bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism and Genetics of
Helicobacter pylori
: the Genome Era
Authors: Marais Armelle , Mendz George L. , Hazell Stuart L. , Mégraud Francis
Published: December 2019

The publication of the complete sequence of Helicobacter pylori 26695 in 1997 and more recently that of strain J99 has provided new insight into the biology of this organism. In this review, we attempt to analyze and interpret the information provided by sequence annotations and to compare these data with those provided by experimental analyses. After a brief description of the general features of the genomes of the two sequenced strains, the principal metabolic pathways are analyzed. In particular, the enzymes encoded by H. pylori involved in fermentative and oxidative metabolism, lipopolysaccharide biosynthesis, nucleotide biosynthesis, aerobic and anaerobic respiration, and iron and nitrogen assimilation are described, and the areas of controversy between the experimental data and those provided by the sequence annotation are discussed. The role of urease, particularly in pH homeostasis, and other specialized mechanisms developed by the bacterium to maintain its internal pH are also considered. The replicational, transcriptional, and translational apparatuses are reviewed, as is the regulatory network. The numerous findings on the metabolism of the bacteria and the paucity of gene expression regulation systems are indicative of the high level of adaptation to the human gastric environment. Arguments in favor of the diversity of H. pylori and molecular data reflecting possible mechanisms involved in this diversity are presented. Finally, we compare the numerous experimental data on the colonization factors and those provided from the genome sequence annotation, in particular for genes involved in motility and adherence of the bacterium to the gastric tissue.
Role of α
v
Integrins in Adenovirus Cell Entry and Gene Delivery
Authors: Nemerow Glen R. , Stewart Phoebe L.
Published: December 2019

Adenoviruses (Ad) are a significant cause of acute infections in humans; however, replication-defective forms of this virus are currently under investigation for human gene therapy. Approximately 20 to 25% of all the gene therapy trials (phases I to III) conducted over the past 10 years involve the use of Ad gene delivery for treatment inherited or acquired diseases. At present, the most promising applications involve the use of Ad vectors to irradicate certain nonmetastatic tumors and to promote angiogenesis in order to alleviate cardiovascular disease. While specific problems of using Ad vectors remain to be overcome (as is true for almost all viral and nonviral delivery methods), a distinct advantage of Ad is the extensive knowledge of its macromolecular structure, genome organization, sequence, and mode of replication. Moreover, significant information has also been acquired on the interaction of Ad particles with distinct host cell receptors, events which strongly affect virus tropism. This review provides an overview of the structure and function of Ad attachment (coxsackievirus and Ad receptor [CAR]) and internalization (α
v
integrins) receptors and discusses their precise role in virus infection and gene delivery. Recent structure studies of integrin-Ad complexes by cryoelectron microscopy are also highlighted. Finally, unanswered questions arising from the current state of knowledge of Ad-receptor interactions are presented in the context of improving Ad vectors for future human gene therapy applications.
Recombinational Repair of DNA Damage in
Escherichia coli
and Bacteriophage λ
Authors: Kuzminov Andrei
Published: December 2019

Although homologous recombination and DNA repair phenomena in bacteria were initially extensively studied without regard to any relationship between the two, it is now appreciated that DNA repair and homologous recombination are related through DNA replication. In Escherichia coli, two-strand DNA damage, generated mostly during replication on a template DNA containing one-strand damage, is repaired by recombination with a homologous intact duplex, usually the sister chromosome. The two major types of two-strand DNA lesions are channeled into two distinct pathways of recombinational repair: daughter-strand gaps are closed by the RecF pathway, while disintegrated replication forks are reestablished by the RecBCD pathway. The phage λ recombination system is simpler in that its major reaction is to link two double-stranded DNA ends by using overlapping homologous sequences. The remarkable progress in understanding the mechanisms of recombinational repair in E. coli over the last decade is due to the in vitro characterization of the activities of individual recombination proteins. Putting our knowledge about recombinational repair in the broader context of DNA replication will guide future experimentation.
Rhizobium
-Legume Symbiosis and Nitrogen Fixation under Severe Conditions and in an Arid Climate
Authors: Zahran Hamdi Hussein
Published: December 2019

