Health care access, psychosocial outcomes and mental health in adults living with epilepsy during the COVID-19 pandemic.

PURPOSE: People living with epilepsy (PLWE) have a higher prevalence of mental health comorbidities and poorer psychosocial outcomes compared to the general population. The aim of this study was to examine psychosocial outcomes, mental health, healthcare accessibility, and seizure burden in PLWE during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study of adults with epilepsy treated in an urban multicenter health system from 2021 to 2022. A standardized questionnaire assessed for COVID-19 history, comorbidities, access to antiseizure medications (ASMs) and neurological care, seizure burden, and psychosocial outcomes (e.g., employment, social and financial support). The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were administered to evaluate for depression and anxiety. Frequency and proportions for categorical variables and median and interquartile ranges for continuous variables were calculated. RESULTS: Fifty-five PLWE participated (95 % response rate). Median age was 40 years (IQR 31.5-66.5), 61.8 % were women, 47.3 % had a bachelor's degree or higher and 29.1 % each had Medicaid and Medicare insurance. Race (from highest to lowest %) was: 32.7 % White, 20 % Black, 20 % Latinx, 14.5 % Asian, and 12.7 % selected "other" or "prefer not to say." COVID-19 had been diagnosed in 21.8 % of participants. Symptoms of anxiety and depression were self-reported by 43.6 % and 34.5 % of patients, respectively, with many describing this symptom as new post-pandemic (37.5 % and 31.6 %, respectively). Using validated scales, 52.7 % had depression (PHQ-9 score ≥ 5) with 30.9 % having moderate/severe depression (PHQ-9 score ≥ 10), while 29.1 % had probable generalized anxiety disorder (GAD-7 score ≥ 8). Seizure burden increased in 21.8 % of participants, while 20 % reported fewer seizures and 29.1 % were seizure free since the COVID-19 pandemic. Economic impacts of the pandemic included job loss (25 % amongst those employed at onset of pandemic), new or worsened financial difficulties (40 %), and new or worsened social support issues (30.9 %). Of all participants, 18.2 % reported difficulties accessing ASMs and 25.5 % cancelled visits, but of those with cancelled visits, 78.6 % had their appointments rescheduled as a telehealth visit. CONCLUSION: Our cohort of PLWE experienced some challenges during the COVID-19 pandemic including poorer mental health and financial and employment-related stressors. Encouragingly, healthcare access was relatively spared during the COVID-19 crisis, with some patients even reporting a reduction in seizure burden. However, PLWE require ongoing psychosocial support with particular attention to decompensation of mental health and social stressors that may be exacerbated by the COVID-19 pandemic.

Production of tailored hydroxylated prodiginine showing combinatorial activity with rhamnolipids against plant-parasitic nematodes.

Bacterial secondary metabolites exhibit diverse remarkable bioactivities and are thus the subject of study for different applications. Recently, the individual effectiveness of tripyrrolic prodiginines and rhamnolipids against the plant-parasitic nematode Heterodera schachtii, which causes tremendous losses in crop plants, was described. Notably, rhamnolipid production in engineered Pseudomonas putida strains has already reached industrial implementation. However, the non-natural hydroxyl-decorated prodiginines, which are of particular interest in this study due to a previously described particularly good plant compatibility and low toxicity, are not as readily accessible. In the present study, a new effective hybrid synthetic route was established. This included the engineering of a novel P. putida strain to provide enhanced levels of a bipyrrole precursor and an optimization of mutasynthesis, i.e., the conversion of chemically synthesized and supplemented monopyrroles to tripyrrolic compounds. Subsequent semisynthesis provided the hydroxylated prodiginine. The prodiginines caused reduced infectiousness of H. schachtii for Arabidopsis thaliana plants resulting from impaired motility and stylet thrusting, providing the first insights on the mode of action in this context. Furthermore, the combined application with rhamnolipids was assessed for the first time and found to be more effective against nematode parasitism than the individual compounds. To obtain, for instance, 50% nematode control, it was sufficient to apply 7.8 µM hydroxylated prodiginine together with 0.7 µg/ml (~ 1.1 µM) di-rhamnolipids, which corresponded to ca. » of the individual EC50 values. In summary, a hybrid synthetic route toward a hydroxylated prodiginine was established and its effects and combinatorial activity with rhamnolipids on plant-parasitic nematode H. schachtii are presented, demonstrating potential application as antinematodal agents. Graphical Abstract.

What is the evidence that advertising policies could have an impact on gambling-related harms? A systematic umbrella review of the literature.

