bluuebunny/crossref_metadata_2025 huggingface dataset:
Biologic treatments for elderly patients with psoriasis
Authors: Momose Mami , Asahina Akihiko , Hayashi Mitsuha , Yanaba Koichi , Umezawa Yoshinori , Nakagawa Hidemi
Published: April 2017

The number of elderly patients with psoriasis is increasing in Japan. However, biologic treatment is generally considered to be challenging in elderly patients, due to their increased risk of complications compared with younger patients. Our retrospective study aimed to evaluate the safety profile and efficacy of biologics in senior elderly patients (≥75 years old) with psoriasis. The study involved a cohort of 27 patients aged 75–88 years who were being treated with biologics over a period of more than 1 year. Initial biologics administrated to were adalimumab (five cases) and ustekinumab (22 cases). Eight patients discontinued treatment: two developed cancer; one was transferred to hospital; and five others experienced either bone fracture, interstitial pneumonia, cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy following prophylactic tuberculosis treatment. Efficacy, evaluated by the percentage of patients achieving 75% reduction of Psoriasis Area and Severity Index score, was 76.9% at week 16 (n = 26), 88.0% at week 24 (n = 25) and 90.5% at week 52 (n = 21). Biologic treatments thus show clear efficacy in elderly patients with psoriasis, however, the increased frequency of adverse events requires rigorous patient observation.
Subacute pyridostigmine exposure increases heart rate recovery and cardiac parasympathetic tone in rats
Authors: Bharadwaj Manushree , Pope Carey , Davis Michael , Katz Stuart , Cook Christian , Maxwell Lara
Published: April 2017

Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can enhance parasympathetic tone by increasing cholinergic input to the heart. The objective of this study was to develop a rodent model of HRR to test the hypothesis that subacute pyridostigmine administration decreases cholinesterase activity and accelerates HRR in rats. Ten days after implantation of radiotelemetry transmitters, male Sprague Dawley rats were randomized to control (CTL) or treated (PYR; 0.14 mg/mL pyridostigmine in the drinking water, 29 days) groups. Rats were exercised on a treadmill to record HRR, and blood samples were collected on days 0, 7, 14, and 28 of pyridostigmine administration. Total cholinesterase and acetylcholinesterase (AChE) activity in plasma was decreased by 32%‐43% and 57%‐80%, respectively, in PYR rats on days 7‐28, while plasma butyrylcholinesterase activity did not significantly change. AChE activity in red blood cells was markedly reduced by 64%‐66%. HRR recorded 1 minute after exercise was higher in the PYR group on days 7, 14 and 28, and on day 7 when HRR was estimated at 3 and 5 minutes. Autonomic tone was evaluated pharmacologically using sequential administration of muscarinic (atropine) and adrenergic (propranolol) blockers. Parasympathetic tone was increased in PYR rats as compared with the CTL group. These data support the study hypothesis that subacute pyridostigmine administration enhances HRR by increasing cardiac parasympathetic tone.
Effect of Fuzhuan brick‐tea addition on the quality and antioxidant activity of skimmed set‐type yoghurt
Authors: Liu Dong
Published: April 2017

The effects of the addition of Fuzhuan brick‐tea (FZT) on the sensory characteristics, physicochemical quality, lactic acid bacteria content and antioxidant activity of yoghurt were evaluated. The results demonstrated that FZT was compatible with yoghurt and slightly improved the β‐galactosidase and proteolytic activity. Fuzhuan brick‐tea significantly reduced syneresis, improved the viscosity and total numbers of Streptococcus thermophilus and Lactobacillus acidophilus. The antioxidant activity, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity, inhibition of lipid peroxidation (ILP) and Fe2+ chelating activity of FZTY were significantly higher than those of the control and positively correlated with the concentration of FZT.
Effect on nutritional, sensory, textural and microbiological properties of low‐fat yoghurt supplemented with Jerusalem artichoke powder
Authors: Guo Xiulan , Xie Zhenjian , Wang Guoze , Zou Qiang , Tang Renyong
Published: April 2017

The effect of supplementing two types of Jerusalem artichoke powder (JAP) with three different concentrations on the properties of low‐fat (LF) yoghurt was investigated. The results indicated that supplementation with JAPs improved the yoghurt's nutritional value, sensory score and microbial counts, while also ameliorating the syneresis, firmness and adhesiveness that was increased by the LF nature of the yoghurt. Although yoghurts with freeze‐dried (FD) JAP had higher viable counts of probiotics compared with oven‐dried (OD) JAP, the higher firmness and adhesiveness of yoghurts with the added FD JAP were undesirable. The yoghurt supplemented with 4% OD JAP had similar textural property and sensory scores to the full‐fat control. Therefore, OD JAP may be recommended based on its properties and low cost; 4% OD JAP could function as a nutritious prebiotic ingredient and fat replacer in LF yoghurt.
The effect of zinc and vitamin B12 together with thyme and Aloe vera extracts on the viability of Lactobacillus acidophilusLA‐5® and physicochemical properties of Iranian yoghurt drink (Doogh)
Authors: Karami Mostafa
Published: April 2017

