our current understanding of skin biomechanics and mechanobiology underlying wound healing and scar formation, with an emphasis on the development of novel mechanomodulatory wound dressings with the capacity to offload mechanical tension in the wound environment.

The coronavirus, COVID-19 pandemic spread across the globe in 2020, with an initial high case mortality in those requiring intensive care treatment due to serious complication. A vaccine programme was quickly developed and currently the UK is one of highest double vaccinated and boosted countries in the world. Despite tremendous efforts by the UK, new cases of COVID-19 are still occurring, due to viral mutation. A major problem associated with COVID-19 is the large a-symptomatic spread within the population. Little investigation into the a-symptomatic population has been carried out and therefore we pose that the residual effects of a-symptomatic infection is still largely unknown. Prior to mass vaccination, a multi-phased single cohort study of IgM and IgG COVID-19 antibody prevalence and the associated haemostatic changes were assessed in a Welsh cohort of 739 participants, at three time points. Positive antibody participants with age and gender matched negative antibody controls were assessed at 0, 3 and 6 months. Antibody positive females appeared to have lower antibody responses in comparison to their a-symptomatic male counterparts. Despite this initial testing showed a unique significant increase in TRAP-6-induced platelet aggregation, prothrombin time (PT) and clot initiation time. Despite coagulation parameters beginning to return to normal at 3 months, significant decreases are observed in both haemoglobin and haematocrit levels. The production of extracellular vesicles (EV) was also determined in this study. Although the overall number of EV does not change throughout the study, at the initial 0 months' time point a significant increase in the percentage of circulating pro-coagulant platelet derived EV is seen, which does not appear to be related to the extent of platelet activation in the subject. We conclude that early, but reversible changes in haemostatic pathways within the a-symptomatic, female, antibody positive COVID-19 individuals are present. These changes may be key in identifying a period of pro-coagulative risk for a-symptomatic female patients.

BackgroundOver the last decades, a decrease in short-term mortality in cancer patients admitted to the ICU has been described in literature. However, it is unclear whether this decrease also results in a decrease in long-term mortality. Therefore, we examined the 1-year mortality of cancer patients (either haematological or solid) with an unplanned ICU admission.Methods and dataAll adult patients registered in the National Intensive Care Evaluation registry with an unplanned ICU admission in the Netherlands between 2008 and 2017 were included. The primary outcome was 1-year mortality, analysed with a mixed-effects cox-proportional hazard regression. We examined the trend in mortality rates over the inclusion period. Furthermore, we compared the 1-year mortality of cancer patients to that of patients without cancer. ResultsWe included 470,305 patients: 10,401 with haematological cancer, 35,920 with solid tumours, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% (pConclusionThe 1-year mortality in cancer patients with an unplanned ICU admission (either haematological or solid) was significantly higher than that of patients without cancer. A visual inspection showed a slight decrease in 1-year mortality in haematological patients, while the 1-year mortality in patients with a solid tumour varied per year. After hospital discharge, a considerable part of the patients with a malignancy died within 1 year. Physicians should discuss the long-term prognosis after an ICU admission with patients and relatives in order to manage treatments and expectations. Future research should focus on identifying cancer patients who will benefit from an ICU admission.

BACKGROUND: We conducted a feasibility and acceptability study of video-observed therapy (VOT) among patients with multidrug-resistant TB (MDR-TB) and other types of drug-resistant TB (DR-TB) in the Philippines.METHODS: Patients aged ≥13 years were approached to use VOT. A smartphone with VOT mobile application to video-record medication intake was provided. Healthcare workers (HCWs) monitored adherence by watching videos via a web-based dashboard. Good adherence was defined as intake of >90% of expected doses. Feasibility and acceptability were assessed using a semi-structured questionnaire on a Likert scale.RESULTS: Of 308 patients, 110 (36%) patients chose VOT; 67 completed treatment using VOT and 43 stopped VOT prior to treatment outcome; 74/110 (67%) had good adherence. The treatment success rate was 88% and the loss to follow-up rate was 8.1%. Among HCWs, 90% (9/10) had a positive perception of VOT. All HCWs agreed that VOT data accurately reflect medication intake of the patients; 88/89 (99%) mentioned benefits of VOT, notably convenience, sense of comfort, privacy and security.CONCLUSIONS: VOT is feasible and acceptable for both patients and HCWs. This study could provide guidance to the country programme to launch VOT for treatment of patients with MDR-TB and other DR-TB.

