Glycemic control and its associated factors among diabetes mellitus patients at Ayder comprehensive specialized hospital, Mekelle-Ethiopia.

Abstract: Diabetes is one of the largest health emergencies of the twenty-first century and it is increasing with alarming rate throughout the world. Glycemic Control in diabetes patients is an important issue in minimizing diabetes related complications and deaths. Institution based comparative cross-sectional study was conducted from March to April, 2017. Glycated Hemoglobin A1c and biochemical profiles were determined using Huma Meter A1c and ABX PENTRA 400 clinical chemistry analyzer. Independent t-test to compare groups, bivariate and multi variable logistic regression analysis were used. A P-value <0.05 was considered as statistically significance. A total of 336 study participants were enrolled in this study. Overall, 208(61.9%) of the study participants had poor glycemic control. The poor glycemic control was significantly higher in glucometer non-users 120(71.4%) compared to glucometer users 88(52.4%) (P < 0.001). Income, the number of visits, high-triglyceride, high low-density lipoprotein and non-glucometer use were significantly associated with the poor glycemic control.

Mideksa|Seifu|S|
Ambachew|Sintayehu|S|
Biadgo|Belete|B|0000-0002-4468-0242
Baynes|Habtamu Wondifraw|HW|

glycemic control
Diabetes mellitus
glucometer
self-monitoring blood glucose


Association of pro-inflammatory cytokines with QCT-measured bone mineral density and its gender difference in a Chinese population - a pilot study.

Abstract:
INTRODUCTION
The primary objective of this study was to explore the association of pro-inflammatory cytokines with quantitative computed tomography (QCT)-measured bone mineral density (BMD) and its sexual difference in a Chinese population.

MATERIAL AND METHODS
In a cross-sectional study, a total of 85 participants aged 48-85 years were recruited and classified into three groups: normal bone mass with BMD > 120 mg/cm³, osteopaenia with BMD 80-120 mg/cm³, and osteoporosis with BMD < 80 mg/cm³. ANOVA analysis and multivariable ordinal logistic regression was used to estimate the associations of interest.

RESULTS
The proportions of osteoporosis, osteopaenia, and normal BMD were 29.41% (25), 37.65% (32), and 32.94% (28), respectively. Males had the highest proportion of osteopaenia while females had osteoporosis (p < 0.01). In contrast with the null findings in males, significant statistical difference was observed in females. Compared to the normal BMD, the OR for increasing IL-6 level of decreasing BMD groups (osteoporosis and/or osteopaenia) was 9.50 (95% CI: 1.44-62.80). TNF-a and IL-17 tended to show an increased risk (OR > 1) but did not reach significance. Current OR result cannot confirm these relationships of IL-1b, and ORs of PAI-1 and MCP-1 are too close to 1 to determine the practical meaning.

CONCLUSIONS
IL-6 is an obviously independent risk factor of QCT-measured osteoporosis in Chinese females. Sex hormones and fat-related factors are important confounders in the research of osteoimmunology.

Zeng|Jing|J| Li|Kai|K| Gong|Yanping|Y| Xu|Li|L| Li|Chunlin|C| Wang|Ling|L| Zhang|Yong|Y| Cheng|Xiaoguang|X|

pro-inflammatory cytokines
bone mineral density
cross-sectional study
QCT


A blind spot? Confronting the stigma of hepatitis B virus (HBV) infection - A systematic review.

Abstract: Background: The Global Hepatitis Health Sector Strategy is aiming for the elimination of viral hepatitis as a public health threat by 2030. Successful diagnostic, treatment and preventive strategies can reduce incidence and morbidity; it is important to ensure that these interventions and services are not only available, but also accessible. Stigma, poverty, and lack of knowledge may present a substantial barrier, especially in resource limited settings. We therefore set out to assimilate evidence for the nature and impact of stigma on the lives of people with HBV infection and on the community, and to suggest ways to tackle stigma and discrimination. Methods: We carried out a literature search in PubMed using the search terms 'hepatitis B', 'stigma' to identify relevant papers published between 2007 and 2017 (inclusive), with a particular focus on Africa. Results: We identified a total of 34 articles, of which only one study was conducted in Africa. Lack of knowledge on HBV was consistently identified: there were misconceptions about HBV transmission among the public, healthcare workers (HCWs) provided inaccurate information to individuals diagnosed with HBV, and poor understanding resulted in lack of preventive precautions. Stigma negatively impacted on health behaviour such as help-seeking, screening, disclosure, prevention of transmission, and adherence to treatment. Conclusion: Stigma is a potentially major barrier to the successful implementation of preventive, diagnostic and treatment strategies for HBV infection, and yet there is very limited recognition of the magnitude of this challenge, especially in Africa. There is a need for more research in this area, to identify and evaluate interventions that can be used effectively to tackle stigma in HBV, and to inform collaborative efforts between policy makers, HCWs, traditional healers, religious leaders, charity organisations and support groups, to improve awareness and tackle stigma in HBV in Africa.

stigma
hepatitis B virus
elimination
barriers
discrimination
Africa
ethics
funding


A Dual Palladium and Copper Hydride Catalyzed Approach for Alkyl-Aryl Cross-Coupling of Aryl Halides and Olefins.

Abstract: We report an efficient means of sp2 -sp3 cross coupling for a variety of terminal monosubstituted olefins with aryl electrophiles using Pd and CuH catalysis. In addition to its applicability to a range of aryl bromide substrates, this process was also suitable for electron-deficient aryl chlorides, furnishing higher yields than the corresponding aryl bromides in these cases. The optimized protocol does not require the use of a glovebox and employs air-stable Cu and Pd complexes as precatalysts. A reaction on 10 mmol scale further highlighted the practical utility of this protocol. Employing a similar protocol, a series of cyclic alkenes were also examined. Cyclopentene was shown to undergo efficient coupling under these conditions. Lastly, deuterium-labeling studies indicate that deuterium scrambling does not take place in this sp2 -sp3 cross coupling, implying that β-hydride elimination is not a significant process in this transformation.

palladium
copper
cross-coupling
alkenes
homogeneous catalysis


Maximal blood flow acceleration analysis in the early diastolic phase for aortocoronary artery bypass grafts: a new transit-time flow measurement predictor of graft failure following coronary artery bypass grafting.

Abstract:
PURPOSE
Maximal graft flow acceleration (max df/dt) determined using transit-time flowmetry (TTFM) in the diastolic phase was assessed as a potential predictor of graft failure for aortocoronary artery (AC) bypass grafts in coronary artery bypass patients.

METHODS
Max df/dt was retrospectively measured in 114 aortocoronary artery bypass grafts. TTFM data were fitted to a 9-polynomial curve, which was derived from the first-derivative curve, to measure max df/dt (9-polynomial max df/dt). Abnormal TTFM was defined as a mean flow of <15 ml/min, a pulsatility index of >5 or a diastolic filling ratio of <50 %. Postoperative assessments were routinely performed by coronary artery angiography (CAG) at 1 year after surgery.

RESULTS
Using TTFM, 68 grafts were normal, 4 of which were failing on CAG, and 46 grafts were abnormal, 21 of which were failing on CAG. 9-polynomial max df/dt was significantly lower in abnormal TTFM/failing by the CAG group compared with abnormal TTFM/patent by the CAG group (1.08 ± 0.89 vs. 2.05 ± 1.51 ml/s(2), respectively; P < 0.01, Mann-Whitney U test, Holm adjustment).

CONCLUSIONS
TTFM 9-polynomial max df/dt in the early diastolic phase may be a promising predictor of future graft failure for AC bypass grafts, particularly in abnormal TTFM grafts.

Handa|Takemi|T| Orihashi|Kazumasa|K| Nishimori|Hideaki|H| Yamamoto|Masaki|M|

Coronary artery bypass
TTFM
Decision support techniques


Effects of photofunctionalization on early osseointegration of titanium dental implants in the maxillary posterior region: a randomized double-blinded clinical trial.

Abstract:
BACKGROUND
This study aimed to investigate the effects of ultraviolet (UV) photofunctionalization on the stability of implants during the early phase in the posterior region of the maxilla. The study was a randomized double-blinded clinical trial. Half of the participants received conventional commercial implants while the other half received UV-irradiated implants. The surgical sites were classified into three bone quality groups (II, III, IV) based on the grayscale value measured on cone-beam computed tomography. The values obtained from resonance frequency analysis were recorded immediately after implant placement and at 4 weeks and at 4 months postoperatively. The marginal bone level of the implants was evaluated using periapical radiographs at 4 weeks, 4 months, and 1 year postoperatively.

RESULTS
Fifty-seven implants placed in 34 participants were analyzed in this study. In group III, significant differences were observed in terms of the differences of resonance frequency analysis values at 4 weeks (p = 0.004) and 4 months (p = 0.017) postoperatively. In group II, the UV-treated group showed significantly lesser bone loss at 4 weeks post-operatively (p = 0.037).

CONCLUSIONS
Within the limitation of the present study, we concluded that UV surface treatment on implants may increase the initial stability in the region of the maxilla with poor bone quality.

Choi|Bada|B|
Lee|Ye Chan|YC|
Oh|Kyung Chul|KC|
Lee|Jae Hoon|JH|0000-0003-2281-8885

Photofunctionalization
Early osseointegration
Titanium dental implants
Maxillary posterior region
Bone quality


Characterization of Myocardial Microstructure and Function in an Experimental Model of Isolated Subendocardial Damage.

Abstract: Subendocardial damage is among the first cardiac manifestations of hypertension and is already present in asymptomatic disease states. Accordingly, markers of subendocardial impairment may facilitate early detection of cardiac damages and risk stratification under these conditions. This study aimed to investigate the impact of subendocardial damage on myocardial microstructure and function to elucidate early pathophysiologic processes and to identify corresponding diagnostic measures. Mice (n=38) were injected with isoproterenol to induce isolated subendocardial scarring or saline as corresponding control. Cardiac function and myocardial deformation were determined by high-frequency echocardiography. The cardiac stress response was assessed in a graded exercise test and during dobutamine stress echocardiography. Myocardial microstructure was studied ex vivo by 7 T diffusion tensor magnetic resonance imaging at a spatial resolution of 100×100×100 µm 3 . Results were correlated with histology and biomarker expression. Subendocardial fibrosis was accompanied by diastolic dysfunction, impaired longitudinal deformation (global peak longitudinal strain [LS]: -12.5±0.5% versus -15.6±0.5%; P<0.001) and elevated biomarker expression (ANP [atrial natriuretic peptide], Galectin-3, and ST2). Systolic function and cardiac stress response remained preserved. Diffusion tensor magnetic resonance imaging revealed a left-shift in helix angle towards lower values in isoproterenol-treated animals, which was mainly determined by subepicardial myofibers (mean helix angle: 2.2±0.8° versus 5.9±1.0°; P<0.01). Longitudinal strain and subepicardial helix angle were highly predictive for subendocardial fibrosis (sensitivity, 82%-92% and specificity, 89%-90%). The results indicate that circumscribed subendocardial damage alone can cause several hallmarks observed in cardiovascular high-risk patients. Microstructural remodeling under these conditions involves also remote regions, and corresponding changes in longitudinal strain and helix angle might serve as diagnostic markers.

