bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter‐population differences in feeding ecology under nitrogen‐limited diets: Field growth and the role of cannibalism in limiting/improving reserve accumulation
Authors: Bas Claudia , Nuñez Jesús , Spivak Eduardo , Luppi Tomás
Published: June 2019

Growth is determined by an organism's physiology, physical environment, and biological conditions, including food availability and any intra‐ and inter‐specific interactions that can affect feeding activity. To analyse how all these factors interact to produce final growth in the herbivorous/detritivorous crab Neohelice granulata, we performed field and laboratory experiments with juveniles and adults from three populations which differed genetically as well as in their physical environment and the organic matter (OM) content in the soil that serves as food. We evaluated (a) growth in the field: Juveniles of the three populations were cross‐transplanted in exclusion cages; (b) effect of the presence of adults on juvenile feeding: We measured the feeding activity of small juveniles in presence/absence of an adult male as potential predator in the field; and (c) effect of diet on cannibalism: We analysed the cannibalistic behavior of adult males from two of the populations in the laboratory after they had received protein‐rich (24%) and protein‐poor (3%) diets. In experiment (a), final size was similar for the crabs from all three origins but growth differed between sites. Experiment (b) showed that the presence of adults interfered with feeding activity at the two sites with lower weight indicators. In experiment (c), we observed that low protein diet increased the cannibalistic behavior of adult males, and this effect was more intense in crabs from the poorest food site. Our results contribute to understanding the set of factors and interactions involved in the response of individuals to the prevailing conditions in natural environments in order to maintain a growth rate, perhaps at the expense of different reserve accumulation. They also enable discussion of the limitations of approaches used in laboratory experiments.
Regulated, sequential processing by multiple proteases is required for proper maturation and release of Bordetella filamentous hemagglutinin
Authors: Nash Zachary M. , Cotter Peggy A.
Published: June 2019

Filamentous hemagglutinin (FHA) is a critically important virulence factor produced by Bordetella species that cause respiratory infections in humans and other animals. It is also a prototypical member of the widespread two partner secretion (TPS) pathway family of proteins. First synthesized as a ~370 kDa protein called FhaB, its C‐terminal ~1,200 amino acid ‘prodomain’ is removed during translocation to the cell surface via the outer membrane channel FhaC. Here, we identify CtpA as a periplasmic protease that is responsible for the regulated degradation of the prodomain and for creation of an intermediate polypeptide that is cleaved by the autotransporter protease SphB1 to generate FHA. We show that the central prodomain region is required to initiate degradation of the prodomain and that CtpA degrades the prodomain after a third, unidentified protease (P3) first removes the extreme C‐terminus of the prodomain. Stepwise proteolysis by P3, CtpA and SphB1 is required for maturation of FhaB, release of FHA into the extracellular milieu, and full function in vivo. These data support a substantially updated model for the mechanism of secretion, maturation and function of this model TPS protein.
The ParB homologs, Spo0J and Noc, together prevent premature midcell Z ring assembly when the early stages of replication are blocked in Bacillus subtilis
Authors: Hajduk Isabella V. , Mann Riti , Rodrigues Christopher D. A. , Harry Elizabeth J.
Published: June 2019

Precise cell division in coordination with DNA replication and segregation is of utmost importance for all organisms. The earliest stage of cell division is the assembly of a division protein FtsZ into a ring, known as the Z ring, at midcell. What still eludes us, however, is how bacteria precisely position the Z ring at midcell. Work in B. subtilis over the last two decades has identified a link between the early stages of DNA replication and cell division. A recent model proposed that the progression of the early stages of DNA replication leads to an increased ability for the Z ring to form at midcell. This model arose through studies examining Z ring position in mutants blocked at different steps of the early stages of DNA replication. Here, we show that this model is unlikely to be correct and the mutants previously studied generate nucleoids with different capacity for blocking midcell Z ring assembly. Importantly, our data suggest that two proteins of the widespread ParB family, Noc and Spo0J are required to prevent Z ring assembly over the bacterial nucleoid and help fine tune the assembly of the Z ring at midcell during the cell cycle.
Need to re‐look cut‐off of Aspergillus‐specific IgE levels in children with ABPA
Authors: Singh Manvi , Chauhan Anil , Paul Nandini , Jaiswal Nishant , Singh Shreya , Chakrabarti Arunaloke , Singh Meenu
Published: June 2019

