bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrative review of the factors influencing older nurses’ timing of retirement
Authors: Markowski Marianne , Cleaver Karen , Weldon Sharon Marie
Published: June 2020

Aims

To summarize the international empirical literature to provide a comprehensive understanding of older nurses’ decision‐making surrounding the timing of their retirement.

Background

The global nursing shortage is increasing. Among some countries it has become an economic imperative to consider raising the state pension age and to extend working lives.

Design

An integrative literature review using an integrated design.

Data sources

MEDLINE, CINAHL and Business Source Premier databases were searched for studies between January 2007 – October 2019.

Review Methods

Quality appraisal of the studies was conducted. Findings were summarized, grouped into categories and themes extracted. Two models were developed for data representation.

Results

A total of 132 studies were identified by the search strategy. Of these, 27 articles were included for appraisal and synthesis. Sixteen papers were quantitative, seven qualitative, and four mixed methods. The research took place in 13 different geographical locations. Most studies were of a questionnaire design, followed by interviews and focus groups. The total participant sample was 35,460. Through a synthesis of the studies, four themes were identified: Health, Well‐being, and Family factors; Employer factors; Professional factors; and Financial factors.

Conclusion

This review not only revealed the heterogeneity of studies on this subject and confirmed previous findings but also established a ranking of criteria that influences nurses’ decision‐making: age, followed by personal and organizational factors. Four extracted themes of push and pull factors map onto these factors. No ‘one‐size‐fits‐all’ strategy exists to ensure the extension of older nurses’ working lives. Organizations need to foster an environment where older nurses feel respected and heard and where personal and professional needs are addressed.

Impact

Organizations need to implement HR policies addressing nurses’ personal well‐being and retirement preparation. Older nurses are more likely to extend their working lives if they feel committed to their organization and when professional standards are maintained.
Selection on fruit traits is mediated by the interplay between frugivorous birds, fruit flies, parasitoid wasps and seed‐dispersing ants
Authors: Palacio Facundo X. , Siepielski Adam M. , Lacoretz Mariela V. , Ordano Mariano
Published: June 2020

Every organism on Earth must cope with a multitude of species interactions both directly and indirectly throughout its life cycle. However, how selection from multiple species occupying different trophic levels affects diffuse mutualisms has received little attention. As a result, how a given species amalgamates the combined effects of selection from multiple mutualists and antagonists to enhance its own fitness remains little understood. We investigated how multispecies interactions (frugivorous birds, ants, fruit flies and parasitoid wasps) generate selection on fruit traits in a seed dispersal mutualism. We used structural equation models to assess whether seed dispersers (frugivorous birds and ants) exerted phenotypic selection on fruit and seed traits in the spiny hackberry (Celtis ehrenbergiana), a fleshy‐fruited tree, and how these selection regimes were influenced by fruit fly infestation and wasp parasitoidism levels. Birds exerted negative correlational selection on the combination of fruit crop size and mean seed weight, favouring either large crops with small seeds or small crops with large seeds. Parasitoids selected plants with higher fruit fly infestation levels, and fruit flies exerted positive directional selection on fruit size, which was positively correlated with seed weight. Therefore, higher parasitoidism indirectly correlated with higher plant fitness through increased bird fruit removal. In addition, ants exerted negative directional selection on mean seed weight. Our results show that strong selection on phenotypic traits may still arise in perceived diffuse species interactions. Overall, we emphasize the need to consider diverse direct and indirect partners to achieve a better understanding of the mechanisms driving phenotypic trait evolution in multispecies interactions.
Susceptibility of Oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae) larvae and pupae to native entomopathogenic nematodes
Authors: Patil Jagadeesh , Vijayakumar Rangasamy , Linga Vaddar , Sivakumar Gopalsamy
Published: June 2020

