bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foetal programming by maternal thyroid disease
Authors: Andersen Stine Linding , Olsen Jørn , Laurberg Peter 
Published: February 2015

SummaryFoetal programming is an emerging concept that links a wide range of exposures during foetal life to later development of disease. Thyroid disorders are common in women of reproductive age, and careful management of pregnant women suffering from thyroid disease is important considering the crucial role of thyroid hormones during early brain development. It is possible that maternal thyroid dysfunction in pregnancy may lead to structural and/or functional changes during foetal brain development. Such an effect could later predispose the offspring to an increased risk of neurologic or psychiatric disease. We recently observed that children born to mothers with thyroid dysfunction had an increased risk of developing seizure disorders, autism spectrum disorders, attention‐deficit hyperactivity disorders and psychiatric disease in adolescence and young adulthood. In the review, we discuss the concept of potential foetal programming by maternal thyroid disease.
Association of erythropoietin gene polymorphisms with retinopathy in a Chinese cohort with type 2 diabetes mellitus
Authors: Song Qi , Zhang Yue , Wu Yongzhong , Zhou Fang , Qu Yi 
Published: February 2015

AbstractBackgroundThis study was performed to investigate the correlation of erythropoietin gene polymorphisms with diabetic retinopathy (DR) in a Chinese cohort with type 2 diabetes mellitus (T2DM).DesignCase–control study held in Qilu hospital of Shandong University, China.Participants792 T2DM individuals were involved, classified as groups DR (n = 448) and non‐DR (NDR; n = 344). The DR group was subdivided into groups proliferative DR (PDR; n = 220) and non‐PDR (NPDR; n = 228).MethodsThree single‐nucleotide polymorphisms, rs1617640, rs507392 and rs551238, in the erythropoietin gene were genotypedMain Outcome MeasuresOdds ratios (ORs) for the effects of erythropoietin gene polymorphisms on DR risk.ResultsThe genotype CC frequency in rs507392 was significantly lower in DR group (additive: OR, 0.45; 95% confidence interval [CI], 0.23–0.89; P = 0.027; recessive: OR, 0.44; 95%CI, 0.23–0.86; P = 0.012) or PDR group (additive OR, 0.18; 95%CI, 0.05–0.63; P = 0.002; recessive OR, 0.19; 95%CI, 0.06–0.66; P = 0.003) than in NDR group. The genotype CC frequency in rs551238 was significantly lower in DR group (additive OR, 0.42; 95%CI, 0.21–0.38; P = 0.016; recessive OR, 0.40; 95%CI, 0.20–0.79; P = 0.010) or PDR group (additive OR, 0.18; 95%CI, 0.05–0.62; P = 0.002; recessive OR, 0.18; 95%CI, 0.05–0.61; P = 0.002). No significant differences were detected in the distributions of rs1617640 genotype or all polymorphisms' alleles between groups NDR and DR, PDR or NPDR. Haplotype analyses did not provide any evidence for the correlation between the three polymorphisms and DR.ConclusionsOur data suggest that rs507392 and rs551238 in the erythropoietin gene probably act to lessen the risk for DR and PDR in the Chinese T2DM cohort.
First phylogenetic analysis of the tribe Phyllotini (Rodentia: Sigmodontinae) combining morphological and molecular data
Authors: Carrizo Luz V. , Catalano Santiago A. 
Published: February 2015

AbstractPrevious phylogenetic analyses of the tribe Phyllotini, one of the largest components of the subfamily Sigmodontinae, have been based on a single source of evidence. In particular, morphological analyses were largely based on craniodental data, almost neglecting the potential phylogenetic information present in the postcranium. Despite the significant advances made in relation to the knowledge of phyllotine phylogeny in recent times, there are several unsolved issues that highlight the importance of a phylogenetic analysis that integrates multiple sources of evidence, including previously considered sources as well as new sources of data. We present here the first combined phylogenetic analysis (morphological and molecular) of phyllotines, which includes the widest taxon and character sampling to date. Our dataset includes 164 morphological characters, of which 83 are postcranial characters, plus 3561 molecular characters, scored for 52 species from 34 genera of Oryzomyalia. In this study 75 postcranial characters not previously considered in this group are thoroughly described, and their utility for solving the relationships within Phyllotini is evaluated by means of different complementary analyses. Phyllotini was retrieved as a monophyletic clade in the combined analysis, with a composition that matches that obtained in most other recent analyses. All genera of phyllotines were monophyletic and show high support values. Abrotrichini, Akodontini and Oryzomyini were also monophyletic. The inclusion of postcranial data appears to be of limited utility to solve the phylogenetic relationships within Phyllotini.
Abutment height influences the effect of platform switching on peri‐implant marginal bone loss
Authors: Galindo‐Moreno Pablo , León‐Cano Ana , Monje Alberto , Ortega‐Oller Inmaculada , O′Valle Francisco , Catena Andrés 
Published: February 2015

