bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Durability of a Diaphragm for a Total Artificial Heart
Authors: Gräf Felix , Rossbroich Ralf , Finocchiaro Thomas , Steinseifer Ulrich
Published: December 2015

One of the most critical components regarding the durability of the ReinHeart total artificial heart (TAH) is its biocompatible diaphragm, which separates the drive unit from the ventricles. Hence, a durability tester was designed to investigate its required 5‐year lifetime. The aim of this study was to prove the validity of accelerated testing of the polyurethane diaphragm. The durability tester allows simultaneous testing of 12 diaphragms and mimics physiological conditions. To accelerate the time of testing, it operates with an increased speed at a frequency of 8 Hz. To prove the correctness of this acceleration, a servo‐hydraulic testing machine was used to study the effect of different frequencies and their corresponding loads. Thereby the viscoelastic behavior of the polyurethane was investigated. Additionally, high‐speed video measurements were performed. The force against frequency and the high‐speed video measurements showed constant behavior. In the range of 1–10 Hz, the maximum resulting forces varied by 3%, and the diaphragm movement was identical. Frequencies below 10 Hz allow a valid statement of the diaphragm's mechanical durability. Viscoelasticity of the polyurethane in the considered frequency‐range is negligible. The accelerated durability test is applicable to polyurethane diaphragms, and the results are applicable to TAH use. The reliability of the diaphragm for a lifetime of 5 years was found to be 80% with a confidence of 62%.
Optimal Vagus Nerve Stimulation Frequency for Suppression of Spike‐and‐Wave Seizures in Rats
Authors: Jiao Jianhang , Harreby Kristian R. , Sevcencu Cristian , Jensen Winnie
Published: December 2015

Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug‐resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10–30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike‐and‐wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9–21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130–180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today.
Towards a trans‐disciplinary methodology for a game‐based intervention development process
Authors: Arnab Sylvester , Clarke Samantha
Published: December 2015

The application of game‐based learning adds play into educational and instructional contexts. Even though there is a lack of standard methodologies or formulaic frameworks to better inform game‐based intervention development, there exist scientific and empirical studies that can serve as benchmarks for establishing scientific validity in terms of the efficacy of using games to achieve serious outcomes. The development of these games does not normally follow a specific set of guidelines, which limits replication. There is a need to reflect on such a multidisciplinary process and infuse knowledge from relevant disciplines towards developing a unity of considerations and approaches beyond the disciplinary perspectives. An infused and trans‐disciplinary methodological framework could serve as a guideline to inform the development process of a game‐based approach. With these perspectives, this paper aims to provide an example of how relevant theories and frameworks can be adopted collectively in order to inform a development process. Based on a digital game intervention aiming to support the delivery of Relationships and Sex Education (RSE) in the UK, this paper reflects on trans‐disciplinary considerations, informed by frameworks such as the Four‐Dimensional Framework (4DF), the Intervention Mapping (IM) approach, Mechanics Dynamics Aesthetics model (MDA) and Learning Mechanics‐Game Mechanics (LM‐GM) mapping. IM, when infused with the game design considerations of 4DF, provides a more procedural perspective to game‐based intervention development, collectively reflecting a participatory development approach. This subsequently provides the basis upon which other theoretical and methodological frameworks such as the MDA and the LM‐GM models can be embedded in order to marry the pedagogical aspects with the entertainment attributes of gameplay. These components, when integrated, may formulate a trans‐disciplinary model that can be adopted and adapted by other researchers, designers and developers.
Immunotherapy of melanoma: efficacy and mode of action
Authors: Wieder Thomas , Brenner Ellen , Braumüller Heidi , Röcken Martin
Published: December 2015

Forty years of research have brought about the development of antibodies that induce effective antitumor immune responses through sustained activation of the immune system. These “immune checkpoint inhibitors” are directed against immune inhibitory molecules, such as cytotoxic T lymphocyte antigen 4 (CTLA‐4), programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1). Disruption of the PD‐1/PD‐L1 interaction improves the intermediate‐term prognosis even in patients with advanced stage IV melanoma. One and a halfyears after treatment initiation, 30–60 % of these patients are still alive. While cancer immunotherapies usually do not eradicate metastases completely, they do cause a regression by 20–80 %. It is well established that the immune system is able to kill tumor cells, and this has also been demonstrated for immunotherapies. Preclinical data, however, has shown that anti‐cancer immunity is not limited to killing cancer cells. Thus, through interferon gamma and tumor necrosis factor, the immune system is able to induce stable tumor growth arrest, referred to as senescence. Ensuring patient survival by long‐term stabilization of metastatic growth will therefore become a central goal of antitumor immunotherapies. This therapeutic approach is effective in melanoma and non‐small‐cell lung cancer. Once immunotherapies also have an indication for common cancer types, drug prices will have to drop considerably in order to be able to keep them available to those dependent on such therapies.
Hand dermatitis – differential diagnoses, diagnostics, and treatment options
Authors: Mahler Vera
Published: December 2015

The pathogenesis of hand dermatitis is multifactorial, and includes factors such as genetic predisposition and exposure. A high incidence rate is associated with female gender, contact allergy, atopic dermatitis, and wet work. The most important risk factors for the persistence of hand dermatitis include its extent, contact allergic or atopic etiology, childhood dermatitis, and early onset (before the age of 20). The cost of illness of hand dermatitis corresponds to this seen in moderate to severe psoriasis.

