bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators to retaining a cohort of street-based cisgender female sex workers recruited in Baltimore, Maryland, USA: results from the SAPPHIRE study
Authors: Silberzahn Bradley E. , Morris Miles B. , Riegger Katelyn E. , White Rebecca Hamilton , Tomko Catherine A. , Park Ju Nyeong , Footer Katherine H.A. , Huettner Steven S. , Sherman Susan G.
Published: April 2020

Background

Despite experiencing HIV/STIs, violence, and other morbidities at higher rates than the general public, street-based female sex workers are often absent from public health research and surveillance due to the difficulty and high costs associated with engagement and retention. The current study builds on existing literature by examining barriers and facilitators of retaining a street-based cohort of cisgender female sex workers recruited in a mobile setting in Baltimore, Maryland who participated in the SAPPHIRE study. Participants completed interviews and sexual health testing at baseline, 3-, 6-, 9-, and 12-months.

Methods

Retention strategies are described and discussed in light of their benefits and challenges. Strategies included collecting several forms of participant contact information, maintaining an extensive field presence by data collectors, conducting social media outreach and public record searches, and providing cash and non-cash incentives. We also calculated raw and adjusted retention proportions at each follow-up period. Lastly, baseline sample characteristics were compared by number of completed visits across demographic, structural vulnerabilities, work environment, and substance use variables using F-tests and Pearson’s chi-square tests.

Results

Although there were drawbacks to each retention strategy, each method was useful in tandem in achieving a successful follow-up rate. While direct forms of contact such as phone calls, social media outreach, and email were useful for retaining more stable participants, less stable participants required extensive field-based efforts such as home and site visits that increase the likelihood of random encounters. Overall, adjusted retention exceeded 70% for the duration of the 12-month study. Participants who were younger, recently experienced homelessness, and injected drugs daily were less likely to have completed all or most follow-up visits.

Conclusion

Retention of street-based female sex workers required the simultaneous use of diverse retention strategies that were tailored to participant characteristics. With familiarity of the dynamic nature of the study population characteristics, resources can be appropriately allocated to strategies most likely to result in successful retention.
Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya
Authors: Karinja Miriam , Schlienger Raymond , Pillai Goonaseelan Colin , Esterhuizen Tonya , Onyango Evance , Gitau Anthony , Ogutu Bernhards
Published: April 2020

Background

Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities.

Methods

Cases were defined as patients attending the health facility due to diarrhea or a respiratory infection while controls were patients attending the same health facility for a non-communicable disease defined as an event other than diarrhea, respiratory infection. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the risk of diarrheal or respiratory infection in association with exposure to the health education program.

Results

There were 324 cases and 308 controls recruited for the study with 57% of the cases and 59% of the controls being male. Overall, 13% of cases vs. 20% of control patients were exposed to the education program. Participants exposed to the program had 38% lower odds of diarrhea and respiratory infections compared to those not exposed to the program (adjusted OR 0.62, 95% CI 0.41–0.96). A similar risk reduction was observed for participants in the study who resided in areas with water improvement initiatives (adjusted OR 0.65, 95% CI 0.47–0.90). Variables in the adjusted model included water improvement projects in the area and toilet facilities.

Conclusion

Findings from this study suggest participants exposed to the education program and those residing in areas with water improvement initiatives have a reduced risk of having diarrhea or respiratory infection.
The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice
Authors: Boots Agnes W. , Veith Carmen , Albrecht Catrin , Bartholome Roger , Drittij Marie-José , Claessen Sandra M. H. , Bast Aalt , Rosenbruch Martin , Jonkers Leonie , van Schooten Frederik-Jan , Schins Roel P. F.
Published: April 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of which the etiology is still not fully understood. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities that is suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2 that regulates endogenous antioxidant levels. Therefore, the aim of the present study was to investigate if the dietary antioxidant quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance.

Methods

Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg quercetin per kg diet from 7 days prior to a single 1 μg/2 μl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of tumor necrosis factor-α (TNFα) and keratinocyte chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts).

Results

Mice fed the enriched diet for 7 days prior to the bleomycin challenge had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 μM versus 7.05 ± 0.2 μM) combined with increased expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet in lung tissue. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed.

Conclusion

Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.
Worldwide clinical practices in perioperative antibiotic therapy for lung transplantation
Authors: Coiffard Benjamin , Prud’Homme Eloi , Hraiech Sami , Cassir Nadim , Le Pavec Jérôme , Kessler Romain , Meloni Federica , Leone Marc , Thomas Pascal Alexandre , Reynaud-Gaubert Martine , Papazian Laurent
Published: April 2020

Background

Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices.

Methods

We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period.

Results

We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%).

