bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of human dermal allograft thickness on glenohumeral stability for superior capsular reconstruction in irreparable supraspinatus tears: A biomechanical analysis of the superior capsular reconstruction – A cadaveric study
Authors: Smith Geoffrey CS , Im Heon Y , Lam Patrick H
Published: May 2020

Purpose

The objective of this study was to compare the biomechanics of using a double layered human dermal allograft to a single layered human dermal allograft in superior capsular reconstruction.

Methods

Five cadaveric shoulders were tested. The superior translation of the humerus and the subacromial contact pressure were measured at 0°, 30° and 60° of glenohumeral abduction in the following six conditions: (1) intact rotator cuff, (2) irreparable supraspinatus tear, (3) superior capsular reconstruction using a double layered human dermal allograft with and (4) without posterior suturing, (5) superior capsular reconstruction using a single human dermal allograft with and (6) without posterior suturing.

Results

There was a significant increase in superior translation of the humerus and subacromial contact pressure when comparing torn supraspinatus to intact shoulder. All superior capsular reconstruction repairs lead to a reduction in superior translation and subacromial contact pressures compared to after the supraspinatus tear except for single layered superior capsular reconstruction repair without posterior suturing. There was no difference in superior translation and subacromial contact pressures comparing the intact shoulder to any of the superior capsular reconstruction constructs.

Conclusion

Superior capsular reconstruction using a single or double layered human dermal allograft improves superior translation after supraspinatus repair. There is some biomechanical benefit of a double layered human dermal allograft technique over a single layered graft technique in superior capsular reconstruction.

Level of Evidence

IV
Applications and Implications of Service Robots in Hospitality
Authors: Tuomi Aarni , Tussyadiah Iis P. , Stienmetz Jason
Published: May 2020

Service robots continue to permeate and automate the hospitality sector. In doing so, these technological innovations pose to radically change current service production and delivery practices and, consequently, service management and marketing strategies. This study explores the various impacts of robotization in the sector by offering one of the first empirical accounts on the current state-of-the-art of service robotics as deployed in hospitality service encounters. The results suggest that service robots either support or substitute employees in service encounters. They also offer hospitality businesses a novel point of differentiation, but only if properly integrated as part of wider marketing efforts. Finally, the automation of tasks, processes, and, ultimately, jobs has serious socioeconomic implications both at the microlevel and macrolevel. Consequently, hospitality executives need to consider where and how to apply robotization to strike a balance between operational efficiency and customer expectations. Displaying ethical leadership is key to reaping the benefits of the robot revolution.
Protecting Democracy from Disinformation: Normative Threats and Policy Responses
Authors: Tenove Chris
Published: May 2020

Following public revelations of interference in the United States 2016 election, there has been widespread concern that online disinformation poses a serious threat to democracy. Governments have responded with a wide range of policies. However, there is little clarity in elite policy debates or academic literature about what it actually means for disinformation to endanger democracy, and how different policies might protect it. This article proposes that policies to address disinformation seek to defend three important normative goods of democratic systems: self-determination, accountable representation, and public deliberation. Policy responses to protect these goods tend to fall in three corresponding governance sectors: self-determination is the focus of international and national security policies; accountable representation is addressed through electoral regulation; and threats to the quality of public debate and deliberation are countered by media regulation. The article also reveals some of the challenges and risks in these policy sectors, which can be seen in both innovative and failed policy designs.
Relationships between body mass index with oral estradiol dose and serum estradiol concentration in transgender adults undergoing feminising hormone therapy
Authors: Nolan Brendan J. , Brownhill Adam , Bretherton Ingrid , Wong Peggy , Fox Susan , Locke Peter , Russell Nicholas , Grossmann Mathis , Zajac Jeffrey D. , Cheung Ada S.
Published: May 2020

Aim:

Feminising hormone therapy with estradiol is used to align an individual’s physical characteristics with their gender identity. Given considerable variations in doses of estradiol therapy administered as gender-affirming hormone therapy (GAHT), we aimed to assess if body mass index (BMI) correlated with estradiol dose/concentration and assess the correlation between estradiol dose and estradiol concentrations.

Methods:

In a retrospective cross-sectional study, we analysed transgender individuals attending a primary or secondary care clinic in Melbourne, Australia who were prescribed oral estradiol valerate for at least 6 months and had estradiol dose and concentration available. Estradiol concentration was measured by immunoassay. Outcomes were the correlation between estradiol dose and BMI, and estradiol dose and estradiol concentration.

Results:

Data were available for 259 individuals {median age 25.8 [interquartile range (IQR) 21.9, 33.5] years}. Median duration of estradiol therapy was 24 (15, 33) months. Median estradiol concentration was 328 (238, 434) pmol/l [89 (65, 118) pg/ml] on 6 (4, 8) mg estradiol valerate. Median BMI was 24.7 (21.8, 28.6) kg/m2. There was a weak positive correlation between estradiol dose and estradiol concentration ( r = 0.156, p = 0.012). There was no correlation between BMI and estradiol concentration achieved ( r = −0.063, p = 0.413) or BMI and estradiol dose ( r = 0.048, p = 0.536). Estradiol concentrations were within the target range recommended in consensus guidelines in 172 (66%) individuals.