The possibility of a Bio‐Doogh production with active and live probiotic bacteria was investigated. In this study, the effect of zinc and vitamin B12 as micronutrients together with thyme and Aloe vera extracts at days 1, 11 and 21 of production on the development and viability of Lactobacillus acidophilusLA‐5® at 4 °C was studied. The addition of vitamin B12 (1.9 μg/L) and zinc (17.6 mg/L) increased the bacterial count of the probiotic strain; the effect of zinc was greater than that of vitamin B12. In addition, the data obtained indicated that the logarithmic bacterial count of the probiotic strain increased with addition of the thyme and Aloe vera extracts (10 mg/L). The simultaneous use of zinc and Aloe vera extract resulted in the highest probiotic bacterial count. Statistical analysis indicated that there were significant differences in the acidity and pH between the samples. The syneresis and odour of the test samples were different from the untreated samples.
Comparing induction of labour with oral misoprostol or Foley catheter at term: cost‐effectiveness analysis of a randomised controlled multi‐centre non‐inferiority trial
Authors: ten Eikelder MLG , van Baaren G‐J , Oude Rengerink K , Jozwiak M , de Leeuw JW , Kleiverda G , Evers I , de Boer K , Brons J , Bloemenkamp KWM , Mol BW
Published: April 2017

Objective

To assess the costs of labour induction with oral misoprostol versus Foley catheter.

Design

Economic evaluation alongside a randomised controlled trial.

Setting

Obstetric departments of six tertiary and 23 secondary care hospitals in the Netherlands.

Population

Women with a viable term singleton pregnancy in cephalic presentation, intact membranes, an unfavourable cervix (Bishop score <6) without a previous caesarean section, were randomised for labour induction with oral misoprostol (n = 924) or Foley catheter (n = 921).

Methods

We performed economic analysis from a hospital perspective. We estimated direct medical costs associated with healthcare utilisation from randomisation until discharge. The robustness of our findings was evaluated in sensitivity analyses.

Main outcome measures

Mean costs and differences were calculated per women induced with oral misoprostol or Foley catheter.

Results

Mean costs per woman in the oral misoprostol group and Foley catheter group were €4470 versus €4158, respectively [mean difference €312, 95% confidence interval (CI) –€508 to €1063]. Multiple sensitivity analyses did not change these conclusions. However, if cervical ripening for low‐risk pregnancies in the Foley catheter group was carried out in an outpatient setting, with admittance to labour ward only at start of active labour, the difference would be €4470 versus €3489, respectively (mean difference €981, 95% CI €225–1817).

Conclusions

Oral misoprostol and Foley catheter generate comparable costs. Cervical ripening outside labour ward with a Foley catheter could potentially save almost €1000 per woman.

Tweetable abstract

Oral misoprostol or Foley catheter for induction of labour generates comparable costs.
Endometrial immune markers are potential predictors of normal fertility and pregnancy after in vitro fertilization
Authors: Kofod Louise , Lindhard Anette , Bzorek Michael , Eriksen Jens Ole , Larsen Lise Grupe , Hviid Thomas Vauvert F.
Published: April 2017

Problem

Elucidating immune mechanisms in the endometrium, which lead to the success of implantation and pregnancy, is important in reproductive medicine. Studies of immune cell abundance have shown conflicting results, and the expression and importance of HLA class Ib proteins in pre‐implantation endometrium have not yet been investigated.

Method of study

The study population consisted of four subgroups: a hydrosalpinx, a salpingectomy, an unexplained infertility, and a fertile control group. Endometrial samples were collected during the implantation window. Immune markers (CD56+ and CD16+ cells, FoxP3+ Tregs, HLA‐G, HLA‐F) were quantified in the samples. The outcome of the subsequent IVF treatment was recorded.

Results

Increased CD56+ uNK cells and high HLA‐G expression served as predictor for successful pregnancy outcome. HLA‐F expression was positively correlated with uNK cells, being indirectly predictive for achieving pregnancy.

Conclusion

Endometrial uNK cell abundance in the pre‐implantation endometrium seems to be important for normal fertility and pregnancy success, and they may be used as clinical markers to predict implantation success in IVF.
Prevalence of herpes simplex virus types 1 and 2 at maternal and fetal sides of the placenta in asymptomatic pregnant women
Authors: Finger‐Jardim Fabiana , Avila Emiliana C. , da Hora Vanusa P. , Gonçalves Carla V. , de Martinez Ana Maria B. , Soares Marcelo A.
Published: April 2017

Problem

Herpes simplex virus 1 (HSV‐1) commonly causes orolabial infection, but can also infect the genital mucosa. In contrast, HSV‐2 is usually genital. Genital herpes can transmit the virus vertically to the fetus during pregnancy. We sought to estimate the prevalence of HSV‐1/2 on the maternal and fetal sides of the placenta.

Method of study

Placental tissues were collected from pregnant women seen at the Rio Grande University Hospital. HSV‐1 and HSV‐2 were detected by nested PCR.

Results

The prevalence of HSV‐1 and HSV‐2 was, respectively, 28% and 12.6% (maternal side) and 29.9% and 8.3% (fetal side). All HSV‐positive women were asymptomatic. Sexual behavior, vaginal delivery, and presence of HSVs on one side of the placenta were risk factors associated with HSV infection.

Conclusion

The occurrence of HSVs in placental tissue was high, especially for HSV‐1. Novel strategies need to be implemented for the management of asymptomatic women who might transmit HSV to their newborns.
Hypoxia‐inhibited DUSP2 expression promotes IL‐6/STAT3 signaling in endometriosis
Authors: Hsiao Kuei‐Yang , Chang Ning , Tsai Jia‐Ling , Lin Shih‐Chieh , Tsai Shaw‐Jenq , Wu Meng‐Hsing
Published: April 2017

Problem

How does hypoxia‐mediated downregulation of dual‐specificity phosphatase‐2 (DUSP2) promote the development of endometriotic lesions?

Method of study

The levels of IL‐6 and DUSP2 were assessed in eutopic stromal cells with DUSP2 knockdown or hypoxia treatment. Bromodeoxyuridine (BrdU) incorporation was applied for evaluating cell proliferation. The protein levels of DUSP2, cleaved caspase‐3, phosphorylated STAT3, and STAT3 were analyzed using immunoblot.

Results

The genomewide analysis of cells with DUSP2 overexpression indicated IL‐6 regulates multiple pathways related to inflammation, proliferation, and apoptosis. DUSP2 overexpression significantly suppressed IL‐6 expression, while DUSP2 knockdown promoted IL‐6 expression. The hypoxia‐treated eutopic stromal cells expressed higher levels of IL‐6, recapitulating the elevated levels of IL‐6 in ectopic stromal cells. The treatment with IL‐6 elicited the phosphorylation of STAT3, mimicking the elevated levels of phosphorylated STAT3 in the ectopic stromal cells. The IL‐6‐treated eutopic stromal cells showed more BrdU incorporation and less cleaved caspase‐3, which can be reversed by STAT3 inhibitor.

Conclusion

Hypoxia‐induced IL‐6 production in endometriotic lesions is mediated via downregulation of DUSP2, which causes aberrant activation of STAT3 signaling pathway and helps the endometriotic cells survive under the ectopic environment.
Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the TOPICOP score
Authors: Stalder J.‐F. , Aubert H. , Anthoine E. , Futamura M. , Marcoux D. , Morren M.‐A. , Trzeciak M. , Szalai Z. , Veres K. , Deleuran M. , Vestergaard C. , Boralevi F. , Chu C.‐Y. , De Raeve L. , Svensson Å. , Fölster‐Holst R. , Buchner M. , Takaoka R. , Aoki V. , Chernyshov P. , Chernyshova L. , Murrell D. F. , Zhao C. , Mckinster C. D. , Von Kobyletzky L. , Eichenfield L. , Totri C. , Lio P. , Seneschal J. , Moret L. , Barbarot S.
Published: April 2017

Background

Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries.

Methods

This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire.

Results

A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country.

Conclusions

The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.
Effect of anti‐IgE in occupational asthma caused by exposure to low molecular weight agents
Authors: Ollé‐Monge M. , Cruz M.J. , Gomez‐Ollés S. , Ojanguren I. , Vanoirbeek J. , Muñoz X.
Published: April 2017

Background

The role of immunoglobulin (Ig)‐E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In this study, we evaluate whether anti‐IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts.

Methods

On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18, and 21, animals were injected intraperitoneally with anti‐IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyper‐responsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue, and total free IgE in serum samples were analyzed 24, 48, and 96 hours after the last challenge.

Results

Anti‐IgE mAb treatment almost completely neutralized free serum IgE. In AP‐sensitized and challenged mice, anti‐IgE mAb treatment abolished AHR 24 hour and 48 hour after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48 hour and 96 hour after the last AP challenge compared with nontreated mice. Levels of interleukin (IL)‐13 in BAL were also significantly decreased after anti‐IgE administration 24 hour and 48 hour after the last AP challenge. Histological analysis of the lung sections from anti‐IgE‐treated mice revealed normal inflammatory patterns similar to control groups 48 hour after the last challenge.