Conclusion

Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.
Better pulmonary function is associated with greater handgrip strength in a healthy Chinese Han population
Authors: Chen Liangmei , Liu Xiaomin , Wang Qian , Jia Linpei , Song Kangkang , Nie Sasa , Zhang Yinping , Cao Dan , Zhao Delong , Li Zuoxiang , Dong Zheyi , Zheng Ying , Duan Shuwei , Sun Xuefeng , Feng Zhe , Cai Guangyan , Zhang Weiguang , Chen Xiangmei
Published: April 2020

Background

Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analysed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters.

Methods

HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student’s t-tests or Mann–Whitney U-tests were used for continuous variables. Pearson’s correlation coefficients were used to analyse the normally distributed variables, and Spearman correlation coefficients were used to analyse the non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set atp < 0.01.

Results

Cross-sectional data were available for 1519 subjects (59.0% females, 57.9 ± 13.3 years old). Males had higher average HGS than females (40.2 vs. 25.0 kg,p < 0.01), as well as better pulmonary function. Both HGS and pulmonary function parameters were significantly inversely correlated with age (r ≤ − 0.30,p < 0.01). The maximum value of vital capacity (VC max), forced expiratory volume in 3 s (FEV 3) and forced vital capacity (FVC) were strongly correlated with HGS among the pulmonary function indices (r = 0.72, 0.70 and 0.69, respectively,p < 0.001). In the multivariate linear regression analysis, HGS and height were positively correlated, while age and pulse pressure were negatively correlated with HGS. In males, the FVC, VC max and FEV3 increased by 0.02 L, 0.023 L and 0.03 L in per 1 kg increase in HGS, respectively. The HGS coefficients for females were smaller than those for males.

Conclusions

Both pulmonary function and HGS were inversely correlated with age, and better pulmonary function was associated with greater handgrip strength.
Laparoscopic Beger procedure for the treatment of chronic pancreatitis: a single-centre first experience
Authors: Cai He , Cai Yunqiang , Wang Xin , Peng Bing
Published: April 2020

Background

The Beger procedure is a common surgical option in the management of the unremitting abdominal pain of chronic pancreatitis (CP). As an organ-sparing surgery, it might be a better choice than pancreatoduodenectomy (PD). However, it is rather challenging for surgeons to perform the Beger procedure laparoscopically, especially for patients with CP; indeed, it has rarely reported. Here, we describe the technique and results of our early experience in laparoscopic Beger procedure for the treatment of CP.

Case presentation

Five patients (1 male) with CP (alcohol induced, n = 3; idiopathic, n = 2) who underwent laparoscopic Beger procedure from May to October 2019 in West China Hospital were included in this study. The median pancreatic duct diameter was 6.8 (4 to 12) mm. The median operating time was 275 (150 to 305) minutes without conversion. Only one patient (20%) developed a grade B pancreatic fistula. One patient required re-operation for jejunal anastomotic bleeding on the first post-operative day. The median hospital stay was 11 (9 to 34) days. No patient experienced biliary fistula, gastroparesis, duodenal necrosis, or abdominal bleeding. The 90-day mortality rate was 0%. All the patients were pain free in the two months after the operation.

Conclusion

The laparoscopic Beger procedure is feasible and safe with good short-term results and some potential benefits in selected patients with chronic pancreatitis. Further study and longer follow-up are required.
The five primary prostaglandins stimulate contractions and phasic activity of the urinary bladder urothelium, lamina propria and detrusor
Authors: Stromberga Zane , Chess-Williams Russ , Moro Christian
Published: April 2020

Background

Inflammation is often associated with several bladder dysfunctions, including overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/PBS). As such, inflammation of the bladder and the actions of inflammatory mediators may contribute to the development of urinary symptoms. This study assessed the actions of PGE2, PGF2, PGD2, TXA2, and PGI2 on urinary bladder urothelium with lamina propria (U&LP), and detrusor smooth muscle.

Methods

Studies were carried out using isolated tissue baths, where strips of porcine bladder U&LP or detrusor were exposed to varying concentrations of prostaglandin agonists (1 μM and 10 μM).

Results

All assessed prostaglandin agonists contracted both the U&LP and detrusor smooth muscle, with the rank order of contractile response effectiveness as: PGE2 > PGF2α > TXA2 > PGD2 > PGI2. In U&LP, treatment with PGE2 (10 μM) increased tonic contractions by 1.36 ± 0.09 g (n = 42, p < 0.001) and phasic contractions by 40.4 ± 9.6% (n = 42, p < 0.001). In response to PGF2α (10 μM), U&LP tonic contractions increased by 0.79 ± 0.06 g (n = 14, p < 0.001) and phasic activity by 13.3% ± 5.3% (n = 15, p < 0.05). In detrusor preparations, PGE2 (10 μM) increased tonic contractions by 1.32 ± 0.13 g (n = 38, p < 0.001) and PGF2α (10 μM) by 0.97 ± 0.14 g (n = 12, p < 0.001). Only 34% (n = 48) of all detrusor preparations exhibited spontaneous activity prior to the addition of any agonist at a frequency of 2.03 ± 0.12 cpm. In preparations that did not exhibit initial phasic activity, all of the prostaglandin agonists were capable of commencing phasic activity.

