Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not specifically or substantially reversible with nicotine

Nicotine effects in adolescence and adulthood on cognition and α₄β₂-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia

Rational Nicotine use in schizophrenia has traditionally been explained as ‘self-medication’ of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food–reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p.40), whereas nicotine history elevated nAChRs across both regions (>30%, p<0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. Conclusions Although replicating nicotine-induced up-regulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities

Associations between Fall Distance, Age, and Trauma Outcomes in Older Adult Patients

Introduction. Falls are the leading cause of injury death amongolder adults. This study sought to determine if there are differencesbetween fall distance (ground level vs greater than groundlevel) and age (old vs very old) in terms of in-hospital mortality,orthopedic consultations, and neurological consultations. Methods. A retrospective trauma registry review was conductedof older adult patients (aged &gt; 65 years), admitted to aMidwestern Level I trauma facility (2005 - 2010) due to a fall.Results. Of the 1,064 patients analyzed, the majority fell fromground level compared to greater than ground level (64% and36%, respectively). Median age was 80 years. Fall distance wasnot associated significantly with in-hospital mortality (OR0.88; CI 0.50 - 1.54) or neurological consultations (OR 1.02; CI0.72 - 1.43), but was associated with orthopedic consultations(OR 1.49; CI 1.09 - 2.04). Age was not associated with in-hospitalmortality or neurological or orthopedic consultations. Conclusions. Fall distance was not associated with in-hospitalmortality or receiving a neurological consultation.However, older adults who fell from greater than groundlevel were more likely to receive orthopedic consultations.There were no differences in in-hospital mortality or receivinga neurological or orthopedic consultation based onage. These findings indicated that as the older adult populationincreases, burden of care will increase for trauma centersand neurological services. KS J Med 2016;9(3):54-57

Emergence of a non trivial fluctuating phase in the XY model on regular networks

We study an XY-rotor model on regular one dimensional lattices by varying the number of neighbours. The parameter $2\ge\gamma\ge1$ is defined. $\gamma=2$ corresponds to mean field and $\gamma=1$ to nearest neighbours coupling. We find that for $\gamma<1.5$ the system does not exhibit a phase transition, while for $\gamma > 1.5$ the mean field second order transition is recovered. For the critical value $\gamma=\gamma_c=1.5$, the systems can be in a non trivial fluctuating phase for whichthe magnetisation shows important fluctuations in a given temperature range, implying an infinite susceptibility. For all values of $\gamma$ the magnetisation is computed analytically in the low temperatures range and the magnetised versus non-magnetised state which depends on the value of $\gamma$ is recovered, confirming the critical value $\gamma_{c}=1.5$

Evaluation of Online Consumer Health Information for Idiopathic Scoliosis Identified by a Google Search

Introduction. This study sought to assess the quality of online consumerhealth information about idiopathic scoliosis. Previous studiesshowed that quality of online health information varies and oftenlacks adherence to expert recommendations and guidelines. Nevertheless,72% of internet users seek health information online. A 2005analysis of online scoliosis information found that the informationwas limited and of poor quality. Methods. Two reviewers vetted the top 10 websites resulting from aGoogleTM search for “scoliosis.” Content was organized into categoriesand rated by three physician evaluators using a 1 - 5 scale basedon quality, accuracy, completeness of information, readability, andwillingness to recommend. Additional information, such as numberof ads and Flesch-Kinkaid reading level, also was collected. Results. The average overall physician score was 47.6 (75 possible).All websites included content that was mostly accurate but varied incompleteness. Physicians unanimously recommended Mayo Clinic,MedicineNet, and Kids Health; none recommended the GoogleTMKnowledge Graph. The Scoliosis Research Society website reachedthe highest overall physician score. Readability ranged from 7th gradeto college level; only that of Kids Health was below 10th grade level. Conclusions. Most essential information provided by the websiteswas accurate and generally well rated by physicians. Website rankingby physicians was inconsistent with the ranking order by GoogleTM,indicating that health seekers reviewing the top GoogleTM-rankedwebsites may not be viewing the websites rated highest by physicians.Physicians should consider patient literacy in website recommendations,as many have an above average literacy level.Kans J Med 2018;11(4):95-101

The dynamic action of SecA during the initiation of protein translocation

Biotechnology and Biological Sciences Research Council (BBSRC) [a doctoral training grant Ph.D. studentship to S.W. and project grant number BB/I008675/1] and the Wellcome Trust [project grant number 084452]

Postpartum glucose follow-up and lifestyle management after gestational diabetes mellitus:general practitioner and patient perspectives

