bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and palliative care outcomes for patients of poor performance status treated with antiprogrammed death‐1 monoclonal antibodies for advanced melanoma
Authors: Wong Annie , Williams Molly , Milne Donna , Morris Kortnye , Lau Peter , Spruyt Odette , Fullerton Sonia , McArthur Grant
Published: June 2017

Background

Antiprogrammed death‐1 antibodies (anti‐PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti‐PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti‐PD1 is lacking.

Methods

Retrospective review of outcomes for all patients with advanced melanoma treated with anti‐PD1 between 2012 and June 2015 at Peter MacCallum Cancer Centre, a tertiary specialist cancer center in Australia.

Results

Between 2012 and 2015, 91 patients received anti‐PD1: median age 63, 65% males, 77% elevated LDH>1xULN (37/48 patients). Fifty‐eight patients had baseline ECOG PS of 0–1 (64%), 24 patients ECOG PS 2–3 (26%) and ECOG PS was not recorded in nine patients (10%). Median overall survival (OS) for the ECOG PS 0–1 group was 19.5 months and 1.8 months for ECOG PS 2–3 (HR 5.5; 95% CI, 9.1–50.3; P = 0.0001). Tumor response was 23/58 (39%) in ECOG PS 0–1, 2/16 (12%) in ECOG PS 2 and 0/8 in ECOG PS 3. Toxicity did not differ between different groups. ECOG PS 2–3 patients were more likely to be treated and hospitalized within the last month of life compared to ECOG PS 0–1 patients, RR 1.75 (95% CI, 1.04–2.56, P = 0.019) and RR 1.73 (95% CI, 1.10–2.16, P = 0.009), respectively. ECOG PS 2–3 patients were more likely to die in an acute hospital RR 2.68 (95% CI, 1.17–6.51, P = 0.016).

Conclusions

Patients with poor baseline PS have a significantly lower OS and reduced response to anti‐PD1. Further quality of life and palliative care research is needed.
A rare form of extremely wide QRS complex due to reversed homologous electrical ventricular separation of acute heart failure
Authors: Yan Sujuan , Yu Jianhua , Xia Zhen , Zhu Bo , Hu Jinzhu , Li Juxiang
Published: June 2017

Electrical ventricular separation, as a special complete intraventricular block, denotes that ventricles be electrically separated into two or more parts caused by severe and wide damage of myocardium and conduction. Electrical ventricular separation can be divided into homologous and heterologous, homologous electrical ventricular separation is a rare phenomenon, literally the excitement of whole ventricle originate from supraventricle, on ECG, there are two different QRS waves which connect with an isoelectric line, one ST segment and T wave. We report a valve heart disease presented with complicated electrophysiological characteristics, which has reversed complex homologous electrical ventricular separation with second degree intraventricular block.
Predictors of visual outcome in patients operated for craniopharyngioma – a Danish national study
Authors: Jacobsen Mads Forslund , Thomsen Ann Sofia Skou , Bach‐Holm Daniella , Doroudian Ghazaleh , Nissen Kamilla Rothe , Fugleholm Kåre , Poulsgaard Lars , Siersma Volkert , Heegaard Steffen
Published: June 2017

Purpose

Craniopharyngioma often causes visual loss due to the close relation to the anterior visual pathways. This study investigates the incidence and predictors of visual outcomes in patients with craniopharyngioma.

Methods

Data from sixty‐six patients who underwent surgery for craniopharyngioma from 2009 to 2013 in Denmark were reviewed. Primary outcomes were visual acuity (VA) and visual field (VF) defects from pre‐and postoperative visits. Secondary outcomes were optic nerve atrophy (OA) and papilledema.

Results

Fifty‐eight patients were included. The VA of the patients 1‐year after surgery improved by −0.16 log(MAR) (95%CI: −0.30 to −0.02; p = 0.0266). Visual field (VF) defects worsened in 17 eyes (30%), remained stable in 21 eyes (37%) and improved in 19 eyes (33%). The presence of papilledema and the absence of OA were significantly correlated with an improvement in VA postoperatively (p = 0.011 and p = 0.011, respectively). Patients undergoing surgery within a week or less after their first ophthalmological examination had a significant improvement in VA (−0.36; 95%CI: −0.62 to −0.09; p = 0.0099). Patients undergoing surgery using a subfrontal approach also showed improvement in VA (p = 0.048). Tumour recurrence had a significantly worse VA outcome (p = 0.0074).

Conclusion

Patients show a slight improvement in VA 1‐year after operation for craniopharyngioma. The presence of papilledema and early surgical intervention is associated with a significant improvement in VA. Early involvement of a dedicated ophthalmologist is recommended to secure an early detection of a visual decline and potential tumour recurrence.
Delays in the diagnosis and initial treatment of bladder cancer in Western Australia
Authors: McCombie Steve P. , Bangash Haider K. , Kuan Melvyn , Thyer Isaac , Lee Fran , Hayne Dickon
Published: June 2017

Objectives

To quantify and examine the causes of delays in the diagnosis and initial treatment of patients with bladder cancer in Western Australia.