Conclusions

The urinary bladder U&LP and detrusor respond to a variety of prostaglandin agonists, with their activation resulting in direct contractions, as well as increases to spontaneous contractile activity. This study presents the prostaglandin receptor system as a potential therapeutic target for lower urinary tract dysfunction.
Ten years with biosimilar rhGH in clinical practice in Sweden – experience from the prospective PATRO children and adult studies
Authors: Lundberg Elena , Kriström Berit , Zouater Hichem , Deleskog Anna , Höybye Charlotte
Published: April 2020

Background

In 2007, Omnitrope® was the first biosimilar recombinant human growth hormone (rhGH) to be approved in Sweden for treatment in adults and children. Over 10 years’ safety and effectiveness data for biosimilar rhGH can now be presented.

Methods

PATRO Children and PATRO Adults are multicenter, longitudinal, observational, post-marketing surveillance studies. Eligible patients include children 0–18 years and adults receiving biosimilar rhGH treatment. Adverse events (AEs) are monitored for safety evaluation. Growth variables in children and metabolic data in adults are recorded for effectiveness evaluation.

Results

As of January 2019, data from 136 children (48% male) were reported from Swedish centers. Mean age in rhGH treatment-naïve patients at study entry (n = 114) was 7.5 years, with mean 3.6 years treatment duration. No severe AEs of diabetes, impaired glucose tolerance, or malignancy were reported. The most frequently reported AE was nasopharyngitis (n = 16 patients). No clinically relevant anti-hGH or neutralizing antibodies were observed. The mean change from baseline in height standard deviation score (SDS) in naïve prepubertal GH deficiency patients was + 0.79 at 1 year, + 1.27 at 2 years, and + 1.55 at 3 years. Data from 293 adults (44% rhGH-naïve, 51% male) were included. Fatigue was the most frequently reported AE (n = 26 patients). The incidence of new neoplasms or existing neoplasm progression was 23.8 patients per 1000 patient-years. Type 2 diabetes mellitus was reported in four patients. At baseline in rhGH-naïve adults, mean (SD) body mass index (BMI) was 29.1 (5.6) kg/m2 and mean (SD) insulin-like growth factor (IGF)-I SDS was − 3.0 (1.4). Mean daily dose increased from 0.1 mg at baseline to 0.3 mg after 4 years. IGF-I SDS normalized during the first year of treatment. Mean BMI and glucose were unchanged over 4 years, while low−/high-density lipoprotein cholesterol ratio decreased.

Conclusions

For the first time, Swedish data from the PATRO Children and Adults studies are presented. The 10-year data suggest that biosimilar rhGH is well tolerated across pediatric and adult indications. Safety and effectiveness were similar to previous reports for other rhGH preparations. These results need to be confirmed in larger cohorts, highlighting the importance of long-term post-marketing studies.
Comparison of microbiomes in ulcerative and normal mucosa of recurrent aphthous stomatitis (RAS)-affected patients
Authors: Yang Zhongjun , Cui Qingyu , An Ran , Wang Juan , Song Xiaobo , Shen Yu , Wang Mingyu , Xu Hai
Published: April 2020

Background

Recurrent aphthous stomatitis (RAS) is the most common form of oral ulcerative disease, whose cause is still unknown. Researchers have found the association of many factors with the occurrence of RAS, and proposed oral bacterial infection could be a cause for this disease.

Methods

To investigate whether the occurrence of RAS is associated with oral bacterial infection, we performed high throughput sequencing analysis of bacterial samples collected from the normal oral mucosa and aphthous ulcers of 24 patients.

Results

Firmicutes, Proteobacteria and Bacteriodetes were the most abundant phyla in the microbiomes analysed. The alpha diversities of the oral mucosa and aphthous ulcer microbiomes were similar, suggesting a similar richness and diversity. The NMDS analysis showed the oral mucosa and aphthous ulcer microbiomes are significantly different. This suggestion is further supported by Anosim, MRPP, and Adonis analyses. More detailed comparison of the two groups of microbiomes suggested that the occurrence of RAS is significantly associated with the increase of Escherichia coli and Alloprevotella, as well as the decrease of Streptococcus.