The Oriental armyworm, Mythimna separata Walker (Lepidoptera: Noctuidae) is a major pest of cereal crops, and its outbreaks result in complete crop loss. In this study, we tested the pathogenicity and reproductive potential of indigenous entomopathogenic nematodes (EPNs), Heterorhabditis indica Poinar, Karunakar, & David NBAIIH38, Steinernema abbasi Elawad NBAIISa01, S. carpocapsae Weiser NBAIISc05 and S. siamkayai Stock, Somsook and Reid NBAIRS92 against larval and pupal stages of M. separata under laboratory conditions. Steinernema carpocapsae caused significantly greater mortality in second‐ and fourth‐instar larval stages than other EPNs species. Steinernema carpocapsae caused greatest mortality 100% in larval stages and 75% in pupal stages. Significant differences were observed in the lethal concentration values (LC50 and LC90) of EPNs species against different stages of M. separata. Differences in penetration and multiplication in the fourth‐instar larval stages of M. separata were observed amongst the EPNs species. However, further studies are needed to reveal the field performance of EPN isolates tested to be included in the IPM programme of M. separata.
Pharmacological characterization of the cardiovascular effect of Nibethione: ex vivo, in vivo and in silico studies
Authors: Sánchez-Recillas Amanda , Navarrete-Vázquez Gabriel , Hidalgo-Figueroa Sergio , Bonilla-Hernández Marcos , Ortiz-Andrade Rolffy , Ibarra-Barajas Maximiliano , Yáñez-Pérez Víctor , Sánchez-Salgado Juan Carlos
Published: June 2020

Objective

This work describes the vasorelaxant and antihypertensive effects and the mechanism of action on vascular smooth muscle cells of Nibethione, a synthetic thiazolidinedione derivative. Additionally, evidence of its cytotoxicity is assessed.

Methods

Nibethione (NB) was synthesized, and its vasorelaxant effect and mechanism of action were assessed through ex vivo experiments. Molecular docking studies were used to predict the mode of interaction with L-type Ca2+ channel, and in vivo antihypertensive activity was assayed on spontaneously hypertensive rats (SHR). The cytotoxicity potential was evaluated in porcine aortic endothelial cells (PAECs) from primary explants.

Key findings

Nibethione vasorelaxant effect was efficient on KCl (80 mm) and NE-contraction. This effect was deleteriously modified in the presence of potassium channel block drugs, while the maximal contraction induced with NE was significantly decreased by NB; the CaCl2-induced contraction was abolished entirely. In vivo experiments showed that NB decreased diastolic blood pressure in 20.3 % after its administration on SHR. The molecular docking showed that NB blocks L-type Ca2+ channel, and in vitro tests showed that NB did not produce cytotoxic activity on PAECs (IC50 >1000 µm).

Conclusions

Nibethione showed in vivo antihypertensive and ex vivo vasorelaxant effects with implication of voltage-dependent L-type Ca2+ channel blocking, and this may contribute to the research of novel antihypertensive drugs.
Biogeography and ecological niche evolution in Diapensiaceae inferred from phylogenetic analysis
Authors: Gaynor Michelle L. , Fu Chao‐Nan , Gao Lian‐Ming , Lu Li‐Min , Soltis Douglas E. , Soltis Pamela S.
Published: June 2020

Diapensiaceae (Ericales) are a small family of about 15 species. Within this clade, two species are broadly distributed throughout the Northern Hemisphere, whereas the remaining species have a disjunct distribution between eastern North America and eastern Asia. To address patterns and processes of diversification in Diapensiaceae, we conducted biogeographic analyses and inferred shifts in the ecological niche across the phylogeny of the clade. Although Diapensiaceae have been the focus of multiple phylogenetic and biogeographic studies, previous studies have been taxonomically limited. This study has greatly improved the phylogenetic underpinning for Diapensiaceae with the most inclusive taxonomic sampling thus far, employing both nuclear and plastid gene sequence data for at least one sample per species in the family. Our estimates indicate that genera of Diapensiaceae variously diverged in the Eocene, Oligocene, and early to mid‐Miocene. The biogeographic analysis suggests that the probable ancestor of the Diapensiaceae crown clade originated in the Nearctic, with vicariance events contributing to the current distribution of the disjunct taxa. Ecological niche, when considered in a phylogenetic context, was observed to be clustered on the basis of biogeographic realm. In general, a greater ecological overlap was found at younger nodes and a greater niche divergence was found among distantly related species. Diversification in Diapensiaceae appears to have been shaped by both large‐scale biogeographic factors, such as vicariance, and divergence in an ecological niche among closely related species.
Determinants of stigma among patients with hepatitis C virus infection
Authors: Saine M. Elle , Szymczak Julia E. , Moore Tyler M. , Bamford Laura P. , Barg Frances K. , Schnittker Jason , Holmes John H. , Mitra Nandita , Lo Re Vincent
Published: June 2020