The cut‐offs for total and specific IgE used for diagnosing ABPA in children have been adopted from adult literature and have not been validated in the paediatric population. To establish the ideal cut‐offs of total IgE and Aspergillus‐specific IgE for the diagnosis of ABPA in children. This study was a prospective observational case‐control study, conducted in a tertiary care hospital in North India, enrolling 140 children with partly controlled and uncontrolled asthma. Seventy children had ABPA based on the Rosenberg‐Patterson Criteria (Cases) whereas 70 children were without ABPA (Controls). All children were subjected to clinical examination and investigations such as absolute eosinophil count, total IgE, Aspergillus‐specific IgE, Aspergillus skin prick test and radiological tests. ROC curve analysis was done to determine the ideal cut‐offs of total and specific IgE to diagnose ABPA. The ROC curve analysis determined 1204IU/L as the cut‐off value of total IgE with a sensitivity of 79.7% (95%CI 68.31% to 88.44%) and specificity of 53.1% (95%CI 40.23 to 65.7). The ROC analysis of specific IgE levels of children with ABPA determined the cut‐off value of 0.49 KAU/L with a sensitivity of 94.03% (95%CI 85.41 to 98.35) and specificity of 88.89% (95%CI 75.94% to 96.29%). We propose that the cut‐offs of total and specific IgE need to be relooked in the paediatric population. Cut‐offs of total IgE as 1204 IU/L and for Aspergillus‐specific IgE as 0.49KAU/L seem appropriate. Large multicentric studies should be conducted to determine the ideal values for diagnosing paediatric ABPA.
The prevalence of clinically meaningful malocclusion among US adults
Authors: Asiri Saeed N. , Tadlock Larry P. , Buschang Peter H.
Published: June 2019

Objective

The primary purpose of this study was to statistically evaluate age, ethnic and sex differences in the prevalence of clinically meaningful malocclusions among adults.

Setting and Sample Population

A random sample of 8804 untreated US adults between 17 and 46 years of age was selected from the Third National Health and Nutrition Examination Survey data.

Materials & Methods

Three ethnic (non‐Hispanic White, non‐Hispanic Black and Mexican Americans) and three age (17‐26, 27‐36 and 37‐46 years) groups were evaluated. Subjects with and without clinically meaningful malocclusions were categorized based on the established cut‐off values. Chi‐square analyses were performed to determine differences in prevalence.

Results

The prevalence of clinically meaningful mandibular incisor irregularity, overjet and overbite increased significantly (P < 0.05) with age, while posterior crossbite decreased. There were statistically significant ethnic differences in the prevalence of incisor irregularity, overbite, overjet, open bite and reverse overjet. Males had a significantly higher prevalence of clinically meaningful mandibular incisor irregularity, overbite, open bite and reverse overjet than females. One‐third of US adults exhibited no clinically meaningful malocclusions.

Conclusions

There are age, ethnic and sex differences in the prevalence of clinically meaningful malocclusions that characterize approximately two‐thirds of untreated US adults.
Anesthetic management of a pediatric patient with Loeys‐Dietz syndrome: A case report
Authors: Kamikado Yosuke , Mihara Takahiro , Ka Koui
Published: June 2019

Loeys‐Dietz syndrome, a rare autosomal dominant disease, is characterized by arterial tortuosity and skeletal manifestations. We report anesthetic management of scoliosis surgery for a pediatric Loeys‐Dietz syndrome patient. During surgery, severe hypotension occurred when a rotation‐correction was performed; blood pressure returned to the baseline level after the maneuver was abandoned. We decided to not conduct rotation correction after discussing risks and benefits of the maneuver with surgeons. Since severe hemodynamic instability is expected in scoliosis surgery for Loeys‐Dietz syndrome patients, we should be prepare for hemodynamic collapse and risks and benefits of the operative procedure should be discussed before undertaking the procedure.
Effect of oxygen tension on in vitro viability and development of dog follicles enclosed within the ovarian cortex
Authors: Pereira Leda Maria Costa , Lopes Maria Denise , Songsasen Nucharin
Published: June 2019

Oxygen concentration has been shown to influence in vitro viability and growth of ovarian follicles. The present study examined the effect of oxygen tension on in vitro development of dog follicles enclosed within the ovarian cortex. Ovaries were obtained from domestic dogs (age, 8 months to 2 years), and cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 4‐well culture plate containing Eagle Minimum Essential Medium (MEM). Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability and diameter immediately after collection (Control) or after 2 or 5 days of in vitro incubation. Apoptotic cells were assessed using TUNEL assay. Comparisons of follicular viability and diameter were performed using analysis of variance followed by Tukey's test (p < 0.05). Comparisons of follicle density and apoptosis among treatments were conducted using Non‐parametric Kruskal–Wallis test followed by Friedman's test (p < 0.05). No difference (p > 0.05) in follicle density was observed among groups at Day 2 of in vitro culture. However, the density of follicles within cortices cultured in 20% oxygen for 5 days significantly reduced compared to the Control and those incubated in 5% concentration. The viability of cultured follicles in all treatments decreased (p < 0.05) compared to the Control after 2 days incubation, and this value further reduced (p < 0.05) in 20% oxygen group at Day 5. There were no differences in the percentages of apoptotic follicles between the two treatment groups (p > 0.05). Nevertheless, after 5 days of culture, the percentage of TUNEL‐positive follicles increased significantly (p < 0.05) in cortices incubated in 20% oxygen environment. In conclusion, our findings demonstrated that 5% oxygen level was superior to 20% concentration in sustaining in vitro viability of dog follicles enclosed within the ovarian cortex.
Adolescents’ Engagement with Crisis Hotline Risk‐management Services: A Report from the Emergency Department Screen for Teen Suicide Risk (ED‐STARS) Study
Authors: Busby Danielle R. , King Cheryl A. , Brent David , Grupp‐Phelan Jaqueline , Gould Madelyn , Page Kent , Casper Theron Charles ,   The Pediatric Emergency Care Applied Research Network (PECARN)
Published: June 2019

Objective

This study examines the feasibility of a risk‐management protocol for adolescent research participants at risk for suicide that relies on engagement with telephone crisis counselors. The study also examines whether engagement is moderated by adolescent demographics and clinical characteristics.