Subjects and Methods

All attendances at a one‐stop haematuria clinic at a public tertiary‐level hospital in Western Australia between May 2008 and April 2014 were reviewed retrospectively. All patients diagnosed with a bladder tumour over this period were identified. These patients and their general practitioners were contacted retrospectively and invited to participate in telephone interviews, with additional data collected from clinical records as required. Waiting times to presentation, referral, assessment, and initial treatment were established for patients who presented with visible haematuria.

Results

Of 1 365 attendances, 151 patients were diagnosed with a bladder tumour and 100 of these were both suitable and agreed to participate in the study. For patients with visible haematuria the median (range) waiting time from initial bleeding to surgery was 69.5 (9–1 165) days. This was comprised of a median (range) pre‐referral waiting time of 12 (0–1 137) days, assessment waiting time of 23.5 (0–207) days, and treatment waiting time of 20 (1–69) days. Reasons for prolonged waiting times included poor public awareness, patient fear and anxiety, delayed and non‐referral from primary care, administrative delays, and resource limitations.

Conclusion

Many patients experience significant delays in the diagnosis and treatment of their bladder cancer in Western Australia, and this probably reflects national trends. These concerning data warrant consideration of how delays can be reduced to improve outcomes for these patients.
Experiences of two multidisciplinary team members of systemic consultations in a community learning disability service
Authors: Johnson Clair , Viljoen Nina
Published: June 2017

Accessible Summary

People with learning disabilities may have help from their families, paid carers and professionals such as nurses, psychologists etc. Professionals (like psychologists) can help people with learning disabilities and their families, carers and other professionals by meeting to talk about solutions together. This is called a systemic consultation.

We asked two people who came to the systemic consultations what they thought was helpful and unhelpful about the systemic consultations. The two people we asked were two professionals who worked with people with learning disabilities.

The helpful things were that the systemic consultations might have helped people to feel better about themselves and speak about their worries. People may feel that others care about them too. People with learning disabilities started to find their own answers to the difficulties they had. We found that the people who were responsible for the systemic consultations asked some helpful questions. For example, they spoke in a positive way and tried to talk about the things that people were good at. Another helpful thing was that coming to the systemic consultations helped people to get on better with each other.

The unhelpful things were that people coming to the systemic consultations thought that something else would happen at the consultations. They also thought that sometimes there were too many people at the systemic consultations. They said that it was not helpful if the people who help in the systemic consultations change.

After looking at the answers the people gave, we talked about the things that can be done to make sure that systemic consultations become more helpful for everyone.

Background

Systemic approaches can be useful in working with people with learning disabilities and their network. The evidence base for these approaches within the field of learning disabilities, however, is currently limited.

Materials and Methods

This article presents part of a service evaluation of systemic consultations in a Community Learning Disability Service (CLDS). Two multidisciplinary team professionals were interviewed about what they found helpful and unhelpful in their experiences of attending systemic consultations. Interview data were analysed via applying thematic analysis principles.

Results

Five main themes were elicited: differing expectations, enabling for the client, positive techniques, uncertainty regarding “forum” (“forum” meaning the collective of all of the individuals meet, which could include the professionals, lead therapist, reflecting team, etc.) composition and strengthening the network.

Conclusions

Systemic consultations provided some positive and valuable experiences along with important caveats. Considerations for clinical practice are therefore discussed. Continued evaluation of systemic consultations within CLDSs is recommended.
Identification of lateralized compensatory neural activities within the social brain due to autism spectrum disorder in adolescent males
Authors: Subbaraju Vigneshwaran , Sundaram Suresh , Narasimhan Sundararajan
Published: June 2017

Socio‐behavioral impairments are important characteristics of autism spectrum disorders (ASD) and MRI‐based studies are pursued to identify a neurobiological basis behind these conditions. This paper presents an MRI‐based study undertaken to (i) identify the differences in brain activities due to ASD, (ii) verify whether such differences exist within the ‘social brain’ circuit which is hypothesized to be responsible for social functions, and (iii) uncover potential compensatory mechanisms within the identified differences in brain activities. In this study, a whole‐brain voxel‐wise analysis is performed using resting‐state fMRI data from 598 adolescent males, that is openly available from the ABIDE consortium. A new method is developed, which can (i) extract the discriminative brain activities, that provide high separability between the blood oxygenation time‐series signals from ASD and neurotypical populations, (ii) select the activities that are relevant to ASD by evaluating the correlation between the separability and traditional severity scores, and (iii) map the spatial pattern of regions responsible for generating the discriminative activities. The results show that the most discriminative brain activities occur within a subset of the social brain that is involved with affective aspects of social processing, thereby supporting the idea of the social brain and also its fractionalization in ASD. Further, it has also been found that the diminished activities in the posterior cingulate area are potentially compensated by enhanced activities in the ventromedial prefrontal and anterior temporal areas within the social brain. Hemispherical lateralization is also observed on such compensatory activities.
Climate change vulnerability for species—Assessing the assessments
Authors: Wheatley Christopher J. , Beale Colin M. , Bradbury Richard B. , Pearce‐Higgins James W. , Critchlow Rob , Thomas Chris D.
Published: June 2017

