bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphodiesterase type 5 in men with vasculogenic and post‐radical prostatectomy erectile dysfunction: is there a molecular difference?
Authors: Karakus Serkan , Musicki Biljana , Burnett Arthur L. 
Published: June 2018

ObjectivesTo clarify the molecular basis of penile erection at the human level and distinguish the mechanisms underlying vasculogenic and post‐radical prostatectomy (RP) erectile dysfunction (ED) subtypes.Patients and MethodsErectile tissue was obtained from men without history of ED who underwent penile surgery for Peyronie's disease (control group, n = 5) and from men with ED who underwent penile prosthesis implantation (n = 17). ED was categorized into vasculogenic (n = 8) and post‐RP (n = 9) subtypes. Penile erectile tissue samples were collected for molecular analyses of protein expressions of neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively), phospho‐nNOS (Ser‐1412), phospho‐eNOS (Ser‐1177), phospho‐protein kinase B (Ser‐473), phosphodiesterase type 5 (PDE5), α‐smooth muscle actin, phospho‐myosin phosphatase target subunit 1, RhoA/Rho‐associated protein kinase (ROCK)‐α, ROCK‐β, 4‐hydroxy‐2‐nonenal, and nNOS and eNOS uncoupling by Western blot.ResultsVasculogenic ED was characterized by decreased eNOS protein expression and eNOS and nNOS phosphorylation on their activatory sites (Ser‐1177 and Ser‐1412, respectively), uncoupled eNOS, upregulated PDE5 protein expression, increased ROCK activity, and increased oxidative stress in erectile tissue. Post‐RP ED was characterized by decreased nNOS protein expression, increased nNOS phosphorylation on its activatory site (Ser‐1412), uncoupled nNOS, downregulated PDE5 protein expression, and increased oxidative stress in erectile tissue.ConclusionThe mechanisms of vasculogenic and post‐RP ED in the human penis involve derangements in constitutive nitric oxide synthase function, PDE5 protein expression and ROCK activity, and increased oxidative stress, which conceivably provide a molecular basis for chronically reduced nitric oxide bioavailability and increased smooth muscle contraction contributing to erectile impairment. Selective differences in PDE5 protein expression suggest distinct molecular mechanisms are in play for these ED subtypes.
Svalbard glaciers re‐advanced during the Pleistocene–Holocene transition
Authors: Farnsworth Wesley R. , Ingólfsson Ólafur , Retelle Michael , Allaart Lis , Håkansson Lena M. , Schomacker Anders 
Published: June 2018

Despite warming regional conditions and our general understanding of the deglaciation, a variety of data suggest glaciers re‐advanced on Svalbard during the Lateglacial–early Holocene (LGEH). We present the first well‐dated end moraine formed during the LGEH in De Geerbukta, NE Spitsbergen. This landform was deposited by an outlet glacier re‐advancing into a fjord extending 4.4 km beyond the late Holocene (LH) maximum. Comparing the timing of the De Geerbukta glacier re‐advance to a synthesis of existing data including four palaeoclimate records and 15 other proposed glacier advances from Svalbard does not suggest any clear synchronicity in glacial and climatic events. Furthermore, we introduce six additional locations where glacier moraines have been wave‐washed or cut by postglacial raised marine shorelines, suggesting the landforms were deposited before or during high relative sea‐level stands, thus exhibiting a similar LGEH age. Contrary to current understanding, our new evidence suggests that the LGEH glaciers were more dynamic, exhibited re‐advances and extended well beyond the extensively studied LH glacial expansion. Given the widespread occurrence of the LGEH glacier deposits on Svalbard, we suggest that the culmination of the Neoglacial advances during the Little Ice Age does not mark the maximum extent of most Svalbard glaciers since deglaciation; it is just the most studied and most visible in the geological record.
Investigating the agreement between the clinician and research diagnosis of attention deficit hyperactivity disorder and how it changes over time; a clinical cohort study
Authors: Longridge Rachel , Norman Shelley , Henley William , Newlove Delgado Tamsin , Ford Tamsin 
Published: June 2018