Method

Participants were 234 adolescents (83% female; 63% White) ages 12–18 (M = 15.3 years) drawn from the national study, Emergency Department Screen for Teens at Risk for Suicide (ED‐STARS) Study One sample of adolescents randomized for 3‐month telephone follow‐up (n = 2,850). This study's sample was comprised of adolescents who completed the follow‐up (69% retention), met study risk criteria, and were transferred to a crisis hotline for risk management. Engagement with a counselor was assessed by successful call connection, call duration, and information sharing.

Results

Ninety‐four percent of calls resulted in a successful call transfer, and the majority of youth (84%) shared information with counselor about one or more coping strategies. Average call length was 12.6 min (SD = 9.9). Engagement did not vary by gender, race, age, ethnicity, or clinical characteristics.

Conclusions

Adolescents’ engagement with telephone risk‐management services was strong, suggesting that this strategy can address safety. Further, findings suggest telephone risk‐management services effectively engage youth across demographic and clinical subgroups.
Cellular stress leads to the formation of membraneless stress assemblies in eukaryotic cells
Authors: van Leeuwen Wessel , Rabouille Catherine
Published: June 2019

In cells at steady state, two forms of cell compartmentalization coexist: membrane‐bound organelles and phase‐separated membraneless organelles that are present in both the nucleus and the cytoplasm. Strikingly, cellular stress is a strong inducer of the reversible membraneless compartments referred to as stress assemblies. Stress assemblies play key roles in survival during cell stress and in thriving of cells upon stress relief. The two best studied stress assemblies are the RNA‐based processing‐bodies (P‐bodies) and stress granules that form in response to oxidative, endoplasmic reticulum (ER), osmotic and nutrient stress as well as many others. Interestingly, P‐bodies and stress granules are heterogeneous with respect to both the pathways that lead to their formation and their protein and RNA content. Furthermore, in yeast and Drosophila, nutrient stress also leads to the formation of many other types of prosurvival cytoplasmic stress assemblies, such as metabolic enzymes foci, proteasome storage granules, EIF2B bodies, U‐bodies and Sec bodies, some of which are not RNA‐based. Nutrient stress leads to a drop in cytoplasmic pH, which combined with posttranslational modifications of granule contents, induces phase separation.
One and two-phase cell cycle models
Authors: Pichor Katarzyna , Rudnicki Ryszard
Published: June 2019

In this review paper we present deterministic and stochastic one and two-phase models of the cell cycle. The deterministic models are given by partial differential equations of the first order with time delay and space variable retardation.В The stochastic models are given by stochastic iterations orВ by piecewise deterministic Markov processes. We study asymptotic stability and sweeping of stochastic semigroups which describe the evolution of densities of these processes.В We also present some results concerning chaotic behaviour of models and relations between different types of models.
Multifaceted Roles of microRNAs in Host-Bacterial Pathogen Interaction
Authors: Aguilar Carmen , Mano Miguel , Eulalio Ana
Published: June 2019

MicroRNAs (miRNAs) are a well-characterized class of small noncoding RNAs that act as major posttranscriptional regulators of gene expression. Accordingly, miRNAs have been associated with a wide range of fundamental biological processes and implicated in human diseases. During the past decade, miRNAs have also been recognized for their role in the complex interplay between the host and bacterial pathogens, either as part of the host response to counteract infection or as a molecular strategy employed by bacteria to subvert host pathways for their own benefit. Importantly, the characterization of downstream miRNA targets and their underlying mechanisms of action has uncovered novel molecular factors and pathways relevant to infection. In this article, we review the current knowledge of the miRNA response to bacterial infection, focusing on different bacterial pathogens, including
Salmonella enterica
,
Listeria monocytogenes
,
Mycobacterium
spp., and
Helicobacter pylori
, among others.
Host-Encoded Sensors of Bacteria: Our Windows into the Microbial World
Authors: Odendall Charlotte , Kagan Jonathan C.
Published: June 2019

Bacterial pathogens can be very efficient at causing disease and are the cause of some of the worst epidemics that have affected humanity. However, most infections are prevented by the actions of our immune system. Immune activation depends on the rapid detection of bacteria by a diverse family of sensory proteins known as pattern recognition receptors. These receptors detect conserved features of bacteria that are not found in humans but are often necessary for survival within the host or environment. In this review, we discuss the strategies used by pattern recognition receptors to detect bacteria and their products. We also discuss emerging evidence that some pattern recognition receptors can be activated by bacterial pathogens specifically, through the surveillance of host activities that are commonly targeted by virulence factors. This collection of surveillance mechanisms provides an interconnected network of defense, which is important to maintain the germ-free environment of the inner organs of humans and other multicellular organisms.
Successful treatment of aTSC2-mutant glioblastoma with everolimus
Authors: Zureick Andrew H , McFadden Kathryn A , Mody Rajen , Koschmann Carl
Published: June 2019