The diagnostic workup of hand dermatitis and its differential diagnoses requires a detailed assessment of occupational and recreational exposure. In case of possible work‐related triggers, early notification of the accident insurer should be sought (via the dermatologist's report). Exposure to a contact allergen is a contributing factor in one‐half of all cases of hand dermatitis. It is therefore imperative that all patients with hand dermatitis persisting for more than three months undergo patch testing.

Successful and sustainable treatment of hand dermatitis starts with the proper identification and elimination of individual triggers, including the substitution of identified contact allergens and irritants, as well as optimizing preventive measures. Graded therapy taking the clinical severity into account is essential. Validated instruments may be used to monitor therapeutic efficacy.
Retrospektive Datenerhebung der Psoriasis‐Behandlung mit Fumarsäureestern bei Kindern und Jugendlichen in Deutschland (KIDS FUTURE‐Studie)
Authors: Reich Kristian , Hartl Christoph , Gambichler Thilo , Zschocke Ina
Published: December 2015

Hintergrund

Mit dieser nicht‐interventionellen, multizentrischen, retrospektiven Studie sollten Wirksamkeits‐ und Sicherheitsdaten zu Fumarsäureestern (FSE) in der systemischen Langzeittherapie der Psoriasis vulgaris bei Kindern und Jugendlichen erhoben werden, da es in dieser Patientengruppe bisher keine systemische Standardtherapie gibt.

Patienten und Methodik

Wirksamkeits‐ und Sicherheitsdaten von Patienten < 18 Jahre bei Therapiebeginn mit FSE wurden mindestens 36 Monate retrospektiv erhoben.

Ergebnisse

Von 127 Patienten (Alter 6–17 Jahre) wurden Daten von bis zu 60 Monaten Behandlungsdauer erfasst. Physician's Global Assessment, Psoriasis Area and Severity Index und Body Surface Area haben sich in den ersten 6 Monaten deutlich verbessert. Nach 36 Monaten zeigten sich Verbesserungen dieser Parameter um durchschnittlich bis zu zwei Drittel des Ausgangswertes. Bei 37 Patienten wurde mindestens ein unerwünschtes Ereignis (UE) berichtet, bei 36 Patienten im Zusammenhang mit FSE‐Therapie. Drei UEs (Proteinurie, zweimal Flush) waren im Beobachtungszeitraum unter Therapie anhaltend. Fünfzehn UEs führten zum Behandlungsabbruch; in fast allen Fällen waren dies gastrointestinale Beschwerden.

Schlussfolgerungen

Die KIDS FUTURE‐Studie erfasst erstmals eine größere Population Kinder und Jugendlicher mit Psoriasis, die mit FSE therapiert wurden. Diese Daten legen nahe, dass eine Langzeittherapie mit FSE bei der Behandlung dieser Patientengruppe wirksam und sicher sein kann. In einer derzeit laufenden klinischen Prüfung werden diese Erkenntnisse validiert.
Eine Untersuchung von Faktoren, die mit der gesundheitsbezogenen Lebensqualität und der psychologischen Belastung bei Vitiligo verbunden sind
Authors: Bonotis Konstantinos , Pantelis Konstantinos , Karaoulanis Sokratis , Katsimaglis Chrysanthos , Papaliaga Maria , Zafiriou Efterpi , Tsogas Panagiotis
Published: December 2015

Hintergrund und Ziele

Hautkrankheiten stören das Körperbild und können negative Auswirkungen auf die Lebensqualität und die psychosoziale Gesundheit von Patienten haben. Vitiligo beeinflusst zwar nicht das physische Wohlbefinden, kann aber psychologisch belastend sein. Die vorliegende Untersuchung basiert auf der Hypothese, dass bestimmte Faktoren kritisch für die Anpassung an die Krankheit sein könnten.

Patienten und Methoden

Wir untersuchten bei 216 Patienten die Vitiligo‐bedingt veränderte Lebensqualität und psychische Belastung im Verhältnis zu demographischen Faktoren, Krankheitskomponenten und Persönlichkeitsmerkmalen. Zu diesem Zweck wendeten wir die vom Patienten selbst auszufüllenden Fragebogen Dermatological Quality of Life Index, General Health Questionnaire, Eysenck Personality Inventory und Rosenberg Self‐Esteem Scale an.

Ergebnisse

Die statistische Analyse ergab eine positive Korrelation zwischen der Belastung der Patienten und der gesundheitsbezogenen Lebensqualität. Darüber hinaus bestand eine signifikante Assoziation zwischen dem Einfluss der Vitiligo auf die Lebensqualität und Krankheitsvariablen sowie Persönlichkeitsmerkmalen und dem Geschlecht. Andererseits war die psychologische Belastung signifikant mit Persönlichkeitsmerkmalen und dem Geschlecht assoziiert, nicht aber mit Krankheitskomponenten.

