bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantiomeric Identification of Pregabalin by GC‐MS via Methylation and S‐TPC Chiral Derivatization
Authors: Hitchcock Michael L. , Marginean Ioan
Published: August 2018

Pregabalin is a Schedule V controlled substance which is defined as the (S) enantiomer of 3‐(aminomethyl)‐5‐methylhexanoic acid. It is used legitimately to treat neuropathy in patients with diabetes as well as for epilepsy and fibromyalgia. Pregabalin is an amino acid and an amphoteric compound, which makes it difficult to analyze using the conventional GC‐MS instrumentation found in most forensic drug analysis laboratories. Problems associated with the traditional GC‐MS analysis of pregabalin include selective solubility, ring closure to the corresponding lactam in the GC injection port and/or the MS transfer line and difficulty with chiral derivatization due to the presence of a carboxylic acid moiety. Here, we show that these challenges can be overcome by methylating (capping) the carboxylic acid portion of the pregabalin molecule and converting to the corresponding methyl ester. Once the methyl ester is synthesized, chiral derivatization at the amine can be achieved to identify the controlled (S) enantiomer of pregabalin via GC‐MS.
CREDENTIALING DECISIONS AND CRIMINAL RECORDS: A NARRATIVE APPROACH*
Authors: DENVER MEGAN , EWALD ALEC
Published: August 2018

Decision makers such as employers and state occupational licensing officials are often encouraged or required to incorporate evidence of rehabilitation into hiring decisions when applicants have criminal records. Current policy movements at the local, state, and federal levels may increase the use of such individualized assessments. Yet little is known about which types of information these decision makers use, how they evaluate evidence, and how they ultimately make determinations. We examine a sample of 50 unarmed security guard licensing decisions in New York State using content analysis. We find that administrative law judges rely on a narrative framework to document whether applicants currently have a prosocial identity and merit licensure. Judges typically describe one of two prosocial identity narratives for successful applicants: The applicant demonstrates achieving meaningful change, or his or her criminal record represents an aberration. Two factors seem vital to these assessments: applicants’ postconviction trustworthiness, as demonstrated through good conduct or inferred through positive appraisals, and credible testimony. In narrative explanations, personal responsibility and adult milestones are often discussed, reflecting a judicial nod to the notion of a “transition to adulthood.” The results hold implications for scholars and policy makers examining employment barriers, stigma remediation, and collateral sanctions for individuals with criminal records.
Antecedents and Consequences of Eco‐Control Deployment: Evidence from Canadian Manufacturing Firms
Authors: Henri Jean‐François , Journeault Marc
Published: August 2018

Environmental issues have become an important consideration for a growing number of organizations. Eco‐control may represent a valuable tool to help organizations address such issues. The aim of this study is to provide an overview of the eco‐control practices adopted by Canadian organizations and to understand the antecedents and consequences of their adoption. More specifically, this study examines (i) the extent to which eco‐control practices are deployed within organizations, (ii) the factors and motivations that lead organizations to implement eco‐control practices, and (iii) the impact of adoption on firms’ managerial and operational environmental actions as well as on environmental and economic performance. Using survey data from a sample of 249 Canadian manufacturing firms, this article shows that environmental missions, environmental policies, environmental strategic planning, environmental budgets and environmental performance indicators are the most frequently adopted eco‐control practices among the investigated firms, while environmental incentives seem to be less frequently adopted. The results of this study also suggest that competitive and ethical motivations as well as size, environmental exposure and stakeholder pressure are all important factors in explaining eco‐control practice adoption by Canadian manufacturing firms. Moreover, the results of this study show that organizations that have undertaken more intensive managerial and operational environmental actions have also adopted more intensive eco‐control practices. Organizations adopting more intensive eco‐control practices perform better both environmentally and economically performance than firms adopting less intensive eco‐control practices.
Mind the gap
Authors: FRANKS JULIAN
Published: August 2018

The gap between the owners and managers of listed companies is narrowing, says Julian Franks – and that can only be a good thing
Politicians' lies and the power of imagination
Authors: EFFRON DANIEL
Published: August 2018

We're more likely to excuse leaders' false claims if we can imagine a scenario where they might be true — but only if they fit with our personal views, says Daniel Effron
How to be a better Boss
Authors: BIRKINSHAW JULIAN
Published: August 2018

Want to get the most out of the people who work for you? There are five things you need to do, says Julian Birkinshaw
Prevalence and prediction of higher estimated gastric content in parturients at full cervical dilatation: A prospective cohort study
Authors: Desgranges François‐Pierrick , Simonin Marine , Barnoud Sophie , Zieleskiewicz Laurent , Cercueil Eloise , Erbacher Julien , Allaouchiche Bernard , Chassard Dominique , Bouvet Lionel
Published: August 2018

Background

Emergent obstetrical procedures may require general anaesthesia in parturients at full cervical dilatation or immediately after vaginal birth. This study aimed to determine the prevalence and the predictive factors of higher estimated gastric content in parturients at full cervical dilatation with epidural analgesia and allowed to drink during the labour, and to assess the ability of the antral area measured in the semirecumbent position (SR‐CSA) to identify higher estimated gastric content in this setting.

