bluuebunny/crossref_metadata_2025 huggingface dataset:
Procalcitonin as a diagnostic indicator for systemic bacterial infections in patients with Stevens–Johnson syndrome/toxic epidermal necrolysis
Authors: Wang Qian , Tian Xiao‐Bing , Liu Wei , Zhang Li‐Xia
Published: June 2018

Elevated serum procalcitonin (PCT) level has been reported to be a diagnostic index in systemic bacterial infections, but it can also increase in some non‐infectious inflammatory diseases. Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immune‐mediated cutaneous mucosal reaction which is susceptible to bacterial infections and may have elevated PCT levels. The value of serum PCT has not been assessed in series of SJS/TEN patients. We aimed to investigate the PCT levels in SJS/TEN patients with systemic bacterial infections (systemic infected group), with skin surface bacterial infections (skin surface infected group) and without infections (non‐infected group), to assess whether PCT was a valuable indicator for systemic bacterial infections in SJS/TEN patients. The PCT and C‐reactive protein (CRP) levels of 42 inpatients with SJS/TEN were retrospectively analysis. The receiver–operator curve (ROC) was used to determine the diagnostic efficacy of PCT for systemic bacterial infections in SJS/TEN patients. The results demonstrated that PCT levels in the systemic infected group were significantly higher than those in the other two groups (P < 0.05). There was no significant difference in CRP between the three groups. The cut‐off PCT level of 0.65 ng/mL calculated by ROC had optimal diagnostic efficacy, with sensitivity and specificity of 84.6% and 89.7%, respectively. PCT and severity‐of‐illness score for toxic epidermal necrolysis were positively correlated (P < 0.05). In conclusion, PCT is a valuable index and superior to CRP in detecting systemic bacterial infections in SJS/TEN patients. The level of PCT can partially reflect the severity of the disease.
Analysis of possible structures of inducible skin‐associated lymphoid tissue in lupus erythematosus profundus
Authors: Kogame Toshiaki , Yamashita Ryosuke , Hirata Masahiro , Kataoka Tatsuki R. , Kamido Hisashi , Ueshima Chiyuki , Matsui Miho , Nomura Takashi , Kabashima Kenji
Published: June 2018

Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin‐associated lymphoid tissues (iSALT). We subsequently reported structures analogous to iSALT in human secondary syphilis, suggesting that iSALT can also exist in humans. Here, we studied ectopic lymphoid tissues in the lesions of LEP by immunohistochemistry and compared their characteristics with those of TLO. We demonstrated that LF of LEP were composed of B‐cell follicles intermingled with CXCL13‐expressing cells, distinct aggregations of T cells, and some blood vessels expressing peripheral node addressin. These findings indicate that LF of LEP can be considered as a type of iSALT.
Attitudes of Australian primary school teachers towards the inclusion of students with autism spectrum disorders
Authors: Garrad Traci‐Ann , Rayner Christopher , Pedersen Scott
Published: June 2018

Diagnoses of autism spectrum disorder (ASD) have risen dramatically in the last 10 years, with recent estimates at one in every 100 children within Australia. This has resulted in considerable increases in the number of students with ASD entering mainstream education. Teachers’ attitudes towards inclusion have been recognised as a key indicator for students’ successful inclusion. The main factors posited for determining teachers’ attitudes towards the inclusion of students with disabilities, consists of the amount of specialist training received and the length of specific ASD teaching experience. Utilising the Autism Attitude Scale for Teachers for the first time in Australia, we examined 107 primary school teachers’ attitudes towards the inclusion of students with ASD within their classrooms. The resulting scores were then analysed to examine the correlations, if any existed, between the amount of specialised training and years of ASD‐specific teaching on teachers’ attitude scores. While teachers’ attitudes were found to be highly positive, contrary to previous studies, low correlation coefficients were reported between their attitudes and ASD‐specific teaching experience, and their attitudes and the number of ASD‐specific professional development courses they attended. Findings of this study are discussed in the context of the sample population and explore the notion of a sociological and philosophical shift, attributed to the positive promotion efforts of the inclusive education movement, as one possible reason for the divergence in the findings from past research in the field.
Empirical‐Based Typology of Health Care Utilization by Medicare Eligible Veterans
Authors: Vaughan Sarrazin Mary , Rosenthal Gary E. , Turvey Carolyn L.
Published: June 2018

Objective

Up to 70 percent of patients who receive care through Veterans Health Administration (VHA) facilities also receive care from non‐VA providers. Using applied classification techniques, this study sought to improve understanding of how elderly VA patients use VA services and complementary use of non‐VA care.

Methods

The study included 1,721,900 veterans age 65 and older who were enrolled in VA and Medicare during 2013 with at least one VA encounter during 2013. Outpatient and inpatient encounters and medications received in VA were classified, and mutually exclusive patient subsets distinguished by patterns of VA service use were derived empirically using latent class analysis (LCA). Patient characteristics and complementary use of non‐VA care were compared by patient subset.