Schlussfolgerungen

Unsere Ergebnisse weisen darauf hin, dass die psychosoziale Anpassung an die Krankheit vor allem durch subjektive Faktoren beeinflusst wird. Dies könnte bedeuten, dass bei der Behandlung der Vitiligo gezielte unterstützende Interventionen erforderlich sind.
Enamel organ proteins as targets for antibodies in celiac disease: implications for oral health
Authors: Sóñora Cecilia , Arbildi Paula , Rodríguez‐Camejo Claudio , Beovide Verónica , Marco Alicia , Hernández Ana
Published: December 2015

Enamel defects in permanent and deciduous teeth may be oral manifestations of celiac disease. Sometimes they are the only sign that points to this underdiagnosed autoimmune pathology. However, the etiology of these specific enamel defects remains unknown. Based on previously reported cross‐reactivity of antibodies to gliadin with the enamel proteins, amelogenin and ameloblastin, we analyzed (using immunohistochemistry) the ability of anti‐gliadin IgG, produced during untreated disease, to recognize enamel organ structures. We used swine germ teeth as a tissue model because they are highly homologous to human teeth in terms of proteins and development biology. Strong staining of the enamel matrix and of the layer of ameloblasts was observed with serum samples from women with celiac disease; high IgG reactivity was found against both gliadin peptides and enamel matrix protein extract, but there was no IgG reactivity against tissue antigens. In line with these findings, the gamma globulin fraction from gliadin‐immunized BALB/c mice showed a similar staining pattern to that of amelogenin‐specific staining. These results strongly suggest a pathological role for antibodies to gliadin in enamel defect dentition for both deciduous and permanent teeth, considering that IgG can be transported through the placenta during fetal tooth development.
Proximal suspensory desmopathy in hindlimbs: A correlative clinical, ultrasonographic, grosspost mortemand histological study
Authors: Dyson S. , Murray R. , Pinilla M.‐J.
Published: December 2015

Reasons for performing study

It has been suggested that ultrasonography is unreliable for the detection of hindlimb proximal suspensory desmopathy (PSD) based on comparisons between ultrasonographic and magnetic resonance images.

Objectives

To compare ultrasonography with gross and histopathologicalpost mortemexamination in horses withPSDdiagnosed based on ultrasonography and control horses.

Study design

Retrospective descriptive study.

Methods

Part 1: 19 horses with hindlimbPSDand 10 control horses were humanely destroyed. Twenty control limbs and 37 lame limbs were examined grossly and 40 suspensory ligaments (SLs) were examined histologically and graded blindly. Part 2: 3 horses with recurrent lameness after surgical management ofPSDand 4 withPSDwere assessed ultrasonographically and by grosspost mortemexamination.

Results

Part 1: ultrasonographic lesions were graded moderate in 31/38 (81.6%) and severe in 7/38 (18.4%) lame limbs; in 4/37 (10.8%) limbs adhesion formation between the proximal aspect of theSLand the accessory ligament of the deep digital flexor tendon was predicted. Grosspost mortemand histological examinations of control limbs revealed no abnormalities. Grosspost mortemexamination revealed substantial adhesions between the proximal aspect of theSLand adjacent soft tissues in 10/37 (27.0%) lame limbs; in 10/37 (27.0%) limbs there were adhesions between the body of theSLand the mid plantar aspect of the third metatarsal bone, extending distally in 6 (16.2%) limbs. Histology revealed abnormalities (grades 1–3) of the collagenous tissue in 25/36 (69.4%) limbs; muscle was abnormal (grades 1–3) in 35/36 (97.2%) limbs and adipose tissue (grades 1–3) in 16/36 (44.4%) limbs. Part 2: adhesions between theSLand adjacent soft tissues were predicted ultrasonographically and confirmedpost mortem.

Conclusions

Ultrasonography was reliable for the detection ofSLpathology based on histology as the gold standard. Adhesions may be a reason for recurrent lameness after surgery.
Interpreting Variations in Groundwater Flows from Repeated Distributed Thermal Perturbation Tests
Authors: Hausner Mark B. , Kryder Levi , Klenke John , Reinke Richard , Tyler Scott W.
Published: December 2015

To better understand the groundwater resources of southern Nye County, Nevada, a multipart distributed thermal perturbation sensing (DTPS) test was performed on a complex of three wells. These wells penetrate an alluvial aquifer that drains the Nevada National Security Site, and characterizing the hydraulic properties and flow paths of the regional groundwater flow system has proven very difficult. The well complex comprised one pumping well and two observation wells, both located 18 m from the pumping well. Using fiber‐optic cables and line heaters, DTPS tests were performed under both stressed and unstressed conditions. Each test injects heat into the water column over a period of one to two days, and observes the rising temperature during heat injection and falling temperatures after heating ceases. Aquifer thermal properties are inferred from temperature patterns in the cased section of the wells, and fluxes through the 30‐m screened section are estimated based on a model that incorporates conductive and advective heat fluxes. Vertical variations in flux are examined on a scale of tens of cm. The actively flowing zones of the aquifer change between the stressed and unstressed test, and anisotropy in the aquifer permeability is apparent from the changing fluxes between tests. The fluxes inferred from the DTPS tests are compared to solute tracer tests previously performed on the same site. The DTPS‐based fluxes are consistent with the fastest solute transport observed in the tracer test, but appear to overestimate the mean flux through the system.
A Survey of the Influencing Factors for International Academic Mobility of Chinese University Students
Authors: Cao Chun , Zhu Chang , Meng Qian
Published: December 2015