Methods

This prospective observational study was conducted between December 2016 and July 2017. Ultrasonographic examination of the antrum was performed at full cervical dilatation, within the hour preceding the beginning of expulsive efforts. Higher estimated gastric content was defined when solid content was observed and/or if the calculated gastric fluid volume was >1.5 mL/kg.

Results

Seventeen of 62 parturients (27%) presented higher estimated gastric content. Maximal pain intensity during the last hour of labour and time interval between the insertion of the epidural catheter and ultrasonographic examination were significantly increased in parturients with higher estimated gastric content. The threshold value of the SR‐CSA to identify a higher estimated gastric content was 393 mm2, with sensitivity = 88% and specificity = 87%.

Conclusion

Around a quarter of parturients with epidural analgesia and free access to clear fluids during labour presented higher estimated gastric content at full cervical dilatation. The SR‐CSA may be of interest for the fast ultrasound assessment of the gastric content status in case of emergent obstetrical procedures at full cervical dilatation.
Elevated serum S‐100β in patients with septic shock is associated with delirium
Authors: Erikson Kristo , Ala‐Kokko Tero Ilmari , Koskenkari Juha , Liisanantti Janne Henrik , Kamakura Remi , Herzig Karl Heinz , Syrjälä Hannu
Published: August 2018

Background

A high prevalence of delirium is observed in sepsis, yet specific markers for this brain dysfunction in sedated patients are still lacking. Cytoplasmic low molecular weight calcium‐binding protein, S‐100β, is a commonly used nonspecific marker for brain injury. Here, we evaluated whether delirium is associated with increases in S‐100β levels.

Methods

This observational study included 22 patients with septic shock. Delirium was assessed by CAM‐ICU and blood samples were obtained to measure inflammatory (CRP, PCT, IL‐6, IL‐17, TNF‐α) and cerebral biomarkers (S‐100β, NSE, HAB42, SUBP). Patients were categorized according to the presence of delirium.

Results

Delirium was present in 10/22 of the patients (45.5%). Serum S‐100β levels were above the laboratory cutoff value of 0.15 μg/L in 13/22 (59.1%) of the patients. The odds ratio for risk of developing delirium in cases with an S‐100β >0.15 μg/L was 18.0 (95%CI, 1.7‐196.3, P = 0.011). Patients with delirium had higher plasma levels of IL‐6 compared to those without; 138.3 pg/mL [28.0‐296.7] vs 53.6 pg/mL [109.3‐505, P = 0.050]. There was a positive correlation between S100 β and IL‐6 levels (r = 0.489, P = 0.021). Delirium patients had higher SOFA scores; 10 [5‐9] vs 7[8‐10.5], P = 0.036.

Conclusions

Delirium in septic shock was associated with an elevated protein S‐100β when using a laboratory cutoff value of 0.15 μg/L and with more severe organ dysfunction during the ICU stay.
Risk factors for suicide in bipolar disorder: a cohort study of 12 850 patients
Authors: Hansson C. , Joas E. , Pålsson E. , Hawton K. , Runeson B. , Landén M.
Published: August 2018

Objective

Bipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder.

Method

A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipoläR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models.

Results

Of 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow‐up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women.

Conclusions

Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis‐specific factors.
Genome‐wide association study to identify genomic regions affecting prolificacy in Lori‐Bakhtiari sheep
Authors: Abdoli R. , Mirhoseini S. Z. , Ghavi Hossein‐Zadeh N. , Zamani P. , Gondro C.
Published: August 2018

Several causative mutations in candidate genes affecting prolificacy have been detected in various sheep breeds. A genome‐wide association study was performed on estimated breeding values for litter size in Lori‐Bakhtiari sheep. Prolific ewes with twinning records and others with only singleton records were genotyped using the medium‐density Illumina Ovine SNP50 array. Four single nucleotide polymorphisms (SNPs) associated with litter size were identified on chromosomes 3, 6 and 22. The region on sheep chromosome 3 between 75 739 167 and 75 745 152 bp included two significant SNPs (s52383.1 and OAR3_80038014_X.1) in high linkage disequilibrium with each other. The region that surrounds these SNPs contains a novel putative candidate gene: luteinizing hormone/choriogonadotropin receptor (LHCGR), known to be involved in ovarian steroidogenesis and organism‐specific biosystem pathways in sheep. Known prolificacy genes BMPR1B, BMP15 and GDF9 were not associated with litter size in Lori‐Bakhtiari sheep, suggesting that other biological mechanisms could be responsible for the trait's variation in this breed.
Decidual stromal cell‐derived PGE2 regulates macrophage responses to microbial threat
Authors: Rogers Lisa M. , Anders Anjali P. , Doster Ryan S. , Gill Elizabeth A. , Gnecco Juan S. , Holley Jacob M. , Randis Tara M. , Ratner Adam J. , Gaddy Jennifer A. , Osteen Kevin , Aronoff David M.
Published: August 2018

Problem

Bacterial chorioamnionitis causes adverse pregnancy outcomes, yet host‐microbial interactions are not well characterized within gestational membranes. The decidua, the outermost region of the membranes, is a potential point of entry for bacteria ascending from the vagina to cause chorioamnionitis. We sought to determine whether paracrine communication between decidual stromal cells and macrophages shaped immune responses to microbial sensing.

