bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non‐metastatic breast cancer
Authors: Bernadou Guillemette , Campone Mario , Merlin Jean‐Louis , Gouilleux‐Gruart Valérie , Bachelot Thomas , Lokiec François , Rezai Keyvan , Arnedos Monica , Diéras Véronique , Jimenez Marta , Paintaud Gilles , Ternant David
Published: December 2015

Aims

Trastuzumab, an antibody binding to epidermal growth factor receptor‐2 (HER2), has been approved to treat HER2‐positive breast cancer in different settings. This study aimed at evaluating the influence of tumour size on trastuzumab pharmacokinetics (PK) in non‐metastatic breast cancer patients treated with short term pre‐operative trastuzumab.

Methods

Trastuzumab PK data were obtained from a multicentre, randomized and comparative study. This antibody was administered pre‐operatively to patients with localized HER2‐positive breast cancer as a single 4 mg kg−1 loading dose followed by 5 weekly 2 mg kg−1 doses. Trastuzumab concentrations were measured repeatedly using an ELISA technique. Tumour size was evaluated at baseline using breast echography. Trastuzumab pharmacokinetics were studied using a population approach and a two compartment model. The influence of tumour burden on trastuzumab pharmacokinetics was quantified as a covariate.

Results

A total of 784 trastuzumab concentrations were available from the 79 eligible patients. Estimated parameters (interindiviual standard deviation) were central volume of distribution =2.1 l (23%), peripheral volume of distribution =1.3 l (38%), intercompartment clearance =0.36 l day−1, with an elimination half‐life of 11.8 days. Typical clearance was 0.22 l day−1 (19%) and its value was increased with tumour size. In patients with the highest tumour size, trastuzumab clearance was 50% [18%–92%] higher than in patients with the lowest tumour size.

Conclusions

In non‐metastatic breast cancer patients, trastuzumab clearance increases with tumour size. The elimination half‐life of trastuzumab was shorter in the present population of patients than in metastatic breast cancer patients previously studied.
Emerging pedagogies for the use of iPads in schools
Authors: Geer Ruth , White Bruce , Zeegers Yvonne , Au Wing , Barnes Alan
Published: December 2015

iPads are becoming popular as 1:1 devices in many classrooms, enabling teachers to implement pedagogies that will enhance student learning. Such mobile tools offer many affordances which can increase student motivation and autonomy. Nevertheless, without a change in pedagogy, they are unlikely to bring about any significant impact on student learning. Using the SAMR model, this initial study of four schools explores the impact of iPads on pedagogy and the changes that were evident. Using multiple data collection techniques, the study has shown that there have been some changes in teachers’ pedagogy that lead to increased collaboration, communication, student self‐reliance and the development of authentic experiences. However, more time and professional learning are needed to bring about a transformation in pedagogy across the school.
Using empirical models of species colonization under multiple threatening processes to identify complementary threat‐mitigation strategies
Authors: Tulloch Ayesha I.T. , Mortelliti Alessio , Kay Geoffrey M. , Florance Daniel , Lindenmayer David
Published: December 2015

Approaches to prioritize conservation actions are gaining popularity. However, limited empirical evidence exists on which species might benefit most from threat mitigation and on what combination of threats, if mitigated simultaneously, would result in the best outcomes for biodiversity. We devised a way to prioritize threat mitigation at a regional scale with empirical evidence based on predicted changes to population dynamics—information that is lacking in most threat‐management prioritization frameworks that rely on expert elicitation. We used dynamic occupancy models to investigate the effects of multiple threats (tree cover, grazing, and presence of an hyperaggressive competitor, the Noisy Miner (Manorina melanocephala) on bird‐population dynamics in an endangered woodland community in southeastern Australia. The 3 threatening processes had different effects on different species. We used predicted patch‐colonization probabilities to estimate the benefit to each species of removing one or more threats. We then determined the complementary set of threat‐mitigation strategies that maximized colonization of all species while ensuring that redundant actions with little benefit were avoided. The single action that resulted in the highest colonization was increasing tree cover, which increased patch colonization by 5% and 11% on average across all species and for declining species, respectively. Combining Noisy Miner control with increasing tree cover increased species colonization by 10% and 19% on average for all species and for declining species respectively, and was a higher priority than changing grazing regimes. Guidance for prioritizing threat mitigation is critical in the face of cumulative threatening processes. By incorporating population dynamics in prioritization of threat management, our approach helps ensure funding is not wasted on ineffective management programs that target the wrong threats or species.
Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones
Authors: Patrick Megan E. , O'Malley Patrick M. , Kloska Deborah D. , Schulenberg John E. , Johnston Lloyd D. , Miech Richard A. , Bachman Jerald G.
Published: December 2015

Introduction and Aims

The current study documents the characteristics associated with the use of two novel psychoactive substances: synthetic cannabinoids and synthetic cathinones.

Design and Methods

Nationally representative samples of students in 8th (n = 9665), 10th (n = 10 655) and 12th (n = 10 057) grades across the US were included in the Monitoring the Future study from 2012 to 2014.

Results

There were relatively few differences in prevalence based on sociodemographic characteristics, although boys were at greater risk for use of synthetic cannabinoids in 12th grade (used by 10.3% of boys and 6.4% of girls) and for use of synthetic cathinones in 10th grade (used by 1.0% of boys and 0.4% of girls). Synthetic drug use was also associated with truancy and use of cigarettes, alcohol, and marijuana.