Individuals with chronic hypoparathyroidism may experience suboptimal medical care with high frequency of unplanned hospitalisation and iatrogenic harm. In 2015 the European Society for Endocrinology published consensus guidelines on the management of chronic hypoparathyroidism. We set out to audit compliance with these guidelines.Using these recommendations as audit standards we worked with the Society for Endocrinology and Parathyroid UK to conduct a national audit of management of chronic hypoparathyroidism in the United Kingdom. Endocrine leads in 117 endocrine departments were invited to participate in the survey by completing a data collection tool on up to 5 sequential cases of chronic hypoparathyroidism seen in their outpatient clinics in the preceding 12 months. Data were collected on 4 treatment standards and 9 monitoring standards. Data on hospitalisations and Quality of Life monitoring were also collected.Responses were received from 22 departments giving a response rate of 19%, concerning 80 individual cases. The mean age of subjects was 48.4 years. The main findings were that the commonest cause of hypoparathyroidism was post surgical (66.3%). Treatments taken by the group included activated vitamin D analogues (96.3%), oral calcium salts (66.3%), vitamin D supplements (17.5%), thiazide diuretics (5%) and rhPTHsub1-34/sub(1.3%). Compliance with the audit standards varied between 98.8% and 60% for the treatment standards and between 91.3% and 20% for the monitoring standards. Some of the areas of weakness revealed include low rates of 24 h urinary calcium excretion monitoring, serum magnesium monitoring and low rates of renal imaging where indicated. In addition and importantly, 16.3% of subjects had experienced at least one hospital admission in the preceding 12 months.We conclude that further improvements in the UK national standard of management of chronic hypoparathyroidism should be made and that this will benefit both quality of life, morbidity and potentially mortality in this group of patients.

Alzheimer’s disease (AD) is the most common cause of dementia that affects one patient every seven seconds, with over 35 million people currently affected worldwide. The aim of the study was to investigate the modulation of memory and neurochemical responses by resveratrol and environmental enrichment (EE) in aluminium chloride (AlCl3) model of Alzheimer’s disease in mice. Male mice used for the study were divided into nine groups, of seven animals each. Group I (negative control): 0.2 ml normal saline/kg, Group II: 0.2 ml CMC/kg. Group III: resveratrol (200 mg/kg/), Group IV: CMC and kept in EE, Group V: AlCl3 at dose of 50 mg/kg, Group VI: resveratrol at dose of 200 mg/kg and kept in EE, Group VII: AlCl3 (50 mg/kg) + resveratrol (200 mg/kg), Group VIII: AlCl3 (50 mg/kg) and kept in EE, Group IX: AlCl3 (50 mg/kg) + resveratrol (200 mg/kg) and kept in enriched environment. All treatments were oral and lasted for 8 weeks. Assessments of memory was carried out before treatment, and at weeks 4 and 8, after the first treatment. The mice were sacrificed and hippocampal samples collected for neurochemical analysis. The findings of the study suggest that AlCl3 induced contextual fear memory deficit over time (p < 0.05), which was improved by resveratrol. Both Aβ and Nrf2 significantly (p < 0.05) increased in AlCl3 + EE + resveratrol group. In conclusion, Individual treatment with either resveratrol or EE improved memory over the combined treatment in AlCl3 model of AD by decreasing Aβ protein concentration.

Sensory modulation symptoms form a diagnostic criterion for autism spectrum disorder and are associated with significant daily functional limitations. Utilizing caregiver report on Short Sensory Profile-2 (SSP-2) for 919 autistic children (3-14.11 years), we examined the expression of sensory modulation symptoms by age and sex and investigated the existence of specific sensory modulation subtypes. Sensory modulation symptoms appeared to peak in frequency during middle childhood, particularly in sensory sensitivity and avoidance. Symptoms associated with sensory hypo-reactivity and seeking tended not differ between age cohorts. Males and females demonstrated similar overall sensory modulation profiles, however, females showed elevated symptoms relating to sensory sensitivity. Model-based cluster analysis revealed five interpretable sensory modulation subtypes which related to symptom severity (low, mid-range, high). Subtypes demonstrating mid-range symptom severity differed in focus on sensory hyper-reactivity or seeking symptoms. The findings of this study report for the first time that age-related differences in sensory modulation symptoms may be associated with sensory hyper-reactivity only. The subtyping results also suggest that sensory modulation symptom severity is a reliable means of classifying variance within autistic children, however, consideration of differences in the behavioral strategies employed by individuals to manage sensory modulation symptoms may inform tailored supportive strategies. LAY SUMMARY: We studied sensory symptoms such as over-responding, under-responding and sensation seeking behaviors in 919 autistic children and adolescents. We found that 6-12-year-olds and females displayed the most sensory over-responding symptoms. Autistic children could be grouped into mild, moderate, and severe levels of sensory symptoms, however, children differed in the type of strategies used to cope with their sensory symptoms meaning that they may require different intervention approaches.