Method of study

Decidual cell‐macrophage interactions were modeled in vitro utilizing decidualized, telomerase‐immortalized human endometrial stromal cells (dTHESCs) and phorbol ester‐differentiated THP‐1 macrophage‐like cells. The production of inflammatory mediators in response to LPS was monitored by ELISA for both cell types, while phagocytosis of bacterial pathogens (Escherichia coli and Group B Streptococcus (GBS)) was measured in THP‐1 cells or primary human placental macrophages. Diclofenac, a non‐selective cyclooxygenase inhibitor, and prostaglandin E2 (PGE2) were utilized to interrogate prostaglandins as decidual cell‐derived paracrine immunomodulators. A mouse model of ascending chorioamnionitis caused by GBS was utilized to assess the colocalization of bacteria and macrophages in vivo and assess PGE2 production.

Results

In response to LPS, dTHESC and THP‐1 coculture demonstrated enhancement of most inflammatory mediators, but a potent suppression of macrophage TNF‐α generation was observed. This appeared to reflect a paracrine‐mediated effect of decidual cell‐derived PGE2. In mice with GBS chorioamnionitis, macrophages accumulated at sites of bacterial invasion with increased PGE2 in amniotic fluid, suggesting such paracrine effects might hold relevance in vivo.

Conclusion

These data suggest key roles for decidual stromal cells in modulating tissue responses to microbial threat through release of PGE2.
Preterm premature rupture of membranes: Which criteria contraindicate home care management?
Authors: Petit Céline , Deruelle Philippe , Behal Hélène , Rakza Thameur , Balagny Sara , Subtil Damien , Clouqueur Elodie , Garabedian Charles
Published: August 2018

Introduction

Home care management offers a suitable alternative to hospitalization for management of preterm premature rupture of membranes (PPROM). Eligibility criteria have not been clearly established. Our aim was to determine predictive factors of complication during home care management of PPROM in order to define optimal eligibility criteria.

Material and methods

Retrospective cohort study of all women with singleton pregnancies with PPROM managed as outpatients between 2009 and 2015. Complications were defined as the occurrence of one of these events: fetal death, placental abruption, umbilical cord prolapse, delivery outside maternity hospital, neonatal death.

Results

In all, 187 women with PPROMs were managed as outpatients, of whom 12 had a complication (6.4%). In the “complication” group, gestational age at diagnosis (P = 0.006) and at delivery (P < 0.001) were lower, with no difference in latency between these two events. Three criteria significantly increased the risk for a severe complication: PPROM occurring before 26 weeks (P = 0.008), non‐cephalic fetal presentation (P = 0.02) and oligoamnios (P = 0.02). When unfavorable criteria were associated with PPROM, the risk was increased (1 criterion, odds ratio [OR] 1.6; 2 criteria, OR 6.9 and 3 criteria, OR 32.8).

Conclusions

Combination of these three criteria is an indication for conventional hospitalization to limit maternal and fetal morbidity. When two criteria are combined, home care should be discussed for each case. If only one unfavorable criteria is present, outpatient management is suitable. To validate these results, a prospective randomized study should be conducted.
Artificial Sphincters to Manage Urinary Incontinence: A Review
Authors: Marziale Leonardo , Lucarini Gioia , Mazzocchi Tommaso , Gruppioni Emanuele , Castellano Simona , Davalli Angelo , Sacchetti Rinaldo , Pistolesi Donatella , Ricotti Leonardo , Menciassi Arianna
Published: August 2018

Urinary incontinence affects more than 300 million people worldwide. The implantation of a medical device called an artificial urinary sphincter (AUS) is the gold standard treatment when conservative and minimally invasive therapies fail. In this article, the AUSs (extra‐urethral and endo‐urethral sphincters) available on the market, both presented at the research level and filed as patents, are reviewed. The ability of the different solutions to effectively replace the natural sphincter are discussed, together with advantages and some possible side effects, such as tissue atrophy, overall invasiveness of the implant, and so forth. Finally, future research priorities are discussed for both endo‐urethral and extra‐urethral approaches considering key engineering aspects, such as materials, compression and closure mechanisms, and implantation methods, with the long‐term aim of developing an effective, reliable, durable, and minimally invasive AUS capable of restoring a normal quality of life for incontinent patients.
Case of reduction en masse who presented with no symptoms
Authors: Cao Yuchen , Kohga Atsushi , Kawabe Akihiro , Yajima Kiyoshige , Okumura Takuya , Yamashita Kimihiro , Isogaki Jun , Suzuki Kenji
Published: August 2018

The early and accurate diagnosis of reduction en masse followed by proper treatment is important but has been difficult. Here, we report the case of a 58‐year‐old Japanese man who presented with abdominal pain and vomiting at a nearby clinic. He was referred to our hospital on suspicion of small bowel obstruction. Despite the total disappearance of his symptoms, the abdominal X‐ray examination showed distended loops of small bowel. The preoperative diagnosis of small bowel strangulation due to an internal hernia was made by CT, and we therefore performed emergency exploratory laparoscopy. We intraoperatively diagnosed the patient with the reduction en masse of a right inguinal hernia, and we conducted a transabdominal preperitoneal hernioplasty. This patient's case demonstrates that even when a patient is asymptomatic after the reduction of an inguinal hernia, the possibility of a reduction en masse remains.
Planned cesarean or vaginal delivery for women in spontaneous labor with a twin pregnancy: A secondary analysis of the Twin Birth Study
Authors: Mei‐Dan Elad , Dougan Claire , Melamed Nir , Asztalos Elizabeth V. , Aviram Amir , Willan Andrew R. , Barrett Jon F. R.
Published: August 2018

Background

The Twin Birth Study, a multicenter randomized controlled trial, found no differences in neonatal outcomes in women with twins randomized to planned cesarean or vaginal delivery. Nevertheless, women who present in spontaneous labor might expect a better outcome following a trial of vaginal delivery than undergoing cesarean delivery. In this secondary analysis, we aimed to compare neonatal outcomes of women who presented in spontaneous labor in the two arms of the Twin Birth Study.