Discussion and Conclusions

Prevention and intervention efforts for novel psychoactive substance use should focus primarily on polysubstance users and youth who are disengaged from school.[Patrick M, O'Malley P, Kloska D, Schulenberg J, Johnston L, Miech R, Bachman J. Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones. Drug Alcohol Rev 2016;35:586–590]
Immuntherapie des Melanoms: Wirksamkeit und Wirkungsmechanismen
Authors: Wieder Thomas , Brenner Ellen , Braumüller Heidi , Röcken Martin
Published: December 2015

Die Erkenntnisse aus 40 Jahren Forschung erlauben es, durch Antikörper‐vermittelte Aktivierung des Immunsystems eine therapeutisch wirksame Antitumorantwort zu induzieren. Die „Immun‐Checkpoint‐Inhibitoren“ sind gegen immuninhibitorische Moleküle wie cytotoxic T lymphocyte antigen 4 (CTLA4), programmed‐death‐1 (PD‐1) oder programmed‐death‐ligand‐1 (PD‐L1) gerichtet. Die Unterbrechung der PD‐1/PD‐L1‐Interaktion verbessert mittelfristig auch die Prognose bei Patienten mit Melanomen im Stadium IV. So sind unter Therapie mit Anti‐PD‐1‐Antikörpern 30–60 % dieser Patienten nach eineinhalb Jahren am Leben. Antitumorale Immuntherapien verursachen nur selten eine vollständige Zerstörung der Metastasen, sondern eine Regression um 20–80 %. Fest etabliert ist, dass das Immunsystem Tumorzellen abtöten kann; dies wurde auch für Immuntherapien belegt. Präklinische Daten zeigten jedoch, dass Immunantworten Tumoren nicht nur töten können. So kann das Immunsystem über die Zytokine Interferon‐γ und Tumornekrosefaktor in Tumoren einen stabilen Wachstumsarrest hervorrufen, der Seneszenz genannt wird. Ein Ziel antitumoraler Immuntherapien wird also darin liegen, das Überleben der Patienten durch eine langfristige Stabilisierung der Metastasen zu sichern. Dies gilt für das Melanom und das nichtkleinzellige Lungenkarzinom. Sobald Immuntherapien auch bei häufigen Tumoren indiziert sein werden, müssen die Medikamentenpreise deutlich fallen, um sie weiterhin jenen zur Verfügung stellen zu können, die die Therapien benötigen.
Retrospective data collection of psoriasis treatment with fumaric acid esters in children and adolescents in Germany (KIDS FUTURE study)
Authors: Reich Kristian , Hartl Christoph , Gambichler Thilo , Zschocke Ina
Published: December 2015

Background

Given that there is no standard systemic treatment for children and adolescents with plaque psoriasis, this non‐interventional, multicenter, retrospective study collected data on the efficacy and safety of long‐term treatment with fumaric acid esters (FAEs) in this particular patient group.

Patients and methods

In patients younger than 18 years of age at the start of FAE treatment, data on efficacy and safety was retrospectively collected for at least 36 months.

Results

Data from 127 patients (aged 6–17 years) was collected for treatment durations of up to 60 months. Physician's Global Assessment, Psoriasis Area and Severity Index, and Body Surface Area showed marked improvement in the first six months. After 36 months, these parameters had, on average, improved by up to two‐thirds of baseline values. Thirty‐seven patients experienced at least one adverse event (AE), which was FAE‐related in 36 individuals. Three AEs (proteinuria (one case), flushing (two cases)) persisted during the observation period while on treatment. Fifteen AEs led to the discontinuation of therapy; nearly all of these cases were related to gastrointestinal disorders.

Conclusions

The KIDS FUTURE study – for the first time – included a larger population of children and adolescents with psoriasis who were treated with FAEs. The data obtained suggests that long‐term FAE therapy in this patient group may be effective and safe. The results are currently being verified in an ongoing clinical study.
Misdiagnosed microcystic adnexal carcinoma on the lateral forehead and challenges in reconstruction of a large and bone‐deep defect
Authors: Fallaha Amgiad , Thuile Tobias , Tappeiner Lukas , Pichler Maria , Deluca Jenny , Perino Franco , Eisendle Klaus
Published: December 2015

Background

Microcystic adnexal carcinoma (MAC) is a rare cutaneous malignancy characterized by aggressive local infiltration, including a high propensity for perineural invasion. Histologically it can be easily confused with benign adnexal tumors, which often leads to inappropriate initial treatment. As a consequence delayed surgical excision often requires removal of large cutaneous masses which can be followed by challenges in reconstruction.

Methods

We report the case of a challenging reconstruction of a large forehead defect by a modified AT flap with central Burow's triangle grafting and previous wound conditioning using hyaluronic acid after complete micrographic removal of MAC.

Results

A 80‐year‐old healthy female presented with an almost six year history of an asymptomatic slowly progressing skin mass previously biopsied and diagnosed as benign syringoma five years in advance. Deep biopsies confirmed MAC. She underwent staged surgical excision with Tübingen torte technique with removal of the frontal periostium. A skin substitute of esterified hyaluronic acid was applied for three weeks to the bone‐deep 6×7 cm defect leading to good granulation tissue above the bone. Final reconstruction was achieved by an AT flap combined with full thickness skin transplantation of the central dog ear. The cosmetic outcome was satisfactory, no recurrence was observed within 18 months follow‐up.

