Sociocultural and behavioural features of anticipated COVID-19 vaccine acceptance in Papua New Guinea: a mixed methods study proposal

BACKGROUND: Coronavirus disease 2019 (COVID-19) was characterised by the World Health Organisation (WHO) as a pandemic in 2020. Papua New Guinea (PNG) has remained on high alert ever since its National Control Centre continues to coordinate national preparedness and response measures guided by its Emergency Preparedness and Response Plan for COVID-19. As part of the WHO, Gavi and other global partners' COVAX program, PNG received several COVID-19 vaccine doses. A national-wide vaccine roll-out for COVID-19 was initiated in PNG in May 2021. Despite the availability of vaccines and the capacity of health systems to vaccinate frontline workers and community members, including high-risk groups, questions on vaccine safety, confidence, and acceptance remain critical for the effectiveness of the COVID-19 vaccination campaign. Evidence from studies on COVID-19 vaccine acceptance and demand in low- and middle-income countries (LMICs) suggests that sociocultural factors of the community and behaviours of different vaccine stakeholders, including vaccine recipients, vaccine providers and policymakers, determine the effectiveness of vaccination interventions or strategies. OBJECTIVE: This study will examine sociocultural determinants of anticipated acceptance of the COVID-19 vaccine in the population of urban and rural areas of different regions in PNG, and healthcare providers' views on vaccine acceptance. METHODS: The study design includes a mixed methods approach to implement in PNG's coastal and highlands regions. The first research activity will use a qualitative methodology in which the epistemological foundation is based on constructivism. This design elicits and listens to community members' accounts of ways culture as a rich source provides meaning to the COVID-19 pandemic, adherence to 'niupela pasin' (New normal) and vaccination acceptance. The second activity will be a cross-sectional survey to assess the distribution of features of vaccine acceptance, priorities and practices. The third activity will be in-depth interviews of healthcare providers actively involved in either COVID-19 clinical management or public health-related pandemic control activities. RESULTS: The project proposal has been reviewed and approved by the Medical Research Advisory Committee of Papua New Guinea. The qualitative data collection started in December 2022 and the survey will begin in May 2023. The findings will be disseminated to the participated communities later this year followed by the publications. CONCLUSIONS: Proposed research on community views and experience concerning sociocultural and behavioural features of anticipated acceptance of the vaccine will provide a better understanding of communication and education needs for vaccine action for COVID-19 control in PNG and other LMICs. The research also considers the influence of healthcare providers' and policymakers' roles in the awareness and use of the COVID-19 vaccine. INTERNATIONAL REGISTERED REPORT: PRR1-10.2196/44664

Importance of access to epilepsy monitoring units during the COVID-19 pandemic: Consensus statement of the International League against epilepsy and the International Federation of Clinical Neurophysiology

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic. Long-term video-EEG monitoring is an essential diagnostic service. Access to video-EEG monitoring of the patients in the EMUs must be given high priority. Patients should be screened for COVID-19, before admission, according to the local regulations. Local policies for COVID-19 infection control should be adhered to during the video-EEG monitoring. In cases of differential diagnosis where reduction of antiseizure medication is not required, consider home video-EEG monitoring as an alternative in selected patients

Comparative efficacy of two fipronil spot-on formulations against experimental tick infestations (Ixodes ricinus) in dogs

A parallel-group-design, randomized, unicentre and blinded controlled study was undertaken to assess the efficacy of a new fipronil-based spot-on formulation applied once to dogs against experimental Ixodes ricinus infestations. Six dogs served as negative controls (group 1), six dogs served as positive controls (group 2) receiving the original fipronil spot-on (Frontline® spot-on Dog, Merial) at a dosage of 0.67 mL for a dog weighing from 2 to 10 kg and 1.34 mL for a dog weighing from 10.1 to 20 kg and six dogs were treated with a 10% w/v fipronil-based spot-on solution (Effipro® Spot-on, Virbac SA) at an identical dosage (group 3, 0.67 mL for a dog weighing from 2 to 10 kg and 1.34 mL for a dog weighing from 10.1 to 20 kg). Each dog was sedated and subsequently infested with 50 unfed adult I. ricinus on days −7, −2, 7, 14, 21, 28 and 35. Forty-eight hours after the treatment and 48 h after each challenge (days −5, 2, 9, 16, 23, 30 and 37), the population of the remaining ticks was assessed for each animal. Geometric mean tick counts obtained were reduced by 99% and 94% on day 2 in groups 2 and 3, respectively, compared to the negative control group. Dogs were protected from re-infestations with an efficacy of >90% for 3 weeks in group 2 and for 5 weeks in group 3. Both 10% w/v fipronil-based spot-on solutions, despite different vehicles, were equally able to eradicate tick infestation, to prevent new infestations and were equally well tolerated