Methods

Women in whom the first twin was in the cephalic presentation were randomized between 32 + 0 and 38 + 6 weeks to planned vaginal delivery or cesarean. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity.

Results

Of the 2804 women included in the Twin Birth Study, 823 women in the planned vaginal delivery arm and 612 in the planned cesarean arm presented in spontaneous labor. Although the odds ratio favored planned vaginal delivery, there was no statistically significant difference in the rate of primary outcome between the vaginal delivery and cesarean arms (1.8% vs 2.7%, respectively; P = 0.16; OR 1.49; 95% CI, 0.87‐2.55). Similarly, the rates of the individual components of the primary outcome and of maternal adverse outcome were similar between the two arms.

Conclusion

In women with twins who present in spontaneous labor between 32 + 0 and 38 + 6 weeks’ gestation, where the first twin is cephalic, a policy of planned vaginal delivery or cesarean is not associated with significant differences in neonatal or maternal outcomes.
The MCL35 gene expression proliferation assay predicts high‐risk MCL patients in a Norwegian cohort of younger patients given intensive first line therapy
Authors: Holte Harald , Beiske Klaus , Boyle Merrill , Trøen Gunhild , Blaker Yngvild N. , Myklebust June , Kvaløy Sunniva , Rosenwald Andreas , Lingjærde Ole C. , Rimsza Lisa M. , Smeland Erlend B. , Scott David W. , Kolstad Arne
Published: August 2018

Patients with mantle cell lymphoma (MCL) generally have a dismal prognosis. Intensified induction treatment with rituximab and high dose cytarabine (R_HDAC), and consolidation with high‐dose therapy with autologous stem cell support has resulted in 10‐year overall survival (OS) higher than 60%. However, the clinical course varies. Diagnostic tools capable of stratifying patients include the MCL International Prognostic Index (MIPI), gene expression‐based proliferation signature, Ki‐67 proliferation index or tumour cell morphology. Here, we tested the performance of a newly developed Nanostring‐based RNA expression‐based proliferation assay (MCL35) on formalin‐fixed paraffin‐embedded tumour tissue from younger patients recruited in or treated according to Nordic MCL protocols compared to the prognosticators listed above. Seventy‐four patients were included and the assay performed well in all cases except four, which had inadequate RNA quality. The patients were evenly distributed in the MCL35 low‐, intermediate‐ and high‐risk categories. MCL35 low‐ and intermediate‐ risk groups had overlapping progression‐free survival (PFS), while patients in the high‐risk category had significantly inferior PFS. Combining MCL35 with MIPI or the MIPI‐C (MIPI with the addition of binary Ki67 score +/−30%) showed a better discrimination than either assessment alone. In conclusion, the MCL35 assay alone or combined with MIPI or MIPI‐C scores can identify patients who still have a dismal outcome despite intensified treatment.
Inherited variation in the xenobiotic transporter pathway and survival of multiple myeloma patients
Authors: Macauda Angelica , Castelli Eleonora , Buda Gabriele , Pelosini Matteo , Butrym Aleksandra , Watek Marzena , Kruszewski Marcin , Vangsted Annette Juul , Rymko Marcin , Jamroziak Krzysztof , Abildgaard Niels , Haastrup Eva Kannik , Mazur Grzegorz , Ríos Rafael , Jurczyszyn Artur , Zawirska Daria , Dudziński Marek , Raźny Małgorzata , Dutka Magdalena , Tomczak Waldemar , Suska Anna , Druzd‐Sitek Agnieszka , Marques Herlander , Petrini Mario , Markiewicz Miroslaw , Martinez‐Lopez Joaquin , Ebbesen Lene Hyldahl , Iskierka‐Jażdżewska Elżbieta , Sainz Juan , Canzian Federico , Campa Daniele
Published: August 2018