Stigma around hepatitis C virus (HCV) infection is an important and understudied barrier to HCV treatment and elimination. The determinants of HCV‐related stigma, including the impacts of stage of HCV treatment (ie spontaneously cleared; diagnosed, untreated; previously treated, not cured; currently being treated; and treated, cured) and coinfection with human immunodeficiency virus (HIV), remain unknown. To address these gaps, we conducted a cross‐sectional study among patients with a history of HCV infection (n = 270) at outpatient clinics in Philadelphia from July 2018 to May 2019. We evaluated stigma using the validated HCV Stigma Scale, adapted from the Berger HIV Stigma Scale. Associations among HCV‐related stigma and hypothesized demographic, behavioural, and clinical risk factors were evaluated by multivariable linear regression. Most participants (95.5%) experienced HCV‐related stigma. Mean stigma scores did not differ significantly between HCV‐monoinfected and HIV/HCV‐coinfected participants (P = .574). However, we observed significant interactions between HIV status and multiple determinants; therefore, we stratified analyses by HIV status. Among HIV/HCV‐coinfected participants, previous HCV treatment without cure, female gender, Hispanic/Latinx ethnicity and some college education were significantly associated with higher HCV‐stigma scores. An annual income of $10 000‐$40 000 was associated with significantly lower stigma scores. No significant associations were observed among HCV‐monoinfected participants. We found that most participants experienced stigma associated with HCV diagnosis. While stigma scores were similar between HCV‐monoinfected and HIV/HCV‐coinfected participants, the determinants associated with HCV stigma differed by HIV status. Understanding how experiences of stigma differ between HCV‐monoinfected and HIV/HCV‐coinfected patients may aid in the development of targeted interventions to address the HCV epidemic.
Survival characteristics and prognostic importance of echocardiographic measurements of right heart size and function in dogs with pulmonary hypertension
Authors: Visser Lance C. , Wood James E. , Johnson Lynelle R.
Published: June 2020

Background

The clinical relevance of echocardiographic measurements of right heart size and function in dogs with pulmonary hypertension (PH) is unknown.

Objective

To determine if echocardiographic measurements of right heart size and right ventricular (RV) function are associated with survival times in dogs with PH.

Animals

Eighty‐two client‐owned dogs.

Methods

Retrospective study where data from medical records and baseline echocardiographic examinations were collected and measured in a standardized manner. Owners or primary veterinarians were contacted for outcome data.

Results

Enlargement of the right atrium (88%), RV (69%), and pulmonary artery (72%) was common. One‐third of the cases had reduced RV function quantified by two‐dimensional echocardiography‐derived tricuspid annular plane systolic excursion (TAPSE). Decreased TAPSE was significantly (P = .008) more common in dogs with PH not secondary to left heart disease (LHD; 43%) compared to dogs with PH secondary to LHD (14%) but median survival times (182, 95% confidence interval [CI] = 39‐309 versus 298, 95% CI = 85‐314 days, respectively) were not significantly different (P = .78). Right atrial area (hazard ratio [HR] = 2.72, 95% CI = 1.58‐4.70), TAPSE < 3.23 mm/kg0.284 (HR = 2.19, 95% CI = 1.28‐3.74), and right heart failure (HR = 2.05, 95% CI = 1.18‐3.57) were independently associated with shorter survival time (P ≤ .04).

Conclusions and Clinical Importance

Right atrial area, RV function (TAPSE < 3.23 mm/kg0.284), and right heart failure offer clinically relevant prognostic information in dogs with PH. Results support the quantitative assessment of right heart size and function in dogs with PH.
Complete remission and proviral load negativization after allogeneic‐SCT in a patient with Adult T‐cell lymphoma: Case report
Authors: Warley Fernando , Cristaldo Nancy , Barcan Laura , Valledor Alejandra , García‐Rivello Hernán , Arbelbide Jorge , Basquiera Ana L. , Otero Victoria
Published: June 2020

Adult T‐cell lymphoma is an aggressive and poor prognosis HTLV1‐associated lymphoma. There is no standard treatment, but it is known that intensive chemotherapy regimens are necessary, with or without concomitant antiretroviral therapy, plus consolidation with allogeneic stem cell transplantation. Our case report shows a favorable outcome after 2 cycles of chemotherapy and allogeneic stem cell transplantation without antiretroviral agents, achieving complete remission, and a negative proviral load.
Influence of oversewing the transverse staple line during functional end‐to‐end stapled intestinal anastomoses in dogs
Authors: Duffy Daniel J. , Moore George E.
Published: June 2020

Objective

To determine the effect of oversewing the transverse staple line after functional end‐to‐end stapled intestinal anastomoses (FEESA) on canine jejunal leakage pressures.