BACKGROUND: Several studies have investigated the distribution of hip-knee-ankle (HKA) angle in healthy populations; however, few have evaluated this metric in patients undergoing total knee arthroplasty (TKA). The purpose of this study was to compare HKA angle distribution in early and advanced knee osteoarthritis (OA) patients. METHODS: Full limb radiographs were used to measure HKA angle for 983 subjects from the Osteoarthritis Initiative (OAI) cohort and 4901 pre-TKA patients from an institutional cohort. Measurements were made using a previously-validated deep learning algorithm. Linear regression models were used to determine the association of HKA alignment angle with patient characteristics. RESULTS: The mean± standard deviation HKA angle was −1.3° ± 3.2° in the OAI cohort and −4.1° ± 6.1° in the pre-TKA cohort. In the OAI cohort, normal alignment (64%) was the most common knee alignment followed by varus (29%), and valgus (7%). In pre-TKA patients, the most common alignment was varus (62%), followed by normal (27%) and valgus (11%). In pre-TKA patients, mean HKA angle in primary knee OA, post-traumatic knee OA and rheumatoid arthritis patients were −4.3° ± 6.1°, −3.2° ± 6.4° and −2.9° ± 6.1°, respectively. HKA angle was strongly associated (p

Intensive care medicine 47(10), 1115-1129 (2021). doi:10.1007/s00134-021-06484-1, Published by Springer, Berlin

Background Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. Objectives This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. Methods A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. Results Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. Conclusions Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.

Background: Down syndrome (DS) is associated with elevated rates of autism spectrum disorder (ASD) and autism symptomatology. To better characterise heterogeneity in ASD symptomatology in DS, profiles of caregiver-reported ASD symptoms were modelled for children and adolescents with DS. Methods: Participants (n = 125) were recruited through several multi-site research studies on cognition and language in DS. Using the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), two latent profile analyses (LPA) were performed, one on the broad composite scores of social communication and interaction and restricted interests and repetitive behaviour, and a second on the four social dimensions of social communication, social motivation, social awareness, and social cognition. Results: A three-profile model was the best fit for both analyses, with each analysis yielding a low ASD symptom profile, an elevated or mixed ASD symptom profile and a high ASD symptom profile. Associations were observed between profile probability scores and IQ, the number of co-occurring biomedical conditions reported, sex, and SRS-2 form. Conclusions: Characterising heterogeneity in ASD symptom profiles can inform more personalised supports in this population, and implications for potential therapeutic approaches for individuals with DS are discussed.

Statement of problem The acrylic resin used in dental prostheses, which is subject to changes in its properties caused by hygiene chemicals, brushing, and colored beverages, can benefit from mechanical polishing methods. However, studies evaluating whether such procedures can be performed continuously without damaging the prosthetic materials are lacking. Purpose The purpose of this in vitro study was to evaluate the effect of a continuous mechanical polishing protocol on the color stainability, surface roughness, microhardness, and mass of a denture base acrylic resin. Material and methods The polishing protocol was tested in specimens submitted to one of the following conditions: immersion in coffee (CF) (n=20); toothbrushing (Br, 35 600 cycles in a brushing simulation machine) (n=20); and immersion in 1% sodium hypochlorite (HYP) (n=20). For each condition, half of the specimens were polished (aluminum oxide paste and felt wheel attached to an electric motor, 3000 rpm) at simulated biweekly intervals. Two groups (n=10) of specimens were immersed in distilled water and used as the control for the immersion groups. Thus, the present study consisted of a total of 8 groups (n=80). Before and after simulated periods of 12 and 24 months, surface roughness was evaluated by using a contact profilometer; a spectrophotometer was used to calculate color changes (ΔE00); and a Knoop microdurometer and a precision balance were used to assess microhardness and mass changes. Data were compared by using 2-way mixed ANOVA. The Tukey HSD and Student t tests were used for post hoc analysis (α=.05). Results The polishing influenced surface roughness (Br, CF, HYP: P 1.30) for the Br group, exceeding the clinical acceptability threshold for the CF group (ΔE00= 2.51). Polishing reduced ΔE00 in these groups, making values similar to those found in the groups immersed in distilled water. The color in the HYP group was not influenced by polishing. Conclusions In general, the tested polishing protocol reduced the deleterious effects of brushing and contact with 1% sodium hypochlorite and coffee, reducing surface roughness and color change without affecting microhardness and mass in any clinically relevant way.

Background Corona virus disease 2019 (COVID-19) is a multi-systemic illness that can present with cardiac complications. This report describes the preliminary findings of cardiac manifestations seen in patients managed in three centres in Lagos, Nigeria. Methods Ten patients, part of an ongoing study of patients admitted in three centres in Lagos, Nigeria, with COVID-19 diagnosed with reverse transcriptase polymerase chain reaction (RT-PCR) or serology were retrospectively studied for cardiac manifestations. Results The mean (SD) age was 52.5 ± 18.79 years (with a minimum of 17 years and maximum of 79 years). Six patients were female and four were male. Hypertension was seen in 70%, diabetes in 50% and obesity in 60% of patients. All had elevated inflammatory markers. Only four patients had bilateral pneumonia. The rest had only cardiac manifestations. Six patients presented with de novo heart failure and one had decompensated heart failure. A set of three patients had individually fulminant myocarditis, probable pulmonary embolism and stress cardiomyopathy, respectively. Conclusions This study shows that co-morbidities are common in patients with COVID-19 and cardiac complications. The array of cardiac complications is large, with the commonest being heart failure.

Despite their high prevalence and clinical importance in autism, unusual and restricted interests remain under-researched and poorly understood. This study aimed to characterize the frequency and type of interests in autism by coding caregivers’ open-ended responses in a sample of 237 autistic children and adolescents ( Mage = 8.27 years, SDage = 4.07; range: 2.08–18.25 years). It further aimed to explore the effects of age, sex, cognitive functioning and social and communication deficits on the number and type of interests. We found that 75% of autistic youth had at least one interest and that 50% of those children showed two or more different interests. The most frequent interests were sensory-based (43%), with a majority of these interests relating to the visual modality. Interest within vehicles/transportation, fictional characters, television/digital versatile disk/movies, computers, and video games, constructive, mechanical objects, animals and plants, and attachment to specific objects were also prevalent. Logistic regression showed that being male, having a co-occurring intellectual disability and having more severe social and communication impairments were associated with a higher probability of having one or more restricted interests. Sex was significantly associated with the type (χ2 = 37.52, Phi = 0.37, p = 0.021) of restricted interests, with females showing a significantly higher percentage of creative interests and males significantly higher percentage of interest in characters, vehicles/transportation, computers/video games, mechanical objects and constructive interests. Theoretical and measurement implications are discussed. Lay abstract Despite being highly prevalent among people with autism, restricted and unusual interests remain under-researched and poorly understood. This article confirms that restricted interests are very frequent and varied among children and adolescents with autism. It also further extends current knowledge in this area by characterizing the relationship between the presence, number, and type of restricted interests with chronological age, sex, cognitive functioning, and social and communication symptoms.

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2−/− hiPSCs but not from isogenic TSC2+/− or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2−/− renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo., The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test new therapies in vivo. Here the authors present a tissue bioengineering strategy for the study of a rare kidney tumor called angiomyolipoma, in vitro and in vivo, using patient-derived hiPSCs.