Climate change vulnerability assessments are commonly used to identify species at risk from global climate change, but the wide range of methodologies available makes it difficult for end users, such as conservation practitioners or policymakers, to decide which method to use as a basis for decision‐making. In this study, we evaluate whether different assessments consistently assign species to the same risk categories and whether any of the existing methodologies perform well at identifying climate‐threatened species. We compare the outputs of 12 climate change vulnerability assessment methodologies, using both real and simulated species, and validate the methods using historic data for British birds and butterflies (i.e. using historical data to assign risks and more recent data for validation). Our results show that the different vulnerability assessment methods are not consistent with one another; different risk categories are assigned for both the real and simulated sets of species. Validation of the different vulnerability assessments suggests that methods incorporating historic trend data into the assessment perform best at predicting distribution trends in subsequent time periods. This study demonstrates that climate change vulnerability assessments should not be used interchangeably due to the poor overall agreement between methods when considering the same species. The results of our validation provide more support for the use of trend‐based rather than purely trait‐based approaches, although further validation will be required as data become available.
Hepatocellular malignant neoplasm, NOS: a clinicopathological study of 11 cases from a single institution
Authors: Zhou Shengmei , Venkatramani Rajkumar , Gupta Shveta , Wang Kasper , Stein James E , Wang Larry , Mascarenhas Leo
Published: June 2017

Aims

The primary aim of this study is to characterize hepatocellular malignant neoplasm, NOS (HEMNOS), a new provisional entity describing a subset of paediatric hepatocellular tumours, which have histological features of neither typical hepatoblastoma (HB) nor hepatocellular carcinoma (HCC).

Methods and results

The clinicopathological features of 11 patients with HEMNOS were analysed retrospectively. The median age and serum alpha‐fetoprotein level at diagnosis was 7 years and 182 000 ng/ml, respectively. Ten patients presented with pretreatment extent of disease (PRETEXT) stages III/IV multifocal tumours, eight with major vascular involvement, three with lung metastases and three with extrahepatic extension. The original pathology diagnoses were: HB in seven patients, HCC in two and HEMNOS in two. Our pathology review of pre‐chemotherapy specimens showed that six tumours had equivocal/overlapping histological features of HB and HCC, four had predominant HB histology along with focal HCC‐like histology and one had HB histology. Seven of nine post‐chemotherapy resection specimens showed predominant HCC‐like histology. Beta‐catenin, glypican 3 and spalt‐like transcription factor 4 immunostaining showed that all the tumours had a mixed HB/HCC immunophenotype. Telomerase reverse transcriptase immunostaining showed nuclear staining in nine of the 11 tumours. All patients received chemotherapy and achieved gross total primary tumour resection. Nine of the 11 patients were treated with established HB chemotherapy regimens. After a median follow‐up of 6.1 years (range: 1.2–11.8 years), all patients were in remission.

Conclusions

HEMNOS is a subtype of HB with focal HCC‐like histology, a high‐risk clinical profile but favourable outcome following chemotherapy and complete tumour resection.
From intention to STI prevention: An online questionnaire on barriers and facilitators for discussing sexual risk behaviour among HIV nurses
Authors: de Munnik Suzanne , Vervoort Sigrid C.J.M. , Ammerlaan Heidi S.M. , Kok Gerjo , den Daas Chantal
Published: June 2017

Aims

We aimed to elucidate facilitators and barriers that HIV nurses experience in discussing sexual risk behaviour with HIV‐positive men who have sex with men, using variables from a previous qualitative study and the theory of planned behaviour.

Background

HIV‐positive men who have sex with men are frequently diagnosed with sexually transmitted infections, which can be reduced if HIV nurses discuss sexual risk behaviour.

Design

An online questionnaire was disseminated in April 2015 among all HIV nurses in the Netherlands.

Methods

We assessed variables, such as attitudes, shame, ability, knowledge and time concerns. A regression analysis was conducted with “intention to discuss sexual risk behaviour” as an outcome variable.

Results

The questionnaire was completed by 60 of 79 HIV nurses. Overall, participants reported high intentions to discuss sexual risk behaviour, and 38% of the variance was explained by attitude, sexual preference, knowing ways to introduce the topic and experiencing enough time or viewing it as a priority. In addition, high intenders significantly differed from low intenders in “experienced shame,” “relation with patients,” “non‐verbal communication,” “subjective norm” and “knowledge.”