Beyhoff|Niklas|N|
Lohr|David|D|
Foryst-Ludwig|Anna|A|
Klopfleisch|Robert|R|
Brix|Sarah|S|
Grune|Jana|J|
Thiele|Arne|A|
Erfinanda|Lasti|L|
Tabuchi|Arata|A|
Kuebler|Wolfgang M|WM|
Pieske|Burkert|B|
Schreiber|Laura M|LM|
Kintscher|Ulrich|U|

D019028:Magnetic Resonance Imaging, Cine


Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials.

Abstract:
Purpose
The aim of this study was to assess the neuroprotective effect of progesterone administration on severe traumatic brain injury (TBI) for different follow-up periods and administration route by completing a meta-analysis of randomized clinical trials (RCTs).

Methods
A systematic literature search of PubMed, Embase, and Cochrane databases and the Web of Science (from establishment of each to September 1, 2018) was performed to identify original RCTs that evaluated the associations between progesterone treatment and the prognosis of patients with severe TBI.

Results
Eight RCTs enrolling 2,251 patients with severe TBI were included. Within 3 months post-injury, patients with progesterone administration had a lower mortality (risk ratio [RR] =0.59; 95% CI [0.42-0.81], P=0.001) and better neurologic outcomes (RR =1.51; 95% CI [1.12-2.02], P=0.007) than those who received placebo. However, these differences did not persist at 6 months post-injury for mortality (RR =0.96; 95% CI [0.65-1.41], P=0.83) or neurologic outcomes (RR =1.09; 95% CI [0.93-1.27], P=0.31). The analysis stratified by administration route showed that beneficial effects were only observed in patients who received progesterone intramuscularly (RR =1.61, 95% CI [1.19-2.18], P=0.002); no benefit was observed with intravenous administration (RR =0.99, 95% CI [0.91-1.07], P=0.75).

Conclusion
Progesterone administration improved the clinical outcomes of severe TBI patients within 3 months but may not have significant long-term benefits 6 months post-injury.

Pan|Zhi-Yong|ZY| Zhao|Yu-Hang|YH| Huang|Wen-Hong|WH| Xiao|Zhi-Ze|ZZ| Li|Zhi-Qiang|ZQ|

D016032:Randomized Controlled Trials as Topic

progesterone
severe traumatic brain injury
neuroprotection


Management of epilepsy in Laos: Perceptions of healthcare professionals from Vientiane Capital province and traditional healers in Southern Laos.

Abstract:
Background and aim
Traditional practices are deeply rooted in Lao people's perceptions and beliefs about health and illness.The objective of the study was to understand the perceptions of healthcare professionals and traditional healers regarding the management of epilepsy in Laos, and their reciprocal views.

Experimental procedure
An observational study was carried out in two areas of Laos from February to May 2017. Semi directive questionnaires were used to collect quantitative and qualitative data. Semiotic square was carried out to highlight relationships between attitudes of traditional healers and healthcare professionals. For quantitative approach, the proportions were reported, and the test used was Fisher's test for nominal variables. The mean and standard deviation expressed the continuous variables and the Student's t-test was used.

Results and conclusion
Epilepsy was cited by 90.9% of traditional healers as a convulsive disease with saliva or urine, and herbal medicines were predominantly used (86.4%) to treat it. Few healthcare professionals (26.5%) pointed out that they knew remedies to treat epilepsy other than antiepileptic drugs (AEDs), and 76.5% of healthcare professionals mentioned that epilepsy was a disease which only AEDs could treat. On the other hand, 54.5% of traditional healers confirmed a traditional remedy could cure completely epilepsy through long-term use. Ninety percent of traditional healers said the collaboration with healthcare professionals was a good idea and 44.1% of the healthcare professionals group said was complicated.The combination of these medicines for the management of epilepsy needs to be adapted to Lao's medical context.

Bounlu|Mayoura|M| Auditeau|Emilie|E| Vorachit|Somchit|S| Chivorakoun|Phetvongsinh|P| Souvong|Vimalay|V| Soukhasem|Thidachanh|T| Sannikone|Sonesimmaly|S| Preux|Pierre-Marie|PM| Boumediene|Farid|F|

Epilepsy
Traditional healer
Conventional medicine
Traditional medicine
Treatment gap


Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program.

Abstract: Introduction: Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation. Objectives: The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center. Methods: All EPIs (<28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated. Results: We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (all p < 0.01). In addition, the first SSC was performed earlier (p = 0.03) and lasted longer (p < 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p = 0.02) and the time from birth to first extubation (p = 0.02), and an increase of weight gain at discharge (p = 0.02). Conclusion: NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.

Klein|Valérie|V|
Zores-Koenig|Claire|C|
Dillenseger|Laurence|L|
Langlet|Claire|C|
Escande|Benoît|B|
Astruc|Dominique|D|
Le Ray|Isabelle|I|
Kuhn|Pierre|P|
|||


Pathotype Classification of Plasmodiophora brassicae Isolates Using Clubroot-Resistant Cultivars of Chinese Cabbage.

Abstract: Clubroot disease caused by Plasmodiophora brassicae is one of the most serious diseases in Brassica crops worldwide. In this study, the pathotypes of 12 Korean P. brassicae field isolates were determined using various Chinese cabbage including 22 commercial cultivars from Korea, China, and Japan, and 15 inbred lines. All P. brassicae isolates exhibited the typical clubroot disease on non-clubroot resistant cultivar, indicating that the isolates were highly pathogenic. According to the reactions on the Williams' hosts, the 12 field isolates were initially classified into five races. However, when these isolates were inoculated onto clubroot-resistant (CR) cultivars of Chinese cabbage, several isolates led to different disease responses even though the isolates have been assigned to the same race by the Williams' host responses. Based on the pathogenicity results, the 12 field isolates were reclassified into four different groups: pathotype 1 (GN1, GN2, GS, JS, and HS), 2 (DJ and KS), 3 (HN1, PC, and YC), and 4 (HN2 and SS). In addition, the CR cultivars from Korea, China, and Japan exhibited distinguishable disease responses to the P. brassicae isolates, suggesting that the 22 cultivars used in this study, including the non-CR cultivars, are classified into four different host groups based on their disease resistance. Combining these findings, the four differential hosts of Chinese cabbage and four pathotype groups of P. brassicae might provide an efficient screening system for resistant cultivars and a new foundation of breeding strategies for CR Chinese cabbage.

Kim|Hun|H|
Jo|Eun Ju|EJ|
Choi|Yong Ho|YH|
Jang|Kyoung Soo|KS|
Choi|Gyung Ja|GJ|

Chinese cabbage
clubroot
resistance
differential hosts
breeding


Risk factors associated with surveillance loss after endoscopic submucosal dissection in patients with gastric neoplasm.

Abstract:
Background
After endoscopic submucosal dissection of gastric neoplasms, surveillance endoscopy is required for patients with synchronous or metachronous neoplasms. We aimed to evaluate the risk factors associated with surveillance loss in patients who underwent endoscopic submucosal dissection.

Methods
Ninety-five patients treated with endoscopic submucosal dissection for gastric neoplasms between May 2015 and June 2016 were retrospectively reviewed. Clinicopathologic factors, sociodemographic factors, psychiatric measures, and associated risk factors for surveillance loss were evaluated. The chi-square or Fisher exact test, t-test, and logistic regression analysis were used in data analysis.

Results
Twenty-five (26.3%) patients were identified as having surveillance loss. Compared to the surveillance group, the surveillance loss group was old and had dysplasia, and a healthy American Society of Anesthesiologists physical status. Similarly, surveillance loss was related to low symptom perception, low incidence of alexithymia, mindful awareness, and high trait forgiveness. Logistic regression analysis showed that dysplasia (odds ratio, 15.23; 95% CI, 1.56-149.09, P=0.019), old age (odds ratio, 7.14; 95% CI, 1.90-26.88, P=0.004), and American Society of Anesthesiologists physical status 1 (odds ratio, 3.99; 95% CI, 1.09-14.60, P=0.037) were associated with surveillance loss.

Conclusions
Dysplasia, old age, and the American Society of Anesthesiologists physical status 1 were associated with surveillance loss in patients who underwent gastric endoscopic submucosal dissection. It could be helpful to proactively monitor patients with such conditions after gastric endoscopic submucosal dissection.

Lee|Manwoo|M|
Kim|Kyungchul|K|
Lee|Yong Kang|YK|
Park|Byung Kyu|BK|
Lee|San|S|
Jeon|Han Ho|HH|

surveillance
Gastric neoplasm
endoscopic resection


MR study of longitudinal variations in proximal femur 3D morphological shape and associations with cartilage health in hip osteoarthritis.

Abstract: The goal of this study was to use quantitative MRI analysis to longitudinally observe the relationship between 3D proximal femur shape and hip joint degenerative changes. Forty-six subjects underwent unilateral hip MR imaging at three time points (baseline, 18 and 36 months). 3D shape analysis, hip cartilage T1ρ /T2 relaxation time quantification, and SHOMRI MRI grading were performed at each time point. Subjects were grouped based on KL, SHOMRI, and HOOS pain scores. Associations between these score groupings, time, and longitudinal variation in shape, were analyzed using a generalized estimating equation. One-way ANCOVA was conducted to evaluate change in shape as a predictor of the worsening of degenerative changes at 36 months. Our results demonstrated that subjects displayed an increase in the volume of the femoral head and neck (Mode 3) over time. This shape mode was significantly more prevalent in patients that reported pain. Longitudinal changes in this shape mode also served as borderline predictors of elevated T1ρ values (p = 0.055) and of cartilage lesions (p = 0.068). Subjects showed a change in the Femoral Neck Anteversion angle (FNA) over time (Mode 6). This shape mode showed a significant interaction with the presence of cartilage lesions. The results of this study suggest that specific variations in bone shape quantified through 3D-MRI based Statistical Shape modeling show an observable relationship with hip joint compositional and morphological changes. The shapes observed lead to early degenerative changes, which may lead into OA, thus confirming the important role of bone shape changes in the pathogenesis of OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Inamdar|Gaurav|G|
Pedoia|Valentina|V|
Rossi-Devries|Jasmine|J|
Samaan|Michael A|MA|0000-0003-0597-1159
Link|Thomas M|TM|
Souza|Richard B|RB|
Majumdar|Sharmila|S|

hip
osteoarthritis
MRI
bone shape
statistical shape modeling (SSM)


A review of abstract concept learning in embodied agents and robots.

