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Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood–brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-β/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.

Background: China contributes to almost half of the esophageal cancer cases diagnosed globally each year. However, the prognosis information of this disease in this large population is scarce. Methods: Data on a population-based cohort consisting of residents of Shandong Province, China who were diagnosed with esophageal cancer during the period from 2005 to 2014 were analyzed. The cancer-specific survival rates were estimated using Kaplan–Meier analysis. Discrete-time multilevel mixed-effects survival models were used to investigate socioeconomic status (SES) disparities on esophageal cancer survival. Results: The unadjusted 1-, 3-, and 5-year cause-specific survival rates were 59.6% [95% confidence interval (CI), 59.2%–59.9%], 31.9% (95% CI, 31.5%–32.3%), and 23.6% (95% CI, 23.1%–24.0%), respectively. Patients of blue-collar occupations had higher risk of esophageal cancer–related death than those of white-collar occupations in the first 2 years after diagnosis. Rural patients had higher risk of death than urban patients in the first 3 years after diagnosis. The risks of esophageal cancer–related death among patients living in low/middle/high SES index counties were not different in the first 2 years after diagnosis. However, patients living in high SES index counties had better long-term survival (3–5 years postdiagnosis) than those living in middle or low SES index counties. Conclusions: Socioeconomic inequalities in esophageal cancer survival exist in this Chinese population. Higher individual- or area-level SES is associated with better short-term or long-term cancer survival. Impact: Elucidation of the relative roles of the SES factors on survival could guide interventions to reduce disparities in the prognosis of esophageal cancer.

This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

© 2017 The Authors Objective: To examine if geographic variations in the participation rates in the National Bowel Cancer Screening Program (NBCSP) are related to population-level socio-demographic characteristics. Methods: Data reflecting participation in the NBCSP for 504 Local Government Areas (LGAs) between July 2011 and June 2013 were extracted from the Social Health Atlas of Australia. Logistic regression models were used to examine independent associations (odds ratios [ORs]) between participation, Remoteness Area (RA) and selected socio-demographic variables. Results: Compared to the participation rate for major cities (33.4%), participation was significantly higher in inner regional areas (36.5%, OR=1.15), but was much lower in remote (27.9%, OR=0.77) or very remote areas (25.0%, OR=0.65). When controlling for study period, gender, proportion of persons aged 65 years and older, Indigenous status, cultural background and socioeconomic status, significantly higher rates were observed in all non-metropolitan areas than in major cities. Indigenous status was strongly related to the poorer participation in remote areas. Conclusions: Socio-demographic characteristics, particularly Indigenous status, cultural background and population ageing, seem to be more important drivers of regional disparities in NBCSP participation than geographic remoteness. Implications for public health: This study provides important evidence to understand the regional disparities in participating in the national screening program.

Purpose: Almost half of the global esophageal cancer (EC) deaths occurred in China. This study aims to examine the geographic spread of EC mortality in two periods in a large Chinese population. Methods: Age-standardized mortality rates (ASMRs) for 140 county-level units in Shandong Province during the periods 1970-74 and 2011-13 were derived using data from the First National Cause-of-Death Survey and the Shandong Death Registration System, respectively. ASMRs were smoothed using Area-to-Area Poisson kriging technique. Spatial scan statistics were used to detect spatial clusters with higher EC mortality and clusters with greater temporal changes in EC mortality. Results: The provincial average ASMR decreased from 13.0 per 100,000 in 1970-74 to 5.8 in 2010-13. Almost all counties or districts have experienced a decrease in EC mortality, while the reduction was particularly pronounced in the mid-west region. This study has identified a geographical cluster with much higher EC mortality rates and the clustering pattern has largely unchanged over the past 40 years. Residents living in the cluster during 1970-74 were 2.7 (95% CI: 2.2-3.4) times more likely to die from EC than the rest of the province. The corresponding risk ratio for the 2011-13 cluster was 3.7 (95% CI: 2.8-5.0). Conclusions: This study detected a geographically defined subpopulation in Shandong, China with much higher risk of dying from EC. This spatial pattern has been consistent over the past few decades. The results suggest the key drives for geographic variations in esophageal cancer may not have changed.

