Evolution of brain MRI lesions in paediatric myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and its relevance to disease course.

BACKGROUND: Lesion resolution is often observed in children with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and asymptomatic lesions are less commonly reported in MOGAD than in multiple sclerosis (MS). OBJECTIVE: We aimed to evaluate brain MRI changes over time in paediatric MOGAD. METHODS: Retrospective study in eight UK paediatric neuroscience centres. Acute brain MRI and available follow-up MRIs were reviewed. Predictors for lesion dynamic were evaluated using multivariable regression and Kaplan-Meier survival analyses were used to predict risk of relapse, disability and MOG-Ab status. RESULTS: 200 children were included (MOGAD 97; MS 103). At first MRI post attack, new symptomatic and asymptomatic lesions were seen more often in MS versus MOGAD (52/103 vs 28/97; p=0.002 and 37/103 vs 11/97; p<0.001); 83% of patients with MOGAD showed at least one lesion's resolution at first follow-up scan, and 23% had normal MRI. Only 1 patient with MS had single lesion resolution; none had normal MRI. Disappearing lesions in MOGAD were seen in 40% after the second attack, 21% after third attack and none after the fourth attack.New lesions at first follow-up scan were associated with increased likelihood of relapse (p=0.02) and persistent MOG-Ab serostatus (p=0.0016) compared with those with no new lesions. Plasma exchange was associated with increased likelihood of lesion resolution (p=0.01). Longer time from symptom onset to steroids was associated with increased likelihood of new lesions; 50% increase at 20 days (p=0.01). CONCLUSIONS: These striking differences in lesion dynamics between MOGAD and MS suggest greater potential to repair. Early treatment with steroids and plasma exchange is associated with reduced likelihood of new lesions.

International consensus definitions for infection-triggered encephalopathy syndromes.

AIM: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES. METHOD: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes. RESULTS: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed. INTERPRETATION: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.

Electroconvulsive Therapy in Refractory and Super-Refractory Status Epilepticus in Adults: A Scoping Review.

BACKGROUND: Electroconvulsive therapy (ECT) has been suggested as a treatment option for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). OBJECTIVE: The objective of this scoping review was to conduct an extensive literature review on the role of ECT as a treatment option for RSE and SRSE. METHODS: We searched Ovid MEDLINE and Scopus for journal articles from database inception until February 2024. Articles were then selected based on predetermined inclusion and exclusion criteria. RESULTS: We identified five retrospective case series with 28 adult patients receiving ECT for RSE or SRSE. ECT was administered within 3-70 days (mean 20 days) after the development of SE, and the mean number of ECT courses ranged from 1 to 12 sessions for each patient. ECT was administered in fixed or titrated doses. A total of 20 out of 28 patients (71%) showed clinical improvement, with two (7%) having complete cessation of seizures. It is essential to note that given the lack of control, there could be overreporting of clinical improvement in these studies. 11 patients (39%) were reported as deceased due to causes that were not directly related to ECT treatment. Four patients (14%) reported adverse effects of ECT, including memory, concentration, and/or cognitive impairment. CONCLUSIONS: There are level-4 Oxford Centre for Evidence-Based Medicine evidence and low-level Grading of Recommendations Assessment Development and Education evidence that suggest ECT as a treatment option for RSE and SRSE. In light of the limitations of the existing evidence, clinicians should carefully consider individual patients' clinical contexts when deciding on the appropriateness of ECT as a treatment option. Further research, including prospective studies with controlled designs, is needed to elucidate the efficacy, safety, and optimal regime of ECT in the management of RSE and SRSE.

Plant-derived chelators and ionophores as potential therapeutics for metabolic diseases.

Transition metal dysregulation is associated with a host of pathologies, many of which are therapeutically targeted using chelators and ionophores. Chelators and ionophores are used as therapeutic metal-binding compounds which impart biological effects by sequestering or trafficking endogenous metal ions in an effort to restore homeostasis. Many current therapies take inspiration or derive directly from small molecules and peptides found in plants. This review focuses on plant-derived small molecule and peptide chelators and ionophores that can affect metabolic disease states. Understanding the coordination chemistry, bioavailability, and bioactivity of such molecules provides the tools to further research applications of plant-based chelators and ionophores.

A Qualitative Study of Aboriginal Peoples' Health Care Experiences With Chronic Obstructive Pulmonary Disease.

