bluuebunny/crossref_metadata_2025 huggingface dataset:
Amniocentesis and chorionic villus sampling in HIV‐infected pregnant women: a multicentre case series
Authors: Floridia M , Masuelli G , Meloni A , Cetin I , Tamburrini E , Cavaliere AF , Dalzero S , Sansone M , Alberico S , Guerra B , Spinillo A , Chiadò Fiorio Tin M , Ravizza M ,   on behalf of The Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy
Published: June 2016

Objectives

To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures.

Design

Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used.

Setting

University and hospital clinics.

Population

Pregnant women with HIV.

Methods

Temporal trends were analysed by analysis of variance and by the Chi‐square test for trend. Quantitative variables were compared by Student's t‐test and categorical data by the Chi‐square test, with odds ratios and 95% confidence intervals calculated.

Main outcome measures

Rate of invasive testing, intrauterine death, HIV transmission.

Results

Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005.

Conclusions

The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment.

Tweetable abstract

No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti‐HIV regimens.
A Reappraisal of Developing Permanent Tooth Length as an Estimate of Age in Human Immature Skeletal Remains
Authors: Cardoso Hugo F.V. , Spake Laure , Liversidge Helen M.
Published: June 2016

This study expands on existing juvenile age prediction models from tooth length by increasing sample size and using classical calibration. A sample of 178 individuals from two European known sex and age skeletal samples was used to calculate prediction formulae for each tooth for each sex separately and combined. Prediction errors, residuals, and percentage of individuals whose real age fell within the 95% prediction interval were calculated. An ANCOVA was used to test sex and sample differences. Tooth length for age does not differ between the samples except for the canine and second premolar, and no statistically significant sex differences were detected. The least prediction error was found in the incisors and the first molar, and the highest prediction error was found in the third molar. Age prediction formulae provided here can be easily used in a variety of contexts where tooth length is measured from any isolated tooth.
Skeletal Indicators of Stress: A Component of the Biocultural Profile of Undocumented Migrants in Southern Arizona,
Authors: Beatrice Jared S. , Soler Angela
Published: June 2016

The ability of forensic anthropologists in the United States to distinguish the remains of foreign nationals from those of American citizens may be crucial to the identification process. This study adds new criteria for identifying Hispanic foreign nationals in southern Arizona to those previously outlined by Birkby et al. (J Forensic Sci 53, 2008, 29) in the “cultural profile.” Skeletal indicators of nonspecific stress were evaluated in undocumented border crossers (UBCs) at the Pima County Office of the Medical Examiner and in documented American samples. Odds ratios show significant associations betweenUBCstatus and the presence of porotic hyperostosis and enamel hypoplasias, which are, respectively, 7.9 and 3 times more prevalent amongUBCs. These findings are consistent with disparities in access to adequate nutrition and health care during childhood. In conjunction with context and other biocultural factors, the presence of these conditions should prompt practitioners to consider that unidentified remains may represent foreign nationals.
Stepping strategy used to recover balance during an induced fall is associated with impaired function and strength in people with knee osteoarthritis
Authors: Levinger Pazit , Downie Calum , Nagano Hanatsu , Petersen Aaron , Hayes Alan , Sanders Kerrie M. , Cicuttini Flavia , Begg Rezaul
Published: June 2016

Aim

We investigated differences in function, strength and pain in those with knee osteoarthritis (OA) who responded with a single step compared to multiple steps during balance recovery during an induced forward fall.

Method

The stepping response of 24 participants with knee OA (50% female, age 68.6 ± 6.2 years) as they recovered balance from an induced forward fall was recorded. Participants were grouped based on their stepping response as single‐stepper and multi‐stepper. Comparison was made between the groups for functional and strength tests and self‐reported pain, function, quality of life, fear of falls and physical activity.

Results

Fourteen of the participants (58%) responded with a multiple step response. Multiple steppers demonstrated greater time for the up and go (P = 0.01), the stair climb tests (P = 0.05), as well as reduced distance during the 2 min walk test (P = 0.001) and reduced isokinetic knee extension strength (P = 0.02).

Conclusion

Those who demonstrated multiple step response had impaired function, reduced strength and were less physically active. Given the high prevalence of falls in people with knee OA, further studies are required to better understand the ability of people with knee OA to respond and avoid falls.
Fatal Fentanyl: One Pill Can Kill
Authors: Sutter Mark E. , Gerona Roy R. , Davis M. Thais , Roche Bailey M. , Colby Daniel K. , Chenoweth James A. , Adams Axel J. , Owen Kelly P. , Ford Jonathan B. , Black Hugh B. , Albertson Timothy E.
Published: June 2016

Objective

The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen.

Methods

Over an 8‐day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their “normal dose” of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills.

Results

One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag‐valve‐mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26–39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600–6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units.

Conclusions

A serious outbreak of exaggerated opioid toxicity caused by fentanyl‐adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law enforcement, and healthcare facilities and resources.
Functional limitation and cognitive impairment among 80+ year old Chinese
Authors: Zheng Jiakun , Liu Junyi , An Ruopeng
Published: June 2016

Aim

This study examined functional limitation in relation to cognitive impairment among 80+ year old Chinese.