// Zhentao Fu 1, * , Yingmei Li 2, * , Zilong Lu 1, * , Jie Chu 1 , Jiandong Sun 3 , Jiyu Zhang 1 , Gaohui Zhang 1 , Fuzhong Xue 4 , Xiaolei Guo 1, ** and Aiqiang Xu 1, ** 1 Department for Chronic and Non-Communicable Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China 2 The Second People's Hospital of Jinan, Jinan, China 3 School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia 4 School of Public Health, Shandong University, Jinan, China * The first three authors contributed equally to this work ** The last two authors contributed equally to this work Correspondence to: Xiaolei Guo, email: guoxiaolei@126.com Aiqiang Xu, email: aqxuepi@163.com Keywords: lung cancer, spatial scan statistics, mortality, epidemiology Received: March 27, 2017 Accepted: August 06, 2017 Published: September 21, 2017 ABSTRACT Lung cancer has long been a major health problem in China. This study aimed to examine the temporal trend and spatial pattern of lung cancer mortality in Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained from Shandong Death Registration System and three nationwide retrospective cause-of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson models was used to detect possible high-risk spatial clusters. The results show that lung cancer mortality rate in Shandong Province increased markedly from 1970-1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase was associated with both demographic and non-demographic factors. Several significant spatial clusters with high lung cancer mortality were identified. The most likely cluster was located in the northern region of Shandong Province during both 1970-1974 and 2011-2013. It appears the spatial pattern remained largely consistent over the last 40 years despite the absolute increase in the mortality rates. These findings will help develop intervention strategies to reduce lung cancer mortality in this large Chinese population.

Pulmonary edema is a fatal complication of EV71-associated hand, foot, and mouth disease (HFMD). The pathogenesis of EV71-induced pulmonary edema remains largely unclear. In this study, we aimed to explore the roles of the capsid protein VP1 in the occurrence of EV71-induced pulmonary edema. The intranasal inoculation of recombinant VP1 protein caused lung inflammation with an elevation of inflammatory cytokines and neutrophils infiltration. Moreover, neutrophil extracellular traps (NETs) were observed in the lung parenchyma of the mice treated with VP1. VP1 directly induced the formation of NETs, which depended on PAD4. VP1 also damaged the lung barrier via the reduction of the tight junction protein occludin. Moreover, the EV71 attachment receptor vimentin was increased upon VP1 administration. In contrast, NETs decreased vimentin levels, suggesting a novel role for NETs in viral immune defense. These results evidenced a direct role of VP1 in EV71-induced pulmonary edema and demonstrated that NETs may be both harmful and beneficial in EV71 infection.

Esophageal cancer (EC) is a leading cause of cancer death in China. Within Shandong Province, a geographic cluster with high EC mortality has been identified, however little is known about how area-level socioeconomic status (SES) is associated with EC mortality in this province. Multilevel models were applied to EC mortality data in 2011–13 among Shandong residents aged 40+ years. Area-level SES factors consisted of residential type (urban/rural) of the sub-county-level units (n = 262) and SES index (range: 0–10) of the county-level units (n = 142). After adjustment for age and sex, residents living in rural areas had a 22% (95% CI: 13–32%) higher risk of dying from EC than those in urban areas. With each unit increase in the SES index, the average risk of dying from EC reduced by 10% (95% CI: 3–18%). The adjustment of area-level SES variables had little impact on the risk ratio of EC mortality between the high-mortality cluster and the rest of Shandong. In conclusion, rural residence and lower SES index are strongly associated with elevated risks of EC death. However, these factors are independent of the high mortality in the cluster area of Shandong. The underlying causes for this geographic disparity need to be further investigated.