A 14-year-old boy with familial Li-Fraumeni syndrome presented with diplopia. Brain MRI revealed a right temporoparietal rim-enhancing mass. Following surgical resection and diagnosis of a gigantocellular-type glioblastoma multiforme (GBM), his family wished to avoid cytotoxic chemotherapy given the amplified risk of secondary malignancy. As such, we performed whole exome and transcriptome sequencing, which revealed germlineTP53and somaticTSC2mutations. On completion of adjuvant radiotherapy, he was started on maintenance therapy with everolimus per recommendations from our multi-institutional brain tumour precision medicine tumour board. He has achieved a complete remission with resolution of visual symptoms and remains on everolimus therapy with concurrent electromagnetic field therapy, now 33 months from diagnosis. Our data highlight the benefit of precision medicine in children with GBM and offer insight into a targetable pathway that may be involved in similar cases.
Sister Mary Joseph nodule: an unusual site for endometrioid cancer metastasis
Authors: Petch Sarah , Sobota Aleksandra , Abu Saadeh Feras
Published: June 2019

Sister Mary Joseph (SMJ) nodules are rare malignant metastatic umbilical nodules, indicating disseminated disease and associated with a poor prognosis. This is the case of an 80-year-old woman who presented with umbilical discomfort and an ulcerated umbilical nodule. She was noted to have a bulky uterus and vaginal bleeding. CT abdomen-pelvis showed an enlarged uterus and right-sided lymphadenopathy, extending from the groin to the para-aortic area. Upper and lower endoscopies were normal. Biopsy of the umbilical nodule revealed metastatic endometrioid adenocarcinoma grade 1–2 with the endometrium and the ovary suggested as potential primary sites. The patient had cytoreductive surgery including en bloc resection of the umbilical tumour. Final histology confirmed Stage IVb endometrioid adenocarcinoma of the uterus. This unusual case highlights the diagnostic challenges faced with the presentation of an umbilical nodule. Gynaecological malignancy should always be considered within the initial differential diagnosis of an SMJ nodule.
Abdominal cocoon: preoperative diagnosis on CT
Authors: Mohakud Sudipta , Juneja Aparna , Lal Hira
Published: June 2019

A 23-year-old man presented to the emergency department with a history of recurrent episodes of subacute intestinal obstruction. Palpation revealed a firm, non-tender, mobile, non-pulsatile mass of size 8–10 cm with indistinct margins and smooth surface in the hypogastrium. Contrast-enhanced CT scan of the abdomen showed clumping of the small bowel loops within a well-defined membrane-like structure without dilatation or thickening of bowel loops. The patient underwent a laparotomy with incision of the membrane and separation of all the small bowel loops inside the cocoon. Abdominal cocoon is the idiopathic variety of sclerosing encapsulating peritonitis and is an unusual cause of acute or subacute intestinal obstruction. Clinical diagnosis is difficult because of non-specific symptoms. CT has facilitated accurate preoperative diagnosis, long before the patient presents with full-fledged symptoms of acute intestinal obstruction. CT scan plays a significant role in excluding the secondary causes and helps in patient management.
Is loneliness associated with increased health and social care utilisation in the oldest old? Findings from a population-based longitudinal study
Authors: Wang Hanyuying , Zhao Emily , Fleming Jane , Dening Tom , Khaw Kay-Tee , Brayne Carol
Published: June 2019

Objectives

The present study aimed to examine the impact of loneliness on health and social care service use in the oldest old over a 7-year follow-up.

Design

Prospective study.

Setting

UK population-based cohort.

Participants

713 people aged 80 years or older were interviewed at wave 3 of the Cambridge City over-75s Cohort Study. Of these, 665 provided data on loneliness. During 7 years’ follow-up, 480 participants left the study, of which 389 due to death. 162 still in the study answered the loneliness question.

Main outcome measure

Use of health and social care services, assessed at each wave from wave 3 to wave 5.

Results

At wave 3, of 665 participants who had data on loneliness, about 60% did not feel lonely, 16% felt slightly lonely and 25% felt lonely. Being slightly lonely at wave 3 was associated with a shorter time since last seeing a general practitioner (β=−0.5, 95% CI: −0.8 to –0.2); when examining the association between time-varying loneliness and health and social care usage, being lonely was associated with three times greater likelihood of having contact with community nurses and using meals on wheels services (community nurse contact: incidence rate ratio (IRR)=3.4, 95% CI: 1.4 to 8.7; meals on wheels service use: IRR=2.5, 95% CI: 1.1 to 5.6). No associations between loneliness and other health and social care services use were found.

Conclusion

Loneliness was a significant risk factor for certain types of health and social care utilisations, independently of participants’ health conditions, in the oldest old. Study findings have several implications, including the need for awareness-raising and prevention of loneliness to be priorities for public health policy and practice.
Health-related educational inequalities in paid employment across 26 European countries in 2005–2014: repeated cross-sectional study
Authors: Schram Jolinda L D , Schuring Merel , Oude Hengel Karen M , Burdorf Alex
Published: June 2019

Objective

The study investigates the trends in health-related inequalities in paid employment among men and women in different educational groups in 26 countries in 5 European regions.

