bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin and sulodexide restore cardiac microvascular perfusion capacity in diet-induced obese rats
Authors: van Haare Judith , Kooi M. Eline , van Teeffelen Jurgen W. G. E. , Vink Hans , Slenter Jos , Cobelens Hanneke , Strijkers Gustav J. , Koehn Dennis , Post Mark J. , van Bilsen Marc 
Published: April 2017

Abstract
Background
Disturbances in coronary microcirculatory function, such as the endothelial glycocalyx, are early hallmarks in the development of obesity and insulin resistance. Accordingly, in the present study myocardial microcirculatory perfusion during rest and stress was assessed following metformin or sulodexide therapy in a rat model of diet-induced obesity. Additionally, the effect of degradation of the glycocalyx on myocardial perfusion was assessed in chow-fed rats.

Methods
Rats were fed a high fat diet (HFD) for 8 weeks and were divided into a group without therapy, and groups that received the anti-diabetic drug metformin or the glycocalyx-stabilizing drug sulodexide in their drinking water during the last 4 weeks of the feeding period. Myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle. In an acute experimental setting, hyaluronidase was administered to chow-fed control rats to determine the effect of enzymatical degradation of the glycocalyx on myocardial perfusion.

Results
HFD-rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. We confirmed our earlier findings that the robust increase in myocardial perfusion in chow-fed rats after an adenosine challenge (+56%, p = 0.002) is blunted in HFD rats (+8%, p = 0.68). In contrast, 4-weeks treatment with metformin or sulodexide partly restored the increase in myocardial perfusion during adenosine infusion in HFD rats (+81%, p = 0.002 and +37%, p = 0.02, respectively). Treating chow-fed rats acutely with hyaluronidase, to enzymatically degrade the glyocalyx, completely blunted the increase in myocardial perfusion during stress.

Conclusions
In early stages of HFD-induced insulin resistance myocardial perfusion becomes compromised, a process that can be countered by treatment with both metformin and sulodexide. The adverse effect of acute glycocalyx degradation and protective effect of long-term sulodexide administration on myocardial perfusion provides indirect evidence, suggesting a role for the glycocalyx in preserving coronary microvascular function in pre-diabetic animals.
Using cone beam CT to assess the upper airway after surgery in children with sleep disordered breathing symptoms and maxillary-mandibular disproportions: A clinical pilot
Authors: Alsufyani Noura A. , Noga Michelle L. , Witmans Manisha , Cheng Irene , El-Hakim Hamdy , Major Paul W. 
Published: April 2017

Background The surgical excision of anatomic obstructions such as adenoids, palatine or lingual tonsils are commonly performed in children with sleep disordered breathing (SDB). Imaging studies measuring airway changes post-surgery in the SDB pediatric population are scarce, rarely addresses the nasal cavity, and are based on global measures (e.g. volume) that do not represent the complexity of the upper airway anatomy. The purpose of this pilot is to test the feasibility in using cone beam CT (CBCT) to analyze the nasal and pharyngeal airway space post-surgery using meaningful methods of analyses, and correlating imaging findings with clinical outcomes in children with SDB symptoms and maxillary-mandibular disproportion. Methods Twelve non-syndromic children with SDB symptoms and jaw disproportions were evaluated by interdisciplinary airway team before and after upper airway surgery. CBCT and OSA-18 quality of life questionnaire pre and post-operatively were completed. Conventional and new airway variables were measured based on 3D models of the upper airways and correlated with OSA-18. Conventional measures include volume, surface area, and cross-sectional area. New airway measures include constriction and patency; point-based analyses. Results Eight females and four males were 8.8 ± 2 years with mean BMI of 18.7 ± 3. OSA-18 improved, median (lower quartile-upper quartile) from 64.2 (54.7–79.5) to 37.6 (28.7–43) postoperatively, p < 0.001. The median of all airway measures improved however with very wide range. Subjects with the smallest amounts of constriction relief and/or gain in airway patency presented with least improvement in OSA-18. New airway measures show strong correlation with changes in OSA-18 ( ρ = 0.44 to 0.71) whereas conventional measures showed very weak correlation ( ρ = −0.04 to 0.37). Conclusions Using point-based analyses, new airway measures better explained changes in clinical symptoms compared to conventional measures. Airway patency gained by at least 150% and constriction relief by at least 15% showed marked improvement in OSA-18 by 40–55%, after surgery in the tested cohort.
Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Khorana Alok A. , Mangu Pamela B. , Berlin Jordan , Engebretson Anitra , Hong Theodore S. , Maitra Anirban , Mohile Supriya G. , Mumber Matthew , Schulick Richard , Shapiro Marc , Urba Susan , Zeh Herbert J. , Katz Matthew H.G. 
Published: April 2017

Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.
PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients
Authors: Iwata Hiroji , Im Seock-Ah , Masuda Norikazu , Im Young-Hyuck , Inoue Kenichi , Rai Yoshiaki , Nakamura Rikiya , Kim Jee Hyun , Hoffman Justin T. , Zhang Ke , Giorgetti Carla , Iyer Shrividya , Schnell Patrick T. , Bartlett Cynthia Huang , Ro Jungsil 
Published: April 2017

PurposeTo assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer.Patients and MethodsThe Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment.ResultsThis preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant.ConclusionThis is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.
Genetics of Sex Hormone-Binding Globulin and Testosterone Levels in Fertile and Infertile Men of Reproductive Age
Authors: Grigorova Marina , Punab Margus , Poolamets Olev , Adler Mart , Vihljajev Vladimir , Laan Maris 
Published: April 2017

Context:
Testosterone (T) is a central androgenic hormone, and sex hormone-binding globulin (SHBG) is the major determinant of its bioactivity. There are no acknowledged genetic variants with clear-cut clinical implications, modulating T levels in men.

Objective:
To confirm genetic associations of top loci (SHBG, GCKR, SLCO1B1, and JMJD1C) from genome-wide association (GWA) studies for serum SHBG and T.

Design, Patients:
Groups differing in general and reproductive parameters: young men (n = 540; 19.3 ± 1.8 years), severe idiopathic male infertility patients (n = 641; 31.6 ± 6.0 years), and male partners of pregnant women (n = 324; 31.9 ± 6.6 years). All patients were recruited at the Andrology Centre, Tartu University Hospital, Estonia.

Main Outcome Measure(s):
Genetic associations with reproductive hormones, testicular and sperm parameters (linear regression, additive model); intergroup allele/genotype distribution comparisons.

Results:
Associations with serum SHBG levels were robust for SHBG −68 G&gt;A [rs1799941; meta-analysis: P = 3.7 × 10−14; allelic effect (standard error) = 4.67 (0.62) nmol/L], SHBG +1091 C&gt;T [rs727428; P = 7.3 × 10−11; −3.74 (0.57)], SHBG Pro185Leu [rs6258; P = 1.2 × 10−4, −12.2 (3.17)], and GCKR Pro446Leu [rs1260326; P = 1.5 × 10−4; −2.2 (0.59)]. Measured T concentrations correlated with genetically modulated levels of SHBG (r = 0.48 to 0.74, P &lt; 0.0001), guaranteeing stable availability of free T. Among infertile men, SHBG Pro185Leu substitution showed additional downstream effect on luteinizing hormone [P = 5.1 × 10−5; −1.66 (0.57) IU/L] and follicle-stimulating hormone [P = 3.4 × 10−3; −2.48 (1.23) IU/L]. No associations with male reproductive parameters were detected for SHBG Asp327Asn (rs6259), SLCO1B1 Val174Ala (rs4149056), and JMJD1C intronic variant rs7910927.

Conclusions:
Claims were replicated and additional associations were detected for four of seven tested GWAS top loci. Perspective clinical investigations of these variants are hypotestosteronemia among aging men and pharmacogenetics of hormone replacement therapy.
Defining the inflammatory signature of human lung explant tissue in the presence and absence of glucocorticoid
Authors: Rimington Tracy L , Hodge Emily , Billington Charlotte K , Bhaker Sangita , K C Binaya , Kilty Iain , Jelinsky Scott , Hall Ian P , Sayers Ian 
Published: April 2017

Background: Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. Method: Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM). Inflammatory responses were assessed using Luminex analysis of tissue culture supernatants to measure levels of 21 chemokines, growth factors and cytokines. Results: A robust and reproducible inflammatory signal was detected across all donors for 12 of the analytes measured following LPS stimulation with a modest fold increase (<2-fold) in levels of CCL22, IL-4, and IL-2; increases of 2-4-fold in levels of CXCL8, VEGF and IL-6 and increases >4-fold in CCL3, CCL4, GM-CSF, IL-10, TNF-α and IL-1β. The inflammatory signal induced by IL-1β stimulation was less than that observed with LPS but resulted in elevated levels of 7 analytes (CXCL8, CCL3, CCL4, GM-CSF, IL-6, IL-10 and TNF-α). The inflammatory responses induced by both stimulations was supressed by dexamethasone for the majority of analytes. Conclusions: These data provide proof of concept that this ex vivo human lung explant model is responsive to inflammatory signals and could be used to investigate the anti-inflammatory effects of existing and novel compounds. In addition this model could be used to help define the mechanisms and pathways involved in development of inflammatory airway disease. Abbreviations: COPD: Chronic Obstructive Pulmonary Disease; ICS: inhaled corticosteroids; LPS: lipopolysaccharide; IL-1β: interleukin-1 beta; PSF: penicillin, streptomycin and fungizone
Analysis of Biological Interactions by Affinity Chromatography: Clinical and Pharmaceutical Applications
Authors: Hage David S 
Published: April 2017

