COHESION: a core outcome set for the treatment of neonatal encephalopathy.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment. CONCLUSION: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS. IMPACT: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy.

Rapid immunohistological measurement of tyrosine hydroxylase in rat midbrain by near-infrared instrument-based detection.

We present a robust, fresh-frozen approach to immunohistochemistry (IHC), without committing the tissue to IHC via fixation and cryopreservation while maintaining long-term storage, using LiCor-based infrared (IR) quantification for sensitive assessment of TH in immunoreacted midbrain sections for quantitative comparison across studies. In fresh-frozen tissue stored up to 1 year prior to IHC reaction, we found our method to be highly sensitive to rotenone treatment in 3-month-old Sprague-Dawley rats, and correlated with a significant decline in rotarod latency-to-fall measurement by approximately 2.5 fold. The measured midbrain region revealed a 31 % lower TH signal when compared to control (p < 0.01 by t test, n = 5). Bivariate analysis of integrated TH counts versus rotarod latency-to-fall indicates a positive slope and modest but significant correlation of R2 = 0.68 (p < 0.05, n = 10). These results indicate this rapid, instrument-based quantification method by IR detection successfully quantifies TH levels in rat brain tissue, while taking only 5 days from euthanasia to data output. This approach also allows for the identification of multiple targets by IHC with the simultaneous performance of downstream molecular analysis within the same animal tissue, allowing for the use of fewer animals per study.

Trends in the Detection, Management and 30-Day Outcomes of Spontaneous Coronary Artery Dissection: A Six-Year, New Zealand Centre Experience.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important but under-recognised cause of acute coronary syndrome (ACS), particularly in younger women. We assessed trends in the detection, management and outcomes of all patients with SCAD over 6 consecutive years. METHODS: All patients with first diagnosis of SCAD at Christchurch Public Hospital, New Zealand, between January 2014 and January 2020 were included. Patient management and outcomes were determined by retrospective review of medical records. SCAD presentations were compared to total ACS presentations, obtained from a national ACS (ANZACS-QI) database. RESULTS: We identified 113 patients with angiographic diagnosis of SCAD. Median age was 54 years (88% female). The detection of SCAD increased over the period, both as a total number (Kendall's τ 0.87, p=0.015) and as a proportion of all ACS (p value for trend <0.0001). In 2019, SCAD represented 2.4% of all ACS and 18% of ACS in females aged less than 60 years. The most common presentation was non-ST elevation myocardial infarction (NSTEMI) in 72%; and, there was an increase in NSTEMI compared with STEMI over the period (p=0.023). Initial strategy of percutaneous coronary intervention (PCI) was undertaken in 12% of patients, with a significant trend towards a more conservative approach over the study period (p=0.019). The rate of 30-day major adverse cardiovascular events (MACE) was 8.8% overall, and significantly reduced over the study period to 3% in 2019 (p value for trend, 0.006). CONCLUSIONS: The detection of SCAD has increased and is a particularly important cause of ACS in younger women. This increase has been largely driven by an increasing number of NSTEMI patients diagnosed with SCAD, associated with a significant improvement in 30-day MACE.

Incorporating hydrology into climate suitability models changes projections of malaria transmission in Africa.

Continental-scale models of malaria climate suitability typically couple well-established temperature-response models with basic estimates of vector habitat availability using rainfall as a proxy. Here we show that across continental Africa, the estimated geographic range of climatic suitability for malaria transmission is more sensitive to the precipitation threshold than the thermal response curve applied. To address this problem we use downscaled daily climate predictions from seven GCMs to run a continental-scale hydrological model for a process-based representation of mosquito breeding habitat availability. A more complex pattern of malaria suitability emerges as water is routed through drainage networks and river corridors serve as year-round transmission foci. The estimated hydro-climatically suitable area for stable malaria transmission is smaller than previous models suggest and shows only a very small increase in state-of-the-art future climate scenarios. However, bigger geographical shifts are observed than with most rainfall threshold models and the pattern of that shift is very different when using a hydrological model to estimate surface water availability for vector breeding.

Prevalence of the sternalis muscle in a sample of routinely dissected human cadavers.

PURPOSE: Sternalis muscle is an uncommon muscle head attaching between the sternoclavicular joint superiorly and the costal cartilage near the xiphoid process. METHODS: In this study, 36 cadavers (18 male, 18 female) were obtained through the Anatomical Board of the State of Florida and complete, routine musculoskeletal dissection was performed while adhering to all relevant laws and practices. RESULTS: Two examples of the sternalis muscle belly (5%) were identified, one in a black male and one a white female. The sternalis muscles were bilateral in both cases and each was formed of a single muscle belly. The superior attachments were continuous with the sternal attachment of sternocleidomastoid, and the inferior attachments connected to the costal cartilages. Sternalis did not cross the midline and the T2-T5 anterior intercostal neurovasculature associated closely with the muscle belly. In the female, a well-formed unilateral chondrocoracoideus muscle was apparent with a branch from the medial pectoral nerve closely associated on the deep surface. No other abnormalities in the chest, axilla, or brachial plexus were noted on either cadaver, and the pectoralis major and minor muscles were normally formed and innervated in both cases. CONCLUSION: This study supports other evidence in the literature that indicates the sternalis muscle has an average prevalence in the population of approximately 5%, and it appears across race and sex. Education about this structure is important for radiologists, surgeons, and doctors of physical therapy that may be involved in treatment and post-surgical rehabilitation of this region.