OBJECTIVE: To summarise the evidence on the impacts of gambling-related advertising that could lead to gambling-related harm, including impacts on vulnerable individuals and inequalities in the distribution of harms. STUDY DESIGN: An umbrella review of studies investigating the impact of gambling advertising. METHODS: A review was undertaken of systematic reviews of qualitative, quantitative and mixed method studies reporting outcomes associated with gambling advertising and marketing. The search strategy included database searches (Web of Science, PsycInfo) and website searches. The quality of the included reviews was determined using A MeaSurement Tool to Assess systematic Reviews 2. RESULTS: 1024 papers were identified by database searches. Eight systematic reviews, including 74 unique studies, met inclusion criteria. Included studies, using quantitative and qualitative methods, consistently support the existence of a causal relationship between exposure to advertising of gambling products/brands and more positive attitudes to gambling, greater intentions to gamble and increased gambling activity at both individual and population level. There is evidence of a 'dose-response' effect; greater advertising exposure increases participation which leads to a greater risk of harm. There was more evidence for the impact on children and young people and for those already at risk from current gambling activity with those most vulnerable more likely to be influenced. CONCLUSION: Gambling advertising restrictions could reduce overall harm and mitigate the impact of advertising on gambling-related inequalities. Public health harm prevention strategies should include policies which limit exposure to advertising, particularly among children and vulnerable groups.

A scoping review of the experience of implementing population testing for SARS-CoV-2.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - also known as the coronavirus disease (COVID-19) - pandemic has led to the swift introduction of population testing programmes in many countries across the world, using testing modalities such as drive-through, walk-through, mobile and home visiting programmes. Here, we provide an overview of the literature describing the experience of implementing population testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). STUDY DESIGN: Scoping review. METHODS: We conducted a scoping review using Embase, Medline and the Cochrane library in addition to a grey literature search. We identified indicators relevant to process, quality and resource outcomes related to each testing modality. RESULTS: In total, 2999 titles were identified from the academic literature and the grey literature search, of which 22 were relevant. Most studies were from the USA and the Republic of Korea. Drive-through testing centres were the most common testing modality evaluated and these provided a rapid method of testing whilst minimising resource use. CONCLUSIONS: The evidence base for population testing lacks high quality studies, however, the literature provides evaluations of the advantages and limitations of different testing modalities. There is a need for robust evidence in this area to ensure that testing is deployed in a safe and effective manner in response to the COVID-19 pandemic.

Multiscale modeling reveals inhibitory and stimulatory effects of caffeine on acetaminophen-induced toxicity in humans.

Acetaminophen (APAP) is a widely used analgesic drug that is frequently co-administered with caffeine (CAF) in the treatment of pain. It is well known that APAP may cause severe liver injury after an acute overdose. However, the understanding of whether and to what extent CAF inhibits or stimulates APAP-induced hepatotoxicity in humans is still lacking. Here, a multiscale analysis is presented that quantitatively models the pharmacodynamic (PD) response of APAP during co-medication with CAF. Therefore, drug-drug interaction (DDI) processes were integrated into physiologically based pharmacokinetic (PBPK) models at the organism level, whereas drug-specific PD response data were contextualized at the cellular level. The results provide new insights into the inhibitory and stimulatory effects of CAF on APAP-induced hepatotoxicity for crucially affected key cellular processes and individual genes at the patient level. This study might facilitate the risk assessment of drug combination therapies in humans and thus may improve patient safety in clinical practice.

Promoting and maintaining physical activity in the transition to retirement: a systematic review of interventions for adults around retirement age.

It has been argued that transition points in life, such as the approach towards, and early years of retirement present key opportunities for interventions to improve the health of the population. Research has also highlighted inequalities in health status in the retired population and in response to interventions which should be addressed. We aimed to conduct a systematic review to synthesise international evidence on the types and effectiveness of interventions to increase physical activity among people around the time of retirement. A systematic review of literature was carried out between February 2014 and April 2015. Searches were not limited by language or location, but were restricted by date to studies published from 1990 onwards. Methods for identification of relevant studies included electronic database searching, reference list checking, and citation searching. Systematic search of the literature identified 104 papers which described study populations as being older adults. However, we found only one paper which specifically referred to their participants as being around the time of retirement. The intervention approaches for older adults encompassed: training of health care professionals; counselling and advice giving; group sessions; individual training sessions; in-home exercise programmes; in-home computer-delivered programmes; in-home telephone support; in-home diet and exercise programmes; and community-wide initiatives. The majority of papers reported some intervention effect, with evidence of positive outcomes for all types of programmes. A wide range of different measures were used to evaluate effectiveness, many were self-reported and few studies included evaluation of sedentary time. While the retirement transition is considered a significant point of life change, little research has been conducted to assess whether physical activity interventions at this time may be effective in promoting or maintaining activity, or reducing health inequalities. We were unable to find any evidence that the transition to retirement period was, or was not a significant point for intervention. Studies in older adults more generally indicated that a range of interventions might be effective for people around retirement age.