Biological N
2
fixation represents the major source of N input in agricultural soils including those in arid regions. The major N
2
-fixing systems are the symbiotic systems, which can play a significant role in improving the fertility and productivity of low-N soils. The Rhizobium-legume symbioses have received most attention and have been examined extensively. The behavior of some N
2
-fixing systems under severe environmental conditions such as salt stress, drought stress, acidity, alkalinity, nutrient deficiency, fertilizers, heavy metals, and pesticides is reviewed. These major stress factors suppress the growth and symbiotic characteristics of most rhizobia; however, several strains, distributed among various species of rhizobia, are tolerant to stress effects. Some strains of rhizobia form effective (N
2
-fixing) symbioses with their host legumes under salt, heat, and acid stresses, and can sometimes do so under the effect of heavy metals. Reclamation and improvement of the fertility of arid lands by application of organic (manure and sewage sludge) and inorganic (synthetic) fertilizers are expensive and can be a source of pollution. The Rhizobium-legume (herb or tree) symbiosis is suggested to be the ideal solution to the improvement of soil fertility and the rehabilitation of arid lands and is an important direction for future research.
Intracranial vessel occlusion preceding the development of mycotic aneurysms in patients with endocarditis
Authors: Goldschmidt Ezequiel , Faraji Amir H , Salvetti David , Zussman Benjamin M , Jadhav Ashutosh
Published: December 2019

Mycotic aneurysms (MA) are an uncommon complication of infectious endocarditis. Septic emboli are thought to be the precipitating event in their development, but the evidence for this is sparse. We present three cases in which septic embolic occlusion preceded MA development at the occlusion site, suggesting that documented angiographic emboli in patients with infectious endocarditis and bacteremia constitute a risk factor for MA formation. Two adult patients with a history of intravenous drug use and one child with congenital heart disease are described. They were all diagnosed with infectious endocarditis and developed neurological symptoms during their hospital course. Initial catheter-based cerebral angiograms demonstrated vascular occlusions, which were followed by the development of MA at the same sites within 1 month. Septic emboli, documented on cerebral angiogram, in patients with infectious endocarditis may precede the appearance of MA. Patients with angiographic occlusions in the setting of endocarditis warrant close follow-up.
Paternal uniparental disomy for chromosome 14: prenatal management
Authors: Igreja da Silva Joana Isabel , Ribeiro Barbara , Cadilhe Alexandra , Nogueira-Silva Cristina
Published: December 2019

We present a case of a 34-year-old multiparous woman who had been diagnosed with a 14 weeks’ gestation showing an abdominal wall bulge possibly representing an omphalocele, containing liver and intestinal loops, at her first-trimester ultrasound scan. At 16 weeks’ gestation, an amniocentesis was performed and karyotype analysis revealed a balanced Robertsonian translocation between chromosomes 13 and 14 in a female fetus (45,XX,der(13;14)(q10;q10)). Given this result and ultrasound findings, karyotype and molecular study of the couple were suggested. The results pointed out the absence of maternal contribution to the analysed regions by paternal uniparental disomy for chromosome 14 (isodisomy), which is associated with a severe phenotype. The correlation between ultrasound findings and the genetic study is primordial to guide the diagnostic assessment and to establish the prognosis of the fetal pathology.
Adrenocortical carcinoma: an ominous cause of hirsutism
Authors: Radi Suhaib , Tamilia Michael
Published: December 2019

Hirsutism is a common medical presentation to family physicians, internists and endocrinologists. Although the cause is commonly benign, a more serious or life-threatening one should not be missed. Here we report a 58-year-old woman, assessed for hirsutism and 15-pound weight gain, with associated easy bruising and mood swings. On physical examination, she was hypertensive with central obesity. Laboratory work was significant for erythrocytosis, leukocytosis with lymphopenia and transaminitis. With this initial clinical picture, a provisional diagnosis of cortisol and androgen hypersecretion was suspected. Further investigations revealed non-suppressible early morning cortisol after low-dose dexamethasone, elevated 24 hours urinary-free cortisol and late night salivary cortisol. In addition, serum adrenocorticotropin hormone was low and androgens were elevated. These results supported the provisional diagnosis and imaging of the adrenals showed a large 10.4×7.7×5.2 cm right adrenal mass, consistent with adrenocortical carcinoma, for which she underwent surgical resection.
Rationale and methods for the Exercise for Type 1 Diabetes Education program: a pilot randomized controlled trial of an education program to support adults with type 1 diabetes mellitus (T1DM) to undertake exercise
Authors: Narendran Parth , Quann Niamh , Nagi Dinesh , Gallen Ian , Gorton Janet , Daly Heather , Thompson Catherine , Bhupendra Jaicim Nishal , Davies Melanie , Andrews Robert C
Published: December 2019

Objective

Regular exercise in people with type 1 diabetes mellitus (T1DM) can result in considerable improvements in health and reduction in cardiovascular events and death. However, a large proportion of people with T1DM are not active. Fear of hypoglycemia and lack of knowledge on how to manage their diabetes are major barriers to exercise in people with T1DM, but few patients receive specific advice about how to adjust insulin and carbohydrate for activity. Furthermore, healthcare professionals (HCP) currently lack the knowledge to advise patients on how to manage their diabetes when active and would like formal training in exercise prescription for people with T1DM.