Conclusions

We confirm the histological difficulties in the diagnosis of this tumor entity and the large extension of MAC due to delay in diagnosis and treatment. Deep tumor removal including the periostium might be necessary to achieve tumor free margins. Fast granulation tissue above the frontal bone might be achieved by applying hyaluronic acid products. The combination an AT flap with transplantation of the adjacent Burow's triangles gives optimal skin texture and color matching and seems to be a good option to close even large defects of the front especially for supra brow defects.
S2k‐Leitlinie Neurodermitis [atopisches Ekzem; atopische Dermatitis] – Kurzversion
Authors: Werfel Thomas , Heratizadeh Annice , Aberer Werner , Ahrens Frank , Augustin Matthias , Biedermann Tilo , Diepgen Thomas , Fölster‐Holst Regina , Gieler Uwe , Kahle Julia , Kapp Alexander , Nast Alexander , Nemat Katja , Ott Hagen , Przybilla Bernhard , Roecken Martin , Schlaeger Martin , Schmid‐Grendelmeier Peter , Schmitt Jochen , Schwennesen Thomas , Staab Doris , Worm Margitta
Published: December 2015

Bei dem Krankheitsbild der Neurodermitis handelt es sich um eine chronische oder chronisch‐rezidivierende, nichtkontagiöse, entzündliche Hauterkrankung mit in der Regel starkem Juckreiz. Darüber hinaus besteht ein Risiko für komplizierte Verläufe mit bakteriellen oder viralen Superinfektionen. Sowohl die genetische Prädisposition als auch zahlreiche Auslösefaktoren spielen für die Erstmanifestation und das Auftreten der Erkrankungsschübe eine wichtige Rolle, so dass auch die Therapiekonzepte vielfältig sind. Bei zahlreichen für die Neurodermitis zur Verfügung stehenden Behandlungsoptionen gilt es, in Abstimmung mit den Patienten bzw. Eltern erkrankter Kinder fallorientiert einen optimalen Behandlungsplan aufzustellen, der im Verlauf ggf. erneut angepasst werden muss.

Die vorliegende Kurzfassung der S2k‐Leitlinie gibt einen Überblick über alle bisher zur Verfügung stehenden, evidenzbasierten Diagnoseverfahren und Therapiemöglichkeiten sowie über die entsprechenden Empfehlungen, die durch die an dieser Leitlinie beteiligten Fachgesellschaften und Verbände ausgesprochen werden. Diese Empfehlungen wurden auf der Grundlage der bislang zu dem jeweiligen Verfahren vorliegenden klinisch‐wissenschaftlichen Datenlage, die in der ausführlichen Fassung dieser Leitlinie (unter www.awmf.org und jddg.org) beschrieben ist, konsentiert.
Cardiac Complications in 38 Cases of Kawasaki Disease with Coronary Artery Aneurysm Diagnosed by Echocardiography
Authors: Wei Ya Juan , Zhao Xiao Lan , Liu Bao Min , Niu Hua , Li Qian
Published: December 2015

Background

The long‐term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) is unclear. The aim of this study was to evaluate the complications of KD with CAAs.

Method

We retrospectively analyzed the clinical data and complications of 38 KD patients with CAAs who were treated and underwent regular follow‐up with echocardiography between January 1989 and May 2013.

Results

During a period of 29 days to 19 years after disease onset, complications seen included coronary stenosis and occlusion (six patients), thrombosis (17 patients), myocardial infarction (six patients), and calcification of CAAs (seven patients). Rupture of giant CAAs occurred in two patients and caused sudden death in one of these patients at 29 days and in the other patient at 5 months after disease onset. A total of seven deaths occurred, with five deaths caused by myocardial infarction. Three of these had undiagnosed incomplete KD or had not received regular treatment, while two experienced sudden death after several asymptomatic myocardial infarctions.

Conclusion

Cardiac complications of KD with CAAs include thrombosis, coronary stenosis, myocardial infarction, sudden death, and calcification. Although rare, rupture of giant CAAs is fatal and might occur earlier after the onset of disease. Mortality occurred primarily in the earlier cases when anticoagulant therapy was insufficient and in patients who did not receive regular treatment. Echocardiography can provide reliable information for assessing the progression and prognosis of this condition.
Smoldering multiple myeloma risk factors for progression: a Danish population‐based cohort study
Authors: Sørrig Rasmus , Klausen Tobias W. , Salomo Morten , Vangsted Annette J. , Østergaard Brian , Gregersen Henrik , Frølund Ulf Christian , Andersen Niels F. , Helleberg Carsten , Andersen Kristian T. , Pedersen Robert S. , Pedersen Per , Abildgaard Niels , Gimsing Peter ,   the Danish Myeloma Study Group
Published: December 2015

Several risk scores for disease progression in patients with smoldering multiple myeloma (SMM) have been proposed; however, all have been developed using single‐center registries. To examine risk factors for time to progression (TTP) to multiple myeloma (MM) for SMM, we analyzed a nationwide population‐based cohort of 321 patients with newly diagnosed SMM registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M‐protein ≥30 g/L and immunoparesis significantly influenced TTP (HR 2.7, 95%CI (1.5;4.7), P = 0.001, and HR 3.3, 95%CI (1.4;7.8), P = 0.002, respectively). High free light chain (FLC) ratio did not significantly influence TTP in our cohort. Therefore, our data do not support recent IMWG proposal of identifying patients with FLC ratio above 100 as having ultra high‐risk of transformation to MM. Using only immunoparesis and M‐protein ≥30 g/L, we created a scoring system to identify low‐, intermediate‐, and high‐risk SMM. This first population‐based study of patients with SMM confirms that an M‐protein ≥30 g/L and immunoparesis remain important risk factors for progression to MM.
Spanish consensus guidelines on prophylaxis with bypassing agents for surgery in patients with haemophilia and inhibitors
Authors: Mingot‐Castellano María Eva , Álvarez‐Román María Teresa , López‐Fernández María Fernanda , Altisent‐Roca Carmen , Canaro‐Hirnyk Mariana Isabel , Jiménez‐Yuste Víctor , Cid‐Haro Ana Rosa , Pérez‐Garrido Rosario , Sedano‐Balbas Carmen
Published: December 2015

Introduction

Patients with severe haemophilia and inhibitors against factor VIII who require surgery need a prophylactic approach to prevent bleeding complications. Scientific evidence to decide the best prophylactic treatment is very limited and mainly based on retrospective or case series.

Aims

To develop evidence‐ and expert opinion‐based guidelines for prophylactic therapy for patients with haemophilia and inhibitors undergoing surgery.

Methods

A panel of nine Spanish haematologists undertook a systematic review of the literature and selected publications providing relevant information regarding the prophylactic management of patients with haemophilia and inhibitors undergoing dental extraction, minor surgery or major surgery.

Results

Although evidence is very limited, the panel considers that it seems advisable that prophylaxis should be given in most cases with a bypassing agent (aPCC or rFVIIa) and should start immediately before minor or major surgery. Patients should be closely monitored to enable dose/product modification as needed.

Conclusion

It is necessary to communicate clinical experience in a detailed way in order to ensure optimal schemes of prophylaxis for patients with haemophilia and inhibitors. Development of objective outcomes to evaluate efficacy is crucial.
Qualitative muscle mass index as a predictor of skeletal muscle function deficit in Asian older adults
Authors: Chang Jae Seung , Kim Tae Ho , Kim Hanul , Choi Eun Hee , Kim Nahyun , Kong In Deok
Published: December 2015

Aim

The present cross‐sectional study was carried out among community‐dwelling Koreans to determine the validity of various muscle mass indices and to propose more clinically relevant diagnostic criteria.

Methods

This study measured the anthropometrics, body composition and physical capability of 415 older Koreans. Skeletal muscle indices were calculated by dividing appendicular lean mass by height or weight. Apart from this, we adjusted appendicular lean mass for body mass index, body surface area or waist‐to‐height ratio, which we then named the qualitative muscle mass index. Skeletal muscle function deficit was defined as a combination of weakness and slowness.

Results

Qualitative muscle indices were closely associated with physical capabilities. Receiver operating characteristic and logistic analyses showed that qualitative muscle indices had significantly greater discriminatory powers regarding low muscle function than did the height‐adjusted index in both men and women, and even showed higher discriminatory potentials than the weight‐adjusted index in men (all P < 0.05). The cut‐off values of qualitative muscle indices of body mass index‐, body surface area‐, and waist‐to‐height ratio‐adjusted indices for identifying functional deficits were 0.760, 11.40 and 34.18 for men, and 0.530, 8.91 and 23.07 for women, respectively.

Conclusions

The present study suggests that qualitative muscle indices are more accurate in predicting low muscle function than are height‐ and weight‐adjusted indices, because they consider anthropometric characteristics as part of the definition. The results might provide new avenues for conceptualizations of sarcopenia accompanied by obesity, and can be used as ethnic‐specific reference values of muscle mass indices based on functional outcome in an elderly Korean/Asian population. Geriatr Gerontol Int 2017; 17: 99–107.
Effect of oral cleaning using mouthwash and a mouth moisturizing gel on bacterial number and moisture level of the tongue surface of older adults requiring nursing care
Authors: Kobayashi Kenichiro , Ryu Masahiro , Izumi Sachi , Ueda Takayuki , Sakurai Kaoru
Published: December 2015

Aim

To evaluate the effect of oral cleaning using a mouthwash and a mouth moisturizing gel on the number of bacteria and moisture level of the tongue surface of older adults requiring nursing care.

Methods

The 60 participants were randomly divided into groups according to their use of oral cleaning procedures as follows: group 1, mouthwash and a moisturizing gel (M + m); group 2, mouthwash (M); group 3, water and a moisturizing gel (W + m); and group 4, water (W). The number of anaerobic bacteria, tongue coating index and moisture level of the tongue surface were measured at baseline, and after 1 and 2 weeks after cleaning commenced to compare the effectiveness of oral cleaning among the groups.

Results

There was no significant difference in baseline measurements among the groups. The numbers of anaerobic bacteria decreased for all groups, and there were significant differences in the rates of decrease after 2 weeks between the M + m and W + m groups, M + m and W groups, and M and W groups. The tongue coating index decreased for all groups. There was no significant difference in the rate of decrease among the groups after 1 week, and there was a significant difference after 2 weeks between the M + m and W groups. The moisture levels of all groups increased, and there were significant differences after 2 weeks between the M + m and M groups, the M + m and W groups, and the W + m and W groups.