Results

Five patterns of VA service use were identified that were distinguished by quantity of VA medical and specialty services, medication complexity, and mental health services. Low VA Medical users tend to be healthier and rely on non‐VA services, while High VA users have multiple high cost illnesses and concentrate their care in the VA.

Conclusions

VA patients distinguished by patterns of VA service use differ in illness burden and the use of non‐VA services. This information may be useful for framing efforts to optimize access to care and care coordination for elderly VA patients.
Expertise Redundancy, Transactive Memory, and Team Performance in Interdisciplinary Care Teams
Authors: Zhu Xi , Wholey Douglas R.
Published: June 2018

Objective

To examine how expertise redundancy and transactive memory (TM) in interdisciplinary care teams (ICTs) are related to team performance.

Data Sources/Study Setting

Survey and administrative data were collected from 26 interdisciplinary mental health teams.

Study Design

The study used a longitudinal, observational design. Independent variables were measured at baseline, 6, and 12 months: expertise redundancy (the extent to which team members possess highly overlapping knowledge), TM accuracy (the extent to which team members accurately recognize experts in relevant knowledge domains), and TM consensus (the extent to which team members agree on who is expert in which knowledge domain). Team performance was measured as risk‐adjusted average number of client hospitalization for the 6 months following each survey.

Data Collection Methods

Survey data were collected by the authors. Administrative data were collected by the state's administrative agency.

Principal Findings

Expertise redundancy had a negative effect on performance. TM accuracy had a positive effect on performance, and such effect was stronger when expertise redundancy was higher. No significant effect was found on TM consensus.

Conclusions

Transactive memory could serve as a cognitive coordination mechanism for mitigating the negative effect of complex knowledge structure in ICTs.
Nonrecurring Items in Debt Contracts
Authors: Beatty Anne , Cheng Lin , Zach Tzachi
Published: June 2018

Using a large sample of debt contracts, we study the determinants of excluding nonrecurring items from covenant calculations. We investigate this choice across firms, across items, and through time. We find that nonrecurring items are more likely to be excluded when the agency costs of debt are higher and less likely to be excluded when they predict borrowers' performance. Our evidence further suggests that the interplay between agency costs and nonrecurring items' predictive ability affects the decision to exclude these items from covenant computations. Finally, when examining the exclusion by different nonrecurring item types, we find confirmatory evidence that the probability of exclusion decreases with the predictive ability for borrowers' future performance of major nonrecurring item types. Overall, our research extends the literature on the determinants of contract design and improves understanding of the usefulness of accounting information in debt contracting.
MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment
Authors: Xu Rongyao , Shen Xiang , Si Yameng , Fu Yu , Zhu Weiwen , Xiao Tao , Fu Zongyun , Zhang Ping , Cheng Jie , Jiang Hongbing
Published: June 2018

The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.
Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?
Authors: Prytkova Iya , Goate Alison , Hart Ronald P. , Slesinger Paul A.
Published: June 2018

Alcohol use disorder (AUD) affects millions of people and costs nearly 250 billion dollars annually. Few effective FDA‐approved treatments exist, and more are needed. AUDs have a strong heritability, but only a few genes have been identified with a large effect size on disease phenotype. Genomewide association studies (GWASs) have identified common variants with low effect sizes, most of which are in noncoding regions of the genome. Animal models frequently fail to recapitulate key molecular features of neuropsychiatric disease due to the polygenic nature of the disease, partial conservation of coding regions, and significant disparity in noncoding regions. By contrast, human induced pluripotent stem cells (hiPSCs) derived from patients provide a powerful platform for evaluating genes identified by GWAS and modeling complex interactions in the human genome. hiPSCs can be differentiated into a wide variety of human cells, including neurons, glia, and hepatic cells, which are compatible with numerous functional assays and genome editing techniques. In this review, we focus on current applications and future directions of patient hiPSC‐derived central nervous system cells for modeling AUDs in addition to highlighting successful applications of hiPSCs in polygenic neuropsychiatric diseases.
Clinical disease activity is associated with anxiety and depressive symptoms in adolescents and young adults with inflammatory bowel disease
Authors: van den Brink G. , Stapersma L. , Vlug L. E. , Rizopolous D. , Bodelier A. G. , van Wering H. , Hurkmans P. C. W. M. , Stuyt R. J. L. , Hendriks D. M. , van der Burg J. A. T. , Utens E. M. W. J. , Escher J. C.
Published: June 2018

Background

Youths with inflammatory bowel disease (IBD) are at risk for developing anxiety and depressive symptoms with a reported 20%‐50% prevalence rate.

Aims

This prospective study aimed to: (1) describe the prevalence and severity of anxiety and depressive symptoms in a large Dutch cohort of young IBD patients, and (2) identify demographic and clinical risk factors for anxiety and depression.

Methods

IBD patients (n = 374; 10‐25 years) were screened for anxiety, depression and quality of life using validated age‐specific questionnaires. Patients with elevated scores for anxiety and/or depressive symptoms received a diagnostic interview assessing psychiatric disorders. Demographic and clinical characteristics were retrieved from medical charts. Multiple logistic regression analysis was performed to identify risk factors for anxiety and/or depression.