Aboriginal Australians experience a high prevalence of chronic obstructive pulmonary disease (COPD), with high rates of potentially preventable hospitalisations. However, little is known about Aboriginal peoples' experiences of living with COPD and how they navigate health care systems. This study used thematic analysis and Aboriginal methodology to explore Aboriginal peoples' lived experiences of COPD, their health care journey from receiving a diagnosis of COPD to the clinical management, and the impact of COPD on their daily lives. We conducted in-depth semi-structured interviews over a 6-month period with 18 Aboriginal adults diagnosed with COPD from four Aboriginal Community Controlled Health Services (ACCHS) in New South Wales, Australia. Reflexive thematic analysis was employed to ensure rigour. The findings revealed deeply personal and reflective stories shaped by historical, social, and cultural realities of Aboriginal peoples living with COPD. Four themes were identified characterising their experiences. Based on the findings, the following guidance is provided on future COPD care for Aboriginal peoples: Better alignment of existing COPD management with Aboriginal peoples' cultural contexts and perspectives to improve access to culturally safe care; Increased funding for ACCHS to enhance COPD management, such as early detection through case finding and access to ACCHS-led pulmonary rehabilitation; Engaging family members in COPD management and providing culturally centred COPD education that facilitates discussions and builds health literacy and self-management skills; Implementing health promotion initiatives to increase awareness and counteract fear and shame to improve early COPD detection.

Factors associated with outcomes of severe acute necrotizing encephalopathy: A multicentre experience in Malaysia.

This case series compared clinical variables and various combinations of immunotherapy received with outcomes of patients with severe acute necrotizing encephalopathy (ANE). We performed a retrospective review of clinical variables, immunotherapy received, and outcomes (based on the modified Rankin Scale) in Malaysia between February 2019 and January 2020. Twenty-seven children (12 male), aged 7 months to 14 years (mean 4 years) at diagnosis were included. Of these, 23 had an ANE severity score of 5 to 9 out of 9 (high risk). Eleven patients received tocilizumab (four in combination with methylprednisolone [MTP], seven with MTP + intravenous immunoglobulin [IVIG]) and 16 did not (two received MTP alone, 14 received MTP + IVIG). Nine died. Among the survivors, six had good outcomes (modified Rankin Score 0-2) at 6 months follow-up. All patients who received tocilizumab in combination with MTP + IVIG survived. Twenty children received first immunotherapy within 48 hours of admission. No significant association was found between the timing of first immunotherapy with outcomes. Those with brainstem dysfunction (p = 0.016) were observed to have poorer outcomes. This study showed a trend towards better survival when those with severe ANE were treated with tocilizumab in combination with MTP + IVIG. However, larger studies will be needed to determine the effect of this regime on the long-term outcomes.

Cognitive impairment and health-related quality of life amongst older Australians: evidence from a longitudinal investigation.

INTRODUCTION: Australia's population is steadily growing older, with older persons expected to make up over 20% of the population by 2066. Ageing is strongly associated with a significant drop in cognitive ability, ranging from mild cognitive impairment to severe cognitive impairment (dementia). This study examined the association between cognitive impairment and health-related quality of life (HRQoL) in older Australians. METHODS: Two waves of longitudinal data from the nationally representative Household, Income and Labour Dynamics in Australia (HILDA) survey were utilised, with the age cut-off for older Australians defined as above 50. The final analysis included 10,737 person-year observations from 6892 unique individuals between 2012 and 2016. This study utilised the Backwards Digit Span (BDS) test and Symbol Digit Modalities test (SDMT) to assess cognitive function. HRQoL was measured using the physical and mental component summary scores of the SF-36 Health Survey (PCS and MCS). Additionally, HRQoL was measured using health state utility values (SF-6D score). A longitudinal random-effects GLS regression model was used to analyse the association between cognitive impairment and HRQoL. RESULTS: This study found that approximately 89% of Australian adults aged 50 or older had no cognitive impairment, 10.16% had moderate cognitive impairment, and 0.72% had severe cognitive impairment. This study also found that moderate and severe cognitive impairment were both negatively associated with HRQoL. Older Australians with moderate cognitive impairment scored worse on the PCS (ß = - 1.765, SE = 0.317), MCS (ß = - 1.612, SE = 0.326), and SF-6D (ß = - 0.024, SE = 0.004) than peers without cognitive impairment given other covariates reference categories remain constant. Older adults experiencing severe cognitive had lower PCS (ß = - 3.560, SE = 1.103), and SF-6D (ß = - 0.034, SE = 0.012) scores compared to their counterparts with no cognitive impairment given other covariates reference categories remain constant. CONCLUSION: We found evidence that HRQoL is negatively associated with cognitive impairment. Our findings will be beneficial for the future cost-effectiveness intervention targeted at reducing cognitive impairment since it provides information on the disutility associated with moderate and severe cognitive impairment.