This study aimed to explore the geographic distribution and risk clusters of pancreatic cancer mortality from 2011 to 2013 in Shandong, China, and to detect the differences between urban and rural areas. Our data were obtained from the Shandong Death Registration System (SDRS) and were adjusted according to the underreporting level. The distribution of mortality was displayed with GIS-based maps at the county level. The results showed an increasing trend in pancreatic cancer mortality from the western region to the eastern region of Shandong. Additionally, four significant risk clusters were detected, and the most likely cluster was focused in the northeastern and northern regions. Urban-rural differences in the mortality distribution and risk clusters were also detected. In conclusion, our study identified pancreatic cancer mortality clusters in Shandong in urban and rural areas; these results can contribute to the development of effective and targeted strategies to control pancreatic cancer in different areas.

Background Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. Methods In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. Results The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). Conclusions Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Infertility caused by environmental pollution is becoming a global problem, but an effective prevention or treatment is lacking. Icariin (ICA) is a flavonoid used in traditional Chinese medicine. The present study investigated the possible roles of ICA in preventing testicular dysfunction caused by di(2-ethylhexyl) phthalate (DEHP), one of the most studied environmental endocrine disruptors. Cultured mouse Leydig cells were pretreated with ICA and exposed to DEHP to determine ICA effects upon cell proliferation, reactive oxygen species (ROS) levels, mitochondrial membrane potential (Δψm), testosterone levels and the expression of transcription factor SF-1 and steroidogenic enzymes (CYP11, 3β-HSD and 17β-HSD), which play critical roles in androgen production. Our results showed that ICA reversed the adverse effect of DEHP on Leydig cell proliferation, and decreased ROS levels and elevated Δψm levels. Also, ICA promoted testosterone production and up-regulated the expression of SF-1 and steroidogenic enzymes. We investigated ICA actions in vivo, using male mice administrated DEHP followed by ICA. Exposure to DEHP decreased epididymal sperm counts and disrupted seminiferous tubules, and both of these effects were reversed by ICA treatment. These results showed that the mechanisms of ICA in protecting mouse testes against DEHP-induced damage involves the prevention of ROS accumulation and promotion of testosterone secretion.

International patterns suggest germ cell testicular cancer (GCTC) incidence may be lower in lower latitudes. To investigate this possibility, we examined GCTC incidence by latitude (population centroid in 2000) for men ≥15 years within two reasonably homogeneous countries, the United States and Australia. In the United States, we examined age-adjusted incidence/latitude trends using data from states (2001-2010) and local-area registries (1980-2011). In Australia, we evaluated incidence/latitude trends in 61 Statistical Divisions (2000-2009). In U.S. White men (68 566 cases), state incidences increased by latitude, rising 5.74% (4.45-7.05%) per 5°North latitude increment. Similar trends were found for seminoma and nonseminoma subtypes (P < 0.001). In U.S. Black men (2256 cases), the association was also seen (4.9%; 0.2-9.7%). In local U.S. data, similar increases in incidence with latitude were present in each of the last three decades. In Australia (6042 cases), the incidence increased by 4.43% (95% CI: 1.54-7.39%) per 5°South, and trends for subtypes were similar. Thus, we found that incidence of GCTC in both White and Black men increased significantly with distance from the equator, approximately 1% per degree within the range of latitudes studied.

While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation.

SummaryA CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

The present study aimed to understand spirituality and its relationships with socioeconomic status (SES), religious background, social support, and mental health among Indian university students. It was hypothesized that (1) female university students will be more spiritual than male university students, (2) four domains of spirituality will differ significantly across socioeconomic and religious background of the university students in addition to social support, and (3) there will be a positive relationship between spirituality and mental health of university students, irrespective of gender. A group of 475 postgraduate students aged 20-27 years, 241 males and 234 females, from various disciplines of Pondicherry University, India, participated in the study. Students' background was collected using a structured questionnaire. Overall spirituality and its four dimensions were measured using the Spirituality Attitude Inventory, while mental health status was estimated based on scores of the psychological subscale of the WHO Quality of Life Questionnaire. Female students were significantly more spiritual than male students, particularly in spiritual practice and sense of purpose/connection. Hindu religion and lower family income were associated with lower spirituality. Higher spirituality was associated with congenial family environment and more support from teachers and classmates. There was a strong association between overall spirituality and two spirituality domains (spiritual belief and sense of purpose/connection) with better mental health. Findings suggest an opportunity for open dialogue on spirituality for university students as part of their mental health and support services that fosters a positive mind set and enhancement of resilience.

