bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of season of birth with DNA methylation and allergic disease
Authors: Lockett G. A. , Soto‐Ramírez N. , Ray M. A. , Everson T. M. , Xu C.‐J. , Patil V. K. , Terry W. , Kaushal A. , Rezwan F. I. , Ewart S. L. , Gehring U. , Postma D. S. , Koppelman G. H. , Arshad S. H. , Zhang H. , Karmaus W. , Holloway J. W. 
Published: March 2016

AbstractBackgroundSeason of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long‐lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.MethodsIn a subset of 18‐year‐old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome‐wide DNA methylation was measured, and season‐associated CpGs detected using a training‐and‐testing‐based technique. Validation method examined the 8‐year‐old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third‐generation cohort newborns.ResultsAutumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome‐wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season‐associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season‐associated methylation was largely absent in newborns, suggesting it arises post‐natally.ConclusionsThis study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.
Current views on the diagnosis and management of hypokalaemia in children
Authors: Zieg Jakub , Gonsorcikova Lucie , Landau Daniel 
Published: March 2016

AbstractHypokalaemia is a common electrolyte disorder in children, caused by decreased potassium intake, increased gastrointestinal and urinary losses or transcellular shift. Patients with severe hypokalaemia may suffer from symptoms such as life‐threatening cardiac arrhythmias. The aim of our study was to review the aetiology of hypokalaemia, suggest a diagnostic algorithm and discuss the management of patients with various aetiologies of hypokalaemia.ConclusionUnderstanding the pathophysiology of hypokalaemic states, along with a detailed medical history, physical examination and specific laboratory tests are required for proper diagnosis and appropriate treatment.
Cardiotrophin‐1 decreases intestinal sugar uptake in mice and in Caco‐2 cells
Authors: López‐Yoldi M. , Castilla‐Madrigal R. , Lostao M. P. , Barber A. , Prieto J. , Martínez J. A. , Bustos M. , Moreno‐Aliaga M. J. 
Published: March 2016

AbstractAimCardiotrophin‐1 (CT‐1) is a member of the IL‐6 family of cytokines with a key role in glucose and lipid metabolism. In the current investigation, we examined the in vivo and in vitro effects of CT‐1 treatment on intestinal sugar absorption in different experimental models.MethodsrCT‐1 effects on α‐Methyl‐D‐glucoside uptake were assessed in everted intestinal rings from wild‐type and CT‐1−/− mice and in Caco‐2 cells. rCT‐1 actions on SGLT‐1 expression in brush border membrane vesicles and the identification of the potential signalling pathways involved were determined by Western blot.ResultsIn vivo administration (0.2 mg kg−1) of rCT‐1 caused a significant decrease on α‐Methyl‐D‐glucoside uptake in everted intestinal rings from wild‐type and CT‐1−/− mice after short‐term and long‐term treatments. Similarly, in vitro treatment (1–50 ng mL−1) with rCT‐1 reduced α‐Methyl‐D‐glucoside uptake in everted intestinal rings. In Caco‐2 cells, rCT‐1 treatment (20 ng mL−1, 1 and 24 h) lowered apical uptake of α‐Methyl‐D‐glucoside in parallel with a decrease on SGLT‐1 protein expression. rCT‐1 promoted the phosphorylation of STAT‐3 after 5 and 15 min treatment, but inhibited the activation by phosphorylation of AMPK after 30 and 60 min. Interestingly, pre‐treatment with the JAK/STAT inhibitor (AG490) and with the AMPK activator (AICAR) reversed the inhibitory effects of rCT‐1 on α‐Methyl‐D‐glucoside uptake. AICAR also prevented the inhibition of SGLT‐1 observed in rCT‐1‐treated cells.ConclusionsCT‐1 inhibits intestinal sugar absorption by the reduction of SGLT‐1 levels through the AMPK pathway, which could also contribute to explain the hypoglycaemic and anti‐obesity properties of CT‐1.
Effects of static magnetic fields on bone regeneration of implants in the rabbit: micro‐CT, histologic, microarray, and real‐time PCR analyses
Authors: Kim Eun‐Cheol , Leesungbok Richard , Lee Suk‐Won , Hong Ji‐Youn , Ko Eun‐Jin , Ahn Su‐Jin 
Published: March 2016