AbstractBACKGROUNDThe interactions between biochemical and chemical agents in the body are important in many clinical processes. Affinity chromatography and high-performance affinity chromatography (HPAC), in which a column contains an immobilized biologically related binding agent, are 2 methods that can be used to study these interactions.CONTENTThis review presents various approaches that can be used in affinity chromatography and HPAC to characterize the strength or rate of a biological interaction, the number and types of sites that are involved in this process, and the interactions between multiple solutes for the same binding agent. A number of applications for these methods are examined, with an emphasis on recent developments and high-performance affinity methods. These applications include the use of these techniques for fundamental studies of biological interactions, high-throughput screening of drugs, work with modified proteins, tools for personalized medicine, and studies of drug–drug competition for a common binding agent.SUMMARYThe wide range of formats and detection methods that can be used with affinity chromatography and HPAC for examining biological interactions makes these tools attractive for various clinical and pharmaceutical applications. Future directions in the development of small-scale columns and the coupling of these methods with other techniques, such as mass spectrometry or other separation methods, should continue to increase the flexibility and ease with which these approaches can be used in work involving clinical or pharmaceutical samples.
‘Going far is returning’: Dance Movement Psychotherapists find resilience and learning and call for more collaboration and dialogue
Authors: Coaten Richard , Williams Sarah 
Published: April 2017

Abstract
Dance Movement Psychotherapy (DMP) can contribute more to the care of people with dementia, a subject of increasing interest and importance in the United Kingdom and globally. This article was first presented at the International Centre for Research in Arts Therapies Conference at Anglia Ruskin University, Cambridge. It contributes to growing knowledge in the field by discussing and analysing two different, yet complementary narratives about practice then and now: first, from the perspective and learning of someone just starting out in their career as a dance movement psychotherapist and second from one who started out using dance therapeutically in the mid-1980s. The outcomes of this dialogue have helped build resilience, have fostered dialogue and learning between practitioners, and are clinically relevant to students in training and experienced practitioners alike. Outcomes also shed light on transference and counter-transference, and make a call for more collaboration and communication between dance movement psychotherapists just starting out in their careers and those more experienced. Much can be learnt from more collaboration and dialogue between DMP’s, dancers and other somatic practitioners working in the dementia care field.
Reconnecting to the feminine: Transformative effects of Sensual Movement and Dance
Authors: Fasullo Lisa , Lurquin John , Bodeker Gerard 
Published: April 2017

Abstract
Dance is documented to produce substantive neurophysiological, psychological and quality-of-life benefits. Adding to that research we document the therapeutic effects of Sensual Movement and Dance in restoring women to a state of wholeness, enhanced self-expression and a general sense of ease. Specifically, we report on the physical, psychological, emotional and spiritual findings of an eight-week pilot research study. Informing the design of the pilot are reports over a ten-year period by women participants in a Sensual Movement and Dance programme that indicate consistent growth in self-confidence, reduction in stress, marked decrease in levels of self-consciousness, and improvements in women’s senses of autonomy and overall quality of life. In the pilot study, most participants also reported improvements in emotional regulation and a decrease in anxiety and depression. According to study participants, more than simply talking about sensuality, women want to feel more of it in themselves and in their lives.
Avaliação da infiltração marginal por corante em dentes apicectomizados e recobertos com materiais adesivos após irradiação com laser Nd:YAG
Authors: Gomes Ana Paula Martins , Hakumata Lilian Yoshiko , Kubo Claudio Hideki , Damião Álvaro José , Lavras Luis Carlos 
Published: April 2017