Methods

Cognitively‐intact adults ≥80 years old (n = 5161) came from the 1998 Chinese Longitudinal Healthy Longevity Survey. Cognitive impairment was assessed by Mini‐Mental State Examination. Functional limitation was assessed by Katz activities of daily living (ADLs). Cox regressions were performed to examine the relationship between functional limitation in 1998 and cognitive impairment onset during the follow‐up period of 1998–2012.

Results

Compared to those without ADLs limitation at baseline, participants with ADLs limitations were 49% more likely to develop cognitive impairment during follow‐up. A dose‐response relationship was identified – compared to those without ADLs limitation at baseline, those with one, two to five and all six ADLs limitations were 46, 50 and 180% more likely to develop cognitive impairment during follow‐up, respectively.

Conclusion

Baseline functional limitation strongly predicted cognitive impairment incidence in 80+ year old Chinese.
Modified internal limiting membrane peeling technique (maculorrhexis) for myopic foveoschisis surgery
Authors: Lee Chia‐Ling , Wu Wen‐Chuan , Chen Kuo‐Jen , Chiu Li‐Yi , Wu Kwou‐Yeung , Chang Yo‐Chen
Published: June 2016

Purpose

Myopic foveoschisis occurs in 9–34% of highly myopic eyes with posterior staphyloma. The pathogenesis is still not fully understood. But the relative inflexibility of the inner retina and a tangential traction induced inward traction force in the posterior staphyloma are possible mechanisms. Conventional internal limiting membrane (ILM) peeling generally yields good results. However, a postoperative full‐thickness macular hole happens in 13–28% of cases. Therefore, this study describes a modified ILM peeling technique named ‘ILM maculorrhexis’ to minimize the occurrence of postoperative macular hole in patients with foveoschisis.

Methods

This retrospective case review that included 10 eyes of 10 consecutive patients who underwent vitrectomy with ILM maculorrhexis to treat myopic foveoschisis was studied. After surgery, complete ophthalmic examination and SD‐optic coherence tomographic examinations were performed 1, 3, 6, 9 and 12 months postoperatively.

Results

After surgical intervention, the foveoschisis resolved dramatically in all 10 eyes. The mean central foveal thickness decreased significantly from 840 μ to 273 μ at 12 months postoperatively. Mean LogMAR best‐corrected visual acuity improved from 1.04 preoperatively to 0.59 12 months postoperatively. After the follow‐up time of at least 12 months, all 10 eyes remained fovea attached, and none of the 10 eyes developed macular hole.

Conclusions

This technique minimizes traction force over the extremely thinned foveal tissue in highly myopic eyes. In the long‐term follow‐up of at least 12 months, all 10 cases had good anatomic and visual results. But we still need a larger case number and longer follow‐up for further evaluation.
Self‐refraction, ready‐made glasses and quality of life among rural myopic Chinese children: a non‐inferiority randomized trial
Authors: Zhou Zhongqiang , Chen Tingting , Jin Ling , Zheng Dongxing , Chen Shangji , He Mingguang , Silver Josh , Ellwein Leon , Moore Bruce , Congdon Nathan G.
Published: June 2016

Purpose

To study, for the first time, the effect of wearing ready‐made glasses and glasses with power determined by self‐refraction on children's quality of life.

Methods

This is a randomized, double‐masked non‐inferiority trial. Children in grades 7 and 8 (age 12–15 years) in nine Chinese secondary schools, with presenting visual acuity (VA) ≤6/12 improved with refraction to ≥6/7.5 bilaterally, refractive error ≤−1.0 D and <2.0 D of anisometropia and astigmatism bilaterally, were randomized to receive ready‐made spectacles (RM) or identical‐appearing spectacles with power determined by: subjective cycloplegic retinoscopy by a university optometrist (U), a rural refractionist (R) or non‐cycloplegic self‐refraction (SR). Main study outcome was global score on the National Eye Institute Refractive Error Quality of Life‐42 (NEI‐RQL‐42) after 2 months of wearing study glasses, comparing other groups with the U group, adjusting for baseline score.

Results

Only one child (0.18%) was excluded for anisometropia or astigmatism. A total of 426 eligible subjects (mean age 14.2 years, 84.5% without glasses at baseline) were allocated to U [103 (24.2%)], RM [113 (26.5%)], R [108 (25.4%)] and SR [102 (23.9%)] groups, respectively. Baseline and endline score data were available for 398 (93.4%) of subjects. In multiple regression models adjusting for baseline score, older age (p = 0.003) and baseline spectacle wear (p = 0.016), but not study group assignment, were significantly associated with lower final score.