AbstractObjectivesThe aim of this study was to investigate the effects of static magnetic fields (SMFs) on bone regeneration around titanium implants by μCT, histologic analysis, microarrays, and quantitative real‐time PCR (qRT‐PCR).Materials and methodsNeodymium magnets provided the source of SMFs, the specimens were grade 5 titanium implants, and the animals were twenty‐seven adult male New Zealand white rabbits. These implants were divided into six groups according to the presence of a magnet and predetermined healing period (1, 4, and 8 weeks). Each group comprised six specimens for μCT (n = 6) and histologic examination, and three specimens (n = 3) for microarrays and qRT‐PCR, yielding a total of 54 specimens.ResultsThe μCT data showed that SMFs increased bone volume fraction (bone volume/total volume, BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th). Histologic observation indicated that SMFs promoted new bone formation and direct bony contact with implants. Microarray analysis identified 293 genes upregulated (>twofold) in response to SMFs. The upregulated genes included extracellular matrix (ECM)‐related genes (COL10A1, COL9A1, and COL12A1) and growth factor (GF)‐related genes (CTGF and PDGFD), and the upregulation was confirmed by qRT‐PCR. Gene Ontology (GO) and pathway analysis revealed the involvement of the mitogen‐activated protein kinase (MAPK), Wnt, and PPAR‐gamma signaling pathways in implant healing.ConclusionsμCT, histology, microarrays, and real‐time PCR indicate that SMFs could be an effective approach to improving bone regeneration around dental implants.
Behandlung von erosivem oralem Lichen planus mit Methotrexat
Authors: Lajevardi Vahideh , Ghodsi Seyedeh Zahra , Shafiei Zahra , Aghazadeh Nessa , Akbari Zahra 
Published: March 2016

ZusammenfassungHintergrund und ZielsetzungErosiver oraler Lichen planus (EOLP) ist eine chronisch‐entzündliche Erkrankung der Mundschleimhaut, welche erhebliche Schmerzen verursacht und die Lebensqualität einschränkt. Besonders bei den chronischen und hartnäckigen Formen gibt es keine unmittelbare und endgültige Heilung. Ziel dieser Studie war es, die Wirksamkeit einer Behandlung mit Methotrexat bei EOLP zu beurteilen.Patienten und MethodenEine prospektive, offene Studie mit oralem Methotrexat 15 mg QWK bei 18 Patienten mit EOLP (klinisch und histopathologisch bestätigt), die auf mindestens ein vormals verabreichtes topisches oder systemisches Medikament nicht ansprachen. Dauer: Zwölf Wochen, gefolgt von einer zwölfwöchigen Nachbehandlung.ErgebnisseEin mindestens teilweises Ansprechen wurde bei 15 (83,3 %) Patienten erreicht. Eine statistisch relevante Verminderung des Thongprasom‐Werts wurde beobachtet (Durchschnitt 5 als Basiswert, 3,08 ± 1,11 in Woche 12, 2,94 ± 0,97 in Woche 24, P‐Wert < 0,001). Auf der visuellen Analogskala wurde eine statistisch relevante Schmerzverminderung festgestellt (Durchschnitt 6,55 ± 2,33 als Basiswert, 2,46 ± 2,18 in Woche 12, 2,29 ± 1,93 in Woche 24, P‐Wert < 0,001). Unerwünschte Wirkungen traten bei vier (22,2 %) Patienten auf; bei einer Patientin erforderten diese den Abbruch der Behandlung.SchlussfolgerungenMethotrexat ist eine wertvolle Behandlungsoption bei langanhaltendem hartnäckigen EOLP, besonders in Bezug auf die Verbesserung subjektiver Symptome. Randomisierte kontrollierte Studien sind erforderlich.
Cofactors and comorbidities of necrobiosis lipoidica: analysis of the German DRG data from 2012
Authors: Jockenhöfer Finja , Kröger Knut , Klode Joachim , Renner Regina , Erfurt‐Berge Cornelia , Dissemond Joachim 
Published: March 2016