Study design

Experimental, ex vivo, randomized study.

Sample population

Jejunal segments from three adult canine cadavers.

Methods

Jejunal segments were harvested within 2 hours of euthanasia and anastomosed (24 jejunal segments per group, consisting of two segments per construct with n = 12/ group). Constructs were then randomly assigned to receive FEESA alone, FEESA + Cushing oversew, or FEESA + simple‐continuous oversew of the transverse staple line with 3‐0 polydioxanone. Results for initial leakage pressure (ILP) and maximal leakage pressure (MLP) and initial leakage location (LL) were compared between groups.

Results

Mean ILP was 1.8‐fold higher for FEESA + Cushing oversew (62.4 ± 7.8 mm Hg) compared with FEESA alone and FEESA + simple‐continuous oversew (P < .001). Mean MLP were higher for both oversewn techniques compared with FEESA alone (P < .001). Oversewing the transverse staple line with either pattern increased mean MLP by 1.4‐fold compared with FEESA alone. Leakage occurred at the level of the transverse staple line in nonoversewn constructs (P < .001).

Conclusion

Oversewing the transverse staple line after FEESA increased MLP and decreased the occurrence of leakage at this location. Oversewing with a Cushing pattern increased ILP compared with oversew with a simple‐continuous pattern.

Clinical significance

Our results provide evidence to support oversewing the transverse staple line after FEESA. Doing so may reduce the occurrence of postoperative dehiscence. These findings warrant additional focused investigation in vivo through a prospective randomized clinical trial.
Calibration of matrix-dependent biases in isotope and trace element analyses of carbonate minerals
Authors: McCain Kaitlyn A. , Liu Ming-Chang , McKeegan Kevin D.
Published: June 2020

The timing of important events in the early history of the solar system can be established by using the decay of the short-lived radionuclide 53Mn to stable 53Cr. Carbonate minerals found in meteorite samples can be dated using this system provided that an accurate and precise value for the Mn/Cr ratio can be established. However, the ion yields of Mn and Cr vary substantially based upon the elemental composition of the matrix and require calibration using standards of known Mn and Cr concentrations to relate the measured Mn/Cr ratio to the true ratio with a “relative sensitivity factor.” The authors implant 52Cr+ into a suite of terrestrial calcite and dolomite samples of varied elemental compositions to produce matrix-matched standards for 53Mn-53Cr analysis. Depth profiling of the implanted carbonates reveals variation in the relative sensitivity factors between carbonates low in Fe and Mn and dolomite rich in Fe and Mn. For carbonates with FeCO3 > 8 mol. %, the relative sensitivity factor is constant at 0.88 ± 0.08 (2SD). For carbonates with FeCO3 < 2 mol. %, the relative sensitivity factor is approximately 1.1. The authors also show that the use of an inappropriate relative sensitivity factor can lead to systematic errors in the age determined for meteoritic carbonate.
Manipulation of thin silver film growth on weakly interacting silicon dioxide substrates using oxygen as a surfactant
Authors: Pliatsikas Nikolaos , Jamnig Andreas , Konpan Martin , Delimitis Andreas , Abadias Gregory , Sarakinos Kostas
Published: June 2020