A mixed methods study of Aboriginal health workers' and exercise physiologists' experiences of co-designing chronic lung disease 'yarning' education resources.

BACKGROUND: Despite the high incidence of chronic obstructive pulmonary disease (COPD) in Aboriginal communities in Australia, Aboriginal Health Workers (AHWs) have limited knowledge about effective management. AIM: To evaluate an online education program, co-designed with AHWs and exercise physiologists (EPs) or physiotherapists (PTs), to increase knowledge about COPD and its management. METHODS: AHWs and EPs from four Aboriginal Community Controlled Health Services (ACCHS) were recruited. An Aboriginal researcher and a physiotherapist experienced in COPD management and pulmonary rehabilitation (PR) delivered seven online education sessions. These sessions used co-design principles and an Aboriginal pedagogy framework '8 Ways of learning', which incorporates Aboriginal protocols and perspectives to realign teaching techniques and strengthen learning outcomes. Topics covered were: How the lungs work; What is COPD; Medications and how to use inhalers and COPD Action Plans; Why exercise is important; Managing breathlessness; Healthy eating; Managing anxiety and depression. After each session, AHWs with support from EPs, co-designed education 'yarning' resources using Aboriginal ways of learning to ensure topics were culturally safe for the local Aboriginal community and practiced delivering this at the following session. At the end of the program participants completed an anonymous online survey (5-point Likert scale) to assess satisfaction, and a semi-structured interview about their experience of the online education. RESULTS: Of the 12 participants, 11 completed the survey (7 AHWs, 4 EPs). Most (90%) participants strongly agreed or agreed that the online sessions increased knowledge and skills they needed to support Aboriginal patients with COPD. All (100%) participants felt: their cultural perspectives and opinions were valued and that they were encouraged to include cultural knowledge. Most (91%) reported that delivering their own co-designed yarning scripts during the online sessions improved their understanding of the topics. Eleven participants completed semi-structured interviews about participating in online education to co-design Aboriginal 'yarning' resources. Themes identified were: revealing the Aboriginal lung health landscape; participating in online learning; structuring the online education sessions; co-designing with the facilitators. CONCLUSIONS: Online education using co-design and 8 Ways of learning was rated highly by AHWs and EPs for improving COPD knowledge and valuing cultural perspectives. The use of co-design principles supported the cultural adaptation of COPD resources for Aboriginal people with COPD. TRIAL REGISTRATION: PROSPERO (registration number: CRD42019111405).

Copper-mediated oxidation of imidazopyrazinones inhibits marine luciferase activity.

The development of bioluminescence-based tools has seen steady growth in the field of chemical biology over the past few decades ranging in uses from reporter genes to assay development and targeted imaging. More recently, coelenterazine-utilizing luciferases such as Gaussia, Renilla, and the engineered nano-luciferases have been utilized due to their intense luminescence relative to firefly luciferin/luciferase. The emerging importance of these systems warrants investigations into the components that affect their light production. Previous work has reported that one marine luciferase, Gaussia, is potently inhibited by copper salt. The mechanism for inhibition was not elucidated but was hypothesized to occur via binding to the enzyme. In this study, we provide the first report of a group of nonhomologous marine luciferases also exhibiting marked decreases in light emission in the presence of copper (II). We investigate the mechanism of action behind this inhibition and demonstrate that the observed copper inhibition does not stem from a luciferase interaction but rather the chemical oxidation of imidazopyrazinone luciferins generating inert, dehydrated luciferins.

Pannexin 3 deletion reduces fat accumulation and inflammation in a sex-specific manner.

