Dentate granule cell axon (mossy fiber) sprouting is a common abnormality in patients with temporal lobe epilepsy. Mossy fiber sprouting creates an aberrant positive-feedback network among granule cells that does not normally exist. Its role in epileptogenesis is unclear and controversial. If it were possible to block mossy fiber sprouting from developing after epileptogenic treatments, its potential role in the pathogenesis of epilepsy could be tested. Previous attempts to block mossy fiber sprouting have been unsuccessful. The present study targeted the mammalian target of rapamycin (mTOR) signaling pathway, which regulates cell growth and is blocked by rapamycin. Rapamycin was focally, continuously, and unilaterally infused into the dorsal hippocampus for prolonged periods beginning within hours after rats sustained pilocarpine-induced status epilepticus. Infusion for 1 month reduced aberrant Timm staining (a marker of mossy fibers) in the granule cell layer and molecular layer. Infusion for 2 months inhibited mossy fiber sprouting more. However, after rapamycin infusion ceased, aberrant Timm staining developed and approached untreated levels. When onset of infusion began after mossy fiber sprouting had developed for 2 months, rapamycin did not reverse aberrant Timm staining. These findings suggest that inhibition of the mTOR signaling pathway suppressed development of mossy fiber sprouting. However, suppression required continual treatment, and rapamycin treatment did not reverse already established axon reorganization.

BackgroundNo clear synthesis of evidence examining household and area-level social determinants of multimorbidity exists. This study aimed to systematically review the existing literature on associations between household and area-level social determinants of health (SDoH) and multimorbidity prevalence or incidence in the general population.MethodsSix databases (MedLine, EMBASE, PsychINFO, Web of Science, CINAHL Plus and Scopus) were searched. The search was limited to peer-reviewed studies conducted in high-income countries and published in English between 2010 and 2019. A second reviewer screened all titles with abstracts and a subset of full texts. Study quality was assessed and protocol pre-registered (CRD42019135281).Results41 studies spanning North America, Europe and Australasia were included. Household income and area-level deprivation were the most explored with fairly consistent findings. The odds of multimorbidity were up to 4.4 times higher for participants with the lowest level of income compared with the highest level. Those living in the most deprived areas had the highest prevalence or incidence of multimorbidity (pooled OR 1.42, 95% CI 1.41 to 1.42). Associations between deprivation and multimorbidity differed by age and multimorbidity type. Findings from the few studies investigating household tenure, household composition and area-level rurality were mixed and contradictory; homeownership and rurality were associated with increased and decreased multimorbidity, while living alone was found to be associated with a higher risk of multimorbidity and not associated.ConclusionImproving our understanding of broader social determinants of multimorbidity—particularly at the household level—could help inform strategies to tackle multimorbidity.

Governmental and other agencies may require dog caregivers (owners) to provide breed identification of their dogs. This study compares breed identification by adoption agencies with identification by DNA analysis in 20 dogs of unknown parentage. Of the 20 dogs who had been adopted from 17 different locations, the study identified 16 dogs as having (or probably having) 1 or 2 specific breed(s) in their ancestry. DNA analysis of these dogs indicated that 25% (4/16) did in fact contain genetic evidence of an adoption agency's identified breed as one of the predominant breeds in a dog's ancestry. DNA analysis did not detect all specified breeds in 14 of these dogs. That is, 87.5% of the dogs identified by an adoption agency as having specific breeds in their ancestry did not have all of those breeds detected by DNA analysis. The discrepancies between opinions of adoption agencies and identification by DNA analysis suggest that it would be worthwhile to reevaluate the reliability of breed identification as well as the justification of current public and private policies pertaining to specific dog breeds.

Most dogs recovered well with surgical decompression. Increasing degree of deficits preoperatively is significantly correlated with longer recovery time.