Alcohol screening and a brief intervention (SBI) can be effective in changing harmful drinking behaviour and reducing the chance of future alcohol-related traumas. However, there is no standardised method in its application. This study aims to deliver a novel method of SBI to patients with alcohol-related facial fractures and to assess changes in their alcohol intake and attitudes to drinking following this intervention. Twenty consecutive patients at two Victorian Hospitals were consented to undergo a novel SBI program. This study analysed the results of the initial survey and the follow-up survey completed at least 3 months later. Of the 20 patients recruited for the initial survey, 18 returned for the follow-up (90% response rate). All patients were males, 50% were aged between 18 and 29 years, 61% involved in interpersonal violence, 56% sustained mandibular fractures and 89% underwent surgery. The alcohol risk score increased in the follow-up survey; however, the relationship is not statistically significant. A high proportion of the patients were still unaware of their risk. Patients showed greater awareness of their drinking and willingness to accept help and more readiness to accept written advice rather than computerised materials. This study found a high rate of acceptance among trauma patients to the intervention program. Although there was no significant change in the risk scores between the initial and follow-up surveys, certain subgroup was more amenable to the intervention given. There is generally an improvement in the attitudes towards and knowledge of harmful drinking.

NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The current study evaluated its possible application for the treatment of Angelman Syndrome. Incubation of acute hippocampal slices from wild-type mice with NSI-189 resulted in a time- and dose-dependent increase in the magnitude of long-term potentiation (LTP) elicited by theta burst stimulation (TBS). The same protocol enhanced TBS-induced LTP in acute hippocampal slices from AS mice. A short treatment with daily injections of NSI-189 in AS mice reversed impairments in cognitive and motor functions, while it slightly enhanced performance of WT mice. The effects of NSI-189 on synaptic plasticity and cognitive functions were associated with activation of the TrkB and Akt pathways. These results suggest that NSI-189 could represent a potential treatment for AS patients.

Accumulating evidence indicates that the lysosomal Ragulator complex is essential for full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A. Here we report that Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in hippocampus of AS mice results in increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, such as RagA, and increased mTORC1 activity. P18 down-regulation by siRNA or shRNA in hippocampal CA1 neurons of AS mice reduces elevated mTORC1 activity and improves long-term potentiation (LTP) and dendritic spine maturation. Our results indicate that Ube3a-mediated regulation of p18 and subsequent mTORC1 signaling is critical for typical synaptic plasticity and dendritic spine development.

Underreporting is a quality concern in mortality statistics. The purpose of this study was to assess and adjust underreporting in the population-based cause-of-death statistics. The total population (96 million) in Shandong, China was divided into 262 subcounty level populations geographically and by residence type (urban/rural). For each subpopulation, the total number of deaths during the years 2011-2013 was determined using data from the Household Registration System (HRS), and was used as a reference to assess the underreporting rate (UR) in the cause-of-death data from the Shandong Death Registration System (SDRS). It was estimated that 454,615 deaths, or 21.5% (95% CI: 21.4-21.5%) were unreported. Underreporting was more pronounced in rural (22.1%) versus urban communities (20.0%), in economically underdeveloped regions (32% versus 16% in least disadvantaged areas), and in newly included sites with no prior experience in cause-of-death reporting (24% versus 17%). Geographic variation was large with a UR at the prefectural level ranging from 11.2% to 43.7%. A stratified analysis showed that UR was higher in rural populations in high-income regions, but in middle- and low-income regions, was higher in urban communities. An adjustment factor (AF) was calculated for each of the 262 subpopulations (ranging from 0.9 to 2.5 with an average of 1.27). The total morality rate was adjusted from 6.03 to 7.67 deaths per 1000 persons. Underreporting in the SDRS varies greatly between areas and populations and is related to residence type, prior experience and local economy. Correcting underreporting at a local level is needed especially for comparative analyses across geographical areas or populations.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of maternally inherited UBE3A, an ubiquitin E3 ligase. Despite recent progress in understanding the mechanism underlying UBE3A imprinting, there is no effective treatment. Further investigation of the roles played by UBE3A in the central nervous system (CNS) is needed for developing effective therapies.This review covers the literature related to genetic classifications of AS, recent discoveries regarding the regulation of UBE3A imprinting, alterations in cell signaling in various brain regions and potential therapeutic approaches. Since a large proportion of AS patients exhibit comorbid autism spectrum disorder (ASD), potential common molecular bases are discussed.Advances in understanding UBE3A imprinting provide a unique opportunity to induce paternal UBE3A expression, thus targeting the syndrome at its 'root.' However, such efforts have yielded less-than-expected rescue effects in AS mouse models, raising the concern that activation of paternal UBE3A after a critical period cannot correct all the CNS defects that developed in a UBE3A-deficient environment. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects in preclinical research. Thus, combined reinstatement of paternal UBE3A expression with targeting abnormal signaling pathways should provide better therapeutic effects.