Conclusions

Anti‐IgE‐treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti‐IgE mAb has positive effects in OA induced by persulfate salts.
Identification of a polygalacturonase (Cup s 2) as the majorCCD‐bearing allergen inCupressus sempervirenspollen
Authors: Shahali Y. , Sutra J.‐P. , Hilger C. , Swiontek K. , Haddad I. , Vinh J. , Guilloux L. , Charpin D. , Sénéchal H. , Poncet P.
Published: April 2017

As IgE glyco‐epitopes, also referred to as cross‐reactive carbohydrate determinants (CCDs), can share significant structural homologies between different plants, they are prone to extensive cross‐reactivity among allergen pollen extracts. Here, cypress pollen allergens, especially a polygalacturonase (PG), were further characterized using double one‐dimensional electrophoresis (D1‐DE). The presence of specific IgE directed againstCCDs was investigated by bromelain IgE inhibition and concanavalin A binding assays using sera of cypress pollen‐sensitized patients. Our results showed that IgE reactivity toCCDs inCupressus sempervirenspollen extracts is mainly related to bromelain‐type epitopes of a newly identified cypressPG. This glycoprotein has been further characterized through an immunoproteomic approach and officially indexed as Cup s 2 by theWHO/IUISallergen nomenclature. Cup s 2 could thus be associated with the increased prevalence of IgE reactivity to cypress pollen extracts because ofCCDinterference.
Der f 35: An MD‐2‐like house dust mite allergen that cross‐reacts with Der f 2 and Pso o 2
Authors: Fujimura T. , Aki T. , Isobe T. , Matsuoka A. , Hayashi T. , Ono K. , Kawamoto S.
Published: April 2017

Background

Dermatophagoides farinae is a source of airborne house dust mite (HDM) allergens. We elucidated IgE‐reactive allergens from D. farinae by two‐dimensional immunoblotting‐based allergenome analysis, and identified one new allergen, named Der f 35, that possesses IgE‐binding capacity comparable to that of Der f 2. The aim of this study was to clarify the allergenic capacity of new HDM allergen Der f 35.

Methods

We cloned der f 35 from D. farinae mRNA and produced recombinant Der f 35 in Escherichia coli. The IgE‐binding capacity of Der f 35 and its cross‐reactivity with group 2 allergens from D. farinae and Psoroptes ovis were determined by enzyme‐linked immunosorbent assay (ELISA) and ELISA inhibition assays, respectively.

Results

The deduced amino acid sequence for der f 35, which possesses the MD‐2‐related lipid‐recognition domain, showed higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE‐binding frequencies of 77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for recombinant structure by ELISA. Der f 35 showed cross‐reactivity with Der f 2 and Pso o 2 in reaction with HDM‐allergic patients' IgE by ELISA inhibition assay.

Conclusion

Der f 35 is a candidate major allergen from D. farinae, which is more similar to group 2 allergens from sheep scab mite and storage mites. Der f 35 could be responsible for the cross‐reactivity among group 2 mite allergens.
Effect of B9 and B12 vitamin intake on semen parameters and fertility of men with MTHFR polymorphisms
Authors: Najafipour R. , Moghbelinejad S. , Aleyasin A. , Jalilvand A.
Published: April 2017

The methylenetetrahydrofolate reductase (MTHFR) gene codes a crucial enzyme which involve in folate metabolism. The effect of MTHFR gene polymorphisms on male fertility status is uncertain and controversial. We evaluated the effect of B vitamin family intake on total homocysteine content and semen parameters of men with MTHFR gene polymorphisms. MTHFR genotypes frequency and serum total homocysteine concentration were measured among 280 men with impaired spermatogenesis (asthenospermia, oligospermia, severe oligospermia and azoospermia) and 85 control participants. B vitamin family dietary intakes were assessed using a semi‐quantitative food‐frequency questionnaire. In addition, concentrations of vitamins B9 and B12 were evaluated in serum samples of some participants (n = 60). We observed significantly higher frequency of TC or TT genotypes in C677T polymorphism among oligospermic, severe oligospermic and azoospermic men. CC genotype of A1298C polymorphism was significantly higher only in azoospermic men. Also, we observed critical effect of vitamin B9 and B12 intake on decreasing of total homocysteine and improving of semen parameters among the men with T allele of MTHFR C677T polymorphism. Our investigation showed that sufficient consumption of vitamins B9 and B12 influences sperm parameters of men with different MTHFR polymorphisms, especially genotypes with T allele.
Impact of T wave amplitude in lead aVR on predicting cardiac events in ischemic and nonischemic cardiomyopathy patients with an implantable cardioverter defibrillator
Authors: Tanaka Yoshihiro , Konno Tetsuo , Tamura Yudai , Tsuda Toyonobu , Furusho Hiroshi , Takamura Masayuki , Sakata Kenji , Yamagishi Masakazu , Hayashi Kenshi
Published: April 2017

Background

T wave amplitudes during ventricular repolarization in the lead aVR (TAaVR) are shown to be associated with adverse cardiac events in patients with several cardiovascular diseases, such as postmyocardial infarction. However, the utility of TAaVR has not been previously evaluated in patients with cardiomyopathy who have received implantable cardioverter defibrillators (ICD). Patients with ischemic or nonischemic cardiomyopathy (ICM or NICM, respectively) and who received an ICD may experience worsening of their condition due to the introduction of electric shock during treatment. This study aimed to investigate the utility of TAaVR in the prediction of cardiac events in ICM or NICM patients with ICD.

Methods

Ninety‐three consecutive ICM or NICM patients with ICD were retrospectively analyzed (median age: 64 years; male: 77.4%; ICD for secondary prevention: 76.3%; NICM: 64.5%). The median follow‐up period was 31 months. The primary endpoint was defined as composite cardiac events, including cardiac death, major ventricular arrhythmic events (MVAE), or hospitalization due to heart failure (HHF).

Results

Multivariate Cox regression analysis demonstrated that less negative TAaVR (−0.1 mV ≤ TAaVR <0 mV and 0 mV ≤ TAaVR) was independently associated with the primary endpoint (HR: 3.75; 95% confidence interval [CI]: 1.09–23.7; p = .04). Kaplan–Meier curve also revealed that the event free survival rate in the less negative TAaVR group was significantly lower than that in the normal TAaVR group (<−0.1 mV) (p < .01).

Conclusions

TAaVR is useful in risk stratification for cardiac events in ICM or NICM patients with ICD.
Impact of atrial fibrillation detected by extended monitoring—A population‐based cohort study
Authors: Busch Mathias C. , Gross Stefan , Alte Dietrich , Kors Jan A. , Völzke Henry , Ittermann Till , Werner André , Krüger Anne , Busch Raila , Dörr Marcus , Felix Stephan B.
Published: April 2017

Background

The clinical relevance of extended monitoring of AF in the general population is unclear. The study evaluated the detection of AF using transtelephonic electrocardiography and the clinical relevance of additional AF findings, especially with regard to stroke risk and mortality.

Methods

The data of 1678 volunteers participating in the tele‐ECG‐subproject of the Study of Health in Pomerania was evaluated. Occurrence of AF as revealed by tele‐ECG and conventional ECG was evaluated. Associations with mortality, history of stroke, and other clinical parameters were analyzed.

Results

AF was detected in 21 subjects (1.3%) by conventional ECG (ECG‐AF) and in 43 (2.6%) by tele‐ECG. All individuals with AF revealed by conventional ECG were also diagnosed to have AF by tele‐ECG; 22 were diagnosed by tele‐ECG only (Tele‐AF).

During follow‐up (median: 6.3 years) 42/1635, 1/22, and 5/21 participants died in the no‐AF‐, tele‐AF‐, and ECG‐AF groups (p < .001). Whereas, in comparison to the no‐AF group, the risk of death was higher in the ECG‐AF group (HR 9.4; 3.7–23.8; p < .001), there was no significant increase in mortality in the tele‐AF group (HR 1.9; 0.26–14.0; p = .52).

Prevalence of stroke history was higher in the ECG‐AF group (19%; 5.5–42%) than with the no‐AF (1.9%; 1.3–2.7%; p = .001) and the tele‐AF groups (0%; 0–15%; p = .05).

Conclusions

Tele‐ECG identifies significantly more AF cases in a population‐based setting compared to conventional ECG. The impact of AF diagnosed only by extended monitoring differs from conventionally diagnosed AF. Additional studies are warranted, since this might have an impact on clinical management.
A review of high‐mountain acidophilous vegetation in the Iberian Peninsula
Authors: Gavilán Rosario G. , Vilches Beatriz , Font Xavier , Jiménez‐Alfaro Borja
Published: April 2017

Aims

We study the high‐mountain grasslands growing on siliceous substrata of the Iberian Peninsula to determine floristic patterns and affinities that best define the structure and phytosociological classification of this vegetation.

Location

Cantabrian Range, Sierra Nevada, Sistema Central, Sistema Ibérico and the Pyrenees.

Methods

We analysed 1484 relevés representing 25 phytosociological associations of high‐mountain grasslands on siliceous substrata previously described in the study area. A first classification using noise clustering produced a large noise group containing over 50% of the relevés. We then carried out a DCA to check the relative position of the noise group components with respect to the whole pool, and a K‐means combined with species indicator analysis to obtain a more precise delimitation of clusters through their representative species.

Results

We considered 17 groups as the optimum number of clusters when considering K‐means and the corresponding indicator species. Pyrenean alpine vegetation separated first, showing a homogeneous pattern with a set of diagnostic taxa organized around two groups that coincide with one European class (Juncetea trifidi) and two alliances: Festucion eskiae in chionophilous environments and Festucion supinae in chionophobous habitats. The rest of the data correspond to the Iberian class Festucetea indigestae, recognized in three alliances corresponding to three territories: the Cantabrian Range, Central Iberian Peninsula (Sistema Central and Sistema Ibérico) and Sierra Nevada. Four groups were extracted from the Cantabrian Range, which correspond to temperate (two groups) and Mediterranean (two groups) plant communities included in Teesdaliopsio‐Luzulion. Two groups from Sierra Nevada ‐ one oro‐ (Thymion serpylloidis) and another cryoromediterranean (Ptilotrichion purpurei) ‐ were separated later on. Some relationships were found between the oromediterranean communities in the Central Mountains (Sierra de Guadarrama) and Sierra Nevada. This highlights the mediterranean character of this central Iberian mountain, compared to the rest of the central ranges (four groups representing cryoromediterranean vegetation) that were independently separated by the analysis and have a more submediterranean character. All are included in Jasionion carpetanae.