Over the past four decades, remarkable progress has been made in the treatment and prognosis of multiple myeloma (MM), although it remains an incurable disease. Chemotherapy resistance is a major hurdle for treatment efficacy. Drug resistance can be innate and so driven by genes involved in the drug metabolism pathways. We performed an association study of 71 germline variants within the major genes in those pathways (ABCB1, ABCC2, ABCG2, and their regulators NR1I2/PXR and NR1I3/CAR) in the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 1365 MM cases with survival information recruited in 5 European countries. Two of the SNPs showed a significant association with the survival of MM patients, namely rs2235013, located in ABCB1 [Hazard ratio (HR) = 1·52, 95% confidence interval (CI) = 1·18–1·95, P = 0·00087], and rs4148388, located in ABCC2 (HR = 2·15, 95% CI = 1·44–3·22, P = 0·0001). ABCC2 plays an essential role in transporting various anticancer drugs, including several used against MM, out of the cell. In silico analyses predict that the variant alleles of four SNPs in linkage disequilibrium with ABCC2‐rs4148388 are associated with increased gene expression. Overexpression of ABCC2 increases drug clearance and therefore may induce drug resistance mechanisms. In conclusion, we found a promising association between ABCC2‐rs4148388 and MM outcome that is supported by a plausible biological explanation.
Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer
Authors: van Leeuwen Pim J. , Donswijk Maarten , Nandurkar Rohan , Stricker Phillip , Ho Bao , Heijmink Stijn , Wit Esther M.K. , Tillier Corinne , van Muilenkom Erik , Nguyen Quoc , van der Poel Henk G. , Emmett Louise
Published: August 2018

Objective

To determine the value of gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA)‐11 positron emission tomography (PET) /computed tomography (CT) in men with newly diagnosed prostate cancer.

Patients and methods

We analysed results of 140 men with intermediate‐ and high‐risk prostate cancer. All men underwent 68Ga‐PSMA‐11 PET/CT and multiparametric magnetic resonance imaging (mpMRI) before radical prostatectomy (RP) with extended pelvic lymph node (LN) dissection. For each patient, the clinical and pathological features were recorded. Prostate‐specific antigen (PSA) was documented at staging scan, and after RP, at a median (interquartile range) of 110 (49–132) days. A PSA level of ≥0.03 ng/mL was classified as biochemical persistence (BCP). Logistic regression was performed for association of clinical variables and BCP.

Results

In these 140 patients with intermediate‐ and high‐risk prostate cancer, 27.1% had PSMA PET/CT‐positive findings in the pelvic LNs. Sensitivity and specificity for detection of LN metastases were 53% and 88% (PSMA PET/CT) and 14% and 99% (mpMRI), respectively. The overall BCP rate was 25.7%. The BCP rate was 16.7% in men who were PSMA PET/CT LN‐negative compared to 50% in men who were PSMA PET/CT LN‐positive (P < 0.05). The presence of PSMA‐positive pelvic LNs was more predictive of BCP after RP than cT‐stage, PSA level, and the Gleason score, adjusted for surgical margins status.

Conclusions

68Ga‐PSMA‐11 PET/CT is highly predictive of BCP after RP, and should play an important role informing men with intermediate‐ or high‐risk prostate cancer.
Early‐life events and developmental defects of enamel in the primary dentition
Authors: Pinto Gabriela dos Santos , Costa Francine dos Santos , Machado Tanielley Vieira , Hartwig Andreia , Pinheiro Ricardo Tavares , Goettems Marília Leão , Demarco Flávio Fernando
Published: August 2018

Objective

To investigate the occurrence of developmental defects of enamel (DDE) in the primary teeth of children aged 24‐36 months and their association with early‐life events.

Methods

This study was undertaken with children aged 24‐36 months in Pelotas, Southern Brazil. Information on demographic and socioeconomic characteristics, events occurring during pregnancy and neonatal events was collected previously. In this study, information on the health‐related behaviours of mothers and children was collected using questionnaires and information about children's oral health was achieved through clinical oral examination. The outcome, the prevalence of DDE (≥1), was determined using the DDE index (FDI). Bivariate and multivariate logistic regression analyses were performed.

Results

Five hundred and three mother/child dyads were evaluated, and 13.1% of the children had DDE. Multivariate analysis showed that children with Apgar scores less than 7 had around 2.5‐fold higher odds of developing DDE than children with Apgar scores between 7 and 10 (OR = 2.78; 95% confidence interval [CI], 1.35‐5.73). The analysis of different types of enamel defects shows that the presence of hypoplasia (OR 3.13; 95% CI, 1.35‐7.27) and diffuse opacities (OR 3.95; 95% CI, 1.68‐9.27) remained associated in adjusted analysis with Apgar scores.

Conclusion

Early‐life events may cause DDE. A lower Apgar score was associated with a higher prevalence of enamel defects.
Decomposing early and adult life social position effects on oral health and chronic diseases in a cross‐sectional study of Southern Brazil
Authors: Vendrame Édina , Goulart Mariél de Aquino , Hilgert Juliana B. , Hugo Fernando N. , Celeste Roger Keller
Published: August 2018

Objectives

As the socio‐economic trajectory can influence on individual health during the life course, the aim of this study was to test a model of socio‐economic life course effects on chronic diseases, tooth loss and on oral health‐related quality of life using structural equation model (SEM) to decompose direct and indirect effects.

Methods

This cross‐sectional study was performed in southern Brazil, within public healthcare users with 18 years old or more (n = 433). Latent variables were the Oral Health Impact Profile (OHIP), Childhood Socio‐economic Status (SESC) and Adulthood (SESA), and Chronic Diseases (CD), and observed variables were sex, age, smoking status and tooth loss. The statistical analysis was performed using structural equation modelling (SEM) using WLSMV estimator. For the final model, we kept only plausible significant paths with P < 0.30.