The algorithm for maxillofacial trauma management is well defined; however, provision of alcohol assessment for patients after trauma is not widely practiced. This study aims to investigate the rate of alcohol assessment achieved within the demographic characteristics of patients with facial trauma and the circumstances where this intervention was implemented.This study retrospectively examined the Victorian Admitted Episodes Data Set (VAED) from 2004 to 2013.Of a total of 54,730 presentations with facial fractures to all Victorian hospitals, 0.9% in the non-alcohol-involved group and 4.3% in the alcohol-involved group received alcohol assessment during their inpatient stay (P .001). Among patients with alcohol involvement, the likelihood of assessment was significantly different with regard to length of stay, age, trauma mechanism, and gender. Positive blood alcohol test did not relate to probability of assessment. Those with acute alcohol intoxication were less likely to be assessed (P .001), whereas those with harmful alcohol use, alcohol dependence, or alcohol withdrawal state were much more likely to be assessed (P .001).This study found no consistent practice of alcohol support to patients following alcohol-related facial fractures. Post-trauma alcohol support may optimize perioperative management of patients and education regarding alcohol harm and may reduce future trauma risk. Development and refinement of such practice is an area for further research.

Objectives This study aimed to address 2 important aspects of temporal pattern in alcohol-related facial fractures: (1) comparison of temporal pattern of alcohol-related facial fracture (alcohol group) presentation with non-alcohol-related fracture (non-alcohol group) presentation; (2) temporal pattern of patient demographic characteristics, injury characteristics, and surgical management in the alcohol group presentation. Study Design This study retrospectively examined the Victorian admitted episodes data set (VAED) for the years 2010 to 2013. VAED is a standardized set of data collected during all hospital presentations in Victoria. Results The study found higher incidence of alcohol-related facial fracture presentations during weekends and during the summer and spring months compared with non–alcohol-related fractures (statistically significant). Alcohol-related facial fractures are more likely to involve male patients in the 20- to 29-year age group, occur as a result of interpersonal violence, and require shorter hospital stays during weekend admissions (statistically significant). No statistically significant relationship has been observed in seasonal variation across all variables. Conclusions This study found distinct characteristics in temporal distribution of alcohol-related facial fractures. These characteristics are, in particular, significant in weekend trauma admissions. Such information is important in workforce planning, resource distribution, and implementation of injury prevention programs.

This study aimed to detect the spatial distribution and high-risk clusters of female breast cancer mortality for the years 2011 to 2013 in Shandong Province, China. The urban-rural difference in the spatial distribution and clusters of disease mortality were also examined. Breast cancer mortality data were obtained from the Shandong Death Registration System (SDRS) during 2011 to 2013 and were adjusted for the underreporting rate. The purely spatial scan Statistics method was performed using Discrete Poisson model. Seven significant spatial clusters for high mortality of female breast cancer were detected in Shandong Province at the county level; these clusters were mainly located in the eastern, southern, southwestern, central and northern regions. The spatial distributions differed significantly between urban and rural populations. Population ageing influenced the distribution of breast cancer clusters for the urban eastern residents. This study provided evidence for the presence of clusters of breast cancer mortality in Shandong, China and found urban-rural difference in the clusters, which is helpful for developing effective strategies to control breast cancer in different areas.