Conclusion

The most effective cleaning technique was the combination of a mouthwash and a moisturizing gel. Geriatr Gerontol Int 2017; 17: 116–121.
Videoendoscopic evaluation of food bolus preparation: A comparison between normal adult dentates and older adult dentates
Authors: Matsuno Kohei , Nohara Kanji , Fukatsu Hikari , Tanaka Nobukazu , Fujii Nami , Sasao Yasuhiro , Sakai Takayoshi
Published: December 2015

Aim

Food bolus preparation plays an important role in swallowing food. The ability to carry out oral functions varies with age, and the same might be true of the ability to prepare food boluses. Previously developed methods for assessing food bolus preparation were not able to evaluate swallowed boluses; that is, the boluses were spat out before they were swallowed. The aim of the present study was to evaluate food bolus preparation in older adults using videoendoscopy, and to compare the food bolus preparation abilities of older adults and younger healthy adults.

Methods

The participants were 30 older adults and 30 younger healthy adults. None of the participants showed any symptoms of dysphagia or eating difficulties. In each examination, an endoscope was inserted into the nasal passage, and the participant was instructed to eat cooked rice. The grinding, mixing and aggregation of each bolus was graded from 0 to 2, with higher numbers indicating more marked grinding, mixing and aggregation. We simultaneously investigated the number of chewing cycles.

Results

The older adults showed higher grinding scores and lower mixing scores than the younger healthy adults. However, neither of these differences was significant. In contrast, the older adults showed significantly lower aggregation scores and carried out a significantly greater number of chewing cycles than the younger healthy adults.

Conclusions

Using videoendoscopy, we found that older adults showed lower aggregation scores and carried out a greater number of chewing cycles than younger healthy adults. These results suggest that older adults are less able to prepare food boluses than younger healthy adults. Geriatr Gerontol Int 2017; 17: 226–231.
Defining continuity of care from the perspectives of mental health service users and professionals: an exploratory, comparative study
Authors: Sweeney Angela , Davies Jonathon , McLaren Susan , Whittock Margaret , Lemma Ferew , Belling Ruth , Clement Sarah , Burns Tom , Catty Jocelyn , Jones Ian Rees , Rose Diana , Wykes Til
Published: December 2015

Background

Continuity of care (COC) is central to the organization and delivery of mental health services. Traditional definitions have excluded service users, and this lack of involvement has been linked to poor conceptual clarity surrounding the term. Consequently, very little is known about the differences and similarities in the conceptualization of COC by mental health service users and professionals.

Objective

To explore and compare mental health service users’ and professionals’ definitions of COC.

Methods

Using an exploratory, qualitative design, five focus groups with 32 service users each met twice. Data were analysed thematically to generate a service user‐defined model of COC. In a cross‐sectional survey, health and social care professionals (n = 184) defined COC; responses were analysed thematically. Service user and professional definitions were conceptually mapped and compared to identify similarities and differences.

Results

There was crossover between the service user and professional derived models of COC. Both contained temporal, quality, systemic, staff, hospital and needs‐related elements of COC. Service users prioritized access, information, peer support and avoiding services; health professionals most frequently referred to staff, cross‐sectional and temporal COC. Service users alone identified service avoidance, peer support and day centres as COC elements; professionals alone identified cross‐sectional working.

Conclusions

Important similarities and differences exist in service user and professional conceptualizations of COC. Further research is necessary to explore these differences, prior to integrating service user and professional perspectives in a validated COC framework which could enable the development and evaluation of interventions to improve COC, informing policy and practice.
Reappraisal of hMLH1 promoter methylation and protein expression status in the serrated neoplasia pathway
Authors: Lee Eun‐Jung , Chun Sung‐Min , Kim Mi‐Jung , Jang Se‐Jin , Kim Do Sun , Lee Doo Han , Youk Eui Gon
Published: December 2015

Aims

The aim of this study was to determine whether human mutL homologue 1 (hMLH1) inactivation precedes the progression of sessile serrated lesion (SSL) into SSL with cytological dysplasia (SSL/D) and to define the histological stage at which promoter methylation and inactivation of hMLH1 occur.

Methods and Results

Using the MassARRAY EpiTYPER assay and immunohistochemistry, we examined methylation levels and the protein expression status of hMLH1 in 33 SSL/Ds with conventional epithelial dysplasia and compared the results with those of control hyperplastic polyps (HPs) and SSLs. The methylation level of hMLH1 was higher in the dysplastic component than in the non‐dysplastic component of SSL/Ds (P = 0.005), and differed significantly with regard to the degree of dysplasia (P = 0.002). The methylation levels of hMLH1 in the dysplastic component of SSL/Ds tended to be higher than those of control SSLs and HPs (P = 0.063 and P = 0.017, respectively). The loss of hMLH1 protein expression was identified in only 13 of 33 (39.39%) dysplastic components of SSL/Ds.