Conclusion:

Estradiol dose was only weakly correlated with estradiol concentration, suggesting significant interindividual variability. Prescription of estradiol dose should not be based upon an individual’s BMI, which did not correlate with estradiol concentration achieved. In all, 66% of individuals achieved estradiol concentrations recommended in Australian consensus guidelines with a relatively high oral estradiol dose.
Cardinal Mazarin’s Breviary of politics: Exploring parallelisms between the Baroque and public relations in a post-truth society
Authors: García César
Published: May 2020

This article suggests we live in a neo-Baroque era of communication between organizations and publics. The 17th and 18th centuries are particularly rich in literature about the importance of building a reputation to get and retain power. These authors consider communication management, a key factor in how monarchs, princes, and governments must relate to their constituencies to make their power sustainable. A chief minister to the French kings Louis XIII and Louis XIV, Cardinal Mazarin’s Breviary of Politics offers a solid representation of Baroque thought on communication and power. A critical analysis of his book shows that many of the elements associated with Baroque art, a style born with a propagandistic purpose that appeals to irrationality and primary emotions through a combination of dramatic visual elements, could be found to have profound resemblances with the way public relations is practiced in our current post-truth era. This era shows how communication managers and leaders have been able to reach their objectives by being irrational, thanks to the echo chamber provided by both social media and mainstream media with their multiplicity of truths, where a community of like-minded individuals, sort of a correlate of the ‘believers’ in the Baroque period, are looking to confirm their preconceptions. The resemblances between Mazarin and Baroque’s simulation art, privileging appearances, the visual and emotional over facts, squares surprisingly well with how recent or current leaders such as Donald J. Trump, Boris Johnson or George W. Bush connect with the masses. Perhaps these political leaders are being irrational, but there is a rationality in using irrationality to their advantage.
Development and Evaluation of Health Promotion Training Program for Community Pharmacists in Oyo State, Nigeria
Authors: Oseni Yejide O. , Afolabi Margaret O.
Published: May 2020

Background. Community pharmacists have considered training in health promotion services to improve their practice, but no published study in Nigeria has provided such training to improve practice change. Objectives. The study aims to develop and evaluate the appropriateness and applicability of health promotion training provided for community pharmacists after identifying the gaps in the provision of health promotion services in community pharmacies in Oyo State, Nigeria. Materials and Methods. A 2-day training was developed, conducted, and evaluated on a 5-point Likert-type scale, semistructured questionnaire administered to randomly sampled 80 respondents. It rated participants’ opinions on the training content, resource persons, and perceived sufficiency of the training. Data were analyzed using IBM SPSS Version 21 with descriptive statistics while open-ended responses were analyzed thematically. Results. Response rate was 72.5%. Total mean score of participants’ opinions on the training program was 45.67 ± 5.802 (range of 10–50; midpoint 30). An average score ranged from 3.97 to 4.61 out of the total score of 5 was obtained for good presentation abilities of the resource persons. Respondents (93.1%) strongly agreed and agreed that the training was sufficient to deliver the health promotion services (4.36 ± 0.765). They suggested the need to organize the training periodically (15.5%), training to cover other areas like use of diagnostic test kit and immunization (13.8%) and allowance of more time for interaction and sharing of experiences by participants (10.3%). Conclusion. The training was adequate for use by community pharmacists and fit for the purpose it was designed for.
Advanced Data Collection and Analysis in Data-Driven Manufacturing Process
Authors: Xu Ke , Li Yingguang , Liu Changqing , Liu Xu , Hao Xiaozhong , Gao James , Maropoulos Paul G.
Published: May 2020

The rapidly increasing demand and complexity of manufacturing process potentiates the usage of manufacturing data with the highest priority to achieve precise analyze and control, rather than using simplified physical models and human expertise. In the era of data-driven manufacturing, the explosion of data amount revolutionized how data is collected and analyzed. This paper overviews the advance of technologies developed for in-process manufacturing data collection and analysis. It can be concluded that groundbreaking sensoring technology to facilitate direct measurement is one important leading trend for advanced data collection, due to the complexity and uncertainty during indirect measurement. On the other hand, physical model-based data analysis contains inevitable simplifications and sometimes ill-posed solutions due to the limited capacity of describing complex manufacturing process. Machine learning, especially deep learning approach has great potential for making better decisions to automate the process when fed with abundant data, while trending data-driven manufacturing approaches succeeded by using limited data to achieve similar or even better decisions. And these trends can demonstrated be by analyzing some typical applications of manufacturing process.
Bone density of first and second segments of normal and dysmorphic sacra
Authors: Radley Joseph M. , Hill Brian W. , Nicolaou Daemeon A. , Huebner Stephen B. , Napier Kelby B. , Salazar Dane H.
Published: May 2020

Background

Iliosacral screw fixation is safe and effective but can be complicated by loss of fixation, particularly in patients with osteopenic bone. Sacral morphology dictates where iliosacral screws may be placed when stabilizing pelvic ring injuries. In dysmorphic sacra, the safe osseous corridor of the upper sacral segment (S1) is smaller and lacks a transsacral corridor, increasing the need for fixation in the second sacral segment (S2). Previous evidence suggests that S2 is less dense than S1. The aim of this cross-sectional study is to further evaluate bone mineral density (BMD) of the S1 and S2 iliosacral osseous pathways through morphology stratification into normal and dysmorphic sacra.