Conclusions

The Pyrenees and the Cantabrian Range show relationships in high‐mountain vegetation but also differences since the Cantabrian Range has a major influence of Mediterranean taxa in their plant communities. Central Iberian mountains showed relationships with the other Mediterranean mountains through the presence of species of the Festuca indigesta gr. and other endemic taxa. The particular pattern of Sierra Nevada – very patchy and with lower cover values – hindered the separation of groups, but two groups were finally detected in the analysis based on the altitudinal gradient.
Epigenetic repression of miR‐375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma
Authors: Tatekawa Shotaro , Chinen Yoshiaki , Ri Masaki , Narita Tomoko , Shimura Yuji , Matsumura‐Kimoto Yayoi , Tsukamoto Taku , Kobayashi Tsutomu , Kawata Eri , Uoshima Nobuhiko , Taki Tomohiko , Taniwaki Masafumi , Handa Hiroshi , Iida Shinsuke , Kuroda Junya
Published: April 2017

Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR‐375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre‐malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR‐375 expression in patient‐derived plasma cells regardless of the clinical stage, compared to normal plasma cells. Introduction of miR‐375 reduced PDPK1 expression in human myeloma cell lines (HMCLs), indicating that miR‐375 is the dominant regulator of PDPK1 expression. In addition, miR‐375 introduction also downregulated IGF1R and JAK2 in HMCLs. CpG islands in the MIR375 promoter were pathologically hypermethylated in all 8 HMCLs examined and in most of 58 patient‐derived myeloma cells. Treatment with SGI‐110, a hypomethylating agent, and/or trichostatin A, a histone deacetylase inhibitor, increased miR‐375 expression, but repressed PDPK1, IGF1R and JAK2 in HMCLs. Collectively, these results show the universal involvement of overlapping epigenetic dysregulation for abnormal miR‐375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways.
The new era of chelation treatments: effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major
Authors: Di Maggio Rosario , Maggio Aurelio
Published: April 2017

This review outlines the effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major (TM). For each treatment, the strength of the evidence was documented according to the guidelines of the American College of Cardiology and the American Heart Association. Serum ferritin (SF), liver iron concentration (LIC), heart T2* signal, heart damage and survival were used to assess effectiveness. Five chelation regimens out of 10 showed Level A Evidence in controlling iron overloading, as determined by SF levels and LIC. Three out of 10 chelation regimens were able to control heart iron levels, as determined by T2* signals with Level A Evidence. Two chelation regimens were able to improve/reverse heart damage and four increased of survival with Level B Evidence. These advances mean that the current survival of TM patients is now similar to that of thalassaemia intermedia patients.
Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia
Authors: Karlsson Lene , Forestier Erik , Hasle Henrik , Jahnukainen Kirsi , Jónsson Ólafur G. , Lausen Birgitte , Norén Nyström Ulrika , Palle Josefine , Tierens Anne , Zeller Bernward , Abrahamsson Jonas
Published: April 2017

Given that 30–40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5‐year overall survival (OS5y) was 39 ± 4% for the whole group and 43 ± 4% for the 190 patients given re‐induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse ≥1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 ± 5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re‐induction followed by SCT can give cure rates of 40% in children with relapsed AML.
Roles of the PDZ‐binding motif of HPV 16 E6 protein in oncogenic transformation of human cervical keratinocytes
Authors: Yoshimatsu Yuki , Nakahara Tomomi , Tanaka Katsuyuki , Inagawa Yuki , Narisawa‐Saito Mako , Yugawa Takashi , Ohno Shin‐ichi , Fujita Masatoshi , Nakagama Hitoshi , Kiyono Tohru
Published: April 2017

The high‐risk human papillomavirus E6 proteins have been shown to interact with and lead to degradation of PDZ‐domain‐containing proteins through its carboxy‐terminal motif. This PDZ‐binding motif plays important roles in transformation of cultured cells and carcinogenesis of E6‐transgenic mice. However, its biological effects on the natural host cells have not been elucidated. We have examined its roles in an in vitro carcinogenesis model for cervical cancer, in which E6 and E7 together with activated HRAS (HRASG12V) can induce tumorigenic transformation of normal human cervical keratinocytes. In this model, E6Δ151 mutant, which is defective in binding to PDZ domains, almost lost tumorigenic ability, whereas E6SAT mutant, which is defective in p53 degradation showed activity close to wild‐type E6. Interestingly, we found decreased expression of PAR3 in E6‐expressing cells independently of E6AP, which has not been previously recognized. Therefore, we knocked down several PDZ‐domain containing proteins including PAR3 in human cervical keratinocytes expressing E7, HRASG12V and E6Δ151 to examine whether depletion of these proteins can restore the tumorigenic ability. Single knockdown of SCRIB, MAGI1 or PAR3 significantly but partially restored the tumorigenic ability. The combinatorial knockdown of SCRIB and MAGI1 cooperatively restored the tumorigenic ability, and additional depletion of PAR3 further enhanced the tumorigenic ability surpassing that induced by wild‐type E6. These data highlight the importance of the carboxy‐terminal motif of the E6 protein and downregulation of PAR3 in tumorigenic transformation of human cervical keratinocytes.
Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease
Authors: Diana T , Krause J , Olivo P D , König J , Kanitz M , Decallonne B , Kahaly G J
Published: April 2017