Conclusion

Quality of life wearing ready‐mades or glasses based on self‐refraction did not differ from that with cycloplegic refraction by an experienced optometrist in this non‐inferiority trial
Regional Characteristics, Industry Agglomeration and Location Choice: Evidence from Japanese Manufacturing Investments in Korea*
Authors: Lee Ki‐Dong , Hwang Seok‐Joon
Published: June 2016

Using extensive firm‐level data for the years 1998–2006, we analyze the regional location decision of Japanese manufacturing foreign direct investors in Korea by focusing on the role of agglomeration economies. Our logit estimates indicate that horizontal agglomeration matters in the location decision, but vertical agglomeration does not. Strong evidence of country‐of‐origin effects is found. Japanese foreign direct investments in high‐technology industries show a typical ‘follow‐the‐leader’ pattern, while those in the in low‐technology industries are influenced by regional endowments. In addition, Japan's high‐technology firms are likely to prefer urban locations so that they can enjoy the externalities of business services.
Gender, Sibling Order, and Differences in the Quantity and Quality of Education: Evidence from Japanese Twins*
Authors: Vu Tien Manh , Matsushige Hisakazu
Published: June 2016

Using information on 1045 pairs of Japanese monozygotic twins, we examined differences in education by considering both the years of schooling (quantity) and the reputation of the last attended school (quality). We found that a difference in learning performance at 15 years of age is one of the key factors determining the differences. We also found that a female eldest child in the family from the 1950s and 1960s birth cohorts averaged 0.54 years less schooling than did her ‘younger’ twin. However, for the same birth cohorts, a male eldest child in the family generally had access to higher‐quality education than his ‘younger’ twin. Nonetheless, as the Japanese economy matured in the 1970s and thereafter, educational differences between twins disappeared, regardless of gender and sibling order.
Information Effects on Consumers' Preferences and Willingness to Pay for a Functional Food Product: The Case of Red Ginseng Concentrate*
Authors: Ahn Byeong‐il , Bae Mo‐Se , Nayga Rodolfo M.
Published: June 2016

This paper elicits consumers' preferences associated with attributes of a very popular food product in Asia: red ginseng concentrate. The results of a choice experiment suggest that an asymmetric information problem can cause consumers' preferences and valuation for red ginseng concentrate to be significantly influenced by objective information about the product's attributes. The results imply that while objective information can result in differential changes in valuation for different product attributes, it can increase consumers' willingness to pay for red ginseng concentrate. The paper also discuss important policy and marketing implications from the results of the study.
Petersen Estimator, Chapman Adjustment, List Effects, and Heterogeneity
Authors: Mao Chang Xuan , Huang Ruochen , Zhang Sijia
Published: June 2016

We use a nonparametric mixture model for the purpose of estimating the size of a population from multiple lists in which both the individual effects and list effects are allowed to vary. We propose a lower bound of the population size that admits an analytic expression. The lower bound can be estimated without the necessity of model-fitting. The asymptotical normality of the estimator is established. Both the estimator itself and that for the estimable bound of its variance are adjusted. These adjusted versions are shown to be unbiased in the limit. Simulation experiments are performed to assess the proposed approach and real applications are studied.
Exploring Women's Preferences for the Mode of Delivery in Twin Gestations: Results of the Twin Birth Study
Authors: Murray‐Davis Beth , McVittie Jennifer , Barrett Jon F. , Hutton Eileen K. ,   the Twin Birth Study Collaborative Group
Published: June 2016

Objective

The Twin Birth Study, an international, multi‐center randomized controlled trial was conducted to compare the risks of planned cesarean with planned vaginal delivery for twin pregnancies. The aim of this component of the trial was to understand participants' perspectives of study participation and preferences for the mode of delivery.

Methods

A mixed‐methods questionnaire was distributed to study participants 3 months after giving birth. The questionnaire contained Likert scales and open‐ended questions about the experience of being enrolled in a clinical trial and of childbirth, including the mode of delivery. Quantitative data were analyzed using SAS to generate descriptive statistics. Qualitative data were analyzed to identify categories and themes.

Results

Ninety‐one percent of trial participants completed the questionnaire. Across all groups, the majority of women would participate in a study like this one again if given the opportunity. Main benefits of participating were as follows: benefits to one and one's babies, altruism, and receiving quality care. Randomization for the mode of delivery was challenging for women because of the desire to be involved in decision‐making. Findings related to childbirth experience and the mode of delivery demonstrated a preference for vaginal birth across all groups. Those who had a vaginal birth were more satisfied with their birth experience.

Conclusions

This study provides evidence to inform practitioners about what women who have twin pregnancies like or dislike about birth and their desire for involvement in decision‐making. Vaginal birth was preferred across all study groups and was associated with greater satisfaction with childbirth experience.
What is the outcome of paediatric gastrocystoplasty when the patients reach adulthood?
Authors: Boissier Romain , Di Crocco Eugenie , Faure Alice , Hery Geraldine , Delaporte Véronique , Lechevallier Eric , Mouriquand Pierre D. E. , Guys Jean‐Michel , Karsenty Gilles
Published: June 2016

Objective

To document the long‐term outcomes of paediatric augmentation gastrocystoplasty (AGC) in terms of preservation of renal function and maintenance of dryness, and to analyse the rate of complications.