Abstract: This paper reviews computational modelling approaches to the learning of abstract concepts and words in embodied agents such as humanoid robots. This will include a discussion of the learning of abstract words such as 'use' and 'make' in humanoid robot experiments, and the acquisition of numerical concepts via gesture and finger counting strategies. The current approaches share a strong emphasis on embodied cognition aspects for the grounding of abstract concepts, and a continuum, rather than dichotomy, view of concrete/abstract concepts differences.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.

abstract concept learning
numerical concepts
embodied cognition
cognitive robotics
symbol grounding


Scrub typhus initially manifested as diabetic ketoacidosis: A case report.

Abstract: We report a case of a patient with scrub typhus who presented with diabetic ketoacidosis (DKA). The patient initially manifested with DKA, and was diagnosed with acute scrub typhus after evaluation the precipitating factors of DKA. No other complications of scrub typhus were noted. This case report suggests that acute scrub typhus should be considered as a precipitating factor of DKA, especially during the endemic season.

Jo|Dong Ho|DH|
Yu|Tae Yang|TY|
Kim|Young Jun|YJ|
Lee|Jae Hoon|JH|

Scrub typhus
Diabetic ketoacidosis
Complication


How to build personalized multi-omics comorbidity profiles.

Abstract: Multiple diseases (acute or chronic events) occur together in a patient, which refers to the disease comorbidities, because of the multi ways associations among diseases. Due to shared genetic, molecular, environmental, and lifestyle-based risk factors, many diseases are comorbid in the same patient. Methods for integrating multiple types of omics data play an important role to identify integrative biomarkers for stratification of patients into groups with different clinical outcomes. Moreover, integrated omics and clinical information may potentially improve prediction accuracy of disease comorbidities. However, there is a lack of effective and efficient bioinformatics and statistical software for true integrative data analysis. With the availability of the wide spread huge omics, phenotype and ontology information, it is becoming more and more practical to help doctors in clinical diagnostics and comorbidity prediction by providing appropriate software tool. We developed an R software POGO to compute novel estimators of the disease comorbidity risks and patient stratification. Starting from an initial diagnosis, omics and clinical data of a patient the software identifies the association risk of disease comorbidities. The input of this software is the initial diagnosis of a patient and the output provides evidence of disease comorbidities. The functions of POGO offer flexibility for diagnostic applications to predict disease comorbidities, and can be easily integrated to high-throughput and clinical data analysis pipelines. POGO is compliant with the Bioconductor standard and it is freely available at www.cl.cam.ac.uk/~mam211/POGO/.

multi-omics
comorbidity
ontology
data integration
multiplex network


Utility of rapid on-site cytologic evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions.

Abstract:
Objective
The utility of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions is unclear. The aim of this study was to evaluate the role of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions.

Methods
Consecutive patients who underwent endobronchial ultrasound with a guide sheath for the diagnosis of peripheral pulmonary lesions at our hospital between September 2012 and July 2014 were included in this retrospective study. Cytology slides were air-dried, and modified Giemsa (Diff-Quik) staining was used for rapid on-site evaluation. Additional smears were prepared for Papanicolaou staining and tissue samples were placed in formalin for histologic evaluation. The results of rapid on-site evaluation were compared with the final diagnoses of endobronchial ultrasound with a guide sheath.

Results
A total of 718 cases were included in the study population. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions was 88.6%, 65.9%, 81.2%, 77.7% and 80.1%, respectively. There were no procedure-related deaths.

Conclusions
Rapid on-site evaluation during endobronchial ultrasound with a guide sheath had high sensitivity for peripheral pulmonary lesions. When carrying out rapid on-site evaluation of transbronchial biopsy samples from peripheral pulmonary lesions, careful interpretation and clinical correlation are necessary.

Izumo|Takehiro|T| Matsumoto|Yuji|Y| Sasada|Shinji|S| Chavez|Christine|C| Nakai|Toshiyuki|T| Tsuchida|Takaaki|T|

rapid on-site evaluation
EBUS-GS
bronchoscopy
ground glass opacity
radial EBUS


Mountain gorilla ranging patterns: influence of group size and group dynamics.

Abstract: Since the 1980s, the Virunga mountain gorilla population has almost doubled, now reaching 480 individuals living in a 430-km(2) protected area. Analysis of the gorillas' ranging patterns can provide critical information on the extent and possible effects of competition for food and space. We analyzed 12 years of daily ranging data and inter-group encounter data collected on 11 gorilla groups monitored by the Karisoke Research Center in Rwanda. During that period, the study population increased in size by almost 50% and the number of groups tripled. Groups had small yearly home ranges compared to other known gorilla populations, with an average 90% kernel density estimate of 8.07 km2 and large between-group variations (3.17-23.59 km2). Most groups had consistent home range location over the course of the study but for some, we observed gradual range shifts of up to 4 km. Neighboring groups displayed high home range overlap, which increased dramatically after the formation of new groups. On average, each group used only 28.6% of its 90% kernel home range exclusively, and in some areas up to six different groups had overlapping home ranges with little or no exclusive areas. We found a significant intra-group positive relationship between the number of weaned individuals in a group and the home range size, but the fitted models only explained 17.5% and 13.7% of the variance in 50% and 90% kernel home range size estimates, respectively. This suggests that despite the increase in size, the study population is not yet experiencing marked effects of feeding competition. However, the increase in home range overlap resulting from the formation of new groups led to a sixfold increase in the frequency of inter-group encounters, which exposes the population to elevated risks of fight-related injuries and infanticide.

Caillaud|Damien|D|
Ndagijimana|Felix|F|
Giarrusso|Anthony J|AJ|
Vecellio|Veronica|V|
Stoinski|Tara S|TS|

group dynamics
Gorilla beringei beringei
animal movement
inter-group interactions
kernel home range analysis


Cardiovascular Disease in Relation to Placental Abruption: A Population-Based Cohort Study from Denmark.

Abstract:
BACKGROUND
Cardiovascular (CVD) complications stemming from vascular dysfunction have been widely explored in the setting of preeclampsia. However, the impact of abruption, a strong indicator of microvascular disturbance, on the risk of CVD mortality and morbidity remains poorly characterised.

METHODS
We designed a cohort analysis of 828 289 women who delivered singletons in Denmark between 1978 and 2010. We linked the National Patient Registry and the Registry of Causes of Death to the Danish Birth Registry to ascertain CVD events. We estimated CVD risks in relation to abruption from Cox proportional hazards regression following adjustments for confounders.

RESULTS
With 13 231 562 person-years of follow-up of women with at least one delivery, 11 829 pregnancies were complicated by abruption. The median (interquartile range) follow-up in the non-abruption and abruption groups was 16 (8, 24) and 18 (10, 25) years, respectively. CVD mortality rates in women with and without abruption were 0.9 and 0.3 per 10 000 person-years, respectively (adjusted hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.5, 5.0). The corresponding CVD morbidity complication rates were 16.7 and 10.0 per 10 000 person-years, respectively (HR 1.5, 95% CI 1.4, 1.8). The increased risks were evident for ischaemic heart disease, acute myocardial infarction, hypertensive heart disease, non-rheumatic valvular disease, and congestive heart failure.

CONCLUSIONS
This study shows increased hazards of CVD morbidity and mortality in relation to abruption. A better understanding of the pathogenesis of distorted placental microvasculature is needed as this appears to be a harbinger of CVD later in life.

Ananth|Cande V|CV|0000-0002-0410-2595
Hansen|Anne Vinkel|AV|
Williams|Michelle A|MA|
Nybo Andersen|Anne-Marie|AM|

cardiovascular disease
placental abruption
ischaemic placental disease
preterm delivery
prospective cohort study


Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder.

Abstract: The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell-matrix and cell-cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol (EtOH) exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, EtOH exposure generally increases perineuronal net components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD.

Extracellular Matrix
Perineuronal Nets
Synaptic Plasticity
Matrix Metalloproteinases
Tissue Plasminogen Activator


HDAC10 Is Positively Associated With PD-L1 Expression and Poor Prognosis in Patients With NSCLC.

Abstract: Currently, non-small cell lung carcinoma (NSCLC) is a major worldwide health problem. Meanwhile accumulating evidence indicates that histone deacetylase (HDAC) activation could induce PD-L1 expression in various types of cancer, especially in myeloma and B-cell lymphomas. Therefore, we hypothesized that high-level expression of HDAC10 is associated with PD-L1 induction and poor prognosis in patients with NSCLC. In total 180 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection were enrolled from April 2004 to August 2009. The patients with integrated clinicopathological records were followed up. The expression level of HDAC10 and PD-L1 in tissue samples was determined by immunohistochemistry. We observed that HDAC10 expression in lung cancer tissue is significantly higher than that in corresponding para-cancer tissue. Moreover, HDAC10 expression positively correlated with the expression level of PD-L1 (r = 0.213, P < 0.05) in NSCLC patients. Subgroup, multivariate analysis showed that the expression level of HDAC10 can be an independent prognostic factor and high-level expression of HDAC10 indicated poor overall survival for pulmonary carcinoma (r = 0.540, P < 0.001). Our findings suggest that the expression level of HDAC10 is positively associated with PD-L1 expression and may predict the outcome of patients with NSCLC.

Liu|Xiaomei|X| Wang|Yuxi|Y| Zhang|Rong|R| Jin|Ting|T| Qu|Liangliang|L| Jin|Qianwen|Q| Zheng|Jiasu|J| Sun|Jiaqi|J| Wu|Ziqing|Z| Wang|Linxi|L| Liu|Tianxu|T| Zhang|Yinxu|Y| Meng|Xiao|X| Wang|Ying|Y| Wei|Ning|N|


A qualitative study exploring personal recovery meaning and the potential influence of clinical recovery status on this meaning 20 years after a first-episode psychosis.