SUMMARY Objective To compare the ability of two calcium-releasing restorative materials to inhibit root dentin demineralization in an artificial caries model. Methods and Materials Preparations were made at the cementum–enamel junction of extracted human molars (40, n=10/material) and restored with two calcium-releasing materials (Experimental composite, Pulpdent Corporation and Cention N, Ivoclar Vivadent), a resin composite (Filtek Supreme Ultra, 3M Oral Care), and a resin-modified glass ionomer (RMGI) (Fuji II LC, GC). All materials (other than the RMGI) were used with an adhesive (Scotchbond Universal Adhesive, 3M Oral Care) in the self-etch mode, which was light cured for 10 seconds. All restorative materials were light cured in 2-mm increments for 20 seconds and then finished with a polishing disc. Teeth were incubated (37°C) for 24 hours in water. An acid-resistant varnish was painted onto the teeth around the restoration, leaving a 2-mm border of uncovered tooth. A demineralization solution composed of 0.1 M lactic acid, 3 mM Ca3(PO4)2, 0.1% thymol, and NaOH (to adjust pH=4.5), and a remineralization solution composed of 1.5 mM Ca, 0.9 mM P, and 20 mM Tris(hydroxymethyl)–aminomethane (pH=7.0) were prepared. Specimens were placed in the demineralization solution for 4 hours, followed by the remineralization solution for 20 hours and cycled daily for 30 days. The specimens were embedded, sectioned into 100-μm sections, and the interface between the restorative material and root dentin was viewed with polarized light microscopy. A line was drawn parallel with the zone of demineralization for each tooth. The area of “inhibition” (defined as the area external to the line) or “wall lesion” (defined as the area internal to the line) was measured with image evaluation software. Areas of inhibition were measured as positive values, and areas of wall lesions were measured as negative areas. Results A one-way analysis of variance (ANOVA) found significant differences between materials for “inhibition/wall lesion” areas in root dentin (p Cention N (2768±1576) and experimental composite (1484±1585) > Filtek Supreme Ultra (−1119±1029). Conclusion The experimental composite and Cention N materials (used with an adhesive) showed net areas of inhibition greater than a reference resin composite, albeit at a lower level than a reference RMGI material (used with no adhesive).

Colletotrichum is one of the most economically important fungal genera, which affects a wide range of hosts, specifically tropical and subtropical crops. Thus far, there have been several records of mycovirus infection in Colletotrichum spp., primarily by viruses of the Partitiviridae family. There have also been records of infections by mycoviruses of the Chrysoviridae family. Mycoviruses are (+)ssRNA and dsRNA genome viruses, which may or may not be enveloped. To date, no mycovirus with a DNA genome has been isolated from Colletotrichum spp. Typically, mycoviruses cause latent infections, although hypo- and hypervirulence have also been reported in Colletotrichum spp. In addition to its effects on pathogenic behavior, mycovirus infection can lead to important physiological changes, such as altered morphological characteristics, reduced vegetative growth, and suppressed conidia production. Therefore, research on mycoviruses infecting phytopathogenic fungi can help develop alternative methods to chemical control, which can cause irreversible damage to humans and the environment. From an agricultural perspective, mycoviruses can contribute to sustainable agriculture as biological control agents via changes in fungal physiology, ultimately resulting in the total loss of or reduction in the virulence of these pathogens.

Dental care has been the most commonly reported unmet service need among individuals with special health care needs.To assess the oral health status and treatment needs of individuals with special health care needs in a selected special education centre in South South Nigeria.A cross sectional, descriptive study conducted among students of Special Education Centre in Calabar. Sociodemographic data was collected while oral health conditions and treatment needs of the participants were assessed through oral examination. Data entry and analysis was by IBM SPSS version 21 and statistical significance was set at p0.05.Eighty-one participants were recruited for this study. More than half of the participants were males (56.8%) and had hearing impairments alone (56%). The most common oral condition was dental caries (40.7%) with a mean DMFT/dmft of 0.4 (±1.0). Majority of the participants had fair oral hygiene and the mean OHIS was 2.4(±1.3). Male participants and participants within the 21-30 years age group had poorer oral hygiene than their female counterparts and other age groups respectively. The preventive and restorative treatment needs were 56% and 18.5% respectively.Dental caries was the most prevalent oral health condition among this population with high unmet preventive and restorative treatment needs.Les soins dentaires sont le besoin de service non satisfait le plus souvent signalé chez les personnes ayant des besoins spéciaux en matière de santé.Évaluer l’état de santé bucco-dentaire et les besoins de traitement des personnes ayant des besoins spéciaux en matière de soins de santé dans un centre d’éducation spéciale sélectionné dans le sud du Nigeria.Étude descriptive transversale menée auprès des étudiants du centre d’éducation spéciale de Calabar. Des données sociodémographiques ont été recueillies tandis que les conditions de santé bucco-dentaire et les besoins de traitement des participants ont été évalués par un examen bucco-dentaire. La saisie et l’analyse des données ont été effectuées par IBM SPSS version 21 et la signification statistique a été fixée à p0,05.Quatre-vingt-un participants ont été recrutés pour cette étude. Plus de la moitié des participants étaient des hommes (56,8%) et présentaient uniquement des déficiences auditives (56%). L’affection buccale la plus fréquente était la carie dentaire (40,7 %), avec un indice CAOD/CAOD moyen de 0,4 (+1,0). La majorité des participants avaient une hygiène bucco-dentaire correcte et l’OHIS moyen était de 2,4 (+1,3). Les hommes et les participants de la tranche d’âge 21–30 ans avaient une hygiène bucco-dentaire moins bonne que leurs homologues féminins et les autres tranches d’âge respectivement. Les besoins en traitements préventifs et restaurateurs étaient respectivement de 56% et 18,5%.Les caries dentaires étaient le problème de santé bucco-dentaire le plus répandu dans cette population, avec des besoins élevés en traitements préventifs et restaurateurs non satisfaits.Santé bucco-dentaire, caries dentaires, hygiène buccodentaire, éducation spéciale, besoins en soins spéciaux.

