bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, southwestern Nigeria
Authors: Faleye Temitope Oluwasegun Cephas , Adewumi Moses Olubusuyi , Ifeorah Ijeoma Maryjoy , Omoruyi Ewean Chukwuma , Bakarey Solomon Adeleye , Akere Adegboyega , Awokunle Funmilola , Ajibola Hannah Opeyemi , Makanjuola Deborah Oluwaseyi , Adeniji Johnson Adekunle
Published: January 2015

Perinatal transmission of hepatitis B virus (HBV) and its associated immune escape mutants (IEMs), is the major vehicle through which a population of chronically infected people who serve as infectious HBV reservoirs is maintained in communities. Therefore, to assess the risk of perinatal transmission, 272 pregnant women attending ante-natal clinics in Ibadan metropolis, southwestern, Nigeria, were screened for HBsAg using ELISA technique. Samples positive for HBsAg were subjected to HBV DNA detection by PCR amplification of the S-gene and amplicon sequencing. Isolates were genotyped and subtyped using a combination of molecular techniques.

Fifteen (5.5%) of the pregnant women were positive for HBsAg of which HBV DNA was detected in seven. Five of the isolates were typed as genotype E subtype ayw4 using amino acid residues at positions 122, 127, 134 and 160. Another could only be typed as genotype E subtype ayw4 by further phylogenetic analysis. The remaining one isolate did not belong to any of genotypes A – H. Three of the HBV isolates including the untypable, had mutations in the ‘a’ determinant associated with IEMs.

This study confirms the endemicity of HBV, the risk of perinatal transmission and the circulation of genotype E subtype ayw4 in Nigeria. It further demonstrates the presence of IEMs in Nigeria.
Amino acids inhibit kynurenic acid formation via suppression of kynurenine uptake or kynurenic acid synthesis in rat brain in vitro
Authors: Sekine Airi , Okamoto Misaki , Kanatani Yuka , Sano Mitsue , Shibata Katsumi , Fukuwatari Tsutomu
Published: January 2015

The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor at endogenous brain concentrations. Recent studies have suggested that increase of brain KYNA levels is involved in psychiatric disorders such as schizophrenia and depression. KYNA-producing enzymes have broad substrate specificity for amino acids, and brain uptake of kynurenine (KYN), the immediate precursor of KYNA, is via large neutral amino acid transporters (LAT). In the present study, to find out amino acids with the potential to suppress KYNA production, we comprehensively investigated the effects of proteinogenic amino acids on KYNA formation and KYN uptake in rat brain in vitro. Cortical slices of rat brain were incubated for 2 h in Krebs-Ringer buffer containing a physiological concentration of KYN with individual amino acids. Ten out of 19 amino acids (specifically, leucine, isoleucine, phenylalanine, methionine, tyrosine, alanine, cysteine, glutamine, glutamate, and aspartate) significantly reduced KYNA formation at 1 mmol/L. These amino acids showed inhibitory effects in a dose-dependent manner, and partially inhibited KYNA production at physiological concentrations. Leucine, isoleucine, methionine, phenylalanine, and tyrosine, all LAT substrates, also reduced tissue KYN concentrations in a dose-dependent manner, with their inhibitory rates for KYN uptake significantly correlated with KYNA formation. These results suggest that five LAT substrates inhibit KYNA formation via blockade of KYN transport, while the other amino acids act via blockade of the KYNA synthesis reaction in brain. Amino acids can be a good tool to modulate brain function by manipulation of KYNA formation in the brain. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with increased KYNA levels.
Effects of early and late-onset treatment with carvedilol in an experimental model of aortic regurgitation
Authors: Eskesen Kristian , Olsen Niels Thue , Dimaano Veronica L , Fritz-Hansen Thomas , Sogaard Peter , Abraham Theodore P
Published: January 2015

Background

Beta-blockade is contraindicated in severe aortic regurgitation (AR) due to the fear of prolonging diastole and thus aggravate regurgitation. However, this has never been scientifically proven and positive effects of targeting the sympathetic system in AR has been demonstrated in several studies.

Method

Thirty-nine Sprague–Dawley rats with AR were randomized to ten weeks of medical treatment with carvedilol or no treatment. Treatment was initiated either early or late after AR induction. The effect of carvedilol was assessed by serial echocardiography and invasive hemodynamic measurements.

Results

AR resulted in eccentric hypertrophy and left ventricular (LV) dysfunction. LV remodeling and function as measured by echocardiography was unaffected by treatment. LV dimensions were similar between treated and untreated groups and measures of LV performance (including strain and strain rate) were also unaltered. This result was confirmed by invasive measurements showing maximal and minimal pressure–time development, LV volumes, and LV pressures, to be unaltered by treatment. On the contrary, despite relative bradycardia carvedilol did not reflect any negative impact on the heart.