Results

Patients (mean age 18.9 years, 44.1% male, Crohn's disease 60.4%) had disease in remission (75.4%), or mild, moderate and severe clinical disease activity in, respectively, 19.8%, 2.7% and 2.1%. Mild anxiety/depressive symptoms were present in 35.2% and severe symptoms in 12.4% of patients. Elevated symptoms of either anxiety (28.3%), depression (2.9%) or both (15.8%) were found and did not differ between adolescents (10‐17 years) and young adults (18‐25 years). Active disease significantly predicted depressive symptoms (odds ratio (OR): 4.6 [95% confidence interval [CI]: 2.4‐8.8], P < 0.001). Female gender (OR: 1.7 [95% CI: 1.1‐2.7]), active disease (OR: 1.9 [95% CI: 1.1‐3.2]) and a shorter disease duration (OR: 1.3 [95% CI: 0.6‐1.0) (all P < 0.025) significantly predicted anxiety and/or depressive symptoms.

Conclusions

Considering the high prevalence of anxiety and depressive symptoms, psychological screening is recommended in young IBD patients. Screening facilitates early recognition and psychological treatment. Female patients and patients with active disease are the most vulnerable.
Excellent Preservation of Archaeological, Mercury‐Enriched Dental Remains
Authors: Ochoa‐Lugo M. , Cervini‐Silva J. , Muñoz M. D. L. , Palacios E. , Pérez‐Ramirez G. , Ramos‐Cruz E. , Romano‐Pacheco A.
Published: June 2018

In this study, we assessed the notable preservation of mercury‐enriched ancient dental remains. The studied specimen belonged to a 30‐year‐old woman, and it was collected from Temple XIII at the archaeological site of Palenque, Mexico (17°29’2.32”N, 92°2’46.78”W; a UNESCO World Heritage Site). The preservation of an ancient molar was studied by high‐resolution scanning electron microscopy and energy‐dispersive X‐ray spectroscopy (HRSEM–EDS), and the obtained results were compared to those recorded for contemporary tooth specimens. Measured and conventional carbon ages for the ancient molar were 1000 ± 30 and 1260 ± 30 bp, respectively. Energy‐dispersive spectroscopy (EDS) analysis showed that the accumulated Hg in the ancient molar was 66% (by weight). In contrast, the Hg content in the contemporary molar was observed to be below the analytical detection limits. Clearly, Hg accumulated preferentially in ancient dental structures. Aging favoured the overall exchange of Hg for structural Ca; namely, chemical migration from one dental compartment to the other, mineral transformations, enamel hypoplasia, and the accumulation of Hg and Al in bio‐organic structures. Overall, we observed excellent preservation of biogenic material with varying physiological function(s), including abundant odontoblasts (tubules and spheres), dentinal tubules and nervous system fibrils.
Call type signals caller goal: a new take on ultimate and proximate influences in vocal production
Authors: Schamberg Isaac , Wittig Roman M. , Crockford Catherine
Published: June 2018

After 40 years of debate it remains unclear whether signallers produce vocalizations in order to provide receivers with information about call context or external stimuli. This has led some researchers to propose that call production is arousal‐ or affect‐based. Although arousal influences certain acoustic parameters within a call type, we argue that it cannot explain why individuals across vertebrates produce different call types. Given emerging evidence that calls are goal‐based, we argue that call type is a signal of a caller's goal to elicit a change in receiver behaviour. Using chimpanzees (Pan troglodytes) and vervet monkeys (Cercopithecus aethiops) as case studies, we demonstrate the two benefits of viewing call production as signalling both caller goal (which determines call type) and caller arousal (which affects within‐call‐type variation). Such a framework can explain first, why a single class of calls is apparently given in multiple contexts, and, second, why some species have larger call repertoires than others. Previous studies have noted links between sociality and repertoire size, but have not specified exactly why animals living in societies that are more complex might require a greater number of differentiated signals. The caller‐goal framework potentially clarifies how social complexity might favour call diversification. As social complexity increases, callers may need to elicit a larger number of distinct behaviours from a wider range of distinct audiences.
Pre‐treatment CD8+ tumour‐infiltrating lymphocyte density predicts distant metastasis after definitive treatment in patients with stage III/IV hypopharyngeal squamous cell carcinoma
Authors: Ono T. , Azuma K. , Kawahara A. , Akiba J. , Kakuma T. , Chitose S. , Umeno H.
Published: June 2018

Objectives

Although inflammatory markers, such as the neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio and local immune markers have been shown to have prognostic utility, limited information is available regarding inflammatory and pre‐existing tumour‐infiltrating lymphocyte density and their association with prognosis in patients with hypopharyngeal squamous cell carcinoma. We investigated the prognostic ability of inflammatory markers and tumour‐infiltrating lymphocyte density in stage III and stage IV hypopharyngeal squamous cell carcinoma patients receiving definitive treatment.