This research aims to understand the factors influencing international academic mobility within the Chinese higher education context. The inventory of University Students’ Perceptions of Influencing Factors for International Academic Mobility was developed and tested to enquire about Chinese university students’ perceptions of factors influencing their decisions on international academic mobility. The findings reveal that ‘mobility cost’, ‘quality of host institutions’, ‘future career prospects’, ‘financial aid and employment rate and income in host country’ play leading roles in international academic mobility. Important differences were identified in ‘gender’, ‘major‐ and family‐education background’. Hierarchical multiple regression analysis was conducted to predict the interest in mobility from the external factors. The results indicated that ‘future career prospects’, ‘quality of host institutions’, ‘mobility cost’ and ‘climate environment in host country’ emerged as significant favourable pull factors for Chinese university students' interest in mobility. ‘Geographical distance’ emerged as a significant unfavourable pull factor. ‘Impact from parents’ and ‘language and intercultural training of home institutions’ emerged as favourable push factors. ‘Economic situation of home country’ emerged as an unfavorable push factor.
The risk of malignancy or progression of existing malignancy in patients with psoriasis treated with biologics: case report and review of the literature
Authors: Patel Shailee , Patel Tejas , Kerdel Francisco A.
Published: December 2015

There is some debate regarding the risk of developing malignancy and progression of malignancy in patients with psoriasis treated with biologics. The lack of extensive, long‐term, and large studies, including patients with psoriasis, to assess these aforementioned risks makes it difficult to ascertain the safety profile of biologic therapy in these patients. Several studies do support the favorability of the safety profile of biologics in patients with psoriasis in terms of the risk of developing malignancy. A few studies include patients with a previous history of cancer that were thereafter treated with biologics and show no increased risk of recurrence in those treated with biologics compared to non‐biologic therapy. Although recent studies do not show an increased risk of new or recurrent malignancy in patients with psoriasis treated with biologic agents, there is still hesitancy in the widespread use of biologic agents in these patients. Considering all of the current data and opinions, the benefits of biologic therapy to improve quality of life often outweigh the negligible risk of solid organ malignancy associated with biologics in patients with existing or previous malignancies. Coordinating the management of patients that develop or have a history of previous malignancy with an oncology team is crucial for patient‐centered care until clear evidence‐based guidelines are developed.
Prevalence and clinical features of pigmented oral lesions
Authors: Hassona Yazan , Sawair Faleh , Al‐karadsheh Omar , Scully Crispian
Published: December 2015

Background

To examine the relative prevalence, types, and clinical features of pigmented lesions of the oral mucosa in 1275 patients attending a university hospital for dental care.

Methods

Patients attending dental clinics at The University of Jordan Hospital over a 1‐year period were examined for the presence of oral pigmentations. Histopathological examination was performed on focally pigmented lesions with a suspicious or uncertain clinical diagnosis.

Results

A total of 386 (30.2%) patients were found to have oral pigmentations. Of these, racial pigmentation (39.9%) and smokers' melanosis (32.9%) were the most common causes of oral pigmentations. Other causes included amalgam tattoo (18.9%), focal melanotic macules (5.7%), postinflammatory pigmentation (1.6%), pigmentation due to medications or systemic disease (0.52%), heavy metal deposits (0.26%), and oral nevus (0.26%). Gingivae and buccal mucosae were the most common sites for oral pigmentations.

Conclusion

Pigmentations of the oral mucosa are common. Gingivae and buccal mucosae are the most common sites for oral pigmentations. Proper history and recognition of clinical features are important for effective management.
Literature‐based immunization recommendations for patients requiring immunosuppressive medications for autoimmune bullous dermatoses
Authors: Laniosz Valerie , Lehman Julia S. , Poland Gregory A. , Wetter David A.
Published: December 2015

Autoimmune bullous diseases, such as pemphigus, pemphigoid, and dermatitis herpetiformis, are uniquely associated with vulnerability in the mucocutaneous barrier against infection. The management of immunobullous diseases is complex and may at times require immunosuppressive medications. Iatrogenic immunosuppression may increase susceptibility to vaccine‐preventable illnesses. Currently, there are no guidelines to assist the clinician treating patients with immunobullous disease regarding the delivery of various vaccinations. The aim of this review is to provide recommendations for immunization in the unique setting of immunobullous disease. Recommendations are based on careful review of the literature in other conditions requiring iatrogenic immunosuppression, as well as the most recent Centers for Disease Control and Prevention guidelines. Immunization with nonlive vaccines appears to be a safe and effective strategy for preventing infection in the particularly susceptible patient with immunobullous disease. Opportunities for live vaccine administration may become available at lower levels of immune suppression or during clinical remission when immunosuppressive regimens can be reduced. Anticipatory vaccination before the initiation of iatrogenic immunosuppression is ideal. Although immunologic response to vaccination may be suboptimal during immunosuppression, nonlive vaccination is strongly recommended for this patient population.
Serum level of receptor activator of nuclear factor kappa‐B ligand in patients with psoriasis
Authors: Amin Tarek E. , ElFar Nashwa N. , Ghaly Nahla R. , Hekal Mona M. , Hassan Azza M. , Elsaadany Hanan M.
Published: December 2015