Patients and methods

The medical records of children who had undergone AGC between 1992 and 2000 (minimum time interval of 15 years) were reviewed retrospectively. The following data were collected: age at surgery, the cause of bladder dysfunction, functioning of the AGC, any complications, and the long‐term outcome of the patients. All of the patients were re‐contacted by telephone.

Results

A total of 11 AGCs were carried out between 1992 and 2000, at a median (range) age of 11 (6.5–14) years. The diagnosis of patients undergoing AGC included myelomeningocele (four), bladder exstrophy (four), posterior urethral valves (one), irradiated bladder (one), and Prune Belly syndrome (one). The median [interquartile range (IQR)] follow‐up was 17 (15–19.5) years. Renal function was preserved or improved in seven of the 11 patients and nine patients were dry after AGC. Seven of the 11 patients reported symptoms linked to haematuria‐dysuria syndrome, which was resistant to treatment in one case and requiring excision of the gastric patch. Three of the 11 patients developed a tumour on the gastric graft after a median (range) delay of 20 (11–22) years after the initial procedure. All had gastric adenocarcinoma of which two were metastatic at the time of diagnosis requiring pelvectomy with pelvic lymph node dissection and adjuvant chemotherapy. Seven of the 11 patients underwent excision of the gastric patch after a median (IQR) time of 11 (8.5–20.5) years.

Conclusions

Our long‐term data confirmed that most patients undergoing AGC had preservation of their renal function and were continent. However, long‐term, AGC was associated with a significant risk of malignant transformation and a high rate of surgical re‐intervention involving removal of the gastric patch. These results question the use of this technique for bladder augmentation, irrespective of the indication. We highlight the importance of strict endoscopic follow‐up of all patients already having undergone an AGC and the need to inform and educated patients about tumour‐related symptoms.
Spatial data issues in geographical zoonoses research
Authors: Robertson Colin , Yee Lauren , Metelka Julia , Stephen Craig
Published: June 2016

Key Messages

Spatial data are of increasing use in the investigation of emerging zoonoses.

Due to the heterogeneity of required data sources, issues of scale misalignment, data linkage, and access to data are found to be important factors.

Geographers can make significant contributions to zoonoses research through their expertise in evaluating, integrating, and modelling spatial data.
Pursuing performance and maintaining compliance: Balancing performance improvement and accountability in Ontario's public health system
Authors: Price Alex , Schwartz Robert , Cohen Joanna , Scott Fran , Manson Heather
Published: June 2016

This article examines the compatibility between performance improvement and compliance‐based accountability in the implementation of a new system of public health performance management in Ontario. Findings from this mixed‐method study show that only minor elements of performance improvement get incorporated into pre‐existing compliance‐based accountability structures, that reinforcement of accountability structures works to the detriment of performance improvement intentions, and that limiting managerial influence in developing performance measures and targets diminish the utility of information for improvement. The study concludes that achieving a better balance requires an alternative to top‐down decision making that goes beyond consultation to include partnership.
Pre‐existing condition: Taking media coverage into account when preparing for H1N1
Authors: Quigley Kevin , Macdonald Colin , Quigley John
Published: June 2016

This article examines the claim that the media exaggerated the threat of H1N1, prompting an immediate demand for limited vaccine. We compareThe Australian's and theDaily Telegraph's coverage of H1N1 with that ofThe Globe and Mail, which was comparatively critical of government performance. The events of October 2009 underscore the difficulty and importance of responding to media coverage of “uncertain risks” (Renn), risks for which there is a lack of scientific basis for decision making and potentially generate anxious public responses.
Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy
Authors: Kobayashi Yoshihisa , Mitsudomi Tetsuya
Published: June 2016

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in approximately 20% (in Caucasians) to 40% (in East Asians) of adenocarcinomas of the lung. Targeted therapy for these lung cancers has been established based on evidence regarding mainly common mutations; that is, exon 19 deletions (Del19) and L858R. EGFR‐tyrosine kinase inhibitors (TKI), gefitinib, erlotinib or afatinib showed high objective response rates (ORR) of approximately 60%. Several studies suggested that Del19 might be more sensitive to EGFR‐TKI than L858R. On the other hand, it has been difficult to establish evidence for other less common mutations, accounting for 12% of all EGFR mutations, because there are many variants and many studies have excluded patients with these uncommon mutations. However, recent studies revealed that these rare genotypes could be targetable if appropriate TKI are selected. For example, G719X (X denotes A, S, C and so on), Del18, E709K, insertions in exon 19 (Ins19), S768I or L861Q showed moderate sensitivities to gefitinib or erlotinb with ORR of 30%–50%. However, afatinib appeared to be especially effective for these tumors. Although Ins20s (except for insFQEA) have been regarded as resistant mutations, osimertinib may be effective for rare subtypes of them and nazartinib (EGF816) is promising for the majority of them. For the further development of targeted therapy in all EGFR mutations, it is important to precisely detect targetable mutations, to select the most appropriate TKI for each mutation, and to continue investigating in vitro studies and collecting clinical data on even rare mutations.
Effect of teriparatide treatment on endothelial function, glucose metabolism and inflammation markers in patients with postmenopausal osteoporosis
Authors: Celer Ozgen , Akalın Aysen , Oztunali Cigdem
Published: June 2016

Objective

Teriparatide, an anabolic agent used in the treatment of postmenopausal osteoporosis, can induce effects similar to primary hyperparathyroidism. Our objective was to evaluate the effects of teriparatide on endothelial functions, glucose metabolism and inflammation markers in patients diagnosed with postmenopausal osteoporosis.