Conclusion

Carvedilol did not improve left ventricular remodeling or function in rats with surgically induced AR. Despite relative bradycardia, we did not find carvedilol to negatively impact the heart, either when treatment was initiated early or late in the course of disease.
Jasmonates elicit different sets of stilbenes in Vitis vinifera cv. Negramaro cell cultures
Authors: Taurino Marco , Ingrosso Ilaria , D’amico Leone , De Domenico Stefania , Nicoletti Isabella , Corradini Danilo , Santino Angelo , Giovinazzo Giovanna
Published: January 2015

The plant phenol trans-resveratrol, which is mainly found in grape, displays a wide range of biological effects. A cell suspension culture was developed from calli of grape leaves of Vitis vinifera cv. Negramaro in order to study the bioproduction of resveratrol. The effects of a number of secondary plant metabolism elicitors, namely chitosan, methyl jasmonate, jasmonic acid, coronatine, and 12-oxo-phytodienoic acid, were tested on this cell suspension culture. The identification and quantification of stilbenes was achieved with high performance liquid chromatography, with both spectrophotometric and mass spectrometric detection. Of the tested elicitors, methyl jasmonate was the most effective in inducing the biosynthesis of approximately 4 mg g−1 dry weight (about 60 mg L−1) of resveratrol. Conversely, 12-oxo-phytodienoic acid, jasmonic acid, and coronatine were able to trigger the synthesis of approximately 20 mg g−1 dry weight (200–210 mg L−1) of viniferins. Taken together, our results show for the first time different modulatory effects of closely-related jasmonates on stilbene biosynthesis.
A cross-cultural re-evaluation of the Exercise Addiction Inventory (EAI) in five countries
Authors: Griffiths Mark D , Urbán Robert , Demetrovics Zsolt , Lichtenstein Mia B , de la Vega Ricardo , Kun Bernadette , Ruiz-Barquín Roberto , Youngman Jason , Szabo Attila
Published: January 2015

Research into the detrimental effects of excessive exercise has been conceptualized in a number of similar ways, including ‘exercise addiction’, ‘exercise dependence’, ‘obligatory exercising’, ‘exercise abuse’, and ‘compulsive exercise’. Among the most currently used (and psychometrically valid and reliable) instruments is the Exercise Addiction Inventory (EAI). The present study aimed to further explore the psychometric properties of the EAI by combining the datasets of a number of surveys carried out in five different countries (Denmark, Hungary, Spain, UK, and US) that have used the EAI with a total sample size of 6,031 participants. A series of multigroup confirmatory factor analyses (CFAs) were carried out examining configural invariance, metric invariance, and scalar invariance. The CFAs using the combined dataset supported the configural invariance and metric invariance but not scalar invariance. Therefore, EAI factor scores from five countries are not comparable because the use or interpretation of the scale was different in the five nations. However, the covariates of exercise addiction can be studied from a cross-cultural perspective because of the metric invariance of the scale. Gender differences among exercisers in the interpretation of the scale also emerged. The implications of the results are discussed, and it is concluded that the study’s findings will facilitate a more robust and reliable use of the EAI in future research.
Chemokine receptor CCR7 regulates the intestinal TH1/TH17/Treg balance during Crohnˈs-like murine ileitis
Authors: McNamee Eóin N , Masterson Joanne C , Veny Marisol , Collins Colm B , Jedlicka Paul , Byrne Fergus R , Ng Gordon Y , Rivera-Nieves Jesús
Published: January 2015

The regulation of T cell and DC retention and lymphatic egress within and from the intestine is critical for intestinal immunosurveillance; however, the cellular processes that orchestrate this balance during IBD remain poorly defined. With the use of a mouse model of TNF-driven Crohnˈs-like ileitis (TNFΔARE), we examined the role of CCR7 in the control of intestinal T cell and DC retention/egress during experimental CD. We observed that the frequency of CCR7-expressing TH1/TH17 effector lymphocytes increased during active disease in TNFΔARE mice and that ΔARE/CCR7−/− mice developed exacerbated ileitis and multiorgan inflammation, with a marked polarization and ileal retention of TH1 effector CD4+ T cells. Furthermore, adoptive transfer of ΔARE/CCR7−/− effector CD4+ into lymphopenic hosts resulted in ileo-colitis, whereas those transferred with ΔARE/CCR7+/+ CD4+ T cells developed ileitis. ΔARE/CCR7−/− mice had an acellular draining MLN, decreased CD103+ DC, and decreased expression of RALDH enzymes and of CD4+CD25+FoxP3+ Tregs. Lastly, a mAb against CCR7 exacerbated ileitis in TNFΔARE mice, phenocopying the effects of congenital CCR7 deficiency. Our data underscore a critical role for the lymphoid chemokine receptor CCR7 in orchestrating immune cell traffic and TH1 versus TH17 bias during chronic murine ileitis.
Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles
Authors: Miklavc Pika , Ehinger Konstantin , Sultan Ayesha , Felder Tatiana , Paul Patrick , Gottschalk Kay-Eberhard , Frick Manfred
Published: January 2015