Background

Psoriasis usually precedes the onset of psoriatic arthritis by an average of 10 years in about 70% of patients. Receptor activator of nuclear factor kappa‐B ligand (RANKL) is a natural and necessary surface‐bound molecule, which is a ligand for osteoprotegrin and functions as a key factor for osteoclast differentiation and activation.

Objective

Evaluation of the serum level of RANKL in psoriasis and psoriatic arthritis and its correlation with severity of the disease as a trial to predict the occurrence of psoriatic arthritis in such patients.

Method

This study included 80 subjects; 40 patients had chronic plaque psoriasis, 20 patients had chronic plaque psoriasis with psoriatic arthritis, and 20 were healthy controls. Patients with psoriasis were divided into three subgroups according to psoriasis area severity index score: mild, moderate, and severe. Serum RANKL levels were estimated for all subjects using enzyme‐linked immunosorbent assay.

Results

Serum RANKL level in psoriatic arthritis was significantly higher compared to both patients with plaque psoriasis and control groups. Serum RANKL level significantly correlated to the severity of psoriasis, with a very high correlation coefficient in groups I and II. The diagnostic performance of serum RANKL level for the early prediction of psoriatic arthritis in patients with psoriasis was >170 pg/ml.

Conclusion

Serum RANKL level could be considered as a useful diagnostic marker for the early prediction of psoriatic arthritis in patients with moderate and severe psoriasis. Assessment of soluble RANKL in psoriasis could identify those at increased risk for psoriatic arthritis, and anti‐RANKL agents may be effective in decreasing incidence of psoriatic arthritis.
Learning from mistakes: errors in approaches to melanoma and the urgent need for updated national guidelines
Authors: Simionescu Olga , Blum Andreas , Grigore Mariana , Costache Mariana , Avram Alina , Testori Alessandro
Published: December 2015

Background

The tracking and identification of errors in the detection and follow‐up of melanoma are important because there is huge potential to increase awareness about the most vulnerable aspects of diagnosis and treatment, and to improve both from the perspective of healthcare economics. The present study was designed to identify where errors occur and to propose a minimum set of rules for the routine guidance of any specialist in melanoma management.

Methods

This report describes the evaluation of a unique series of 33 cases in which errors applying to many steps in the diagnosis and treatment of melanoma were detected. Cases were collected at two centers in Romania, one public and one private, as part of a process of obtaining patient‐requested second opinions.

Results

A total of 166 errors were identified across the 33 patients, most of which were treatment errors. The errors fell into six categories: clinical diagnostic errors (36 errors among 30 patients); primary surgical errors (31 errors among 16 patients); pathology errors (24 errors among 17 patients); sentinel lymph node biopsy errors (13 errors among 13 patients); staging errors (17 errors among 13 patients); and treatment or management errors (45 errors among 33 patients).

Conclusions

Based on the present results, we propose that in countries lacking national guidelines, clinicians should adhere to international evidence‐based guidelines for the diagnosis and treatment of melanoma.
Non‐invasive method distinguishes chronic telogen effluvium from mild female pattern hair loss: clinicopathological correlation
Authors: Bittencourt Caroline , Teixeira Fernanda , Ferraro Daniela A. , Soares Tania C.B. , Moraes Aparecida M. , Cintra Maria L.
Published: December 2015

Background

The distinction between chronic telogen effluvium (CTE) and female pattern hair loss (FPHL) is important because of their different prognosis and treatment. Non‐invasive methods have been described to be useful in differentiatingFPHLfromCTE. This prospective study investigated the use of the washing method to differentiateCTEfrom mildFPHL.

Methods

Twenty patients withCTEand 17 withFPHLwere recruited and followed for 18 months. The diagnosis was established through clinical, laboratory, and histological studies. The patients were asked to abstain from washing their hair for 5 days and then shampoo and collect all hair shed in the process. Hair shafts were then counted and divided into two groups: up to 3 cm in length or longer.

Results

In theCTEgroup, the mean hair count was high (438), and in all cases, <10% were short. In patients withFPHL, the mean count was not as high (215) and in only one patient, short hairs comprised <10% of the total. The greater the number of long hairs, the higher was the density of terminal follicles seen histologically. TheCTEgroup presented a greater number of patients with serum iron values <70 μg/dl. Ferritin levels ranged from 6.98 to 128.33, average of 66.65 (CTE), and 16.5–304.8, average of 114.97 ng/ml (FPHL), but no significant differences were found.