Using Motor Tempi to Understand Rhythm and Grammatical Skills in Developmental Language Disorder and Typical Language Development

Children with developmental language disorder (DLD) show relative weaknesses on rhythm tasks beyond their characteristic linguistic impairments. The current study compares preferred tempo and the width of an entrainment region for 5- to 7-year-old typically developing (TD) children and children with DLD and considers the associations with rhythm aptitude and expressive grammar skills in the two populations. Preferred tempo was measured with a spontaneous motor tempo task (tapping tempo at a comfortable speed), and the width (range) of an entrainment region was measured by the difference between the upper (slow) and lower (fast) limits of tapping a rhythm normalized by an individual’s spontaneous motor tempo. Data from N = 16 children with DLD and N = 114 TD children showed that whereas entrainment-region width did not differ across the two groups, slowest motor tempo, the determinant of the upper (slow) limit of the entrainment region, was at a faster tempo in children with DLD vs. TD. In other words, the DLD group could not pace their slow tapping as slowly as the TD group. Entrainment-region width was positively associated with rhythm aptitude and receptive grammar even after taking into account potential confounding factors, whereas expressive grammar did not show an association with any of the tapping measures. Preferred tempo was not associated with any study variables after including covariates in the analyses. These results motivate future neuroscientific studies of low-frequency neural oscillatory mechanisms as the potential neural correlates of entrainment-region width and their associations with musical rhythm and spoken language processing in children with typical and atypical language development

International consensus recommendations for management of new onset refractory status epilepticus including febrile infection-related epilepsy syndrome: Statements and supporting evidence

Objective: This study was undertaken to develop consensus-based recommendations for the management of adult and pediatric patients with new onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) based on best evidence and experience. Methods: The Delphi methodology was followed. A facilitator group of nine experts was established, who defined the scope, users, and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment, and research directions were generated, which were then rated on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was ≥7 and inappropriate if the median score was ≤3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey. Results: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: (1) disease characteristics; (2) diagnostic testing and sampling; (3) acute treatment; (4) treatment in the postacute phase; and (5) research, registries, and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article. Significance: This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Mapping the Spatio-Temporal Pattern of the Mammalian Target of Rapamycin (mTOR) Activation in Temporal Lobe Epilepsy

Growing evidence from rodent models of temporal lobe epilepsy (TLE) indicates that dysregulation of the mammalian target of rapamycin (mTOR) pathway is involved in seizures and epileptogenesis. However, the role of the mTOR pathway in the epileptogenic process remains poorly understood. Here, we used an animal model of TLE and sclerotic hippocampus from patients with refractory TLE to determine whether cell-type specific activation of mTOR signaling occurs during each stage of epileptogenesis. In the TLE mouse model, we found that hyperactivation of the mTOR pathway is present in distinct hippocampal subfields at three different stages after kainate-induced seizures, and occurs in neurons of the granular and pyramidal cell layers, in reactive astrocytes, and in dispersed granule cells, respectively. In agreement with the findings in TLE mice, upregulated mTOR was observed in the sclerotic hippocampus of TLE patients. All sclerotic hippocampus (n = 13) exhibited widespread reactive astrocytes with overactivated mTOR, some of which invaded the dispersed granular layer. Moreover, two sclerotic hippocampus exhibited mTOR activation in some of the granule cells, which was accompanied by cell body hypertrophy. Taken together, our results indicate that mTOR activation is most prominent in reactive astrocytes in both an animal model of TLE and the sclerotic hippocampus from patients with drug resistant TLE