BACKGROUND: Pannexin 3 (PANX3) is a channel-forming glycoprotein that enables nutrient-induced inflammation in vitro, and genetic linkage data suggest that it regulates body mass index. Here, we characterized inflammatory and metabolic parameters in global Panx3 knockout (KO) mice in the context of forced treadmill running (FEX) and high-fat diet (HFD). METHODS: C57BL/6N (WT) and KO mice were randomized to either a FEX running protocol or no running (SED) from 24 until 30 weeks of age. Body weight was measured biweekly, and body composition was measured at 24 and 30 weeks of age. Male WT and KO mice were fed a HFD from 12 to 28 weeks of age. Metabolic organs were analyzed for a panel of inflammatory markers and PANX3 expression. RESULTS: In females there were no significant differences in body composition between genotypes, which could be due to the lack of PANX3 expression in female white adipose tissue, while male KOs fed a chow diet had lower body weight and lower fat mass at 24 and 30 weeks of age, which was reduced to the same extent as 6 weeks of FEX in WT mice. In addition, male KO mice exhibited significantly lower expression of multiple pro-inflammatory genes in white adipose tissue compared to WT mice. While on a HFD body weight differences were insignificant, multiple inflammatory genes were significantly different in quadriceps muscle and white adipose tissue resulting in a more anti-inflammatory phenotype in KO mice compared to WT. The lower fat mass in male KO mice may be due to significantly fewer adipocytes in their subcutaneous fat compared to WT mice. Mechanistically, adipose stromal cells (ASCs) cultured from KO mice grow significantly slower than WT ASCs. CONCLUSION: PANX3 is expressed in male adult mouse adipose tissue and may regulate adipocyte numbers, influencing fat accumulation and inflammation.

Glycemic biomarkers in children with drug-resistant epilepsy on various types of ketogenic diet therapies: A cross-sectional study.

OBJECTIVE: This study was undertaken to determine the hemoglobin A1c (HbA1c) and modified glucose-ketone index (mGKI) in children on different types of ketogenic diet (KD) for treatment of drug-resistant epilepsy, with attempts to evaluate their relationships with components of diet regime and other biomarkers. METHODS: We conducted a cross-sectional study in children with drug resistant epilepsy aged between 6 months and 18 years, who were on various types of KD therapies without any change in regime for at least 3 months. Parental interview, review of medical records, and a single measurement for blood ketone, HbA1c, and plasma carnitine were performed. mGKI was the ratio of an average plasma glucose estimated from HbA1c to blood ß-hydroxybutyrate level. RESULTS: Thirty-four patients were recruited with a median blood ketone of 2.90 mmol·L-1 and median HbA1c of 4.55%. Those on classical KD (cKD) had higher blood ketone (p = .031) and lower HbA1c (p = .010) and mGKI (p = .021) than those receiving modified Atkins diet, although both shared similar percentages of calories from carbohydrate (p = .211). The cKD and medium-chain triglyceride (MCT) KD groups had similar HbA1c (p = .252) and mGKI (p = .510). Blood ketone (p = .045) and the percentage of calories from MCT (p = .037) were the two main independent variables, inversely correlating with HbA1c. Other than plasma acylcarnitine (p = .047), neither blood ketone (p = .188) nor HbA1c (p = .170) could predict seizure reduction reliably. Both plasma acylcarnitine ≥ 6 µmol·L-1 (p = .013) and mGKI ≤ 2.2 (p = .013) were significantly associated with good seizure control. SIGNIFICANCE: HbA1c could potentially be useful for monitoring KD adherence or, indirectly, systemic ketosis in nondiabetic children on KD for drug-resistant epilepsy. Plasma acylcarnitine and mGKI could be important biomarkers in the management of KD therapy.

Implementing evidence into practice to improve chronic lung disease management in Indigenous Australians: the breathe easy, walk easy, lungs for life (BE WELL) project (protocol).

BACKGROUND: Strong evidence exists for the benefits of pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD), however the availability of culturally safe PR for Aboriginal and Torres Strait Islander (Indigenous) Peoples is limited. The study aims to determine whether PR can be implemented within Aboriginal Community Controlled Health Services (ACCHS) to improve outcomes for Indigenous people with COPD. METHODS: Multi-centre cohort study using participatory action research guided by the Knowledge-to-Action Framework. ACCHS supportive of enhancing services for chronic lung disease will be recruited. Aboriginal Health Workers (AHW) and the exercise physiologist (EP) or physiotherapist (PT) within these ACCHS will attend a workshop aimed at increasing knowledge and skills related to management of COPD and the provision of PR. Indigenous people with COPD will be invited to attend an 8-week, twice weekly, supervised PR program. OUTCOMES: AHW, EP/PT knowledge, skills and confidence in the assessment and management of COPD will be measured before and immediately after the BE WELL workshop and at 3, 6 and 12 months using a survey. PR participant measures will be exercise capacity (6-minute walk test (6MWT), health-related quality of life and health status at commencement and completion of an 8-week PR program. Secondary outcomes will include: number, length and cost of hospitalisations for a COPD exacerbation in 12-months prior and 12-months post PR; local contextual factors influencing implementation of PR; specific respiratory services provided by ACCHS to manage COPD prior to project commencement and at project completion. Repeated measures ANOVA will be used to evaluate changes in knowledge and confidence over time of AHWs and EP/PTs. Paired t-tests will be used to evaluate change in patient outcomes from pre- to post-PR. Number of hospital admissions in the 12 months before and after the PR will be compared using unpaired t-tests. DISCUSSION: Pulmonary rehabilitation is an essential component of best-practice management of COPD and is recommended in COPD guidelines. Indigenous peoples have limited access to culturally safe PR programs. This study will evaluate whether PR can be implemented within ACCHS and improve outcomes for Indigenous people with COPD. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001337369, Registered 2nd September 2017 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373585&isClinicalTrial=False.