Materials and methods

Pelvic computed tomography scans of 50 consecutive trauma patients, aged 18 to 50 years, from a level 1 trauma center were analyzed prospectively. Five radiographic features (upper sacral segment not recessed in the pelvis, mammillary bodies, acute alar slope, residual S1 disk, and misshapen sacral foramen) were used to identify dysmorphic characteristics, and sacra with four or five features were classified as dysmorphic. Hounsfield unit values were used to estimate the regional BMD of S1 and S2. Student’s t-test was utilized to compare the mean values at each segment, with statistical significance being set at p < 0.05. No change in clinical management occurred as a result of inclusion in this study.

Results

A statistical difference in BMD was appreciated between S1 and S2 in both normal and dysmorphic sacra (p < 0.0001), with 28.4% lower density in S2 than S1. Further, S1 in dysmorphic sacra tended to be 4% less dense than S1 in normal sacra (p = 0.047). No difference in density was appreciated at S2 based on morphology.

Conclusions

Our results would indicate that, based on BMD alone, fixation should be maximized in S1 prior to fixation in S2. In cases where S2 fixation is required, we recommend that transsacral fixation should be strongly considered if possible to bypass the S2 body and achieve fixation in the cortical bone of the ilium and sacrum.

Level of evidence

Level III.
Multipathway synergy promotes testicular transition from growth to spermatogenesis in early-puberty goats
Authors: Bo Dongdong , Jiang Xunping , Liu Guiqiong , Xu Feng , Hu Ruixue , Wassie Teketay , Chong Yuqing , Ahmed Sohail , Liu Chenhui , Girmay Shishay
Published: May 2020

Background

The microscopic process of postnatal testicular development in early-puberty animals is poorly understood. Therefore, in this study, 21 male Yiling goats with average ages of 0, 30, 60, 90, 120, 150 and 180 days old (each age group comprised three goats) were used to study the changes in organs, tissues and transcriptomes during postnatal testicle development to obtain a broad and deep insight into the dynamic process of testicular transition from growth to spermatogenesis in early-puberty animals.

Results

The inflection point of testicular weight was at 119 days postpartum (dpp), and the testicular weight increased rapidly from 119 dpp to 150 dpp. Spermatozoa were observed in the testis at 90 dpp by using haematoxylin–eosin staining. We found from the transcriptome analysis of testes that the testicular development of Yiling goat from birth to 180 dpp experienced three stages, namely, growth, transition and spermatogenesis stages. The goats in the testicular growth stage (0–60 dpp) showed a high expression of growth-related genes in neurogenesis, angiogenesis and cell junction, and a low expression of spermatogenesis-related genes. The goats aged 60–120 dpp were in the transitional stage which had a gradually decreased growth-related gene transcription levels and increased spermatogenesis-related gene transcription levels. The goats aged 120–180 dpp were in the spermatogenesis stage. At this stage, highly expressed spermatogenesis-related genes, downregulated testicular growth- and immune-related genes and a shift in the focus of testicular development into spermatogenesis were observed. Additionally, we found several novel hub genes,which may play key roles in spermatogenesis, androgen synthesis and secretion, angiogenesis, cell junction and neurogenesis. Moreover, the results of this study were compared with previous studies on goat or other species, and some gene expression patterns shared in early-puberty mammals were discovered.

Conclusions

The postnatal development of the testis undergoes a process of transition from organ growth to spermatogenesis. During this process, spermatogenesis-related genes are upregulated, whereas neurogenesis-, angiogenesis-, cell junction-, muscle- and immune-related genes are downregulated. In conclusion, the multipathway synergy promotes testicular transition from growth to spermatogenesis in early-puberty goats and may be a common rule shared by mammals.
In vitro conjugation kinetics of AmpC, broad spectrum and extended-spectrum beta-lactamase-producing Escherichia coli donors and various Enterobacteriaceae recipients
Authors: Saliu Eva-Maria , Zentek Jürgen , Vahjen Wilfried
Published: May 2020

Background

Extended spectrum beta-lactamase (ESBL)-producing enterobacteria pose a major hazard to public health. Due to the possibility of genetic transfer, ESBL genes might spread to pathogenic enterobacterial strains. Thus, information on possible genetic transfer between enterobacteria is of high interest. It was therefore the aim of this in vitro study to screen the capacity of a wide range of Enterobacteriaceae for differences in conjugation at different time points with five ESBL-producing Escherichia coli strains.