In many secretory cells actin and myosin are specifically recruited to the surface of secretory granules following their fusion with the plasma membrane. Actomyosin-dependent compression of fused granules is essential to promote active extrusion of cargo. Yet, little is known about molecular mechanisms regulating actin coat formation and contraction. Here we provide a detailed kinetic analysis of the molecules regulating actin coat contraction on fused lamellar bodies (LBs) in primary alveolar type II cells. We demonstrate that Rock1 and myosin light chain kinase (MLCK) translocate to fused LBs and activate myosin II on actin coats. Yet, myosin II activity is not sufficient for efficient actin coat contraction. In addition, cofilin-1 and α-actinin translocate to actin coats. Rock1-dependent, regulated actin depolymerisation by cofilin-1 in cooperation with actin crosslinking by α-actinin is essential for complete coat contraction. In summary, our data suggest a complementary role for regulated actin depolymerisation/crosslinking and myosin II activity to contract actin coats and drive secretion.
Pseudo-Dumbbell-Type Molecular Beacon Probes Bearing Modified Deoxyuridine Derivatives and a Silylated Pyrene as a Fluorophore
Authors: Chowdhury Jakir Ahmed , Moriguchi Tomohisa , Shinozuka Kazuo
Published: January 2015

We have recently reported a novel pseudo-dumbbell-type molecular beacon probe (Probe 1) possessing polyamine-connected deoxyuridine (U) and silylated pyrene. The probe showed weak fluorescence signal while it stayed alone. Fluorescence signal of the probe was increased in the presence of the complementary DNA. In this study, we prepared new molecular beacons, Probe 2 and Probe 3, possessing the elongated stem portion of Probe 1. In addition, one U in Probe 2 is substituted by anthraquinone-bearing deoxyuridine residue (Y) in Probe 3. Probe 4 is essentially the same as Probe 1 but one deoxyguanosine in the loop portion of Probe 1 is substituted by deoxyinosine in Probe 4. In Probe 5, 3′-terminal deoxycytidine of Probe 3 is substituted by deoxyadenosine. The fluorescence signal of these probes is effectively quenched in the absence of target DNA. Among all, Probe 3 shows the most effective quenching. On the other hand, the signal is substantially increased in the presence of complementary DNA. The ratio of signal to background in case of Probe 3 is the highest. All these probes also recognize single nucleotide alternation in the target DNA to a different extent. The sequence recognition ability of Probe 3 is also the highest among all the probes.
Hyperspectral near Infrared Imaging of Wooden Surfaces Performed Outdoors and Indoors
Authors: Burud I. , Gobakken L.R. , Flø A. , Thiis T.K. , Kvaal K.
Published: January 2015

Hyperspectral near infrared imaging has been applied in a field study of fungal growth on a variety of wood substrates exposed in an outdoor environment over a six-month period. This study was performed as a follow up to a hyperspectral examination study of fungal growth on wood surfaces in a laboratory setting. Hyperspectral measurements were carried out both outdoors and indoors in order to explore the influence of the different light conditions. Segmentation of the mould growth on the wood surfaces was carried out using principal component analysis, spectral angle mapper and partial least squares-discriminant analysis. Growth curves showing the fungal growth over time were obtained for all the samples from the measurements performed outdoors. However, there are some challenges connected to studies of wood surfaces due to structures caused by growth rings, knots and sometimes cracks. These wood properties will cause a great variation in the spectra from the wood and also cause natural variation in the fungal growth. Determining specific classes in a classification model such as partial least squares-discriminant analysis is proposed as a way to overcome these issues. Moreover, the wood substrates exposed in an outdoor environment will have a colour change due to photodegradation of lignin, wetting/leaching of the upper layer of the wood surface and growth of a variety of wood discolouring fungi. Hyperspectral technology is a promising technique to study wood properties and we plan to carry out a study to be able to separate and model the different effects on colour degradation on wood surfaces.
Repeated Interaction and Rating Inflation: A Model of Double Reputation
Authors: Frenkel Sivan
Published: January 2015

Credit rating agencies have an incentive to maintain a public reputation for credibility among investors but also have an incentive to develop a second, private reputation for leniency among issuers. We show that in markets with few issuers, such as markets for structured assets, these incentives may lead rating agencies to inflate ratings as a strategic tool to form a “double reputation.” The model extends the existing literature on “cheap-talk” reputation to the case of two audiences. Our results can explain why rating inflation occurred specifically in markets for MBSs and CDOs during the recent financial crisis. Policy implications are discussed. (JEL D82, G01, G12, G24, G32)
Information and Extremism in Elections
Authors: Boleslavsky Raphael , Cotton Christopher
Published: January 2015

We model an election in which parties nominate candidates with observable policy preferences prior to a campaign that produces information about candidate quality, a characteristic independent of policy. Informative campaigns lead to greater differentiation in expected candidate quality, which undermines policy competition. In equilibrium, as campaigns become more informative, candidates become more extreme. We identify conditions under which the costs associated with extremism dominate the benefits of campaign information. Informative political campaigns increase political extremism and can decrease voter welfare. Our results have implications for media coverage, the number of debates, and campaign finance reform. (JEL D72, D83)
Online Educational Conference on Professional growth of Teachers
Authors: Горбунова  , Gorbunova L.
Published: January 2015

The article presents issues of additional professional education of teachers and ways of dealing with them. The author connects prospects of effective

reform of additional professional education of teachers with its targeting on teachers’ professional growth through the search of new means of

supporting the process. Online educational conference is considered as one of such means.
Subject Oriented Education: from Depth to Project
Authors: Алексеева  , Alekseeva Lada , Мартынова  , Martynova V.
Published: January 2015