Fatal recurrent disseminated Lomentospora prolificans infection during autologous hematopoietic stem cell transplantation: A case report and review, and discussion on the importance of prolonged neutropenia.

Infections with Scedosporium and Lomentospora species, in particular Lomentospora (previously Scedosporium) prolificans, are nearly universally fatal and rapidly-progressive in the transplant population. We report a case of a patient with diffuse large B-cell lymphoma undergoing myelosuppressive chemotherapy who developed disseminated L. prolificans infection which afterward persisted in his knee joint. The infection was treated with early empiric triple antifungal therapy tailored to synergy studies, growth factors to quickly resolve neutropenia, and aggressive debridement (where possible) of infection sites, including amputation. He achieved an 11-month remission until undergoing autologous hematopoietic stem cell transplantation with deep myelosuppression, wherein recrudescent L. prolificans infection occurred, causing death. We highlight the importance of early treatment, synergy studies, and especially recovery of neutropenia in treating this devastating condition.

The taxonomic position of Anoplotaenia dasyuri (Cestoda) as inferred from molecular sequences.

Anoplotaenia dasyuri Beddard, 1911 (Cestoda), from the Tasmanian devil, Sarcophilus harrisii (Boitard, 1842), is a taxonomic enigma, where a combination of morphological features, host type and geographical location have prevented it from being placed within a family and it is considered incertae sedis, despite its accepted validity. We performed a phylogenetic analysis of three A. dasyuri specimens collected from three Tasmanian devils using 18S and 28S rRNA sequences. Anoplotaenia dasyuri was found to have closest affinity with the family Paruterinidae, especially the genus Cladotaenia Cohn, 1901. The postulated theory of transfer of an ancestor of Anoplotaenia Beddard, 1911 transferring to the Tasmanian devil from an unrelated carnivorous host, such as an accipitriform or other carnivorous bird, is discussed and supported.

The Common Sunstar Crossaster papposus-A Neurotoxic Starfish.

Saxitoxins (STXs) are a family of potent neurotoxins produced naturally by certain species of phytoplankton and cyanobacteria which are extremely toxic to mammalian nervous systems. The accumulation of STXs in bivalve molluscs can significantly impact animal and human health. Recent work conducted in the North Sea highlighted the widespread presence of various saxitoxins in a range of benthic organisms, with the common sunstar (Crossaster papposus) demonstrating high concentrations of saxitoxins. In this study, an extensive sampling program was undertaken across multiple seas surrounding the UK, with 146 starfish and 5 brittlestars of multiple species analysed for STXs. All the common sunstars analysed (n > 70) contained quantifiable levels of STXs, with the total concentrations ranging from 99 to 11,245 µg STX eq/kg. The common sunstars were statistically different in terms of toxin loading to all the other starfish species tested. Two distinct toxic profiles were observed in sunstars, a decarbomylsaxitoxin (dcSTX)-dominant profile which encompassed samples from most of the UK coast and an STX and gonyautoxin2 (GTX2) profile from the North Yorkshire coast of England. Compartmentalisation studies demonstrated that the female gonads exhibited the highest toxin concentrations of all the individual organs tested, with concentrations >40,000 µg STX eq/kg in one sample. All the sunstars, male or female, exhibited the presence of STXs in the skin, digestive glands and gonads. This study highlights that the common sunstar ubiquitously contains STXs, independent of the geographical location around the UK and often at concentrations many times higher than the current regulatory limits for STXs in molluscs; therefore, the common sunstar should be considered toxic hereafter.