Variables Associated with Severity of Bacterial Canker and Wilt Caused by Clavibacter michiganensis subsp. michiganensis in Tomato Greenhouses.

Clavibacter michiganensis subsp. michiganensis, the causal agent of bacterial canker and wilt of tomato, is considered to be one of the most important bacterial pathogens worldwide. In the year 2000 there was an increase in the number of infected greenhouses and in the severity of the disease in Israel. As part of the effort to cope with the disease, a comprehensive survey was conducted. Scouts recorded disease severity monthly in 681 production units. At the end of the season the scouts met with the growers and together recorded relevant details about the crop and cultural practices employed. The results suggested an absence of anisotropy pattern in the study region. Global Moran's I analysis showed that disease severity had significant spatial autocorrelation. The strongest spatial autocorrelation occurred within a 1,500 m neighborhood, which is comparable to the distance between production units maintained by one grower (Farm). Next, we tested three groups of variables including or excluding the Farm as a variable. When the Farm was included the explained variation increased in all the studied models. Overall, results of this study demonstrate that the most influential factor on bacterial canker severity was the Farm. This variable probably encompasses variation in experience, differences in agricultural practices between growers, and the quality of implementation of management practices.

Complete genome sequence of solvent-tolerant Pseudomonas putida S12 including megaplasmid pTTS12.

Pseudomonas putida S12 is a solvent-tolerant gamma-proteobacterium with an extensive track record for production of industrially relevant chemicals. Here we report the annotated complete genome sequence of this organism, including the megaplasmid pTTS12 which encodes many of the unique features of the S12 strain.

Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

M + Ng potential energy curves including spin-orbit coupling for M = K, Rb, Cs and Ng = He, Ne, Ar.

The X(2)Σ(1/2)(+), A(2)Π(1∕2), A(2)Π(3∕2), and B(2)Σ(1/2)(+) potential energy curves and associated dipole matrix elements are computed for M + Ng at the spin-orbit multi-reference configuration interaction level, where M = K, Rb, Cs and Ng = He, Ne, Ar. Dissociation energies and equilibrium positions for all minima are identified and corresponding vibrational energy levels are computed. Difference potentials are used together with the quasistatic approximation to estimate the position of satellite peaks of collisionally broadened D2 lines. The comparison of potential energy curves for different alkali atom and noble gas atom combinations is facilitated by using the same level of theory for all nine M + Ng pairs.

The polyhydroxyalkanoate metabolism controls carbon and energy spillage in Pseudomonas putida.

The synthesis and degradation of polyhydroxyalkanoates (PHAs), the storage polymer of many bacteria, is linked to the operation of central carbon metabolism. To rationalize the impact of PHA accumulation on central carbon metabolism of the prototype bacterium Pseudomonas putida, we have revisited PHA production in quantitative physiology experiments in the wild-type strain vs. a PHA negative mutant growing under low nitrogen conditions. When octanoic acid was used as PHA precursor and as carbon and energy source, we have detected higher intracellular flux via acetyl-CoA in the mutant strain than in the wild type, which correlates with the stimulation of the TCA cycle and glyoxylate shunt observed on the transcriptional level. The mutant defective in carbon and energy storage spills the additional resources, releasing CO(2) instead of generating biomass. Hence, P. putida operates the metabolic network to optimally exploit available resources and channels excess carbon and energy to storage via PHA, without compromising growth. These findings demonstrate that the PHA metabolism plays a critical role in synchronizing global metabolism to availability of resources in PHA-producing microorganisms.

Microbiological quality of raw milk produced in Estonia.