Conclusion

Promoter methylation and loss of protein expression of hMLH1 are not parallel processes that occur concurrently. hMLH1 methylation is an early molecular event which occurs even in HP. However, the loss of hMLH1 expression is a much later step, found in approximately 40% of SSL/Ds at various histological stages. Notably, the loss of hMLH1 protein expression does not necessarily precede the development of cytological dysplasia in SSL.
Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta‐analysis
Authors: Xu Yang , Wang Wenling , Tian Yanli , Liu Jingyang , Yang Rongya
Published: December 2015

Background

Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc.

Methods

Case–control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI).

Results

Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta‐analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27–1.48, P < 0.00001) in the overall population. The presence of limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) scleroderma also showed a significant association with each of the genetic models (P < 0.00001). For IRF5 polymorphism, the T allele was shown to be strongly associated with increased SSc risk (OR = 1.27, 95% CI = 1.17–1.39, P < 0.00001). No significant heterogeneity between studies was found.

Conclusions

The results demonstrated that STAT4 rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc.
Malassezia species in healthy skin and in dermatological conditions
Authors: Prohic Asja , Jovovic Sadikovic Tamara , Krupalija‐Fazlic Mersiha , Kuskunovic‐Vlahovljak Suada
Published: December 2015

The genus Malassezia comprises lipophilic species, the natural habitat of which is the skin of humans and other warm‐blooded animals. However, these species have been associated with a diversity of dermatological disorders and even systemic infections. Pityriasis versicolor is the only cutaneous disease etiologically connected to Malassezia yeasts. In the other dermatoses, such as Malassezia folliculitis, seborrheic dermatitis, atopic dermatitis, and psoriasis, these yeasts have been suggested to play pathogenic roles either as direct agents of infection or as trigger factors because there is no evidence that the organisms invade the skin. Malassezia yeasts have been classified into at least 14 species, of which eight have been isolated from human skin, including Malassezia furfur, Malassezia pachydermatis, Malassezia sympodialis, Malassezia slooffiae, Malassezia globosa, Malassezia obtusa, Malassezia restricta, Malassezia dermatis, Malassezia japonica, and Malassezia yamatoensis. Distributions of Malassezia species in the healthy body and in skin diseases have been investigated using culture‐based and molecular techniques, and variable results have been reported from different geographical regions. This article reviews and discusses the latest available data on the pathogenicity of Malassezia spp., their distributions in dermatological conditions and in healthy skin, discrepancies in the two methods of identification, and the susceptibility of Malassezia spp. to antifungals.
Scanning electron microscopy of hair treated in hard water
Authors: Srinivasan Gautham , Chakravarthy Rangachari Srinivas
Published: December 2015

Background

Hardness of water is determined by the amount of calcium carbonate (CaCO3) and magnesium sulfate (MgSO4) dissolved in it. Hardness of water used for washing hair may damage the hair.

Objectives

The objective of this study is to observe the surface changes due to hard water usage and compare the thickness of hair between hard and soft water treated samples.

Methods

Ten to 15 hair strands of length 15–20 cm, which were lost during combing, were obtained from 15 healthy female volunteers. Each hair sample was cut into two equal halves to obtain two sets per volunteer. Each hair sample was wrapped around a glass rod. One set of 15 samples was washed with hard water, and the other set was washed with distilled water for 10 minutes on alternate days and air‐dried. This procedure was carried out for 30 days. The surface of hair treated in hard and soft water was examined under a scanning electron microscope.

Results

The CaCO3 and MgSO4 content of hard and distilled water samples were determined as 212.5 ppm of CaCO3 and 10 ppm of CaCO3 respectively. The mean calcium deposition in hard and distilled water treated hair was determined as 0.804% and 0.26%, respectively. The mean magnesium deposition in hard and distilled water treated hair was determined as 0.34% and 0.078%, respectively. The mean thickness of hair treated in hard water and distilled water were 72.78 and 78.14 μm, respectively.

Conclusion

The surface of hard water treated hair has a ruffled appearance with higher mineral deposition and decreased thickness when compared with the surface of distilled water treated hair.
Folliculotropic mycosis fungoides: clinical and epidemiological evaluation in a single center in Brazil
Authors: Deonizio Janyana M. D. , Ascef Rogers Diego , Sanches José Antonio
Published: December 2015

Background

Folliculotropic mycosis fungoides (FMF) is a rare variant of mycosis fungoides with clinical peculiarities, refractoriness to conventional treatments, and worse prognosis when compared to classic mycosis fungoides.

Objective

To evaluate the clinical and epidemiological characteristics of FMF patients in a single center in Brazil.

Methods

Data were retrospectively collected from patients with FMF who attended the Cutaneous Lymphoma Clinic, University of São Paulo Medical School, between 1987 and 2013.

Results

Thirty‐three patients were included (median age 46 years old at diagnosis; 20 male; 27 white). The median disease duration before diagnosis was 3 years. Regarding stage at diagnosis, 61% had advanced stage disease (≥IIb). Follicular papules were reported in 66% and alopecia in 59% of the cases. The most involved regions were limbs, followed by trunk and head. Pruritus was present in 81% of the patients. The median time of patients’ follow‐up was 38 months. At the last follow‐up visit, 67% of the patients were alive with active disease, 27% deceased, and 6% were in complete remission. Four patients had large cell transformation. At the time of diagnosis, 25% of the patients showed eosinophilia.

Limitations

Retrospective study with partial unavailable data.