BACKGROUND: Incidence of type 2 diabetes is high after gestational diabetes mellitus (GDM). We aimed to evaluate the adherence to follow-up six-weeks postpartum visits in secondary care after GDM and glucose monitoring in primary care longer than 12-14 months after delivery and the years thereafter. In addition, we examined the women's lifestyle after delivery. METHODS: A cross-sectional follow-up survey among women with a history of GDM and their general practitioners (GP). Rates of attendance at the six-weeks postpartum visit and glucose testing were obtained from hospital records, over the period 2011-2012. Rates of annual follow-up postpartum glucose testing were assessed by a survey among their GP's. Lifestyle of the women on diet and exercise was assessed by questionnaire in 2015. RESULTS: In total 197 women were eligible for the study. Of these, 156 (79%) attended the six-weeks postpartum visit at the diabetes outpatient clinic and in 145 (93%) of these women glucose testing was performed. In total 77 (39%) women responded to the invitation to participate in this study and filled in the lifestyle questionnaire. About one third of the women met the recommendations for sufficient physical activity. A majority of them did not fulfil the Dutch guidelines on healthy diet - fruit intake 35.1%, vegetables intake 7.8%. Of the 74 invited GP's, 61 responded (82%), only 12 (20%) reported that they had performed a follow-up glucose testing within >12-14 months postpartum. Of these women, five were tested only in the first year of follow-up, five also in the second year, and two were tested for three consecutive years. CONCLUSIONS: Despite the high attendance rate of six-weeks postpartum visit and glucose testing, we observed low rates of longer-term follow-up regarding postpartum glucose testing. Moreover, we found a suboptimal adherence to healthy lifestyle for women with a history of GDM

Incidence and characteristics of adverse events in paediatric inpatient care: a systematic review and meta-analysis

Background: Adverse events (AEs) cause suffering for hospitalised children, a fragile patient group where the delivery of adequate timely care is of great importance. Objective: To report the incidence and characteristics of AEs, in paediatric inpatient care, as detected with the Global Trigger Tool (GTT), the Trigger Tool (TT) or the Harvard Medical Practice Study (HMPS) method. Method: MEDLINE, Embase, Web of Science and Google Scholar were searched from inception to June 2021, without language restrictions. Studies using manual record review were included if paediatric data were reported separately. We excluded studies reporting: AEs for a specific disease/diagnosis/treatment/procedure, or deceased patients; study protocols with no AE outcomes; conference abstracts, editorials and systematic reviews; clinical incident reports as the primary data source; and studies focusing on specific AEs only. Methodological risk of bias was assessed using a tool based on the Quality Assessment Tool for Diagnostic Accuracy Studies 2. Primary outcome was the percentage of admissions with ≥1 AEs. All statistical analyses were stratified by record review methodology (GTT/TT or HMPS) and by type of population. Meta-analyses, applying random-effects models, were carried out. The variability of the pooled estimates was characterised by 95% prediction intervals (PIs). Results: We included 32 studies from 44 publications, conducted in 15 countries totalling 33 873 paediatric admissions. The total number of AEs identified was 8577. The most common types of AEs were nosocomial infections (range, 6.8%-59.6%) for the general care population and pulmonary-related (10.5%-36.7%) for intensive care. The reported incidence rates were highly heterogeneous. The PIs for the primary outcome were 3.8%-53.8% and 6.9%-91.6% for GTT/TT studies (general and intensive care population). The equivalent PI was 0.3%-33.7% for HMPS studies (general care). The PIs for preventable AEs were 7.4%-96.2% and 4.5%-98.9% for GTT/TT studies (general and intensive care population) and 10.4%-91.8% for HMPS studies (general care). The quality assessment indicated several methodological concerns regarding the included studies. Conclusion: The reported incidence of AEs is highly variable in paediatric inpatient care research, and it is not possible to estimate a reliable single rate. Poor reporting standards and methodological differences hinder the comparison of study results

Observing Brane Inflation

Linking the slow-roll scenario and the Dirac-Born-Infeld scenario of ultra-relativistic roll (where, thanks to the warp factor, the inflaton moves slowly even with an ultra-relativistic Lorentz factor), we find that the KKLMMT D3/anti-D3 brane inflation is robust, that is, enough e-folds of inflation is quite generic in the parameter space of the model. We show that the intermediate regime of relativistic roll can be quite interesting observationally. Introducing appropriate inflationary parameters, we explore the parameter space and give the constraints and predictions for the cosmological observables in this scenario. Among other properties, this scenario allows the saturation of the present observational bound of either the tensor/scalar ratio r (in the intermediate regime) or the non-Gaussianity f_NL (in the ultra-relativistic regime), but not both.Comment: 31 pages, 12 figures; typo correcte

Less Is More - Estimation of the Number of Strides Required to Assess Gait Variability in Spatially Confined Settings

Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here