Design

Retrospective cohort study.

Setting

Kurume University Hospital.

Participants

Ninety‐six stage III or stage IV hypopharyngeal squamous cell carcinoma patients treated at the Kurume University Hospital between 2000 and 2014.

Main outcome measures

Inflammatory markers and pre‐treatment tumour‐infiltrating lymphocyte density were examined from recorded haematologic data and immunohistochemical analysis.

Results

Multivariate analyses showed that the CD8+ tumour‐infiltrating lymphocyte density was an independent predictive factor for distant metastasis and overall survival, whereas inflammatory markers, including the neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio, were not correlated with distant metastasis or overall survival.

Conclusions

Higher pre‐treatment CD8+ tumour‐infiltrating lymphocyte density is a useful predictive biomarker for reduced distant metastasis and better prognosis.
Author's response. Assessing forearm muscle size with the ultrasound
Authors: Abe Takashi , Loenneke Jeremy P.
Published: June 2018

Click here to view the Letter from Kara et al..
Shedding light on an unknown reality in solid organ transplant patients’ self‐management: A contextual inquiry study
Authors: Vanhoof Jasper M. M. , Vandenberghe Bert , Geerts David , Philippaerts Pieter , De Mazière Patrick , DeVito Dabbs Annette , De Geest Sabina , Dobbels Fabienne ,   the PICASSO‐Tx consortium
Published: June 2018

Traditional quantitative and qualitative research methods inadequately capture the complexity of patients’ daily self‐management. Contextual inquiry methodology, using home visits, allows a more in‐depth understanding of how patients integrate immunosuppressive medication intake, physical activity, and healthy eating in their daily lives, and which difficulties they experience when doing so. This mixed‐method study comprised 2 home visits in 19 purposively selected adult heart, lung, liver, and kidney transplant patients, asking them to demonstrate how they implement the aforementioned health behaviors. Meanwhile, conversations were audio‐taped and photographs were taken. Audio‐visual materials were coded using directed content analysis. Difficulties and supportive strategies were identified via inductive thematic analysis. We learned that few patients understood what “sufficiently active” means. Physical discomforts and poor motivation created variation across activity levels observed. Health benefits of dietary guidelines were insufficiently understood, and their implementation into everyday life considered difficult. Many underestimated the strictness of immunosuppressive medication intake, and instructions on handling late doses were unclear. Interruptions in routine and busyness contributed to nonadherence. We also learned that professionals often recommend supportive strategies, which patients not always like or need. This contextual inquiry study revealed unique insights, providing a basis for patient‐tailored self‐management interventions.
Systematic review and meta‐analysis of psychological interventions in people with diabetes and elevated diabetes‐distress
Authors: Schmidt C. B. , van Loon B. J. Potter , Vergouwen A. C. M. , Snoek F. J. , Honig A.
Published: June 2018

Aims

The clinical relevance of diabetes‐distress is increasingly recognized, but little is known about the efficacy of interventions specifically targeted to treat elevated diabetes‐distress. Therefore, this systematic review sought to determine the efficacy of psychological interventions aimed at treating elevated diabetes‐distress in people with Type 1 or Type 2 diabetes.

Methods

We systematically searched literature from five databases. Randomized controlled trials (RCTs) with an English abstract, describing the results of a psychological intervention in adults with diabetes were included. Articles were eligible for inclusion if the primary outcome was diabetes‐distress measured by the Problem Areas in Diabetes Scale (PAID‐5/PAID‐20) or the Diabetes Distress Scale (DDS‐17). Only mean group diabetes‐distress values above cut‐off at baseline or the results of a subgroup above cut‐off (PAID‐5 ≥ 8, PAID‐20 ≥ 40 or DDS‐17 ≥ 3) were included.

Results

The search yielded 8907 articles. After removing 2800 duplicates, 6107 articles remained. Titles and abstracts were screened, leaving 394 potential articles of interest, nine of which were RCTs. In a random‐effects meta‐analysis, the pooled effect size for diabetes‐distress was 0.48 (Cohen's d), Z = 3.91, P < 0.0001. Statistical heterogeneity was I² = 46.67% (confidence intervals 45.06% to 48.28%). Diabetes‐tailored psychological interventions reduced HbA1c (Cohen's d = 0.57), whereas mindfulness‐based interventions did not (Cohen's d = 0.11).

Conclusions

This systematic review shows that specifically diabetes‐tailored psychological interventions are effective in reducing elevated diabetes‐distress and HbA1c. More rigorous studies are warranted to establish the full potential of these interventions.

PROSPERO database registration ID: CRD42017075290.
Permanent neonatal diabetes: combining sulfonylureas with insulin may be an effective treatment
Authors: Misra S. , Vedovato N. , Cliff E. , De Franco E. , Hattersley A. T. , Ashcroft F. M. , Oliver N. S.
Published: June 2018

Background

Permanent neonatal diabetes caused by mutations in the KCNJ11 gene may be managed with high‐dose sulfonylureas. Complete transfer to sulfonylureas is not successful in all cases and can result in insulin monotherapy. In such cases, the outcomes of combining sulfonylureas with insulin have not been fully explored. We present the case of a woman with diabetes due to a KCNJ11 mutation, in whom combination therapy led to clinically meaningful improvements.

Case

A 22‐year‐old woman was found to have a KCNJ11 mutation (G334V) following diagnosis with diabetes at 3 weeks. She was treated with insulin‐pump therapy, had hypoglycaemia unawareness and suboptimal glycaemic control. We assessed the in vitro response of the mutant channel to tolbutamide in Xenopus oocytes and undertook sulfonylurea dose‐titration with C‐peptide assessment and continuous glucose monitoring. In vitro studies predicted the G334V mutation would be sensitive to sulfonylurea therapy [91 ± 2% block (n = 6) with 0.5 mM tolbutamide]. C‐peptide increased following a glibenclamide test dose (from 5 to 410 pmol/l). Glibenclamide dose‐titration was undertaken: a lower glibenclamide dose did not reduce blood glucose levels sustainably, but at 1.2 mg/kg/day insulin delivery was reduced to 0.1 units/h. However, when insulin was stopped, hyperglycaemia ensued. Glibenclamide was further increased (2 mg/kg/day), but once‐daily long‐acting insulin was still required to maintain glycaemia. This resulted in improved HbA1c of 52 mmol/mol (6.9%), restoration of hypoglycaemia awareness and reduced glycaemic variability.

Conclusion

In people with KCNJ11 mutations causing permanent neonatal diabetes, and where complete transfer is not possible, consideration should be given to dual insulin and sulfonylurea therapy.
Cover Image, Volume 20, Issue 7
Authors: Jung Hoe‐Yune , Kim Bobae , Ryu Hye Guk , Ji Yosep , Park Soyoung , Choi Seung Hee , Lee Dohyun , Lee In‐Kyu , Kim Munki , Lee You Jeong , Song Woojin , Lee Young Hee , Choi Hyung Jin , Hyun Chang‐Kee , Holzapfel Wilhelm H , Kim Kyong‐Tai
Published: June 2018

The cover image, by Hoe‐Yune Jung, et al., is based on the Original Article Amodiaquine improves insulin resistance and lipid metabolism in diabetic model mice, DOI: 10.1111/dom.13284.

image
Intracellular β2 integrin (CD11/CD18) interacting partners in neutrophil trafficking
Authors: Thome Sarah , Begandt Daniela , Pick Robert , Salvermoser Melanie , Walzog Barbara
Published: June 2018

Background

Neutrophil recruitment during acute inflammation critically depends on the spatial and temporal regulation of β2 integrins (CD11/CD18). This regulation occurs by inside‐out and outside‐in signalling via interaction of cytoplasmic proteins with the intracellular domains of the integrin α‐ and β‐subunits. The underlying molecular mechanisms regulating β2 integrins in neutrophils are still incompletely understood.

Aim

This review provides a comprehensive overview of our current knowledge on proteins interacting with the cytoplasmic tail of CD18, the conserved β‐subunit of β2 integrins, their regulation and their functional importance for neutrophil trafficking during acute inflammation.

Results

A total of 22 proteins including Talin, Kindlin 3 and Coronin 1A have been reported to interact with the CD18 cytoplasmic tail. Here, proteins binding to the cytoplasmic domain of CD18 in experiments using purified, recombinant proteins or peptides in, for example, pull‐down assays, are defined as direct interactors. Proteins that have been shown to interact with the cytoplasmic domain of CD18 using whole cell lysates in, for example, pull‐down experiments are claimed as interacting proteins without evidence for direct interaction. In summary, β2 integrin activation and signalling depend on a specific subset of proteins interacting with CD18 and their precise regulation. If disturbed, profound defects of neutrophil recruitment and activation become evident compromising the innate immune response.

Conclusions

The knowledge of proteins interacting with β2 integrins and their regulation during neutrophil trafficking does not only improve our basic understanding of innate immunity but may pave the way to novel therapeutic strategies in the treatment of inflammatory diseases.
What is a “Maison des Adolescents”? A history of integrated youth health care services in France
Authors: Benoit Laelia , Cottin Patrick , Moro Marie R.
Published: June 2018

Aim

Since 1999, the development of more than 100 “Maisons des Adolescents” (MDAs) has enabled young persons to gain access to specific care in integrated youth‐friendly facilities in France. To contribute to the development and standardization of international youth‐friendly health care services, this review provides insight into the French MDA facilities.

Methods

This socio‐historical analysis includes a systematic review of articles referring to the MDAs (selection through title and/or abstract), ministry reports and newspaper articles, from 1999 to 2018.