Conclusions

The characteristics of our patients with FMF correlated with aspects previously described in the literature, which were at a more advanced stage at diagnosis and had a less favorable outcome. Pruritus is a very common complaint. Large cell transformation should be monitored as it is implicated in poor prognosis.
Antimelanogenic activity of a novel adamantyl benzylbenzamide derivative, AP736: a randomized, double‐blind, vehicle‐controlled comparative clinical trial performed in patients with hyperpigmentation during the summer
Authors: Jeong Yeon Su , Kim Jeong‐Hwan , Choi Joonho , Baek Heung Soo , Joo Yung Hyup , Lee Chang Seok , Shin Hong‐Ju , Park Young‐Ho , Kim Beom Joon , Shin Song Seok
Published: December 2015

Background/Purpose

AP736 is a novel compound with an adamantyl benzylbenzamide moiety that has shown antimelanogenic activity in melanocytes in vitro and in artificial skin equivalent through the inhibition of key melanogenic enzymes and suppression of the cAMP‐phosphokinase A‐cAMP response element‐binding protein signaling pathway. To estimate the clinical effectiveness of AP736 for the treatment of facial hyperpigmentation, we examined the efficacy and safety of a topical formulation containing AP736 compared with a vehicle formulation in human facial skin. To evaluate the degree of whitening when used in a real‐life situation, subjects with hyperpigmentation conditions were selected and the trial was performed from mid‐May to the end of June, when there are strong UV rays in Korea.

Materials and Methods

Forty‐eight healthy Korean women aged 20–60 years were enrolled in this study for 6 weeks. Women who were pregnant or undergoing any concurrent therapy were excluded. Subjects were instructed to apply a randomly assigned formulation containing 0.5% AP736 (test formulation; n = 24) or vehicle (vehicle control; n = 24) in addition to an assigned sunscreen with a twice‐daily application protocol. The degree of facial pigmentation was measured objectively using a Mexameter MX18 and Chromameter CM700, in addition to assessment by physicians using clinical photographs.

Results

The AP736 formulation was significantly (P < 0.05) more effective than the vehicle control formation in reducing the appearance of pigmentation at 3‐ and 6‐week follow‐up visits.

Conclusion

A formulation containing a novel skin whitening ingredient, AP736, effectively reduced pigmentation and was well tolerated by study subjects in summer season.
Effect of antipsoriatic therapy on oxidative stress index and sialic acid levels in patients with psoriasis
Authors: Rajappa Medha , Shanmugam Rathika , Munisamy Malathi , Chandrashekar Laxmisha , Rajendiran Kalai Selvi , Thappa Devinder Mohan
Published: December 2015

Background and objectives

Recent studies have implicated the association between oxidative stress and inflammation in pathogenesis of psoriasis and its associated comorbidities. Hence, we undertook to study inflammatory markers such as sialic acids and the oxidative stress index (OSI) in patients with psoriasis vulgaris.

Methods

Sixty cases and 60 healthy controls were included in this cohort study. Disease severity was assessed by psoriasis area severity index scoring. Serum levels of oxidative stress (total oxidant status, total antioxidant status) and inflammation (highly sensitive C‐reactive protein [hs‐CRP], total sialic acid, protein bound sialic acid) markers were estimated in controls and cases at baseline and on follow‐up. OSI was calculated as the ratio of total oxidant status to total antioxidant status.

Results

Baseline serum levels of OSI, hs‐CRP, and sialic acids were significantly higher in cases compared to controls. Baseline OSI and sialic acids demonstrated a significant correlation with disease severity. After 12 weeks of therapy, there was a significant decline in OSI and serum levels of hs‐CRP and sialic acids.

Conclusions

Our results demonstrate that oxidative stress and inflammation are significantly associated with psoriasis, and treatment with methotrexate results in a significant decline of both the inflammatory and oxidative stress parameters.
Policy Streams and Immigration to Russia: Competing and Complementary Interests at the Federal and Local Levels
Authors: Hofmann Erin Trouth , Carboni Julia L. , Mitchneck Beth , Kuznetsov Igor
Published: December 2015

This article uses Kingdon's Multiple Streams Framework to explain forms of national‐ and region‐level governance used in the Russian Federation to manage unprecedented levels of international immigration. First, we identify the ways that the Russian federal government has legislated and governed international migration from 1991 through 2010. We then compare the federal level to the case of the Krasnodar region, an ethnically diverse region in the North Caucasus. We find that that migration policy adoption in Russia at the federal level is relatively immune to economic trends or labour needs but more sensitive to foreign and domestic political objectives. At the regional level, local socio‐political and economic concerns predominate and political objectives are secondary. Finally, we argue that migration policy changes or adopted policy at the regional level may be explained by an interaction effect between changes in political leadership, federal level policy adoption, and regional level context.
The Fibulae of Ingvald Undset
Authors: Ahrens Sven
Published: December 2015