Objective: To analyze the application of transabdominal sonography and transvaginal sonography in early diagnosis of pregnancy and to provide a reference for the selection of diagnosis methods in clinic. Methods: One hundred and eighty patients who were admitted into the hospital from February 2013 to February 2014, received clinical diagnosis and were confirmed as ectopic gestation by surgery were selected as research objects. They were examined by transabdominal sonography, transvaginal sonography, and transabdominal sonography in combination with transvaginal sonography respectively. Besides, the ultrasonic performance was observed and compared with surgical pathological results to analyze and compare diagnostic accordance rate. Results: The positive rate of transabdominal sonography in combination with transvaginal sonography was much higher than that of transabdominal sonography and transvaginal sonography and the differences had statistical significance (P

Objective: To study the clinical value of prenatal diagnosis of umbilical cord entry abnormity (UCEA) by means of color Doppler ultrasound (CDUS). Methods: Clinical data of sixty-four cases with confirmed umbilical cord entry abnormity were reviewed and the specific UCEA conditions and the outcomes of perinatal infants were analyzed. Results: Detection rates of marginal umbilical cord entry abnormity and velamentous umbilical cord entry abnormity by means of CDUS at second trimester were 94.1% and 93.8% respecdtively much higher than 80.0% and 68.8% which were those of third trimester. Discrepancy had statistical significance (P

Background Alcohol-related facial trauma is an increasingly prominent social problem and health hazard. Interpersonal violence (IPV) is often implicated in these trauma presentations and the facial skeleton frequently targeted. This paper examines the characteristics of admitted patients with alcohol-related facial fractures. Methods Electronic data of patients assessed or treated for facial fractures from January 2012 to December 2014 at Western Health was obtained through the Clinical Record Department. Variables analysed include patient age and gender, fracture site(s), alcohol involvement, country of birth, injury mechanism and surgical intervention. Results Of 659 patient records analysed, 18% presentations had alcohol involvement. In the alcohol group, 88% were male, 44% in the 20–34 year age group, 41% suffered nasal fractures, 65% presented following IPV and 60% required surgery. Thirty-seven per cent of patients were non-Australians. Alcohol involvement was significantly correlated with gender, age group and fracture sites but not with surgical intervention or ethnic origin. Conclusions A binge drinking culture has contributed to prevalence of alcohol-related trauma. This study reports alcohol involvement in facial fractures to have high predilection for gender, age group of patients and fracture location. Facial trauma frequently necessitates surgical intervention. Educational programmes should be implemented to raise awareness of this potentially preventable health burden among health providers.

BACKGROUND: Hospital emergency department (ED) use by patients from residential aged care facilities (RACFs) is not always appropriate, and this calls for interventions to avoid some unnecessary uses. This study aims to compare patterns of ED use by RACF patients with and without a Hospital in the Nursing Home (HiNH) program. METHODS: RACF patients presenting to EDs of a hospital with and a hospital without this program during pre- and post-intervention periods were included. Data on patient demographics and ED presentation characteristics were obtained from the Emergency Department Information System database, and were analysed by descriptive and comparative statistics. RESULTS: In both hospitals, most RACF residents presenting to EDs were aged between 75–94 years, female, triaged at scale 3 to 5, and transferred on weekdays and during working hours. Almost half of them were subsequently admitted to hospitals. In accordance with the ICD-10- AM diagnostic coding system, diagnoses that consistently ranked among the top three reasons for visiting the two hospitals before and after intervention included Chapter XIX: injury and poisoning and Chapter X: respiratory diseases. Associated with the intervention, significant decreases in the numbers of presentations per 1 000 RACF beds were identified among patients diagnosed with Chapter XI: digestive diseases [rate ratio (95%CI): 0.09 (0.04, 0.22); P

Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation- (TBS) induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression impairs hippocampus-dependent learning. We previously showed that TBS-induced LTP was associated with calpain-1 mediated truncation of PHLPP1.To better understand the roles of these 2 genes in synaptic plasticity and learning and memory, we generated a double knockout (DKO) mouse by crossing the parent strains. Surprisingly, DKO mice exhibit normal TBS-induced LTP, and the learning impairments in fear conditioning and novel object or novel location recognition were absent in the DKO mice. Moreover, TBS-induced ERK activation in field CA1 of hippocampal slices, which is impaired in both single deletion mice, was restored in the DKO mice. These results further strengthen the roles of both CANP1 and PHLPP1 in synaptic plasticity and learning and memory, and illustrate the complexities of the interactions between multiple pathways participating in synaptic plasticity.