Results

Conjugation frequencies for five potential E. coli donor strains producing the enzymes CTX-M-1, CTX-M-15, SHV-12, TEM-1, TEM-52 and CMY-2, and six potential recipient strains commonly detected in the gastrointestinal tract of poultry (E. coli, Serratia marcescens subsp. marcescens, Enterobacter cloacae, Salmonella (S.) enterica serovar Typhimurium and Proteus mirabilis) were obtained. Different combinations of donor and recipient strains were co-incubated for between 0 and 22 h and spread on selective agar. Conjugation frequencies were calculated as transconjugants per donor.

Some donor and recipient strain combinations did not perform plasmid transfer within 22 h. Hence, the recipient Proteus mirabilis did not accept plasmids from any of the given donors and the E. coli ESBL10716 donor was unable to transfer its plasmid to any recipient. Enterobacter cloacae only accepted the plasmids from the donors E. coli ESBL10708 and E. coli ESBL10716 while E. coli ESBL10708 did not transfer its plasmid to Serratia marcescens subsp. marcescens. E. coli IMT11716 on the other hand did not perform conjugation with the donor E. coli ESBL10689. The remaining mating pairs differed in conjugation frequency, ranging from 10− 5 to 10− 9 transconjugants/donor. The earliest conjugation events were detected after 4 h. However, some mating pairs turned positive only after 22 h of coincubation.

Conclusion

A suitable mating pair for future in vivo studies to combat transfer of antibiotic resistance to pathogenic bacteria in broiler chicken was determined. The results of this study also suggest that the kinetic of conjugation differs between mating pairs and is independent of species origin. This should be considered when performing conjugation experiments.
Exploring patient-reported barriers to advance care planning in family practice
Authors: Bernard Carrie , Tan Amy , Slaven Marissa , Elston Dawn , Heyland Daren K. , Howard Michelle
Published: May 2020

Background

Although patient-centred care has become increasingly important across all medical specialties, when it comes to end of life care, research has shown that treatments ordered are not often concordant with people’s expressed preferences. Patient and family engagement in Advance Care Planning (ACP) in the primary care setting could improve the concordance between patients’ wishes and the healthcare received when patients cannot speak for themselves. The aim of this study was to better understand the barriers faced by older patients regarding talking to their family members and family physicians about ACP.

Methods

In this multi-site cross-sectional study, three free text questions regarding reasons patients found it difficult to discuss ACP with their families or their family physicians were part of a self-administered questionnaire about patients’ knowledge of and engagement in ACP. The questionnaire, which included closed ended questions followed by three probing open ended questions, was distributed in 20 family practices across 3 provinces in Canada. The free text responses were analyzed using thematic analysis and form the basis of this paper.

Results

One hundred two participants provided an analyzable response to the survey when asked why they haven’t talked to someone about ACP. Two hundred fifty-four answered the question about talking to their physician and 340 answered the question about talking to family members. Eight distinct themes emerged from the free text response analysis: 1. They were too young for ACP; 2. The topic is too emotional; 3. The Medical Doctor (MD) should be responsible for bringing up ACP 4. A fear of negatively impacting the patient-physician relationship; 5. Not enough time in appointments; 6. Concern about family dynamics; 7. It’s not a priority; and 8. A lack of knowledge about ACP.

Conclusions

Patients in our sample described many barriers to ACP discussions, including concerns about the effect these discussions may have on relationships with both family members and family physicians, and issues relating to patients’ knowledge and interpretation of the importance, responsibility for, or relevance of ACP itself. Family physicians may be uniquely placed to leverage the longitudinal, person- centred relationship they have with patients to mitigate some of these barriers.
Knowledge and practices of primary care physicians or general practitioners treating post-infectious Irritable Bowel Syndrome
Authors: Austhof Erika , Schaefer Kenzie , Faulkner Jaime , Bach Laura , Riddle Mark , Pogreba-Brown Kristen
Published: May 2020

Background

Post-infectious Irritable Bowel Syndrome (PI-IBS) is a functional bowel disorder which has significant impacts to a patient’s quality of life. No IBS-specific biomarker or treatment regimen for PI-IBS currently exists, therefore understanding practice patterns and variance is of interest.

Methods

This online survey of primary care physicians and general practitioners in the USA aimed to understand the knowledge and treatment of PI-IBS within the physician’s current practice. Summary statistics are provided with a commentary on implications for practices and treatment of PI-IBS.

Results

Most physician survey respondents (n = 50) were aware of PI-IBS, but less than half discussed this condition as a possible outcome in their patients with a recent gastrointestinal infection. Most physicians indicated that they would treat the patients themselves with a focus on managing IBS through different treatment modalities based on severity. Treatment for PI-IBS followed IBS recommendations, but most physicians also prescribed a probiotic for therapy. Physicians estimated that 4 out of 10 patients who develop PI-IBS will have life-long symptoms and described significant impacts to their patient’s quality of life. Additionally, physicians estimated a significant financial burden for PI-IBS patients, ranging from $100–1000 (USD) over the course of their illness. Most physicians agreed that they would use a risk score to predict the probability of their patients developing PI-IBS, if available.