The authors study the morphological evolution of magnetron-sputtered thin silver (Ag) films that are deposited on weakly interacting silicon dioxide (SiO2) substrates in an oxygen-containing (O2) gas atmosphere. In situ and real-time monitoring of electrically conductive layers, along with ex situ microstructural analyses, shows that the presence of O2, throughout all film-formation stages, leads to a more pronounced two-dimensional (2D) morphology, smoother film surfaces, and larger continuous-layer electrical resistivities, as compared to Ag films grown in pure argon (Ar) ambient. In addition, the authors’ data demonstrate that 2D morphology can be promoted, without compromising the Ag-layer electrical conductivity, if O2 is deployed with high temporal precision to target film formation stages before the formation of a percolated layer. Detailed real-space imaging of discontinuous films, augmented by in situ growth monitoring data, suggests that O2 favors 2D morphology by affecting the kinetics of initial film-formation stages and most notably by decreasing the rate of island coalescence completion. Furthermore, compositional and bonding analyses show that O2 does not change the chemical nature of the Ag layers and no atomic oxygen is detected in the films, i.e., O2 acts as a surfactant. The overall results of this study are relevant for developing noninvasive surfactant-based strategies for manipulating noble-metal-layer growth on technologically relevant weakly interacting substrates, including graphene and other 2D crystals.
Immediate Effects of a Single Spinal Manipulation on Lower-Limb Strength in Healthy Individuals: A Critically Appraised Topic
Authors: Wong Christopher Kevin , Conway Lizbeth , Fleming Grant , Gopie Caitlin , Liebeskind Dara , Xue Stephen
Published: June 2020

Clinical Scenario: Many people with lower quarter musculoskeletal dysfunction present with muscle weakness. Strength training hypertrophies muscle and increases strength, but often requires periods over 6 weeks, which can exceed the episode of care. Weakness can persist despite muscle hypertrophy, particularly in the early stages of joint pathology or in the presence of limb or spinal joint hypomobility, which may inhibit muscle activation. Emerging evidence suggests spinal manipulation can increase short-term strength. Screening for specific muscle weakness that could benefit from manipulation to particular spinal segments could facilitate efficient clinical intervention. Although the neuromuscular mechanisms through which manipulation can increase strength remains a topic of investigation, immediate gains can benefit patients by jump-starting an exercise program to train new muscle function gained and enhancing the motivation to continue strengthening. Evidence from randomized controlled trials would provide support for using manipulation to increase muscle strength, while studying healthy people would eliminate confounding factors, such as pain and pathology. Clinical Question: Does randomized controlled trial-level evidence support the concept that a single lumbar spine manipulation session can increase lower-limb strength in healthy individuals? Summary of Key Findings: Level 1b evidence of moderate quality from 3 randomized controlled trials showed immediate small to large effect size muscle strength increases immediately after lumbar spine manipulation. Clinical Bottom Line: Lumbar spine manipulation can result in immediate lower-limb isometric strength increases. While healthy people with normal muscle strength may improve minimally, joint manipulation for people with knee and hip weakness who are otherwise healthy can result in large effect size strength gains. Strength of Recommendation: Moderate quality level 1b evidence from randomized controlled trials with small samples support the use of spinal manipulation to immediately increase lower-limb strength. Additional studies investigating impact on strength and function immediately in people with musculoskeletal pathology are warranted.
Flexible learning, rather than inveterate innovation or copying, drives cumulative knowledge gain
Authors: Miu Elena , Gulley Ned , Laland Kevin N. , Rendell Luke
Published: June 2020

Cumulative cultural evolution is driven by pragmatic individuals who know when to copy, innovate, explore, and take risks flexibly.
Astrocyte dysfunction increases cortical dendritic excitability and promotes cranial pain in familial migraine
Authors: Romanos Jennifer , Benke Dietmar , Pietrobon Daniela , Zeilhofer Hanns Ulrich , Santello Mirko
Published: June 2020

In familial migraine, dysfunction of nonneuronal cells alters frontal cortex physiology and promotes cranial pain.
Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer
Authors: Sarode Poonam , Zheng Xiang , Giotopoulou Georgia A. , Weigert Andreas , Kuenne Carste , Günther Stefan , Friedrich Aleksandra , Gattenlöhner Stefan , Stiewe Thorsten , Brüne Bernhard , Grimminger Friedrich , Stathopoulos Georgios T. , Pullamsetti Soni Savai , Seeger Werner , Savai Rajkumar
Published: June 2020

Targeting β-catenin–dependent gene regulation in macrophages may offer a new immunotherapeutic option in lung cancer.
Long-term patterns of hillslope erosion by earthquake-induced landslides shape mountain landscapes
Authors: Wang Jin , Howarth Jamie D. , McClymont Erin L. , Densmore Alexander L. , Fitzsimons Sean J. , Croissant Thomas , Gröcke Darren R. , West Martin D. , Harvey Erin L. , Frith Nicole V. , Garnett Mark H. , Hilton Robert G.
Published: June 2020