Research design and methods

This study is divided into two stages. The first stage develops an education program aimed to support people with T1DM to exercise using the Medical Research Council framework. The second stage is a pilot randomized controlled trial (RCT) that aims to collect the key variables to design a definitive trial to test the efficacy and cost-effectiveness of the education package. We aim to recruit 96 patients with T1DM at two UK hospitals.

Conclusions

This article outlines the protocol for a pilot RCT to develop a program of education that will support adults with T1DM to undertake safe and effective exercise. This is accompanied by training for HCPs to deliver this educational intervention. Successful completion of this program of work will address some of the barriers to exercise in adults with T1DM, and should facilitate an increase in exercise for this group of people.

Trial registration number

ISRCTN61403534.
Sodium glucose co-transporter 2 inhibitors and cardiovascular event protections: how applicable are clinical trials and observational studies to real-world patients?
Authors: Shao Shih-Chieh , Lin Yi-Han , Chang Kai-Cheng , Chan Yuk-Ying , Hung Ming-Jui , Kao Yang Yea-Huei , Lai Edward Chia-Cheng
Published: December 2019

Objective

This study evaluated the characteristics of new users of sodium glucose co-transporter 2 inhibitors (SGLT2i) in clinical practice to assess the applicability of the findings from clinical trials (Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial, Canagliflozin Cardiovascular Assessment Study (CANVAS) program and the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS-CV) trial) and multinational observational studies (CVD-REAL Nordic study and CVD-REAL 2 study).

Research design and methods

We conducted a retrospective cohort study using the largest electronic medical records database from seven hospitals in Taiwan. We included adult patients with type 2 diabetes initiating canagliflozin, dapagliflozin and empagliflozin between 1 January 2018 and 31 August 2019. We compared the patient characteristics with SGLT2i to examine the data representativeness of clinical trials and to evaluate channeling uses between canagliflozin, dapagliflozin and empagliflozin.

Results

We identified a cohort of 11 650 patients newly initiating SGLT2i, 49.9% of whom received empagliflozin. However, only 18.7%, 19.2%, 50.4% and 57.3% of real-world SGLT2i new users were included in the EMPA-REG OUTCOME trial, VERTIS-CV trial, DECLARE-TIMI 58 trial and CANVAS program, respectively. Reasons for exclusion were largely reduced cardiovascular disease risks in real-world patients, namely 72.8%, 73.6% and 34.2% for EMPA-REG OUTCOME trial, VERTIS-CV trial and DECLARE-TIMI 58 trial and CANVAS program, respectively. However, hemoglobin A1c out of range accounted for the most frequent reason (25.0%) for exclusion of real-world patients from the CANVAS program. We found channeling uses in different SGLT2i, for example, more patients receiving empagliflozin (15.3%) and canagliflozin (19.6%) had poorer renal functions (eg, estimated glomerular filtration rate <60 mL/min/1.73 m2), compared with dapagliflozin (9.3%).

Conclusions

The findings provide clear evidence that results from current studies may be less applicable to real-world patients. Further studies are required to support the concept of real-world cardiovascular event protection through SGLT2i.
Multicentre, non-interventional study of the efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in primary, secondary and tertiary centres: the Alpine study
Authors: Pohl Daniel , Fried Michael , Lawrance Dominic , Beck Elmar , Hammer Heinz F.
Published: December 2019

Objectives

We evaluated the effectiveness and tolerability of linaclotide, a minimally absorbed guanylate cyclase-C agonist, in patients with irritable bowel syndrome with constipation (IBS-C) in routine clinical practice.

Setting

A multicentre, non-interventional study conducted between December 2013 and November 2015 across 31 primary, secondary and tertiary centres in Austria and Switzerland.

Participants

The study enrolled 138 patients aged ≥18 years with moderate-to-severe IBS-C. Treatment decision was at the physician’s discretion. Patients with known hypersensitivity to the study drug or suspected mechanical obstruction were excluded. The mean age of participants was 50 years, and >75% of the patients were women. 128 patients completed the study.