AbstractPurposeThe purpose was to radiographically analyze and compare the marginal bone loss (MBL) between implants with different mismatching distance and to study the influence of the prosthetic abutment height on the MBL in association with the related mismatching distances.Material and methodsThis retrospective study included 108 patients in whom 228 implants were placed, 180 with diameter of 4.5 mm and 48 with diameter of 5 mm. All patients received OsseoSpeed™ implants with internal tapered conical connection (Denstply Implants). Different mismatching distances were obtained, given that all implants were loaded with the same uni‐abutment type (Lilac; Denstply Implants). Data were gathered on age, gender, bone substratum, smoking habits, previous history of periodontitis, and prosthetic features. MBL was analyzed radiographically at 6 and 18 months post‐loading.ResultsMixed linear analysis of mesial and distal MBL values yielded significant effects of abutment, implant diameter, follow‐up period, bone substratum, smoking, and abutment × time interaction. MBL was greater at 18 vs. 6 months, for short vs. long abutments, for grafted vs. pristine bone, for a heavier smoking habit, and for implants with a diameter of 5.0 vs. 4.5 mm.ConclusionGreater mismatching does not minimize the MBL; abutment height, smoking habit, and bone substratum may play a role in the MBL over the short‐ and medium term.
Management of tailgut cysts in a tertiary referral centre: a 10‐year experience
Authors: Patsouras D. , Pawa N. , Osmani H. , Phillips R. K. S. 
Published: February 2015

AbstractAimTailgut cysts are rare congenital lesions typically presenting as presacral masses. A variable clinical presentation often leads to misdiagnosis and unsuccessful operations.MethodA retrospective analysis was performed of tailgut cysts presenting to one surgeon at St Mark's hospital between 2003 and 2013. The patient demographic data and clinicopathological and radiological features, together with perioperative details and recurrence, were reviewed.ResultsA total of 17 patients (15 women) with a median age of 35 (21–64) years were included in the study. The mean duration of symptoms before referral was 40 months, with sepsis predominating in 12 cases. Fifteen of the patients had previously undergone surgery (mean 2.9 procedures). A posterior surgical approach was adopted in all patients with a coccygectomy performed in 13. A loop colostomy was formed in three patients. Two of them went on to have a secondary pull‐through operation after an initial failed local repair of rectal injury. One case was reported to show malignant degeneration on histological examination. There was one recurrence during a median follow‐up period of 13 (3–36) months.ConclusionTailgut cysts are an uncommon yet important cause of chronic perianal sepsis. Suspicion should be raised in a patient, usually female, presenting with a history of unsuccessful procedures. Diagnosis can be made by clinical assessment and MRI. Complete excision usually resolves the problem.
Autologous c‐Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c‐Kit+ Cardiac‐Derived Stem Cells in a Feline Model of Isoproterenol‐Induced Cardiomyopathy
Authors: Taghavi Sharven , Sharp Thomas E. , Duran Jason M. , Makarewich Catherine A. , Berretta Remus M. , Starosta Tim , Kubo Hajime , Barbe Mary , Houser Steven R. 
Published: February 2015

AbstractBackgroundCardiac‐ (CSC) and mesenchymal‐derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously.MethodsMSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L‐isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry.ResultsFractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end‐diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001.ConclusionsBoth CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit.
Neurological level at birth predicts survival to the mid‐40s and urological deaths in open spina bifida: a complete prospective cohort study
Authors: Oakeshott Pippa , Reid Fiona , Poulton Alison , Markus Hugh , Whitaker Robert H , Hunt Gillian M 
Published: February 2015

AimTo conduct a 50‐year complete, community‐based, prospective cohort study to investigate long‐term survival, causes of death, and influence of level of the lesion in treated open spina bifida.MethodThe cohort comprised 117 consecutive cases whose backs were closed non‐selectively at birth between 1963 and 1971 in Cambridge, UK. In 2013 we surveyed the survivors (n=39, 18 males, 21 females; mean age 46y, range 43–49y) by postal questionnaire and telephone interview. We compared outcomes in those born with a neurological deficit in terms of sensory and motor levels of L1 and above versus L2 and below.ResultsTwo‐thirds of the cohort (78/117) had died. Causes of death were cardiorespiratory (n=26), neurological (n=24), urological (n=22), or other (n=6). Only the urological deaths were related to level of the lesion: there were none in those with a sensory level of L2 or below (p<0.001). Birth findings also predicted survival: of the 57 infants with a neurological level of L1 or above, only 12% (n=7) survived compared with 55% (30/55) of the remainder (p<0.001).InterpretationThe increased mortality in those born with an extensive neurological deficit was mainly due to urological deaths. Neurological level, particularly the sensory level, is the best predictor of long‐term outcome and should be assessed routinely at birth.
Compstatin: a C3‐targeted complement inhibitor reaching its prime for bedside intervention
Authors: Mastellos Dimitrios C. , Yancopoulou Despina , Kokkinos Petros , Huber‐Lang Markus , Hajishengallis George , Biglarnia Ali R. , Lupu Florea , Nilsson Bo , Risitano Antonio M. , Ricklin Daniel , Lambris John D. 
Published: February 2015

AbstractThere is a growing awareness that complement plays an integral role in human physiology and disease, transcending its traditional perception as an accessory system for pathogen clearance and opsonic cell killing. As the list of pathologies linked to dysregulated complement activation grows longer, it has become clear that targeted modulation of this innate immune system opens new windows of therapeutic opportunity for anti‐inflammatory drug design. Indeed, the introduction of the first complement‐targeting drugs has reignited a vibrant interest in the clinical translation of complement‐based inhibitors. Compstatin was discovered as a cyclic peptide that inhibits complement activation by binding C3 and interfering with convertase formation and C3 cleavage. As the convergence point of all activation pathways and a molecular hub for crosstalk with multiple pathogenic pathways, C3 represents an attractive target for therapeutic modulation of the complement cascade. A multidisciplinary drug optimization effort encompassing rational ‘wet’ and in silico synthetic approaches and an array of biophysical, structural and analytical tools has culminated in an impressive structure‐function refinement of compstatin, yielding a series of analogues that show promise for a wide spectrum of clinical applications. These new derivatives have improved inhibitory potency and pharmacokinetic profiles and show efficacy in clinically relevant primate models of disease. This review provides an up‐to‐date survey of the drug design effort placed on the compstatin family of C3 inhibitors, highlighting the most promising drug candidates. It also discusses translational challenges in complement drug discovery and peptide drug development and reviews concerns related to systemic C3 interception.
Molecular changes associated with the development of resistance to imatinib in an imatinib‐sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation
Authors: Kobayashi Masato , Kuroki Shiori , Tanaka Yu , Moriya Yukari , Kozutumi Yukari , Uehara Yuji , Ono Kenichiro , Tamura Kyoichi , Washizu Tsukimi , Bonkobara Makoto 
Published: February 2015

AbstractAlthough imatinib has therapeutic activity for certain subsets of patients with mastocytosis, it is not always curative. Here, molecular mechanisms that confer imatinib resistance to neoplastic mast cells were investigated using an imatinib‐sensitive canine neoplastic mast cell line VI‐MC carrying a KIT c.1523A>T activating mutation. Two imatinib‐resistant sublines were established by culturing VI‐MC cells in increasing concentrations of imatinib (1 μM resistant, rVI‐MC1; 10 μM resistant, rVI‐MC10). Both sublines had a second KIT mutation c.2443G>C. Recombinant KIT with the second mutation was insensitive to 1 μM but sensitive to 10 μM imatinib. The effect of imatinib on the phosphorylation of KIT and its downstream signalling proteins was then examined using these sublines. KIT and ERK were constitutively phosphorylated in both sublines, and their phosphorylation was suppressed by 10 μM imatinib in rVI‐MC1 cells. However, KIT but not ERK phosphorylation was suppressed in rVI‐MC10 cells. The phosphorylation of ERK in rVI‐MC10 cells was also not diminished by the Src family kinase (SFK) inhibitor dasatinib. This second mutation in KIT may play an important role in imatinib resistance in neoplastic mast cells. Furthermore, KIT/SFK‐independent activation of ERK would be involved in imatinib resistance when the neoplastic cells are exposed to higher concentrations of imatinib.
Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia
Authors: Arnold Donald M , Nazi Ishac , Toltl Lisa J , Ross Catherine , Ivetic Nikola , Smith James W , Liu Yang , Kelton John G 
Published: February 2015

AbstractObjectivesImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production. Antibody binding to megakaryocytes may occur in ITP, but in vivo evidence of this phenomenon is lacking.MethodsWe determined the proportion of megakaryocytes bound with immunoglobulin G (IgG) in bone marrow samples from primary patients with ITP (n = 17), normal controls (n = 13) and thrombocytopenic patients with myelodysplastic syndrome (MDS; n = 10). Serial histological sections from archived bone marrow biopsies were stained for CD61 and IgG. IgG binding and the number of bone marrow megakaryocytes were determined morphologically by a hematopathologist with four assessors after a calibration exercise to ensure consistency.ResultsThe proportion of ITP patients with high IgG binding (>50% of bone marrow megakaryocytes) was increased compared with normal controls [12/17 (71%) vs. 3/13 (23%), P = 0.03]. However, the proportion of ITP patients with high IgG binding was no different than thrombocytopenic patients with MDS [12/17 (71%) vs. 7/10 (70%), P = 1.00]. IgG binding was associated with increased megakaryocyte numbers. Like platelet‐associated IgG, megakaryocyte‐associated IgG is related to thrombocytopenia but may not be specific for ITP.ConclusionMechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients.
Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1‐yr Phase 2 study
Authors: Cançado Rodolfo , Melo Murilo R. , de Moraes Bastos Roberto , Santos Paulo C. J. L. , Guerra‐Shinohara Elivira M. , Chiattone Carlos , Ballas Samir K. 
Published: February 2015