The article discusses the history of vocational education in Russia and the modern trends of its development. There is a detailed analysis of how different

profiles were built in vocational education, how expanding the list of profiles form the concept of «individual profile». Vocational education is considered

in the context of three types of learning outcomes: subject-oriented, interdisciplinary and personal. Special attention is paid to organizational forms

(multi-discipline educational organization, preuniversitario) and to organization of vocational training. The paper provides integration technology of

subject oriented training and project methods of education.
Personal development planning: a voyage of discovery
Authors: Nash Maggie
Published: January 2015

Personal development plans (PDPs) are a regulatory requirement for all DCPs, but what should they include? The PDP described here is based on some of the theories of development planning and it is hoped that you may find it useful in making your own PDP a more comprehensive and valuable tool
Emergency traumatic dental injuries: the dental nurse's role
Authors: Djemal Serpil , Singh Parmjit , Lonsdale Jennifer
Published: January 2015

This article will aim to outline the risk factors, types of injury along with emergency management of traumatic dental injury and guidance on chair side support for splinting of teeth. Advice for the prevention of traumatic dental injuries will also be discussed
Can your patients hear you?
Authors: Davies Sue
Published: January 2015

Communication between dental professionals and their patients with a hearing loss can be very difficult, but better deaf awareness and assistive devices will improve it
Parents' lived experience in the anaesthetic room
Authors: Muazu Isa M
Published: January 2015

Background:

It is a common practice today in the UK that the majority of children are accompanied to the operating theatre by one or two parents. The Association of Anaesthetists of Great Britain and Ireland (AAGBI) recommends that this is offered to the parents as a recommended standard of care ( AAGBI, 2010 ).

Aim:

To describe the lived experiences of parents whose children had been scheduled for induction of general anaesthesia.

Methods:

This study (n=13) adopted a single-method approach involving purposeful sampling to select the participants aged 18–75 years, recruited from the pre-assessment clinics. The use of in-depth interviews was used to generate data about the participant's personal experiences. It is based on a descriptive approach within a phenomenological framework.

Results:

The analysis of the interviews and narrations of the participants led to the extraction of five major themes consisting of emotional impact, views of the impact of their presence, professional issues, information need and coping strategies.

Conclusion:

The experience of parents witnessing their children in the anaesthetic room being placed under anaesthesia can be considered to be stressful for the parents. Intervention strategies are needed to reduce the stress for the parents during this period. Health professionals need to have a better understanding of the individual coping strategies to support each parent and the impacts on parents' wellbeing.
Moira Crosdale: Team nurturer
Authors: Crosdale Moira
Published: January 2015

Moira Crosdale is an advanced nurse practitioner and facilitator who helps keep her colleagues working together
Health and social care partnership improves lives
Authors: Benison Liam
Published: January 2015

The coordination of health and social care services in south London is helping older people to stay healthy and independent for longer. Liam Benison reports
Tackling FGM is everybody's business
Authors: Bagness Carmel
Published: January 2015

Female genital mutilation is harmful and illegal. Carmel Bagness discusses the practice nurse's responsibilities in identifying and supporting victims, and safeguarding women and girls at risk
Minimizing breast cancer-related lymphoedema
Authors: Acebedo Juanita C
Published: January 2015

The advent of medical breakthroughs has made an impact on the treatment of breast cancer, the second most common type of cancer affecting women. However, breast cancer-related lymphoedema is a major complication affecting women at a high rate. This article reviews previous studies on the care of breast cancer-related lymphoedema and searches for gaps that nurses can fill. CINAHL, Medline, and nursing and health sciences databases were used to search for studies published between 2008 and 2014. Editorial articles and studies in which the full text was not available were excluded. Thirty-five articles were reviewed and five were excluded. The level of evidence of these articles ranged from I-VI. The key results of the studies included indicate the prevalence of BCRL varies greatly owing to the different types of assessment and diagnosing techniques that are used. Nurses usually have initial contact with these patients, and they can make significant contributions to the care of patients with breast cancer-related lymphoedema, in assessment, education and intervention.
Vaccination uptake in pregnant women
Authors: Sisson Helen
Published: January 2015

Vaccination in pregnancy is safe and effective, but the rate of uptake is much lower than recommended. Helen Sisson encourages health professionals to continue vaccinating with confidence
Characterization of Angiogenesis and Lymphangiogenesis in Human Minor Salivary Glands with Sjögren’s Syndrome
Authors: McCall Andrew D. , Baker Olga J.
Published: January 2015

Angiogenesis has been proposed to play a role in the inflammation observed in Sjögren’s Syndrome (SS). However, no studies have validated the degree of angiogenesis in salivary glands with SS. Therefore, the goal of this study was to determine the presence and localization of angiogenesis and lymphangiogenesis in salivary glands with SS. We used frozen tissue sections from human minor salivary glands (hMSG) with and without SS in our analyses. To investigate signs of angiogenesis, hMSG tissue lysates were used to detect levels of the pro-angiogenic protein vascular endothelial growth factor (VEGF) by western blot analyses. Additionally, we labeled blood vessels using antibodies specific to platelet endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand Factor (vWF) to determine blood vessel organization and volume fraction using fluorescence microscopy. Lymphatic vessel organization and volume fraction were determined using antibodies specific to lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Our results suggest that expression levels of VEGF are decreased in hMSG with SS as compared with controls. Interestingly, there were no significant differences in blood or lymphatic vessel organization or volume fraction between hMSG with and without SS, suggesting that angiogenesis and lymphangiogenesis have little impact on the progression of SS.
EFFECTIVENESS OF ANNEALING TREATMENT AND POLYMER BLENDS ON I-V CHARACTERISTSICS OF POLYMER SOLAR CELL
Authors: Rosa Erlyta Septa , Shobih Shobih
Published: January 2015