Results

If the various medical programmes of MDAs depend on the priorities of local teams rather as well as on official regulations, all MDAs offer the following essential services: a “Health and Prevention Space” open daily; multidisciplinary consultations; a mobile team visiting youth hospitalized in medical units; a mobile team able to meet adolescents at their homes; an open centre for art workshops; refresher and remedial courses for school work; network meetings and parent support groups. The MDAs from the start addressed an age group (young people aged 11‐21 years) rather than an illness. They thus provide primary prevention for adolescents according to the World Health Organization definition of health as “a state of complete physical, mental and social well‐being.” This medical and political movement was shaped by the epistemological background of its first leaders.

Conclusion

Although more cohort studies to evaluate their early interventions would be useful, the success of the MDA network is already widely acknowledged by users, professionals and policy makers.
Clinical results according to age in patients with chronic myeloid leukemia receiving imatinib frontline: The younger, the later, the worse?
Authors: Latagliata Roberto , Breccia Massimo , Carmosino Ida , Cesini Laura , De Benedittis Daniela , Mohamed Sara , Vozella Federico , Molica Matteo , Campanelli Melissa , De Luca Maria Lucia , Colafigli Gioia , Quattrocchi Luisa , Loglisci Maria Giovanna , Massaro Fulvio , Canichella Martina , Diverio Daniela , Mancini Marco , Alimena Giuliana , Foà Robin
Published: June 2018

Objectives

To evaluate differences in clinical results according to age among patients with chronic myeloid leukemia (CML).

Methods

207 consecutive CML patients treated with imatinib frontline were revised, dividing them in young adults (>20 < 45 years) (YA), middle‐aged adults (≥45 < 65 years) (MA) and elderly (≥65 years) (EL).

Results

Cumulative incidence of complete cytogenetic response (CCyR) and major molecular response (MMolR) were significantly higher in MA compared with YA and EL (P < .001 for CCyR and P = .001 for MMolR). Number of total events was lower in MA (8 [11.1%] vs 21 [34.4%] in YA and 28 [37.8%] in EL, P = .001): no difference was observed for blastic evolution (P = .478). Number of deaths was higher in the EL (12 [16.2%] vs 2 [3.2%] in YA and 0 in MA, P < .001): however, 11/12 deaths in EL were not related to CML. The PFS curve in MA was significantly longer than in YA and in EL (P = .02). The OS curve in EL was significantly shorter than in YA and in MA (P < .001).

Conclusions

Age at diagnosis influences significantly the course of CML patients treated with imatinib: a possible explanation of the counterintuitive worse course in YA is the delayed diagnosis compared to elderly.
Effects of carbamazepine and lamotrigine on functional magnetic resonance imaging cognitive networks
Authors: Xiao Fenglai , Caciagli Lorenzo , Wandschneider Britta , Sander Josemir W. , Sidhu Meneka , Winston Gavin , Burdett Jane , Trimmel Karin , Hill Andrea , Vollmar Christian , Vos Sjoerd B. , Ourselin Sebastien , Thompson Pamela J. , Zhou Dong , Duncan John S. , Koepp Matthias J.
Published: June 2018

Objective

To investigate the effects of sodium channel–blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy.

Methods

In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel–blocking AED. We propensity‐matched 42 patients taking levetiracetam (LEV) as “patient‐controls” and included further 42 age‐ and gender‐matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out‐of‐scanner psychometric measures of verbal fluency.

Results

Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV‐treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out‐of‐scanner fluency scores correlated positively with left putamen activation.

Significance

Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well‐tolerated sodium channel–blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task‐negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.
De novo mutations of STXBP1 in Chinese children with early onset epileptic encephalopathy
Authors: Li T. , Cheng M. , Wang J. , Hong S. , Li M. , Liao S. , Xie L. , Jiang L.
Published: June 2018

To detect syntaxin‐binding protein 1 (STXBP1) mutations in Chinese patients with early onset epileptic encephalopathy (EOEE) of unknown etiology. Targeted next‐generation sequencing was used to identify STXBP1 mutations in 143 Chinese patients with EOEE of unknown etiology. A filtering process was applied to prioritize rare variants of potential functional significance. Then Sanger sequencing was employed to validate the parental origin of the variants. Detailed clinical and genetic data were collected for 9 STXBP1‐positive patients. Eight de novo heterozygous STXBP1 mutations were identified in 9 patients; 5 were novel mutations (c.1155delC, c.1030‐1G>A, c.217G>C, c.268G>C, c.1480_1481 insT) and 3 were previously reported (c.1216C> T, c.1217G>A [2 cases], c.875G>A). Two patients had Ohtahara syndrome and 1 had West syndrome at onset, whereas the other 6 presented with EOEE that did not fit a specific recognized epilepsy syndrome. Six of these patients later evolved to West syndrome. All but 2 cases were prescribed more than 2 antiepileptic drugs (AEDs) plus other regimens. Four subjects showed good responses to levetiracetam (LEV) alone or in combination with other AEDs, and one case (1/3) achieved complete freedom from seizures with a ketogenic diet (KD). All patients exhibited severe to profound global developmental delay. Five novel heterozygous de novo STXBP1 mutations were discovered in patients with EOEE from China. STXBP1 mutational analysis should be performed in cases of EOEE of unknown etiology. LEV as monotherapy or adjunctive therapy with other regimens, as well as KD should be considered for management of this patient group.
Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome
Authors: Manners M. T. , Yohn N. L. , Lahens N. F. , Grant G. R. , Bartolomei M. S. , Blendy J. A.
Published: June 2018