Primary and secondary outcome measures

Data were collected at weeks 0 and 4 in Austria and weeks 0, 4 and 16 in Switzerland. The primary effectiveness endpoints included severity of abdominal pain and bloating (11-point numerical rating scale [0=no pain/bloating to 10=worst possible pain/bloating]), frequency of bowel movements and physicians’ global effectiveness of linaclotide. Treatment-related adverse events (AEs) were recorded.

Results

Following a 4-week treatment period, the mean intensity score of abdominal pain was reduced from 5.8 at baseline to 2.7, while the bloating intensity score was reduced from 5.8 at baseline to 3.1e (both indices p<0.001). The frequency of mean weekly bowel movements increased from 2.1 at baseline to 4.5 at week 4 (p<0.001). Global effectiveness and tolerability of linaclotide were assessed by the treating physicians as ‘good’ or ‘excellent’ in >70% of patients. In total, 31 AEs were reported in 22 patients, the most common being diarrhoea, reported by 6 (7%) and 8 (15.4%) patients in Austria and Switzerland, respectively.

Conclusions

Patients with IBS-C receiving linaclotide experienced effective treatment of moderate-to-severe symptoms in routine clinical practice. Linaclotide was safe and well tolerated and no new safety concerns were raised, supporting results from previous clinical trials.
B!RTH: a mixed-methods survey of audience members’ reflections of a global women’s health arts and science programme in England, Ireland, Scotland and Switzerland
Authors: McCauley Mary , Thomas Joanne , Connor Cristianne , van den Broek Nynke
Published: December 2019

Objective

Public engagement and science communication are growing as an important forum in the design and dissemination of research. The B!RTH programme is a partnership that uses theatre in combination with scientific expert panel discussions to raise awareness about the global inequality in women’s health and access to healthcare. As part of this project, we assessed the views and experiences of audiences participating in B!RTH events.

Design

We conducted a multi-site mixed-methods survey using paper-based questionnaires.

Settings

Data were collected at four B!RTH theatre and science events: Dublin (Ireland), Edinburgh (Scotland), Geneva (Switzerland) and Liverpool (England) after the performance of four plays and three expert panel discussions.

Participants

All audience members.

Methods

Descriptive analysis was conducted for the responses to the closed-ended survey questions, and thematic analysis was used for written free text provided.

Results

The estimated response rate was 42%; 363 members of the audiences responded. Most respondents had been emotionally moved by the performances (92.8%) and felt challenged and provoked (80.7%). Many respondents (73.6%) agreed that their eyes had been opened by new ideas. Five themes emerged from the free-text analysis: (1) an expression of thanks and positive feedback on the content and performance of the plays, (2) the benefit of and innovative use of art and science, (3) personal feelings in response to the plays and panel discussions, (4) the need for action and (5) suggestions for use of the plays and panel discussions in schools and universities to ‘bring to life the human story behind the statistics’.

Conclusions

The B!RTH programme highlights how art and science can be used in partnership and is an effective tool to engage the public, to deliver key messages and to raise awareness about inequalities in global maternal and reproductive healthcare issues.
Pattern and probability of dispensing of prescription opioids and benzodiazepines among the new users in Australia: a retrospective cohort study
Authors: Islam M Mofizul
Published: December 2019

Objective

Opioids and benzodiazepines are recommended to use for a short duration. Clinicians face a challenge to appraise the risk of new users to become long-term users. This study examined the pattern and probability of opioids and benzodiazepines dispensing among the new users.

Design

A unit-record data of an incident and a point-incident cohort of new users, who were not dispensed in the previous 2 years, was examined and retrospectively followed up for 24 months.

Setting

Australia.

Participants

A random 10% national sample.

Primary and secondary outcome measures

Distribution of total dispensing in calendar months. Probability of staying in the cohort in each successive month. Effect of first month’s dispensing pattern on the total duration of dispensing during 2nd–24th month in total number of calendar months the dispensing was recorded.

Results

In the incident cohort, 68.24% were dispensed opioids, 23.96% were dispensed benzodiazepines and 7.80% were dispensed both medicines. Over 70% in the incident cohort and 50% in the point-incident cohort were dispensed for a month only. Codeine was the most prevalent opioid, dispensed to 52% of opioid users; and diazepam was the most prevalent benzodiazepines, dispensed to 45.34% of benzodiazepine users. The probability of staying in the cohort and hence receiving further dispensing continued to be very high if dispensing did not end in the first month. The quantity (in defined daily dose) and the total number of dispensing episodes in the first month were significant predictors of the total duration of dispensing in the later period.