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) is a common reason for referral to Child and Adolescent Mental Health Services (CAMHS), but families experience long delays between first professional contact and diagnosis, which risks development of secondary impairments. This study explores the agreement between clinician and research diagnoses of ADHD among children attending CAMHS, and their access to interventions. From the limited literature, we anticipated fluctuation and delays, but no other study has focused prospectively on ADHD diagnoses.MethodsThis was a secondary analysis of a cohort of children attending two CAMHS between 2006 and 2009. The sample included 288 consecutive referrals of children aged between 5 and 11 years. Parents and teachers completed the Development and Well‐Being Assessment (DAWBA) when the child was recruited to the study, which provided the research diagnosis of ADHD from the baseline. Clinicians reported no, possible, or definite diagnosis of ADHD and interventions provided at 6‐monthly intervals for up to 2 years while the child attended CAMHS. We assessed agreement between the diagnoses using Kendall's Tau‐B.ResultsOf the 101 children with a research diagnosis of ADHD, 26 received a definite clinician diagnosis during 2‐year follow‐up, and 47 received a possible clinician diagnosis. The chance‐corrected agreement was poor at all time points (Kendall's Tau‐B 0.14–0.48). Clinician diagnoses were unstable, particularly if possible ADHD was recorded at the initial assessment. Of those with a research diagnosis, 15 were prescribed medication and 11 were offered parent training.ConclusionsThe use of standardised diagnostic assessments could reduce diagnostic uncertainty and increase access to evidence‐based interventions.
Socioeconomic and ethnic inequalities in oral health among children and adolescents living in England, Wales and Northern Ireland
Authors: Rouxel Patrick , Chandola Tarani 
Published: June 2018

AbstractObjectivesAlthough adolescence is a sensitive developmental period in oral health, the social equalization hypothesis that suggests health inequalities attenuate in adolescence has not been examined. This study analyses whether the socioeconomic gap and ethnic disadvantage in oral health among children aged 5 reduces among adolescents aged 15.MethodsData from the cross‐sectional Children's Dental Health Survey 2013 were analysed, comprising of 8541 children aged 5, 8, 12 and 15 attending schools in England, Wales and Northern Ireland. Oral health indicators included decayed and filled teeth, plaque, gingivitis and periodontal health. Ethnicity was measured using the 2011 UK census ethnic categories. Socioeconomic position was measured by family, school and residential deprivation. Negative binomial and probit regression models estimated the levels of oral health by ethnicity and socioeconomic position, adjusted for demographic and tooth characteristics.ResultsThe predicted rate of decayed teeth for White British/Irish children aged 5 was 1.54 (95%CI 1.30‐1.77). In contrast, the predicted rate for Indian and Pakistani children was about 2‐2.5 times higher. At age 15, ethnic differences had reduced considerably. Family deprivation was associated with higher levels of tooth decay among younger children but not among adolescents aged 15. The influence of residential deprivation on the rate of tooth decay and filled teeth was similar among younger and older children. Moreover, inequalities in poor periodontal health by residential deprivation was significantly greater among 15‐year‐old children compared to younger children.ConclusionsThis study found some evidence of smaller ethnic and family socioeconomic differences in oral health among British adolescents compared to younger children. However, substantial differences in oral health by residential deprivation remain among adolescents. Community levels of deprivation may be particularly important for the health of adolescents.
Topical axitinib is a potent inhibitor of corneal neovascularization
Authors: Lledó Riquelme Mariola , Campos‐Mollo Ezequiel , Fernández‐Sánchez Laura 
Published: June 2018