Design, patients and measurements

This was a single‐centre, single‐arm, 6‐month prospective study. Twenty‐three postmenopausal women over 65 years old with a lumbar spine or femoral neck T‐score of −4·0 or lower and having at least two compression fractures in thoracic or lumbar spine were studied. Low‐dose intermittent teriparatide (20 μg/day) was supplemented with calcium carbonate (1000 mg elemental calcium) and 880IUcholecalciferol for 6 months. The biochemical parameters for glucose metabolism, inflammation and atherosclerosis were determined. For the assessment of vascular endothelial function, carotid intima‐media thickness (CIMT), brachial artery intima‐media thickness (BIMT), per cent change in flow‐mediated dilation (FMD%) and nitroglycerine‐induced dilations (NID%) were measured on ultrasonography.

Results

The fasting plasma glucose, homoeostatic model assessment of insulin resistance, fibrinogen, homocysteine and high‐density lipoprotein cholesterol increased significantly with teriparatide treatment (P < 0·05 for all). BaselineCIMTandBIMTdid not change significantly with 6 months of teriparatide treatment (P > 0·05); however,FMD% andNID% showed significant decrease after treatment (P < 0·01 for both).

Conclusions

Intermittent teriparatide treatment may adversely affect some parameters of glucose metabolism, inflammation and endothelial function. On the basis of our findings, further large‐scale and controlled studies are needed to clarify the exact effect of teriparatide treatment on glucose metabolism, inflammation and endothelial function.
Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis
Authors: Fraga‐Silva Thais F.C. , Mimura Luiza A.N. , Zorzella‐Pezavento Sofia F.G. , Ishikawa Larissa L.W. , França Thais G.D. , Thomé Rodolfo , Verinaud Liana , Arruda Maria S.P. , Sartori Alexandrina
Published: June 2016

Aims

Multiple sclerosis (MS) is an immune‐mediated demyelinating disorder of the central nervous system (CNS). We described that Candida albicans (Ca) aggravates experimental autoimmune encephalomyelitis (EAE) that is a model to study MS. We also observed that vaccination with a myelin peptide (MOG) in the presence of vitamin D (VitD) protected mice against EAE. In this work, we investigated whether Ca infection interferes with the efficacy of this vaccine.

Methods

EAE was induced in C57BL/6 female mice previously vaccinated with MOG+VitD and then infected 3 days before encephalomyelitis induction.

Results

Vaccination was able to control EAE development in infected mice. These animals gained weight, and only a few progressed to very low clinical scores. Protection was confirmed by a lower inflammatory infiltration in the CNS and was also associated with a reduced production of encephalitogenic cytokines by spleen and CNS cell cultures. The elevated percentage of CD25+FoxP3+ cells suggests that regulatory T cells are involved in the protection. Adoptive transfer of splenocytes from mice vaccinated with MOG+VitD supports the view that protection is mediated by immunoregulatory cells.

Conclusion

Together, these experiments provide evidence demonstrating that EAE can be prevented by the inverse vaccination with MOG+VitD even in the presence of a disease‐aggravating infectious agent.
Functional Genomic Analyses Identify Pathways Dysregulated in Animal Model of Autism
Authors: Huang Ji‐Yun , Tian Yun , Wang Hui‐Juan , Shen Hong , Wang Huan , Long Sen , Liao Mei‐Hua , Liu Zhi‐Rong , Wang Ze‐Ming , Li Dan , Tao Rong‐Rong , Cui Tian‐Tian , Moriguchi Shigeki , Fukunaga Kohji , Han Feng , Lu Ying‐Mei
Published: June 2016

Background

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that display complicated behavioral symptoms.

Methods

Using gene expressing profiling and the weighted gene co‐expression network analysis (WGCNA), we studied genes coregulated by similar factors such as genetic variants or environmental effects in the hippocampus in an animal model of autism.

Results

From microarray data, we identified 21,388 robustly expressed genes of which 721 genes were found to be differently expressed in the valproic acid‐treated group compared to the control group. WGCNA identified multiple co‐expression modules known to associate with cognitive function, inflammation, synaptic, and positive regulation of protein kinase activating. Many of these modules, however, have not been previously linked to autism spectrum disorders which included G‐protein signaling, immunity, and neuroactive ligand–receptor interaction pathway. The downregulation of the highly connected (hub) genes Taar7h and Taar7b in neuroactive ligand–receptor interaction pathway was validated by qRT‐PCR. Immunoblotting and immunohistochemistry further showed that TAAR7 expression was downregulated not only in valproic acid‐treated animals, but also BTBR T+tf/J mice.