Emerging evidence is implicating abnormal activation of the mechanistic target of rapamycin (mTOR) pathway in several monogenetic neuropsychiatric disorders, including Angelman syndrome (AS), which is caused by deficiency in maternally inherited UBE3A. Using an AS mouse model, we show that semi-chronic rapamycin treatment improves long-term potentiation (LTP) and actin polymerization in hippocampal slices, spine morphology, and fear-conditioning learning. Activity of mTORC1 and of its downstream substrate, S6K1, was increased in hippocampus of AS mice. However, mTORC2 activity, as reflected by PKCα levels, was decreased. Both increased mTORC1 and decreased mTORC2 activity were reversed by semi-chronic rapamycin treatment. Acute treatment of hippocampal slices from AS mice with rapamycin or an S6K1 inhibitor, PF4708671, improved LTP, restored actin polymerization, and normalized mTORC1 and mTORC2 activity. These treatments also reduced Arc levels in AS mice. Treatment with Torin 1, an inhibitor of both mTORC1 and mTORC2, partially rescued LTP and actin polymerization in hippocampal slices from AS mice, while partially impairing them in wild-type (WT) mice. Torin 1 decreased mTORC1 and increased mTORC2 activity in slices from AS mice but inhibited mTORC1 and decreased mTORC2 in WT mice. Finally, an mTORC2 activator, A-443654, increased hippocampal LTP in AS mice and actin polymerization in both WT and AS mice. Collectively, these results indicate that events set in motion by increased mTORC1 and decreased mTORC2 activities, including increased Arc translation and impaired actin remodeling, are crucial in AS pathogenesis. Therefore, selectively targeting these two master kinase complexes may provide new therapeutic approaches for AS treatment.

In preparation for the introduction of human papillomavirus (HPV) vaccine, we investigated awareness and knowledge of HPV/HPV vaccine and potential acceptability to HPV vaccine among mothers with a teenage daughter in Weihai, Shandong, China. A cross-sectional survey was conducted in 2013 with a sample of 1850 mothers who had a daughter (aged 9–17 years) attending primary, junior and senior high schools. In the final sample (N = 1578, response rate 85.30%), awareness of HPV was reported by 305 (19.32%) mothers. Awareness varied significantly by daughter’s age (P

Background There has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs). Methods A quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis. Results Significant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67–0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50–0.76); p

Background This study aims to examine the costs associated with a Hospital in the Nursing Home (HiNH) program in Queensland Australia directed at patients from residential aged care facilities (RACFs) with emergency care needs. Methods A cost analysis was undertaken comparing the costs under the HiNH program and the current practice, in parallel with a pre-post controlled study design. The study was conducted in two Queensland public hospitals: the Royal Brisbane and Women’s Hospital (intervention hospital) and the Logan Hospital (control hospital). Main outcome measures were the associated incremental costs or savings concerning the HiNH program provision and the acute hospital care utilisation over one year after intervention. Results The initial deterministic analysis calculated the total induced mean costs associated with providing the HiNH program over one year as AU$488,116, and the total induced savings relating to acute hospital care service utilisation of AU$8,659,788. The total net costs to the health service providers were thus calculated at -AU$8,171,671 per annum. Results from the probabilistic sensitivity analysis (based on 10,000 simulations) showed the mean and median annual net costs associated with the HiNH program implementation were -AU$8,444,512 and–AU$8,202,676, and a standard deviation of 2,955,346. There was 95% certainty that the values of net costs would fall within the range from -AU$15,018,055 to -AU$3,358,820. Conclusions The costs relating to implementing the HiNH program appear to be much less than the savings in terms of associated decreases in acute hospital service utilisation. The HiNH service model is likely to have the cost-saving potential while improving the emergency care provision for RACF residents.