Conclusion

The washing test can be useful to avoid biopsy procedures. Iron serum levels are possibly an additional parameter that may improveCTEdiagnosis if combined with an earlier test.
Morphology and environment in some fossil Hominoids and Pedetids (Mammalia)
Authors: Senut Brigitte
Published: December 2015

Linking the environment to functional anatomy is not an easy exercise, especially when dealing with fossils, which are often fragmentary and represent animals that are extinct. A holistic approach permits us to fill the gaps in reconstructing the evolutionary patterns in fossil groups. Identifying the environment where animals lived can help to interpret some anatomical structures and, vice versa, the functional morphological pattern can help to refine some fossil environments. Two examples focusing on locomotor behaviours in fossil mammals are considered in this paper: the hominoids and the origins of hominid bipedalism and the springing adaptations in fossil rodents (Pedetidae) in connection with different habitats. In the first case, the limits of the chimp‐based models and the necessity to take into account detailed environmental reconstructions will be addressed. The famous ‘savannah hypothesis’ is no longer tenable because the palaeontological data support a more vegetated environment for the origins of bipedal hominids. Data from the environment will be considered. The earliest putative hominid fossils which preserve skeletal remains of the locomotor apparatus show mixed adaptations to terrestrial bipedalism and arboreal activities. The second example focuses on the variation in springing adaptations in Pedetidae in the Lower Miocene of East Africa and Southern Africa. In the East, the sites where Pedetidae were preserved were mainly forested, whereas in the South the region was more open and drier, with extensive grassy patches. In the first case, pedetids were robust and heavy jumpers, whereas in the South they were smaller, their skeleton more gracile and their springing was lighter. During the desertification of the southern part of Africa, the large pedetid species became extinct, but a smaller species developed. In the case of primates, as in the case of rodents, the skeletal morphology was adapted to its environment.
Impact of mode of delivery after 32 weeks’ gestation on neonatal outcome in dichorionic diamniotic twins
Authors: Soong Stephen , Greer Ristan M. , Gardener Glenn , Flenady Vicki , Kumar Sailesh
Published: December 2015

Aim

The purpose of this study was to investigate neonatal outcome of dichorionic diamniotic twins born beyond 32 weeks’ gestation according to mode of delivery at a major tertiary center in Australia.

Methods

This was a retrospective cohort study of women with dichorionic diamniotic twins delivering at ≥32 weeks’ gestation at a large tertiary maternity center in Australia using data from a maternity database. Primary and secondary outcomes included mode of delivery, birthweight, stillbirth, Apgar score, neonatal unit admission, neonatal resuscitation, death and respiratory distress.

Results

Of 1261 women, 82.9% (1045/1261; 2090 babies) delivered at ≥32 weeks’ gestation. The mode of delivery for these babies was as follows: normal vaginal delivery, 419 (20%); instrumental delivery, 179 (8.6%); emergency cesarean section, 658 (31.5%); and elective cesarean section, 834 (39.9%). Babies delivered by emergency cesarean section or instrumental vaginal delivery had worse outcome. In contrast, the lowest complications were seen in the uncomplicated vaginal delivery and elective cesarean section cohorts.

Conclusions

Neonatal outcome was worse for those delivering via emergency cesarean section or instrumental vaginal delivery compared with elective cesarean section or uncomplicated vaginal delivery. The rate of uncomplicated vaginal delivery, however, was low, with only 14.8% of women delivering both babies vaginally without any form of intervention.
Informing health policy in Japan: A mixed‐model estimation to compare the cost of illness of cervical cancer and endometrial cancer
Authors: Hayata Eijiro , Seto Kanako , Kitazawa Takefumi , Matsumoto Kunichika , Morita Mineto , Hasegawa Tomonori
Published: December 2015

Aim

The objective of this study was to inform Japanese health policy by comparing cervical cancer and endometrial cancer from the standpoint of economic burden and examining factors affecting future changes in economic burden.

Methods

Using government‐based nationwide statistical data, we used the cost‐of‐illness (COI) method to estimate the COI from 1996 to 2011 and predicted future estimates for 2014, 2017, and 2020.

Results

In 2011, the COI of cervical cancer was estimated at 159.9 billion yen and that of endometrial cancer was estimated at 99.5 billion yen. Assuming the current trends in health‐related indicators, the COI of cervical cancer is predicted to temporarily decrease in 2014 and then remain constant. Meanwhile, the COI of endometrial cancer is predicted to temporarily decrease in 2014 before returning to an upward trend.

Conclusion

The COI of both cervical cancer and endometrial cancer is estimated to remain constant or increase in the future. The average age of death from cervical cancer is predicted to remain relatively young and the high human capital value of patients who die in their sixties is the most likely explanation for the lack of decrease in future COI. As women's participation in society continues to increase, the future COI may also increase. Regarding endometrial cancer, the increase in direct costs, particularly hospitalization costs, is a likely factor resulting in the increase in the COI. This is because women are surviving longer, and thus receiving care for longer durations, because of advancements in medical care.
Protease inhibitors partially overcome the interferon nonresponse phenotype in patients with chronic hepatitis C
Authors: Duarte‐Rojo A. , Fischer S. E. , Adeyi O. , Zita D. , Deneke M. G. , Selzner N. , Chen L. , Malespin M. , Cotler S. J. , McGilvray I. D. , Feld J. J.
Published: December 2015

