Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines

Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications in dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate of learning and memory. Recent studies have suggested the generation of multi-innervated spines (MIS), in the form of several excitatory presynaptic inputs onto one spine, are crucial for hippocampal memory storage. However, little is known about the molecular mechanisms underlying MIS formation and their contribution to LTP. Using 3D enhanced resolution confocal images, we examined the contribution of Wnt synaptic modulators in MIS formation in the context of LTP. We show that blockage of endogenous Wnts with specific Wnt antagonists supresses the formation of MIS upon chemical LTP induction in cultured hippocampal neurons. Gain- and loss-of-function studies demonstrate that Wnt7a signaling promotes MIS formation through the postsynaptic Wnt scaffold protein Disheveled 1 (Dvl1) by stimulating neuronal nitric oxide (NO) synthase (nNOS). Subsequently, NO activates soluble guanylyl cyclase (sGC) to increase MIS formation. Consistently, we observed an enhanced frequency and amplitude of excitatory postsynaptic currents. Collectively, our findings identify a unique role for Wnt secreted proteins through nNOS/NO/sGC signaling to modulate MIS formation during LTP

Development of an intervention to support the implementation of evidence-based strategies for optimising antibiotic prescribing in general practice.

BACKGROUND: Trials show that antimicrobial stewardship (AMS) strategies, including communication skills training, point-of-care C-reactive protein testing (POC-CRPT) and delayed prescriptions, help optimise antibiotic prescribing and use in primary care. However, the use of these strategies in general practice is limited and inconsistent. We aimed to develop an intervention to enhance uptake and implementation of these strategies in primary care. METHODS: We drew on the Person-Based Approach to develop an implementation intervention in two stages. (1) Planning and design: We defined the problem in behavioural terms drawing on existing literature and conducting primary qualitative research (nine focus groups) in high-prescribing general practices. We identified 'guiding principles' with intervention objectives and key features and developed logic models representing intended mechanisms of action. (2) Developing the intervention: We created prototype intervention materials and discussed and refined these with input from 13 health professionals and 14 citizens in two sets of design workshops. We further refined the intervention materials following think-aloud interviews with 22 health professionals. RESULTS: Focus groups highlighted uncertainties about how strategies could be used. Health professionals in the workshops suggested having practice champions, brief summaries of each AMS strategy and evidence supporting the AMS strategies, and they and citizens gave examples of helpful communication strategies/phrases. Think-aloud interviews helped clarify and shorten the text and user journey of the intervention materials. The intervention comprised components to support practice-level implementation: antibiotic champions, practice meetings with slides provided, and an 'implementation support' website section, and components to support individual-level uptake: website sections on each AMS strategy (with evidence, instructions, links to electronic resources) and material resources (patient leaflets, POC-CRPT equipment, clinician handouts). CONCLUSIONS: We used a systematic, user-focussed process of developing a behavioural intervention, illustrating how it can be used in an implementation context. This resulted in a multicomponent intervention to facilitate practice-wide implementation of evidence-based strategies which now requires implementing and evaluating. Focusing on supporting the uptake and implementation of evidence-based strategies to optimise antibiotic use in general practice is critical to further support appropriate antibiotic use and mitigate antimicrobial resistance

Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.

AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF

A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii

Peer reviewedPublisher PD

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

A case-control study of tackle based head impact event (HIE) risk factors from the first three seasons of the National Rugby League Women's competition

Objective: The tackle is the most injurious event in rugby league and carries the greatest risk of concussion. This study aims to replicate previous research conducted in professional men's rugby league by examining the association between selected tackle characteristics and head impact events (HIEs) in women's professional rugby league. Methods: We reviewed and coded 83 tackles resulting in an HIE and every tackle (6,318 tackles) that did not result in an HIE for three seasons (2018–2020) of the National Rugby League Women's (NRLW) competition. Tackle height, body position of the tackler and ball carrier, as well as the location of head contact with the other player's body were evaluated. Propensity of each situation that caused an HIE was calculated as HIEs per 1,000 tackles. Results: The propensity for tacklers to sustain an HIE was 6.60 per 1,000 tackles (95% CI: 4.87–8.92), similar to that of the ball carrier (6.13 per 1,000 tackles, 95% CI: 4.48–8.38). The greatest risk of an HIE to either the tackler or ball carrier occurred when head proximity was above the sternum (21.66 per 1,000 tackles, 95% CI: 16.55–28.35). HIEs were most common following impacts between two heads (287.23 HIEs per 1,000 tackles, 95% CI: 196.98–418.84). The lowest propensity for both tackler (2.65 per 1,000 tackles, 95% CI: 0.85–8.20) and ball carrier HIEs (1.77 per 1,000 tackles, 95% CI: 0.44–7.06) occurred when the head was in proximity to the opponent's shoulder and arm. No body position (upright, bent or unbalanced/off feet) was associated with an increased propensity of HIE to either tackler or ball carrier. Conclusions: In the NRLW competition, tacklers and ball carriers have a similar risk of sustaining an HIE during a tackle, differing from men's NRL players, where tacklers have a higher risk of HIEs. Further studies involving larger samples need to validate these findings. However, our results indicate that injury prevention initiatives in women's rugby league should focus on how the ball carrier engages in contact during the tackle as well as how the tackler executes the tackle