In 1882 Ingvald Undset (1853-1893) acquired a collection of 122 fibulae and fragments in Rome for the University Museum in Christiania. Very likely it was Undset who catalogued the pieces by grouping them according to typological principals. Fibulae were of particular importance for the studies of Undset and his circle of colleagues and friends, since that artefact group was used to develop typological method in archaeology. Fibulae were also considered an excellent tool for chronological deductions. At the same time some important Scandinavian museum exhibitions were rearranged according to new concepts: pieces of the same artefact groups were aligned together in typological sequences. The didactical possibilities provided by such a large collection of fibulae and the possibility to demonstrate typological method are likely to be the motives behind Undset’s purchase. The typology used in the catalogue shows very strong dependence on recent typological studies, particularly on Oscar Montelius article on Bronze Age fibulae. Despite some problems, which can be blamed on the very limited comparative literature of that time, Undset’s typological grouping of some Roman fibulae show his sure instinct for the definition of new types. A publication of his results would have made a useful contribution to the knowledge of Roman fibulae of that time.
Transmembrane domain is crucial to the subcellular localization and function of Myc target 1
Authors: Wu Shuai , Gui Jinghua , Yin Xiaofei , Pan Qiang , Liu Xinyuan , Chu Liang
Published: December 2015

Deregulation of c‐MYC occurs in a variety of human cancers. Overexpression of c‐MYC promotes cell growth, proliferation, apoptosis, transformation and genomic instability. MYC target 1 (MYCT1) is a direct target gene of c‐MYC, and its murine homologue MT‐MC1 recapitulated multiple c‐Myc‐related phenotypes. However, the molecular mechanism of MYCT1 remains unclear. Here, we identified the transmembrane (TM) domain of MYCT1, not the nuclear localization sequence, is indispensable to the vesicle‐associated localization of MYCT1 protein in the cytoplasmic membrane vesicle. Overexpression of MYCT1, not MYCT1 (ΔTM), decreased cell viability under serum deprivation and increased tumour cell migration ability. We further identified CKAP4 interacted with MYCT1 and contributed to the function of MYCT1. In addition, we found that a mutation, A88D, which is observed in patient sample, changed the localization, and abolished the effect on cell viability and cell migration, suggesting that the TM domain is critical to MYCT1.
Antimicrobial photodynamic therapy as an alternative to systemic antibiotics: results from a double‐blind, randomized, placebo‐controlled, clinical study on type 2 diabetics
Authors: Ramos Umberto D. , Ayub Lauro G. , Reino Danilo M. , Grisi Márcio F.M. , Taba Mário , Souza Sérgio L.S. , Palioto Daniela B. , Novaes Arthur B.
Published: December 2015

Aim

This double‐blind, placebo‐controlled clinical study compared multiple applications of the antimicrobial photodynamic therapy (aPDT) treatment protocol, to systemic doxycycline as adjuvant to scaling and root planing (SRP) on type 2 diabetic patients on clinical, systemic and immune‐inflammatory outcomes.

Materials and Methods

Thirty patients with Hba1c >7% were allocated in two groups, SRP + Doxy (n = 15) using systemic doxycycline 100 mg/day (14 days) and SRP + aPDT (n = 15) with multiple applications (0, 3, 7 and 14 days). Primary outcome was glycated haemoglobin levels (HbA1c). Clinical parameters: plaque score (PS), bleeding on probe, probing depth, suppuration, gingival recession, and clinical attachment level, percentage of pockets with desired clinical endpoint were measured at baseline and 3 months after therapy. Cytokine profile was assessed at 0, 1 and 3 month to measure IL1‐β, TNF‐α and TGF‐β on gingival crevicular fluid.

Results

No significant difference was detected on HbA1c, between treatments. The SRP + aPDT group showed advantage on reducing moderate pockets in single‐rooted teeth at 3 months. SRP + aPDT presented better results at 3 months on IL1‐β levels. There were no significant differences between TNF‐α and TGF‐β.

Conclusions

Both treatments improved clinical and systemic outcomes (Hba1c). SRP + aPDT performed better in moderate probing pocket depth on single‐rooted teeth, reduced favourably inflammation in short term, and may be an alternative to systemic antibiotics. (Clinicaltrials.org ID NCT01595594).
Telomere length and periodontal attachment loss: a prospective cohort study
Authors: Thomson William Murray , Zeng Jiaxu , Broadbent Jonathan M. , Foster Page Lyndie A. , Shalev Idan , Moffitt Terrie E. , Caspi Avshalom , Williams Sheila M. , Braithwaite Antony W. , Robertson Stephen P. , Poulton Richie
Published: December 2015

Aim

The aim of the study was to examine the association between telomere erosion and periodontitis in a long‐standing prospective cohort study of New Zealand adults. Specific hypotheses tested were as follows: (i) that exposure to periodontitis at ages 26 and 38 was associated with accelerated leucocyte telomere erosion and (ii) that accelerated leucocyte telomere erosion was associated with higher rates of periodontitis by ages 26 and 38.

Materials and Methods

Periodontal attachment loss data were collected at ages 26 and 38. Blood samples taken at the same ages were analysed to obtain estimates of leucocyte telomere length and erosion over a 12‐year period.

Results

Overall, the mean telomere length was reduced by 0.15 T/S ratio (adjusted) from age 26 to 38 among the 661 participants reported on here. During the same period, the mean attachment loss increased by 10%, after adjusting for sex, socio‐economic status and smoking. Regression models showed that attachment loss did not predict telomere length, and that telomere erosion did not predict attachment loss.

Conclusions

Although both periodontitis and telomere length are age‐dependent, they do not appear to be linked, suggesting that determination of leucocyte telomere length may not be a promising clinical approach at this age for identifying people who are at risk for periodontitis.