Abstract:
PURPOSE
Long-term data on recovery conceptualisation in psychotic illness are needed to support mental health services to organise themselves according to recovery-oriented frameworks. To our knowledge, no previous research has investigated how first-episode psychosis (FEP) service users (sampled across psychotic illness type) perceive recovery beyond 5 years after diagnosis. We aimed to explore personal recovery meaning with individuals 20 years after their FEP and examine the potential influence of clinical recovery status on how they defined recovery (i.e. personal recovery).

METHODS
Twenty participants were purposefully sampled from an epidemiologically representative FEP incidence cohort. At 20-year follow-up, semi-structured interviews were conducted with 10 cohort members who met full 'functional recovery criteria' (Clinically Recovered Group) and 10 who did not (Not Clinically Recovered Group). A thematic analysis was performed to develop shared themes and group-specific sub-themes to capture agreement and divergence between groups.

RESULTS
Five shared themes were produced: pursuing balance in conflict, generating meaning in life, experiencing a dynamic personal relationship with time, redressing inequality while managing added challenges/vulnerability, and directing life from resilience to flourishing. The five group-specific sub-themes developed illuminate differences in the meaning ascribed to personal recovery by each group.

CONCLUSION
Findings emphasise the role of time in how personal recovery is conceptualised by service users and identify ways clinical recovery may influence personal recovery meaning in FEP at mid-later life. Mental health services failing to consider temporal changes in meaning-making and discounting clinical recovery risk ignoring key factors affecting personal recovery.

Personal recovery
Clinical recovery
First-episode psychosis
Qualitative research
iHOPE-20


Braf V600E mutation in melanoma: translational current scenario.

Abstract: Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy.

Guadarrama-Orozco|J A|JA|
Ortega-Gómez|A|A|
Ruiz-García|E B|EB|
Astudillo-de la Vega|H|H|
Meneses-García|A|A|
Lopez-Camarillo|C|C|

BRAF
V600E
Melanoma
Inhibitor resistance


Minimally invasive surgery for the management of major bile duct injury due to cholecystectomy.

Abstract:
BACKGROUND
In recent years there has been a growing interest in the application of minimally invasive surgery in the management of cholecystectomy-related injury to the biliary tract. The aim of this analysis was to identify and combine the available evidence on the argument, with particular reference to major injuries to the main bile duct requiring biliodigestive anastomosis.

METHODS
The PubMed/MEDLINE, Embase, and Web of Science electronic databases were queried through May 2019. Inclusion criteria considered all studies reporting detailed data about patients with bile duct injury following cholecystectomy receiving minimally invasive (both laparoscopic and robotic) surgical repair. Clinical outcomes data were pooled and analyzed.

RESULTS
A total of 31 studies reporting on the outcomes of 218 patients were eventually included in the analysis, whereby 148 patients with type D or E injury. Of these, there were 31 patients (21%) receiving direct bile duct repair and 117 patients (79%) undergoing bilioenteric reconstruction. Among patients with major bile duct injury, postoperative morbidity was 24%, being 12% the incidence of major complications and 6% the rate of patients requiring subsequent, further surgery.

CONCLUSIONS
The absence of high-level evidences precludes the possibility to draw definitive conclusions. However, the available data derived from a growing number of centers demonstrate that minimally invasive surgery may offer its well-known advantages on postoperative outcomes also in the setting of severe iatrogenic injury to the bile ducts.

D019060:Minimally Invasive Surgical Procedures

minimally invasive surgery
bile duct injury
hepaticojejunostomy
laparoscopic cholecystectomy


Factors associated with polypharmacy and excessive polypharmacy in older people with intellectual disability differ from the general population: a cross-sectional observational nationwide study.

Abstract:
OBJECTIVES
(1) To evaluate the prevalence of polypharmacy (5-9 medicines) and excessive polypharmacy (10+ medicines) and (2) to determine associated demographic and clinical characteristics in an ageing population with intellectual disabilities (IDs).

DESIGN
Observational cross-sectional study.

SETTING
Wave One (2009/2010) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA).

PARTICIPANTS
A nationally representative sample of 753 persons with ID, aged between 41 and 90 years. Participants/proxy reported medicines (prescription and over the counter) taken on a regular basis; medication data was available for 736 participants (98%).

MAIN OUTCOME MEASURES/INTERVENTIONS
Participants were divided into those with no polypharmacy (0-4 medicines), polypharmacy (5-9 medicines) and excessive polypharmacy (10+ medicines). Medication use patterns were analysed according to demographic variables and reported chronic conditions. A multinomial logistic regression model identified factors associated with polypharmacy (5-9 medicines) and excessive polypharmacy (≥10 medicines).

RESULTS
Overall, 90% of participants reported use of medicines. Polypharmacy was observed in 31.5% of participants and excessive polypharmacy in 20.1%. Living in a residential institution, and reporting a mental health or neurological condition were strongly associated with polypharmacy and excessive polypharmacy after adjusting for confounders, but age or gender had no significant effect.

CONCLUSIONS
Polypharmacy was commonplace for older adults with ID and may be partly explained by the high prevalence of multimorbidity reported. Review of appropriateness of medication use is essential, as polypharmacy places ageing people with ID at risk of adverse effects.

O'Dwyer|Máire|M|
Peklar|Jure|J|
McCallion|Philip|P|
McCarron|Mary|M|
Henman|Martin C|MC|

polypharmacy
intellectual disability
multimorbidity


Oncogenic Notch Triggers Neoplastic Tumorigenesis in a Transition-Zone-like Tissue Microenvironment.

Abstract: During the initial stages of tumorigenesis, the tissue microenvironment where the pro-tumor cells reside plays a crucial role in determining the fate of these cells. Transition zones, where two types of epithelial cells meet, are high-risk sites for carcinogenesis, but the underlying mechanism remains largely unclear. Here, we show that persistent upregulation of Notch signaling induces neoplastic tumorigenesis in a transition zone between the salivary gland imaginal ring cells and the giant cells in Drosophila larvae. In this region, local endogenous JAK-STAT and JNK signaling creates a tissue microenvironment that is susceptible to oncogenic-Notch-induced tumorigenesis, whereas the rest of the salivary gland imaginal ring is refractory to Notch-induced tumor transformation. JNK signaling activates a matrix metalloprotease (MMP1) to promote Notch-induced tumorigenesis at the transition zone. These findings illustrate the significance of local endogenous inflammatory signaling in primary tumor formation.

Yang|Sheng-An|SA| Portilla|Juan-Martin|JM| Mihailovic|Sonja|S| Huang|Yi-Chun|YC| Deng|Wu-Min|WM|

D000818:Animals
D063646:Carcinogenesis
D002471:Cell Transformation, Neoplastic
D029721:Drosophila Proteins
D004331:Drosophila melanogaster
D004847:Epithelial Cells
D060227:Imaginal Discs
D053612:Janus Kinases
D020935:MAP Kinase Signaling System
D009369:Neoplasms
D051880:Receptors, Notch
D012469:Salivary Glands
D015398:Signal Transduction
D059016:Tumor Microenvironment

Notch
tumorigenesis
transition zone
imaginal rings
JAK-STAT
JNK
MMP
tumor hotspot


Implementing family-based behavioral treatment in the pediatric primary care setting: Design of the PLAN study.

Abstract: Family-based behavioral treatment (FBT) is an evidence-based treatment for pediatric obesity. FBT has primarily been implemented in specialty clinics, with highly trained interventionists. The goal of this study is to assess effectiveness of FBT implemented in pediatric primary care settings using newly trained interventionists who might implement FBT in pediatric practices. The goal is to randomize 528 families with a child with overweight/obesity (≥85th BMI percentile) and parent with overweight/obesity (BMI ≥ 25) across four sites (Buffalo and Rochester, New York; Columbus, Ohio; St. Louis, Missouri) to FBT or usual care and obtain assessments at 6-month intervals over 24 months of treatment. FBT is implemented using a mastery model, which provides quantity of treatment tailored to family progress and following the United States Preventive Services Task Force recommendations for effective dose and duration of treatment. The primary outcome of the trial is change in relative weight for children, and secondarily, for parents and siblings who are overweight/obese. Between group differences in the tendency to prefer small immediate rewards over larger, delayed rewards (delay discounting) and how this is related to treatment outcome is also evaluated. Challenges in translation of group-based interventions to individualized treatments in primary care settings, and in study implementation that arose due to the COVID-19 pandemic are discussed. It is hypothesized that the FBT intervention will be associated with better changes in relative weight for children, parents, and siblings than usual care. The results of this study can inform future dissemination and implementation of FBT into primary care settings.

Epstein|Leonard H|LH|
Schechtman|Kenneth B|KB|
Kilanowski|Colleen|C|
Ramel|Melissa|M|
Moursi|Nasreen A|NA|
Quattrin|Teresa|T|
Cook|Steven R|SR|
Eneli|Ihouma U|IU|
Pratt|Charlotte|C|
Geller|Nancy|N|
Campo|Rebecca|R|
Lew|Daphne|D|
Wilfley|Denise E|DE|

Behavioral intervention in primary care setting

Dissemination of evidence-based treatment


Multiple MicroRNAs synergistically promote tolerance to epidermal growth factor receptor-targeted drugs in smoked lung cancer therapies.

Abstract:
Aims
Lung cancer is one of the leading causes of cancer-related mortality. Tobacco usage is considered as associated with the carcinogenesis, progression, and prognosis of lung cancer. Previous studies have demonstrated that the smoking inhibited medical therapy results from K-Ras gene mutation through suppressing the epidermal growth factor receptor (EGFR) pathway. However, recent clinical trials have revealed that few smoked lung cancer patients present K-Ras gene mutation; yet, the majority of smoked lung cancer patients remain K-Ras nonmutation. The chemo-resistant mechanism remains unclear. Recently, microRNA (miRNA) interaction has been found to play an important role in drug resistance process. We hypothesized that miRNA may exert medicine resistance during the processes of lung cancer therapy.

Methods
Here, we analyzed miRNA array data from the GEO database.

Results
Our results showed that the interaction network among hsa-miR-30d-3p, hsa-miR-184, hsa-miR-500a, hsa-miR-542-3p, among others, inhibited EGFR-targeted medicine therapy.

Conclusion
The research will provide evidence that promotes novel therapy of lung cancers.