Conclusion

Improving sexual health in HIV care translates into improving opportunities and the facilitating factors in initiating the discussion of sexual risk behaviour rather than removing barriers HIV nurses experience. Interventions should mainly focus on improving the HIV nurses’ perceived ability to initiate the topic of sexual risk behaviour and to utilize the jargon and terminology that is commonly used among men who have sex with men.
Regulatory mode and willingness to increase retirement savings contributions
Authors: Kim Hyungsoo , Shin Serah , Heath Claudia J. , Zhang Qun , Higgins E. Tory
Published: June 2017

This study examined how two self‐regulatory modes, locomotion and assessment, relate to the willingness to increase retirement savings. Locomotion is concerned with making things happen (“just do it”). Assessment is concerned with critical evaluation (“do the right thing”). We hypothesized that individuals who score high (vs. low) in locomotion, but not those who score high (vs. low) in assessment, would be more willing to increase their savings for retirement. In addition, because high (vs. low) assessment can lead to doing the right thing in terms of seeking to maximize economic returns, we hypothesized that combining high locomotion with high assessment would especially motivate willingness to increase retirement savings. We found support for both hypotheses from a survey of university employees.
Rho‐kinase inhibitor Y‐27632 facilitates the proliferation, migration and pluripotency of human periodontal ligament stem cells
Authors: Wang Ting , Kang Wenyan , Du Lingqian , Ge Shaohua
Published: June 2017

The selective in vitro expansion and differentiation of multipotent stem cells are critical steps in cell‐based regenerative therapies, while technical challenges have limited cell yield and thus affected the success of these potential treatments. The Rho GTPases and downstream Rho kinases are central regulators of cytoskeletal dynamics during cell cycle and determine the balance between stem cells self‐renewal, lineage commitment and apoptosis. Trans‐4‐[(1R)‐aminoethyl]‐N‐(4‐pyridinyl)cylohexanecarboxamidedihydrochloride (Y‐27632), Rho‐associated kinase (ROCK) inhibitor, involves various cellular functions that include actin cytoskeleton organization, cell adhesion, cell motility and anti‐apoptosis. Here, human periodontal ligament stem cells (PDLSCs) were isolated by limiting dilution method. Cell counting kit‐8 (CCK8), 5‐ethynyl‐2′‐deoxyuridine (EdU) labelling assay, cell apoptosis assay, cell migration assay, wound‐healing assay, alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, Oil Red O staining, quantitative real‐time polymerase chain reaction (qRT‐PCR) were used to determine the effects of Y‐27632 on the proliferation, apoptosis, migration, stemness, osteogenic and adipogenic differentiation of PDLSCs. Afterwards, Western blot analysis was performed to elucidate the mechanism of cell proliferation. The results indicated that Y‐27632 significantly promoted cell proliferation, chemotaxis, wound healing, fat droplets formation and pluripotency, while inhibited ALP activity and mineral deposition. Furthermore, Y‐27632 induced PDLSCs proliferation through extracellular‐signal‐regulated kinase (ERK) signalling cascade. Therefore, control of Rho‐kinase activity may enhance the efficiency of stem cell‐based treatments for periodontal diseases and the strategy may have the potential to promote periodontal tissue regeneration by facilitating the chemotaxis of PDLSCs to the injured site, and then enhancing the proliferation of these cells and maintaining their pluripotency.
Up‐regulated basigin‐2 in microglia induced by hypoxia promotes retinal angiogenesis
Authors: Yin Jie , Xu Wen‐Qin , Ye Ming‐Xiang , Zhang Yong , Wang Hai‐Yan , Zhang Jian , Li Yu , Wang Yu‐Sheng
Published: June 2017

Retinal microglia cells contribute to vascular angiogenesis and vasculopathy induced by relative hypoxia. However, its concrete molecular mechanisms in shaping retinal angiogenesis have not been elucidated. Basigin, being involved in tumour neovasculogenesis, is explored to exert positive effects on retinal angiogenesis induced by microglia. Therefore, we set out to investigate the expression of basigin using a well‐characterized mouse model of oxygen‐induced retinopathy, which recapitulated hypoxia‐induced aberrant neovessel growth. Our results elucidate that basigin is overexpressed in microglia, which accumulating in retinal angiogenic sprouts. In vitro, conditioned media from microglia BV2 under hypoxia treatment increase migration and tube formation of retinal capillary endothelia cells, compared with media from normoxic condition. The angiogenic capacity of BV2 is inhibited after basigin knockdown by small interfering RNAs. A new molecular mechanism for high angiogenic capacity, whereby microglia cells release basigin via up‐regulation of PI3K‐AKT and IGF‐1 pathway to induce angiogenesis is unveiled. Collectively, our results demonstrate that basigin from hypoxic microglia plays a pivotal pro‐angiogenic role, providing new insights into microglia‐promoting retinal angiogenesis.
AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression
Authors: Wu Shengjie , Yang Li , Wu Dandan , Gao Zhongyuan , Li Ping , Huang Wenbin , Wang Xuerong
Published: June 2017