Na tentativa de eliminar a infiltração apical, muitos materiais foram pesquisados como retrobturadores, mas apesar das vantagens e desvantagens de cada um, sabe-se que o material ideal ainda não foi encontrado. Procurando reduzir a infiltração apical, o laser tem sido utilizado para ocluir túbulos dentinários seccionados pela fusão e recristalização da superfície dentinária, apresentando bons resultados. O objetivo deste trabalho foi avaliar a capacidade de selamento apical de quatro materiais odontológicos empregados no recobrimento de ápices radiculares seccionados após a irradiação com laser Nd:YAG. Foram utilizados 45 dentes unirradiculados humanos extraídos, divididos em três grupos com 15 dentes cada. Os canais radiculares foram preparados e obturados com guta-percha e cimento pela técnica da condensação lateral ativa. Os dentes receberam apicectomia e recobrimento da superfície radicular seccionada com sistema adesivo dentinário e resina composta, cimento de ionômero de vidro e compômero, após a irradiação com laser Nd:YAG. Os espécimes foram imersos em corante azul de metileno a 2% durante uma semana a 370C e as infiltrações ocorridas foram avaliadas com auxílio de um estereomicroscópio. Pôde-se concluir que, no recobrimento apical após a irradiação com laser, o cimento de ionômero de vidro e o compômero foram equivalentes entre si e significativamente melhores que o sistema adesivo dentinário e resina composta.
Valores normais da amplitude do movimento mandibular em crianças
Authors: Leles Cláudio R. , Neto José Jeová Siebra Moreira , Giro Elisa Maria A. , Compagnoni Marco Antonio 
Published: April 2017

A restrição da mobilidade mandibular é um dos principais sinais clínicos de problemas disfuncionais e a medida dos limites de movimento mandibular é uma importante variável na avaliação do estado funcional do sistema mastigatório. Dessa forma, medidas de referência da amplitude mínima e máxima desses movimentos devem ser definidos de acordo com as várias faixas etárias. O objetivo deste trabalho é propor limites de valores normais de mobilidade na avaliação clínica da amplitude de movimento mandibular em crianças. Foram avaliadas 37 crianças, 18 do sexo feminino e 19 do sexo masculino, com idade de 3 a 11 anos (média de 6,7 anos), sendo que nenhuma delas apresentava sinais e sintomas relacionados a desordens funcionais, de acordo com os índices anamnésico e disfuncional de Helkimo. Com o auxílio de uma régua milimetrada foram obtidas medidas da amplitude da abertura máxima voluntária (AMV), abertura assistida (AA) e movimentos excursivos (ME), e estabelecidos os valores de probabilidade dos limites de distribuição normal (probabilidade de 95%). Houve correlação positiva entre as medidas de movimento e a idade das crianças e as médias da amplitude normal de mobilidade mandibular foram: AMV = 41,9 (± 4,7) mm; AA = 44,6 (± 4,7) mm; ME = 6,9 (± 1,5) mm. De acordo com os resultados obtidos, os limites de valores normais do movimento mandibular foram estabelecidos em: 33 > AMV < 51 mm, 35 > AA < 54 mm, e 4 > ME < 10 mm.
Avaliação da capacidade de impermeabilização do cianoacrilato e do adesivo dentinário autocondicionante em canais obturados e preparados para retentor intra-radicular
Authors: Menezes Marcia M. , Andreatta Filho Osvaldo D. , Soares Luiz F. , Valera Marcia C. , Araujo Maria A. M. de 
Published: April 2017

O objetivo deste trabalho foi avaliar a microinfiltração em canais obturados e preparados para retentor intra-radicular após impermeabilização com cianoacrilato ou adesivo dentinário. Utilizaram-se 36 dentes unirradiculados humanos com um único canal que tiveram a coroa seccionada padronizando as raízes em 16mm. Após o preparo biomecânico e para retentor intra-radicular, os canais foram obturados com cimento Sealapex e as obturações cortadas com instrumento aquecido deixando-se um remanescente de 5mm. Os grupos foram divididos de acordo com o material utilizado para impermeabilização das paredes do canal e do remanescente da obturação: G1: etil-cianoacrilato (Super Bonder); G2: adesivo dentinário auto-condicionante One-Up Bond F e G3: sem impermeabilização (controle). As raízes foram incubadas em saliva artificial por 14 dias e após, imersas em solução de rhodamina 2%. Para os dados de infiltração em direção apical utilizou-se a análise estatística ANOVA e Teste de Tukey, e em direção ao cemento os dados foram submetidos ao teste estatístico Kruskall-Wallis e Dunn (p<0,05). Os resultados revelaram que, em direção ao cemento, o G1 mostrou valores menores de infiltração em relação aos G2 e G3 (p=0,0001) e, em direção apical, os G1 e G2 foram equivalentes e o G3 mostrou valores maiores de infiltração estatisticamente significante (p=0,0001). Concluiu se que a impermeabilização de canais radiculares preparados para retentor intra-radicular pode ser realizada com cianoacrilato ou adesivo dentinário sendo o cianoacrilato mais eficaz pois impede também a infiltração em direção ao cemento radicular.