Pan|Li|L| Wang|Hailong|H| Jiang|Chengwen|C| Li|Wei|W| Chen|Yongzi|Y| Ying|Guoguang|G|

D015972:Gene Expression Regulation, Neoplastic

microRNA
smoking
lung cancer
Epidermal growth factor receptor


Compositing climate change vulnerability of a Mediterranean region using spatiotemporally dynamic proxies for ecological and socioeconomic impacts and stabilities.

Abstract: The study presents a new methodology to quantify spatiotemporal dynamics of climate change vulnerability at a regional scale adopting a new conceptual model of vulnerability as a function of climate change impacts, ecological stability, and socioeconomic stability. Spatiotemporal trends of equally weighted proxy variables for the three vulnerability components were generated to develop a composite climate change vulnerability index (CCVI) for a Mediterranean region of Turkey combining Landsat time series data, digital elevation model (DEM)-derived data, ordinary kriging, and geographical information system. Climate change impact was based on spatiotemporal trends of August land surface temperature (LST) between 1987 and 2016. Ecological stability was based on DEM, slope, aspect, and spatiotemporal trends of normalized difference vegetation index (NDVI), while socioeconomic stability was quantified as a function of spatiotemporal trends of land cover, population density, per capita gross domestic product, and illiteracy. The zones ranked on the five classes of no-to-extreme vulnerability were identified where highly and moderately vulnerable lands covered 0.02% (12 km2) and 11.8% (6374 km2) of the study region, respectively, mostly occurring in the interior central part. The adoption of this composite CCVI approach is expected to lead to spatiotemporally dynamic policy recommendations towards sustainability and tailor preventive and mitigative measures to locally specific characteristics of coupled ecological-socioeconomic systems.

Spatiotemporal trends
Time series data
Sustainability
Environmental monitoring
Vulnerability hotspots


Immunohistochemical localization of nerve injury-induced protein-1 in mouse tissues.

Abstract: Nerve injury-induced protein (Ninjurin)-1 is a cell adhesion molecule that is upregulated in neurons and Schwann cells after transection injury in rats. In this study, we investigated the localization of Ninjurin-1 in various tissues, including the cerebrum, sciatic nerve, spleen, lung, stomach, ileum, colon, liver, pancreas, kidney, testis, and skin in C57BL/6 mice, using Western blotting and immunohistochemistry. Western blot analysis showed that Ninjurin-1 was differentially expressed among organs. Ninjurin-1 was abundant in skin and ileum, weakly expressed in cerebrum, and moderately expressed in the other organs studied. Immunohistochemical analysis largely confirmed the results of the western blot analysis with often localization of Ninjurin-1 in the regions with abundant connective tissues. In addition, Ninjurin-1 was differentially expressed in various cell types in the tissues under the investigation. These findings suggest that Ninjurin-1 may play organ-specific roles in development and homeostasis of many organs.


Brazilian pediatric research groups, lines of research, and main areas of activity.

Abstract:
OBJECTIVES
The Brazilian scientific production in the pediatrics field has been increasing significantly. It is important to identify the distribution and activity of these groups in the country and the main study areas, contributing with data for better resource allocation by institutions.

METHODS
An active research was conducted in the National Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq]) website, using as filters the macro area of the research group (Health Sciences), the area (Medicine), and descriptors related to pediatrics. Research lines and main area of pediatric research groups were classified according to the subject predominantly studied by each group. The scientific production of the leader of the pediatric research group between 2011 and 2014 was also analyzed.

RESULTS
Most pediatric research groups in Brazil have more than five years of activity and are concentrated in the Southeast and South regions of the country; São Paulo, Rio Grande do Sul, and Minas Gerais are the states with most groups. Of the 132 specific pediatric research groups analyzed, 14.4% have lines of research in multiple areas and 11.4% in child and adolescent health. Among the 585 lines of research of these groups, the most prevalent areas were: oncology, infectious diseases, epidemiology, and gastroenterology.

CONCLUSIONS
The pediatric research groups in Brazil have relevant scientific production, including works published in international publications, and are concentrated in regions with higher socioeconomic index. Most groups registered in CNPq started their activity in the last five years (46%), reflecting the recent growth of scientific production in this area.

Oliveira|Priscila H A|PH|
Pinheiro|Mariana G|MG|
Isquierdo|Larissa A|LA|
Sukiennik|Ricardo|R|
Pellanda|Lucia C|LC|

Pediatric
Research
Research groups
Research line
Grupos de pesquisa
Linha de pesquisa
Pediatria
Pesquisa


Ageing, retirement and changes in vegetable consumption in France: findings from the prospective GAZEL cohort.

Abstract: The aim of this study was to describe the change in vegetable consumption with ageing and the transition to retirement. Study subjects were the participants of the GAZEL prospective cohort (Gaz and Électricité de France) aged 40-49 years at inclusion in 1989 who retired between 1991 and 2008 (12,942 men and 2739 women). Four FFQ were completed from 1990 to 2009. We used multiple imputation by chained equations in order to avoid dropping incomplete cases. The OR for eating vegetables everyday was estimated as a function of ageing, retirement status and the place of lunch before retirement through generalised estimating equations. Analyses were stratified by sex, and models were adjusted for confounders, including current spousal status. In 1990, 17.7% of men and 31% of women reported eating vegetables daily. The odds of consuming vegetables everyday increased with ageing for both men and women. The usual place of lunch was home for less than half the sample before retirement and for almost every respondent after retirement. For those who changed their place of lunch, the association between being retired and the odds of eating vegetables daily was positive and significant. We found that, in this cohort, vegetable consumption increased with ageing. Retirement had an indirect effect on vegetable consumption mediated by changes in the place of lunch.

Plessz|Marie|M| Guéguen|Alice|A| Goldberg|Marcel|M| Czernichow|Sébastien|S| Zins|Marie|M|

D058620:Elder Nutritional Physiological Phenomena

Ageing
Retirement
Vegetable consumption
GAZEL prospective cohort
Multiple imputations
GAZEL Gaz and Électricité de France
Meal place


Multimodal Assemblies for Prefacing a Dispreferred Response: A Cross-Linguistic Analysis.

Abstract: In this paper we examine how participants' multimodal conduct maps onto one of the basic organizational principles of social interaction: preference organization - and how it does so in a similar manner across five different languages (Czech, French, Hebrew, Mandarin, and Romanian). Based on interactional data from these languages, we identify a recurrent multimodal practice that respondents deploy in turn-initial position in dispreferred responses to various first actions, such as information requests, assessments, proposals, and informing. The practice involves the verbal delivery of a turn-initial expression corresponding to English 'I don't know' and its variants ('dunno') coupled with gaze aversion from the prior speaker. We show that through this 'multimodal assembly' respondents preface a dispreferred response within various sequence types, and we demonstrate the cross-linguistic robustness of this practice: Through the focal multimodal assembly, respondents retrospectively mark the prior action as problematic and prospectively alert co-participants to incipient resistance to the constraints set out or to the stance conveyed by that action. By evidencing how grammar and body interface in related ways across a diverse set of languages, the findings open a window onto cross-linguistic, cross-modal, and cross-cultural consistencies in human interactional conduct.

Pekarek Doehler|Simona|S|
Polak-Yitzhaki|Hilla|H|
Li|Xiaoting|X|
Stoenica|Ioana Maria|IM|
Havlík|Martin|M|
Keevallik|Leelo|L|

multimodality
preference organization
gaze
conversation analysis
epistemic markers
turn-prefacing


Cluster randomised controlled trial evaluating the clinical and humanistic impact of a pharmacist-led minor ailment service.

Abstract:
BACKGROUND
Community pharmacists are well positioned to support patients' minor ailments. The objective was to evaluate the clinical and humanistic impact of a minor ailment service (MAS) in community pharmacy compared with usual pharmacist care (UC).

METHODS
A cluster randomised controlled trial was conducted. Intervention patients received MAS, which included a consultation with the pharmacist. MAS pharmacists were trained in clinical pathways and communication systems mutually agreed with general practitioners and received monthly support. Control patients received UC. All patients were followed up by telephone at 14 days. Clinical and humanistic impact were defined by primary (appropriate referral rate and appropriate non-prescription medicine rate) and secondary outcomes (clinical product-based intervention rate, referral adherence, symptom resolution, reconsultation and EuroQol EQ-5D visual analogue scale (VAS)).

RESULTS
Patients (n=894) were recruited from 30 pharmacies and 82% (n=732) responded to follow-up. Patients receiving MAS were 1.5 times more likely to receive an appropriate referral (relative rate (RR)=1.51; 95% CI 1.07 to 2.11; p=0.018) and were five times more likely to adhere to referral, compared with UC (RR=5.08; 95%CI 2.02 to 12.79; p=0.001). MAS patients (94%) achieved symptom resolution or relief at follow-up, while this was 88% with UC (RR=1.06; 95% CI 1 to 1.13; p=0.035). MAS pharmacists were 1.2 times more likely to recommend an appropriate medicine (RR 1.20, 95% CI 1.1 to 1.3; p=0.000) and were 2.6 times more likely to perform a clinical product-based intervention (RR=2.62, 95% CI 1.28 to 5.38; p=0.009), compared with UC. MAS patients had a greater mean difference in VAS at follow-up (4.08; 95% CI 1.23 to 6.87; p=0.004). No difference in reconsultation was observed (RR=0.98; 95% CI 0.75 to 1.28; p=0.89).

CONCLUSION
The study demonstrates improved clinical and humanistic outcomes with MAS. National implementation is a means to manage minor ailments more effectively in the Australian health system.

TRIAL REGISTRATION NUMBER
ACTRN12618000286246.

cluster randomised controlled trial
minor ailment services
minor ailments
pharmacist
community pharmacy
pharmacy practice research
professional pharmacy services
quality use of medicines
self-care
self-medication


Cartilage matrix-inspired biomimetic superlubricated nanospheres for treatment of osteoarthritis.