Gastric cancer is the third leading cause of cancer‐related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte‐elevated gene‐1 (AEG‐1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG‐1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain‐ or loss‐of‐function of AEG‐1, respectively, promoted or suppressed epithelial–mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG‐1 positively regulated eIF4E, MMP‐9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG‐1‐regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP‐9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG‐1‐induced MMP‐9 and Twist. Finally, silencing of AEG‐1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP‐9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG‐1 promotes gastric cancer metastasis through upregulation of eIF4E‐mediated MMP‐9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis.
Gene‐based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms
Authors: Van Assche Evelien , Moons Tim , Cinar Ozan , Viechtbauer Wolfgang , Oldehinkel Albertine J. , Van Leeuwen Karla , Verschueren Karine , Colpin Hilde , Lambrechts Diether , Van den Noortgate Wim , Goossens Luc , Claes Stephan , van Winkel Ruud
Published: June 2017

Background

Most gene‐environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false‐positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence.

Methods

Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES‐D) was the outcome. We used gene‐based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p‐value per single gene. Significant results at the corrected p‐value of p < 1.90 × 10−4 were examined in an independent replication sample of Dutch adolescents (N = 1354).

Results

Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10−5) and GABRR2 (p = 9.05 × 10−6). No genes interacted significantly with psychological control or harsh punishment. Gene‐based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene‐based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10−4).

Conclusions

We present a gene‐based method for gene–environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E.
Advanced film‐forming gel formula vs spring thermal water and white petrolatum as primary dressings after full‐face ablative fractional CO2 laser resurfacing: a comparative split‐face pilot study
Authors: Marini L.
Published: June 2017

Background

Aesthetically pleasing results and fast, uneventful recovery are highly desirable after rejuvenating ablative laser procedures. Wound dressings following ablative laser procedures should ideally improve and optimize the wound healing environment.

Objective

The purpose of this comparative split‐face, single‐blinded, prospective observational study was to assess the efficacy and acceptability of two primary wound dressings immediately after a full‐face fractional CO2 laser resurfacing procedure.

Methods

The assessments of an innovative film‐forming dressing called Stratacel (SC) vs spring thermal water + Vaseline (V+) were conducted after a standardized, single‐pass, full‐face ablative fractional CO2 laser skin resurfacing procedure. Clinical parameters, such as haemoglobin – HB; surface temperature – ST; micro‐textural modifications – MT; superficial melanin – M; intrafollicular porphyrins – P, were assessed at different phases of the healing process using standardized, non‐invasive technologies.

Results

Five female volunteers were enrolled in this inpatient, controlled pilot study. Most of the clinical parameters considered, including 3D surface texture analysis, revealed a better performance of SC vs. V+ during the early, more delicate phases of the healing process.

Conclusions

This preliminary study, even if performed on a small number of volunteers, confirmed a definite advantage of the tested semipermeable film‐forming formula (SC) over a more conventional postoperative skin care regime (V+). Clinical results could be explained by a better uniformity of distribution of SC over the micro‐irregularities induced by ablative fractional CO2 laser resurfacing. Its thin, semipermeable film might, in fact, act as an efficient, perfectly biocompatible, full contact, temporary skin barrier, able to protect extremely delicate healing surfaces from potential environmental irritations.
Clinical and genetic diversities of Charcot‐Marie‐Tooth disease with MFN2 mutations in a large case study
Authors: Ando Masahiro , Hashiguchi Akihiro , Okamoto Yuji , Yoshimura Akiko , Hiramatsu Yu , Yuan Junhui , Higuchi Yujiro , Mitsui Jun , Ishiura Hiroyuki , Umemura Ayako , Maruyama Koichi , Matsushige Takeshi , Morishita Shinichi , Nakagawa Masanori , Tsuji Shoji , Takashima Hiroshi
Published: June 2017

Charcot‐Marie‐Tooth disease (CMT) constitutes a heterogeneous group affecting motor and sensory neurons in the peripheral nervous system. MFN2 mutations are the most common cause of axonal CMT. We describe the clinical and mutational spectra of CMT patients harboring MFN2 mutations in Japan. We analyzed 1,334 unrelated patients with clinically suspected CMT referred by neurological and neuropediatric departments throughout Japan. We conducted mutation screening using a DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified pathogenic or likely pathogenic MFN2 variants from 79 CMT patients, comprising 44 heterozygous and 1 compound heterozygous variants. A total of 15 novel variants were detected. An autosomal dominant family history was determined in 43 cases, and the remaining 36 cases were reported as sporadic with no family history. The mean onset age of CMT in these patients was 12 ± 14 (range 0–59) years. We observed neuropathic symptoms in all patients. Some had optic atrophy, vocal cord paralysis, or spasticity. We detected a compound heterozygous MFN2 mutation in a patient with a severe phenotype and the co‐occurrence of MFN2 and PMP22 mutations in a patient with an uncommon phenotype. MFN2 is the most frequent causative gene of CMT2 in Japan. We present 15 novel variants and broad clinical and mutational spectra of Japanese MFN2‐related CMT patients. Regardless of the onset age and inheritance pattern, MFN2 gene analysis should be performed. Combinations of causative genes should be considered to explain the phenotypic diversity.
Increased use of heated humidified high flow nasal cannula is associated with longer oxygen requirements
Authors: Heath Jeffery Rachael C , Broom Margaret , Shadbolt Bruce , Todd David A
Published: June 2017