SummaryBackgroundNecrobiosis lipoidica (NL) is a rare granulomatous inflammatory skin disease of unknown pathophysiology. Its potential association with diabetes mellitus is well known. Other relevant cofactors and comorbidities are subject to controversial debate.Patients and methodsDRG (diagnosis‐related groups) data of all inpatients with a coded primary or secondary diagnosis of NL treated at German hospitals in 2012 were evaluated.ResultsData of 262 inpatient cases with the primary or secondary diagnosis of NL were analyzed. Women (63.4 %; n = 166) were nearly twice as frequently affected as men (36.2 %; n = 96). Most NL patients (14.8 %) were in the age group between 50 and 55 years. Among comorbidities included in the metabolic syndrome complex, diabetes mellitus was the most common (34.4 %; IDDM 20.6 %, NIDDM 13.8 %), while essential hypertension was observed in 9.2 %, obesity in 4.6 %, chronic heart failure in 4.1 %, and dyslipidemias in 2.3 % of cases. Leg ulcers were diagnosed in 7.3 % of individuals; other venous disorders, in 5.7 %.ConclusionsOur data analysis describes one of the largest compilations of patient cases with the diagnosis of NL worldwide. Besides the well‐known association with diabetes mellitus, there are numerous other potentially relevant cofactors and comorbidities that should be considered in the diagnosis and management of NL patients.
Kofaktoren und Komorbiditäten bei Necrobiosis lipoidica – Analyse der deutschen DRG‐Daten von 2012
Authors: Jockenhöfer Finja , Kröger Knut , Klode Joachim , Renner Regina , Erfurt‐Berge Cornelia , Dissemond Joachim 
Published: March 2016

ZusammenfassungHintergrundDie Necrobiosis lipoidica (NL) ist eine seltene, granulomatöse inflammatorische Erkrankung der Haut unklarer Pathophysiologie mit potentieller Assoziation zum Diabetes mellitus. Weitere relevante Kofaktoren und Komorbiditäten wurden bislang kontrovers diskutiert.Patienten und MethodikDifferenziert ausgewertet wurden die Diagnosis‐related‐Groups (DRG)‐Daten aller Patienten, die 2012 stationär in Deutschland behandelt und mit der Haupt‐ und Nebendiagnose NL kodiert wurden.ErgebnisseInsgesamt konnten die Datensätze von 262 stationären Patientenfällen mit der Haupt‐ oder Nebendiagnose NL evaluiert werden. Frauen (63,4 %, n = 166) waren fast doppelt so häufig von einer NL betroffen wie Männer (36,6 %, n = 96). Die meisten (14,8 %) der Patienten mit NL lagen in der Altersgruppe zwischen 50 und 55 Jahren. Als Komorbiditäten wurde aus der Gruppe des metabolischen Syndroms am häufigsten ein Diabetes mellitus bei 34,4 % dokumentiert; eine essentielle Hypertonie wurde in 9,2 %, eine Adipositas in 4,6 %, eine Herzinsuffizienz in 4,1 % und eine Lipoproteinstoffwechselstörung in 2,3 % der Fälle gefunden. Bei 7,3 % der Patienten bestand ein Ulcus cruris, bei 5,7 % wurde zudem eine Venenerkrankung diagnostiziert.SchlussfolgerungenUnsere Datenanalyse beschreibt eine der weltweit größten Untersuchungen von Patientenfällen mit NL, in der sich neben der bereits bekannten Assoziation zum Diabetes mellitus weitere potenzielle Kofaktoren und Komorbiditäten zeigen, die in Diagnostik‐ und Behandlungskonzepten der Patienten mit NL zukünftig beachtet werden sollten.
Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency
Authors: Greve Jens , Strassen Ulrich , Gorczyza Marina , Dominas Nina , Frahm Uta‐Marie , Mühlberg Heike , Wiednig Michaela , Zampeli Vasiliki , Magerl Markus 
Published: March 2016

SummaryHereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life‐threatening. In the majority of cases, the disease can be adequately treated with an on‐demand approach – in some cases, however, short‐ or long‐term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German‐speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1‐inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long‐term prophylaxis. According to the most recent international consensus papers and our own experience, self‐administered C1‐inhibitors are now the first option for long‐term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE.
Sézary syndrome: old enigmas, new targets
Authors: Nicolay Jan P. , Felcht Moritz , Schledzewski Kai , Goerdt Sergij , Géraud Cyrill 
Published: March 2016