Case report: cranial angiosarcoma with multiple hemorrhagic brain metastasis in a child.

BACKGROUND AND IMPORTANCE: Angiosarcoma is a rare malignant tumor with an aggressive course and poor prognosis. It is typically seen in adults but very rarely seen in children. Angiosarcoma of the skull with brain metastasis is exceptionally rare. Due to the rare nature of these tumors, much is left unknown about clinical progression and treatment guidelines are not well established. CLINICAL PRESENTATION AND COURSE: A 14-year-old male patient presented with an enlarging mass on the parietal region of the head. Further investigations revealed a mass lesion involving scalp and skull tissue. Biopsy result showed angiosarcoma and the patient underwent multiple surgical interventions including scalp excision, craniectomy on tumor site, and excision of brain metastases. He also received chemotherapy and radiation therapy. Despite aggressive treatment, disease progression could not be controlled. CONCLUSION: Here we report a pediatric patient with intracranially invasive angiosarcoma of the scalp and skull, with recurrent hemorrhagic metastases to the brain. This is a very rare case in pediatric age group with very poor prognosis. Our patient had impressively longer survival than those reported in the literature despite multiple hemorrhagic brain metastasis and this is most likely related to our aggressive treatment strategy that includes multiple craniotomies for metastatic tumor resection in addition to neoadjuvant chemotherapy and radiation therapy. We believe optimal treatment of skull angiosarcoma in children should aim gross total resection of the skull tumor including involving scalp and dura as well as neoadjuvant chemotherapy and radiation therapy, and the patient should be followed closely with repeated brain MRI studies to pursue additional surgeries to remove brain metastasis if feasible.

Multiple New Paralytic Shellfish Toxin Vectors in Offshore North Sea Benthos, a Deep Secret Exposed.

In early 2018, a large easterly storm hit the East Anglian coast of the UK, colloquially known as the 'Beast from the East', which also resulted in mass strandings of benthic organisms. There were subsequent instances of dogs consuming such organisms, leading to illness and, in some cases, fatalities. Epidemiological investigations identified paralytic shellfish toxins (PSTs) as the cause, with toxins present in a range of species and concentrations exceeding 14,000 µg STX eq./kg in the sunstar Crossaster papposus. This study sought to better elucidate the geographic spread of any toxicity and identify any key organisms of concern. During the summers of 2018 and 2019, various species of benthic invertebrates were collected from demersal trawl surveys conducted across a variety of locations in the North Sea. An analysis of the benthic epifauna using two independent PST testing methods identified a 'hot spot' of toxic organisms in the Southern Bight, with a mean toxicity of 449 µg STX eq./kg. PSTs were quantified in sea chervil (Alcyonidium diaphanum), the first known detection in the phylum bryozoan, as well as eleven other new vectors (>50 µg STX eq./kg), namely the opisthobranch Scaphander lignarius, the starfish Anseropoda placenta, Asterias rubens, Luidia ciliaris, Astropecten irregularis and Stichastrella rosea, the brittlestar Ophiura ophiura, the crustaceans Atelecyclus rotundatus and Munida rugosa, the sea mouse Aphrodita aculeata, and the sea urchin Psammechinus miliaris. The two species that showed consistently high PST concentrations were C. papposus and A. diaphanum. Two toxic profiles were identified, with one dominated by dcSTX (decarbamoylsaxitoxin) associated with the majority of samples across the whole sampling region. The second profile occurred only in North-Eastern England and consisted of mostly STX (Saxitoxin) and GTX2 (gonyautoxin 2). Consequently, this study highlights widespread and variable levels of PSTs in the marine benthos, together with the first evidence for toxicity in a large number of new species. These findings highlight impacts to 'One Health', with the unexpected sources of toxins potentially creating risks to animal, human and environmental health, with further work required to assess the severity and geographical/temporal extent of these impacts.

Evaluation of a Novel Bony Landmark-Based Method for Teaching Percutaneous Insertion of Subclavian Venous Catheters in Pediatric Patients.