Design

Individual-level analysis of repeated cross-sectional annual data (2005–2014) from the EU Statistics on Income and Living Conditions.

Setting

26 European countries in 5 European regions.

Participants

1 844 915 individuals aged 30–59 years were selected with information on work status, chronic illness, educational background, age and gender.

Outcome measures

Absolute differences were expressed by absolute differences in proportion in paid employment between participants with and without a chronic illness, using linear regression. Relative differences were expressed by prevalence ratios in paid employment, using a Cox proportional hazard model. Linear regression was used to examine the trends of inequalities.

Results

Participants with a chronic illness had consistently lower labour force participation than those without illnesses. Educational inequalities were substantial with absolute differences larger within lower educated (men 21%–35%, women 10%–31%) than within higher educated (men 5%–13%, women 6%–16%). Relative differences showed that low-educated men with a chronic illness were 1.4–1.9 times (women 1.3–1.8 times) more likely to be out of paid employment than low-educated persons without a chronic illness, whereas this was 1.1–1.2 among high-educated men and women. In the Nordic, Anglo-Saxon and Eastern regions, these health-related educational inequalities in paid employment were more pronounced than in the Continental and Southern region. For most regions, absolute health-related educational inequalities in paid employment were generally constant, whereas relative inequalities increased, especially among low-educated persons.

Conclusions

Men and women with a chronic illness have considerable less access to the labour market than their healthy colleagues, especially among lower educated persons. This exclusion from paid employment will increase health inequalities.
Electronic Alerts for Acute Kidney Injury Amelioration (ELAIA-1): a completely electronic, multicentre, randomised controlled trial: design and rationale
Authors: Mutter Marina , Martin Melissa , Yamamoto Yu , Biswas Aditya , Etropolski Boian , Feldman Harold , Garg Amit , Gourlie Noah , Latham Stephen , Lin Haiqun , Palevsky Paul M , Parikh Chirag , Moreira Erica , Ugwuowo Ugochukwu , Wilson Francis P
Published: June 2019

Introduction

Acute kidney injury (AKI) is common among hospitalised patients and under-recognised by providers and yet carries a significant risk of morbidity and mortality. Electronic alerts for AKI have become more common despite a lack of strong evidence of their benefits. We designed a multicentre, randomised, controlled trial to evaluate the effectiveness of AKI alerts. Our aim is to highlight several challenges faced in the design of this trial, which uses electronic screening, enrolment, randomisation, intervention and data collection.

Methods and analysis

The design and implementation of an electronic alert system for AKI was a reiterative process involving several challenges and limitations set by the confines of the electronic medical record system. The trial will electronically identify and randomise 6030 adults with AKI at six hospitals over a 1.5–2 year period to usual care versus an electronic alert containing an AKI-specific order set. Our primary outcome will be a composite of AKI progression, inpatient dialysis and inpatient death within 14 days of randomisation. During a 1-month pilot in the medical intensive care unit of Yale New Haven Hospital, we have demonstrated feasibility of automating enrolment and data collection. Feedback from providers exposed to the alerts was used to continually improve alert clarity, user friendliness and alert specificity through refined inclusion and exclusion criteria.

Ethics and dissemination

This study has been approved by the appropriate ethics committees for each of our study sites. Our study qualified for a waiver of informed consent as it presents no more than minimal risk and cannot be feasibly conducted in the absence of a waiver. We are committed to open dissemination of our data through clinicaltrials.gov and submission of results to the NIH data sharing repository. Results of our trial will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT02753751; Pre-results.
What motivates general practitioners to change practice behaviour? A qualitative study of audit and feedback group sessions in Dutch general practice
Authors: van Braak Marije , Visser Mechteld , Holtrop Marije , Statius Muller Ilona , Bont Jettie , van Dijk Nynke
Published: June 2019

Objectives

Adopting an attributional perspective, the current article investigates how audit and feedback group sessions contribute to general practitioners’ (GPs) motivation to change their practice behaviour to improve care. We focus on the contributions of the audit and feedback itself (content) and the group discussion (process).

Methods

Four focus groups, comprising a total of 39 participating Dutch GPs, discussed and compared audit and feedback of their practices. The focus groups were analysed thematically.

Results

Audit and feedback contributed to GPs’ motivation to change in two ways: by raising awareness about aspects of their current care practice and by providing indications of the possible impact of change. For these contributions to play out, the audit and feedback should be reliable and valid, specific, recent and recurrent and concern GPs’ own practices or practices within their own influence sphere. Care behaviour attributed to external, uncontrollable or unstable causes would not induce change. The added value of the group is twofold as well: group discussion contributed to GPs’ motivation to change by providing a frame of reference and by affording insights that participants would not have been able to achieve on their own.

Conclusions

In audit and feedback group sessions, both audit and feedback information and group discussion can valuably contribute to GPs’ motivation to change care practice behaviour. Peer interaction can positively contribute to explore alternative practices and avenues for improvement. Local or regional peer meetings would be beneficial in facilitating reflection and discussion. An important avenue for future studies is to explore the contribution of audit and feedback and small-group discussion toactualpractice change.
Is the link between socioeconomic status and resilience mediated by reserve-building activities: mediation analysis of web-based cross-sectional data from chronic medical illness patient panels
Authors: Schwartz Carolyn Emily , Zhang Jie , Stucky Brian Dale , Michael Wesley , Rapkin Bruce David
Published: June 2019

Objectives

The purpose of this study is to test the hypothesis that the link between socioeconomic status (SES) and resilience is mediated by reserve-building activities.