SummarySézary syndrome, the leukemic variant of cutaneous T‐cell lymphoma, is still an enigmatic disease with a fatal prognosis. Recent research, however, has identified a multitude of dysregulated molecular pathways that contribute to malignant transformation and therapy resistance of Sézary cells (SC). With respect to T‐cell development, SC either represent naive T cells, T effector memory or T central memory cells. Functionally, SC may differentiate into Th2, Treg, or even Th17 cells. Despite their plasticity, SC express characteristic diagnostic marker proteins including CD158k, CD164, FcRL3, and PD‐1 as well as skin‐homing receptors such as CLA and CCR4. Already tested in (pre)clinical trials, CD158k, PD‐1, CTLA‐4, and CCR4 also represent promising therapeutic targets. Molecular alterations in SC include transcription factors such as STAT3, 4, and 5, as well as TWIST1 and TOX. TWIST1 induces expression of DNM3os containing the miR‐199a2/214 cluster, a key hub controlling multiple cancer networks. In addition, activation of NFκB and the MAPK pathway as well as altered TCR signaling cause apoptosis resistance. Recently, whole genome and exome sequencing has revealed somatic copy number variations as predominant mutations in SC, primarily affecting apoptosis, NFκB signaling, DNA integrity, and T‐cell activation. In order to facilitate development of novel therapies, improved in vivo models, which better reflect the pathogenesis and clinical course of Sézary syndrome, are currently being generated.
Gestresste Haut? – Aktueller Stand molekularer psychosomatischer Zusammenhänge und ihr Beitrag zu Ursachen und Folgen dermatologischer Erkrankungen
Authors: Peters Eva M.J. 
Published: March 2016

ZusammenfassungIn den 70er Jahren des vergangenen Jahrhunderts wurde zum ersten Mal ein pathogenetisch relevanter Zusammenhang zwischen Stress, im Sinne von psychosozialem Stress, und Krankheit am Beispiel von viralen Erkrankungen der Schleimhäute (wie Rhinovirus‐, Coxsackie‐Infektion) nachgewiesen. Seither nehmen Publikationen, die diese Zusammenhänge bis auf die molekulare Ebene erforschen, jährlich zu. Dennoch sind die Evidenzen für einen Einfluss von psychosozialer Belastung auf chronisch‐entzündliche Hauterkrankungen und auf Hauttumoren wenig bekannt. In diesem Beitrag fassen wir die aktuellen Erkenntnisse aus Epidemiologie, Psychoneuroimmunologie und molekularer Psychosomatik narrativ zusammen. Sie belegen die vielfältigen krankheitsrelevanten Interaktionen zwischen endokrinem System, Nervensystem und Immunsystem. Im Fokus stehen stressinduzierte Verschiebungen in der Immunbalance bei ausgewählten Erkrankungen wie Neurodermitis, Psoriasis oder malignem Melanom. Ziel dieses Beitrages ist die Vermittlung psychosomatischen Grundlagenwissens bei chronischen Dermatosen. Dies reicht von der Ätiologie über die Symptomatik bis zu den therapeutischen Optionen. Besonderes Augenmerk liegt dabei auf den zugrunde liegenden molekularen Zusammenhängen sowohl aus der somatopsychischen als auch aus der psychosomatischen Perspektive.
DL‐β‐Aminobutyric acid application negatively affects reproduction and larval development of the rosy apple aphid, Dysaphis plantaginea, on apple
Authors: Robert Philippe , Braud Ferréol , Aligon Sophie , Brisset Marie‐Noëlle 
Published: March 2016

AbstractThe rosy apple aphid, Dysaphis plantaginea (Passerini) (Hemiptera: Aphididae), is one of the major pests of European apple orchards, commonly controlled by the use of synthetic insecticides. In the present work, the non‐protein amino acid DL‐β‐aminobutyric acid (BABA), known to induce plant resistance against a wide range of abiotic and biotic stresses, has been tested for its protective effect against this pest on apple. We first verified the lack of any contact effect of BABA on the insect itself. Next we applied BABA as a soil drench to apple and monitored its effect on the population development of aphids after artificial infestation. We demonstrated that BABA strongly reduced the population growth and that this compound severely affected various life‐history characteristics of the aphid such as female longevity and fecundity, nymph mortality, and larval development.
Differential Cry toxin detection and effect on Brevicoryne brassicae and Myzus persicae feeding on artificial diet
Authors: Paula Débora P. , Andow David A. 
Published: March 2016