This research reports on a fabrication of polymer solar cells based on blends of two widely used polymeric semiconductors i.e. poly(2-methoxy-5-(3,7-dimethyloctyloxy)-para phenylene vinylene) (MDMO-PPV) and the soluble fullerene C60 derivative [6,6 phenyl C61-butyric acid methyl ester] (PCBM). The devices were fabricated on an indium tin oxide (ITO) coated glass substrate. After cleaned and dried, a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) in H2O was spin coated onto the freshly prepared substrate and then dried in a vacuum oven at 120°C for 60 minutes. A blend of MDMO-PPV and PCBM in chlorobenzene was spin coated on the top and dried in a nitrogen ambient at room temperature for 24 hours. The devices were transferred to a sputtering system where an aluminum was coated. Some of the devices then were annealed in a vacuum oven at 60°C for 60 minutes. Finally, the devices were encapsulated by placing a sealant between the back of the devices and glass slides and then cured in a vacuum oven at temperature 100°C for 10 minutes. For characterization, the devices were illuminated with a xenon lamp at the intensity of 27 mW/cm2 and the temperature at approximately 25°C. The influence of the annealing treatment and polymer blends on the photovoltaic performance of the devices was also discussed here. The best performance was obtained from the device with a blend ratio of 1:1 MDMO-PPV/PCBM without annealing treatment. The typical power efficiency was 0.01% with open circuit voltage of 0.347 V, short circuit current of 0.064 mA, and maximum power of 0.006 mW.
KARAKTERISTIK BATUBARA DAN PENGARUHNYA TERHADAP PROSES PENCAIRAN
Authors: Talla Harli , Amijaya Hendra , Harijoko, Agung , Huda Miftahul
Published: January 2015

Tujuan penelitian ini adalah mempelajari pengaruh karakteristik batubara terhadap proses pencairan dengan menggunakan metoda hidrogenasi katalitik. Sampel batubara yang digunakan adalah batubara Sorong dengan peringkat lignit dan batubara Mulia dengan peringkat sub bituminus. Proses pencairan dilakukan dalam sebuah otoklaf yang berkapasitas 5 liter dengan menggunakan pelarut antrasen dan katalis bijih besi. Kisaran suhu pencairan adalah 375ºC, 400ºC, 425ºC, dan 450ºC, sementara tekanan awal hidrogen ditetapkan 100 bar. Hasil yang diperoleh menunjukan bahwa karakteristik batubara memiliki pengaruh yang signifikan terhadap pencairan. Konversi tertinggi batubara Sorong adalah 89,94% pada suhu 400ºC, sementara untuk batubara Mulia sebesar 87,28% pada suhu 450ºC
Redox imaging using genetically encoded redox indicators in zebrafish and mice
Authors: Breckwoldt Michael O. , Wittmann Christine , Misgeld Thomas , Kerschensteiner Martin , Grabher Clemens
Published: January 2015

Redox signals have emerged as important regulators of cellular physiology and pathology. The advent of redox imaging in vertebrate systems now provides the opportunity to dynamically visualize redox signaling during development and disease. In this review, we summarize recent advances in the generation of genetically encoded redox indicators (GERIs), introduce new redox imaging strategies, and highlight key publications in the field of vertebrate redox imaging. We also discuss the limitations and future potential of in vivo redox imaging in zebrafish and mice.
Phagocytosis‐dependent activation of aTLR9–BTK–calcineurin–NFATpathway co‐ordinates innate immunity toAspergillus fumigatus
Authors: Herbst Susanne , Shah Anand , Mazon Moya Maria , Marzola Vanessa , Jensen Barbara , Reed Anna , Birrell Mark A , Saijo Shinobu , Mostowy Serge , Shaunak Sunil , Armstrong‐James Darius
Published: January 2015

Transplant recipients on calcineurin inhibitors are at high risk of invasive fungal infection. Understanding how calcineurin inhibitors impair fungal immunity is a key priority for defining risk of infection. Here, we show that the calcineurin inhibitor tacrolimus impairs clearance of the major mould pathogenAspergillus fumigatusfrom the airway, by inhibiting macrophage inflammatory responses. This leads to defective early neutrophil recruitment and fungal clearance. We confirm these findings in zebrafish, showing an evolutionarily conserved role for calcineurin signalling in neutrophil recruitment during inflammation. We find that calcineurin–NFATactivation is phagocytosis dependent and collaborates withNF‐κB forTNF‐α production. For yeast zymosan particles, activation of macrophage calcineurin–NFAToccurs via the phagocytic Dectin‐1–spleen tyrosine kinase pathway, but forA. fumigatus, activation occurs via a phagosomalTLR9‐dependent and Bruton's tyrosine kinase‐dependent signalling pathway that is independent of MyD88. We confirm the collaboration betweenNFATandNF‐κB forTNF‐α production in primary alveolar macrophages. These observations identify inhibition of a newly discovered macrophageTLR9–BTK–calcineurin–NFATsignalling pathway as a key immune defect that leads to organ transplant‐related invasive aspergillosis.
Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery
Authors: Khan Aliya , Bilezikian John , Bone Henry , Gurevich Andrey , Lakatos Peter , Misiorowski Waldemar , Rozhinskaya Liudmila , Trotman Marie-Louise , Tóth Miklós
Published: January 2015

Objective

Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or nonsuppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium level and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy.

