Rosin as a Natural Alternative for the effective disinfection of ESKAPE Pathogens and Clostridioides difficile spores.

AIM: Hospital-acquired infections (HAIs) caused by antimicrobial-resistant ESKAPE pathogens are a significant concern for the healthcare industry, with an estimated cost of up to ${\$}$45 billion per year in the US alone. Clostridioides difficile is an additional opportunistic pathogen that also poses a serious threat to immunocompromised patients in hospitals. Infections caused by these pathogens lead to increased hospital stays and repeated readmission, resulting in a significant economic burden. Disinfectants and sporicidals are essential to reduce the risk of these pathogens in hospitals, but commercially available products can have a number of disadvantages including inefficacy, long contact times, short shelf lives, and operator health hazards. In this study we evaluated the effectiveness of Rosin (a natural substance secreted by coniferous trees as a defence mechanism against wounds in tree bark) and its commercial derivative Rosetax-21 as disinfectants and sporicidal against the six ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and spore preparations from Clostridioides difficile. METHODS AND RESULTS: Both Rosin and Rosetax-21 were tested under simulated clean and dirty conditions (with BSA) against the ESKAPE pathogens, and C. difficile spore preparations. In clean conditions, Rosin (5% weight/volume: w/v) demonstrated significant efficacy against five of the ESKAPE pathogens, with A. baumannii and E. faecium being the most susceptible, and K. pneumoniae the most resistant, showing only a one-log reduction after a 5 min treatment. However, in dirty conditions, all pathogens including K. pneumoniae exhibited at least a 3-log reduction to Rosin within 5 min. Rosetax-21 (5% w/v) was found to be less effective than Rosin in clean conditions, a trend that was exacerbated in the presence of BSA. Additionally, both Rosin and Rosetax-21 at 2.5% (w/v) achieved complete eradication of C. difficile spores when combined with 0.5% glutaraldehyde, though their standalone sporicidal activity was limited. CONCLUSIONS: The findings from this study highlight the potential of Rosin and Rosetax-21 as both bactericidal and sporicidal disinfectants, with their efficacy varying based on the conditions and the pathogens tested. This presents an avenue for the development of novel healthcare disinfection strategies, especially against HAIs caused by antimicrobial-resistant ESKAPE pathogens and C. difficile.

Trends in day-case bladder outflow obstruction surgery: a study using Hospital Episode Statistics.

OBJECTIVES: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles. MATERIALS AND METHODS: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions. RESULTS: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations. CONCLUSIONS: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality.

Impact of interventions to improve recovery of older adults following planned hospital admission on quality-of-life following discharge: linked-evidence synthesis.