AIMS: The microbial quality of farm bulk-tank raw milk produced in Estonia during years 2004-2007 was investigated. METHODS AND RESULTS: Bulk-tank milk samples were analysed for lactic acid bacteria count (LABC), psychrotrophic bacteria count (PBC), aerobic spore-forming bacteria count (ASFBC), total bacterial counts using BactoScan and somatic cell count (SCC) using Fossomatic. Randomly selected psychrotrophic isolates were subjected to 16S-23S PCR-ribotyping. LABC remained below 10(4) CFU ml(-1) in most samples, while psychrotrophic micro-organisms dominated in 60% of farms. PBC ranged from 4.2 × 10(2) to 6.4 × 10(4) CFU ml(-1), and ASFBC varied from 5 to 836 CFU ml(-1). CONCLUSIONS: In general, the microbiological quality of the farm bulk-tank milk was good - more than 91% of samples contained <50,000 CFU ml(-1), and SCC in the majority of samples did not exceed the internationally recommended limits. Genus Pseudomonas spp. was the dominating spoilage flora with Pseudomonas fluorescens as the prevailing species. SIGNIFICANCE AND IMPACT OF THE STUDY: Specific bacterial groups (LABC, PBC and ASFBC), not analysed routinely by dairies, were determined in bulk-tank raw milk of numerous dairy farms during 4-year period. Based on the survey, dairy plants can better control their supply chains and select farms (milk) for the production of specific products, i.e. milk with low PBC and high LABC for cheesemaking.

Bilayer microfluidic chip for diffusion-controlled activation of yeast species.

A bilayer microfluidic chip is used, in which multiple laminar streams are generated to define local microenvironments. The bilayer architecture of the microchip separates cell handling and positioning from cell activation by soluble chemicals. Cell activation is diffusion controlled through a porous membrane. By employing time-lapse fluorescence microscopy, gene expression of the enhanced green fluorescent protein (eGFP) in Saccharomyces cerevisiae is studied under various conditions. We demonstrate that the yeast cells remain viable in the microchip for at least 17 h, and that gene expression can be initiated by the supply of the inducer galactose at a spatial precision of a few micrometers.

How do parents' child-feeding behaviours influence child weight? Implications for childhood obesity policy.

BACKGROUND: Parents have some responsibility for children's dietary habits and they are often the focus of public health interventions designed to improve children's diets and thereby reduce the prevalence of childhood obesity. The current UK interventions promote awareness of healthy food choices, but offer little guidance for parents on child-feeding behaviours. METHODS: A review of recent literature regarding child-feeding behaviours and child weight. RESULTS: Parents report using a wide range of child-feeding behaviours, including monitoring, pressure to eat and restriction. Restriction of children's eating has most frequently and consistently been associated with child weight gain. Furthermore, there is substantial evidence for a causal relationship between parental restriction and childhood overweight. CONCLUSIONS: Parents may inadvertently promote excess weight gain in childhood by using inappropriate child-feeding behaviours. We recommend the development of interventions to increase awareness of the possible consequences of inappropriate child-feeding behaviours. Parents who are concerned about their child's weight will also require guidance and support in order to adopt more appropriate child-feeding behaviours.

Physical activity and health: evidence from a study of deprived communities in England.

This study aims to explore the relationship between physical activity levels and the self-reported health status of residents living in deprived communities in England. A cross-sectional interview survey was conducted in communities in receipt of funding from the New Deal for Communities (NDC) regeneration programme. A sample of 848 addresses was selected by random sampling from within each of the 39 NDC areas, and one adult from each household was selected for interview. A total of 19 574 residents were interviewed between July and October 2002. The main outcome measures were physical activity level and health status assessed using four self-reported health measures: health in the last 12 months, health change in the last 12 months, long-standing illness or disability and a mental health-related quality-of-life score. There are large regional and demographic variations in respect of NDC residents' physical activity levels. The areas with the lowest levels of physical activity are mainly located in northern industrial towns. Residents who did little or no physical activity were more than twice as likely to feel that their health was not good (adjusted OR 2.54, 95% CI 2.35-2.75).

Reducing inequalities in access to health care: developing a toolkit through action research.

PROBLEM: Healthcare organisations are expected both to monitor inequalities in access to health services and also to act to improve access and increase equity in service provision. DESIGN: Locally developed action research projects with an explicit objective of reducing inequalities in access. SETTING: Eight different health care services in the Yorkshire and Humber region, including community based palliative care, general practice asthma care, hospital based cardiology clinics, and termination of pregnancy services. KEY MEASURES FOR IMPROVEMENT: Changes in service provision, increasing attendance rates in targeted groups. STRATEGIES FOR CHANGE: Local teams identified the population concerned and appropriate interventions using both published and grey literature. Where change to service provision was achieved, local data were collected to monitor the impact of service change. EFFECTS OF CHANGE: A number of evidence based changes to service provision were proposed and implemented with variable success. Service uptake increased in some of the targeted populations. LESSONS LEARNT: Interventions to improve access must be sensitive to local settings and need both practical and managerial support to succeed. It is particularly difficult to improve access effectively if services are already struggling to meet current demand. Key elements for successful interventions included effective local leadership, identification of an intervention which is both evidence based and locally practicable, and identification of additional resources to support increased activity. A "toolkit" has been developed to support the identification and implementation of appropriate changes.