AbstractThis open‐label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12‐month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.
The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 1: dysphagia incidence, severity and aspiration
Authors: Suntrup S. , Kemmling A. , Warnecke T. , Hamacher C. , Oelenberg S. , Niederstadt T. , Heindel W. , Wiendl H. , Dziewas R. 
Published: February 2015

Background and purposeAlthough early identification of patients at risk for dysphagia is crucial in acute stroke care, predicting whether a particular patient is likely to have swallowing problems based on the brain scan is difficult because a comprehensive model of swallowing control is missing. In this study whether stroke location is associated with dysphagia incidence, severity and the occurrence of penetration or aspiration was systematically evaluated relying on a voxel‐based imaging analysis approach.MethodsTwo hundred acute stroke patients were investigated applying fiberoptic endoscopic evaluation of swallowing within 96 h from admission. Lesion masks were obtained from each patient's brain scan and registered to standard space. The percentage of lesioned volume of 137 atlas‐based brain regions was determined in each case. Region‐specific odds ratios were afterwards calculated with respect to presence of dysphagia, its severity and occurrence of penetration or aspiration.ResultsIn all, 165 patients were diagnosed with dysphagia, 80 of whom had severe swallow impairment. For each investigated item there were significant differences of regional percentage infarction in distinct brain areas between affected patients and those who did not present with that specific dysfunction. In particular, right hemispheric lesions of the pre‐ and post‐central gyri, opercular region, supramarginal gyrus and respective subcortical white matter tracts were related to dysphagia, with post‐central lesions being especially associated with severe swallowing impairment.ConclusionsDistinct brain lesion locations are related to the incidence, severity and pattern of swallowing dysfunction.
Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images
Authors: Whitwell J. L. , Boeve B. F. , Weigand S. D. , Senjem M. L. , Gunter J. L. , Baker M. C. , DeJesus‐Hernandez M. , Knopman D. S. , Wszolek Z. K. , Petersen R. C. , Rademakers R. , Jack C. R. , Josephs K. A. 
Published: February 2015

Background and purposeThe aim of our study was to determine the utility of longitudinal magnetic resonance imaging (MRI) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia (FTD), including microtubule‐associated protein tau (MAPT) and progranulin (GRN) mutations and C9ORF72 repeat expansions, as well as sporadic FTD.MethodsIn this longitudinal study, 58 subjects were identified who had at least two MRI and MAPT mutations (n = 21), GRN mutations (n = 11), C9ORF72 repeat expansions (n = 11) or sporadic FTD (n = 15). A total of 198 serial MRI measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor‐based morphometry. Sample size estimates were calculated.ResultsProgressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in GRN, followed by sporadic FTD, C9ORF72 and MAPT. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in GRN. Regional rates of atrophy across all lobes were greater in GRN compared to the other groups. C9ORF72 showed greater rates of atrophy in the left cerebellum and right occipital lobe than MAPT, and sporadic FTD showed greater rates in the anterior cingulate than C9ORF72 and MAPT. Sample size estimates were lowest using temporal lobe rates in GRN, ventricular rates in MAPT and C9ORF72, and whole brain rates in sporadic FTD.ConclusionThese data support the utility of using rates of atrophy as outcome measures in future drug trials in FTD and show that different imaging biomarkers may offer advantages in the different variants of FTD.
TypeIVrectal prolapse secondary to a long‐standing urinary bladder lithiasis in a donkey
Authors: Robert M. P. , Main de Boissiere A. , Depecker M. C. , de Fourmestraux C. , Touzot‐Jourde G. , Tessier C. 
Published: February 2015

SummaryRectal prolapse has been attributed to conditions generating tenesmus or increasing abdominal pressure in both horses and donkeys. This report presents the case of a 7‐year‐old gelded donkey that sustained atypeIVrectal prolapse secondary to a long‐standing cystic calculus after several episodes of intermittent mucosal prolapse. Rectal prolapse was addressed first on an emergency basis by colorectostomy. After medical stabilisation, pain and straining management with repeated epidural drug administrations, a laparoscopic‐assisted cystotomy was performed one week later to remove the calculus. The donkey was discharged and resumed his normal life at pasture.