Conclusions

This study highlights the advantages of gene microarrays to uncover co‐expression modules associated with autism and suggests that Taars and related gene regulation networks may play a significant role in autism.
Does neoadjuvant therapy increase the incidence of anastomotic leakage after anterior resection for mid and low rectal cancer? A systematic review and meta‐analysis
Authors: Hu M.‐H. , Huang R.‐K. , Zhao R.‐S. , Yang K.‐L. , Wang H.
Published: June 2016

Aim

The aim was to evaluate the association of neoadjuvant therapy with increases in the incidence of anastomotic leakage (AL) after middle and low rectal anterior resection.

Method

The electronic databases of PubMed, Web of Science, Scopus and Ovid were searched between 1980 and 2015. The random effects model was used to model the pooled data to determine the odds ratio with 95% confidence interval. Heterogeneity was evaluated using the Q test and I2 statistics. Subgroup, sensitivity and meta‐regression analysis was conducted to explore heterogeneity.

Results

Neoadjuvant therapy was not shown to increase the incidence of postoperative AL as demonstrated by an OR of 1.16 [95% CI 0.99–1.36; P = 0.07 (random effects model)]. The subgroup analysis of neoadjuvant radiotherapy using the random effects model suggested that it did not increase the rate of postoperative AL (OR = 1.24, 95% CI 0.97–1.58; P = 0.08). The subgroup analysis of neoadjuvant chemoradiotherapy indicated that the rate of postoperative AL again did not increase with an OR = 1.06 [95% CI 0.86–1.30; P = 0.59 (random effects model)]. The interval to surgery after neoadjuvant therapy and preoperative radiotherapy (short or long course) was not associated with an increased incidence of postoperative AL.

Conclusion

Neoadjuvant therapy does not appear to increase the incidence of postoperative AL after anterior resection for mid and low rectal cancer. In addition, neither the interval to surgery after neoadjuvant therapy nor the radiotherapy regimen increases the rate of postoperative AL.
Extending SME to Handle Large‐Scale Cognitive Modeling
Authors: Forbus Kenneth D. , Ferguson Ronald W. , Lovett Andrew , Gentner Dedre
Published: June 2016

Analogy and similarity are central phenomena in human cognition, involved in processes ranging from visual perception to conceptual change. To capture this centrality requires that a model of comparison must be able to integrate with other processes and handle the size and complexity of the representations required by the tasks being modeled. This paper describes extensions to Structure‐Mapping Engine (SME) since its inception in 1986 that have increased its scope of operation. We first review the basic SME algorithm, describe psychological evidence for SME as a process model, and summarize its role in simulating similarity‐based retrieval and generalization. Then we describe five techniques now incorporated into the SME that have enabled it to tackle large‐scale modeling tasks: (a) Greedy merging rapidly constructs one or more best interpretations of a match in polynomial time: O(n2log(n)); (b) Incremental operation enables mappings to be extended as new information is retrieved or derived about the base or target, to model situations where information in a task is updated over time; (c) Ubiquitous predicates model the varying degrees to which items may suggest alignment; (d) Structural evaluation of analogical inferences models aspects of plausibility judgments; (e) Match filters enable large‐scale task models to communicate constraints to SME to influence the mapping process. We illustrate via examples from published studies how these enable it to capture a broader range of psychological phenomena than before.
Interplay between 15‐lipoxygenase‐1 and metastasis‐associated antigen 1 in the metastatic potential of colorectal cancer
Authors: Tunçer S. , Tunçay Çağatay S. , Keşküş A.G. , Çolakoğlu M. , Konu Ö. , Banerjee S.
Published: June 2016

Objectives

Metastasis‐associated antigen 1 (MTA1) is implicated in metastasis while 15‐lipoxygenase‐1 (15‐LOX‐1) reduces cell motility, when re‐expressed in colorectal cancer (CRC). We aimed to understand any potential interplay between MTA1 and 15‐LOX‐1 in CRC metastasis.

Materials and methods

ALOX15 and MTA1 expression in tumour and normal samples were analysed from TCGA RNA‐seq data, microarray data sets and a human CRC cDNA array. Western blots, chromatin immunoprecipitation (ChIP), luciferase assays and electrophoretic mobility shift assays (EMSA) were carried out in HT‐29 and LoVo cells re‐expressing 15‐LOX‐1 to determine NF‐ κB activity at the MTA1 promoter. Functional assays in cells ectopically expressing either 15‐LOX‐1, MTA‐1 or both, were carried out to determine adhesion and cell motility.

Results

Significantly higher expression of MTA1 was observed in tumours compared to normal tissues; MTA1 overexpression resulted in reduced adhesion in CRC cell lines. Re‐expression of 15‐LOX‐1 in the CRC cell lines reduced expression of endogenous MTA1, corroborated by negative correlation between the two genes in two independent human CRC microarray data sets, with greater significance in specific subsets of patients. DNA binding and transcriptional activity of NF‐κB at the MTA1 promoter was significantly lower in cells re‐expressing 15‐LOX‐1. Functionally, the same cells had reduced motility, which was rescued when they overexpressed MTA1, and further corroborated by expressions of E‐cadherin and vimentin.