AbstractThe literature about effects of genetically modified plants expressing Cry toxins has several contrasting results regarding detection and effects of Cry toxins on aphids. To test the hypothesis that this variation could be due to a lack of controlled exposure, and not just a lack of toxicity, we used an artificial aphid rearing system to detect acquisition and examine potential effects of Cry1Ac and Cry1F on mortality and population growth rate of cabbage aphid, Brevicoryne brassicae (L.), and green peach aphid, Myzus persicae (Sulzer) (both Hemiptera: Aphididae). Using enzyme‐linked immunosorbent assay (ELISA), Cry1Ac and Cry1F were not detected in B. brassicae feeding on any of the Cry diets, whereas in M. persicae, Cry1Ac was detected in 55% of samples exposed alone or in combination with Cry1F, and Cry1F was detected in 67% of samples exposed alone or in combination with Cry1Ac. The toxins reduced the net population growth rate of M. persicae, but not of B. brassicae. For M. persicae, the reduction in growth rate was similar for Cry1Ac and Cry1F and there was no synergism from co‐feeding the aphids with both Cry toxins. The toxins had no detectable effect on survival of either aphid species. Variability in detection and effects of Cry toxins on aphids may not depend only on the presence and level of a Cry toxin in the phloem, and on differential experimental conditions as previously suggested, but may also depend on some characteristic of the aphid that remains to be determined.
Risk of Headache‐Related Healthcare Visits in Patients With Celiac Disease: A Population‐Based Observational Study
Authors: Lebwohl Benjamin , Roy Abhik , Alaedini Armin , Green Peter H.R. , Ludvigsson Jonas F. 
Published: March 2016

Background and AimsPatients with celiac disease (CD) are reported to be at increased risk for headaches, though large studies are lacking. We aimed to examine the risk of headache‐related healthcare encounters in patients with CD in a nationwide population‐based setting.MethodsIn this population‐based retrospective cohort study, we searched all (n = 28) pathology departments in Sweden and identified patients with CD based on the presence of villous atrophy (VA). Each patient was matched to up to 5 controls, by age, gender, calendar period, and region. Using Cox proportional hazards, we tested for an association between CD and subsequent headache‐related visit. We also tested this association for those with intestinal inflammation but normal villi, and subjects with positive CD serologies but normal histology.ResultsAmong 28,638 patients with CD and 143,126 controls, headache‐related visit occurred in 1,337 (4.7%) and 4,102 (2.9%), respectively. The incidence of headache‐related visit was 423 per 100,000 person‐years in CD patients and 254 per 100,000 person‐years in controls (HR 1.66; 95% CI 1.56–1.77; P < .0001). Individuals having inflammation without VA on small intestinal biopsy (n = 12,898; HR 2.08; 95% CI 1.90–2.27; P < .0001) and those with normal mucosa but positive CD serology (n = 3,617; HR 1.83; 95% CI 1.57–2.12; P < .0001) were also at increased risk for headache‐related visit.ConclusionsIn this population‐based study we found a significantly increased risk of headache‐related visits in patients with CD; this increase was also present in patients with intestinal inflammation and those with positive CD serology but with normal mucosal architecture on small bowel biopsy. Though limited by surveillance bias, this study indicates that headache‐related visits are more common in these populations.
Pelvic Examination at the 6‐Week Postpartum Visit After Cesarean Birth
Authors: Mahesan Arnold M. , Ilceski David M. , Paul Anthea B. M. , Vengalil Shyla 
Published: March 2016

IntroductionThe objective of this study was to assess the utility of the pelvic examination at the 6‐week postpartum visit after cesarean birth.MethodsData were collected from retrospective chart review in an obstetric resident clinic in Detroit, Michigan. Women included were those who had a cesarean birth between January 2012 and June 2014.ResultsOf 388 women who had a cesarean birth, 211 (54.4%) presented for the 6‐week postpartum visit and underwent pelvic examination. Of these women, 185 (87.7%) were asymptomatic, and 26 (12.3%) reported vaginal discharge. No other concerns were elicited. Of those with symptoms, 4 (15%) had no finding, 13 (50%) had bacterial vaginosis (BV) alone, 2 (8%) had BV and Candida sp, 2 (8%) had BV and Trichomonas vaginalis, 2 (8%) had T vaginalis alone, and 3 (11%) had Chlamydia trachomatis. One woman with C trachomatis had tested positive during pregnancy and possibly had treatment failure. Of the 185 asymptomatic women, 91 (49%) were deemed to have vaginal discharge on examination and underwent testing for Neisseria gonorrhoeae and C trachomatis; results were negative in all cases.DiscussionIn this population, it appears unnecessary to perform routine pelvic examination on asymptomatic women at the 6‐week postpartum visit after cesarean birth. When vaginal discharge was noted during pelvic examination of asymptomatic women, no pathology was identified.