Abstract: The superlubrication of natural joint has been attributed to hydration lubrication of articular cartilage. Here, inspired by the structure of phosphatidylcholine lipid (a typical cartilage matrix) with the presence of zwitterionic charges, we developed superlubricated nanospheres, namely poly (2-methacryloyloxyethyl phosphorylcholine)-grafted mesoporous silica nanospheres (MSNs-NH2@PMPC), via photopolymerization. The biomimetic nanospheres could enhance lubrication due to the formation of a tenacious hydration layer surrounding the zwitterionic charges of polymer brushes (PMPC), and achieve local delivery of an anti-inflammatory drug employing the nanocarriers (MSNs). The tribological and drug release tests showed improved lubrication and sustained drug release of the nanospheres. Additionally, the in vitro and in vivo tests revealed that the superlubricated drug-loaded nanospheres inhibited the development of osteoarthritis by up-regulating cartilage anabolic components and down-regulating catabolic proteases and pain-related gene. The nanospheres, with an integrated feature of both enhanced lubrication and sustained drug delivery, can be an efficient intra-articular nanomedicine for the treatment of osteoarthritis.

Chen|Hao|H| Sun|Tao|T| Yan|Yufei|Y| Ji|Xiuling|X| Sun|Yulong|Y| Zhao|Xin|X| Qi|Jin|J| Cui|Wenguo|W| Deng|Lianfu|L| Zhang|Hongyu|H|

Biomimetic
Nanospheres
Osteoarthritis
Hydration lubrication
Articular cartilage


Liver sinusoidal endothelial cells: Physiology and role in liver diseases.

Abstract: Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells representing the interface between blood cells on the one side and hepatocytes and hepatic stellate cells on the other side. LSECs represent a permeable barrier. Indeed, the association of 'fenestrae', absence of diaphragm and lack of basement membrane make them the most permeable endothelial cells of the mammalian body. They also have the highest endocytosis capacity of human cells. In physiological conditions, LSECs regulate hepatic vascular tone contributing to the maintenance of a low portal pressure despite the major changes in hepatic blood flow occurring during digestion. LSECs maintain hepatic stellate cell quiescence, thus inhibiting intrahepatic vasoconstriction and fibrosis development. In pathological conditions, LSECs play a key role in the initiation and progression of chronic liver diseases. Indeed, they become capillarized and lose their protective properties, and they promote angiogenesis and vasoconstriction. LSECs are implicated in liver regeneration following acute liver injury or partial hepatectomy since they renew from LSECs and/or LSEC progenitors, they sense changes in shear stress resulting from surgery, and they interact with platelets and inflammatory cells. LSECs also play a role in hepatocellular carcinoma development and progression, in ageing, and in liver lesions related to inflammation and infection. This review also presents a detailed analysis of the technical aspects relevant for LSEC analysis including the markers these cells express, the available cell lines and the transgenic mouse models. Finally, this review provides an overview of the strategies available for a specific targeting of LSECs.

Poisson|Johanne|J| Lemoinne|Sara|S| Boulanger|Chantal|C| Durand|François|F| Moreau|Richard|R| Valla|Dominique|D| Rautou|Pierre-Emmanuel|PE|

Liver sinusoidal endothelial cells
Capillarization
Angiogenesis
Liver regeneration
Cirrhosis
Drug delivery system
Endothelial dysfunction
Endothelium


A Single-Cell Approach to the Elusive Latent Human Cytomegalovirus Transcriptome.

Abstract: Herpesvirus latency has been difficult to understand molecularly due to low levels of viral genomes and gene expression. In the case of the betaherpesvirus human cytomegalovirus (HCMV), this is further complicated by the heterogeneity inherent to hematopoietic subpopulations harboring genomes and, as a consequence, the various patterns of infection that simultaneously exist in a host, ranging from latent to lytic. Single-cell RNA sequencing (scRNA-seq) provides tremendous potential in measuring the gene expression profiles of heterogeneous cell populations for a wide range of applications, including in studies of cancer, immunology, and infectious disease. A recent study by Shnayder et al. (mBio 9:e00013-18, 2018, https://doi.org/10.1128/mBio.00013-18) utilized scRNA-seq to define transcriptomal characteristics of HCMV latency. They conclude that latency-associated gene expression is similar to the late lytic viral program but at lower levels of expression. The study highlights the numerous challenges, from the definition of latency to the analysis of scRNA-seq, that exist in defining a latent transcriptome.

cytomegalovirus transcriptome scRNA-seq MARS-Seq herpesviruses


Synthesis and structure-activity relationship studies in serotonin 5-HT4 receptor ligands based on a benzo[de][2,6]naphthridine scaffold.

Abstract: A small series of serotonin 5-HT4 receptor ligands has been designed from flexible 2-methoxyquinoline compounds 7a,b by applying the conformational constraint approach. Ligands 7a,b and the corresponding conformationally constrained analogues 8a-g were synthesized and their interactions with the 5-HT4 receptor were examined by measuring both binding affinity and the ability to promote or inhibit receptor-G protein coupling. Ester derivative 7a and conformationally constrained compound 8b were demonstrated to be the most interesting compounds showing a nanomolar 5-HT4R affinity similar to that shown by reference ligands cisapride (1) and RS-23,597-190 (4). The result was rationalized by docking studies in term of high similarity in the binding modalities of flexible 7a and conformationally constrained 8b. The intrinsic efficacy of some selected ligands was determined by evaluating the receptor-G protein coupling and the results obtained demonstrated that the nature and the position of substituents play a critical role in the interaction of these ligands with their receptor.

Castriconi|Federica|F|
Paolino|Marco|M|
Giuliani|Germano|G|
Anzini|Maurizio|M|
Campiani|Giuseppe|G|
Mennuni|Laura|L|
Sabatini|Chiara|C|
Lanza|Marco|M|
Caselli|Gianfranco|G|
De Rienzo|Francesca|F|
Menziani|Maria Cristina|MC|
Sbraccia|Maria|M|
Molinari|Paola|P|
Costa|Tommaso|T|
Cappelli|Andrea|A|

D058828:Serotonin 5-HT4 Receptor Agonists

Synthesis
Serotonin
5-HT4 receptor ligands
G-protein coupled receptor
Molecular modelling


Particle engineered mannitol for carrier-based inhalation - A serious alternative?

Abstract: In dry powder inhalation (DPI), larger carrier particles, typically lactose, are blended with micronised active pharmaceutical ingredient (API) particles to improve handling, processability and inhalable fraction. Alternative carrier materials were researched for years, but did not enter the market yet. In this study, a common lactose carrier for DPI formulations and a spray granulated mannitol carrier were compared to evaluate if the particle engineered mannitol can be considered a serious alternative. Blends with five different API concentrations (0.1 to 4%) were prepared with two APIs. Physical carrier and blend characterisation regarding particle size, morphology, density, shear cell testing and dosing behaviour were performed. Aerodynamic assessment was done using two different inhaler devices (one capsule-based inhaler and one reservoir-based inhaler). In addition, the influence of different flow rates was examined. Results indicated that uniform dosing in metered mass and delivered dose over this API concentration range was achieved due to good flowability of the blends. Furthermore, linear dose delivery could be seen over the added API concentrations. Impaction analysis showed that the respirable fractions of mannitol blends were comparable (for salbutamol sulphate blends) or higher (for budesonide blends) than with a standard lactose carrier.

Salbutamol sulphate (PubChem CID: 39859)


Presence and Germination of the Probiotic Bacillus subtilis DE111® in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study.

Abstract: Spore-based probiotics offer important advantages over other probiotics as they can survive the harsh gastric conditions of the stomach and bile salts in the small intestine, ultimately germinating in the digestive tract. A novel clinical trial in 11 ileostomy participants was conducted to directly investigate the presence and germination of the probiotic strain Bacillus subtilis DE111® in the small intestine. Three hours following ingestion of DE111®, B. subtilis spores (6.4 × 104 ± 1.3 × 105 CFU/g effluent dry weight) and vegetative cells (4.7 × 104 ± 1.1 × 105 CFU/g effluent dry weight) began to appear in the ileum effluent. Six hours after ingestion, spore concentration increased to 9.7 × 107 ± 8.1 × 107 CFU/g and remained constant to the final time point of 8 h. Vegetative cells reached a concentration of 7.3 × 107 ± 1.4 × 108 CFU/g at 7 h following ingestion. These results reveal orally ingested B. subtilis DE111® spores are able to remain viable during transit through the stomach and germinate in the small intestine of humans within 3 h of ingestion.

Colom|Joan|J|
Freitas|Daniela|D|
Simon|Annie|A|
Brodkorb|Andre|A|
Buckley|Martin|M|
Deaton|John|J|
Winger|Alison M|AM|

germination
probiotic
Bacillus subtilis
DE111®
small intestine
ileostomy


Na(+)/Ca(2+) exchanger 1 (NCX-1) mediates the anti-apoptotic effect of Akt1 in neonatal rat cardiomyocytes during ischemia/reperfusion.

Abstract: The purpose of this study was to investigate the anti-apoptotic role of Akt1 gene in neonatal rat cardiomyocytes and the relationship with Na(+)/Ca(2+) exchanger 1 (NCX1) during ischemia/reperfusion (IR). The cultured original rat cardiomyocytes were randomly divided into five groups: normal control group (C group), hypoxia/reoxygenation group (HR group), the control vector pLVX-EGFP-3FLAG group (CV group), the gene pLVX-EGFP-3FLAG-Akt1 transfection group (A group), and Akt1 inhibitor LY294002 group (LY group). Cardiomyocyte vitality was determined using MTT, and the apoptosis was determined by TUNEL to verify the anti-apoptotic role of Akt1. The mRNA levels of Akt1 and NCX1 were determined by RT-PCR, the protein expression of Akt1, p-Akt1, NCX1 and the apoptotic proteins of mitochondrial pathway cytochrome C (Cyto C) and caspase-9 were measured by Western blot. As a result, transfected Akt1 (A group) showed increased myocardial cell viability and reduced apoptosis, with increase in Akt1 expression and decrease in NCX1 expression. The levels of apoptotic proteins Cyto C and caspase-9 also declined. This study demonstrated that lentivirus-mediated transfection of Akt1 played an anti-apoptotic role during IR of rat cardiomyocytes, via inhibition of NCX1 and other mitochondrial proteins.

Huang|Manman|M| Pan|Defeng|D| Du|Yinping|Y| Zhu|Hong|H| Zhang|Lin|L| Xu|Tongda|T| Luo|Yuanyuan|Y| Li|Dongye|D|


Assessing the Prediction Effect of Various Prognosis Model for 28-Day Mortality in Acute-on-Chronic Liver Failure Patients.

Abstract:
Background
Acute-on-chronic liver failure (ACLF) is an extremely clinical entity associated with short-term high mortality. The CLIF-SOFA score measures both hepatic and extrahepatic organ dysfunction and can discriminate significantly better between survivors and nonsurvivors compared to other methods. The MELD score is widely used for organ allocation in liver transplantation. Recent reports indicate that the PWR is a potential biomarker for predicting clinical outcomes. The ALBI score is a new score model for evaluating the severity of liver dysfunction. We aimed to compare these prognosis models to predict short-term mortality in ACLF patients.

