Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons

The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate whether the beta2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine beta2 subunit expression in selectively injured (tibial and common peroneal nerves) and uninjured (sural nerve) afferents. Three days after SNI, immunohistochemistry and Western blot analysis reveal an increase in the beta2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although beta2 subunit mRNA measured by real-time reverse transcription-PCR and in situ hybridization remains unchanged. Although injured neurons show the most marked upregulation,beta2 subunit expression is also increased in neighboring non-injured neurons and a similar pattern of changes appears in the spinal nerve ligation model of neuropathic pain. That increased beta2 subunit expression in sensory neurons after nerve injury is functionally significant, as demonstrated by our finding that the development of mechanical allodynia-like behavior in the SNI model is attenuated in beta2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the beta2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain

Dravet syndrome patient‐derived neurons suggest a novel epilepsy mechanism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99647/1/ana23897.pd

Complete Closed Genome Sequence of Nontoxigenic Invasive Corynebacterium diphtheriae bv. mitis Strain ISS 3319

The genome sequence of the human pathogen Corynebacterium diphtheriae bv. mitis strain ISS 3319 was determined and closed in this study. The genome is estimated to have 2,404,936 bp encoding 2,257 proteins. This strain also possesses a plasmid of 1,960 bp

Child health nursing in the Solomon Islands: A qualitative evaluation of the impact of the 'Bachelor of nursing - Child health'

Aim: To explore graduates’ perceptions of the impact on nursing practice of a new postgraduate course in child health, developed and implemented in the Solomon Islands in 2016. Background: The Bachelor of Nursing - Child Health was implemented in 2016 to develop nurses’ knowledge and skills in child health and paediatric care with the intent to improve national child health outcomes. Design: A qualitative exploratory, descriptive design was used to evaluate the impact of the Bachelor of Nursing - Child Health on graduates’ nursing practice. Methods: Fourteen nurses who graduated from the first cohort of students enrolled in the child health course were purposively selected to participate. Participants engaged in individual semi-structured interviews, conducted between August and December 2018. A thematic analysis was undertaken following Braun and Clarke's six-phase process. Results: Findings from the study demonstrate positive impacts of the course on graduates’ nursing practice. These include a perceived enhanced quality of care through their commitment to evidence-based practice, the ability to contribute to capacity building of colleagues, the reinforcement of provincial public health programmes and expanded participation in managerial activities. Following graduation, most alumni took on senior roles and greater responsibilities, felt more confident in managing unwell children, felt there was better access to and quality of child health care at the community and broader country levels and felt recognised by colleagues and communities. Some graduates faced resistance from colleagues to change practice and felt that despite being given greater responsibilities, nursing levels and salaries remained unchanged. This reflected a potential lack of recognition from hospital or provincial managers, the Nursing Council as the regulatory body for the nursing profession, and the Ministry of Health and Medical Services. A lack of human and material resources also impacted quality of care. Implications for Nursing and Health Policy: Findings from this study underline the need for the Solomon Islands National University, the Nursing Council, the Public Service and the Ministry of Health and Medical Services to concord and delineate formal accreditation standards for child health nurses. Overall, collaborative efforts and commitments at local, regional and global levels are required to support child health nurses in their ability and ambition to improve national child health outcomes. Conclusions: Findings from this study demonstrate positive impacts of the course on graduates’ nursing practice. The impact of increasing nurses’ knowledge and skills on national child health outcomes could be significant. Ongoing implementation and recognition of this course in the Solomon Islands, as well as more broadly across the Pacific region, are recommended

Scn1b deletion in adult mice results in seizures and SUDEP

Pathogenic lossâ ofâ function variants in SCN1B are linked to Dravet syndrome (DS). Previous work suggested that neuronal pathfinding defects underlie epileptogenesis and SUDEP in the Scn1b null mouse model of DS. We tested this hypothesis by inducing Scn1b deletion in adult mice that had developed normally. Epilepsy and SUDEP, which occur by postnatal day 21 in Scn1b null animals, were observed within 20 days of induced Scn1b deletion in adult mice, suggesting that epileptogenesis in SCN1Bâ DS does not result from defective brain development. Thus, the developmental brain defects observed previously in Scn1b null mice may model other coâ morbidities of DS.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149575/1/acn3785.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149575/2/acn3785_am.pd

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN

The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight‐institution study of 349 patients over 15 years

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/1/jso24582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/2/jso24582.pd

Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during <i>Escherichia coli</i> cell growth

The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment. However, even in one of the best studied organisms, Escherichia coli, there remain gaps in our understanding of how the synthesis of the successive layers of the cell envelope are coordinated during growth and cell division. Here, we used a whole-genome phenotypic screen to identify mutants with a defective cell envelope. We report that loss of yhcB, a conserved gene of unknown function, results in loss of envelope stability, increased cell permeability and dysregulated control of cell size. Using whole genome transposon mutagenesis strategies, we report the comprehensive genetic interaction network of yhcB, revealing all genes with a synthetic negative and a synthetic positive relationship. These genes include those previously reported to have a role in cell envelope biogenesis. Surprisingly, we identified genes previously annotated as essential that became non-essential in a ΔyhcB background. Subsequent analyses suggest that YhcB functions at the junction of several envelope biosynthetic pathways coordinating the spatiotemporal growth of the cell, highlighting YhcB as an as yet unexplored antimicrobial target.</p

Dietary supplement use is common in older adult drivers: an analysis from the AAA LongROAD study

Background Dietary supplement (DS) use is common and increasing among older adults, though much data available on use frequencies are from surveys and performed cross-sectionally. This paper sought to assess the frequency and pattern of dietary supplement use among older adults over time. Methods A secondary analysis of data from the AAA LongROAD study, a longitudinal prospective cohort study of older adult drivers, using data from baseline and the first two years of follow up included a total of 2990 drivers aged 65–79 years recruited at five study sites across the US from July 2015 to March 2017. Participants underwent baseline and annual evaluations, which included a “brown bag” medication review. DS were identified and categorized according to type and key components. Prevalence and pattern of DS use over time and relationship to demographics were measured with frequency and Chi squared analyses. Results 84% of participants took at least one dietary supplement during the 2-year study period, and 55% of participants continually reported use. DS accounted for approximately 30% of the total pharmacologic-pill burden in all years. Participants who were White non-Hispanic, female, 75–79 years of age at baseline, and on more non-supplement medications took significantly more dietary supplements (P < 0.05). Vitamin D, multivitamins, calcium, and omega-3 formulations were the most common supplements, with stable use over time. Use of individual herbal supplements and cannabis products was uncommon (< 1% participants per year). Conclusions DS use among older adults is common and relatively stable over time and contributes to polypharmacy. In clinical settings, providers should consider the influence of DS formulations on polypharmacy, and the associated cost, risk of medication interactions, and effect on medication compliance