Aim

There has been an increased use of heated humidified high flow nasal canula (HFNC) in premature babies (PBs) admitted to our neonatal unit. The aim of this study is to identify clinical characteristics in PBs < 29 weeks gestational age (GA) that distinguish between those who did not or did receive HFNC.

Methods

This study compared prospectively collected data from 2010 to 2012. Comparisons were undertaken between PBs<29 weeks GA who received continuous positive airway pressure (CPAP: 44/72 (61.1%)) to those who received both CPAP and HFNC (28/72 (38.9%)). Data were analysed using general linear models.

Results

There were no significant differences in baseline characteristics between the groups (GA: 27.6 ± 1.1 vs. 27.5 ± 1.1 (weeks), birth weight: 1066 ± 209 vs. 1057 ± 304 (grams) respectively). When analysing outcome measures with multivariate analysis, we found the corrected GA to cease CPAP and oxygen were significantly longer in the HFNC group (31.2 ± 2.1 vs. 32.7 ± 2.0 weeks, P = 0.01 and 32.8 ± 3.5 vs. 36.5 ± 2.8 weeks, P < 0.0001 respectively).

Conclusions

Increased use of HFNC has been associated with increased oxygen requirements. These findings highlight the need to review the use of HFNC in small PBs.
Long‐term serum bile acid concentrations in 51 dogs after complete extrahepatic congenital portosystemic shunt ligation
Authors: Bristow P. , Tivers M. , Packer R. , Brockman D. , Ortiz V. , Newson K. , Lipscomb V.
Published: June 2017

Objectives

To report the long‐term bile acid stimulation test results for dogs that have undergone complete suture ligation of a single congenital extrahepatic portosystemic shunt.

Materials and Methods

Data were collected from the hospital records of all dogs that had undergone a complete suture ligation of a single congenital extrahepatic portosystemic shunt. Owners were invited to return to the referral centre or their local veterinarian for repeat serum bile acid measurement. Dogs diagnosed with idiopathic epilepsy and undergoing bile acid stimulation tests were used as a comparison population.

Results

Fifty‐one study dogs were included, with a mean follow‐up time of 62 months. 48 dogs had no evidence of multiple acquired shunts and a significant reduction in the pre‐ and post‐prandial serum bile acid concentrations at long‐term follow‐up compared with pre‐operative measurements. Pre‐ and post‐prandial serum bile acids were statistically significantly greater for dogs that had undergone a full ligation (with no evidence of multiple acquired shunts) at all time points compared to the control dogs (P<0·001 for all comparisons).

Clinical Significance

The results suggest that in dogs treated with complete suture ligation mild increases in serum bile acids are not clinically relevant if there are no physical examination abnormalities, a normal body condition score and no relapse in clinical signs.
Mountain Railway Alignment Optimization with Bidirectional Distance Transform and Genetic Algorithm
Authors: Li Wei , Pu Hao , Schonfeld Paul , Yang Junsheng , Zhang Hong , Wang Lei , Xiong Jiaxing
Published: June 2017

Various challenging constraints must be satisfied in railway alignment design for topographically complex mountainous regions. The alignment design for such environments is so challenging that existing methodologies have great difficulties in automatically generating viable railway alignment alternatives. We solve this problem with a hybrid method in which a bidirectional distance transform (DT) algorithm automatically selects control points before a genetic algorithm (GA) refines the alignment. This approach solves the problems of (1) determining the appropriate distribution of control points in the GA and (2) producing alignments that deviate significantly from the DT‐optimized paths. Automatic design of backtracking curves and dynamic generation of vertical points of intersection handling multiple constraints are developed to improve the GA performance. This method has been applied to a real case on the Sichuan–Tibet Railway where excessively severe natural gradients must be overcome. It automatically finds an alignment optimized for the given objectives and complex constraints, as well as various promising alternatives.
Resveratrol and pterostilbene as a microRNA‐mediated chemopreventive and therapeutic strategy in prostate cancer
Authors: Kumar Avinash , Rimando Agnes M. , Levenson Anait S.
Published: June 2017