Methods
A retrospective analysis of 89 ACLF patients between 2015 and 2018 was performed. The receiver operating characteristic (ROC) curve was used to assess the power of four prognosis models for predicting 28-day mortality in patients with ACLF.

Results
The ALBI score, MELD score and CLIF-SOFA score were significantly higher, and the PWR was slightly lower in nonsurviving ACLF patients than in surviving patients. The MELD score and ALBI score were positively correlated with the CLIF-SOFA score, while the PWR was inversely related to the CLIF-SOFA score. The area under the ROC curves (AUROCS) of the CLIF-SOFA score, PWR, ALBI score and MELD score were 0.804, 0.759, 0.710 and 0.670, respectively.

Conclusion
The CLIF-SOFA score, PWR and ALBI score can better predict 28-day mortality in ACLF patients, but the MELD score has worse predictability. The CLIF-SOFA score is the best prognosis model among these models. PWR may be a simple and useful tool that can predict 28-day outcome.

Liu|Lin Xiang|LX|
Zhang|Yue|Y|
Nie|Yuan|Y|0000-0001-7367-2359
Zhu|Xuan|X|

prognosis
acute-on-chronic liver failure
CLIF-SOFA score
albumin-bilirubin score
platelet-to-white blood cell ratio


Identification of candidate genes encoding an LDL-C QTL in baboons.

Abstract: Cardiovascular disease (CVD) is the leading cause of death in developed countries, and dyslipidemia is a major risk factor for CVD. We previously identified a cluster of quantitative trait loci (QTL) on baboon chromosome 11 for multiple, related quantitative traits for serum LDL-cholesterol (LDL-C). Here we report differentially regulated hepatic genes encoding an LDL-C QTL that influences LDL-C levels in baboons. We performed hepatic whole-genome expression profiling for LDL-C-discordant baboons fed a high-cholesterol, high-fat (HCHF) diet for seven weeks. We detected expression of 117 genes within the QTL 2-LOD support interval. Three genes were differentially expressed in low LDL-C responders and 8 in high LDL-C responders in response to a HCHF diet. Seven genes (ACVR1B, CALCOCO1, DGKA, ERBB3, KRT73, MYL6B, TENC1) showed discordant expression between low and high LDL-C responders. To prioritize candidate genes, we integrated miRNA and mRNA expression profiles using network tools and found that four candidates (ACVR1B, DGKA, ERBB3, TENC1) were miRNA targets and that the miRNAs were inversely expressed to the target genes. Candidate gene expression was validated using QRT-PCR and Western blotting. This study reveals candidate genes that influence variation in LDL-C in baboons and potential genetic mechanisms for further investigation.

Karere|Genesio M|GM|
Glenn|Jeremy P|JP|
Birnbaum|Shifra|S|
Hafizi|Sassan|S|
Rainwater|David L|DL|
Mahaney|Michael C|MC|
VandeBerg|John L|JL|
Cox|Laura A|LA|

D020133:Reverse Transcriptase Polymerase Chain Reaction

cardiovascular disease
dyslipidemia
diet-responsive liver gene expression
low density lipoprotein-cholesterol


Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis.

Abstract: The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP.

Sussman|Morgan|M| Napodano|Anthony|A| Huang|Simo|S| Are|Abhirup|A| Hsu|Sylvia|S| Motaparthi|Kiran|K|0000-0003-0562-0826

D056150:Acute Generalized Exanthematous Pustulosis


AMPK activates LXRα and ABCA1 expression in human macrophages.

Abstract: ATP-binding cassette transporter A1 (ABCA1) is a key modulator of macrophage cholesterol homeostasis. We studied the impact of AMP-activated protein kinase (AMPK) on ABCA1 expression in primary human and THP-1 macrophages. Pharmacological or genetic activation of AMPK increased mRNA and protein expression of ABCA1 and its transcriptional activator liver X receptor (LXR) α, resulting in increased cholesterol efflux to apolipoprotein AI-containing medium. On the other side, an AMPK knockdown decreased ABCA1 and LXRα mRNA and protein. Silencing LXRα, but not LXRβ, attenuated ABCA1 expression after AMPK activation, and luciferase reporter as well as chromatin immunoprecipitation analyses showed the binding of LXRα to the LXR responsive element in the ABCA1 promoter. Inhibition of extracellular-signal regulated kinase and mechanistic target of rapamycin signalling increased ABCA1 expression, at the same time making it unresponsive to AMPK activation. Considering other potential regulators of ABCA1 expression, we excluded histone deacetylase HDAC9 and FOXO3 involvement in mediating AMPK effects on ABCA1. Our data link AMPK activation to an increased cholesterol efflux capacity of macrophages, suggesting an atheroprotective effect of macrophage AMPK.

Kemmerer|Marina|M| Wittig|Ilka|I| Richter|Florian|F| Brüne|Bernhard|B| Namgaladze|Dmitry|D|

D064286:ATP Binding Cassette Transporter 1

D048049:Extracellular Signal-Regulated MAP Kinases

Macrophages
Cholesterol
Transcription
AMP‐activated protein kinase (AMPK)
Gene expression
Nuclear receptors


Trace metal determination in natural waters by automated solid phase extraction system and ICP-MS: the influence of low level Mg and Ca.

Abstract: A fully automated high pressure pretreatment system with Nobias Chelate-PA1 resin (PA1) was developed for trace metal determination by ICP-MS in natural waters. By varying the concentrations of Mg and Ca to mimic the concentrations in the eluate obtained by PA1 or iminodiacetate type resins, the overall analytical performance of the system was assessed for the determination of Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Cd, Ag, Pb and REE. Comparing with the low mM level Mg and Ca (both ranging from 1 to 4mM) eluted by iminodiacetate type resins, the eluate obtained by PA1 contains sub-μM level Mg and Ca, which remarkably decrease matrix effect in ICP-MS analysis and significantly improve the analytical performance. With recovery better than 90% for most the trace metals examined, the accuracy was further verified through the analysis of five natural water reference materials with salinity spanning from 0 to 35‰. We have successfully applied the pretreatment system to determine trace metals in the seawater samples collected in the Western Philippine Sea through Taiwan GEOTRACES cruise.

Nobias Chelate-PA1
Matrix effect
GEOTRACES
Iminodiacetate resins
Trace metal preconcentration


Pertrochanteric Calcifications in Patients With Greater Trochanteric Pain Syndrome: Description, Prevalence, and Correlation With Intraoperatively Diagnosed Hip Abductor Tendon Injuries.

Abstract:
BACKGROUND
Pertrochanteric calcifications can be found in patients with greater trochanteric pain syndrome (GTPS). A systematic description of the types and prevalence of these calcifications has not been undertaken. Furthermore, there is conflicting evidence regarding their association with abductor tendon injuries.

PURPOSE
(1) To describe the various types and prevalence of pertrochanteric calcifications in patients presenting for the surgical management of recalcitrant GTPS. (2) To evaluate the association of the various calcifications with intraoperatively diagnosed hip abductor tendon injuries, including tendinosis, partial-thickness tears, and full-thickness tears.

STUDY DESIGN
Cross-sectional study; Level of evidence, 3.

METHODS
Patients undergoing surgical management for GTPS, in isolation or as an ancillary procedure during hip arthroscopy for femoroacetabular impingement, between April 2008 and February 2020 were included. Of these, 85 procedures were isolated treatment of GTPS and the remaining 628 were ancillary to hip arthroscopy. Radiographs were scrutinized for the presence of pertrochanteric calcifications. The hip abductor tendon status was intraoperatively classified as intact, partial-thickness tear, or full-thickness tear. The prevalence and correlation of the various radiographic findings in relation to the intraoperatively classified tendon condition were analyzed via the odds ratio (OR).

RESULTS
Surgery was performed on 713 hips with recalcitrant GTPS. No tear was found in 340 hips (47.7%), 289 hips (40.5%) had a partial-thickness tear, and 84 hips (11.8%) had a full-thickness tear. Radiographically, 102 hips (14.3%) demonstrated proximally directed enthesophytes, and 34 (4.8%) had distally directed enthesophytes. In addition, 75 hips (10.5%) had amorphous calcifications, 47 (6.6%) had isolated ossicles, and 110 (15.4%) had surface irregularities. The presence of any calcification was associated with partial-thickness tears (OR, 1.67 [95% CI, 1.21-2.21]; P = .002) and full-thickness tears (OR, 6.40 [95% CI, 3.91-10.47]; P < .001). Distally directed enthesophytes (OR, 10.18 [95% CI, 3.08-33.63]; P < .001) and proximally directed enthesophytes (OR, 8.69 [95% CI, 4.66-16.21]; P < .001) were the findings with the highest OR for the presence of any type of tear. Distally directed enthesophytes were the findings with the highest OR for a full-thickness tear (OR, 15.79 [95% CI, 7.55-33.06]; P < .001). Isolated ossicles were the findings with the highest OR for a partial-thickness tear (OR, 1.73 [95% CI, 0.96-3.13]; P = .070).

CONCLUSION
Pertrochanteric calcifications were common radiographic findings in patients with GTPS and can help guide management in these patients. Proximally and distally directed enthesophytes were strong predictors for the presence of a hip abductor tendon tear, and specifically a full-thickness tear, and increasing size of the findings was associated with more severe tendon injuries.

Rosinsky|Philip J|PJ|
Yelton|Mitchell J|MJ|
Ankem|Hari K|HK|0000-0002-5936-7806
Meghpara|Mitchell B|MB|
Maldonado|David R|DR|
Shapira|Jacob|J|
Yelton|Brent R|BR|
Lall|Ajay C|AC|
Domb|Benjamin G|BG|


How can we optimise the pharmaceutical analysis of radiopharmaceutical pediatric prescriptions?

Abstract:
OBJECTIVES
In France, dispensation is defined by the validation of a prescription associated with a pharmaceutical analysis, preparation of medication and provision of information necessary for proper use. There are very few data available in the literature that describe prescription analysis modality in radiopharmacy. The aim was to secure a place for paediatric prescription analysis in radiopharmacy by designing a flow chart validated by experts.