Conclusions

Expression of MTA1 and 15‐LOX‐1 negatively correlated in specific subsets of CRC. Mechanistically, this is at least in part through reduced recruitment of NF‐κB to the MTA1 promoter.
Postoperative acute respiratory failure caused by adult‐onset Pompe disease
Authors: Tan Dingyu , Xu Jun , Yang Yi , Gu Ming , Yu Xuezhong
Published: June 2016

Pompe disease, which leads to dysfunction of the enzyme acid a‐glucosidase, is a genetic disorder seen in 1 in 40000 births. Adult‐onset Pompe disease is known as a slowly progressive myasthenia with or without respiratory dysfunction. We herein report two cases of adult‐onset Pompe disease, in which postoperative acute respiratory failure was the the initial manifestation. The two patients showed no symptoms of ambulatory and respiratory dysfunction before operation. The diagnosis of Pompe disease was determined by muscle biopsy and acid a‐glucosidase assay in the blood. Rapid deterioration of already struggling diaphragmatic function induced by stress of surgery and anesthesia were thought to be the main reason of postoperative acute respiratory failure. Physicians should be aware of the existence of an adult form of Pompe disease which may present with postoperative acute respiratory failure.
The Safety, Pharmacokinetics, and Nervous System Effects of Two Natural Sources of Caffeine in Healthy Adult Males
Authors: Krieger DR , Kalman DS , Feldman S , Arnillas L , Goldberg D , Gisbert O , Nader S
Published: June 2016

This double‐blind crossover clinical trial randomized 12 adult males to receive 200 mg of caffeine from a green coffee extract, a guayusa leaf extract, and a synthetic control to compare their safety, absorption, and effect on neurotransmitters. The results showed no statistically significant changes in blood pressure or heart rate from baseline to 120 min postdose of each natural source compared with changes from baseline in the control (0.094 < = P < = 0.910). The ratios of Cmax, AUC0‐4, and AUC0‐∞ of each natural source to the control were bioequivalent by US Food and Drug Administration standards (90% CI within 80–125%). The guayusa leaf extract stimulated a significantly lower increase in epinephrine compared with the control (+0.5 vs. +2.78 μg/gCr, P = 0.04), while the green coffee extract provoked an increase in epinephrine similar to the control (+3.21 vs. +2.78 μg/gCr, P = 0.569). Implications for future clinical research are discussed.
Parent‐ and child‐driven effects during the transition to adolescence: a longitudinal, genetic analysis of the home environment
Authors: Hannigan Laurie J. , McAdams Tom A. , Plomin Robert , Eley Thalia C.
Published: June 2016

Theoretical models of child development typically consider the home environment as a product of bidirectional effects, with parent‐ and child‐driven processes operating interdependently. However, the developmental structure of these processes during the transition from childhood to adolescence has not been well studied. In this study we used longitudinal genetic analyses of data from 6646 UK‐representative twin pairs (aged 9–16 years) to investigate stability and change in parenting and household chaos in the context of parent–child bidirectional effects. Stability in the home environment was modest, arising mainly from parent‐driven processes and family‐wide influences. In contrast, change over time was more influenced by child‐driven processes, indicated by significant age‐specific genetic influences. Interpretations of these results and their implications for researchers are discussed.
Changes in breathomics from a 1‐year randomized smoking cessation trial of electronic cigarettes
Authors: Campagna Davide , Cibella Fabio , Caponnetto Pasquale , Amaradio Maria Domenica , Caruso Massimo , Morjaria Jaymin B. , Malerba Mario , Polosa Riccardo
Published: June 2016

Background

Electronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long‐term changes in exhaled breath measurements and respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to ECs.

Materials and methods

Prospective evaluation of cigarette consumption, fractional nitric oxide concentration in exhaled breath (FeNO), exhaled carbon monoxide (eCO) and symptom scores was performed in a 1‐year randomized, controlled trial of ‘healthy’ smokers receiving 2·4% nicotine, 1·8% nicotine or no nicotine ECs. FeNO and eCO data are presented on the basis of participants’ pooled continuous smoking phenotype classification (failures, reducers and quitters).

Results

A significant effect of quitting classification was found on FeNo and eCO at all time points (P < 0·0001). Among quitters, FeNO (medians and interquartile range) rose from 5·5 (4·5–6·9) ppb to 17·7 (13·3–18·9) ppb by week 52. Baseline eCO (medians and interquartile range) decreased from 17 (12–20) ppm to 3 (1–4) ppm by week 52. No significant changes in FeNO and eCO levels were observed in failures and reducers. Improvements in FeNO and eCO levels were correlated with attenuations in symptom scores.