The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = –0·86, P < 0·05). The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with  > 70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.
Immediate and delayed loading of two‐piece reduced‐diameter implants with locator‐analog attachments in edentulous mandibles: One‐year results from a randomized clinical trial examining clinical outcome and patient expectation
Authors: Giannakopoulos Nikolaos Nikitas , Ariaans Kirsten , Eberhard Lydia , Klotz Anna‐Luisa , Oh Keunyoung , Kappel Stefanie
Published: April 2017

Background

Prosthetic management of thin alveolar ridges in the edentulous mandibles of elderly patients, especially the time of loading, the number of implants needed, and patient expectations and perception, is a challenge in implant dentistry.

Purpose

Survival of conventionally and immediately loaded 2‐piece reduced‐diameter implants in the interforaminal region of the edentulous mandible supporting locator‐analog attachments was evaluated. Prosthetic complications and peri‐implant hygiene were also studied, and patient expectation and subjective evaluation of the treatment were documented.

Material and Methods

Twenty‐five patients with adapted complete dentures received 4 reduced‐diameter implants. All anterior implants were immediately loaded. Three months later, patients were allocated by randomization to 1 of 2 treatment groups: 2 locator‐analog attachments on the anterior implants (Group A); or 4 locator‐analog attachments (Group B). After another 3 months patient allocation was changed (crossover design) for the next 3 months. Questionnaires with Likert scales and numeric rating scales were used to assess patients' expectations and subjective overdenture‐related variables, respectively.

Results

One implant was lost in the immediate‐loading group. Survival was 98% and 100% for immediate and delayed loading, respectively. During 12‐month observation, 8 complications required aftercare. At the beginning of treatment, patients' expectations were highly positive. Subjective assessment of overdenture‐related variables 3 months after immediate loading of 2 implants revealed a statistically significant improvement for most of the variables studied; this was maintained 1 year later. In the subjective assessments, there were no statistically significant differences between Groups A and B.

Conclusion

Immediate loading of reduced‐diameter implants supporting locator‐analog attachments resulted in high implant survival, few prosthetic complications, good oral hygiene, and improvement of subjective denture perception in the short‐term. It might be a promising treatment option, especially for elderly patients with a narrow mandibular ridge.
Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours
Authors: Saxton Peter , Newcombe David , Ahmed Arslan , Dickson Nigel , Hughes Anthony
Published: April 2017

Introduction and Aims

Data are lacking on drug use among gay and bisexual men (GBM) in New Zealand. We establish a baseline estimate of drug use and investigate associations with sexual health and HIV risk.

Design and Methods

A cross‐sectional survey of GBM was conducted in gay community settings and online. Participants were asked their frequency of using nine drugs (poppers, cannabis, ecstasy, methamphetamine, amphetamine, cocaine, LSD, gamma hydroxybutyrate and ketamine) in the previous 6 months. We examined associations between selected drugs and number of recent partners, unprotected anal intercourse with a casual partner and sexually transmitted infections using adjusted odds ratios (AOR).

Results

Overall, 3211 participants provided information of whom 55.8% reported any drug use, and 37.9% cannabis, 36.7% poppers, 16.5% ecstasy, 10.5% amphetamine, 7.4% methamphetamine, 6.6% LSD, 6.1% cocaine, 5.3% gamma hydroxybutyrate and 4.4% ketamine use. A quarter of all respondents (25.6%) reported using one drug, 22.8% two to four and 7.4% five or more drugs (polydrugs). Methamphetamine and polydrug use was independently predictive of reporting >20 recent partners (AOR 1.6 and 7.0, respectively), unprotected anal intercourse with a casual partner (AOR 1.8 and 3.2, respectively) and a sexually transmitted infection (AOR 1.6 and 4.3, respectively).

Discussion and Conclusions

Drug use was common in this sample of GBM. Polydrug and methamphetamine users had especially high sexual health needs, but risks remained elevated among GBM consuming other drugs. Drug harm reduction programs and HIV prevention should target GBM with problematic drug use. Limitations include an inability to attribute causation. [Saxton P, Newcombe D, Ahmed A, Dickson N, Hughes A. Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours. Drug Alcohol Rev 2017;00:000‐000]
Explaining the declining rates of past year cannabis use in Australia: A first pass
Authors: Ritter Alison , Sotade Oluwadamisola
Published: April 2017

Introduction and Aims

Cannabis use rates in Australia have declined since 2001. No research to date has examined possible reasons, despite evident policy interest in understanding such a positive public health outcome. In a ‘first pass’ examination, five possible reasons are explored: (i) attitudinal shifts regarding the acceptability of cannabis use; (ii) regulatory or policy changes; (iii) supply/market changes; (iv) changes in other drug use that may operate as substitutes or complements to cannabis; and (v) socio‐cultural factors.