The exponential rise in the prevalence of Type 2 Diabetes (T2DM) necessitates the introduction of strategies for early diagnosis to reduce the burden of the disease. This study assessed the prevalence of prediabetes and also determined the 10-year risk of developing T2DM in Southern Nigerian rural communities by adopting the validated Finnish Diabetes Risk Score (FINDRISC) tool.273 participants from 3 Southern rural communities aged 18 years and older were recruited in this cross-sectional study. Data in the FINDRISC stratification tool and Random Blood Glucose (RBG) variables were obtained for the participants. IBM SPSS version 21 was used to analyze the data with a level of significance put at p0.05.The participants' mean age was 54.20±16.61 years. The prevalence of prediabetes among the study participants based on RBG was 4.8% (3.8% of males and 6.6% of females, respectively). Most of the study participants (41%) had a low risk of developing T2DM which meant that 1 in 100 participants would become diabetic in a 10-year period, based on the FINDRISC scale. Amongst the male participants, the Total Diabetes Risk Score (TDRS) showed significant positive correlation with the RBG (r=0.315, p=0.001); similarly, a weak positive correlation between TDRS and RBG was noted among female participants.The propensity of developing T2DM in 10 years was indisputably low amongst rural dwellers in the Southern Nigerian rural communities studied. Further studies to compare the risk of developing T2DM between rural and urban communities would be required.L’augmentation exponentielle de la prévalence du diabète de type 2 (DT2) nécessite l’introduction de stratégies de diagnostic précoce pour réduire le fardeau de la maladie. Cette étude évalue la prévalence du prédiabète et détermine également le risque sur 10 ans de développer un DT2 dans les communautés rurales du sud du Nigeria en adoptant l’outil validé FINDRISC (Finnish Diabetes Risk Score).273 participants de 3 communautés rurales du sud du pays âgés de 18 ans et plus ont été recrutés dans cette étude transversale. Les données de l’outil de stratification FINDRISC et les variables de la glycémie aléatoire (RBG) ont été obtenues pour les participants. IBM SPSS version 21 a été utilisé pour analyser les données avec un niveau de signification mis à p0,05.L’âge moyen des participants était de 54,20±16,61 ans. La prévalence du prédiabète parmi les participants à l’étude, basée sur le RBG, était de 4,8% (3,8% des hommes et 6,6% des femmes respectivement). La plupart des participants à l’étude (41%) présentaient un faible risque de développer un DT2, ce qui signifie que 1 participant sur 100 deviendrait diabétique sur une période de 10 ans, selon l’échelle FINDRISC. Chez les hommes, le score total de risque de diabète (TDRS) a montré une corrélation positive significative avec le RBG (r=0,315, p=0,001) ; de même, une faible corrélation positive entre le TDRS et le RBG a été notée chez les femmes.La propension à développer un DT2 en 10 ans est indiscutablement faible chez les habitants des communautés rurales du sud du Nigeria étudiées. D’autres études visant à comparer le risque de développer un DT2 entre les communautés rurales et urbaines seraient nécessaires.FINDRISC, Nigeria, TDRS, Diabète de type 2, Prédiabète, Habitants ruraux.