Conclusions

Smokers invited to switch to electronic cigarettes who completely abstained from smoking showed steady progressive improvements in their exhaled breath measurements and symptom scores. FeNo and eCO normalization is highly supportive of improved respiratory health outcomes and adds to the notion that quitting from tobacco smoking can reverse harm in the lung.
Effect of endothelin‐1 and endothelin receptor blockade on the release of microparticles
Authors: Jung Christian , Lichtenauer Michael , Wernly Bernhard , Franz Marcus , Goebel Bjoern , Rafnsson Arnar , Figulla Hans‐Reiner , Pernow John
Published: June 2016

Background

Increased levels of endothelial cell microparticles (EMP) are known to reflect endothelial dysfunction (ED). In diabetes mellitus type 2 (T2DM), the expression of endothelin (ET)‐1 is increased. As treatment with an ET‐1 antagonist significantly inhibited atherosclerosis in animal models, we sought to investigate whether treatment with ET‐1 antagonists affects EMP levels in vitro and in vivo in patients with T2DM.

Materials and methods

In vitro study: Human umbilical vein endothelial cells (HUVEC) were stimulated with ET‐1 alone and ET‐1 in combination with a dual ET‐A and ET‐B endothelin receptor blocker. In vivo study: Patients with T2DM were randomized to treatment with the ET receptor antagonist bosentan or placebo. After 4 weeks, the patients were re‐examined and blood samples were obtained. EMP counts in supernatants and plasma samples were determined using flow cytometry.

Results

In vitro study: In supernatants of ET‐1‐stimulated HUVECs, the increased release of EMP was reduced significantly by co‐incubation with an ET‐1 receptor antagonist (e.g. CD31+/CD42b‐EMP decreased from 37·1% ± 2·8 to 31·5% ± 2·8 SEM, P = 0·0078). In vivo study: No changes in EMP levels in blood samples of patients with T2DM were found after 4 weeks of bosentan treatment (n = 36, P = ns).

Conclusions

Our in vitro results suggest that ET‐1 stimulates the release of EMP from HUVECs via a receptor‐dependent mechanism. Co‐incubation with an endothelin receptor blocker abolished ET‐1‐dependent EMP release. However, treatment with bosentan for 4 weeks failed to alter EMP levels in patients with T2DM. Other factors seem to have influenced EMP release in patients with T2DM independent of ET‐1 receptor‐mediated mechanisms.
Modelling of species distributions, range dynamics and communities under imperfect detection: advances, challenges and opportunities
Authors: Guillera‐Arroita Gurutzeta
Published: June 2016

Building useful models of species distributions requires attention to several important issues, one being imperfect detection of species. Data sets of species detections are likely to suffer from false absence records. Depending on the type of survey, false positive records can also be a problem. Disregarding these observation errors may lead to important biases in model estimation as well as overconfidence about precision. The severity of the problem depends on the intensity of these errors and how they correlate with environmental characteristics (e.g. where species detectability strongly depends on habitat features). A powerful modelling framework that accounts for imperfect detection in the modelling of species distributions has developed in the last 10–15 yr. Fundamental to this framework is that data must be collected in a way that is informative about the observation process. For instance, such data can be in the form of multiple detection/non‐detection records obtained from several visits/observers/detection methods at (at least) some of the sites, or from data on times to detection within a survey visit. The framework can extend to studying species’ range dynamics and the modelling of communities, as well as approaches for analysing data on abundance and multiple occupancy states (rather than binary presence/absence). This paper summarizes these modelling advances, discusses evidence about effects of imperfect detection and the difficulties of working with it, and concludes with the current outlook for future research and application of these methods.
Inhibitory effect of intensity and interstimulus interval of conditioning stimuli on somatosensory evoked magnetic fields
Authors: Onishi Hideaki , Sugawara Kazuhiro , Yamashiro Koya , Sato Daisuke , Kirimoto Hikari , Tamaki Hiroyuki , Shirozu Hiroshi , Kameyama Shigeki
Published: June 2016

Magnetoencephalography (MEG) recordings were performed to investigate the inhibitory effects of conditioning stimuli with various types of interstimulus intervals (ISIs) or intensities on somatosensory evoked magnetic fields (SEFs) using a 306‐ch whole‐head MEG system. Twenty‐three healthy volunteers participated in this study. Electrical stimuli were applied to the right median nerve at the wrist. Six pulse trains with ISIs of 500 ms were presented in Experiment 1. A paired‐pulse paradigm with three kinds of conditioning stimulus (CON) intensities, 500 ms before the test stimulus (TS), was applied in Experiment 2. Finally, three CONs 500 or 1000 ms before TS were presented in Experiment 3. Three main SEF deflections (N20m, P35m, and P60m) were observed, and the source activities of P35m and P60m significantly decreased after the 2nd pulse of a six pulse trains. These source activities also significantly decreased with increasing intensity of CON. In addition, these attenuations of source activities were affected by CON–CON or CON–TS intervals. These results indicated that the source activities were modulated by the intensity and ISIs of CONs. Furthermore, P35m after the stimulation were very sensitive to CONs; however, the attenuation of P60m after the stimulation lasted for a longer period than that of P35m. Our findings suggest that the conditioning stimulation had inhibitory effects on subsequent evoked cortical responses for more than 500 ms. Our results also provide important clues about the nature of short‐latency somatosensory responses in human studies.