METHODS
Experts from different disciplines and health setups (ie, public, private) were selected to represent the various paediatric patient care processes. A review of the literature on pharmaceutical analysis and paediatric prescription in radiopharmacy was conducted. A Delphi approach comprising two rounds (Google Form survey) was used to validate the flow chart. Answers were graded according to a nine-point Likert scale for agreement. Open-ended questions allowed experts to comment on the propositions. A consensus between experts was reached if more than 70% of the experts agreed on an item and fewer than 30% disagreed.

RESULTS
Sixty-five experts were solicited: two oncopaediatricians, three nuclear medicine physicians, 46 radiopharmacists, three residents in radiopharmacy, one hospital pharmacist, five medical physicists, one pharmacy technician, two X-ray technicians and two patients who are pharmacists. The first round survey included a draft of the flow chart: 31 experts answered (48%). All professional disciplines were represented except pharmacy technician. The second round survey was sent with a new flow chart that had been improved by the experts' comments. After 3 weeks, 18 answers were obtained (28%). After the first round, consensus was obtained for each item. Experts gave a total of 97 comments. The second flow chart had three steps: regulatory aspects, patient data, and radiopharmaceutical data, and it was accompanied by descriptive text explaining the field of application.

CONCLUSION
The resulting flow chart will secure the pharmaceutical analysis step for this special patient population.

pediatrics
nuclear medicine
hospital
pharmaceutical preparations
pharmacy service
quality of health care
total quality management


Risk factors for Enterobius vermicularis infection in children in Gaozhou, Guangdong, China.

Abstract:
BACKGROUND
Enterobius vermicularis infection is a prevalent intestinal parasitic disease in children. In this study, we explored the epidemiological status and risk factors for E. vermicularis infection in children in southern China.

METHODS
A cross-sectional survey was carried out in Gaozhou city, Guangdong province, China, in December 2011. Children aged 2-12 years from five schools participated in the study. The adhesive cellophane-tape perianal swab method was applied to detect E. vermicularis infection, while a questionnaire was sent to each child's guardian(s) to collect demographic and socioeconomic data, as well as hygiene behaviors, pertaining to each child. Univariate and multivariate logistic regression analyses were performed to capture the potential risk factors.

RESULTS
Out of the 802 children surveyed, 440 were infected with E. vermicularis, with an average prevalence of 54.86 %, and a range from 45.96 to 68.13 %. The age variable was found to be statistically significant, whereas the sex variable was not. It was found that a mother's education level (low) and not washing hands before dinner were major risk factors in all children (802). After stratification by age, a father's education level (primary or below) and biting pencils (or toys) were significant risk factors in the younger children (508), while not washing hands before dinner and playing on the ground were important risk factors in the older children (294).

CONCLUSION
This study demonstrates the prevalence of E. vermicularis infection in children in Gaozhou and reveals underlying risk factors. Most importantly, it reveals that risk factors differ among the different age groups, which indicates that different control measures targeted at particular age groups should be implemented.

Li|Hong-Mei|HM| Zhou|Chang-Hai|CH| Li|Zhi-Shi|ZS| Deng|Zhuo-Hui|ZH| Ruan|Cai-Wen|CW| Zhang|Qi-Ming|QM| Zhu|Ting-Jun|TJ| Xu|Long-Qi|LQ| Chen|Ying-Dan|YD|

Risk factor
Enterobius vermicularis
Children
China
Prevalence


Knocking on prison's door: a 10-fold rise in the number of psychotic prisoners in Finland during the years 2005-2016.

Abstract:
BACKGROUND
As in many European countries, Finnish psychiatric services experienced a rapid process of deinstitutionalization in the 1990s. In recent decades, the decrease in numbers of psychiatric hospital beds has in several countries been found to be linked with increasing criminality among severely mentally ill individuals. It has been concluded that deinstitutionalization could be the main reason for this development.

AIM
To investigate whether the prevalence of severely mentally ill persons to prison is a growing trend also in Finland.

METHODS
We searched for the annual data in electronic case files of all prisoners about the ICD-10 diagnostic group of the most severe psychotic disorders. We also searched for the comorbid substance use disorders. Psychotic disorders due to substance abuse only were excluded from this study.

RESULTS
During the years 2005-2016, a rapid 10-fold increase in psychotic disorders has occurred in Finnish prisons. In 2016, 185 prisoners (5.9% of all Finnish prisoners) were diagnosed as having a psychotic disorder that was not induced by substance abuse. The causes of this dramatic change are unclear. Comorbid substance abuse disorders were detected in only 39.5% of these prisoners and therefore substance abuse can only partly explain the increasing criminality of the severely mentally ill persons. 80.5% of psychotic disorders were diagnosed in Psychiatric Hospital for prisoners and 19.5% in prison policlinic services.

CONCLUSION
Trans-institutionalization has become a serious challenge for the Finnish criminal justice and mental health systems. Further studies are needed to detect the causes of this change. More specialized services for severely mentally ill persons are needed both in the community psychiatry and also inside the prison services.

prisoners
deinstitutionalization
trans-institutionalization
Penrose’s law
psychosis


miR-214 promotes the proliferation and invasion of osteosarcoma cells through direct suppression of LZTS1.

Abstract: Previous studies have shown that miR-214 functions either as an oncogene or a tumor suppressor in various human cancer types. The role of this microRNA in osteosarcoma (OS) is presently unclear. Here, we demonstrated that miR-214 is frequently upregulated in OS specimens, compared with noncancerous bone tissues. Bioinformatics analysis further revealed leucine zipper, putative tumor suppressor 1 (LZTS1) as a potential target of miR-214. Expression patterns of miR-214 were inversely correlated with those of LZTS1 mRNA and protein in OS tissues. Data from reporter assays showed that miR-214 directly binds to the 3'-untranslated region (3'-UTR) of LZTS1 mRNA and suppresses expression at both transcriptional and translational levels. In functional assays, miR-214 promoted OS cell proliferation, invasion and tumor growth in nude mice, which could be reversed by overexpression of LZTS1. Taken together, our data provide compelling evidence that miR-214 functions as an onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of LZTS1.


Trajectories of cortical surface area and cortical volume maturation in normal brain development.

Abstract: This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article "Trajectories of cortical thickness maturation in normal brain development - the importance of quality control procedures" (Ducharme et al., 2015) [1].

Ducharme|Simon|S|
Albaugh|Matthew D|MD|
Nguyen|Tuong-Vi|TV|
Hudziak|James J|JJ|
Mateos-Pérez|J M|JM|
Labbe|Aurelie|A|
Evans|Alan C|AC|
Karama|Sherif|S|
|||

Cortical surface area
Cortical volume
Brain development
Cortical thickness
Magnetic resonance
imaging


Sonidegib for the Treatment of Advanced Basal Cell Carcinoma.

Abstract: Basal cell carcinoma (BCC) accounts for almost 80% of skin cancers, and its healthcare workload burden is substantial within dermatology departments. Although most BCCs are small, well-defined tumors amenable of surgery or conservative procedures, in a small proportion of patients, BCCs can progress to an advanced stage including locally advanced BCC. The goal of the clinician in the treatment of BCC should be the right therapeutic approach at diagnosis, and different guidelines propose treatment strategies in order to prevent relapses or disease progression. In case of unresectable and untreatable BCC with radiotherapy, the first-choice medical therapy is Hedgehog-GLI (HH) pathway inhibitors. Sonidegib was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a first-line treatment for adult patients with locally advanced BCC, becoming the second HH pathway inhibitor receiving approval after vismodegib. In this review, data on pharmacology, safety, tolerability, and efficacy of sonidegib are summarized and compared to those of vismodegib. Lastly, indications on the management of advanced basal cell carcinoma based on author's clinical experience are provided.

Brancaccio|Gabriella|G| Pea|Federico|F| Moscarella|Elvira|E| Argenziano|Giuseppe|G|

sonidegib
advanced basal cell carcinoma
basal cell carcinoma
skin cancer
hedgehog inhibitors


Association between substance use and concurrent sexual relationships among urban slum dwellers in Nairobi, Kenya.

Abstract: While the overall incidence and prevalence of HIV/AIDS are declining in Africa, substance use-related HIV/AIDS is on the rise. The main objectives of this study were to elicit the types of commonly used substances and to examine the association between substance use and concurrent sexual relationships among slum dwellers in Kenya. Freelisting elicitation techniques were used to identify the most commonly used substances using 53 key informants. This was followed by a self-administered, structured questionnaire using a convenience sample of 506 participants. Findings from our freelisting analysis produced 27 substances that were used in the community. Analysis of the survey data shows that participants who reported using substances in the past three months were more likely to be involved in concurrent sexual relationships than those who did not (86.2% vs. 74.0%; p = .002). In the multivariable model, the odds of ever having concurrent sexual relationships were higher among participants who used any substance in the past three months (aOR 2.46; 95% CI 1.37-4.42, p < .01). The observed association between substance use and concurrent sexual relationships may be influenced by social and economic factors such as poverty and lack of opportunity among urban slum dwellers.

Substance use
concurrent sexual relationships
urban slum
Kenya


Explicit knowledge enhances motor vigor and performance: motivation versus practice in sequence tasks.

Abstract: Motor skill learning involves a practice-induced improvement in the speed and/or accuracy of a discrete movement. It is often thought that paradigms involving repetitive practice of discrete movements performed in a fixed sequence result in a further enhancement of skill beyond practice of the individual movements in a random order. Sequence-specific performance improvements could, however, arise without practice as a result of knowledge of the sequence order; knowledge could operate by either enabling advanced motor planning of the known sequence elements or by increasing overall motivation. Here, we examined how knowledge and practice contribute to performance of a sequence of movements. We found that explicit knowledge provided through instruction produced practice-independent improvements in reaction time and execution quality. These performance improvements occurred even for random elements within a partially known sequence, indicative of a general motivational effect rather than a sequence-specific effect of advanced planning. This motivational effect suggests that knowledge influences performance in a manner analogous to reward. Additionally, practice led to similar improvements in execution quality for both known and random sequences. The lack of interaction between knowledge and practice suggests that any skill acquisition occurring during discrete sequence tasks arises solely from practice of the individual movement elements, independent of their order. We conclude that performance improvements in discrete sequence tasks arise from the combination of knowledge-based motivation and sequence-independent practice; investigating this interplay between cognition and movement may facilitate a greater understanding of the acquisition of skilled behavior.

Wong|Aaron L|AL|
Lindquist|Martin A|MA|
Haith|Adrian M|AM|
Krakauer|John W|JW|

skill learning reward cognition sequential