The outcome of triple therapy with protease inhibitors (PI) depends on the intrinsic response to interferon. Interferon‐stimulated gene (ISG) expression differs by cell type in the liver and is a strong predictor of interferon responsiveness. Patients who respond well to interferon have low/absent ISG expression in hepatocytes but significant ISG expression in macrophages. Nonresponders (NRs) show the opposite pattern. We aimed to determine the association between cell‐type‐specific ISG staining and treatment outcome with PI‐based triple therapy. Liver biopsy tissue from consecutive patients treated with boceprevir or telaprevir with peginterferon and ribavirin was stained for myxovirus A (MxA). Staining was scored 0–3 in macrophages (M‐MxA) and hepatocytes (H‐MxA), and IL28B genotyping was performed. Of 56 patients included 41 achieved SVR (73%) (sustained virological response), 2 (4%) relapsed, 10 (18%) were NRs, and 3 (5%) were lost to follow‐up. Median M‐MxA staining was stronger and H‐MxA staining was weaker in patients who achieved SVR. MxA staining correlated with IL28B genotype and with the HCV RNA decline during lead‐in phase. However, unlike with dual therapy, the negative predictive value (NPV) of absent or weak M‐MxA staining was poor (42%), while the positive predictive value improved (93%). Although by multivariable logistic regression M‐MxA staining was significantly associated with SVR (OR 4.35, 1.32–14.28, P = 0.012), the predictive ability was inadequate to withhold therapy. The interaction between macrophages and hepatocytes plays a critical role in interferon responsiveness; however, the addition of a PI at least partially overcomes the interferon nonresponse phenotype making the predictive ability of ISG staining less clinically useful.
Correlations between estrogen and testosterone concentrations, pairing status and acanthocephalan infection in an amphipod
Authors: Lewis S. E. , Freund J. G. , Wankowski J. L. , Baldridge M. G.
Published: December 2015

Mechanisms by which parasites induce phenotypic alterations are poorly understood in many host–parasite systems. Amphipods are an intermediate host for a range of acanthocephalan parasites, and there is substantial evidence that parasites manipulate the physiology and behavior of amphipods in a variety of ways, including significant reproductive impacts. Evidence suggests such manipulations may result from disruption of serotonergic and dopaminergic pathways. However, correlations with other hormones have not been widely investigated, in part because we lack understanding of the production and action of hormones such as estrogen and testosterone in amphipods. We investigated how estrogen (17β‐estradiol) and testosterone concentrations vary between unparasitized male and female amphipods Gammarus pseudolimnaeus that were and were not in precopulatory pairs. We also investigated whether infection with the acanthocephalan Corynosoma sp. is correlated with differences in estrogen or testosterone concentrations when compared to unparasitized conspecifics. Our results indicate that estrogen and testosterone differ significantly between male and female amphipods, whether paired or unpaired, suggesting they may have sex‐specific functions. The biological relevance of these hormones merits increased attention in light of the prevalence of endocrine‐disrupting compounds in aquatic systems. Further, we found that encysted acanthocephalan parasites are correlated with elevated concentrations of estrogen and depressed concentrations of testosterone in male, but not female amphipods. This correlation suggests the need for a broader investigation of the mechanisms underlying phenotypic alterations of amphipod behavior and physiology by acanthocephalan parasites.
Further insights into the metamorphosis process in a carapid fish
Authors: Parmentier E.
Published: December 2015

In Carapus homei, settlement on the reef corresponds to a metamorphosis during which the length of the fish is reduced by 60%. This phenomenon is unique since it is the only vertebrate in which the vertebrae are ossified before metamorphosis. Metamorphosis involves the complete degradation and disappearance of the caudal tip vertebrae, and there is a reduction in the size of most of the remaining vertebrae. The aim of this study is to gain more data on the process causing the metamorphosis. The shortening of the body axis can be compared to an ‘excision‐splicing’ process. During excision, various cell types, including muscle, notochord and osseous vertebrae are progressively lost. Excision causes the spacing of adjacent vertebrae because of the degeneration of their extremities. Splicing allows the shortening of the body by bringing close together the remaining parts of the vertebrae. The mechanism implies a compressive force whose source seems mainly to involve the notochord. The size reduction of the notochordal cells generates the shortening of the notochord along the longitudinal axis and the displacement of the vertebral bodies. At the end of the metamorphosis, the remaining muscles and the highly developed external ligaments of the vertebrae are able to complete the action of the notochord. The study highlights the morphogenetic role of the notochord, which appears to be responsible for the column remodelling and for its final size. The metamorphosis of C. homei represents a highly interesting model for the study of the degeneration, resorption and remodelling of different tissues.
Peptide and amino acid metabolism is controlled by an OmpR‐family response regulator in Lactobacillus casei
Authors: Alcántara Cristina , Bäuerl Christine , Revilla‐Guarinos Ainhoa , Pérez‐Martínez Gaspar , Monedero Vicente , Zúñiga Manuel
Published: December 2015