Conclusions

Since harms from long-term use of these medicines may outweigh the benefits, and since the probability of further dispensing was high for those who were dispensed for more than a month, clinicians should endeavour to keep the dispensing duration and quantity as small as possible while initiating a prescription for the new users.
Measurement challenge: protocol for international case–control comparison of mammographic measures that predict breast cancer risk
Authors: Dench Evenda , Bond-Smith Daniela , Darcey Ellie , Lee Grant , Aung Ye K , Chan Ariane , Cuzick Jack , Ding Ze Y , Evans Chris F , Harvey Jennifer , Highnam Ralph , Hsieh Meng-Kang , Kontos Despina , Li Shuai , Mariapun Shivaani , Nickson Carolyn , Nguyen Tuong L , Pertuz Said , Procopio Pietro , Rajaram Nadia , Repich Kathy , Tan Maxine , Teo Soo-Hwang , Trinh Nhut Ho , Ursin Giske , Wang Chao , dos-Santos-Silva Isabel , McCormack Valerie , Nielsen Mads , Shepherd John , Hopper John L , Stone Jennifer
Published: December 2019

Introduction

For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk.

Methods and analysis

The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk.

Ethics and dissemination

Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).
Little in Norway: a prospective longitudinal community-based cohort from pregnancy to child age 18 months
Authors: Moe Vibeke , Fredriksen Eivor , Kjellevold Marian , Dahl Lisbeth , Markhus Maria Wik , Stormark Kjell Morten , von Soest Tilmann , Olafsen Kåre Sten , Vannebo Unni Tranaas , Smith Lars
Published: December 2019

Purpose

The Little in Norway (LiN) project is a cross-disciplinary prospective longitudinal study starting in pregnancy. It was set up to investigate maternal and paternal mental health functioning in the transition to parenthood, detect pathways to healthy and aberrant child development and generate new knowledge about mechanisms underlying differential child mental health susceptibility.

Participants

The LiN cohort is a community-based sample comprising 1036 families (1036 mothers, 884 partners, 1017 children). All pregnant women and their partners receiving routine prenatal care at well-baby clinics at nine geographically selected sites across Norway were invited to participate. Enrolment took place from September 2011 to October 2012. This cohort profile comprises 10 data collection waves spanning from enrolment in pregnancy until child age 18 months.

Findings to date

Four types of information have been collected: multi-informant questionnaire reports, direct observation of interaction, test data and biological samples. The most significant findings so far relate to three domains of results. First, when examining risk factors for parental mental health problems, results showed that the parents’ own adverse childhood experiences and attachment style were related to anxiety, depression and stress in the perinatal period. The perception of difficult child temperament was also found to contribute to parenting stress in the first year after birth. Second, we studied how parental mental health risk factors were related to later child development and social emotional functioning, for example, linking maternal symptoms to social-emotional outcomes and paternal symptoms to language outcomes. Third, we investigated the relation between maternal nutrition during pregnancy and aspects of early child development. Results showed that mild to moderate maternal iodine deficiency in pregnancy was associated with poorer language skills up to 18 months, but not with reduced cognitive or fine and gross motor skills.

Future plans

A data collection point at 36 months is completed and currently being analysed. A new data collection wave is planned when the children are 8 years of age.

Trial registration number

ISRCTN66710572.
Complications after surgery for benign prostatic enlargement: a population-based cohort study in Ontario, Canada
Authors: Matta Rano , Dvorani Erind , Wallis Christopher , Hird Amanda , LaBossiere Joseph , Kulkarni Girish , Kodama Ronald , Carr Lesley , Radomski Sidney B , Saskin Refik , Herschorn Sender , Nam Robert K
Published: December 2019

Objectives

To examine the complication rates after benign prostatic enlargement (BPE) surgery and the effects of age, comorbidity and preoperative medical therapy.

Design

A retrospective, population-based cohort study using linked administrative data.

Setting

Ontario, Canada.

Participants

52 162 men≥66 years undergoing first BPE surgery between 1 January 2003 to 31 December 2014.

Intervention

Medical therapy preoperatively and surgery for BPE.

Primary and secondary outcome measures

The primary outcome was overall 30-day postoperative complication rates. Secondary outcomes included BPE-specific event rates (bleeding, infection, obstruction, trauma) and non-BPE specific event rates (cardiovascular, pulmonary, thromboembolic and renal). Multivariable analysis examined the association between preoperative medical therapy and postoperative complication rates.