Conclusions

While this survey is limited due to sample size, physician knowledge and treatment of PI-IBS was consistent across respondents. Overall, the physicians identified significant impacts to patient’s quality of life due to PI-IBS.
Impact of hemodialysis and post-dialysis period on granular activity levels
Authors:   For the HDFIT Study Investigators, Larkin John W. , Han Maggie , Han Hao , Guedes Murilo H. , Gonçalves Priscila Bezerra , Poli-de-Figueiredo Carlos Eduardo , Cuvello-Neto Américo Lourenço , Barra Ana Beatriz L. , de Moraes Thyago Proença , Usvyat Len A. , Kotanko Peter , Canziani Maria Eugenia F. , Raimann Jochen G. , Pecoits-Filho Roberto
Published: May 2020

Background

Physical activity (PA) is typically lower on hemodialysis (HD) days. Albeit intradialytic inactivity is expected, it is unknown whether recovery after HD contributes to low PA. We investigated the impact of HD and post-HD period on granular PA relative to HD timing.

Methods

We used baseline data from the HDFIT trial conducted from August 2016 to October 2017. Accelerometry measured PA over 1 week in patients who received thrice-weekly high-flux HD (vintage 3 to 24 months), were clinically stable, and had no ambulatory limitations. PA was assessed on HD days (0 to ≤24 h after start HD), first non-HD days (> 24 to ≤48 h after start HD) and second non-HD day (> 48 to ≤72 h after start HD). PA was recorded in blocks/slices: 4 h during HD, 0 to ≤2 h post-HD (30 min slices), and > 2 to ≤20 h post-HD (4.5 h slices). Blocks/slices of PA were captured at concurrent/parallel times on first/second non-HD days compared to HD days.

Results

Among 195 patients (mean age 53 ± 15 years, 71% male), step counts per 24-h were 3919 ± 2899 on HD days, 5308 ± 3131 on first non-HD days (p < 0.001), and 4926 ± 3413 on second non-HD days (p = 0.032). During concurrent/parallel times to HD on first and second non-HD days, patients took 1308 and 1128 more steps (both p < 0.001). Patients took 276 more steps and had highest rates of steps/hour 2-h post-HD versus same times on first non-HD days (all p < 0.05). Consistent findings were observed on second non-HD days.

Conclusions

PA was higher within 2-h of HD versus same times on non-HD days. Lower PA on HD days was attributable to intradialytic inactivity. The established PA profiles are of importance to the design and development of exercise programs that aim to increase activity during and between HD treatments.

Trial registration

HDFIT was prospectively registered 20 April 2016 on ClinicalTrials.gov (NCT02787161)
Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer
Authors: Singleton Dean C. , Dechaume Anne-Lise , Murray Pamela M. , Katt William P. , Baguley Bruce C. , Leung Euphemia Y.
Published: May 2020

Background

Glutamine serves as an important nutrient with many cancer types displaying glutamine dependence. Following cellular uptake glutamine is converted to glutamate in a reaction catalysed by mitochondrial glutaminase. This glutamate has many uses, including acting as an anaplerotic substrate (via alpha-ketoglutarate) to replenish TCA cycle intermediates. CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase that has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients.

Methods

A panel of eleven breast cancer cell lines was used to investigate the anti-proliferative effects of the glutaminase inhibitors CB-839 and BPTES in different types of culture medium, with or without additional pyruvate supplementation. The abundance of the TCA cycle intermediate fumarate was quantified as a measure if TCA cycle anaplerosis. Pyruvate secretion by TNBC cultures was then assessed with or without AZD3965, a monocarboxylate transporter 1 (MCT1) inhibitor. Finally, two dimensional (2D) monolayer and three dimensional (3D) spheroid assays were used to compare the effect of microenvironmental growth conditions on CB-839 activity.

Results

The anti-proliferative activity of CB-839 in a panel of breast cancer cell lines was similar to published reports, but with a major caveat; growth inhibition by CB-839 was strongly attenuated in culture medium containing pyruvate. This pyruvate-dependent attenuation was also observed with a related glutaminase inhibitor, BPTES. Studies demonstrated that exogenous pyruvate acted as an anaplerotic substrate preventing the decrease of fumarate in CB-839-treated conditions. Furthermore, endogenously produced pyruvate secreted by TNBC cell lines was able to act in a paracrine manner to significantly decrease the sensitivity of recipient cells to glutaminase inhibition. Suppression of pyruvate secretion using the MCT1 inhibitor AZD3965, antagonised this paracrine effect and increased CB-839 activity. Finally, CB-839 activity was significantly compromised in 3D compared with 2D TNBC culture models, suggesting that 3D microenvironmental features impair glutaminase inhibitor responsiveness.