A Lactobacillus casei BL23 strain defective in an OmpR‐family response regulator encoded by LCABL_18980 (PrcR, RR11), showed enhanced proteolytic activity caused by overexpression of the gene encoding the proteinase PrtP. Transcriptomic analysis revealed that, in addition to prtP expression, PrcR regulates genes encoding peptide and amino acid transporters, intracellular peptidases and amino acid biosynthetic pathways, among others. Binding of PrcR to twelve promoter regions of both upregulated and downregulated genes, including its own promoter, was demonstrated by electrophoretic mobility shift assays showing that PrcR can act as a transcriptional repressor or activator. Phosphorylation of PrcR increased its DNA binding activity and this effect was abolished after replacement of the phosphorylatable residue Asp‐52 by alanine. Comparison of the transcript levels in cells grown in the presence or absence of tryptone in the growth medium revealed that PrcR activity responded to the presence of a complex amino acid source in the growth medium. We conclude that the PrcR plays a major role in the control of the peptide and amino acid metabolism in L. casei BL23. Orthologous prcR genes are present in most members of the Lactobacillaceae and Leuconostocaceae families. We hypothesize that they play a similar role in these bacterial groups.
Narrow band imaging: clinical applications in oral and oropharyngeal cancer
Authors: Vu A , Farah CS
Published: December 2015

Narrow Band Imaging (NBI) is an endoscopic optical imaging enhancement technology that improves the contrast of mucosal surface texture, and enhances visualisation of mucosal and submucosal vasculature. White light is filtered to emit two 30‐nm narrow bands of blue (415 nm) and green light (540 nm) light simultaneously, the former corresponding to the main peak absorption spectrum of haemoglobin, and the latter allowing visualisation of blood vessels in the deeper mucosal and submucosal layers. NBI has been used to better assess oral potentially malignant disorders (OPMD), identify oral and oropharyngeal squamous cell carcinoma (SCC), and to define surgical margins of head and neck malignancies. NBI shows great potential in improving detection rates of OPMD, facilitating better assessment of oral and oropharyngeal SCC, and reducing the risk of recurrence for oral SCC. Although further research is required to better understand and define intrapapillary capillary loop (IPCL) patterns and to relate these with clinical, histopathological and molecular parameters especially for early mucosal changes, there is building evidence to recommend its use as the new gold standard for endoscopic assessment in head and neck oncology.
Study of IRF6 and 8q24 region in non‐syndromic oral clefts in the Brazilian population
Authors: de Souza LT , Kowalski TW , Ferrari J , Monlléo IL , Ribeiro EM , de Souza J , Fett‐Conte AC , de Araujo TK , Gil‐da‐Silva‐Lopes VL , Ribeiro‐dos‐Santos ÂKC , dos Santos SEB , Félix TM
Published: December 2015

Objectives

We investigated the association between non‐syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population.

Subjects and methods

Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms.

Results

A total of 259 probands were analyzed. A TDT detected overtransmission of the rs2235371 G allele (P = 0.0008) in the total sample. A significant association of this allele was also observed in CLP (P = 0.0343) and CLP + CL (P = 0.0027). IRF6 haplotype analysis showed that the G/A haplotype increased the risk for cleft in children (single dose: P = 0.0038, double dose: P = 0.0022) and in mothers (single dose: P = 0.0016). The rs987525 (8q24) also exhibited an association between the A allele and the CLP + CL group (P = 0.0462). These results were confirmed in the probands with European ancestry.

Conclusions

The 8q24 region plays a role in CL/P and the IRF6 G/A haplotype (rs2235371/rs642961) increases the risk for oral cleft in the Brazilian population.
Treatment of infantile subglottic hemangioma with oral propranolol
Authors: Wang Cai‐Fu , Wang Ying‐Shuo , Sun Yue‐Feng
Published: December 2015

Infantile subglottic hemangioma (SH) can cause biphasic stridor, respiratory distress and even life‐threatening airway compromise. Treatment of SH in infants has traditionally been characterized as a challenging situation with multiple therapeutic options without consensus as to which one is the best and with risks of severe side‐effects. Four infants with SH were treated with propranolol. Treatment with oral propranolol resulted in resolution of symptoms within 2 days, followed by complete recovery. Propranolol appears to be an effective treatment for SH and should be used as a first‐line treatment for SH when intervention is required.
Regression of massive cardiac rhabdomyoma on everolimus therapy
Authors: Hoshal Steven G. , Samuel Bennett P. , Schneider Jeffrey R. , Mammen Leena , Vettukattil Joseph J.
Published: December 2015

Cardiac rhabdomyoma is the primary feature of the genetic disease, tuberous sclerosis complex, the most common cardiac tumor diagnosed in neonates and infants. Spontaneous regression is observed in most cases, but these tumors may cause hemodynamic instability, arrhythmias or other complications. We describe the case of a critically ill neonate, resuscitated after cardiac arrest secondary to massive locally invasive cardiac rhabdomyoma, who was successfully treated with everolimus (mammalian target of rapamycin [mTOR] inhibitor). Rapid tumor regression was observed on echocardiography, but it was unlikely that it was confounded by the natural disease course of regression. The presented case suggests that mTOR inhibitors may play a significant role in the treatment of large cardiac rhabdomyomas in critically ill neonates.