Design

Cross-sectional observational study. Structural equation modelling (SEM) was used to test the mediation hypothesis.

Setting

Web-based survey.

Participants

Participants with a chronic medical condition were recruited from Rare Patient Voice.

Primary and secondary outcome measures

DeltaQuest Reserve-Building Measure; demographic variables to capture SES; Centers for Disease Control Healthy Days Core Module; Self-Administered Comorbidity Questionnaire. Resilience was operationalised using residual modelling.

Results

The study sample included 442 patients (mean age 49, 85% female). SES was modelled as a bifactor model composed of general SES and specific factors for personal finance and parent’s education. A series of simple mediation models predicting resilience led to the selection of three reserve-building activities for subsequent SEM-based mediation models: Active in the World, Outdoor and Exercise. The full SEM model supported the hypothesis that the relationships from both general SES and personal finance to resilience were mediated by engaging in the three reserve-building activities. In addition, the number of comorbidities partially mediated the relationship between personal finance and reserve-building. Those with more comorbidities generally had lower levels of resilience.

Conclusions

This study provides suggestive evidence that reserve-building activities may be one pathway by which SES is associated with resilience: people of higher SES are more likely to engage in reserve-building activities that are intellectually stimulating, involve Outdoor pursuits and include physical Exercise. These reserve-building activities are not costly to pursue. These findings may empower patients to introduce more such reserve-building activities into their lives.
Time trend of cardiometabolic risk factors over a 10-year period in the office-working population in China
Authors: Cheng Yang , Yin Hongli , Zheng Hui , Yin Donghua , Yin Gang , Ying Shanping , Li Xiaohong , Dai Hui , Zhao Lvkun , Shen Chong , Shen Zhixiang , Gu Liubao
Published: June 2019

Objectives

Recent dramatic increases in cardiovascular disease mortality in China can be mostly explained by adverse changes in hypertension, dyslipidaemia, diabetes and obesity, known as cardiometabolic risk factors. Our study aimed to assess the trend of these four signatures by a 10-year lag in Nanjing, China.

Methods

8017 subjects attended the routine health examination in 2008, and 9379 subjects in 2017, from multiple work units of Nanjing, were included in the present study. The prevalence and trend of four cardiometabolic risk factors: hypertension, dyslipidaemia, diabetes and obesity were analysed.

Results

From 2008 to 2017, the prevalence of hypertension declined, while the prevalence of dyslipidaemia, diabetes and obesity increased. Besides, the population in 2008 and 2017 had an average of 0.66 and 0.78 risk factors, respectively.

Conclusion

Cardiometabolic risk factors are common for the staff in administrative agencies and institutions of Nanjing, China. Effective screening and interventions against these risk factors should be adopted in high-risk populations such as the office-working population in China.
Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: a large-scale national health screening cohort study
Authors: Kim Kyoung-Nam , Joo Jungmin , Sung Ho Kyung , Kim Chee Hae , Kim Haebin , Kwon Yong Jin
Published: June 2019

Objectives

To investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with mortality.

Design

Cohort study.

Setting, participants and outcome measures

We analysed the data of 484 472 individuals from the National Health Insurance Service-National Health Screening Cohort (2002–2013). We used two exposure indices: (1) deciles of baseline ALT, AST and GGT levels measured in 2002 or 2003 and (2) deciles of changes in ALT, AST and GGT levels over a 4 year period (2002–2006 or 2003–2007). We constructed Cox models to evaluate the associations of these exposure indices with mortality (2008–2013).

Results

We found non-monotonic dose–response associations between the baseline levels of ALT and AST and all-cause mortality. We also found a monotonic non-linear association between the baseline levels of GGT and all-cause mortality (10th decile: HR=2.05, 95% CI: 1.93 to 2.18). Compared with the ninth, sixth and fourth deciles of changes in ALT (8–13 U/L), AST (1 U/L) and GGT (−3 to −2 U/L) over time, respectively, the risks of all-cause mortality increased in both the higher and lower deciles of changes in the corresponding liver enzyme levels (10th decile: HR=1.36, 95% CI 1.24 to 1.48; 1st decile: HR=1.46, 95% CI 1.34 to 1.59 for ALT; 10th decile: 1.55, 95% CI 1.40 to 1.71; 1st decile: HR=1.53, 95% CI 1.38 to 1.69 for AST; 10th decile: HR=1.71, 95% CI 1.56 to 1.88; 1st decile: HR=1.67, 95% CI 1.52 to 1.84 for GGT). These non-monotonic dose–response associations remained when analyses were stratified by the medians or quartiles of the baseline liver enzyme levels.