AbstractBackgroundThis study evaluated the effects of topically applied axitinib, a tyrosine kinase inhibitor, in an experimental model of corneal neovascularization (CNV).MethodsA total of 48 New Zealand rabbits were used. CNV was induced by placing five silk sutures in the upper cornea of one eye per rabbit. Rabbits were randomized into four groups (12 rabbits each): 0.9% saline (control group), 0.02 mg/mL axitinib, 0.35 mg/mL axitinib and 0.5 mg/mL axitinib groups. All treatments were administered three times daily for 14 days. Photographs were taken using a slit lamp on days 7 and 14. The area of neovascularization was measured in mm2, as the percentage of total corneal area and as the percentage of corneal surface covered by sutures (SCS).ResultsOn day 14, the CNV area in the control group (31.50 ± 7.47 mm2; 115.00 ± 22.55% of the corneal SCS) was larger than that in the 0.02 mg/mL axitinib group (19.20 ± 8.92 mm2; 73.89 ± 34.98%), the 0.35 mg/mL axitinib group (8.83 ± 3.92 mm2; 31.90 ± 13.59%) and the 0.5 mg/mL axitinib group (5.12 ± 3.97 mm2; 18.38 ± 13.65%). Compared with saline, CNV was inhibited 39.04% by 0.02 mg/mL axitinib, 71.96% by 0.35 mg/mL axitinib and 84.73% by 0.5 mg/mL axitinib.ConclusionTopical administration of the three axitinib concentrations inhibited CNV in rabbits, blocking both vascular endothelial growth factor and platelet‐derived growth factor pathways. Axitinib at 0.5 mg/mL induced profound inhibition of corneal angiogenesis.
Clinical characteristics and outcomes of PTLD following intestinal transplantation
Authors: Wozniak Laura J. , Mauer Tian L. , Venick Robert S. , Said Jonathan W. , Kao Roy L. , Kempert Pamela , Marcus Elizabeth A. , Hwang Vilayphone , Cheng Elaine Y. , Busuttil Ronald W. , McDiarmid Sue V. , Farmer Douglas G. 
Published: June 2018

AbstractPost‐transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single‐center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy‐proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow‐up time of 6.4 (1.6‐14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re‐ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.
Homicides with direct and indirect links to the night‐time economy
Authors: Tomsen Stephen 
Published: June 2018

AbstractIntroduction and AimsAlcohol use and homicide are a wide community concern with particular interest in understanding and preventing attacks (e.g. ‘one punch’ male on male attacks) in commercial nightlife settings with high levels of collective drinking. There is insufficient knowledge of the long‐term patterns in this violence or the relationship between public drinking and flow on violence in other social settings.Design and MethodsAlcohol‐related homicides were those in which alcohol consumption was a contributing factor. Those also linked to purchase or consumption in locations where alcohol is sold after dark were classified as night‐time economy related. The study comprised a first‐hand analysis of files in the archive of the Australian National Homicide Monitoring Program in 2 years with a decade gap (1998/1999–2007/2008), and it classified 73 of all 238 alcohol‐related incidents by direct or indirect relation to public nightlife settings.ResultsRelated homicides in these years were not highly concentrated in developed night‐time economies, but more spread outside major nightlife zones. Indirectly related killings were even more dispersed and included more women victims killed in domestic settings.Discussion and ConclusionsThere is a consistent though dispersed relationship between heavy public drinking at night and homicide. Concerns about homicide and night‐time drinking leisure with mostly male victims attacked in well‐known areas of busy city nightlife, must also consider the broader gendered patterns of ‘flow on’ nightlife‐related incidents, including fatal semi‐private and domestic violence that is indirectly but importantly related to drinking and alcohol purchase in public commercial nightlife.
Community violence exposure in early adolescence: Longitudinal associations with hippocampal and amygdala volume and resting state connectivity
Authors: Saxbe Darby , Khoddam Hannah , Piero Larissa Del , Stoycos Sarah A. , Gimbel Sarah I. , Margolin Gayla , Kaplan Jonas T. 
Published: June 2018