Spatial and temporal immunoreactivity in the rat brain using an affinity purified polyclonal antibody to DNSP-11.

DNSP-11 antibody signal was investigated in perfusion fixated Fischer 344 rat brains by immunohistochemistry with a custom, affinity purified polyclonal antibody. The DNSP-11-antibody signal was differentially localized from the mature GDNF protein both spatially and temporally. In the mesencephalon of post-natal day 10 animals, when GDNF is maximally expressed, DNSP-11 and GDNF antibody immunoreactivities co-localize extensively but not exclusively. In adult 3-month-old animals, GDNF expression is markedly reduced while the DNSP-11 signal remains intense. DNSP-11-antibody signal was present in the 3-month-old rat brain with signal in the substantia nigra, ventral tegmental area, dentate gyrus of the hippocampus, with the strongest signal observed in the locus ceruleus where GDNF is not expressed. While amino acid sequence homologues such as NPY and Tfg do exist, binding patterns reported in the literature of do not recapitulate the immunoreactive patterns observed for the DNSP-11-antibody signal.

Report of a non-looped variant of ansa cervicalis with omohyoid innervation from accessory nerve branch and omohyoid attachment to mastoid process.

INTRODUCTION: A variant of the innervation of the infrahyoid neck musculature is reported in which the typical looped ansa cervicalis structure is absent. In this variant, the infrahyoid muscles (sternohyoid, sternothyroid omohyoid and thyrohyoid) were innervated by a presumptive superior root of "ansa cervicalis" traveling with vagus nerve (CN X) and not branching from hypoglossal nerve (CN XII). The omohyoid muscle, typically innervated by the inferior root of ansa cervicalis, is instead innervated by nerve fibers branching from the accessory nerve (CN XI). This formation created a non-looping variant of ansa cervicalis. Furthermore, the omohyoid muscle did not attach to the hyoid bone but instead attached to the mastoid process of the temporal bone by merging its fibers superiorly and posteriorly with the clavicular portion of the sternocleidomastoid muscle, creating a "sternocleidoomomastoid" muscle innervated by a branch of accessory nerve. MATERIALS AND METHODS: This variation was found in one black male cadaver from a cohort of 25 male and female cadavers. RESULTS: Only one variation of ansa cervicalis was observed. CONCLUSIONS: As neck dissections and surgical procedures of this region are performed for a variety of conditions-including coronary artery bypass grafting and metastatic neck disease-variations of this type are of broad clinical surgical importance.

Psychopathy to Altruism: Neurobiology of the Selfish-Selfless Spectrum.

The age-old philosophical, biological, and social debate over the basic nature of humans as being "universally selfish" or "universally good" continues today highlighting sharply divergent views of natural social order. Here we analyze advances in biology, genetics and neuroscience increasing our understanding of the evolution, features and neurocircuitry of the human brain underlying behavior in the selfish-selfless spectrum. First, we examine evolutionary pressures for selection of altruistic traits in species with protracted periods of dependence on parents and communities for subsistence and acquisition of learned behaviors. Evidence supporting the concept that altruistic potential is a common feature in human populations is developed. To go into greater depth in assessing critical features of the social brain, the two extremes of selfish-selfless behavior, callous unemotional psychopaths and zealous altruists who take extreme measures to help others, are compared on behavioral traits, structural/functional neural features, and the relative contributions of genetic inheritance versus acquired cognitive learning to their mindsets. Evidence from population groups ranging from newborns, adopted children, incarcerated juveniles, twins and mindfulness meditators point to the important role of neuroplasticity and the dopaminergic reward systems in forming and reforming neural circuitry in response to personal experience and cultural influences in determining behavior in the selfish-selfless spectrum. The underlying neural circuitry differs between psychopaths and altruists with emotional processing being profoundly muted in psychopaths and significantly enhanced in altruists. But both groups are characterized by the reward system of the brain shaping behavior. Instead of rigid assignment of human nature as being "universally selfish" or "universally good," both characterizations are partial truths based on the segments of the selfish-selfless spectrum being examined. In addition, individuals and populations can shift in the behavioral spectrum in response to cognitive therapy and social and cultural experience, and approaches such as mindfulness training for introspection and reward-activating compassion are entering the mainstream of clinical care for managing pain, depression, and stress.

Gridded birth and pregnancy datasets for Africa, Latin America and the Caribbean.