Adolescent stress can impact health and well‐being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long‐term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala—a critical region in the control of emotional states—in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for 2 weeks during adolescence and were used to produce two generations of offspring. Male and female offspring and grandoffspring were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. RNA‐seq analysis of the amygdala from male offspring and grandoffspring identified differentially expressed genes (DEGs) in mice derived from fathers exposed to CUS. The DEGSs clustered into numerous pathways, and the “notch signaling” pathway was the most significantly altered in male grandoffspring. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.
Factors associated with discontinuing or not starting oral anticoagulant therapy in older hospitalized patients with non‐valvular atrial fibrillation
Authors: Díez‐Manglano Jesús , Mostaza José‐María , Pose Antonio , Formiga Francesc , Cepeda José‐María , Gullón Alejandra , Camafort Miguel , Castiella Jesús , Rovira Eduardo , Jarauta Estíbaliz , Suárez Carmen
Published: June 2018

Aim

To determine the factors associated with discontinuing or not starting oral anticoagulation (OA) therapy in older patients with non‐valvular atrial fibrillation (NVAF).

Methods

A prospective, multicenter cohort study was carried out of patients aged >75 years with NVAF hospitalized in internal medicine departments in Spain. For each patient, we recorded creatinine, hemoglobin and platelets levels, as well as CHA2DS2‐VASc and HAS‐BLED scores and the Charlson Comorbidity Index. We measured the ability to carry out basic activities of daily life with the Barthel Index, and the cognitive state with the Short Portable Mental Status questionnaire.

Results

We included 723 patients with NVAF, with a mean age of 84.8 years (SD 5.2 years); 390 (53.9%) of the patients were women. Before admission, 375 (51.9%) patients were treated with OA. Previously diagnosed NVAF (OR 4.099, 95% CI 1.824–9.211, P = 0.001), the number of errors in the Short Portable Mental Status questionnaire (OR 1.180, 95% CI 1.020–1.365, P = 0.026), peripheral arterial disease (OR 0.285, 95% CI 0.114–0.711, P = 0.007) and hemoglobin levels (OR 0.812, 95% CI 0.682–0.966, P = 0.019) were independently associated with not starting OA therapy at discharge. Of the 375 patients treated with OA at admission, 87 (23.2%) had their OA discontinued at discharge. The HAS‐BLED score (OR 1.516, 95% CI 1.211–1.897, P < 0.001) and previous acute myocardial infarction (OR 0.327, 95% CI 0.121–0.883, P = 0.027) were associated with the discontinuation of OA.

Conclusions

There are factors associated with discontinuing or not starting OA in older patients with NVAF, which often have no clinical justification. Geriatr Gerontol Int 2018; 18: 1219–1224.
Insights From a Multi‐Method Recharge Estimation Comparison Study
Authors: Walker David , Parkin Geoff , Schmitter Petra , Gowing John , Tilahun Seifu A. , Haile Alemseged T. , Yimam Abdu Y.
Published: June 2018

Although most recharge estimation studies apply multiple methods to identify the possible range in recharge values, many do not distinguish clearly enough between inherent uncertainty of the methods and other factors affecting the results. We investigated the additional value that can be gained from multi‐method recharge studies through insights into hydrogeological understanding, in addition to characterizing uncertainty. Nine separate groundwater recharge estimation methods, with a total of 17 variations, were applied at a shallow aquifer in northwest Ethiopia in the context of the potential for shallow groundwater resource development. These gave a wide range of recharge values from 45 to 814 mm/a. Critical assessment indicated that the results depended on what the recharge represents (actual, potential, minimum recharge or change in aquifer storage), and spatial and temporal scales, as well as uncertainties from application of each method. Important insights into the hydrogeological system were gained from this detailed analysis, which also confirmed that the range of values for actual recharge was reduced to around 280‐430 mm/a. This study demonstrates that even when assumptions behind methods are violated, as they often are to some degree especially when data are limited, valuable insights into the hydrogeological system can be gained from application of multiple methods.
Breeding ground correlates of the distribution and decline of the Common Cuckoo Cuculus canorus at two spatial scales
Authors: Denerley Chloe , Redpath Steve M. , van der Wal Rene , Newson Stuart E. , Chapman Jason W. , Wilson Jeremy D.
Published: June 2018