Objectives: To understand the impact of multicomponent interventions to improve recovery of older adults following planned hospital treatment, we conducted two systematic reviews, one of quantitative and one of qualitative evidence, and an overarching synthesis. These aimed to: • understand the effect of multicomponent interventions which aim to enhance recovery and/or reduce length of stay on patient-reported outcomes and health and social care utilisation • understand the experiences of patients, carers and staff involved in the delivery of interventions • understand how different aspects of the content and delivery of interventions may influence patient outcomes. Review methods: We searched bibliographic databases including MEDLINE ALL, Embase and the Health Management Information Consortium, CENTRAL, and Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine Database, conducted forward and backward citation searching and examined reference lists of topically similar qualitative reviews. Bibliographic database searches were completed in May/June 2021 and updated in April 2022. We sought primary research from high-income countries regarding hospital inpatients with a mean/median age of minimum 60 years, undergoing planned surgery. Patients experienced any multicomponent hospital-based intervention to reduce length of stay or improve recovery. Quantitative outcomes included length of stay and any patient-reported outcome or experience or service utilisation measure. Qualitative research focused on the experiences of patients, carers/family and staff of interventions received. Quality appraisal was undertaken using the Effective Public Health Practice Project Quality Assessment Tool or an adapted version of the Wallace checklist. We used random-effects meta-analysis to synthesise quantitative data where appropriate, meta-ethnography for qualitative studies and qualitative comparative analysis for the overarching synthesis. Results: Quantitative review: Included 125 papers. Forty-nine studies met criteria for further synthesis. Enhanced recovery protocols resulted in improvements to length of stay, without detriment to other outcomes, with minimal improvement in patient-reported outcome measures for patients admitted for lower-limb or colorectal surgery. Qualitative review: Included 43 papers, 35 of which were prioritised for synthesis. We identified six themes: 'Home as preferred environment for recovery', 'Feeling safe', 'Individualisation of structured programme', 'Taking responsibility', 'Essential care at home' and 'Outcomes'. Overarching synthesis: Intervention components which trigger successful interventions represent individualised approaches that allow patients to understand their treatment, ask questions and build supportive relationships and strategies to help patients monitor their progress and challenge themselves through early mobilisation. Discussion: Interventions to reduce hospital length of stay for older adults following planned surgery are effective, without detriment to other patient outcomes. Findings highlight the need to reconsider how to evaluate patient recovery from the perspective of the patient. Trials did not routinely evaluate patient mid- to long-term outcomes. Furthermore, when they did evaluate patient outcomes, reporting is often incomplete or conducted using a narrow range of patient-reported outcome measures or limited through asking the wrong people the wrong questions, with lack of longer-term evaluation. Findings from the qualitative and overarching synthesis will inform policy-making regarding commissioning and delivering services to support patients, carers and families before, during and after planned admission to hospital. Study registration: This trial is registered as PROSPERO registration number CRD42021230620. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 130576) and is published in full in Health and Social Care Delivery Research; Vol. 11, No. 23. See the NIHR Funding and Awards website for further award information.

More patients aged 60 or over need planned surgery. These patients are more likely to experience difficulties, such as urinary infections or falls, whilst in hospital, so should not spend more time in hospital than necessary. Hospitals use strategies that shorten hospital stay, but we do not know how older patients, or carers, feel about these, or whether they help patients recover in the long term. We wanted to know: how leaving hospital sooner affects how older patients feel and recover after planned surgery; how older patients, carers and staff feel about strategies designed to support older patients to go home earlier; which parts of these hospital care strategies work best? We brought together research about hospital care strategies that shorten the length of time older patients spend in hospital. We looked at patient questionnaires and interviews with patients, carers and hospital staff. Patients and carers helped us plan our research, understand our findings and consider who to share these with. hospital strategies to reduce hospital stay achieve this, without increasing risk of complications; information and follow-up care for patients and carers after discharge are essential; strategies which consider the individual needs of patients and help them understand their treatment, focus on their recovery goals and develop supportive relationships with staff were linked to better outcomes; lots of studies were excluded because they did not use patient questionnaires. Studies using questionnaires often focused on aspects of care delivered whilst patients were in hospital. Carers' voices were often overlooked. Research is needed to develop patient questionnaires to more fully capture the experiences of patients and carers and support hospitals to develop care strategies focused on the needs of individual patients and carers.

UK national bladder outlet obstruction surgery snapshot audit.

OBJECTIVES: To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK. PATIENTS AND METHODS: A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery. RESULTS: There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively. CONCLUSIONS: There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved.

Developmental exposure to vitamin D deficiency and subsequent risk of schizophrenia.

Over the last half century, a body of convergent evidence has accumulated linking disruption of early brain development with an increased risk of mental disorders, including schizophrenia. The orderly cascade of brain development may be disrupted by exposure to suboptimal concentrations of a range of biological substrates and micronutrients. We hypothesized that those exposed to vitamin D deficiency during early life, have an increased risk of neurodevelopmental disorders, including schizophrenia. The hypothesis was based on the link between an increased risk of schizophrenia in (a) those born in winter and spring, when vitamin D deficiency is more prevalent, and (b) the offspring of dark-skinned migrants living in cold climates, who have a markedly increased risk of vitamin D deficiency. In this review, we summarize evidence from analytic epidemiology related to this hypothesis. Two case-control studies based on Danish neonatal dried blood spots have found that neonatal vitamin deficiency is associated with an increased risk of schizophrenia. However, recent genetic analyses have also suggested that common variants linked to schizophrenia may lead to lower vitamin D concentrations (possibly mediated via reduced outdoor activity). We summarize limitations of the current evidence and outline suggestions that can guide future research. Based on currently available data, there is insufficient evidence to support public health recommendations related to this topic. However, we cannot reject the hypothesis that the provision of vitamin D supplementation to pregnant women and/or offspring in groups vulnerable to vitamin D deficiency may subsequently reduce the incidence of schizophrenia in the offspring.

Rosin Soap Exhibits Virucidal Activity.

Chemical methods of virus inactivation are used routinely to prevent viral transmission in both a personal hygiene capacity but also in at-risk environments like hospitals. Several virucidal products exist, including hand soaps, gels, and surface disinfectants. Resin acids, which can be derived from tall oil, produced from trees, have been shown to exhibit antibacterial activity. However, whether these products or their derivatives have virucidal activity is unknown. Here, we assessed the capacity of rosin soap to inactivate a panel of pathogenic mammalian viruses in vitro. We show that rosin soap can inactivate human enveloped viruses: influenza A virus (IAV), respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For IAV, rosin soap could provide a 100,000-fold reduction in infectivity. However, rosin soap failed to affect the nonenveloped encephalomyocarditis virus (EMCV). The inhibitory effect of rosin soap against IAV infectivity was dependent on its concentration but not on the incubation time or temperature. In all, we demonstrate a novel chemical inactivation method against enveloped viruses, which could be of use for preventing virus infections in certain settings. IMPORTANCE Viruses remain a significant cause of human disease and death, most notably illustrated through the current coronavirus disease 2019 (COVID-19) pandemic. Control of virus infection continues to pose a significant global health challenge to the human population. Viruses can spread through multiple routes, including via environmental and surface contamination, where viruses can remain infectious for days. Methods for inactivating viruses on such surfaces may help mitigate infection. Here, we present evidence identifying a novel virucidal product, rosin soap, which is produced from tall oil from coniferous trees. Rosin soap was able to rapidly and potently inactivate influenza virus and other enveloped viruses.

Effect of Vitamin D Supplementation on Outcomes in People With Early Psychosis: The DFEND Randomized Clinical Trial.

Importance: People with psychotic disorders have an increased risk of vitamin D deficiency, which is evident during first-episode psychosis (FEP) and associated with unfavorable mental and physical health outcomes. Objective: To examine whether vitamin D supplementation contributes to improved clinical outcomes in FEP. Design, Setting, and Participants: This multisite, double-blind, placebo-controlled, parallel-group randomized clinical trial from the UK examined adults 18 to 65 years of age within 3 years of a first presentation with a functional psychotic disorder who had no contraindication to vitamin D supplementation. A total of 2136 patients were assessed for eligibility, 835 were approached, 686 declined participation or were excluded, 149 were randomized, and 104 were followed up at 6 months. The study recruited participants from January 19, 2016, to June 14, 2019, with the final follow-up (after the last dose) completed on December 20, 2019. Interventions: Monthly augmentation with 120 000 IU of cholecalciferol or placebo. Main Outcomes and Measures: The primary outcome measure was total Positive and Negative Syndrome Scale (PANSS) score at 6 months. Secondary outcomes included total PANSS score at 3 months; PANSS positive, negative, and general psychopathology subscale scores at 3 and 6 months; Global Assessment of Function scores (for symptoms and disability); Calgary Depression Scale score, waist circumference, body mass index, and glycated hemoglobin, total cholesterol, C-reactive protein, and vitamin D concentrations at 6 months; and a planned sensitivity analysis in those with insufficient vitamin D levels at baseline. Results: A total of 149 participants (mean [SD] age, 28.1 (8.5) years; 89 [59.7%] male; 65 [43.6%] Black or of other minoritized racial and ethnic group; 84 [56.4%] White [British, Irish, or of other White ethnicity]) were randomized. No differences were observed in the intention-to-treat analysis in the primary outcome, total PANSS score at 6 months (mean difference, 3.57; 95% CI, -1.11 to 8.25; P = .13), or the secondary outcomes at 3 and 6 months (PANSS positive subscore: mean difference, -0.98; 95% CI, -2.23 to 0.27 at 3 months; mean difference, 0.68; 95% CI, -0.69 to 1.99 at 6 months; PANSS negative subscore: mean difference, 0.68; 95% CI, -1.39 to 2.76 at 3 months; mean difference, 1.56; 95% CI, -0.31 to 3.44 at 6 months; and general psychopathology subscore: mean difference, -2.09; 95% CI, -4.36 to 0.18 at 3 months; mean difference, 1.31; 95% CI, -1.42 to 4.05 at 6 months). There also were no significant differences in the Global Assessment of Function symptom score (mean difference, 0.02; 95% CI, -4.60 to 4.94); Global Assessment of Function disability score (mean difference, -0.01; 95% CI, -5.25 to 5.23), or Calgary Depression Scale score (mean difference, -0.39; 95% CI, -2.05 to 1.26) at 6 months. Vitamin D levels were very low in the study group, especially in Black participants and those who identified as another minoritized racial and ethnic group, 57 of 61 (93.4%) of whom had insufficient vitamin D. The treatment was safe and led to a significant increase in 25-hydroxyvitamin D concentrations. Conclusions and Relevance: In this randomized clinical trial, no association was found between vitamin D supplementation and mental health or metabolic outcomes at 6 months. Because so few patients with FEP were vitamin D replete, the results of this study suggest that this group would benefit from active consideration in future population health strategies. Trial Registration: isrctn.org Identifier: ISRCTN12424842.

Vitamin D and schizophrenia: 20 years on.

Many epidemiological studies have highlighted the link between vitamin D deficiency and schizophrenia. In particular, two prominent studies report an association between neonatal vitamin D deficiency and an increased risk of schizophrenia. In parallel, much has been learnt about the role of vitamin D in the developing central nervous system over the last two decades. Studies in rodent models of developmental vitamin D (DVD)-deficiency describe how brain development is altered leading to a range of neurobiological and behavioral phenotypes of interest to schizophrenia. While glutamate and gamma aminobutyric acid (GABA) systems have been little investigated in these models, alterations in developing dopamine systems are frequently reported. There have been far more studies reporting patients with schizophrenia have an increased risk of vitamin D deficiency compared to well controls. Here we have conducted a systematic review and meta-analysis that basically confirms this association and extends this to first-episode psychosis. However, patients with schizophrenia also have poorer general health, poorer diets, are frequently less active and also have an increased risk of other medical conditions, all factors which reduce circulating vitamin D levels. Therefore, we would urge caution in any causal interpretation of this association. We also summarize the inconsistent results from existing vitamin D supplementation trials in patients with schizophrenia. In respect to animal models of adult vitamin D deficiency, such exposures produce subtle neurochemical alterations and effects on cognition but do not appear to produce behavioral phenotypes of relevance to schizophrenia. We conclude, the hypothesis that vitamin D deficiency during early life may increase the risk of schizophrenia remains plausible and warrants ongoing research.

High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. Objective: To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. Design, Setting, and Participants: This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. Interventions: High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D3 supplementation from pregnancy week 24 until 1 week after birth. Main Outcomes and Measures: The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). Results: Among 623 women randomized, 315 were randomized to high-dose vitamin D3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D3 supplementation during pregnancy on offspring achievement of motor milestones (ß = 0.08 [95% CI, -0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, -1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication score: 50 [50-55] vs 50 [50-55]; P = .62), or emotional and behavioral problems (odds ratio, 0.76 [95% CI, 0.53 to 1.09]; P = .14). There was no effect on language development expressed by the word production at 1 year (median [IQR], 2 [0-6] words vs 3 [1-6] words; P = .16), although a decreased word production was apparent at 2 years in children in the high-dose vitamin D3 group (median [IQR], 232 [113-346] words vs 253 [149-382.5] words; P = .02). Conclusions and Relevance: In this prespecified secondary analysis of an RCT, maternal high-dose vitamin D3 supplementation during the third trimester of pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life. These findings contribute essential information clarifying the effects of prenatal exposure to vitamin D on neurodevelopment in childhood. Trial Registration: ClinicalTrials.gov Identifier: NCT00856947.

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster.

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 Deepwater Horizon disaster. The aim of this study was to evaluate lung function in workers 4-6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1-3 years, and 4-6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV1; ml), forced vital capacity (FVC; ml), and ratio (FEV1/FVC; %) determined. Linear mixed models were utilized to estimate relationships between OSRC exposures and lung function 4-6 years after the spill and changes since the prior measurement. Despite suggestive reduced lung function at 1-3 years, at the  4-6-year exam workers with total hydrocarbon (THC) exposure 1-2.99 ppm and ≥3 ppm compared to those with ≤0.29 ppm exhibited higher FEV1 (ß: 108 ml, 95% CI: 17, 198) and (ß: 118 ml, 95% CI: 5, 232), respectively. Compared with support workers, those in higher exposed jobs displayed greater improvement in FEV1 between visits: cleanup on water (ß: 143 ml, 95% CI: 35, 250), operations (ß: 132 ml, 95% CI: 30, 234) and response (ß: 149 ml, 95% CI: 43, 256). Greater FEV1 improvement was also associated with higher versus the lowest level THC exposure: 1-2.99 ppm (ß: 134 ml, 95% CI: 57, 210) and ≥3 ppm (ß: 205 ml, 95% CI: 109, 301). Lung function decrements seen shortly after the spill were no longer apparent 4-6 years later, with the greatest improvement among those with the highest exposures.

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. METHODS/DESIGN: The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. DISCUSSION: The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. TRIAL REGISTRATION: ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Genomics-based treatment in a patient with two overlapping heritable skin disorders: Epidermolysis bullosa and acrodermatitis enteropathica.

Next-generation sequencing (NGS) is helpful in diagnosing complex genetic disorders and phenotypes, particularly when more than one overlapping condition is present. From a large cohort of 362 families with clinical manifestations of skin and mucosal fragility, referred by several major medical centers, one patient was found by NGS to have two overlapping heritable skin diseases, recessive dystrophic epidermolysis bullosa (RDEB; COL7A1 mutations) and acrodermatitis enteropathica (AE; SLC39A4 mutations). The pathogenicity of the variants was studied at gene expression as well as ultrastructural and tissue levels. Although there is no specific treatment for RDEB except avoiding trauma, supplementation with oral zinc (3 mg·kg-1 ·day-1 ) for the AE resulted in rapid amelioration of the skin findings. This case demonstrates the power of NGS in identifying two genetically unlinked diseases that led to effective treatment with major clinical benefits as an example of genomics-guided treatment.

The Therapeutic Potential of Mangosteen Pericarp as an Adjunctive Therapy for Bipolar Disorder and Schizophrenia.

New treatments are urgently needed for serious mental illnesses including bipolar disorder and schizophrenia. This review proposes that Garcinia mangostana Linn. (mangosteen) pericarp is a possible adjunctive therapeutic agent for these disorders. Research to date demonstrates that neurobiological properties of the mangosteen pericarp are well aligned with the current understanding of the pathophysiology of bipolar disorder and schizophrenia. Mangosteen pericarp has antioxidant, putative neuroprotective, anti-inflammatory, and putative mitochondrial enhancing properties, with animal studies demonstrating favorable pharmacotherapeutic benefits with respect to these disorders. This review summarizes evidence of its properties and supports the case for future studies to assess the utility of mangosteen pericarp as an adjunctive treatment option for mood and psychotic disorders.

Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial.

BACKGROUND: There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION: Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.

Transforming soil phosphorus fertility management strategies to support the delivery of multiple ecosystem services from agricultural systems.

Despite greater emphasis on holistic phosphorus (P) management, current nutrient advice delivered at farm-scale still focuses almost exclusively on agricultural production. This limits our ability to address national and international strategies for the delivery of multiple ecosystem services (ES). Currently there is no operational framework in place to manage P fertility for multiple ES delivery and to identify the costs of potentially sacrificing crop yield and/or quality. As soil P fertility plays a central role in ES delivery, we argue that soil test phosphorus (STP) concentration provides a suitable common unit of measure by which delivering multiple ES can be economically valued relative to maximum potential yield, in $ ha-1 yr-1 units. This value can then be traded, or payments made against one another, at spatio-temporal scales relevant for farmer and national policy objectives. Implementation of this framework into current P fertility management strategies would allow for the integration and interaction of different stakeholder interests in ES delivery on-farm and in the wider landscape. Further progress in biophysical modeling of soil P dynamics is needed to inform its adoption across diverse landscapes.

Lichen planus and lichenoid dermatoses: Conventional and emerging therapeutic strategies.

Having reviewed the diverse clinical subtypes of lichenoid disease and the postulated molecular basis thereof in the first article in this 2-part continuing medical education series, we discuss herein the existing and emerging treatment strategies in the most common clinical forms of lichenoid inflammation and provide an overview of their pharmacodynamics and evidence base. The scope of this review is not to exhaustively discuss treatment modalities for all lichenoid variants discussed in the previous article of this series. Instead, the focus will be on frequently encountered subtypes of lichen planus and on linking mechanisms of disease with mechanisms of drug action. Future directions and potential avenues for translational research will also be discussed.

Prevalence and correlates of suboptimal vitamin D status in people living with psychotic disorders: Data from the Australian Survey of High Impact Psychosis.

OBJECTIVE: Having sufficient sera concentrations of 25-hydroxyvitamin D is important for a range of health outcomes including cardiometabolic diseases. Clinical studies in people with psychotic disorders suggest that a sizable proportion has suboptimal vitamin D status (i.e. vitamin D deficiency or insufficiency). Individuals with psychosis also have many of the risk factors associated with suboptimal vitamin D status such as smoking, obesity, and reduced physical activity. The aim of this study was to examine the prevalence and socio-demographic and clinical correlates of vitamin D status using a large, population-based sample of adults with psychotic disorders. METHODS: Data were collected as part of the Survey of High Impact Psychosis, a population-based survey of Australians aged 18-64 years with a psychotic disorder. 25-Hydroxyvitamin D concentration was measured in 463 participants. 25-Hydroxyvitamin D concentration was dichotomised into optimal (above 50 nmol/L) and suboptimal (below 50 nmol/L). The influence of a range of socio-demographic and clinical variables on vitamin D status was examined using logistic regression. RESULTS: Nearly half (43.6%) of the participants had suboptimal vitamin D status. Those with (a) increased physical activity or (b) positive symptoms had significantly reduced odds of having suboptimal vitamin D status. However, there were no significant associations between suboptimal vitamin D status and other psychiatric symptom measures or cardiometabolic risk factors. CONCLUSION: Many people with psychotic disorders have suboptimal vitamin D status. As part of the routine assessment of physical health status, clinicians should remain mindful of vitamin D status in this vulnerable population and encourage the use of appropriate vitamin D supplements.

Gestational vitamin D deficiency and autism spectrum disorder.

BACKGROUND: There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood. AIMS: To determine the association between gestational vitamin D status and ASD. METHOD: Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases). RESULTS: Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only. CONCLUSIONS: Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Microbial phylogenetic and functional responses within acidified wastewater communities exhibiting enhanced phosphate uptake.

Acid stimulated accumulation of insoluble phosphorus within microbial cells is highly beneficial to wastewater treatment but remains largely unexplored. Using single cell analyses and next generation sequencing, the response of active polyphosphate accumulating microbial communities under conditions of enhanced phosphorus uptake under both acidic and aerobic conditions was characterised. Phosphorus accumulation activities were highest under acidic conditions (pH 5.5>8.5), where a significant positive effect on bioaccumulation was observed at pH 5.5 when compared to pH 8.5. In contrast to the Betaproteobacteria and Actinobacteria dominated enhanced biological phosphorus removal process, the functionally active polyP accumulators at pH 5.5 belonged to the Gammaproteobacteria, with key accumulators identified as members of the families Aeromonadaceae and Enterobacteriaceae. This study demonstrated a significant enrichment of key polyphosphate kinase and exopolyphosphatase genes within the community metagenome after acidification, concomitant with an increase in P accumulation kinetics.