AbstractCommunity violence exposure is a common stressor, known to compromise youth cognitive and emotional development. In a diverse, urban sample of 22 adolescents, participants reported on community violence exposure (witnessing a beating or illegal drug use, hearing gun shots, or other forms of community violence) in early adolescence (average age 12.99), and underwent a neuroimaging scan 3–5 years later (average age 16.92). Community violence exposure in early adolescence predicted smaller manually traced left and right hippocampal and amygdala volumes in a model controlling for age, gender, and concurrent community violence exposure, measured in late adolescence. Community violence continued to predict hippocampus (but not amygdala) volumes after we also controlled for family aggression exposure in early adolescence. Community violence exposure was also associated with stronger resting state connectivity between the right hippocampus (using the manually traced structure as a seed region) and bilateral frontotemporal regions including the superior temporal gyrus and insula. These resting state connectivity results held after controlling for concurrent community violence exposure, SES, and family aggression. Although this is the first study focusing on community violence in conjunction with brain structure and function, these results dovetail with other research linking childhood adversity with smaller subcortical volumes in adolescence and adulthood, and with altered frontolimbic resting state connectivity. Our findings suggest that even community‐level exposure to neighborhood violence can have detectable neural correlates in adolescents.
Improved glycaemic control and treatment satisfaction with a simple wearable 3‐day insulin delivery device among people with Type 2 diabetes
Authors: Mader J. K. , Lilly L. C. , Aberer F. , Poettler T. , Johns D. , Trautmann M. , Warner J. L. , Pieber T. R. 
Published: June 2018

AbstractAimTo evaluate the PAQ® (CeQur SA, Horw, Switzerland), a wearable 3‐day insulin delivery device that provides set basal rates and bolus insulin on demand, in people with Type 2 diabetes.MethodAdults with Type 2 diabetes with HbA1c concentrations ≥53 and ≤97 mmol/mol (7.0 and 11.0%) while treated with ≥2 insulin injections/day were enrolled in two single‐arm studies comprising three periods: a baseline (insulin injections), a transition and a PAQ treatment period (12 weeks). Endpoints included HbA1c, seven‐point self‐monitored blood glucose, total daily dose of insulin and body weight. Safety was assessed according to examination, hypoglycaemic episodes and adverse device effects.ResultsA total of 28 adults were enrolled (age 63 ± 7 years, 86% men, BMI 32.3 ± 4.3kg/m2, Type 2 diabetes duration 17 ± 8 years, HbA1c 70 ± 12 mmol/mol (8.6 ± 1.1%), total daily insulin dose 58.7 ± 20.7 U), of whom 24 completed the studies. When transitioned to PAQ, 75% of participants continued on the first basal rate selected. After 12 weeks of PAQ wear, significant improvements from baseline were seen [HbA1c –16 ± 9 mmol/mol (95% CI –20, –12) or –1.5 ± 0.9% (95% CI –1.8, –1.1) P<0.0001], and at all seven self‐monitored blood glucose readings time points (P ≤0.03). Total daily insulin dose increased by 12.1 ± 19.5 U (95% CI 3.9, 20.4; P=0.0058), the number of meal time boluses increased by 0.9 ± 1.5/day (95% CI 0.3, 1.5; P=0.0081) and body weight remained stable. Six participants had mild to moderate catheter site reactions and one mild skin irritation occurred. No participant experienced severe hypoglycaemia.ConclusionsAdults with Type 2 diabetes were safely transitioned from insulin injections to the PAQ and had significantly improved glycaemic control and treatment satisfaction with insulin therapy.(ClinicalTrials.gov identifiers: NCT02158078 & NCT02419859)
Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study
Authors: Fioretto Paola , Del Prato Stefano , Buse John B. , Goldenberg Ronald , Giorgino Francesco , Reyner Daniel , Langkilde Anna Maria , Sjöström C. David , Sartipy Peter ,   On Behalf of the DERIVE Study Investigators
Published: June 2018