Results

The 30-day overall complication rate after BPE surgery was 2828 events/10 000 procedures and increased annually over the study period. Receipt of preoperative α-blocker monotherapy (relative rate (RR) 1.05; 95% CI 1.00 to 1.09; p=0.033) and antithrombotic medications (RR 1.27; 95% CI 1.22 to 1.31; p<0.0001) was associated with increased complication rates. Among the ≥80-year-old group, the rate of complications increased by 39% from 2003 to 2014 (RR 1.39; 95% CI 1.21 to 1.61; p<0.0001). The mean duration of medical and conservative management increased by a mean of 2.1 years between 2007 and 2014 (p<0.0001 for trend).

Conclusions

Thirty-day complication rates after BPE surgery have increased annually between 2003 and 2014. Preoperative medical therapy with alpha blockers or antithrombotics was independently associated with higher rates of complications. Over this time, the duration of conservative therapy also increased.
‘Am I really hungry?’ A qualitative exploration of patients’ experience, adherence and behaviour change during hunger training: a pilot study
Authors: de Bruin Willemijn E , Ward Aimee L , Taylor Rachael W , Jospe Michelle R
Published: December 2019

Objectives

Hunger training (HT) is an intervention designed to teach people to eat according to their hunger by connecting physical symptoms of appetite with glucose levels. HT is most effective for weight loss, and improving eating behaviours when adherence is high. However, adherence is a challenge that should be explored prior to wider dissemination. The aim of this study was to explore participants’ experience and self-reported adherence and behaviour change related to HT.

Design

A qualitative study, nested within a randomised controlled pilot study of two different methods of monitoring glucose during HT. Semistructured interviews were audio-recorded, transcribed verbatim and analysed thematically using a phenomenological approach.

Setting

Single-centre study with participants recruited from the local area.

Participants

40 participants began the pilot study and 38 participants (52.6% women) remained at 1 month and completed interviews.

Results

Most participants felt they were able to match their hunger to their glucose levels by the end of the intervention. The main adherence barriers were the social pressure to eat, lack of time and lack of flexibility in participants’ meal schedules. Common adherence enablers were having a set routine, social support and accountability. Participants described increased awareness of hungry versus non-hungry eating and better cognition of feelings of hunger and satiety as a result of the intervention, which in turn led to changes of food choice, portion size and adjusted meal timing and frequency.

Conclusions

Findings show that HT is acceptable from a patient perspective, and results can be used to inform the translation of HT programme to healthcare settings.

Trial registration number

ACTRN12618001257257.
Advanced practice nurses, registered nurses and medical practice assistants in new care models in Swiss primary care: a focused ethnography of their professional roles
Authors: Josi Renata , Bianchi Monica
Published: December 2019

Objectives

We aimed to analyse roles and tasks of advanced practice nurses (APNs), registered nurses (RNs) without advanced practice education and medical practice assistants (MPAs) with regard to chronic care in Swiss primary care (PC). The objective of this study was to explore the potential of new care models, involving these health professionals, which could meet changing future healthcare needs.

Design

An ethnographic design comprising semi-structured interviews and non-participant observations was conducted.

Setting

Health professionals who worked in 10 primary care practices in the German-speaking part of Switzerland were included in the study.

Participants

In total, 16 interviews were conducted with four APNs, six MPAs, two RNs and four general practitioners (GPs). Nine of the health professionals were subsequently observed in their primary care practice.

Results

APNs and MPAs were both involved in chronic care in the PC practice. While APNs cared for older, multimorbid patients with more complex needs, MPAs were involved in counselling of younger patients with chronic disease such as type 2 diabetes. Additionally, APNs were involved in many home visits and visits in elderly peoples — and nursing homes. APNs worked with a high degree of autonomy while MPAs had worked mostly in delegation. Task division between GPs and APNs or MPAs was not clear in every case yet.