Results

Final model presented an adequate fit: RMSA 0.03, Comparative Fit Index (CFI) 0.97, TLI 0.97, and Weighted Root Mean Square Residual (WRMR) 1.19. The direct effect from SESC to tooth loss was β = −0.08 (P = 0.19) and the indirect was β = −0.12 (P = 0.02). The indirect effect from SESC to OHIP was β = −0.14 (P = 0.01) and there is no direct effect. The direct effect from SESA to tooth loss was β = −0.21 (P < 0.01) and there is no indirect effect. The direct effect from SESA to OHIP was β = −0.14 (P = 0.05). The association of SESA on SESC was β = 0.59 (P < 0.01).

Conclusions

SESC had indirect effects on OHIP and number of teeth via SESA, supporting the chain of effects theory, but not for chronic diseases.
Soluble CD14 concentration in human breast milk and its potential role in child atopic dermatitis: Results of the Ulm Birth Cohort Studies
Authors: Logan Chad A. , Weiss Johannes M. , Koenig Wolfgang , Stahl Bernd , Carr Prudence R. , Brenner Hermann , Rothenbacher Dietrich , Genuneit Jon
Published: August 2018

Background

Soluble CD14 (sCD14) is one of many factors in human breast milk which may influence programming of the immune response in the breastfed child. Although previous studies have mostly found little association between sCD14 concentration in breast milk and atopic outcomes, recent evidence continues to support a role of sCD14 in immune‐related disease.

Objective

We aimed to clarify whether an association exists between sCD14 concentration in human breast milk (m‐sCD14) and child atopic dermatitis (AD) diagnosis by age 3 years within the context of two large birth cohorts.

Methods

Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, methodologically similar birth cohort studies, each consisting of approximately 1000 newborns and their mothers recruited from the general population shortly after delivery in Ulm, Southern Germany, respectively, from 11/2000 to 11/2001 and 04/2012 to 05/2013. sCD14 concentrations were measured by different ELISAs (UBCS: IBL, SPATZ: R&D) in breast milk samples collected at 6 weeks post‐delivery in both studies and additionally at 6 months and 1 year in SPATZ. Children's AD diagnosis was assessed using parent and paediatrician reports at 1, 2 and 3 years of age.

Results

Complete exposure and outcome data were available for 659 UBCS and 489 SPATZ children. In both cohorts, sCD14 concentration was significantly associated with breastfeeding frequency (P < 0.01). We observed no association between m‐sCD14 concentration and child AD diagnosis in either study.

Conclusions

Our results do not support an association between sCD14 concentration in mature breast milk and AD among breastfed children.
From stability to dynamics: understanding molecular mechanisms of regulatory T cells throughFoxp3transcriptional dynamics
Authors: Bending D , Ono M
Published: August 2018

Studies on regulatory T cells (Treg) have focused on thymic Treg as a stable lineage of immunosuppressive T cells, the differentiation of which is controlled by the transcription factor forkhead box protein 3 (Foxp3). This lineage perspective, however, may constrain hypotheses regarding the role of Foxp3 and Treg  in vivo, particularly in clinical settings and immunotherapy development. In this review, we synthesize a new perspective on the role of Foxp3 as a dynamically expressed gene, and thereby revisit the molecular mechanisms for the transcriptional regulation of Foxp3. In particular, we introduce a recent advancement in the study of Foxp3-mediated T cell regulation through the development of the Timer of cell kinetics and activity (Tocky) system, and show that the investigation of Foxp3 transcriptional dynamics can reveal temporal changes in the differentiation and function of Treg  in vivo. We highlight the role of Foxp3 as a gene downstream of T cell receptor (TCR) signalling and show that temporally persistent TCR signals initiate Foxp3 transcription in self-reactive thymocytes. In addition, we feature the autoregulatory transcriptional circuit for the Foxp3 gene as a mechanism for consolidating Treg differentiation and activating their suppressive functions. Furthermore, we explore the potential mechanisms behind the dynamic regulation of epigenetic modifications and chromatin architecture for Foxp3 transcription. Lastly, we discuss the clinical relevance of temporal changes in the differentiation and activation of Treg.
Variations in the management of acute illness in children with congenital adrenal hyperplasia: An audit of three paediatric hospitals
Authors: Chrisp Georgina L. , Maguire Ann M. , Quartararo Maria , Falhammar Henrik , King Bruce R. , Munns Craig F. , Torpy David J. , Hameed Shihab , Rushworth R. Louise
Published: August 2018

Objective

Episodes of acute adrenal insufficiency (AI)/adrenal crises (AC) are a serious consequence of congenital adrenal hyperplasia (CAH). This study aimed to assess morbidity from acute illness in CAH and identify factors associated with use of IV hydrocortisone, admission and diagnosis of an AC.

Method

An audit of acute illness presentations among children with CAH to paediatric hospitals in New South Wales, Australia, between 2000 and 2015.

Results

There were 321 acute presentations among 75 children with CAH. Two‐thirds (66.7%, n = 214) of these resulted in admission and 49.2% (n = 158) of the patients received intravenous (IV) hydrocortisone. An AC was diagnosed in (9.0%). Prior to presentation, 64.2% (n = 206) had used oral stress dosing and 22.1% (n = 71) had been given intramuscular (IM) hydrocortisone. Vomiting was recorded in 61.1% (n = 196), 32.7% (n = 64) of whom had used IM hydrocortisone. Admission, AC diagnosis and use of stress dosing varied significantly between hospitals. IM use varied from 7.0% in one metropolitan hospital to 45.8% in the regional hospital. Children aged up to 12 months had the lowest levels of stress dosing and IV hydrocortisone administration. Higher numbers of prior hospital attendances for acute illness were associated with increased use of IM hydrocortisone.