AimsDapagliflozin is a selective inhibitor of sodium glucose co‐transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45–59 mL/min/1.73 m2; chronic kidney disease [CKD] stage 3A).Materials and methodsIn this double‐blind, parallel group, Phase 3 study (NCT02413398, clinicaltrials.gov) patients with inadequately controlled T2D (HbA1c 7.0%‐11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N = 160) or matching placebo (N = 161) for 24 weeks. Randomization was stratified by pre‐enrolment glucose‐lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24.ResultsAt Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], −0.34% [−0.53, −0.15]; P < 0.001), body weight (difference [95% CI], −1.25 kg [−1.90, −0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], −0.9 mmol/L [−1.5, −0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], −3.1 mm Hg [−6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (−2.49 mL/min/1.73 m2 [−4.96, −0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post‐treatment) (0.61 mL/min/1.73 m2 [−1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported.ConclusionsThe findings of this study (NCT02413398, clinicaltrials.gov) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.
Glycaemic control, hypoglycaemia, and weight change with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Japanese adults with type 2 diabetes: A 12‐month comparison by concomitant sulphonylurea and/or glinide use
Authors: Terauchi Yasuo , Riddle Matthew C. , Hirose Takahisa , Koyama Masayoshi , Cheng Xi , Takahashi Yoshinori , Bolli Geremia B. 
Published: June 2018

AimTo explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla‐300) and 100 U/mL (Gla‐100) differed by sulphonylurea and/or glinide (SU/G) treatment.MethodsA post hoc subgroup analysis of 12‐month treatment data from the EDITION Japan 2 trial, a randomized, open‐label, phase 3 study of Japanese people with type 2 diabetes receiving once‐daily Gla‐300/Gla‐100 + oral antihyperglycaemic drugs. Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (‐SU/G). Endpoints included HbA1c, hypoglycaemia and body weight.ResultsFor +SU/G (n = 152, 63%), HbA1c was reduced from baseline to month 12 for Gla‐300 (8.1% to 7.6%) and Gla‐100 (8.2% to 7.8%). For ‐SU/G (n = 89, 37%), reductions were 7.8% to 7.4%, and 7.9% to 7.5% for Gla‐300 and Gla‐100, respectively. A lower annualized rate of hypoglycaemia with Gla‐300 versus Gla‐100 was observed at night (00:00–05:59 hours; p = 0.0001) and any time of day (24 hour; p = 0.0015). Irrespective of the insulin used, the incidence and rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia appeared higher in +SU/G versus ‐SU/G; overall, a reduced incidence of nocturnal hypoglycaemia, and rate of hypoglycaemia at any time, was observed in ‐SU/G versus +SU/G. In the ‐SU/G subgroup, body weight gain differences were observed between Gla‐300 and Gla‐100 (p < 0.0001).ConclusionsParticipants with prior and continued SU/G use had similar therapeutic responses with basal insulin but greater risk of hypoglycaemia than those not using SU/G; hypoglycaemia risk was lower with Gla‐300 than Gla‐100 in both subgroups.
Destigmatizing psychosis: Investigating the effectiveness of a school‐based programme in Hong Kong secondary school students
Authors: Hui Christy L.M. , Leung Whitty W.T. , Wong Andreas K.H. , Loong Ka Yan , Kok Joy , Hwang Amanda , Lee Edwin H.M. , Chan Sherry K.W. , Chang Wing Chung , Chen Eric Y.H. 
Published: June 2018

AimAlthough the reasons behind the stigmatization of psychosis are manifold, poor mental health literacy among the general public is likely to be a major factor. In Hong Kong, the Early Psychosis Foundation (EPISO) was established in 2007 to tackle this issue by providing educational and mental health promotional activities, among other aims and services. The current study evaluated the effectiveness of a school‐based interventional programme, the School Tour, developed by EPISO.MethodsThe School Tour differentiates itself from other interventional programmes by supplementing a traditional psychoeducational talk with 2 additional elements: an engaging drama performance and exercise demonstrations. Twelve secondary schools, with a total of 4520 students, participated in the study. Knowledge and attitudes towards psychosis were evaluated before and after the school programme.ResultsThe School Tour was found to improve both students' knowledge of psychosis (P < .001) and their attitude (P < .001) towards the illness.ConclusionsIts effectiveness in reducing the stigma towards psychosis validates the use of novel strategies like drama performances to engage adolescent students, and urges the government to support increased student participation in the programme by providing funding to the relevant organizations.