Many migratory bird species are undergoing population declines as a result of potentially multiple, interacting mechanisms. Understanding the environmental associations of spatial variation in population change can help tease out the likely mechanisms involved. Common Cuckoo Cuculus canorus populations have declined by 69% in England but increased by 33% in Scotland. The declines have mainly occurred in lowland agricultural landscapes, but their mechanisms are unknown. At both the local scale within the county of Devon (SE England) and at the national (UK) scale, we analysed the breeding season distribution of Cuckoos in relation to habitat variation, the abundance of host species and the abundance of moth species whose caterpillars are a key food of adult Cuckoos. At the local scale, we found that Cuckoos were more likely to be detected in areas with more semi‐natural habitat, more Meadow Pipits Anthus pratensis (but fewer Dunnocks Prunella modularis) and where, later in the summer, higher numbers of moths were captured whose larvae are Cuckoo prey. Nationally, Cuckoos have become more associated with upland heath characterized by the presence of Meadow Pipit hosts, and with wetland habitats occupied by Eurasian Reed Warbler Acrocephalus scirpaceus hosts. The core distribution of Cuckoos has shifted from south to north within the UK. By the end of 2009, the abundance of macro‐moth species identified as prey had also declined four times faster than that of species not known to be taken by Cuckoos. The abundance of these moths has shown the sharpest declines in grassland, arable and woodland habitats and has increased in semi‐natural habitats (heaths and rough grassland). Our study suggests that Cuckoos are likely to remain a very scarce bird in lowland agricultural landscapes without large‐scale changes in agricultural practices.
Body odour aldehyde reduction by acetic acid bacterial extract including enzymes: alcohol dehydrogenase and aldehyde dehydrogenase
Authors: Yoshioka N. , Kurata K. , Takahashi T. , Ariizumi M. , Mori T. , Fujisawa H. , Kameyama N. , Okuyama Y.
Published: June 2018

Objective

The major causes of unpleasant human body odour are aldehydes produced by axillary‐resident bacteria. There are many methods of body odour prevention; however, they all carry risks of destroying indigenous dermal bacteria that are necessary for the maintenance of the normal physical function of the skin. Furthermore, some methods cannot directly reduce the concentrations of substances that cause body odour. Therefore, a novel method of reducing body odour more safely and effectively is required. We focused on acetic acid bacterial enzymes, which can convert aldehydes into carboxylic acids, and investigated their effect on aldehydes and body odour.

Methods

Subjects with strong body odour were recruited using screening questionnaires. Acetic acid bacterial extract including enzymes was applied to subjects’ skin, and their effects were evaluated by trained panellists and by quantitative aldehyde analysis using thermal detector gas chromatography/mass spectrometry.

Results

Acetic acid bacterial extract including enzymes decreased the ratio of dilution to threshold and the concentration of body odour‐producing aldehydes dropped by up to 98.7%.

Conclusion

These results indicate that simply applying acetic acid bacterial enzymes on the skin can reduce the concentration of aldehydes that cause unpleasant body odour by directly converting them into carboxylic acids. Therefore, acetic acid bacterial enzymes can potentially be developed into new products that do not destroy indigenous bacteria and yet can effectively reduce unpleasant body odour.
Upper gastrointestinal bleeding in neck of femur fracture patients: a single tertiary centre experience
Authors: Liu Jessamine , Gupta Rohit , Hay Karen , Pulle Chrys , Rahman Tony , Pandy Shaun
Published: June 2018

This study aimed to identify the incidence of perioperative acute upper gastrointestinal bleeding (UGIB) in our hip fracture patients; to evaluate the characteristics, management and clinical outcomes of these patients; and to explore risk factors and protective factors. Of the 1691 consecutive patients admitted for surgical management of hip fractures, 11 (0.65%) had UGIB and a further four patients for each case were selected as controls for evaluation of risk factors and protective factors. Pre‐existing peptic ulcer disease was identified as a risk factor for acute UGIB (odds ratio 7.9; 95% confidence interval: 1.1–54.9). This study reported a very low incidence of UGIB in hip fracture patients. Despite being a high‐risk population, timely endoscopic evaluation can be safely undertaken to optimise patient outcome. When risk factors such as history of peptic ulcer disease are present, additional precaution including gastro‐protective agent and nutritional support should be undertaken.
Physicians’ perception of their medical college
Authors: Wilson John , Talbot Anthony
Published: June 2018

The relevance of medical colleges has been questioned and their ability to respond to members’ needs and system failures is unknown. We hypothesise that members believe that medical colleges are relevant to the current health agenda. We conducted a survey by email to determine satisfaction with the current state of the Royal Australasian College of Physicians (RACP) relevance and tested agreement with suggestions for change. We found that of 21 000 survey links sent, 13.1% of addressees replied. When questioned regarding the current state, less than 50% of respondents agreed with any of eight positive statements. Over two thirds supported involvement in policy and advocacy, as well as the use of digital plebiscites to express their views. Clarity around the use of members’ subscriptions and value for money had the lowest scores. Of importance was the expression of need for a medical college (71%) and the finding that 58% of respondents would give more time to the RACP if asked. Of all respondents, 22% provided written comments that closely reflected scores on categorical questions. We conclude that, despite reported disengagement and lack of support for the current state, the majority of respondents to a survey of relevance believed in the need for a medical college.