Design

Phase 3, double-blind, multi centere, randomized, placebo-controlled study.

Methods

Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for ≤28 weeks.

Main outcome measure

Achievement of a normal mean corrected total serum calcium concentration of ≤10.3 mg/dl (2.575 mmol/l).

Results

Baseline median (quartile 1 (Q1), Q3) serum PTH was 164.0 (131.0, 211.0) pg/ml and mean (s.d.) serum Ca was 11.77 (0.46) mg/dl. Serum Ca normalized (≤10.3 mg/dl) in 75.8% of cinacalcet- vs 0% of placebo-treated subjects (P<0.001). Corrected serum Ca decreased by ≥1.0 mg/dl from baseline in 84.8% of cinacalcet- vs 5.9% of placebo-treated subjects (P<0.001). Least squares mean (s.e.m.) plasma PTH change from baseline was −23.80% (4.18%) (cinacalcet) vs −1.01% (4.05%) (placebo) (P<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (AEs) (27 vs 20) and serious AEs (three vs four). Most commonly reported AEs were nausea and muscle spasms.

Conclusions

These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.
ENDOCRINE TUMOURS: Familial nonmedullary thyroid carcinoma is a more aggressive disease: a systematic review and meta-analysis
Authors: Wang Xiaofei , Cheng Wenli , Li Jingdong , Su Anping , Wei Tao , Liu Feng , Zhu Jingqiang
Published: January 2015

Objective

There is controversy as to whether familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive than sporadic NMTC (SNMTC). The aim of the study was to evaluate the biological characteristics of patients with FNMTC by a meta-analysis.

Methods

Four databases (PubMed, EMBASE, the Cochrane library databases, and the Web of Science) were searched to identify studies published before September, 2014. All original studies that compared clinical characteristics and prognosis of patients with FNMTC and SNMTC were included. The pooled effect sizes of interesting parameters were calculated by odds ratio (OR), standard mean difference (SMD), or hazard ratio (HR).

Results

Twelve studies with a total of 12 741 participants were included in this analysis. FNMTC patients had an increased rate of recurrence (OR=1.72, 95% CI: 1.34 to 2.20) and decreased disease-free survival (DFS) (HR=1.83, 95% CI: 1.34 to 2.52) in comparison with SNMTC patients. FNMTC possessed more aggressive biological behaviors, characterized by younger age at diagnosis (SMD=−0.91, 95% CI: −1.59 to −0.22), higher risk of multifocal (OR=1.50, 95% CI: 1.32 to 1.71), bilateral (OR=1.29, 95% CI: 1.00 to 1.66), extrathyroidal invasion (OR=1.20, 95% CI: 1.02 to 1.41), and lymph node metastasis (OR=1.18, 95% CI: 1.01 to 1.38).

Conclusion

FNMTC is a more aggressive disease and possesses higher recurrence rate and lower DFS. More attention and careful consideration should be paid regarding the decision about treatment for patients with FNMTC.
Preoperative imaging for focused parathyroidectomy: making a good strategy even better
Authors: Guerin Carole , Lowery Aoife , Gabriel Sophie , Castinetti Frédéric , Philippon Mélanie , Vaillant-Lombard Josiane , Loundou Anderson , Henry Jean-François , Sebag Frédéric , Taïeb David
Published: January 2015

Objective

Surgical treatment for primary hyperparathyroidism (pHPT) has undergone a major paradigm shift during the last decades from bilateral cervicotomy with four-gland neck exploration to image-guided focused approaches. The primary objective of the present study was to compare the performances of parathyroid scintigraphy (PS), parathyroid ultrasonography (US), and the combination of both procedures for guiding a focused approach on the basis of modified interpretation criteria.

Methods

Data from 199 patients operated for apparent sporadic pHPT and evaluated with US and PS using dual-isotope 123I/99mTc-sestamibi planar pinhole and single-photon emission computed tomography (SPECT) acqusitions were evaluated.

Results

A total of 127 patients underwent a focused approach and the remainder had bilateral cervicotomy. In 42 cases, a focused approach was not performed due to the absence of concordant results between US and PS for a single-gland abnormality. Four patients had persistent disease and three had recurrent disease. A localizing preoperative PS had a sensitivity of 93.3%, positive predictive value of 85.8%, negative predictive value of 73.0%, and accuracy of 83.4% for predicting uniglandular disease. Additional SPECT images accurately localize posterior adenomas that are often missed by US. Compared with PS, US had a lower sensitivity (P<0.01). Our imaging protocol also enabled diagnosis of multiglandular disease in 60.6%.