Conclusions

The levels of liver enzymes at baseline and over time showed non-linear associations with mortality.
Development and psychometric testing of the 5Senses screening tool for long-term care: a study protocol
Authors: Backman Chantal , Squires Janet E
Published: June 2019

Introduction

As adults age, their senses tend to decline and a large portion of those most affected by sensory decline reside in long-term care. At present, the creation of a sense-sensitive environment in long-term care is a difficult task as there is minimal evidence or tools available to guide this process. The 5Senses screening tool was developed to measure the sense-sensitivity of a particular environment, with a focus on long-term care. The purpose of this paper is to describe a study protocol to assess the psychometric properties of the newly developed 5Senses screening tool.

Methods and analysis

We will conduct a psychometric evaluation of the 5Senses screening tool in long-term care based on the Standards for Educational and Psychological Testing Framework. In phase I, we will seek input from international content experts (n=20) to assess the content validity of all sections of the tool. In phase II, we will invite auditors (n=3-9), residents (n=3-9) and staff (n=3-9) to partake in think-aloud sessions to assess response process validity. In phase III, we will conduct field testing of the revised 5Senses screening tool with auditors (n=100), residents (n=100) and staff (n=100) to evaluate additional measures including acceptability, inter-rater reliability, internal structure validity and internal consistency reliability, where possible.

Ethics and dissemination

Ethical approval was obtained from the University of Ottawa Research Ethics Board. Findings will be disseminated through a peer-reviewed manuscript, through a dedicated website, through presentations in long-term care communities and through presentations at research conferences.
A tool to improve the performance of multidisciplinary teams in cancer care
Authors: Evans Lynleigh , Donovan Brendan , Liu Yiren , Shaw Tim , Harnett Paul
Published: June 2019

Introduction

While multidisciplinary teams (MDTs) are well established in many healthcare institutions, both how they function and their role in decision-making vary widely. This study adopted an innovative methodology to assess multidisciplinary team performance and engage teams in performance improvement strategies.

Methods

The study comprised a survey to evaluate MDT members’ perceptions of their team’s performance before the implementation of the programme and annually thereafter, and a maturity matrix designed as a self-assessment tool. Each MDT used the matrix to collectively assess its performance and identify areas for improvement.

Results

In the first cycle, 180 member surveys from 19 MDTs were completed. This provided insights into team members’ perceptions of performance. 12 of these teams continued with the study and all 12 completed the matrix. Most teams rated themselves at level one or two (low) on a scale of five for most items.

Conclusions

The MDT survey and maturity matrix have the potential to be useful for cancer care teams to identify their strengths and weaknesses and monitor performance over time and also for management to review its performance against standard criteria and to identify priority areas for improvement and further support.
Improving quality in hospital end-of-life care: honest communication, compassion and empathy
Authors: Rawlings Deb , Devery Kim , Poole Naomi
Published: June 2019

Background

With over half of expected deaths occurring in acute hospitals, and a workforce not trained to care for them, good quality end-of-life care in these settings is hard to achieve. TheNational Consensus Statement on Essential Elements for Safe and High-Quality End-of-Life Carehas been translated into e-learning modules by the End of Life Essentials project, and this study aims to demonstrate how clinicians interpret the Consensus Statement in their day-to-day practice by answering the question at the end of each module: ‘Tomorrow, the one thing I can change to more appropriately provide end-of-life care is…’

Methods

The modules were developed by a palliative care educator with the support of a peer review group and were piloted with 35 health professionals. Pre-post module evaluation data were collected and during a 10-month period from 2016 to 2017 a total of 5181 individuals registered for the project accessing one or more of the six modules. The data from 3201 free-text responses to the post hoc practice change question have been analysed, and themes generated.

Findings

Five themes are derived from the data: communication, emotional insight, professional mindset, person-centred care and professional practice.

Conclusion

Learners who have completed End of Life Essentials have shared the ways they state they can change their practice tomorrow which may well be appreciated as a clinical response to the work by the Australian Commission on Safety and Quality in Health Care in leading and coordinating national improvements in quality and safety in healthcare in Australia. While intent cannot guarantee practice change, theory on intention—behaviour relations indicate that intentions have a strong association with behaviour. This indicates that the modules have the ability to influence end-of-life care in acute hospitals.
APOBEC3B interaction with PRC2 modulates microenvironment to promote HCC progression
Authors: Wang Duowei , Li Xianjing , Li Jiani , Lu Yuan , Zhao Sen , Tang Xinying , Chen Xin , Li Jiaying , Zheng Yan , Li Shuran , Sun Rui , Yan Ming , Yu Decai , Cao Guangwen , Yang Yong
Published: June 2019

Objective

APOBEC3B (A3B), a cytidine deaminase acting as a contributor to the APOBEC mutation pattern in many kinds of tumours, is upregulated in patients with hepatocellular carcinoma (HCC). However, APOBEC mutation patterns are absent in HCC. The mechanism of how A3B affects HCC progression remains elusive.

Design

A3B ­promoter luciferase reporter and other techniques were applied to elucidate mechanisms of A3B upregulation in HCC. A3B overexpression and knockdown cell models, immunocompetent and immune-deficient mouse HCC model were conducted to investigate the influence of A3B on HCC progression. RNA­seq, flow cytometry and other techniques were conducted to analyse how A3B modulated the cytokine to enhance the recruitment of myeloid­-derived suppressor cells (MDSCs) and tumour­-associated macrophages (TAMs).