Conclusion

This study highlights the potential influence that both circulating and tumour-derived pyruvate can have on glutaminase inhibitor efficacy. Furthermore, it highlights the benefits of 3D spheroid cultures to model the features of the tumour microenvironment and improve the in vitro investigation of cancer metabolism-targeted therapeutics.
Independence of HIF1a and androgen signaling pathways in prostate cancer
Authors: Tran Maxine G. B. , Bibby Becky A. S. , Yang Lingjian , Lo Franklin , Warren Anne Y. , Shukla Deepa , Osborne Michelle , Hadfield James , Carroll Thomas , Stark Rory , Scott Helen , Ramos-Montoya Antonio , Massie Charlie , Maxwell Patrick , West Catharine M. L. , Mills Ian G. , Neal David E.
Published: May 2020

Background

Therapeutic targeting of the androgen signaling pathway is a mainstay treatment for prostate cancer. Although initially effective, resistance to androgen targeted therapies develops followed by disease progression to castrate-resistant prostate cancer (CRPC). Hypoxia and HIF1a have been implicated in the development of resistance to androgen targeted therapies and progression to CRCP. The interplay between the androgen and hypoxia/HIF1a signaling axes was investigated.

Methods

In vitro stable expression of HIF1a was established in the LNCaP cell line by physiological induction or retroviral transduction. Tumor xenografts with stable expression of HIF1a were established in castrated and non-castrated mouse models. Gene expression analysis identified transcriptional changes in response to androgen treatment, hypoxia and HIF1a. The binding sites of the AR and HIF transcription factors were identified using ChIP-seq.

Results

Androgen and HIF1a signaling promoted proliferation in vitro and enhanced tumor growth in vivo. The stable expression of HIF1a in vivo restored tumor growth in the absence of endogenous androgens. Hypoxia reduced AR binding sites whereas HIF binding sites were increased with androgen treatment under hypoxia. Gene expression analysis identified seven genes that were upregulated both by AR and HIF1a, of which six were prognostic.

Conclusions

The oncogenic AR, hypoxia and HIF1a pathways support prostate cancer development through independent signaling pathways and transcriptomic profiles. AR and hypoxia/HIF1a signaling pathways independently promote prostate cancer progression and therapeutic targeting of both pathways simultaneously is warranted.
CYP and SXR gene polymorphisms influence in opposite ways acute rejection rate in pediatric patients with renal transplant
Authors: Turolo Stefano , Edefonti Alberto , Ghio Luciana , Testa Sara , Morello William , Montini Giovanni
Published: May 2020

Background

We evaluated the role of CYP3A5, ABCB1 and SXR gene polymorphisms in the occurrence of acute kidney rejection in a cohort of pediatric renal transplant recipients.

Methods

Forty-nine patients were genotyped for CYP3A5, ABCB1 and SXR polymorphisms and evaluated with tacrolimus through levels in a retrospective monocenter study.

Results

Patients with the A allele of CYP3A5 treated with tacrolimus had a higher risk of acute rejection than those without the A allele, while patients carrying the homozygous GG variant for SXR A7635GG did not show any episode of acute rejection.

Conclusion

Genetic analysis of polymorphisms implicated in drug metabolism and tacrolimus trough levels may help to forecast the risk of acute rejection and individualize drug dosage in children undergoing renal transplantation.
Incidence and risk factors of spinal epidural hemorrhage after spine surgery: a cross-sectional retrospective analysis of a national database
Authors: Park Ji Hyun , Park Sunny , Choi Soo An
Published: May 2020

Background

With increasing number of patients undergoing spine surgery, the spinal epidural hemorrhage (SEH) has become a growing concern. However, current studies on SEH rely on case reports or observations from a single center. Our study attempted to demonstrate the incidence rate and risk factors of SEH using a national dataset.

Methods

A total of 17,549 spine surgery cases from the Health Insurance Review and Assessment Service National Inpatient Sample of 2014 were analyzed. After evaluating the incidence of SEH based on severe cases requiring reoperation, a univariate comparison was performed. Variables found to be significant were included in a multivariable analysis model to determine the risk factors.

Results

The incidence of SEH was found to be 1.15% in Korean population, and there were no severe SEH cases. Our analysis confirmed the previous findings that lumbar surgery, intraoperative blood loss, prolonged surgical time, high blood pressure, use of nonsteroidal anti-inflammatory drugs, and concurrent bleeding factors are the risk factors of SEH. Anterior approach showed a protective effect. The use of anticoagulant demonstrated no statistical significance.

Conclusion

Although severe SEH cases were not detected, the incidence of SEH was similar to that reported in literature. Given that SEH is a rare complication of spine surgery and constitutes an important research area that needs to be studied further, our study makes a meaningful contribution based on a rigorous national level sample for the first time and provides the academic circle and health professionals with a reliable evidence of improved clinical outcomes in such cases.
Risk assessment for prolonged sickness absence due to musculoskeletal disorders: protocol for a prospective cohort study
Authors: Tveter Anne Therese , Øiestad Britt Elin , Rysstad Tarjei Langseth , Aanesen Fiona , Tingulstad Alexander , Småstuen Milada Cvancarova , Grotle Margreth
Published: May 2020

Background

Musculoskeletal disorders are the leading cause of sickness absence and disability pension in Norway. There is strong evidence that long-term sickness absence due to musculoskeletal disorders are associated with a reduced probability of return to work (RTW). A way to meet the economic and resource-demanding challenges related to individual follow-up of this group is to identify and treat those individuals with a high risk of prolonged sickness. The overall purposes of this project are 1) to determine the most accurate screening tool to identify people at a high risk of prolonged sickness absence due to an musculoskeletal disorder, and 2) to investigate severity of musculoskeletal health, health-related quality-of-life, health care utilization, and costs across different risk profiles in people on sick leave due to a musculoskeletal disorder.