Conclusions

Considering E. coli is a very common intestinal bacterium, we propose that E. coli colonization could be a cause for RAS, and controlling E. coli colonization could help curing RAS.
Antimicrobial potential, phytochemical profile, cytotoxic and genotoxic screening of Sedum praealtum A. DC. (balsam)
Authors: Boriollo Marcelo Fabiano Gomes , Marques Milene Bueno , da Silva Thaísla Andrielle , da Silva Jeferson Júnior , Dias Reigson Alves , Silva Filho Thyago Henrique Neves , Melo Isadora Letícia Ribeiro , dos Santos Dias Carlos Tadeu , Bernardo Wagner Luís de Carvalho , de Mello Silva Oliveira Nelma , Peters Vera Maria , Höfling José Francisco , Spolidorio Denise Madalena Palomari
Published: April 2020

Background

Sedum praealtumhas been used for a long time in traditional medicine as an analgesic and anti-inflammatory agent. Its beneficial effects have been known since ancient times, when Latinos used it to treat sore and swollen eyes. This research evaluated the antimicrobial potential, the cytotoxic and genotoxic effects, and some chromatographic profiles of the hydroethanolic extract of leaves, stems and roots ofS. praealtum.

Methods

The antimicrobial activities were carried out by broth microdilution and agar diffusion. In vitro cytotoxicity was evaluated by cell cultures ofAedes albopictusand the selectivity index (SI) was estimated: SI=CI50/MIC. Genotoxic and systemic toxic effects ofS. praealtumleaves were analyzed by micronucleus assay in mice bone marrow. Chromatographic profiles and mass spectra were investigated by GC-MS.

Results

Gram-positive (B. subtilis,B. cereus,M. luteus,E. faecalisandS. aureus) and gram-negative (E. coli,E. aerogenes,S. marcescens,P. aeruginosa,P. mirabilisandS. typhimurium) bacteria exhibited MICs ranging from 12.5–50 and 0–50 mg/ml, respectively.Sedum praealtumshowed no efficacy againstM. tuberculosisandM. bovis. Cytotoxicity (CI50) ofS. praealtumwas 4.22 and 5.96 mg/ml for leaves and stems, respectively, while its roots showed no cytotoxicity. Micronucleated polychromatic erythrocytes (MNPCEs) analyzes showed no differences between treatment doses (0.5–2 g/kg) and negative control (NaCl), but the PCE/NCE ratio (polychromatic erythrocyte/normochromatic erythrocyte) showed significant differences. Phytochemical screening identified thirteen compounds in the leaves, stems and roots ofS. praealtumpotentially associated with their biological activities.

Conclusions

This research comprises a first scientific study on genotoxicity, cytotoxicity and antimicrobial effects ofS. praealtum(Balsam), and it provides an initial theoretical foundation for its comprehensive use. Results showed antibacterial action ofS. praealtumagainst gram-positive bacteria and some gram-negative species (depending on the plant anatomical part), but ineffective antimycobacterial action. However,S. praealtumleaves and stems display potential cytotoxicity, contributing to the SI < 1 values. In addition,S. praealtumleaves exhibit no clastogenic and/or aneugenic effects, but it has systemic toxicity dose-independent.
The effect of aged garlic extract on the atherosclerotic process – a randomized double-blind placebo-controlled trial
Authors: Wlosinska Martiné , Nilsson Ann-Christin , Hlebowicz Joanna , Hauggaard Anders , Kjellin Maria , Fakhro Mohammed , Lindstedt Sandra
Published: April 2020

Background

One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP–DM).

Method

This was a single-center parallel randomized controlled study in a university hospital in Europe. Patients were randomized, in a double-blind manner, through a computer-generated randomization chart. Patients with a Framingham risk score ≥ 10 after CT scan (n = 104) were randomized to an intake of placebo or AGE (2400 mg daily) for 1 year.

Main outcome measures were changes in CAC score and secondary outcome measures changes in blood pressure, fasting blood glucose, blood lipids and inflammatory biomarkers.

Result

104 patients were randomized and 46 in the active group and 47 in the placebo group were analyzed. There was a significant (p < 0.05) change in CAC progression (OR: 2.95 [1.05–8.27]), blood glucose (OR: 3.1 [1.09–8.85]) and IL-6 (OR 2.56 [1.00–6.53]) in favor of the active group. There was also a significant (p = 0.027) decrease in systolic blood pressure in the AGE group, from a mean of 148 (SD: 19) mmHg at 0 months, to 140 (SD: 15) mmHg after 12 months. The AGE Algorithm, at a selected probability cut-off value of 0.5, the accuracy score for CAC progression was 80%, precision score of 79% and recall score 83%. The score for blood pressure was 74% (accuracy, precision and recall). There were no side-effects in either group.