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27–41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%–ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.

Some studies have been conducted worldwide on the preparedness of dentists and even dental students for infection prevention and control with regard to the ongoing COVID-19 pandemic but very few studies have been done among other Oral Health Care Workers (OHCWs). The purpose of this study was to assess the knowledge and practices of dental health care workers in Nigeria on infection prevention and control with regards to COVID-19.This was a descriptive study on the knowledge and practices regarding infection control protocols and procedures with regard to the COVID-19 pandemic among dental personnel in Nigeria. A validated self-administered questionnaire was utilised for data collection. Bivariate analysis was done with a Chi-squared test to determine the association between the participants age, gender, profession and place of practice with knowledge and practices regarding COVID 19 infection. Statistical significance in associations was inferred at P-value0.05.The majority of the OHCWs (77.4%) had good knowledge about infection prevention and control, and regulations regarding COVID-19, but most of them (58.5%) displayed poor practices with regard to infection prevention and control regulations related to COVID-19. Male respondents (68.8%), those aged between 55-64 (83.3%) years and Dental therapists (71.4%) had a higher proportion of those with good practices with the male gender and profession (Dental Therapist) being significantly associated with good practices. (P0.05).Our study identified a high rate of knowledge but low compliance with infection prevention and control guidelines regarding COVID-19. Better compliance with recommended infection control and waste management practices for all OHCWs and continuing education programs promoting infection control awareness are vital to improving the practices of these OHCWs.

Funding: Office of Naval Research - N000142012697, N000142112096; Strategic Environmental Research and Development Program - RC20-1097, RC20-7188, RC21-3091. Assessing cumulative effects of human activities on ecosystems is required by many jurisdictions, but current science cannot meet regulatory demands. Regulations define them as effect(s) of one human action combined with other actions. Here we argue for an approach that evaluates the cumulative risk of multiple stressors for protected wildlife populations within their ecosystems. Monitoring effects of each stressor is necessary but not sufficient to estimate how multiple stressors interact to affect wildlife populations. Examining the mechanistic pathways, from cellular to ecological, by which stressors affect individuals can help prioritize stressors and interpret how they interact. Our approach uses health indicators to accumulate the effects of stressors on individuals and to estimate changes in vital rates, driving population status. We advocate using methods well-established in human health and integrating them into ecosystem-based management to protect the health of commercially and culturally important wildlife populations and to protect against risk of extinction for threatened species. Our approach will improve abilities to conserve and manage ecosystems but will also demand significant increases in research and monitoring effort. We advocate for increased investment proportional to the economic scale of human activities in the Anthropocene and their pervasive effects on ecology and biodiversity. Publisher PDF

Peer reviewed: True, Funder: CR UK PhD Studentship, The HIF-1 and HIF-2 (HIF1/2) hypoxia responses are frequently upregulated in cancers, and HIF1/2 inhibitors are being developed as anticancer drugs. How could cancers resist anti-HIF1/2 therapy? We studied metabolic and molecular adaptations of HIF-1β-deficient Hepa-1c4, a hepatoma model lacking HIF1/2 signalling, which mimics a cancer treated by a totally effective anti-HIF1/2 agent. [1,2-13C2]-D-glucose metabolism was measured by SiDMAP metabolic profiling, gene expression by TaqMan, and metabolite concentrations by 1H MRS. HIF-1β-deficient Hepa-1c4 responded to hypoxia by increasing glucose uptake and lactate production. They showed higher glutamate, pyruvate dehydrogenase, citrate shuttle, and malonyl-CoA fluxes than normal Hepa-1 cells, whereas pyruvate carboxylase, TCA, and anaplerotic fluxes decreased. Hypoxic HIF-1β-deficient Hepa-1c4 cells increased expression of PGC-1α, phospho-p38 MAPK, and PPARα, suggesting AMPK pathway activation to survive hypoxia. They had higher intracellular acetate, and secreted more H2O2, suggesting increased peroxisomal fatty acid β-oxidation. Simultaneously increased fatty acid synthesis and degradation would have “wasted” ATP in Hepa-1c4 cells, thus raising the [AMP]:[ATP] ratio, and further contributing to the upregulation of the AMPK pathway. Since these tumour cells can proliferate without the HIF-1/2 pathways, combinations of HIF1/2 inhibitors with PGC-1α or AMPK inhibitors should be explored.