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.

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.

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.

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.

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.

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.

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.

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.

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.

The extent of lateral lymph node dissection in differentiated thyroid cancer in the N+ neck.

The management of the lateral neck in metastatic differentiated thyroid cancer (DTC) varies widely. Most groups advocate dissection of nodal levels II-IV but many perform a more extensive dissection. We aimed to asses whether there was any evidence for a modified radical neck dissection over a selective neck dissection by looking at the extent to which DTC metastases to levels I and V. We performed a review of the current literature including adult and paediatric patients who underwent a lateral neck dissection for metastatic DTC. The primary endpoint was histological confirmation of metastases in nodal levels I and V. 650 abstracts were identified and reviewed. 23 papers were included in the study. The incidence of level V metastases during routine level V dissection in patients with DTC is 20 % and the incidence of level I metastases during routine level I dissection in patients with DTC is 8 %. Histologically proven metastases were found in 22.5 % of level V neck dissection of which 2.5 % were pre-operatively suspected of metastases. 20 % had histologically proven metastases to level I of which 12 % were pre-operatively suspected of metastases. Our study has shown a 20 % incidence of level V metastases in the N+ neck suggesting that level V should be part of a planned neck dissection. Evidence is lacking for routine dissection of level I. A future prospective study is required to asses the question of risk factors for lateral nodal metastases, recurrence and survival.

An evidence based review of the assessment and management of penetrating neck trauma.

BACKGROUND: Although relatively uncommon, penetrating neck trauma has the potential for serious morbidity and an estimated mortality of up to 6%. The assessment and management of patients who have sustained a penetrating neck injury has historically been an issue surrounded by significant controversy. OBJECTIVES OF REVIEW: To assess recent evidence relating to the assessment and management of penetrating neck trauma, highlighting areas of controversy with an overall aim of formulating clinical guidelines according to a care pathway format. TYPE OF REVIEW: Structured, non-systematic review of recent medical literature. SEARCH STRATEGY: An electronic literature search was performed in May 2011. The Medline database was searched using the Medical Subject Headings terms 'neck injuries' and 'wounds, penetrating' in conjunction with the terms 'assessment' or 'management'. Embase was searched with the terms 'penetrating trauma' and 'neck injury', also in conjunction with the terms 'assessment' and 'management'. Results were limited to articles published in English from 1990 to the present day. EVALUATION METHOD: Abstracts were reviewed by the first three authors to select full-text articles for further critical appraisal. The references and citation links of these articles were hand-searched to identify further articles of relevance. RESULTS: 147 relevant articles were identified by the electronic literature search, comprising case series, case reports and reviews. 33 were initially selected for further evaluation. CONCLUSIONS: Although controversy continues to surround the management of penetrating neck trauma, the role of selective non-operative management and the utility of CT angiography to investigate potential vascular injuries appears to be increasingly accepted.

A promoting early presentation intervention increases breast cancer awareness in older women after 2 years: a randomised controlled trial.

BACKGROUND: We have developed the Promoting Early Presentation (PEP) Intervention to equip older women with the knowledge, skills, confidence and motivation to present promptly with breast symptoms, and thereby improve survival from breast cancer. The PEP Intervention consists of a 10-min interaction between a radiographer and an older woman, supported by a booklet. Our previous report showed that at 1 year, the PEP intervention increased the proportion who were breast cancer aware compared with usual care. METHODS: We randomised 867 women aged 67-70 years attending for their final routine appointment on the National Health Service Breast Screening Programme to receive the PEP Intervention, a booklet alone or usual care. The primary outcome was breast cancer awareness measured using a validated questionnaire asking about knowledge of breast cancer symptoms, knowledge that the risk of breast cancer increases with age and breast checking behaviour. RESULTS: At 2 years, the PEP Intervention increased the proportion who were breast cancer aware compared with usual care (21 vs 6%; odds ratio 8.1, 95% confidence interval 2.7-25.0). CONCLUSIONS: The uniquely large and sustained effect of the PEP Intervention on breast cancer awareness increases the likelihood that a woman will present promptly should she develop breast cancer symptoms up to many years later.

PDGF-D, a new protease-activated growth factor.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer, fibrotic diseases and arteriosclerosis. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha, whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

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.

Application of quantitative reverse-transcription PCR (qRT-PCR) for the determination of the total viable count (TVC) on meat samples.

AIM: To apply a quantitative reverse-transcription PCR (qRT-PCR) method to determine the total viable count (TVC) on meat samples. METHODS AND RESULTS: Using two sets of primers to target the ribonuclease-P (RNase P) RNA transcripts of Gram-positive and Gram-negative bacteria, standard curves were generated using the LightCycler 2.0 instrument (Roche Diagnostics). RNA standards were extracted from known cell numbers and subsequently converted to cDNA for the construction of standard curves for quantification of the TVC of beef carcass swabs (n = 60) and beef (n = 30), chicken (n = 50) and pork (n = 49) pieces. A high correlation between the standard plate count method and the qRT-PCR was observed for beef swabs (R(2) = 0·93) and beef pieces (R(2) = 0·82). The correlation coefficient for chicken pieces and pork pieces were R(2) = 0·34 and 0·55, respectively. Using beef pieces (n = 13), an interlaboratory study was conducted and each participating laboratory (n = 3) found a reasonable degree of agreement between the cultural method and the PCR method. CONCLUSIONS: The qRT-PCR assay used in this study can enumerate the total bacteria on beef samples with a high degree of accuracy. SIGNIFICANCE AND IMPACT OF THE STUDY: The qRT-PCR method may have the potential to be applied to various sample types as an alternative rapid method for determining TVCs; however, further validation would be required.

Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers.

BACKGROUND: It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation. METHODS: We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these. RESULTS: Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, 'misdiagnosis' occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results. CONCLUSION: Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately.