bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lesion of intergeniculate leaflet GABAergic neurons attenuates sleep in mice exposed to light
Authors: Shi Huan-Ying , Xu Wei , Guo Han , Dong Hui , Qu Wei-Min , Huang Zhi-Li 
Published: September 2019

Abstract
Light has immediate effects on sleep in rodents, but the neural pathways underlying the effect remain to be elucidated. The intergeniculate leaflet (IGL) containing GABAergic neurons receives direct retinal inputs. We hypothesized that IGL GABAergic neurons may mediate light-induced sleep. EEG/electromyogram recording, immunohistochemistry, electrophysiology, optogenetics, fiber photometry, behavioral tests, and cell-specific destruction were employed to investigate the role of IGL GABAergic neurons in the regulation of acute light-induced sleep. Here, EEG/electromyogram recordings revealed that acute light exposure during the nocturnal active phase in mice induced a significant increase in non-rapid eye movement and rapid eye movement sleep compared with controls. Immunohistochemistry showed that acute light exposure for 2 hours in the active phase induced an increase in c-Fos expression in the IGL, whereas lights-off in the rest phase inhibited it. Patch clamp coupled with optogenetics demonstrated that retinal ganglion cells had monosynaptic functional connections to IGL GABAergic neurons. Calcium activity by fiber photometry in freely behaving mice showed that light exposure increased the activity of IGL GABAergic neurons. Furthermore, lesion of IGL GABAergic neurons by caspase-3 virus significantly attenuated the sleep-promoting effect of light exposure during active phases. Collectively, these results clearly indicated that the IGL is one of key nuclei mediating light-induced sleep in mice.
A Reliability Analysis of Entrustment-Derived Workplace-Based Assessments
Authors: Kelleher Matthew , Kinnear Benjamin , Sall Dana , Schumacher Daniel , Schauer Daniel P. , Warm Eric J. , Kelcey Ben 
Published: September 2019

Purpose
To examine the reliability and attributable facets of variance within an entrustment-derived workplace-based assessment system.

Method
Faculty at the University of Cincinnati Medical Center internal medicine residency program (a 3-year program) assessed residents using discrete workplace-based skills called observable practice activities (OPAs) rated on an entrustment scale. Ratings from July 2012 to December 2016 were analyzed using applications of generalizability theory (G-theory) and decision study framework. Given the limitations of G-theory applications with entrustment ratings (the assumption that mean ratings are stable over time), a series of time-specific G-theory analyses and an overall longitudinal G-theory analysis were conducted to detail the reliability of ratings and sources of variance.

Results
During the study period, 166,686 OPA entrustment ratings were given by 395 faculty members to 253 different residents. Raters were the largest identified source of variance in both the time-specific and overall longitudinal G-theory analyses (37% and 23%, respectively). Residents were the second largest identified source of variation in the time-specific G-theory analyses (19%). Reliability was approximately 0.40 for a typical month of assessment (27 different OPAs, 2 raters, and 1–2 rotations) and 0.63 for the full sequence of ratings over 36 months. A decision study showed doubling the number of raters and assessments each month could improve the reliability over 36 months to 0.76.

Conclusions
Ratings from the full 36 months of the examined program of assessment showed fair reliability. Increasing the number of raters and assessments per month could improve reliability, highlighting the need for multiple observations by multiple faculty raters.
Late-onset Crohn’s disease: a comparison of disease behaviour and therapy with younger adult patients: the Italian Group for the Study of Inflammatory Bowel Disease ‘AGED’ study
Authors: Viola Anna , Monterubbianesi Rita , Scalisi Giuseppe , Furfaro Federica , Rea Matilde , Saibeni Simone , Aratari Annalisa , Bringiotti Roberto , Casella Giovanni , Cantoro Laura , Frankovic Iris , Calella Francesca , Pugliese Daniela , Orlando Stefania , Samperi Leonardo , Cappello Maria , Mocci Giammarco , Manetti Natalia , Annese Vito , Privitera Antonino C. , Inserra Gaetano , Caprioli Flavio , D’Incà Renata , Principi Mariabeatrice , Papi Claudio , Castiglione Fabiana , Danese Silvio , Ardizzone Sandro , Bossa Fabrizio , Kohn Anna , Manguso Francesco , Alibrandi Angela , Fiorino Gionata , Armuzzi Alessandro , Fries Walter 
Published: September 2019

Background:
Disease phenotype and outcome of late-onset Crohn’s disease are still poorly defined.

Methods:
In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16–39 years and adult-onset Crohn’s disease 40–64 years. Data were collected for 3 years following diagnosis.

Results:
A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF’s even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn’s disease patients.

Conclusion:
Thirty-two percent of late-onset Crohn’s disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.
Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects
Authors: Naftali Timna , Bar-Lev Schleider Lihi , Sklerovsky Benjaminov Fabiana , Lish Ido , Konikoff Fred M. , Ringel Yehuda 
Published: September 2019

Objective
Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease.

Methods
Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects.

Results
The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24–56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients’ social or occupational status.

Conclusions
Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.
Insulin Therapy in Type 2 Diabetes
Authors: Aschner Pablo 
Published: September 2019

Background:
Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available.

Areas of Uncertainty:
The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines.

Data Sources:
When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases.

Therapeutic Advances:
Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. “Smart insulins” are under investigation and may become available for clinical use in the near future.

Conclusions:
Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.
Thromboprophylaxis Management in Surgical Patients: The Efficacy of a Protocol in the Electronic Prescription Program
Authors: Ribed Almudena , de Lorenzo-Pinto Ana , Lallana-Sainz Elena , Llorente-Parrado Cesar , Chana-Rodríguez Francisco , Sanjurjo-Sáez Maria 
Published: September 2019

Background and Objective:
Venous thromboembolism (VTE) continues to be a problem in surgical patients, but thromboprophylactic measures are not always implemented. This study aimed to evaluate thromboprophylaxis practice in surgical patients at our institution by assessing appropriateness during admission and discharge; 60-day clinical outcomes are analyzed, and finally further interventions are discussed for continued improvement.

Methods:
A cross-sectional, observational study was conducted in patients undergoing orthopedic and abdominal surgical procedures. Initially, the institution protocol was updated and embedded in the Computerized Physician Order Entry system. We then assessed prospective adequacy of thromboprophylaxis as per established in the protocol. The primary endpoint was thromboprophylaxis initiation and, secondarily, the quality of related prescriptions during hospitalization and at discharge.

Results:
A total of 114 patients were included in the study. According to VTE risk, thromboprophylaxis was initiated in 85.1% of the patients as needed during hospitalization and 94.8% at discharge. The following inadequacies versus the protocol were found: no duration information in the discharge summary (32.5%), incorrect postsurgical administration time of pharmacological prophylaxis (15.8%), omission of mechanical prophylaxis (13.7%), misdosing (9.6%), and omission of pharmacological prophylaxis (2.6%). No VTE events occurred 60 days postdischarge.

Conclusion:
The electronic protocol was an effective tool, as evidenced by the fact that thromboprophylaxis was initiated in the majority of surgical patients in our institution during hospitalization and at discharge. Still, some aspects leave room for improvement (duration, dosing, and timing), and further measures such as implementation of Electronic Medication Administration Records and new functionalities in the Clinical Decision Support systems are proposed.
Differences of attentional networks function in athletes from open-skill sports: an functional near-infrared spectroscopy study
Authors: Yu Miao , Liu Yi Bing , Yang Guang 
Published: September 2019

Objective
The purpose of this study was to investigate the attentional networks function characteristics of interceptive and strategic sports athletes from open-skill sports.

Methods
We used a revised lateralized attention network task to measure attentional networks efficiency and activation related to flanker conflict effects, alerting effects, and orienting effects changes on the right frontoparietal network using functional near-infrared spectroscopy in 20 strategic sports athletes, 20 interceptive sports athletes, and 22 college students.

Results
The interceptive sports athletes had the fastest overall reaction time. Strategic sports athletes had the highest accuracy and smallest flanker conflict effect on accuracy. Compared with non-athletes, strategic sports athletes had a higher alerting effect, validity effect, and disengaging effect on reaction time; the disengaging effect was particularly higher than that in the interceptive sports athletes. This was accompanied by higher activity in the right frontoparietal network.

Conclusions
The open-skill athletes demonstrate significantly more efficient attentional function compared to non-athletes. Athletes from interceptive sports demonstrated increased speed when solving conflict, while those from strategic sports demonstrated higher accuracy. In addition, top-down control appears to play an important role in strategic sports athletes making a cautious decision. This can be attributed to the right frontoparietal network.
Investigating the added value of biomarkers compared with self-reported smoking in predicting future e-cigarette use: Evidence from a longitudinal UK cohort study
Authors: Khouja Jasmine N. , Munafò Marcus R. , Relton Caroline L. , Taylor Amy E. , Gage Suzanne H. , Richmond Rebecca C. 
Published: September 2019

AbstractIntroductionBiomarkers can be used to assess smoking behaviour more accurately and objectively than self-report. This study assessed the association between cotinine (a biomarker of smoke exposure) and later e-cigarette use among a population who were unexposed to e-cigarettes in youth.MethodsYoung people in the Avon Longitudinal Study of Parents and Children took part in the study. We observed associations between cotinine at 15 years (measured between 2006 and 2008 before the wide availability of e-cigarettes) and self-reported ever use of e-cigarettes at 22 (measured between 2014 and 2015 when e-cigarettes were widely available) using logistic regression. A range of potential confounders were adjusted for (age, sex, body mass index, alcohol use and passive smoke exposure). Additionally, we adjusted for the young people’s self-reported smoking status/history to explore potential misreporting and measurement error.ResultsIn a sample of N=1,194 young people, cotinine levels consistent with active smoking at 15 years were associated with increased odds of e-cigarette ever use at 22 years (Odds Ratio [OR]=7.24, 95% CI 3.29 to 15.93) even when self-reported active smoking status at age 16 (OR=3.14, 95% CI 1.32 to 7.48) and latent classes of smoking behaviour from 14 to 16 (OR=2.70, 95% CI 0.98 to 7.44) were included in the model.ConclusionsCotinine levels consistent with smoking in adolescence were strongly associated with increased odds of later e-cigarette use, even after adjusting for reported smoking behaviour at age 16 and smoking transitions from 14 to 16.
A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Aging
Authors: Atkins Janice L , Jylhävä Juulia , Pedersen Nancy L , Magnusson Patrik K , Lu Yi , Wang Yunzhang , Hägg Sara , Melzer David , Williams Dylan M , Pilling Luke C 
Published: September 2019

ABSTRACTFrailty is a common geriatric syndrome, strongly associated with disability, mortality and hospitalisation. The mechanisms underlying frailty are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 19 and 45%. Understanding the genetic determinants and biological mechanisms underpinning frailty may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) of a frailty index (FI) in European descent participants from UK Biobank (n=164,610, aged 60-70 years). FI calculation was based on 49 self-reported items on symptoms, disabilities and diagnosed diseases. We identified 26 independent genetic signals at 24 loci associated with the FI (p<5*10−8). Many of these loci have previously been associated with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, three appear to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 14% (0.14, SE 0.006). A genetic risk score for the FI, derived solely from the UK Biobank data, was significantly associated with FI in the Swedish TwinGene study (n=10,616, beta: 0.11, 95% CI: 0.02-0.20, p=0.015). In pathway analysis, genes associated with synapse function were significantly enriched (p<3*10−6). We also used Mendelian randomization to identify modifiable traits and exposures that may affect the risk of frailty, with a higher educational attainment genetic risk score being associated with a lower risk of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on synapse maintenance pathways.
Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not cognitive control: converging fMRI evidence from Go-Nogo and Flanker tasks
Authors: Lesage E. , Sutherland M.T. , Ross T.J. , Salmeron B.J. , Stein E.A. 
Published: September 2019

ABSTRACTCognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here, we examine the effects of nicotine dependence (trait; smokers versus non-smoking controls), and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of cognitive control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence and pharmacological manipulation. However, effects were driven entirely by conditions that required less cognitive control. When demand for cognitive control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task, or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus, findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.
Range Extension of Cryptonanus agricolai (Didelphimorphia, Didelphidae) and First Record in the Atlantic Forest Core
Authors: Guerra Edú Baptista , Costa Leonora Pires 
Published: September 2019

ABSTRACTAccording to the Wallacean shortfall, knowledge about the geographic distribution of most species is still incomplete. Cryptonanus agricolai (Moojen, 1943) is a didelphid marsupial considered Data Deficient by IUCN, since species records are few and sparse. Although little information is available for the species, it is commonly associated with xeric habitats from Caatinga and open formations of the Cerrado in east-central Brazil. Here we report the first records of C. agricolai in the Atlantic Forest core, a new ecoregion of occurrence for the species, based on a recent collected voucher - identified through morphological and molecular analysis - from a Mussununga formation in Reserva Biológica do Córrego do Veado, southeastern Brazil. This record extends the occurrence of the species to more than 1 700 000 km2 and lower its altitudinal range limit to 108 m.RESUMOAmpliação da distribuição de Cryptonanus agricolai (Didelphimorphia, Didelphidae) e primeiro registro no centro da Mata Atlântica. De acordo com a Lacuna Wallaceana, o conhecimento sobre a distribuição geográfica da maioria das espécies está incompleto. Cryptonanus agricolai (Moojen, 1943) é um marsupial didelfídeo classificado pela IUCN na categoria Dados Insuficientes, uma vez que os registros existentes são poucos e esparsos. Embora haja pouca informação disponível para tal espécie, ela é comumente associada a habitats xéricos da Caatinga e formações abertas do Cerrado no centro-leste do Brasil. Aqui relatamos os primeiros registros de C. agricolai na Mata Atlântica, notadamente uma nova ecorregião de ocorrência para a espécie, com base em um espécime recentemente coletado – e identificado através de análises morfológicas e moleculares - em formação de Mussununga na Reserva Biológica do Córrego do Veado, sudeste do Brasil. Nossos achados ampliam a ocorrência da espécie para mais de 1 700 000 km2 e estabelece novo limite inferior de altitude para 108 m. Palavras-chave. Corredor Central da Mata Atlântica. Lacuna Wallaceana. Marsupial. Mussununga.