Regional differences in the provision of adult renal dialysis services in the UK.

BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To analyse these differences in provision and investigate their causes. DESIGN: Questionnaire-based survey. METHODS: A questionnaire was posted to all renal provider units and renal commissioning groups in the UK. Questions covered issues such as dialysis modalities and patient choice. Data were collected by telephone interview (or post in some cases) and analysed using SPSS. RESULTS: All renal provider units in the UK responded. A full range of modalities was provided by the majority of units. Clear variations in the level and quality of dialysis provision were seen between the UK regions. These included variation in choice of dialysis modality, provision of high-cost drugs, vascular access waiting times, number of support staff and availability of spare dialysis slots. DISCUSSION: The considerable variation between UK regions in the provision of adult renal dialysis services cannot be entirely explained by age or ethnic variation, and is in part due to limited bed space, dialysis machines and support staff, as well as changes in commissioning arrangements. To meet the requirements of the renal national service framework in most regions, changes to policy and funding will be required, such that the relatively new commissioning groups implement more appropriate funding structures in closer dialogue with their provider units.

The AMORE protocol as salvage treatment for non-orbital head and neck rhabdomyosarcoma in children.

AIM: To investigate the feasibility and outcome of the AMORE protocol as salvage treatment in paediatric head and neck rhabdomyosarcoma (HNRMS). METHODS: The AMORE protocol is a local treatment regimen, consisting of Ablative surgery, Moulage technique brachytherapy and surgical Reconstruction, scheduled in 1 week. Patients with recurrent or residual non-orbital HNRMS were eligible for AMORE salvage treatment. RESULTS: The procedure was feasible in nine out of 11 eligible patients. Five patients were treated for recurrent or residual parameningeal RMS after prior chemoradiation. Local complete remission was achieved in all five patients and maintained in four. Three patients are without evidence of RMS with a follow-up duration of 4-10 years. Two patients developed a distant relapse, together with a local recurrence in one. Both patients died of their disease. Four patients were included for recurrent non-parameningeal HNRMS. Long-term local control at the site of recurrence was obtained in all four patients (follow-up 5-10 years). CONCLUSIONS: The AMORE protocol is a feasible salvage strategy for non-orbital HNRMS even after external beam radiotherapy. The local salvage rate in this series is promising.

A novel local treatment strategy for advanced stage head and neck rhabdomyosarcomas in children: results of the AMORE protocol.

The AMORE protocol is a local treatment regimen for head and neck rhabdomyosarcomas (HNRMS), consisting of Ablative surgery, Moulage technique brachytherapy and surgical Reconstruction. The aim of AMORE is to intensify local treatment for children with HNRMS and to avoid external beam radiation therapy (EBRT) and its long-term sequelae. All children with primary irresectable, non-orbital HNRMS in whom EBRT was indicated, were evaluated for the feasibility of AMORE. In 20 children, AMORE was performed (15 with parameningeal disease and five with non-parameningeal disease). Complete remission was achieved in all 20 patients. Local complications were limited. 5 patients experienced a local relapse and 1 patient developed distant metastases. Estimated 5-year OS and EFS were 67.5 and 64.1% for the entire group, and 64.2 and 60.0% for the parameningeal subgroup. We conclude that the AMORE protocol is a feasible strategy, with a good local control rate. Long-term sequelae of EBRT might be avoided although, to date, the follow-up is too short for definitive conclusions regarding these sequelae.

Acute toxicity of conventional radiation therapy for high-risk prostate cancer in EORTC trial 22863.

OBJECTIVES: We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer (EORTC) randomised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients. METHODS: Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment. Toxicity was grouped in a few categories: general, genito-urinary, and lower gastro-intestinal. Univariate and multivariate analyses were performed using the World Health Organisation (WHO) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups. RESULTS: Overall, our data show that age, previous surgery and irradiation dose are important predictive factors for acute toxicity, but not the use of combined hormone therapy. Fifteen percent of patients suffered of moderate to severe acute toxicity (WHO G3-G4). Life threatening toxicity was observed in six cases (1.5%). CONCLUSIONS: The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature. Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation. These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques.