Fast neurotransmitter identity of MCH neurons: Do contents depend on context?

Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.

Improved life expectancy for Indigenous and non-Indigenous people in the Northern Territory, 1999-2018: overall and by underlying cause of death.

OBJECTIVES: To provide updated estimates of life expectancy at birth for Indigenous and non-Indigenous people in the Northern Territory, 1999-2018; to quantify the contributions of changes in life years lost to disease-specific causes of death to overall changes in life expectancy. DESIGN, SETTING, PARTICIPANTS: Analysis of Australian Coordinating Registry data on underlying and nine multiple causes of death (ICD-10) for deaths in the NT, by age, sex, and Indigenous status, 1 January 1999 - 31 December 2018. MAIN OUTCOME MEASURES: Life expectancy at birth by year and 5-year period, by Indigenous status and sex; change in life expectancy by year and 5-year period, by Indigenous status and sex; contributions in changes in life years lost to leading underlying causes of death, by 5-year period, Indigenous status and sex. RESULTS: Life expectancy for Indigenous men increased from 56.6 years in 1999 to 65.6 years in 2018 (change, 9.0 years; 95% CI, 7.9-10.0 years) and from 64.8 to 69.7 years for Indigenous women (4.9 years; 95% CI, 3.2-6.7 years); for non-Indigenous men, it increased from 77.4 to 81.0 years (3.6 years; 95% CI, 2.8-4.4 years), and from 84.3 to 85.1 years for non-Indigenous women (0.8 years; 95% CI, -0.4 to 1.9 years). Increased life expectancy for Indigenous men was primarily linked with fewer years of life lost to cancer (23% of overall change), unintentional injuries (18%), and cardiovascular disease (17%), and for Indigenous women with fewer life years lost to cancer (24%), intentional injuries (17%), and kidney disease (14%). During 1999-2018, the difference in life expectancy between Indigenous and non-Indigenous people declined by 26% for men (from 20.8 to 15.4 years) and by 21% for women (from 19.5 to 15.4 years). CONCLUSIONS: Life expectancy improved markedly during 1999-2018 for Indigenous people in the NT, particularly with respect to fewer years of life lost to cancer, injuries, and chronic disease. The smaller gains in life expectancy for non-Indigenous people were linked with improved survival for those with cancer and neurological conditions.

Nasal septal angiofibroma: less vascular behaviour than observed in radiological imaging, a rare case in a 51-year-old woman.

Angiofibroma of the head and neck is classically found in the nasopharynx of an adolescent male. We present a rare case where an angiofibroma was diagnosed in the anterior nasal septum of a 51-year-old woman, the eighth nasal septal angiofibroma reported in a female. This case highlights how an angiofibroma in an older woman has a less vascular behaviour than one in an adolescent male, even though radiological enhancement may suggest that the lesion is highly vascularised. Nasal septal angiofibromas can be managed by biopsy and removed by simple endoscopic resection with minimal haemorrhage. Although very rare, extranasopharyngeal angiofibroma/nasal septal angiofibroma should be included in the differential diagnosis when patients of all ages present with nasal obstruction secondary to a nasal mass, with or without epistaxis.

Examining the efficacy of mushroom industry biocides on Listeria monocytogenes biofilm.

AIMS: The aim of this study was to test the efficacy of new and currently used biocides in the mushroom industry for inactivating Listeria monocytogenes biofilm. METHODS AND RESULTS: A laboratory-scale study was initially carried out to test the efficacy of eleven biocidal products against a cocktail of five L. monocytogenes strains that were grown to 3-day biofilms on stainless steel coupons. Biocidal efficacy was then tested under clean and dirty conditions based on the EN 13697:2015 method. The results for the biocides tested ranged between 1·7-log and 6-log reduction of biofilm, with only the efficacy of the sodium hypochlorite-based biocide being significantly reduced in dirty conditions. A pilot-scale trial was then carried out on a subset of biocides against L. monocytogenes on concrete floors in a mushroom growing room and it was found that biocide efficacy in laboratory-scale did not translate well in pilot-scale. CONCLUSIONS: Biocides that are used in the mushroom industry and potential alternative biocides were determined to be effective against L. monocytogenes biofilm in both laboratory-scale and pilot-scale experiments. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has direct impact for the industry as it provides information on the efficacy of currently used biocides and other biocidal products against L. monocytogenes, an added benefit to their primary use.

Inactivation efficacy and mechanisms of plasma activated water on bacteria in planktonic state.

AIMS: The study aimed to investigate the inactivation efficacy and mechanisms of plasma activated water (PAW) on selected bacteria in planktonic state. METHODS AND RESULTS: Plasma activated water was generated using an atmospheric cold plasma jet at 15, 22 and 30 kV for 5 min. Escherichia coli, Listeria innocua, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas fluorescens and Shewanella putrefaciens were selected as the representative bacterial species. Each bacterial suspension was inoculated into PAW immediately after generation, and the viable counts at different exposure times of 0·5, 1, 3, 5 and 24 h during 4°C storage were measured to determine the inactivation efficacy. Scanning electron microscopy images of the bacteria were conducted to examine the structural changes. Physicochemical properties of PAW, including pH, conductivity, oxidation reduction potential (ORP), and reactive species of H2 O2 , NO2 - and NO3 - were measured. The results demonstrated that inactivation efficacy was in positive correlation with voltage and exposure time. Gram-negative bacteria were more susceptible to PAW than Gram-positive bacteria. Morphology damage was observed for all the bacterial species. PAW was significantly acidified, conductivity and ORP were significantly increased, and reactive species were detectable after 48 h. CONCLUSIONS: This study offered a better understanding of the inactivation mechanisms of PAW, and the inactivation efficacy can be affected by voltage, exposure time and bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the potential usage of PAW as an alternative disinfectant.

Cardiovascular disease risk assessment for Aboriginal and Torres Strait Islander adults aged under 35 years: a consensus statement.

Cardiovascular disease (CVD) is a leading cause of preventable morbidity and mortality in Aboriginal and Torres Strait Islander peoples. This statement from the Australian Chronic Disease Prevention Alliance, the Royal Australian College of General Practitioners, the National Aboriginal Community Controlled Health Organisation and the Editorial Committee for Remote Primary Health Care Manuals communicates the latest consensus advice of guideline developers, aligning recommendations on the age to commence Aboriginal and Torres Strait Islander CVD risk assessment across three guidelines. MAIN RECOMMENDATIONS: In Aboriginal and Torres Strait Islander peoples without existing CVD: CVD risk factor screening should commence from the age of 18 years at the latest, including for blood glucose level or glycated haemoglobin, estimated glomerular filtration rate, serum lipids, urine albumin to creatinine ratio, and other risk factors such as blood pressure, history of familial hypercholesterolaemia, and smoking status. Individuals aged 18-29 years with the following clinical conditions are automatically conferred high CVD risk: ▶type 2 diabetes and microalbuminuria; ▶moderate to severe chronic kidney disease; ▶systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg; ▶familial hypercholesterolaemia; or ▶serum total cholesterol > 7.5 mmol/L. Assessment using the National Vascular Disease Prevention Alliance absolute CVD risk algorithm should commence from the age of 30 years at the latest - consider upward adjustment of calculated CVD risk score, accounting for local guideline use, risk factor and CVD epidemiology, and clinical discretion. Assessment should occur as part of an annual health check or opportunistically. Subsequent review should be conducted according to level of risk. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: From age 18 years (at the latest), Aboriginal and Torres Strait Islander adults should undergo CVD risk factor screening, and from age 30 years (at the latest), they should undergo absolute CVD risk assessment using the NVDPA risk algorithm.

'We can work together, talk together': an Aboriginal Health Care Home.

Objective The aim of this study was to identify an Aboriginal community's aspirations for health service improvement during implementation of the Commonwealth's Health Care Homes (HCH) reform. Methods This study was a qualitative study consisting of Aboriginal-controlled phenomenological enquiry in a large Aboriginal community in north-central Arnhem Land. Results A representative sample of 60 Aboriginal health service users identified shortcomings in their current experience of primary health care, including low cultural security. These shortcomings reduced access to care. Participants described several ways that care could be reorientated to match their needs during HCH implementation. Principally, patients voiced the need for: (1) restructuring care teams to foster culturally secure relationship-based care; and (2) reorientating the Aboriginal Health Practitioner role from acute care to strength-based competencies as the focal point of care continuity: self-management support, care coordination and navigation, health coaching and cultural mentorship for non-Aboriginal staff. Conclusions For HCH to be successful, service providers need to engage with service users to identify and implement patient-centred strategies to improve access, acceptability and patient activation. What is known about the topic? Success of the Commonwealth's HCH reform is contingent on improving care access and patient activation to better manage chronic conditions What does this paper add? This is the first opportunity that this Aboriginal community has had to articulate their aspirations for high quality healthcare. Beyond the strong alignment with the HCH building blocks, their care preferences posit practical and achievable workforce and delivery system reforms that may improve primary health care in other remote Aboriginal communities. What are the implications for practitioners? The long-term success of the HCH reform will require iterative engagement with service users to identify and implement patient-centred strategies to improve access and acceptability of care. Service model alignment with patient care preferences will improve patient activation and is particularly important when working with vulnerable populations.

Electric Single-Molecule Hybridization Detector for Short DNA Fragments.

By combining DNA nanotechnology and high-bandwidth single-molecule detection in nanopipets, we demonstrate an electric, label-free hybridization sensor for short DNA sequences (<100 nucleotides). Such short fragments are known to occur as circulating cell-free DNA in various bodily fluids, such as blood plasma and saliva, and have been identified as disease markers for cancer and infectious diseases. To this end, we use as a model system an 88-mer target from the RV1910c gene in Mycobacterium tuberculosis, which is associated with antibiotic (isoniazid) resistance in TB. Upon binding to short probes attached to long carrier DNA, we show that resistive-pulse sensing in nanopipets is capable of identifying rather subtle structural differences, such as the hybridization state of the probes, in a statistically robust manner. With significant potential toward multiplexing and high-throughput analysis, our study points toward a new, single-molecule DNA-assay technology that is fast, easy to use, and compatible with point-of-care environments.

Real World Evidence: A Quantitative and Qualitative Glance at Participant Feedback from a Free-Response Survey Investigating Experiences of a Structured Exercise Intervention for Men with Prostate Cancer.

AIM: To explore patient experiences of a structured exercise intervention for men with prostate cancer (PCa). SAMPLE: 41 men with either localised or advanced PCa who had been referred for a structured exercise programme by their physician and then subsequently consented to a telephone survey. METHOD: Participants underwent a 10-week supervised exercise programme within a large cancer centre hospital consisting of 8 sessions. They then completed a short multiple choice telephone survey, elaborating on their responses where appropriate. Views expressed by participants were analysed using an affinity diagram and common themes were identified. RESULTS: Feedback from our telephone surveys was consistently positive and suggests that the structured exercise intervention provides exercise confidence, motivation to exercise, and social support and promotes positive health behaviour change in the context of exercise. Individual differences arose amongst participants in their perceived utility of the intervention, with 73.3% expressing a preference for structured exercise classes and 19.5% expressing a preference for exercising independently. CONCLUSION: Design of a structured exercise intervention for patients with PCa should embrace the positive aspects outlined here but consider patients' individual differences. Ongoing feedback from patients should be utilised alongside traditional study designs to inform intervention design in this area.

The fate of verocytotoxigenic Escherichia coli C600φ3538(Δvtx2 ::cat) and its vtx2 prophage during grass silage preparation.

AIMS: Silage is grass, preserved by fermentation and used as winter feed for cattle. The impact of a range of current grass silage preparation practices on the survival of Escherichia coli C600φ3538(Δvtx2 ::cat) and on the induction, release and infectivity of free phage were investigated. METHODS AND RESULTS: Wilted and fresh grass samples, from plots with and without slurry application, were ensiled with or without formic acid. Each treatment combination was inoculated with approximately 6 log10 CFU per g E. coli C600φ3538(Δvtx2 ::cat) (donor strain) and E. coli C600::kanamycinR (recipient strain) in test-tube model silos and incubated in the dark at 15°C. The physico-chemical (pH, ammonia, ethanol, lactic acid and volatile fatty acids) and microbiological (total viable counts, TVC, total Enterobacteriaceae counts, TEC, E. coli counts, ECC and lactic acid bacteria, LAB) properties of each fermentation were monitored throughout the experiment as were the concentrations of E. coli C600φ3538(Δvtx2 ::cat), E. coli C600::kanamycinR , free phage and transductants, using culture and PCR-based methods. Over the course of the experiment the pH of the grass samples typically decreased by 2 pH units. TVC, TEC and ECC decreased by up to 2·3, 6·4 and 6·2 log10 CFU per g, respectively, while the LAB counts remained relatively stable at 5·2-7·1 log10 CFU per g. Both donor and recipient strains decreased by approximately 5 log10 CFU per g. Free phages were detected in all treatments and transductants were detected and confirmed by PCR in the silo containing wilted grass, pretreated with slurry and ensiled without formic acid. CONCLUSIONS: Verocytotoxigenic E. coli may survive the ensiling process and the conditions encountered are sufficient to induce vtx2 bacteriophage leading to low levels of phage-mediated vtx2 gene transfer. SIGNIFICANCE AND IMPACT OF THE STUDY: These studies suggest that the ensiling of grass may create an environment which facilitates the emergence of new verocytotoxigenic E. coli.

Survival studies of a temperate and lytic bacteriophage in bovine faeces and slurry.

AIMS: Cattle are the main reservoir of verocytotoxigenic Escherichia coli (VTEC), food-borne pathogens that express verocytotoxins (vtx) encoded by temperate bacteriophage. Bovine faeces and unturned manure heaps can support the survival of VTEC and may propagate and transmit VTEC. This study investigated the survival of a vtx2 bacteriophage, φ24B ::Kan, in bovine faeces and slurry. The survival of an anti-Escherichia coli O157:H7 lytic bacteriophage, e11/2, was examined in the same matrices, as a possible bio-control option for VTEC. METHODS AND RESULTS: Samples were inoculated with φ24B ::Kan and/or e11/2 bacteriophage at a concentration of 7-8 log10  PFU g(-1)  (faeces) or ml(-1) (slurry), stored at 4 and 14°C and examined every 2 days for 36 days. The ability of φ24B ::Kan to transduce E. coli cells was examined. Moreover, E. coli concentrations in the faeces and slurry were monitored throughout the experiment as were the pH and aw (faeces only). Both bacteriophages survived well in faeces and slurry. In addition, φ24B ::Kan was able to form lysogens. CONCLUSIONS: φ24B ::Kan and e11/2 phage can survive and remain infective in bovine faeces and slurry for at least 30 days under representative Irish temperatures. SIGNIFICANCE AND IMPACT OF THE STUDY: Bovine faeces and slurry may act as a reservoir for vtx bacteriophages. The survival of the anti-O157 phage suggests it may be a suitable bio-control option in these matrices.

The Survival of a Temperate vtx Bacteriophage and an Anti-Verocytotoxigenic Escherichia coli O157 Lytic Phage in Water and Soil Samples.

Verocytotoxigenic (vtx) Escherichia coli (VTEC) are zoonotic foodborne pathogens with the vtx operon encoded by lambdoid bacteriophage (phage). Despite much research on the host bacteria, similar data on the persistence of verocytotoxin converting phage and the ecological niches where transduction occurs are lacking and novel VTEC of important public health significance, have and continue to emerge. This study investigated the survival of a temperate vtx bacteriophage (24B ::kanamycinR ) in water (raw farm, pasteurized farm, laboratory tap and autoclaved purified water) and soil (sandy loam and loam soil). It also examined the persistence of an anti-VTEC lytic phage (e11/2) in the same matrices as this may be one option for controlling the emergence of novel VTEC, especially in farm ecological niches where other control options, such as chemical, heat or high pressure treatments, are not feasible. Samples inoculated with 24B ::kanamycinR and e11/2 bacteriophage (8 log10 pfu/ml or pfu/g) separately were incubated at 4°C and 14°C, representative Irish Winter and Summer temperatures, respectively, and tested every 2 days for 40 days. The transduction of 24B ::kanamycinR was also continuously assessed. Both phages survived with reductions observed, regardless of matrix or storage temperature. Moreover, 24B ::kanamycinR was able to transduce its host E. coli strain. It was therefore concluded that aquatic and soil environments on farms may serve as a vtx phage reservoir and transduction point but anti-VTEC phage is a possible biocontrol option.

Early Mucosal Healing with Exclusive Enteral Nutrition is Associated with Improved Outcomes in Newly Diagnosed Children with Luminal Crohn's disease.

BACKGROUND: Exclusive Enteral Nutrition (EEN) induction in children with luminal Crohn's disease (CD) gives early mucosal healing (MH), but the long-term benefits of EEN-induced MH are just emerging. AIMS & METHODS: We prospectively followed an Australian cohort of newly diagnosed children with predominantly luminal CD who completed at least six weeks EEN and with paired clinical Pediatric Crohn's Disease Activity Index (PCDAI), biochemical (C-reactive protein; CRP) and endoscopic assessment at diagnosis and post EEN. All commenced immunomodulators (IMs) early (<3 months from diagnosis) and had a minimum of 1 year follow-up. Complete MH was a simple endoscopic score for Crohn's disease (SES-CD) of 0, and SES-CD≥1 was ascribed to active endoscopic disease (aED) and further divided into near complete MH (SES 1-3), mild active disease (SES-CD 4-10) and moderate to severe disease (SES-CD>10). The primary outcome was long-term supervised sustained remission (SR) on IMs alone without need for corticosteroids, infliximab (IFX) or surgery. RESULTS: A total of 54 eligible children (33 males) completing EEN induction were analysed. The median duration between pre and post EEN assessments was 60.5 days [interquartile range (IQR), 56-69.5]. Post EEN: clinical remission (PCDAI < 10) was observed in 45/54 (83%), and biochemical remission (PCDAI < 10 and CRP < 5 mg/dl) was observed in 39/54 (72%). Complete MH was observed in 18/54 (33%), near complete in 10/54(19%). SR was superior in those with complete MH vs. aED; 13/18, (72%) vs. 10/36 (28%), p = 0.003 at 1 year, 8/16, (50%) vs. 3/24, (8%), p = 0.008 at 2 years and (8/16, (50%) vs. 1/19, (6%), p = 0.005) at 3 years. Near-complete MH did not lead to superior SR. CONCLUSIONS: Only complete MH post EEN induction predicts more favourable SR for up to 3 years.

Wilate use in 47 children with von Willebrand disease: the North London paediatric haemophilia network experience.

Children with von Willebrand disease (VWD) in whom DDAVP is ineffective or contraindicated require treatment with a coagulation factor concentrate containing von Willebrand factor (VWF) and factor VIII (FVIII). The aim of this study was to monitor the safety, efficacy and tolerability of Wilate(®) (a VWF:FVIII concentrate with a 1:1 ratio) used across the North London Paediatric Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years) with type 1 (n = 28), type 2 (n = 7), type 3 (n = 10) and acquired VWS (n = 2) have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU Wilate(®). Analysis of dose and frequency of treatment show expected responses to treatment with mean doses of 55, 50 and 50 IU kg(-1) for bleeds, surgery and prophylaxis respectively. Most bleeds responded to a single treatment. Surgical procedures were covered with clinician approved dosing schedules with 95% (39/41) reported as having excellent or good efficacy. There was no accumulation of FVIII or VWF and no thromboembolic events. This case series confirms the efficacy, safety and tolerability of Wilate(®) in neonates, children and adolescents when used on-demand, prophylactically and in the surgical setting.

Stretchable liquid-crystal blue-phase gels.

Liquid-crystalline polymers are materials of considerable scientific interest and technological value. An important subset of these materials exhibit rubber-like elasticity, combining the optical properties of liquid crystals with the mechanical properties of rubber. Moreover, they exhibit behaviour not seen in either type of material independently, and many of their properties depend crucially on the particular mesophase employed. Such stretchable liquid-crystalline polymers have previously been demonstrated in the nematic, chiral-nematic, and smectic mesophases. Here, we report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that remains electro-optically switchable under a moderate applied voltage, and whose optical properties can be manipulated by an applied strain. We also find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and possibilities for low-voltage electro-optic devices.

Attenuation of mania-like behavior in Na(+),K(+)-ATPase α3 mutant mice by prospective therapies for bipolar disorder: melatonin and exercise.

Bipolar disorder is a neuropsychiatric disease characterized by states of mania with or without depression. Pharmacological treatments can be inadequate at regulating mood for many individuals. Melatonin therapy and aerobic exercise are independent prospective therapies for bipolar disorder that have shown potential as mood stabilizers in humans. Myshkin mice (Myk/+) carry a heterozygous missense mutation in the neuronal Na(+),K(+)-ATPase α3 and model mania-related symptoms of bipolar disorder including increased activity, risk-taking behavior and reductions in sleep. One cohort of Myk/+ and wild-type littermates (+/+) was treated with melatonin and a separate cohort was treated with voluntary exercise. Mania-related behavior was assessed in both cohorts. The effect of melatonin on sleep and the effect of exercise on brain-derived neurotrophic factor (BDNF) expression in the hippocampus were assayed. Melatonin and voluntary wheel running were both effective at reducing mania-related behavior in Myk/+ but did not affect behavior in +/+. Melatonin increased sleep in Myk/+ and did not change sleep in +/+. Myk/+ showed higher baseline levels of BDNF protein in the hippocampus than +/+. Exercise increased BDNF protein in +/+ hippocampus, while it did not significantly affect BDNF levels in Myk/+ hippocampus. These findings support initial studies in humans indicating that melatonin and exercise are useful independent adjunct therapies for bipolar disorder. Their effects on mood regulation should be further examined in randomized clinical trials. Our results also suggest that hippocampal BDNF may not mediate the effects of exercise on mania-related behavior in the Myk/+ model of mania.

Functional outcomes following endoscopic laser cricopharyngeal myotomy with mucosal repair.

Endoscopic laser cricopharyngeal myotomy is an effective treatment for cricopharyngeal dysfunction, but concern remains over the risk of serious complications following the procedure. Some authors have therefore considered endoscopic laser cricopharyngeal myotomy with mucosal repair; however, outcome data for the procedure is scanty. This study aims to identify functional outcomes in a series of patients following endoscopic laser cricopharyngeal myotomy with mucosal repair. Endoscopic laser cricopharyngeal myotomy with mucosal repair was performed on 38 subjects in two centres over a period of 33 months. Pre- and post-operative outcomes were evaluated in 32 subjects using the Sydney Swallow Questionnaire and Reflux Symptom Index. An improvement in swallowing scores was seen in 30 subjects (94%, p < 0.001). The Reflux Symptom Index improved 28 subjects (88%, p < 0.001). Mean procedure time was 58 min. One subject (2.6%) developed mediastinitis following surgery, and four experienced (12.5%) a recurrence of dysphagic symptoms. Endoscopic laser cricopharyngeal myotomy with mucosal repair is an effective treatment for cricopharyngeal dysfunction. The complication rate observed in this study was comparable or lower than previously reported studies into endoscopic laser cricopharyngeal myotomy without mucosal repair. Larger studies may be required to determine the additional benefit of mucosal repair over endoscopic laser cricopharyngeal myotomy alone.