Understanding the fine scale spatial distribution of births and pregnancies is crucial for informing planning decisions related to public health. This is especially important in lower income countries where infectious disease is a major concern for pregnant women and new-borns, as highlighted by the recent Zika virus epidemic. Despite this, the spatial detail of basic data on the numbers and distribution of births and pregnancies is often of a coarse resolution and difficult to obtain, with no co-ordination between countries and organisations to create one consistent set of subnational estimates. To begin to address this issue, under the framework of the WorldPop program, an open access archive of high resolution gridded birth and pregnancy distribution datasets for all African, Latin America and Caribbean countries has been created. Datasets were produced using the most recent and finest level census and official population estimate data available and are at a resolution of 30 arc seconds (approximately 1 km at the equator). All products are available through WorldPop.

Semi-Automatic Electronic Stent Register: a novel approach to preventing ureteric stents lost to follow up.

BACKGROUND: Ureteric stents are indispensable tools in modern urology; however, the risk of them not being followed-up once inserted poses medical and medico-legal risks. Stent registers are a common solution to mitigate this risk; however, manual registers are logistically challenging, especially for busy units. METHODS: Western Sydney Local Health District developed a novel Semi-Automatic Electronic Stent Register (SAESR) utilizing billing information to track stent insertions. To determine the utility of this system, an audit was conducted comparing the 6 months before the introduction of the register to the first 6 months of the register. RESULTS: In the first 6 months of the register, 457 stents were inserted. At the time of writing, two of these are severely delayed for removal, representing a rate of 0.4%. In the 6 months immediately preceding the introduction of the register, 497 stents were inserted, and six were either missed completely or severely delayed in their removal, representing a rate of 1.2%. A non-inferiority analysis found this to be no worse than the results achieved before the introduction of the register. CONCLUSION: The SAESR allowed us to improve upon our better than expected rate of stents lost to follow up or severely delayed. We demonstrated non-inferiority in the rate of lost or severely delayed stents, and a number of other advantages including savings in personnel costs. The semi-automatic register represents an effective way of reducing the risk associated with a common urological procedure. We believe that this methodology could be implemented elsewhere.

Life after prostate cancer diagnosis: protocol for a UK-wide patient-reported outcomes study.

BACKGROUND: Prostate cancer and its treatment may impact physically, psychologically and socially; affecting the health-related quality of life of men and their partners/spouses. The Life After Prostate Cancer Diagnosis (LAPCD) study is a UK-wide patient-reported outcomes study which will generate information to improve the health and well-being of men with prostate cancer. METHODS AND ANALYSIS: Postal surveys will be sent to prostate cancer survivors (18-42 months postdiagnosis) in all 4 UK countries (n=∼70 000). Eligible men will be identified and/or verified through cancer registration systems. Men will be surveyed twice, 12 months apart, to explore changes in outcomes over time. Second, separate cohorts will be surveyed once and the design will include evaluation of the acceptability of online survey tools. A comprehensive patient-reported outcome measure has been developed using generic and specific instruments with proven psychometric properties and relevance in national and international studies. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). To ensure detailed understanding of issues of importance, qualitative interviews will be undertaken with a sample of men who complete the survey across the UK (n=∼150) along with a small number of partners/spouses (n=∼30). ETHICS AND DISSEMINATION: The study has received the following approvals: Newcastle and North Tyneside 1 Research Ethics Committee (15/NE/0036), Health Research Authority Confidentiality Advisory Group (15/CAG/0110), NHS Scotland Public Benefit and Privacy Panel (0516-0364), Office of Research Ethics Northern Ireland (16/NI/0073) and NHS R&D approval from Wales, Scotland and Northern Ireland. Using traditional and innovative methods, the results will be made available to men and their partners/spouses, the funders, the NHS, social care, voluntary sector organisations and other researchers.

Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease.

BACKGROUND: To circumvent the challenges associated with delivering large compounds directly to the brain for the treatment of Parkinson's disease (PD), non-invasive procedures utilizing smaller molecules with protective and/or restorative actions on dopaminergic neurons are needed. NEW METHOD: We developed a methodology for evaluating the effects of a synthetic neuroactive peptide, DNSP-11, on the nigrostriatal system using repeated intranasal delivery in both normal and a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. RESULTS: Normal rats repeatedly administered varying doses of DNSP-11 intranasally for 3 weeks exhibited a significant increase in dopamine (DA) turnover in both the striatum and substantia nigra (SN) at 300µg, suggestive of a stimulative effect of the dopaminergic system. Additionally, a protective effect was observed following repeated intranasal administration in 6-OHDA lesioned rats, as suggested by: a significant decrease in d-amphetamine-induced rotation at 2 weeks; a decrease in DA turnover in the lesioned striatum; and an increased sparing of tyrosine hydroxylase (TH) positive (+) neurons in a specific sub-region of the lesioned substantia nigra pars compacta (SNpc). Finally, tracer studies showed (125)I-DNSP-11 distributed diffusely throughout the brain, including the striatum and SN, as quickly as 30min after a single intranasal dose. COMPARISON WITH EXISTING METHODS: The results of bilateral intranasal administration of DNSP-11 are compared to our unilateral single infusion studies to the brain in rats. CONCLUSIONS: These studies support that DNSP-11 can be delivered intranasally and maintain its neuroactive properties in both normal rats and in a unilateral 6-OHDA rat model of PD.