Growing evidence indicates that deregulation of the epigenetic machinery comprising the microRNA (miRNA) network is a critical factor in the progression of various diseases, including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA‐mediated health‐beneficial properties, such as anti‐inflammatory, cardioprotective, antioxidative, and anticancer properties. Available experimental data have suggested that dietary polyphenols may be effective miRNA‐modulating chemopreventive and therapeutic agents. Moreover, noninvasive detection of changes in miRNA expression in liquid biopsies opens enormous possibilities for their clinical utilization as novel prognostic and predictive biomarkers. In our published studies, we identified resveratrol‐regulated miRNA profiles in prostate cancer. Resveratrol downregulated the phosphatase and tensin homolog (PTEN)–targeting members of the oncogenic miR‐17 family of miRNAs, which are overexpressed in prostate cancer. We have functionally validated the miRNA‐mediated ability of resveratrol and its potent analog pterostilbene to rescue the tumor suppressor activity of PTEN in vitro and in vivo. Taken together, our findings implicate the use of resveratrol and its analogs as an attractive miRNA‐mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development.
Campylobacter fetus impairs barrier function in HT‐29/B6 cells through focal tight junction alterations and leaks
Authors: Bücker Roland , Krug Susanne M. , Fromm Anja , Nielsen Hans Linde , Fromm Michael , Nielsen Henrik , Schulzke Jörg‐Dieter
Published: June 2017

Infections by Campylobacter species are the most common foodborne zoonotic disease worldwide. Campylobacter jejuni and C. coli are isolated most frequently from human stool samples, but severe infections by C. fetus (Cf), which can cause gastroenteritis, septicemia, and abortion, are also found. This study aims at the characterization of pathological changes in Cf infection using an intestinal epithelial cell model. The Cf‐induced epithelial barrier defects appeared earlier than those of avian Campylobacter species like C. jejuni/C. coli. Two‐path impedance spectroscopy (2PI) distinguished transcellular and paracellular resistance contributions to the overall epithelial barrier impairment. Both transcellular and paracellular resistance of Cf‐infected HT‐29/B6 monolayers were reduced. The latter was attributed to activation of active anion secretion. Western blot analysis showed no decrease in tight junction (TJ) protein expression (claudin‐1, ‐2, ‐3, and ‐4) but showed redistribution of claudin‐1 off the TJ domain. In addition, Cf induced epithelial cell death, cell detachment, and lesions (focal leaks), as the result of which macromolecule flux (10‐kDa dextran) was increased in Cf‐invaded cell monolayers. In conclusion, barrier dysfunction from Cf infection was due to TJ protein redistribution, cell death induction, and leak formation, resulting in bacterial translocation, ion leak flux, and antigen uptake (leaky gut).
A vicious circle in chronic lymphoedema pathophysiology? An adipocentric view
Authors: Cucchi F. , Rossmeislova L. , Simonsen L. , Jensen M. R. , Bülow J.
Published: June 2017

Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These events seem to maintain and reinforce themselves through a positive feedback loop: regardless of the initial cause of lymphatic stasis, the dysfunctional adipose tissue and its secretion products can worsen lymphatic vessels' function, aggravating lymph leakage and stagnation, which can promote further adipose tissue deposition and fibrosis, similar to what may happen in obesity. In addition to the current knowledge about the tight and ancestral interrelation between immunity system and metabolism, there is evidence for similarities between obesity‐related and lymphatic damage‐induced lymphoedema. Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle.
Centre‐level variation in treatment and outcomes and predictors of outcomes in 5‐year‐old children with non‐syndromic unilateral cleft lip treated within a centralized service: the Cleft Care UK study. Part 6: summary and implications
Authors: Ness A. R. , Wills A. K. , Mahmoud O. , Hall A. , Sell D. , Smallridge J. , Southby L. , Stokes D. , Toms S. , Waylen A. , Wren Y. , Sandy J. R.
Published: June 2017

Structured Abstract

Objectives

To summarize and discuss centre‐level variation across a range of treatment and outcome measures and examine individual and ecological determinants of outcome in children in Cleft Care UK (CCUK).

Setting and sample population

Two hundred and sixty‐eight 5‐year‐old British children with non‐syndromic unilateral cleft lip and palate (UCLP) recruited to CCUK and treated within a centralized service.

Materials and Methods

Children had a range of treatment and outcome measures collected at a 5‐year audit clinic. These outcomes included dento‐alveolar arch relationships from study models, measures of facial appearance from cropped photographs, hearing loss from audiological assessment, speech from speech recordings, self‐confidence and strengths and difficulties from parental self‐report. Data were collected on educational attainment at age 7 using record linkage. Centre variation was examined using hierarchical regression and associations between variables were examined using logistic or poisson regression.

Results

There was centre‐level variation for some treatments (early grommet placement, fitting of hearing aids, fluoride treatment, secondary speech surgery and treatment for cleft speech characteristics) and for some outcomes (intelligibility of speech). Hearing loss was associated with a higher risk of poor speech while speech therapy was associated with a lower risk of poor speech. Children had high levels of caries but levels of preventative treatment (fluoride varnish and tablets) were low.

Conclusions

Further improvements to and monitoring of the current centralized model of care are required to ensure the best outcomes for all children with cleft lip and palate.
Improving adaptation to drought stress in white pea bean (Phaseolus vulgaris L.): Genotypic effects on grain yield, yield components and pod harvest index
Authors: Assefa Teshale , Rao Idupulapati M. , Cannon Steven B. , Wu Jixiang , Gutema Zenbaba , Blair Matthew , Otyama Paul , Alemayehu Fitsume , Dagne Belete
Published: June 2017

Common bean (Phaseolus vulgaris L.) is the most important food legume crop in Africa and Latin America where rainfall pattern is unpredictable. The objectives were to identify better yielding common bean lines with good canning quality under drought, and to identify traits that could be used as selection criteria for evaluating drought‐tolerant genotypes. In all, 35 advanced lines were developed through single seed descent and evaluated with a standard check under drought and irrigated conditions at two locations over 2 years in Ethiopia. Grain yield (GY), pod number per m2, seed number per m2 and seed weight decreased by 56%, 47%, 49% and 14%, respectively, under drought stress. Eight genotypes had better yield with good canning quality under drought compared to the check. Moderate to high proportion of genetic effects were observed under drought conditions for GY and yield components compared to genotype × environment effects. Significant positive correlations between GY and pod harvest index (PHI) in drought suggest that PHI could be used as an indirect selection criterion for common bean improvement.
A molecular‐genetic understanding of diapause in spider mites: current knowledge and future directions
Authors: Bryon Astrid , Kurlovs Andre H. , Van Leeuwen Thomas , Clark Richard M.
Published: June 2017

During unfavourable conditions, many arthropods have the ability to enter into diapause and synchronize their development and reproduction to seasonal patterns. Diapause or winter hibernation in insects and mites is set off by a number of cues, with photoperiod being the most well‐defined and strongest signal. This review focuses on the current knowledge of ‘‐omics’ data and the genetics of diapause in the two‐spotted spider mite Tetranychus urticae, a member of the family Tetranychidae (Arthropoda: Chelicerata: Arachnida: Acari). This species is a serious polyphagous pest and females undergo a reproductive facultative diapause when immature stages are exposed to long nights. Winter hibernation induces different physiological processes characterized by a metabolic suppression, different energy use, increased stress tolerance and the production of cryoprotectants, all initiated by a complex signal transduction pathway. Keto‐carotenoids are known to cause the deeply orange colour typical for diapausing females. Furthermore, research with colour mutants of T. urticae has shown the need for carotenoids with respect to the induction of diapause, even though the molecular‐genetic mechanisms underlying these colour phenotypes are still unknown. In addition, marked latitudinal variation in diapause incidence among populations has been observed in nature, with modes of inheritance ranging from recessive to dominant, as well as monogenic to polygenic. We end by highlighting the emerging opportunities for functional studies that aim to unravel the complex factors underlying diapause in spider mites.
Frances Harriet Williams: Unsung Social Equity Pioneer
Authors: Gooden Susan T.
Published: June 2017

Frances Harriet Williams was an unsung social equity pioneer in the field of public administration. Long before the Minnowbrook I Conference convened in the 1960s to discuss the importance of fairness in the provision of public services, Williams successfully promoted values of social equity and racial fairness within public administration scholarly and practitioner communities. Raised by progressive parents in the South, Williams was the only high‐ranking African‐American woman in the federal government during President Franklin D. Roosevelt's administration. She was directly involved in leading the Office of Price Administration to a staff that was at least 13 percent black when the rest of government was no more than 1 percent black. This work was the focus of her 1947 article in Public Administration Review, the first publication on racial equity to appear in the field's flagship journal. Her efforts and accomplishments undergird many of the ideals and practices that constitute the concept of social equity in public administration today.
Regional Governance and Institutional Collective Action for Environmental Sustainability
Authors: Yi Hongtao , Suo Liming , Shen Ruowen , Zhang Jiasheng , Ramaswami Anu , Feiock Richard C.
Published: June 2017

This research investigates why various mechanisms of cooperation among local authorities are chosen using the theoretical lens of institutional collective action (ICA). The article analyzes 564 local collaboration agreements drawn from four urban regions of China to explain the choices of environmental collaboration agreements among cities. Examples of three forms of interlocal agreements—informal, formal, and imposed agreements—are analyzed. Ordinal logistic regressions are estimated to test which factors predicted by the ICA framework influence the form of collaboration selected. The results indicate that the involvement of national or provincial government, the number of policy actors involved, heterogeneity of economic conditions, and differences in administrative level among the actors involved influence how collaboration agreements are structured. Examining the choice of agreement type contributes to the understanding of interlocal collaboration and provides practical insights for public managers to structure interlocal collaboration.