Conclusions

PS using a highly sensitive dual-tracer subtraction method is the most accurate technique for directing a focused approach. PS could be sufficient for directing a focused approach in the presence of a negative US in two major circumstances: posterior locations due to acquired ectopia that could be missed by US, and previous history of thyroidectomy due to interpretation difficulties.
THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing's syndrome
Authors: Daniel Eleni , Newell-Price John D C
Published: January 2015

Steroidogenesis enzyme inhibitors are the mainstay of medical therapy in Cushing's syndrome (CS). Ketoconazole (KTZ) and metyrapone are the most commonly used agents. Although there is considerable experience of their use in individual specialist centres, these drugs have not been rigorously tested in prospective clinical trials. Clinicians face uncertainties and concerns with respect to the safety profile of these agents, and best means to monitor effect. We review steroidogenesis inhibitors in the management of CS, including older agents (KTZ, metyrapone, etomidate and mitotane) and those currently under development (LCI699, non-racemic KTZ), and offer a practical approach for their use in clinical practice.
Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS
Authors: Hauge-Evans Astrid C , Bowe James , Franklin Zara J , Hassan Zoheb , Jones Peter M
Published: January 2015

The inhibitory effect of somatostatin (SST) on insulin secretionin vivois attributed to a direct effect on pancreatic beta cells, but this is inconsistent with somein vitroresults in which exogenous SST is ineffective in inhibiting secretion from isolated islets. We therefore investigated whether insulin secretion from the pancreatic islets may partly be regulated by an indirect effect of SST mediated via the CNS. Islet hormone secretion was assessedin vitroby perifusion and static incubations of isolated islets andin vivoby i.v. or i.c.v. administration of the SST analogue BIM23014C with an i.v. glucose challenge to conscious, chronically catheterised rats. Hormone content of samples was assessed by ELISA or RIA and blood glucose levels using a glucose meter. Exogenous SST14/SST28 or BIM23014C did not inhibit the release of insulin from isolated rodent isletsin vitro, whereas peripheral i.v. administration of BIM23014C (7.5 μg) with glucose (1 g/kg) led to decreased plasma insulin content (2.3±0.5 ng insulin/ml versus 4.5±0.5 ng/ml att=5 min,P<0.001) and elevated blood glucose levels compared with those of the controls (29.19±1.3 mmol/l versus 23.5±1.7 mmol/l,P<0.05). In contrast, central i.c.v. injection of BIM23014C (0.75 μg) had no significant effect on either plasma insulin (3.3±0.4 ng/ml,P>0.05) or blood glucose levels (23.5±1.7 mmol/l,P>0.05) although i.v. administration of this dose increased blood glucose concentrations (32.3±0.7 mmol/l,P<0.01). BIM23014C did not measurably alter plasma glucagon, SST, GLP1 or catecholamine levels whether injected i.v. or i.c.v. These results indicate that SST does not suppress insulin secretion by a centrally mediated effect but acts peripherally on islet cells.
TheDrosophilaGenome Nexus: A Population Genomic Resource of 623Drosophila melanogasterGenomes, Including 197 from a Single Ancestral Range Population
Authors: Lack Justin B , Cardeno Charis M , Crepeau Marc W , Taylor William , Corbett-Detig Russell B , Stevens Kristian A , Langley Charles H , Pool John E
Published: January 2015

Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets.
The importance of ubiquitin E3 ligases, SCF and APC/C, in human cancers
Authors: Bochis Ovidiu Vasile , Fetica Bogdan , Vlad Catalin , Achimas-Cadariu Patriciu , Irimie Alexandru
Published: January 2015

A normal evolution of the cell-cycle phases consists of multiple consecutive events, which makes it a highly complex process. Its preservation is regulated by Cyclin-Cdks (cyclin-dependent kinases) interactions and protein degradation, which is often controlled by the ubiquitin-mediated proteolysis.The goal of this review is to emphasize the most important features of the regulation of the cell-cycle involved in cancerogenesis, by presenting the involvement of E3 ubiquitin ligases SCF (Skp1-Cul1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome) in human malignancies. Also, we discuss the importance of the ubiquitin proteasome pathway blockade in cancer treatment. We know that a better understanding of the regulatory biology of the cell cycle can lead to the development of new target therapies for cancer.
The surgical treatment of inguinal hernia using the laparoscopic totally extra-peritoneal (TEP) technique
Authors: Mihaileanu Florin , Chiorescu Stefan , Grad Ovidiu , Negrea Voicu , Silaghi Horatiu , Mironiuc Aurel
Published: January 2015

The surgical repair of inguinal hernia represents one of the most frequent procedures used in general surgery. The new surgical techniques are simpler, with a lower morbidity and recurrence of less than 2%. The laparoscopic totally extra-peritoneal (TEP) technique is contraindicated in complicated hernias (occlusion, incarceration) and in voluminous inguino-scrotal hernias.Purpose. the evaluation of the TEP technique, of the risk factors and of the postoperative results on the group of patients who have undergone surgery in the Surgical Clinic 2 Cluj Napoca.Material and method. The study is prospective, on a group of 40 patients operated with the TEP technique in the Surgical Clinic 2 during the period May 2013 – July 2014. The following have been assessed: the demographic data, the risk factors, the immediate complications, the recurrence of the hernias.Results. The average duration of hospitalization was 6.79 days. The intraoperative incidents were: 7 minimal peritoneal lesions with pneumoperitoneum and a hemorrhagic lesion of the epigastric vessels repaired endoscopically by the clipping of the lesion. There were 2 recurrences, 24 hours and 1 year after surgery, solved by the Lichtenstein technique. After 30 interventions, the average duration of the surgery was of 64 minutes, being longer in the case of bilateral hernias and being influenced by the team’s learning curve.Conclusions. The TEP technique is a safe option followed by a low rate of complications, a low recurrence rate and low intensity postoperative pain.
Subantral augmentation with a 1/1 alloplastic and autologous material mixture. Histological characteristics and dimensional stability of the newly formed bone
Authors: Onișor-Gligor Florin , Juncar Mihai , Băciuț Grigore , Bran Simion , Juncar Raluca-Iulia , Dumitrașcu Dinu-Iuliu , Băciuț Mihaela-Felicia
Published: January 2015

Background and aim. The maxillary sinus augmentation procedure is the most frequent method used to prepare the posterior maxillary area, with bone deficit, for the placement of dental implants. For this purpose, several types of materials have been used as bone grafts, each of these materials having a number of advantages and disadvantages. The present study is aimed at evaluating the histological and volumetric properties of an alloplastic and autologous material mixture. Patients and methods. The study included 7 selected patients who underwent subantral bone augmentation with a 1/1 autologous and alloplastic material mixture. Subsequently, at the time of dental implant placement, biological samples were taken from the bone augmentation area and were histologically analyzed. The subantral bone resorption rate was also evaluated in parallel. Results. Histological examination evidenced the presence of residual amorphous material in the bone augmentation area. The mean bone resorption rate was 15.15%. The presence of a high bone resorption rate was correlated with the presence of a smaller residual amorphous material amount in the subantral bone augmentation area. Conclusions. The association of autologous and alloplastic material for subantral bone augmentation improves the characteristics of the two material types.
Lepidobatrachus asper Budgett,1899 (Amphibia: Anura: Ceratophryidae): new country record, distribution map and natural history notes
Authors: Sugai José Luiz Massao Moreira , Faggioni Gabriel Paganini , Piatti Liliana , Lemos Anderson Aparecido , Souza Franco Leandro , Prado Cynthia Peralta de Almeida
Published: January 2015

Lepidobatrachus asper is a large to medium frog known from the Chaco lowlands of Paraguay and Argentina. We provide the first species record for the Brazilian Chaco, which extends the species geographical distribution ca. 73 km northeast from Puerto Casado, Alto Paraguay Departament, Paraguay. We also provide a distribution map and information about the species habitat conditions and diet. The Brazilian Chaco is still poorly surveyed, and the rapid environmental degradation can lead to local extinctions of certain species.
Occurrence record of Sus scrofa Linnaeus, 1758 (Mammalia: Artiodactyla) at Estação Ecológica de Itirapina, São Paulo state, Brazil
Authors: Trovati Roberto Guilherme
Published: January 2015

Invasive species are the second cause of biodiversity decline in the world. Among the many invasive species, the Sus scrofa (wild boar) is amongst those that cause more impacts. Our aim was to report the presence of the wild boar in the last remaining open area of Cerrado in the São Paulo state, Brazil. In September 2007 an individual was seen and tracks were also observed during the same period at the Estação Ecológica de Itirapina.
Distribution record of Tantilla alticola Boulenger, 1903 (Squamata: Colubridae) in Coclé Province, Republic of Panama
Authors: Myers Edward A. , Ruane Sara , Knight Karin , Knight James L. , Ray Julie M.
Published: January 2015

A single specimen of Tantilla alticola was collected from Parque Nacional G. D. Omar Torrijos Herrera of Coclé Province, Republic of Panama. This record fills in a gap in the distribution for this species within the cloud forests of Central America.
Plant diversity of Gadchiroli district of Maharashtra, India: a brief survey
Authors: Jagtap Suresh , Mukherjee Sourav
Published: January 2015

A qualitative survey was carried out during 2005- 2010 of all indigenous and naturalized plants of Gadchiroli district, Maharashtra, India. There are 237 species belonging to 184 genera and 73 families which are listed in this paper. Out of 73 families listed, 63 belong to dicotyledonae and 10 belong to monocotyledonae. Dominant families were Fabaceae (21 genera), Acanthaceae (12 genera) followed by Asteracece (9 genera). The nomenclature system followed in this paper is up to date. Three plants (1.63%) listed in this paper come under Vulnerable (VU) and two (1.09%) comes under Lower Risk (LR) categories. Eleven genera (5.98%) are reported to be endemic to Maharashtra state of India. Only one plant species (Agave americana var. americana) was not native of the area and is cultivated. Voucher specimens of the representative plants are submitted at Medicinal Plants Conservation Center (MPCC), Pune, Maharashtra, and the voucher number is provided along with names of plants.