Conclusions

APNs and MPAs have a high potential to contribute to optimal care in new care models, which address needs of the elderly population. The experience from our sample may inform international health policymakers and practitioners about the tasks and responsibilities those health professionals can take over in PC when implementing new models of care. The practical experience with new models of care involving APNs and MPAs may also influence the future regulation with regard to the scope of practice of these health professionals in Switzerland.
Intermittent theta burst stimulation applied during early rehabilitation after stroke: study protocol for a randomised controlled trial
Authors: Hensel Lukas , Grefkes Christian , Tscherpel Caroline , Ringmaier Corinna , Kraus Daria , Hamacher Stefanie , Volz Lukas J , Fink Gereon R
Published: December 2019

Introduction

Intermittent theta burst stimulation (iTBS) applied to primary motor cortex (M1) has been shown to modulate both the excitability and connectivity of the motor system. A recent proof-of-principle study, based on a small group of hospitalised patients with acute ischemic stroke, suggested that iTBS applied to the ipsilesional M1 combined with physical therapy early after stroke can amplify motor recovery with lasting after effects. A randomised controlled clinical trial using a double-blind design is warranted to justify the implementation of iTBS-assisted motor rehabilitation in neurorehabilitation from an acute ischaemic stroke.

Methods/design

We investigate the effects of daily iTBS on early motor rehabilitation after stroke in an investigator-initiated, longitudinal randomised controlled trial. Patients (n=150) with hemiparesis receive either iTBS (600 pulses) applied to the ipsilesional motor cortex (M1) or a control stimulation (ie, coil placement over the parieto-occipital vertex in parallel to the interhemispheric fissure and with a tilt of 45°). On 8 consecutive workdays, a 45 min arm-centred motor training follows the intervention . The relative grip strength, defined as the grip force ratios of the affected and unaffected hands, serves as the primary outcome parameter. Secondary outcome parameters are measures of arm function (Action Research Arm Test, Fugl-Meyer Motor Scale), stroke severity (National Institutes of Health Stroke Scale), stroke-induced disability (modified Rankin Scale, Barthel Index), duration of inpatient rehabilitation, quality of life (EuroQol 5D), motor evoked potentials and the resting motor threshold of the ipsilesional M1.

Ethics and dissemination

The study was approved by the Ethics Commission of the Medical Faculty, University of Cologne, Germany (reference number 15-343). Data will be disseminated through peer-reviewed publications and presentations at conferences. Study title: Theta-Burst Stimulation in Early Rehabilitation after Stroke (acronym: TheSiReS). Study registration at German Registry for Clinical Trials (DRKS00008963) and at ClinicalTrials.gov (NCT02910024).
‘It’s difficult, it’s life changing what happens to you’ patient perspective on life with chronic hypersensitivity pneumonitis: a qualitative study
Authors: Aronson Kerri I , Hayward Bradley J , Robbins Laura , Kaner Robert J , Martinez Fernando J , Safford Monika M
Published: December 2019

Rationale

Chronic hypersensitivity pneumonitis (CHP) is a distinct form of interstitial lung disease caused by an inhaled environmental antigen. Some patients with CHP develop progressive pulmonary fibrosis and varying degrees of symptom severity, with heterogeneous impact on functioning and overall well-being. There are no universally accepted diagnostic criteria, few FDA-approved (Food and Drug Administration) therapies and no standardised approach to identifying an antigen. The impact that living with CHP has on patients’ quality of life is understudied, preventing the identification of patient-centred research questions and endpoints for future CHP clinical trials.

Objectives

We explored patients’ experiences, perceptions and expectations of living with CHP.

Methods

We conducted semistructured interviews with patients with CHP. Patients were recruited using a purposive heterogeneous sampling strategy. Interviews were audio recorded and transcribed verbatim. Data were analysed using the grounded theory method.

Results

Eighteen patients were interviewed. Six major themes emerged from the interviews: (1) suffering due to lack of knowledge and uncertainty, (2) hypervigilance, (3) psychosocial, (4) physical impacts, (5) interpersonal and (6) self-perception and identity. The need to identify and avoid an antigen played a prominent role across the themes and subthemes.

Conclusions

We identified several key influences on quality of life in patients with CHP that have not been adequately explored. The prevalence of these influences should be quantified, and they should be included in quality of life assessment and should guide the development of targeted interventions to improve quality of life in this patient population.
Indoleamine 2,3-dioxgenase-transfected mesenchymal stem cells suppress heart allograft rejection by increasing the production and activity of dendritic cells and regulatory T cells
Authors: He Ji-Gang , Li Bei-Bei , Zhou Liang , Yan Dan , Xie Qiao-Li , Zhao Wei
Published: December 2019

Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-β1), TGF-β2, and TGF-β3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.
A Study on the Mechanism of High-Speed Railways’ Influences on Cities Along the Line
Authors: ZHANG Xiling , ZHANG Yan
Published: December 2019