Results

A3B upregulation through non-classical nuclear factor-κB (NF-κB)signalling promotes HCC growth in immunocompetent mice, associated with an increase of MDSCs, TAMs and programmed cell death1 (PD1) exprssed CD8+T cells. A CCR2 antagonist suppressed TAMs and MDSCs infiltration and delayed tumour growth in A3B and A3BE68Q/E255Q­ expressing mouse tumours. Mechanistically, A3B upregulation in HCC depresses global H3K27me3 abundance via interaction with polycomb repressor complex 2 (PRC2) and reduces an occupancy of H3K27me3 on promoters of the chemokine CCL2 to recruit massive TAMs and MDSCs.

Conclusion

Our observations uncover a deaminase-independent role of the A3B in modulating the HCC microenvironment and demonstrate a proof for the concept of targeting A3B in HCC immunotherapy.
Clinical determinants of plasma cardiac biomarkers in patients with stable chest pain
Authors: Bing Rong , Henderson James , Hunter Amanda , Williams Michelle C , Moss Alastair J , Shah Anoop S V , McAllister David A , Dweck Marc R , Newby David E , Mills Nicholas L , Adamson Philip D
Published: June 2019

Objective

Troponin and B-type natriuretic peptide (BNP) concentrations are associated with cardiovascular risk in stable patients. Understanding their determinants and identifying modifiable clinical targets may improve outcomes. We aimed to establish clinical and cardiac determinants of these biomarkers.

Methods

This was a prespecified substudy from the randomised Scottish Computed Tomography of the Heart trial, which enrolled patients 18–75 years with suspected stable angina between 2010 and 2014 (NCT01149590). We included patients from six centres in whom high-sensitivity troponin I and BNP were measured (Singulex Erenna). Patients with troponin >99th centile upper reference limit (10.2 ng/L) or BNP ≥400 ng/L were excluded to avoid inclusion of patients with myocardial injury or heart failure. Multivariable linear regression models were constructed with troponin and BNP as dependent variables.

Results

In total, 885 patients were included; 881 (99%) and 847 (96%) had troponin and BNP concentrations above the limit of detection, respectively. Participants had a slight male preponderance (n=513; 56.1%), and the median age was 59.0 (IQR 51.0–65.0) years. The median troponin and BNP concentrations were 1.4 (IQR 0.90–2.1) ng/L and 29.1 (IQR 14.0–54.0) ng/L, respectively. Age and atherosclerotic burden were independent predictors of both biomarkers. Male sex, left ventricular mass and systolic blood pressure were independent predictors of increased troponin. In contrast, female sex and left ventricular volume were independent predictors of increased BNP.

Conclusions

Troponin and BNP are associated with coronary atherosclerosis but have important sex differences and distinct and contrasting associations with CT-determined left ventricular mass and volume.

Clinical Trial registration

NCT01149590; Post-results.
Optimal sampling of pelvic lymphadenectomy specimens following radical prostatectomy: is complete tissue submission justified?
Authors: Ni Mhaolcatha Sarah , Power Elaine , Mayer Nick , Prendeville Susan
Published: June 2019

There is currently no consensus among pathologists on the optimal method of sampling pelvic lympadenectomy specimens (PLND) in prostate cancer. We evaluated the impact of complete PLND submission on lymph node (LN) yield, detection of metastasis and laboratory workload in a series of 141 cases. Following isolation of grossly identifiable LNs/potential LNs, the remaining fatty tissue was embedded in toto. Complete PLND submission increased median LN yield from 10 (1–42) to 17 (3–57). Metastatic deposits were identified in nine non-palpable LNs, which altered the pN category in four cases (3%). The primary tumour (pT) was grade group ≥3 and/or pT3 at radical prostatectomy in 96% of pN+ cases. A median of seven additional blocks (1–28) was required for complete tissue embedding. Our findings indicate that submission of the entire fat can optimise PLND assessment but has a significant impact on laboratory workload. Complete submission of selected high-risk cases may be a reasonable alternative.
Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance
Authors: Adhikary Jayashree , Chakraborty Sourabrata , Dalal Subhamita , Basu Souradip , Dey Abhijit , Ghosh Amlan
Published: June 2019

The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis, molecular alteration and its probable role in oncogenesis, have been conducted for research and clinical interest. In this review, a first attempt has been made to summarise the available data on circPVT1 from PubMed and other relevant databases with special emphasis on its role in development, progression and prognosis of various malignant conditions. CircPVT1 is derived from the same genetic locus encoding for long non-coding RNA lncPVT1; however, existing literature suggested circPVT1 and lncPVT1 are transcripted independently by different promoters. The interaction between circRNA and microRNA has been highlighted in majority of the few malignancies in which circPVT1 was studied. Besides its importance in diagnostic and prognostic procedures, circPVT1 seemed to have huge therapeutic potential as evident from differential drug response of cancer cell line as well as primary tumors depending on expression level of the candidate. circPVT1 in cancer therapeutics might be promising as a biomarker to make the existing treatment protocol more effective and also as potential target for designing novel therapeutic intervention.