ObjectiveThis study investigated the barriers and facilitators that senior leaders’ experience when using knowledge generated from the analysis of administrative health or care records (‘analytics’) to inform strategic health and care decision-making.SettingOne London-based sustainability and transformation partnership (STP) in England, as it was on the cusp of forming an integrated care system (ICS).Participants20 senior leaders, including health and social care commissioners, public health leads and health providers. Participants were eligible for inclusion if they were a senior leader of a constituent organisation of the STP and involved in using analytics to make decisions for their own organisations or health and care systems.DesignSemi-structured interviews conducted between January 2020 and March 2020 and analysed using the framework method to generate common themes.ResultsOrganisational fragmentation hindered use of analytics by creating siloed data systems, barriers to data sharing and different organisational priorities. Where trusted and collaborative relationships existed between leaders and analysts, organisational barriers were circumvented and access to and support for analytics facilitated. Trusted and collaborative relationships between individual leaders of different organisations also aided cross-organisational priority setting, which was a key facilitator of strategic health and care decision-making and use of analytics. Data linked across health and care settings were viewed as an enabler of use of analytics for decision-making, while concerns around data quality often stopped analytics use as a part of decision-making, with participants relying more so on expert opinion or intuition.ConclusionsThe UK Governments’ 2021 White Paper set out aspirations for data to transform care. While necessary, policy changes to facilitate data sharing across organisations will be insufficient to realise this aim. Better integration of organisations with aligned priorities could support and sustain cross-organisational relationships between leaders and analysts, and leaders of different organisations, to facilitate use of analytics in decision-making.

Background: Health-justice partnerships (HJPs) are collaborations between healthcare and legal services which support patients with social welfare issues such as welfare benefits, debt, housing, education and employment. HJPs exist across the world in a variety of forms and with diverse objectives. This review synthesizes the international evidence on the impacts of HJPs.Methods: A systematic scoping review of international literature was undertaken. A wide-ranging search was conducted across academic databases and grey literature sources, covering OECD countries from January 1995 to December 2018. Data from included publications were extracted and research quality was assessed. A narrative synthesis approach was used to analyze and present the results.Results: Reported objectives of HJPs related to: prevention of health and legal problems; access to legal assistance; health improvement; resolution of legal problems; improvement of patient care; support for healthcare services; addressing inequalities; and catalyzing systemic change. There is strong evidence that HJPs: improve access to legal assistance for people at risk of social and health disadvantage; positively influence material and social circumstances through resolution of legal problems; and improve mental wellbeing. A wide range of other positive impacts were identified for individuals, services and communities; the strength of evidence for each is summarized and discussed.Conclusion: HJPs are effective in tackling social welfare issues that affect the health of disadvantaged groups in society and can therefore form a key part of public health strategies to address inequalities.

Purpose The aim of this study was to explore how small area deprivation is associated with attitudes towards mental illness in a large sample of individuals living in private households in England. Method Cross-sectional data from Health Survey for England (2014) were analysed using multilevel models. The exposure of interest was the deprivation level of the small area in which an individual resides as measured by Index of Multiple Deprivation (IMD) score. The primary outcome was an individual's overall attitude towards mental illness, measured using a 12 item version of the Community Attitudes toward the Mentally Ill (CAMI) scale. Further outcomes were the two subscales of the CAMI, reflecting attitudes of (1) prejudice and exclusion and (2) tolerance and support. Individuals were nested within household and small geographical area. Results 5820 participants were included. Results from unadjusted models found strong evidence that individuals residing in the most deprived areas of England have worse attitudes towards mental illness compared to individuals living in the least deprived areas (estimated difference = − 3.5 points; 95% CI − 4.8 to − 2.2; P < 0.001). After adjusting for age, sex, education level, ethnicity and weekly income there was no longer evidence for this association (adjusted difference = − 0.1 points, 95% CI − 1.3 to 1.2; P = 0.931). Similar patterns of results were found for the CAMI subscales. Conclusions The relationship between small area-level deprivation and attitudes towards mental illness is no longer observed when controlling for certain individual-level characteristics.

SUMMARYPurpose: It would be useful to selectively block granule cell axon (mossy fiber) sprouting to test its functional role in temporal lobe epileptogenesis. Targeting axonal growth cones may be an effective strategy to block mossy fiber sprouting. L-type calcium channels and calcineurin, a calcium-activated phosphatase, are critical for normal growth cone function. Previous studies have provided encouraging evidence that blocking L-type calcium channels or inhibiting calcineurin during epileptogenic treatments suppresses mossy fiber sprouting. Methods: Rats were treated systemically with pilocarpine to induce status epilepticus, which lasted at least 2 h. Then, osmotic pumps and cannulae were implanted to infuse calcineurin inhibitors (FK506 or cyclosporin A) or an L-type calcium channel blocker (nicardipine) into the dorsal dentate gyrus. After 28 days of continuous infusion, extent of mossy fiber sprouting was evaluated with Timm staining and stereological methods. Results: Percentages of volumes of the granule cell layer plus molecular layer that were Timm-positive were similar in infused and noninfused hippocampi. Conclusions: These findings suggest inhibiting calcineurin or L-type calcium channels does not block mossy fiber sprouting in the pilocarpine-treated rat model of temporal lobe epilepsy.