High-speed railway as a rapid and convenient modern means of transportation has increasingly been chosen as an important travel tool or even a preferred one for the travel of a specific distance. Based on the knowledge of distance attenuation rules and urban gravitational model, a high-speed railway will shorten the temporal distance between the cities along the line, and further shorten the psychological, social, economic and probability distances, thus resulting in the weak attenuation of economic and social distances between the cities and strengthening the correlation of these cities. It is the weak distance attenuation between the cities along a high-speed railway that highlights the accessibility, openness and node-based features of these cities, and jointly drives the alternation of energy for the development of these cities through the catalytic effects, distribution effects, integration effects and gradient effects of high-speed railways. The influences of high-speed railways on urban development can be surveyed at several stages. The governments as the planners and builders of high-speed railway lines, stations and related cities should take macroeconomic measures in a scientific manner, so as to make best of high-speed railway effects and guide the path of urban development towards an era of high-speed railways.
A preliminary strategy for screening the combination of active components based on Bu–Shen–Yi–Qi Decoction for bronchial asthma
Authors: Yan Chen , Luo Qingli , Ma Cheng , Liu Jiaqi , Dong Jingcheng
Published: December 2019

Objective: The anti-asthma herbal medicine Bu–Shen–Yi–Qi Decoction (BSYQ Decoction), a combination of three traditional Chinese medicine herbs developed in our lab, has shown demonstrated efficacy in Ovalbumin (OVA)-induced acute bronchial asthma. However, the obscure substances, multiple potential targets and the unclear molecular mechanisms are obstacles to control drug quality, stability and standardization. Multi-component formulae with a clear pharmacodynamic material and specific mechanism are an innovation worth exploring. They may also partly reserve a potential synergistic and additive effect compared with single components extracted from traditional Chinese herbs. This study was designed to select three standard multi-component formulae of the combination of effective components preliminarily based on four effective components [total flavonoids of Herba Epimedii ([Formula: see text]; Astragalus polysaccharide ([Formula: see text]; Astragaloside ([Formula: see text]; and Catalpol ([Formula: see text]] in BSYQ Decoction.

Methods: OVA-induced asthmatic murine models were established. A uniform design was applied to select 10 proportions from four target components, and 3 formulae which showed best effect aimed at IFN-[Formula: see text], IL-4 and IgE in the serum respectively were screened based on stepwise regression analysis.

Results: According to the regression analysis, Formula I ([Formula: see text]:[Formula: see text]:[Formula: see text]:6:29), Formula II ([Formula: see text]:[Formula: see text]:[Formula: see text]:8:2) and Formula III ([Formula: see text]:[Formula: see text]:[Formula: see text]:[Formula: see text]:50:8:2) are the three potential proper ratios for the new multi-component formula aimed at serum IFN-[Formula: see text], IL-4 and IgE in OVA-induced asthma mice, respectively.

Conclusion: Three multi-component formulae derived from BSYQ Decoction could exert anti-inflammatory effect against OVA-induced asthma, which might provide evidences and lay foundations for further study of standard modern Chinese drug for treating asthma based on BSYQ Decoction.
1α,25-Dihydroxyvitamin D3 prevents renal oxidative damage via the PARP1/SIRT1/NOX4 pathway in Zucker diabetic fatty rats
Authors: Wang Dongxia , Li Yanyan , Wang Ning , Luo Gang , Wang Jun , Luo Can , Yu Wei , Hao Liping
Published: December 2019

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.
Treatment of Miller Class I Gingival Recession with Using Nonpedicle Adipose Tissue after Bichectomy Surgical Technique: A Case Report
Authors: Storrer Carmen Lucia Mueller , Muller Leonardo Luiz , Pissaia Janes Francio , Andrade Carla Frehner , Trevisani Claudia Roberta Tenório , Deliberador Tatiana Miranda
Published: December 2019

Gingival recession is an oral health problem that affects a large part of the population. Several treatments are suggested in the current literature; among them is the use of buccal fat pad grafting. The objective of this case report is to describe the treatment of a Miller Class I gingival recession using a nonpedicled buccal fat pad graft immediately after performing the surgery for buccal fat pad removal (bichectomy technique). First, bilateral surgical removal of the buccal fat pad was performed with the main objective of eliminating oral mucosa biting. The recipient site was prepared to receive a portion of the fat pad that was cut and macerated in a size that was sufficient to cover the recession. The patient was followed up at 15, 30, 60, and 365 days postsurgery, and the results showed an elimination of the oral mucosa biting and complete coverage of the gingival recession. It was concluded that the nonpedicled buccal fat pad graft is another option for the treatment of Miller Class I recessions.