Conclusions

AGE inhibits CAC progression, lowers IL–6, glucose levels and blood pressure in patients at increased risk of cardiovascular events in a European cohort. An algorithm was made and was used to predict with 80% precision which patient will have a significantly reduced CAC progression using AGE. The algorithm could also predict with a 74% precision which patient will have a significant blood pressure lowering effect pressure using AGE.

Trial registration

Clinical trials NCT03860350, retrospectively registered (1/32019).
Medical student volunteerism and interest in working with underserved and vulnerable populations
Authors: Rogers Anna Joy G.
Published: April 2020

Background

The desire of medical students to eventually work with underserved and vulnerable populations (hereafter ‘service interest’), has been shown to be shaped by individual factors including job satisfaction and financial considerations. School-level factors such as required longitudinal primary care experiences and the availability of extracurricular opportunities to work with underserved patients also affect service interest, but little is known about the impact of student volunteer activities.

Methods

This cross-sectional study gathered data from preclinical medical students via an online questionnaire. The data were linked to academic records, deidentified, and analysed using an ordinal logistic regression model with interest in caring ‘primarily for underserved or vulnerable populations’ as the outcome variable.

Results

Of 121 respondents (33% response rate), 24.8% expressed a definite interest, 55.3% expressed possible interest, and 19.9% expressed no service interest. Intent to work with the underserved was not related to age, sex, race/ethnicity, being from a rural hometown, academic qualifications prior to medical school, or anticipated debt at medical school graduation. Students with no service interest had a higher average academic performance in medical school and plans of subspecialising. When considering volunteerism prior to medical school, students in the highest and middle volunteerism tertiles had 5.68 (95% CI: 1.63, 19.81) and 4.34 (1.32, 14.32) times the odds, respectively, of having definite or possible service interest relative to those who were in the lowest volunteerism tertile, after adjusting for potential confounders. Volunteerism in a student-run clinic for the underserved during medical school was not correlated with service interest.

Conclusions

Medical schools looking to enroll more students interested in working with underserved or vulnerable populations may choose to emphasise applicant premedical volunteerism record in their admissions decisions.
Development of a patient decision aid for the management of superficial basal cell carcinoma (BCC) in adults with a limited life expectancy
Authors: Junn Alexandra , Shukla Neha R , Morrison Lily , Halley Meghan , Chren Mary-Margaret , Walter Louise C. , Frosch Dominick L. , Matlock Dan , Torres Jeanette S. , Linos Eleni
Published: April 2020

Background

Basal cell carcinoma (BCC) is a slow-growing, rarely lethal skin cancer that affects people 65 years or older. A range of treatment options exist for BCC, but there is little evidence available to guide patients and providers in selecting the best treatment options.

Objectives

This study outlines the development of a patient decision aid (PDA) for low-risk BCC that can be used by patients and providers to assist in shared decision-making.

Methods

In accordance with the International Patient Decision Aids Standards (IPDAS) Collaboration framework, feedback from focus groups and semi-structured interviews with patients and providers, an initial prototype of the PDA was developed. This was tested using cognitive interviews and iteratively updated.

Results

We created eighteen different iterations using feedback from 24 patients and 34 providers. The key issues identified included: 1) Addressing fear of cancer; 2) Communicating risk and uncertainty; 3) Values clarification; and 4) Time lag to benefit.

Limitations

The PDA does not include all possible treatment options and is currently paper based.

Conclusions

Our PDA has been specifically adapted and designed to support patients with a limited life expectancy in making decisions about their low risk BCC together with their doctors.
Understanding health professional role integration in complex adaptive systems: a multiple-case study of physician assistants in Ontario, Canada
Authors: Burrows Kristen E. , Abelson Julia , Miller Patricia A. , Levine Mitchell , Vanstone Meredith
Published: April 2020

Background

To meet the complex needs of healthcare delivery, the Ministry of Health and Long Term Care (MOHLTC) introduced Physician Assistants (PAs) into the Ontario health care system in 2006 with the goal of helping to increase access to care, decrease wait times, improve continuity of care and provide a flexible addition to the healthcare workforce. The characterization of healthcare organizations as complex adaptive systems (CAS) may offer insight into the relationships and interactions that optimize and restrict successful PA integration. The aim of this study is to explore the integration of PAs across multiple case settings and to understand the role of PAs within complex adaptive systems.

Methods

An exploratory, multiple-case study was used to examine PA role integration in four settings: family medicine, emergency medicine, general surgery, and inpatient medicine. Interviews were conducted with 46 healthcare providers and administrators across 13 hospitals and 6 family medicine clinics in Ontario, Canada. Analysis was conducted in three phases including an inductive thematic analysis within each of the four cases, a cross-case thematic analysis, and a broader, deductive exploration of cross-case patterns pertaining to specific complexity theory principles of interest.

Results

Forty-six health care providers were interviewed across 19 different healthcare sites. Support for PA contributions across various health care settings, the importance of role awareness, supervisory relationship attributes, and role vulnerability are interconnected and dynamic. Findings represent the experiences of PAs and other healthcare providers, and demonstrate how the PAs willingness to work and ability to build relationships allows for the establishment of interprofessional, collaborative, and person-centered care. As a self-organizing agent in complex adaptive systems (i.e., health organizations), PA role exploration revealed patterns of team behavior, non-linear interconnections, open relationships, dynamic systems, and the legacy of role implementation as defined by complexity theory.

Conclusions

By exploring the role of PAs across multiple sites, the complexity theory lens concurrently fosters an awareness of emerging patterns, relationships and non-linear interactions within the defined context of the Ontario healthcare system. By establishing collaborative, interprofessional care models in hospital and community settings, PAs are making a significant contribution to Ontario healthcare settings.
Integrated nomogram based on five stage-related genes and TNM stage to predict 1-year recurrence in hepatocellular carcinoma
Authors: Liu Haohan , Yan Yongcong , Chen Ruibing , Zhu Mengdi , Lin Jianhong , He Chuanchao , Shi Bingchao , Wen Kai , Mao Kai , Xiao Zhiyu
Published: April 2020

Background

The primary tumor, regional lymph nodes and distant metastasis (TNM) stage is an independent risk factor for 1-year hepatocellular carcinoma (HCC) recurrence but has insufficient predictive efficiency. We attempt to develop and validate a nomogram to predict 1-year recurrence in HCC and improve the predictive efficiency of the TNM stage.

Methods

A total of 541 HCC patients were enrolled in the study. The risk score (RS) model was established with the logistic least absolute shrinkage and selector operation algorithm. The predictive nomogram was further validated in the internal testing cohort and external validation cohort. The area under the receiver operating characteristic curves (AUCs), decision curves and clinical impact curves were used to evaluate the predictive accuracy and clinical value of the nomogram.

Results

In the training cohort, we identified a RS model consisting of five stage-related genes (NUP62, EHMT2, RANBP1, MSH6 and FHL2) for recurrence at 1 year. The 1-year disease-free survival of patients was worse in the high-risk group than in the low-risk group (P < 0.0001), and 1-year recurrence was more likely in the high-risk group (Hazard ratio: 3.199, P < 0.001). The AUC of the nomogram was 0.739, 0.718 and 0.693 in the training, testing and external validation cohort, respectively, and these values were larger than the corresponding AUC of the TNM stage (0.681, 0.688 and 0.616, respectively).

Conclusions

A RS model consisting of five stage-related genes was successfully identified for predicting 1-year HCC recurrence. Then, a novel nomogram based on the RS model and TNM stage to predict 1-year HCC recurrence was also developed and validated.
Roles of eIF3m in the tumorigenesis of triple negative breast cancer
Authors: Han Wei , Zhang Cong , Shi Chun-tao , Gao Xiao-jiao , Zhou Ming-hui , Shao Qi-xiang , Shen Xiao-jun , Wu Cheng-jiang , Cao Fang , Hu Yong-wei , Yuan Jian-liang , Ding Hou-zhong , Wang Qing-hua , Wang Hao-nan
Published: April 2020

Background

Without targets, triple negative breast cancer (TNBC) has the worst prognosis in all subtypes of breast cancer (BC). Recently, eukaryotic translation initiation factor 3 m (eIF3m) has been declared to be involved in the malignant progression of various neoplasms. The aim of this study is to explore biological functions of eIF3m in TNBC.

Methods

Multiple databases, including Oncomine, KM-plotter and so on, were performed to analyze prognosis and function of eIF3m in TNBC. After transfection of eIF3m-shRNA lentivirus, CCK-8, colony formation assay, cell cycle analysis, wound healing assay, transwell assays, mitochondrial membrane potential assay and cell apoptosis analysis were performed to explore the roles of eIF3m in TNBC cell bio-behaviors. In addition, western blotting was conducted to analyze the potential molecular mechanisms of eIF3m.

Results

In multiple databases, up-regulated eIF3m had lower overall survival, relapse-free survival and post progression survival in BC. EIF3m expression in TNBC was obviously higher than in non-TNBC or normal breast tissues. Its expression in TNBC was positively related to differentiation, lymph node invasion and distant metastasis. After knockdown of eIF3m, cell proliferation, migration, invasion and levels of mitochondrial membrane potential of MDA-MB-231 and MDA-MB-436 were all significantly suppressed, while apoptosis rates of them were obviously increased. In addition, eIF3m could regulate cell-cycle, epithelial–mesenchymal transition and apoptosis-related proteins. Combined with public databases and RT-qPCR, 14 genes were identified to be modulated by eIF3m in the development of TNBC.

Conclusions

eIF3m is an unfavorable indicator of TNBC, and plays a vital role in the process of TNBC tumorigenesis.
Association between sleep quality and domains of quality of life amongst patients with first episode psychosis
Authors: Ong Wei Jie , Tan Xiao Wei , Shahwan Shazana , Satghare Pratika , Cetty Laxman , Ng Boon Tat , Tang Charmaine , Verma Swapna , Chong Siow Ann , Subramaniam Mythily
Published: April 2020

Background

There is a lack of studies exploring associations between sleep and quality of life (QOL) among patients with schizophrenia who have limited exposure to antipsychotics and are in the early stage of their illness. Our study investigates the association of poor sleep quality and its components with domains of QOL amongst patients with first episode psychosis (FEP).

Methods

Data was utilized from a longitudinal study that examined sleep, smoking and alcohol use amongst patients with FEP who were enrolled in the Early Psychosis Intervention Programme (EPIP). The data were collected during the patients’ baseline visit; i.e., within 3 months of admission into the EPIP. The Pittsburgh Sleep Quality Index (PSQI) was employed to examine sleep quality and its 7 components over the last month. The WHO quality of life-BREF was used to examine QOL and its 4 domains: physical health, psychological, social relationship, and environment. Clinical data such as Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores were obtained from a clinical data base. Linear regression analyses were conducted to investigate the association between poor sleep quality and the domains of QOL.

Results

Amongst the 280 recruited patients, 62.9% suffered from poor sleep quality. Poor sleep quality was associated with significantly lower scores in all domains of QOL, despite controlling for socio-demographics and clinical variables. Respondents with higher scores in subjective sleep quality and daytime dysfunction were associated with lower scores in the physical health and social relationship domain. Furthermore, respondents with higher scores in subjective sleep quality, sleep latency and daytime dysfunction were associated with lower scores in the psychological domain of QOL. Finally, respondents with higher scores in subjective sleep quality were associated with lower scores in the environment domain of QOL.

Conclusions

Our findings highlight the importance of monitoring sleep quality amongst patients with FEP to improve their QOL. Clinical programmes should also pay more attention to sleep components in order to maintain satisfactory QOL amongst patients with FEP. Future interventions should focus on improving the relevant sleep components to ensure better treatment outcomes.
Stand Out in Class: restructuring the classroom environment to reduce sitting time – findings from a pilot cluster randomised controlled trial
Authors: Clemes Stacy A. , Bingham Daniel D. , Pearson Natalie , Chen Yu-Ling , Edwardson Charlotte L. , McEachan Rosemary R. C. , Tolfrey Keith , Cale Lorraine , Richardson Gerry , Fray Mike , Altunkaya James , Bandelow Stephan , Jaicim Nishal Bhupendra , Salmon Jo , Dunstan David W. , Barber Sally E.
Published: April 2020

Background

Excessive sedentary behaviour (sitting) is a risk factor for poor health in children and adults. Incorporating sit-stand desks in the classroom environment has been highlighted as a potential strategy to reduce children’s sitting time. The primary aim of this study was to examine the feasibility of conducting a cluster randomised controlled trial (RCT) of a sit-stand desk intervention within primary school classrooms.

Methods

We conducted a two-armed pilot cluster RCT involving 8 primary schools in Bradford, United Kingdom. Schools were randomised on a 1:1 basis to the intervention or usual practice control arm. All children (aged 9–10 years) in participating classes were eligible to take part. Six sit-stand desks replaced three standard desks (sitting 6 children) in the intervention classrooms for 4.5-months. Teachers were encouraged to use a rotation system to ensure all pupils were exposed to the sit-stand desks for > 1 h/day on average. Trial feasibility outcomes (assessed using quantitative and qualitative measures) included school and participant recruitment and attrition, intervention and outcome measure completion rates, acceptability, and preliminary effectiveness of the intervention for reducing sitting time. A weighted linear regression model compared changes in weekday sitting time (assessed using the activPAL accelerometer) between trial arms.

Results

School and child recruitment rates were 33% (n = 8) and 75% (n = 176). At follow-up, retention rates were 100% for schools and 97% for children. Outcome measure completion rates ranged from 63 to 97%. A preliminary estimate of intervention effectiveness revealed a mean difference in change in sitting of − 30.6 min/day (95% CI: − 56.42 to − 4.84) in favour of the intervention group, after adjusting for baseline sitting and wear time. Qualitative measures revealed the intervention and evaluation procedures were acceptable to teachers and children, except for some problems with activPAL attachment.

Conclusion

This study provides evidence of the acceptability and feasibility of a sit-stand desk intervention and evaluation methods. Preliminary evidence suggests the intervention showed potential in reducing children’s weekday sitting but some adaptations to the desk rotation system are needed to maximize exposure. Lessons learnt from this trial will inform the planning of a definitive trial.

Trial registration

ISRCTN12915848 (registered: 09/11/16).
Dimethyl itaconate, an itaconate derivative, exhibits immunomodulatory effects on neuroinflammation in experimental autoimmune encephalomyelitis
Authors: Kuo Ping-Chang , Weng Wen-Tsan , Scofield Barbara A. , Paraiso Hallel C. , Brown Dennis A. , Wang Pei-Yu , Yu I-Chen , Yen Jui-Hung
Published: April 2020

Background

Inflammatory stimuli induce immunoresponsive gene 1 (IRG1) expression that in turn catalyzes the production of itaconate from the tricarboxylic acid cycle. Itaconate has recently emerged as a regulator of immune cell functions, especially in macrophages. Studies show that itaconate is required for the activation of anti-inflammatory transcription factor Nrf2 by LPS in mouse and human macrophages, and LPS-activatedIRG1-/-macrophages that lack endogenous itaconate production exhibit augmented inflammatory responses. Moreover, dimethyl itaconate (DMI), an itaconate derivative, inhibits IL-17-induced IκBς activation in keratinocytes and modulates IL-17-IκBς pathway-mediated skin inflammation in an animal model of psoriasis. Currently, the effect of itaconate on regulating macrophage functions and peripheral inflammatory immune responses is well established. However, its effect on microglia (MG) and CNS inflammatory immune responses remains unexplored. Thus, we investigated whether itaconate possesses an immunomodulatory effect on regulating MG activation and CNS inflammation in animal models of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE).

Methods

Chronic C57BL/6 EAE was induced followed by DMI treatment. The effect of DMI on disease severity, blood-brain barrier (BBB) disruption, MG activation, peripheral Th1/Th17 differentiation, and the CNS infiltration of Th1/Th17 cells in EAE was determined. Primary MG was cultured to study the effect of DMI on MG activation. Relapsing-remitting SJL/J EAE was induced to assess the therapeutic effect of DMI.

Results

Our results show DMI ameliorated disease severity in the chronic C57BL/6 EAE model. Further analysis of the cellular and molecular mechanisms revealed that DMI mitigated BBB disruption, inhibited MMP3/MMP9 production, suppressed microglia activation, inhibited peripheral Th1/Th17 differentiation, and repressed the CNS infiltration of Th1 and Th17 cells. Strikingly, DMI also exhibited a therapeutic effect on alleviating severity of relapse in the relapsing-remitting SJL/J EAE model.

Conclusions

We demonstrate that DMI suppresses neuroinflammation and ameliorates disease severity in EAE through multiple cellular and molecular mechanisms, suggesting that DMI can be developed as a novel therapeutic agent for the treatment of MS/EAE through its immunomodulatory and anti-inflammatory properties.
The ticking clock: does actively making an enhanced care team aware of the passage of time improve pre-hospital scene time following traumatic incidents?
Authors: Curtis L. , ter Avest E. , Griggs J. , Wiliams J. , Lyon R. M.
Published: April 2020

Introduction

Pre-hospital enhanced care teams like Helicopter Emergency Medical Services (HEMS) are often dispatched to major trauma patients, including patients with traumatic brain injuries and those with major haemorrhage. For these patients, minimizing the time to definitive care is vital. The aim of this study was to determine whether increased awareness of elapsed on scene time produces a relevant time performance improvement for major trauma patients attended by HEMS, and weather introducing such a timer was feasible and acceptable to clinicians.

Methods

We performed a prospective cohort study of all single casualty traumatic incidents attended by Air Ambulance Kent Surrey Sussex (AAKSS) between 15 October 2016 and 23 May 2017 to test if introduction of a prompting scene timer within the service resulted in a reduction in pre-hospital scene times.

Results

The majority of the patients attended were male (74%) and sustained blunt trauma (92%). Overall, median scene time was 25.5 [IQR16.3] minutes before introduction of the scene timer and 23.0 [11.0] minutes after introduction, p = 0.13). Scene times for patients with a GCS < 8 and for patients requiring prehospital anaesthesia were significantly lower after introduction of the timer (28 [IQR 14] vs 25 [1], p = 0.017 and 34 [IQR 13] vs 28 [IQR11] minutes, p = 0.007 respectively). The majority of clinicians felt the timer made them more aware of passing time (91%) but that this had not made a difference to scene time (62%) or their practice (57%).

Conclusion

Audible scene timers may have the potential to reduce pre-hospital scene time for certain single casualty trauma patients treated by a HEMS team, particularly for those patients needing pre-hospital anaesthesia. Regular use of on-scene timers may improve outcomes by reducing time to definitive care for certain subgroups of trauma patients.