This study attempts to understand the nature of violence suffered by the adolescents of Kolkata (erstwhile Calcutta) and to identify its relation with their socio-economic background and mental health variables such as anxiety, adjustment, and self-concept. It is a cross-sectional study covering a total of 370 adolescents (182 boys and 188 girls) from six higher secondary schools in Kolkata. The data was gathered by way of a semi-structured questionnaire and three standard psychological tests. Findings revealed that 52.4%, 25.1%, and 12.7% adolescents suffered psychological, physical, and sexual violence in the last year. Older adolescents (aged 17–18 years) suffered more psychological violence than the younger ones (15–16 years) (p < 0.05). Sixty nine (18.6%) adolescent students stood witness to violence between adult members in the family. More than three-fifth (61.9%) adolescents experienced at least one type of violence, while one-third (32.7%) experienced physical or sexual violence or both. Whatever its nature is, violence leaves a scar on the mental health of the victims. Those who have been through regular psychological violence reported high anxiety, emotional adjustment problem, and low self-concept. Sexual abuse left a damaging effect on self-concept (p < 0.05), while psychological violence or the witnessing of violence prompted high anxiety scores (p < 0.05), poor emotional adjustment (p < 0.05), and low self-concept (p < 0.05). This study stresses the need to provide individual counselling services to the maltreated adolescents of Kolkata so that their psychological traumas can heal and that they can move on in life with new hopes and dreams.

Background: Alcohol screening and brief intervention (SBI) in trauma patients has been reported in literature to be effective in changing harmful drinking patterns and injury recurrence. Despite good evidence that SBI can benefit patients and provide a more holistic care, it is not routinely implemented in acute medical settings in Australia, in particular emergency departments (EDs). Objective: This paper aims to assess the knowledge, confidence, and practice of alcohol SBI in trauma patients by emergency physicians throughout Australia and New Zealand through an online survey. Methods: Major EDs in Australia and Zealand were approached to participate in an online survey. Results from the survey were analyzed using simple descriptive summary statistics. Results: Fifty-eight physicians participated in the online survey. Almost all physicians reported at least 10% of all patients managed in ED had traumatic injuries and 35% had alcohol involvement. About 66% were consultant physicians and 84% had 5 or more years of practice. Sixty-four percent agreed to have adequate training in SBI, 22% had adequate time and resources, 47% would like more training in patient screening, and 72% were more likely to deliver SBI in 5 min. Limited time and resources were seen as major barriers. It was found that better understating of SBI may lead to higher confidence and more practice, or vice versa. Conclusion: High proportion of participants in this survey felt under-equipped to deliver SBI due to time limitation, perceived lack of resources, unsuitable environment, and supportive staff. There exists an opportunity to develop a shortened and efficient SBI program that can improve utilization of SBI in an emergency setting.

An adequate vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D) concentration, is important in humans for maintenance of healthy bones and muscle function. Serum 25(OH)D concentration was assessed in participants from Melbourne, Australia (37.81S, 144.96E), who were provided with the current Australian guidelines on sun exposure for 25(OH)D adequacy (25(OH)D ≥50 nmol/L). Participants were interviewed in February (summer, n = 104) and August (winter, n = 99) of 2013. Serum 25(OH)D concentration was examined as a function of measures of sun exposure and sun protection habits with control of key characteristics such as dietary intake of vitamin D, body mass index (BMI) and skin colour, that may modify this relationship. The mean 25(OH)D concentration in participants who complied with the current sun exposure guidelines was 67.3 nmol/L in summer and 41.9 nmol/L in winter. At the end of the study, 69.3% of participants who complied with the summer sun exposure guidelines were 25(OH)D adequate, while only 27.6% of participants who complied with the winter sun exposure guidelines were 25(OH)D adequate at the end of the study. The results suggest that the current Australian guidelines for sun exposure for 25(OH)D adequacy are effective for most in summer and ineffective for most in winter. This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’.