Conclusion

Prehospital and in‐hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self‐management of CAH in the context of acute illness in educated patient populations.
A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome
Authors: Roche Edna F. , McGowan Anne , Koulouri Olympia , Turgeon Marc‐Olivier , Nicholas Adeline K. , Heffernan Emmeline , El‐Khairi Ranna , Abid Noina , Lyons Greta , Halsall David , Bonomi Marco , Persani Luca , Dattani Mehul T. , Gurnell Mark , Bernard Daniel J. , Schoenmakers Nadia
Published: August 2018

Objective

Loss‐of‐function mutations in IGSF1 result in X‐linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.

Design, Patients and Measurements

A novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH, and its functional consequences were characterized in vitro. Genotype‐phenotype correlations were investigated in the wider kindred.

Results

The mutant IGSF1 protein (c.2318T > C, p.L773P) exhibited decreased plasma membrane expression in vitro due to impaired trafficking from the endoplasmic reticulum. Ten hemizygous males and 11 heterozygous females exhibited characteristic endocrine deficits. Ireland operates a TSH‐based CH screening programme, which does not detect CeCH; therefore, genetic ascertainment preceded biochemical diagnosis of moderate CH in five of seven boys as well as their 75‐year‐old grandfather. Clinical features potentially attributable to hypothyroidism were variable; normal free T3 (FT3) and low/low normal reverse T3 (rT3) concentrations suggested that preferential deiodination of FT4 to FT3 may help maintain tissue euthyroidism in some individuals. However, neonatal jaundice, delayed speech or growth, and obesity were observed in seven subjects in whom diagnosis was delayed.

Conclusions

As observed with other IGSF1 mutations, p.L773P results in variably penetrant IGSF1 deficiency syndrome. Our observations emphasize the need for multi‐generation genetic ascertainment in affected families, especially where TSH‐based CH screening programmes may fail to detect CeCH at birth.
Mothers and fathers in treatment for methamphetamine addiction—Parenting, parental stress, and children at risk
Authors: Dyba Janina , Moesgen Diana , Klein Michael , Leyendecker Birgit
Published: August 2018

Parents addicted to methamphetamine (“crystal meth”) are likely to be impaired in meeting parental responsibilities, and the developmental settings can be highly disadvantageous for children. Therefore, parenting by methamphetamine‐addicted mothers and fathers needs further exploration, while considering the impact on children affected by parental substance use. In our study, we analysed parenting practices and parental stress as well as children's behavioural problems using standardized assessments. The sample consisted of 87 methamphetamine‐addicted parents in recovery. We obtained data on parents' current substance use and on their psychological distress. Multiple regression analysis was performed to identify predictors of children's overall problems.

Parents reported high levels of parental and psychological distress, even after achieving abstinence. Especially depressive perceptions of parenthood appeared problematic. While recovering from methamphetamine addiction, parents exhibited a precarious psychosocial situation and problematic parenting behaviour. Dysfunctional parenting practices were evident in both indifferent and overreactive tendencies. Children were at risk of behavioural and emotional problems. Variables associated with parenting showed significant predictive value for children's overall problems, beyond current substance use, and psychological distress. These findings are discussed in terms of a family‐oriented perspective in order to promote parenting capabilities of methamphetamine‐addicted parents and to prevent problematic development of their children.
Assessing effects of non‐native crayfish on mosquito survival
Authors: Bucciarelli Gary M. , Suh Daniel , Lamb Avery Davis , Roberts Dave , Sharpton Debra , Shaffer H. Bradley , Fisher Robert N. , Kats Lee B.
Published: August 2018

Introductions of non‐native predators often reduce biodiversity and affect natural predator–prey relationships and may increase the abundance of potential disease vectors (e.g., mosquitoes) indirectly through competition or predation cascades. The Santa Monica Mountains (California, U.S.A.), situated in a global biodiversity hotspot, is an area of conservation concern due to climate change, urbanization, and the introduction of non‐native species. We examined the effect of non‐native crayfish (Procambarus clarkii) on an existing native predator, dragonfly nymphs (Aeshna sp.), and their mosquito larvae (Anopheles sp.) prey. We used laboratory experiments to compare the predation efficiency of both predators, separately and together, and field data on counts of dragonfly nymphs and mosquito larvae sampled from 13 local streams. We predicted a lower predation efficiency of crayfish compared with native dragonfly nymphs and a reduced predation efficiency of dragonfly nymphs in the presence of crayfish. Dragonfly nymphs were an order of magnitude more efficient predators than crayfish, and dragonfly nymph predation efficiency was reduced in the presence of crayfish. Field count data showed that populations of dragonfly nymphs and mosquito larvae were strongly correlated with crayfish presence in streams, such that sites with crayfish tended to have fewer dragonfly nymphs and more mosquito larvae. Under natural conditions, it is likely that crayfish reduce the abundance of dragonfly nymphs and their predation efficiency and thereby, directly and indirectly, lead to higher mosquito populations and a loss of ecosystem services related to disease vector control.
Influence of pretransplant midodrine use on outcomes after kidney transplantation
Authors: Pottebaum April A. , Hagopian Jennifer C. , Brennan Daniel C. , Gharabagi Ara , Horwedel Timothy A.
Published: August 2018