Methods

People older than 18 years of age on sick leave for at least 4 weeks due to a musculoskeletal disorder will be invited to participate in this prospective observational cohort study conducted within the Norwegian Welfare and Labor Administration (NAV) system in collaboration with OsloMet – Oslo Metropolitan University. The main outcome is sickness absence, obtained from the NAV registry. Data on sickness absence will be retrieved prospectively in the period from study inclusion to 12 months follow-up, and retrospectively 12 months before inclusion in the study. Possible risk factors will be self-reported by the participants at inclusion while health care utilization will be retrieved from registry data. To conduct analyses including 15 to 20 predictor variables, we aim at including 500–600 people on sick leave due to musculoskeletal disorders.

Discussion

This study may provide tools that can be used to identify individuals with high risk of prolonged sickness absence and may thus be important from both a socioeconomic and individual perspective. Further, the study may give valuable insight into identification of sickness absence profiles and the associations between these profiles and musculoskeletal health status, health-related quality of life and costs.

Trial registration

Retrospectively registered in ClinicalTrials.gov (NCT04196634, 27.11.2019).
Year-round spatiotemporal distribution pattern of a threatened sea duck species breeding on Kolguev Island, south-eastern Barents Sea
Authors: Karwinkel Thiemo , Pollet Ingrid L. , Vardeh Sandra , Kruckenberg Helmut , Glazov Petr , Loshchagina Julia , Kondratyev Alexander , Merkel Benjamin , Bellebaum Jochen , Quillfeldt Petra
Published: May 2020

Background

The long-tailed duck (Clangula hyemalis) was categorized as ´Vulnerable` by the IUCN after a study revealed a rapid wintering population decline of 65% between 1992–1993 and 2007–2009 in the Baltic Sea. As knowledge about the European long-tailed duck’s life cycle and movement ecology is limited, we investigate its year-round spatiotemporal distribution patterns. Specifically, we aimed to identify the wintering grounds, timing of migration and staging of this population via light-level geolocation.

Results

Of the 48 female long-tailed ducks tagged on Kolguev Island (western Russian Arctic), 19 were recaptured to obtain data. After breeding and moulting at freshwater lakes, ducks went out to sea around Kolguev Island and to marine waters ranging from the White Sea to Novaya Zemlya Archipelago for 33 ± 10 days. After a rapid autumn migration, 18 of 19 birds spent their winter in the Baltic Sea and one bird in the White Sea, where they stayed for 212 ± 3 days. There, they used areas known to host long-tailed ducks, but areas differed among individuals. After a rapid spring migration in mid-May, the birds spent 23 ± 3 days at sea in coastal areas between the White Sea and Kolguev Island, before returning to their freshwater breeding habitats in June.

Conclusions

The Baltic Sea represents the most important wintering area for female long-tailed ducks from Kolguev Island. Important spring and autumn staging areas include the Barents Sea and the White Sea. Climate change will render these habitats more exposed to human impacts in the form of fisheries, marine traffic and oil exploitation in near future. Threats that now operate in the wintering areas may thus spread to the higher latitude staging areas and further increase the pressure on long-tailed ducks.
Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer’s disease through a network pharmacology approach
Authors: Qu Yan-Jie , Zhen Rong-Rong , Zhang Li-Min , Gu Chao , Chen Lei , Peng Xiao , Hu Bing , An Hong-Mei
Published: May 2020

Background

Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer’s disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach.

Methods

The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool.

Results

A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and β-sitosterol were obtained from the analysis of the key targets.

Conclusions

Ursolic acid, anethole and β-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.
Standard setting made easy: validating the Equal Z-score (EZ) method for setting cut-score for clinical examinations
Authors: Shulruf Boaz , Yang Ying-Ying , Huang Pin-Hsiang , Yang Ling-Yu , Huang Chin-Chou , Huang Chia-Chang , Liu Chih-Wei , Huang Shiau-Shian , Chen Chen-Huan , Lee Fa-Yauh , Kao Shou-Yen
Published: May 2020

Abstracts

Background

This study aims to assess the feasibility, reliability and validity of the panel-based Equal Z-score (EZ) method applied to objective structural clinical examination (OSCE) of Chinese medical students and undertaking a comparison with the statistical techniques-based Borderline Regression Method (BRM).

Methods

Data received from two cohorts of 6th and 7th year medical students in Taiwan who set the mock OSCE as a formative assessment. Traditionally this medical school uses BRM to set the pass/fail cut-score. For the current study, 31 OSCE panellists volunteered to participate in the EZ method in parallel to the BRM.