Factors associated with smoking in pregnancy

The aim of this cross-sectional study was to identify factors related to smoking during pregnancy. The sample included 267 puerperae hospitalized in the maternity unit of a university hospital in Porto Alegre/RS. The data were collected through a self-applied instrument and statistically analyzed. The majority of the puerperae (51.3%) were between 18 and 25 years old, 55.4% were nonsmokers, 25.5% were smokers, 19.1% had recently ceased smoking (in abstinence). The nonsmokers had more consultations than the smokers and the abstinent smokers (p=0.025). The number of women who had more than one child was higher among smokers than among nonsmokers and abstinent smokers (p=0.002). Women were more likely to stop smoking before pregnancy when they had a partner who was a nonsmoker (p=0.007). Several factors influence smoking and smoking cessation and these are important in prenatal interventions aimed at pregnant women and their partners

The propensity of non-concussive and concussive head contacts during elite-level women's rugby league matches: A prospective analysis of over 14,000 tackle events

Objectives Identify the frequency, propensity, and factors related to tackle events which result in contact with the head in elite-level women's rugby league. Design Prospective video analysis study. Methods Video footage from 59 Women's Super League matches were analysed (n = 14,378 tackle events). All tackle events were coded as no head contact or head contact. Other independent variables included: area contacting head, impacted player, concussion outcome, penalty outcome, round of competition, time in match and team standard. Results There were 83.0 ± 20.0 (propensity 304.0/1000 tackle events) head contacts per match. The propensity of head contact was significantly greater for the tackler than ball-carrier (178.5 vs. 125.7/1000 tackle events; incident rate ratio 1.42, 95 % confidence interval 1.34 to 1.50). Head contacts occurring from an arm, shoulder, and head occurred significantly more than any other contact type. The propensity of concussions was 2.7/1000 head contacts. There was no significant influence of team standard or time in match on the propensity of head contacts. Conclusions The observed head contacts can inform interventions, primarily focusing on the tackler not contacting the ball-carrier's head. The tackler's head should also be appropriately positioned to avoid contact with the ball-carrier's knee (highest propensity for concussion). The findings are consistent with other research in men's rugby. Law modifications and/or enforcement (reducing the number of un-penalised head contacts), concurrent with coaching interventions (optimising head placement or reducing the head being contacted) may help minimise head contact risk factors for women's rugby league

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

A study of cleft lip/palate in a community in the South East of Ghana

The previous study in Wudoaba villages suggested that cleft lip and cleft palate (CL/CP) may be endemic in the Wudoaba cluster of villages in the Ketu South District of the Volta Region in South East Ghana. The study was to detect the prevalence of CL/CP in the Wudoaba communities and to investigate the factors associated with the causes of this malformation in the area. Two different interview-based questionnaires were designed to collect data over a period of 3 days from March 27 to 29, 2006. A purposive and accidental random sampling technique was used in the administering of the various questionnaires to the respondents. Data collected were recorded and analyzed with SPSS version 17.0. A total 99 respondents, with a mean age of 55.0 years, were interviewed. Out of it, 57.6% (n = 57) were related to their spouses: 54 first cousins and three other family relations. The prevalence of CL/CP is at least 6.3 per 1,000 people (i.e., 25/4,000). Majority (56.0%, n = 14) of the cleft cases were unilateral. Interviews revealed that genetic homogeneity and vitamin deficiencies in this community may be a causal factor for the high prevalence of CL/CP. This community provides clues suggesting that the magnitude of CL/CP may be larger than other studies and identifies the Wudoaba population as one that could be further studied to explore the underlying factors causing this congenital malformation