BACKGROUND: Surgical trainees performing subclavian vein (SCV) cannulation often incorrectly perceive needle trajectory and anatomical relations. As surface landmark-based methods derived from adult surgical practice may be less effective in younger patients, we developed and evaluated a novel bony landmark-based method for teaching SCV cannulation for central venous access device (CVAD) placement in children. METHODS: Over 2 sequential 3-year periods, pediatric surgical trainees were taught infraclavicular SCV cannulation via surface- and bony-landmark approaches, respectively. We prospectively recorded patient, surgeon and operative details on all Hickman line and port-a-cath insertions placed by trainees as the first surgeon via percutaneous infraclavicular SCV puncture and compared procedural outcomes and complications across both periods. RESULTS: Of 271 cases included in the study, trainees performed 52 (50.5%) and 92 (54.8%) procedures in the first and second periods, respectively. Patients in both periods did not differ by gender, disease, CVAD device, or prior CVAD, chemotherapy or infection status. In the second (bony landmark) period, although patients were younger (6.0 vs. 8.7 years, P = 0.003) mean procedural duration was shorter (42.5 vs. 58.3 min, P < 0.001). Also, cannulation attempts and complication rates did not differ significantly between study periods (P = 0.257 and 1.0, respectively). CONCLUSIONS: With the bony landmark approach, trainees could perform the procedures faster despite operating on younger patients, without impacting complication rates and cannulation attempts. Bony landmarks may better approximate SCV position across a range of ages, thus improving the consistency of SCV cannulation in CVAD placements in children.

Norepinephrine enhances song responsiveness and encoding in the auditory forebrain of male zebra finches.

Norepinephrine (NE) can dynamically modulate excitability and functional connectivity of neural circuits in response to changes in external and internal states. Regulation by NE has been demonstrated extensively in mammalian sensory cortices, but whether NE-dependent modulation in sensory cortex alters response properties in downstream sensorimotor regions is less clear. Here we examine this question in male zebra finches, a songbird species with complex vocalizations and a well-defined neural network for auditory processing of those vocalizations. We test the hypothesis that NE modulates auditory processing and encoding, using paired extracellular electrophysiology recordings and pattern classifier analyses. We report that a NE infusion into the auditory cortical region NCM (caudomedial nidopallium; analogous to mammalian secondary auditory cortex) enhances the auditory responses, burst firing, and coding properties of single NCM neurons. Furthermore, we report that NE-dependent changes in NCM coding properties, but not auditory response strength, are transmitted downstream to the sensorimotor nucleus HVC. Finally, NE modulation in the NCM of males is qualitatively similar to that observed in females: in both sexes, NE increases auditory response strengths. However, we observed a sex difference in the mechanism of enhancement: whereas NE increases response strength in females by decreasing baseline firing rates, NE increases response strength in males by increasing auditory-evoked activity. Therefore, NE signaling exhibits a compensatory sex difference to achieve a similar, state-dependent enhancement in signal-to-noise ratio and coding accuracy in males and females. In summary, our results provide further evidence for adrenergic regulation of sensory processing and modulation of auditory/sensorimotor functional connectivity. NEW & NOTEWORTHY This study documents that the catecholamine norepinephrine (also known as noradrenaline) acts in the auditory cortex to shape local processing of complex sound stimuli. Moreover, it also enhances the coding accuracy of neurons in the auditory cortex as well as in the downstream sensorimotor cortex. Finally, this study shows that while the sensory-enhancing effects of norepinephrine are similar in males and females, there are sex differences in the mode of action.

The Collaborative Improvement and Innovation Network (CoIIN) to Reduce Infant Mortality: An Outcome Evaluation From the US South, 2011 to 2014.

OBJECTIVES: To evaluate the impact of the Southern Public Health Regions' (Regions IV and IV) Collaborative Improvement and Innovation Network (CoIIN) to Reduce Infant Mortality, supported by the US Health Resources and Services Administration. METHODS: We examined pre-post change (2011-2014) for CoIIN strategies with available outcome data from vital records (early elective delivery, smoking) and the Pregnancy Risk Assessment Monitoring System (safe sleep) as well as preterm birth and infant mortality for Regions IV and VI relative to all other regions. RESULTS: For most outcomes, CoIIN improvements were greater in Regions IV and VI than in other regions. For example, early elective delivery decreased by 22% versus 14% in other regions, smoking cessation during pregnancy increased by 7% versus 2%, and back sleep position increased by 5% versus 2%. Preterm birth decreased by 4%, twice that observed in other regions, but infant mortality reductions did not differ significantly. CONCLUSIONS: The CoIIN approach to public health improvement shows promise in accelerating progress in intermediate outcomes and preterm birth. Impact on infant mortality may require additional strategies and sustained efforts.