Results

In the conduct of this study, each panel completed this task for an OSCE exam comprising 12 stations within less than 60 min. Moreover, none of the 31 panellists, whose are busy clinicians, had indicated that the task was too difficult or too time-consuming. Although EZ method yielded higher cut-scores than the BRM it was found reliable. Intraclass correlation (ICC) measuring absolute agreement, across the three groups of panellists was .893 and .937 for the first and second rounds respectively, demonstrating high level of agreement across groups with the EZ method and the alignment between the BRM and the EZ method was visually observed. The paired t-test results identified smaller differences between the cut-scores within methods than across methods.

Conclusions

Overall this study suggests that the EZ method is a feasible, reliable and valid standard setting method. The EZ method requires relatively little resources (takes about an hour to assess a 12 station OSCE); the calculation of the cut-score is simple and requires basic statistical skills; it is highly reliable even when only 10 panellists participate in the process; and its validity is supported by comparison to BRM. This study suggests that the EZ method is a feasible, reliable and valid standard setting method.
From research to clinical practice: a systematic review of the implementation of psychological interventions for chronic headache in adults
Authors: Perlini Cinzia , Donisi Valeria , Del Piccolo Lidia
Published: May 2020

Background

Psychological interventions have been proved to be effective in chronic headache (CH) in adults. Nevertheless, no data exist about their actual implementation into standard clinical settings. We aimed at critically depicting the current application of psychological interventions for CH into standard care exploring barriers and facilitators to their implementation. Secondarily, main outcomes of the most recent psychological interventions for CH in adults have been summarized.

Methods

We conducted a systematic review through PubMed and PsycINFO in the time range 2008–2018. A quality analysis according to the QATSDD tool and a narrative synthesis were performed. We integrated results by: contacting the corresponding author of each paper; exploring the website of the clinical centers cited in the papers.

Results

Of the 938 identified studies, 28 papers were selected, whose quality largely varied with an average %QATSDD quality score of 64.88%. Interventions included CBT (42.85%), multi-disciplinary treatments (22.43%), relaxation training (17.86%), biofeedback (7.14%), or other interventions (10.72%). Treatments duration (1 day-9 months) and intensity varied, with a prevalence of individual-basis implementation. The majority of the studies focused on all primary headaches; 4 studies focused on medication-overuse headache. Most of the studies suggest interventions as effective, with the reduction in frequency of attacks as the most reported outcome (46.43%). Studies were distributed in different countries, with a prevalent and balanced distribution in USA and Europe. Ten researches (35.71%) were performed in academic contexts, 11 (39.28%) in clinical settings, 7 (25%) in pain/headache centres. Interventions providers were professionals with certified experience. Most of the studies were funded with private or public funding. Two contacted authors answered to our e-mail survey, with only one intervention implemented in the routine clinical practice. Only in three out of the 16 available websites a reference to the implementation into the clinical setting was reported.

Conclusion

Analysis of contextual barriers/facilitators and cost-effectiveness should be included in future studies, and contents regarding dissemination/implementation of interventions should be incorporated in the professional training of clinical scientists. This can help in filling the gap between the existing published research and treatments actually offered to people with CH.
A nation-wide cross-sectional study of variations in homecare nurses’ assessments of informational continuity – the importance of horizontal collaboration and municipal context
Authors: Veenstra Marijke , Skinner Marianne Sundlisæter , Sogstad Maren Kristine Raknes
Published: May 2020

Background

Numerous studies have revealed challenges associated with ensuring informational continuity in municipal care services for older adults with comprehensive, prolonged and complex care needs. Most research is qualitative and on the micro-level. The aim of the current study is to map variation in homecare nurses’ assessments of available information in the municipalities’ documentation system and investigate the extent to which these assessments are associated with perceived quality of collaborations and with municipal context.

Methods

We used data from a nationwide web-based survey among 1612 nurses working with older adults (65+) in homecare services in Norway. Responses from individual homecare nurses were linked with municipal-level data from the public registers. Data were analysed with descriptive statistics and multilevel regression analyses.

Results

Information on the recipients’ medications and medical condition was considered most often available (42.8 and 20.0% responding very often/always), whereas information related to psychosocial needs and future follow-up was perceived less available (4.5 and 6.7% responding very often/always). Homecare nurses’ perceptions of the quality of collaboration with the GP and the allotment office were independently and positively associated with assessments of informational continuity (ß =0.86 and ß =0.96). A modest share of the total variation (8%) in assessments of informational continuity was at the structural level of municipality. Small municipalities (< 5000 inhabitants) had, on average, better informational continuity compared to larger municipalities (ß = -0.47).

Conclusions

Documentation systems have a limited focus on long-term care needs of older care recipients beyond clinical and medical information. There is a potential for enhanced communication- and care-pathways between GPs, the allotment office and nurses in homecare services. This can support the coordinating role of homecare nurses in ensuring informational continuity for older adults with prolonged and complex care needs and help develop the facilitating role of (electronic) documentation systems.