Evaluation of potential kidney transplant recipients is important to identify and treat conditions that may influence graft or patient survival after transplantation. We performed a single‐center, observational cohort study to determine whether pretransplant midodrine use influences outcomes after kidney transplantation. We analyzed graft and patient outcomes for adult patients who underwent a kidney‐only transplantation at Barnes‐Jewish Hospital from January 1999 to December 2015. We quantified adjusted associations of pretransplant midodrine use with post‐transplant complications by multivariable Cox regression. Among the 2621 kidney transplant recipients analyzed, 37 (1.4%) were taking midodrine immediately prior to transplantation. Midodrine users were more commonly older (56.5 vs 50.4 years) and obese (67.6% vs 33.6%). Midodrine users were also more likely to be on hemodialysis (86.5% vs 59.2%), to have a longer duration of dialysis dependence (646 months vs 577 months), and to have higher levels of sensitization (peak panel reactive antibody >20%, 32.4% vs 15.8%) compared to nonusers. Pretransplant midodrine users had significantly higher rates of delayed graft function (DGF) (32.4% vs 6.7%, P < 0.001). No difference in the incidence of DGF was observed based on the midodrine dosing regimen. After multivariable adjustment for recipient and donor characteristics, pretransplant midodrine use was independently associated with graft failure at 1 year (adjusted hazard ratio, 5.11; 95% confidence interval, 2.09‐12.49).
Ten‐year observational follow‐up of a randomized trial comparing cyclosporine and tacrolimus therapy combined with steroid withdrawal in living‐donor renal transplantation
Authors: Kim Jinhae , Park Jeeeun , Hwang Subin , Yoo Heejin , Kim Kyunga , Park Jae Berm , Jang Hye Ryoun , Lee Jung Eun , Kim Sung‐Joo , Kim Yoon‐Goo , Kim Dae Joong , Oh Ha Young , Huh Wooseong
Published: August 2018

Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long‐term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5‐year prospective, randomized, single‐center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low‐risk patients. We now report the 10‐year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10‐year patient survival, death‐censored graft survival, and acute rejection‐free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low‐risk patients, there was no difference in long‐term patient and graft survival between TAC‐ and CsA‐based late steroid withdrawal regimens that included MMF treatment. More long‐term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.
Urinary angiotensinogen level is increased in renal transplant recipients with masked hypertension and is correlated with left ventricular mass index and albuminuria in these patients
Authors: Tiryaki Ozlem , Usalan Celalettin , Kul Seval , Tarakcioglu Mehmet , Sucu Murat , Yildiz Fahrettin , Coban Sacit
Published: August 2018

Activation of the local renin‐angiotensin system (RAS) is an independent risk factor for the development of proteinuria and left ventricular hypertrophy (LVH) more commonly seen in masked hypertensives. It has been reported that urinary angiotensinogen (UAGT) level provides a specific index of the intrarenal RAS status. The aim of this study was to evaluate the association between UAGT and left ventricular mass index (LVMI) and urinary albumin‐creatinine ratio (UACR) in renal transplant recipients (RTRs) with masked hypertension (HT). A total of 116 non‐diabetic‐treated hypertensive RTRs were included in this study. The patients were divided into two groups: masked hypertensives and controlled hypertensives. Forty‐two (36.2%) of RTRs had masked HT. Mean UACR and LVMI levels were higher in RTRs with masked HT than in RTRs with controlled HT (P < 0.001). UAGT level was also higher in masked hypertensives compared to controlled hypertensives (P < 0.001). Multivariable regression analysis showed that UAGT was positively correlated with UACR (β = 0.024, P = 0.001) and LVMI (β = 0.082, P = 0.001) in masked hypertensives. Consequently, masked HT was considerably frequent (36.2%) in treated hypertensive RTRs and high UAGT levels accompanied by high albuminuria and LVMI levels were seen in these patients. Overproduction of the UAGT may play a pivotal role in the development of LVH and proteinuria in masked hypertensives.
Reply to Dr Ozden et al.
Authors: Decaussin‐Petrucci Myriam , Descotes Françoise , Lifante Jean‐Christophe , Borson‐Chazot Françoise , Lopez Jonathan
Published: August 2018

Author's response to the letter from Dr S. Ozden et al. in this issue regarding the article by Decaussin‐Petrucci et al. published in Cytopathology, Volume 28, issue 6 (‘Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy’).
Clinical approach for molecular testing on thyroid fine needle aspirates
Authors: Özden Sabri , Er Sadettin , Tez Mesut
Published: August 2018

This letter has been written in response to the paper by Decaussin‐Petrucci et al. published in Cytopathology, Volume 28, issue 6 (‘Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy’). Indeterminate FNAB results (Bethesda 3) can be controversial in regards to treatment. In their article, Decaussin‐Petrucci et al. demonstrated that molecular tests can be routinely performed and are strong predictors of malignancy. In our letter we comment on this hypothesis from the clinicians’ perspective.