Methods

Secondary analyses from three publically available national surveys (the National Drug Strategy Household Survey 2001 to 2013, the Illicit Drug Reporting System 2004 to 2013 and the Illicit Drug Data Report 2002 to 2013) were used to explore the five reasons.

Results

It appears that all five explanations are reasonable and have preliminary evidence to indicate they are worth pursuing empirically. Attitudes have not softened towards cannabis in Australia, and regulatory changes appear to have tightened. Perceived purity may have declined, and with stable prices, this suggests an increase in purity‐adjusted price that would also be consistent with decreased use. The significant declines in tobacco and alcohol use in Australia, which operate as complements to cannabis, also plausibly account for the significant decrease.

Discussion and Conclusions

This work suggests future directions for cannabis research in Australia. New multi‐disciplinary research that has the potential to explore multiple hypotheses simultaneously is required. [Ritter A, Sotade O. Explaining the declining rates of past year cannabis use in Australia: A first pass. Drug Alcohol Rev 2017;00:000‐000]
Atypical inter‐hemispheric communication correlates with altered motor inhibition during learning of a new bimanual coordination pattern in developmental coordination disorder
Authors: Blais Mélody , Amarantini David , Albaret Jean‐Michel , Chaix Yves , Tallet Jessica
Published: April 2017

Impairment of motor learning skills in developmental coordination disorder (DCD) has been reported in several studies. Some hypotheses on neural mechanisms of motor learning deficits in DCD have emerged but, to date, brain‐imaging investigations are scarce. The aim of the present study is to assess possible changes in communication between brain areas during practice of a new bimanual coordination task in teenagers with DCD (n = 10) compared to matched controls (n = 10). Accuracy, stability and number of mirror movements were computed as behavioural variables. Neural variables were assessed by electroencephalographic coherence analyses of intra‐hemispheric and inter‐hemispheric fronto‐central electrodes. In both groups, accuracy of the new coordination increased concomitantly with right intra‐hemispheric fronto‐central coherence. Compared to typically developing teenagers, DCD teenagers presented learning difficulties expressed by less stability, no stabilization of the new coordination and a greater number of mirror movements despite practice. These measures correlated with reduced inter‐hemispheric communication, even after practice of the new coordination. For the first time, these findings provide neuro‐imaging evidence of a kind of inter‐hemispheric ‘disconnection’ related to altered inhibition of mirror movements during motor learning in DCD.
Herpes simplex virus‐induced anti‐N‐methyl‐d‐aspartate receptor encephalitis: a systematic literature review with analysis of 43 cases
Authors: Nosadini Margherita , Mohammad Shekeeb S , Corazza Francesco , Ruga Ezia Maria , Kothur Kavitha , Perilongo Giorgio , Frigo Anna Chiara , Toldo Irene , Dale Russell C , Sartori Stefano
Published: April 2017

Aim

To conduct a systematic literature review on patients with biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.

Method

We conducted a case report and systematic literature review (up to 10 December 2016), focused on differences between herpes simplex encephalitis (HSE) and anti‐NMDAR encephalitis phases, age‐related characteristics of HSV‐induced anti‐NMDAR encephalitis, and therapy. For statistical analyses, McNemar's test, Fisher's test, and Wilcoxon rank sum test were used (two‐tailed significance level set at 5%).

Results

Forty‐three patients with biphasic disease were identified (31 children). Latency between HSE and anti‐NMDAR encephalitis was significantly shorter in children than adults (median 24 vs 40.5d; p=0.006). Compared with HSE, anti‐NMDAR encephalitis was characterized by significantly higher frequency of movement disorder (2.5% vs 75% respectively; p<0.001), and significantly lower rate of seizures (70% vs 30% respectively; p=0.001). Compared with adults, during anti‐NMDAR encephalitis children had significantly more movement disorders (86.7% children vs 40% adults; p=0.006), fewer psychiatric symptoms (41.9% children vs 90.0% adults; p=0.025), and a slightly higher median modified Rankin Scale score (5 in children vs 4 in adults; p=0.015). During anti‐NMDAR encephalitis, 84.6 per cent of patients received aciclovir (for ≤7d in 22.7%; long‐term antivirals in 18.0% only), and 92.7 per cent immune therapy, but none had recurrence of HSE clinically or using cerebrospinal fluid HSV polymerase chain reaction (median follow‐up 7mo).

Interpretation

Our review suggests that movement disorder may help differentiate clinically an episode of HSV‐induced anti‐NMDAR encephalitis from HSE relapse. Compared with adults, children have shorter latency between HSE and anti‐NMDAR encephalitis and, during anti‐NMDAR encephalitis, more movement disorder, fewer psychiatric symptoms, and slightly more severe disease. According to our results, immune therapy given for HSV‐induced anti‐NMDAR encephalitis does not predispose patients to HSE recurrence.