Large earthquakes shape mountain landscapes at high elevations.
HIV envelope trimer-elicited autologous neutralizing antibodies bind a region overlapping the N332 glycan supersite
Authors: Nogal Bartek , McCoy Laura E. , van Gils Marit J. , Cottrell Christopher A. , Voss James E. , Andrabi Raiees , Pauthner Matthias , Liang Chi-Hui , Messmer Terrence , Nedellec Rebecca , Shin Mia , Turner Hannah L. , Ozorowski Gabriel , Sanders Rogier W. , Burton Dennis R. , Ward Andrew B.
Published: June 2020

Strain-specific autologous neutralizing antibodies may compete with N332 supersite targeting broadly neutralizing precursors.
Vascular disrupting agent induced aggregation of gold nanoparticles for photothermally enhanced tumor vascular disruption
Authors: Hong Sheng , Zheng Di-Wei , Zhang Cheng , Huang Qian-Xiao , Cheng Si-Xue , Zhang Xian-Zheng
Published: June 2020

Vascular disrupting agent mediated gold nanoparticles assembly for tumor vascular disruption with photothermal effect.
Oral epithelial IL-22/STAT3 signaling licenses IL-17–mediated immunity to oral mucosal candidiasis
Authors: Aggor Felix E. Y. , Break Timothy J. , Trevejo-Nuñez Giraldina , Whibley Natasha , Coleman Bianca M. , Bailey Rachel D. , Kaplan Daniel H. , Naglik Julian R. , Shan Wei , Shetty Amol C. , McCracken Carrie , Durum Scott K. , Biswas Partha S. , Bruno Vincent M. , Kolls Jay K. , Lionakis Michail S. , Gaffen Sarah L.
Published: June 2020

IL-22 signaling limits oral candidiasis via proliferation of basal epithelial cells and replenishment of an IL-17–responsive layer.
Parent experience of caring for neonates with seizures
Authors: Lemmon Monica , Glass Hannah , Shellhaas Renee A , Barks Mary Carol , Bailey Bria , Grant Katie , Grossbauer Lisa , Pawlowski Kamil , Wusthoff Courtney J , Chang Taeun , Soul Janet , Chu Catherine J , Thomas Cameron , Massey Shavonne L , Abend Nicholas S , Rogers Elizabeth E , Franck Linda S
Published: June 2020

Objective

Neonates with seizures have a high risk of mortality and neurological morbidity. We aimed to describe the experience of parents caring for neonates with seizures.

Design

This prospective, observational and multicentre (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. At the time of hospital discharge, parents answered six open-ended response questions that targeted their experience. Responses were analysed using a conventional content analysis approach.

Results

144 parents completed the open-ended questions (732 total comments). Four themes were identified. Sources of strength: families valued medical team consensus, opportunities to contribute to their child’s care and bonding with their infant. Uncertainty: parents reported three primary types of uncertainty, all of which caused distress: (1) the daily uncertainty of the intensive care experience; (2) concerns about their child’s uncertain future and (3) lack of consensus between members of the medical team. Adapting family life: parents described the many ways in which they anticipated their infant’s condition would lead to adaptations in their family life, including adjusting their family’s lifestyle, parenting approach and routine. Many parents described financial and work challenges due to caring for a child with medical needs. Emotional and physical toll: parents reported experiencing anxiety, fear, stress, helplessness and loss of sleep.

Conclusions

Parents of neonates with seizures face challenges as they adapt to and find meaning in their role as a parent of a child with medical needs. Future interventions should target facilitating parent involvement in clinical and developmental care, improving team consensus and reducing the burden associated with prognostic uncertainty.
Safety of medical compression stockings in patients with diabetes mellitus or peripheral arterial disease
Authors: Rother Ulrich , Grussler Anna , Griesbach Colin , Almasi-Sperling Veronika , Lang Werner , Meyer Alexander
Published: June 2020

Introduction

Compression therapy is highly effective in the treatment of many venous diseases, including leg edema. However, its relevance in patients with peripheral arterial disease (PAD) or diabetes mellitus is critically discussed. The aim of the present study was to assess the influence of compression therapy on microperfusion and its safety in patients with PAD or diabetes mellitus.

Research design and methods

A prospective analysis of 94 consecutive patients (44 patients with diabetes, 45 patients with PAD and 5 healthy controls) undergoing medical compression therapy was performed. Microperfusion was assessed by a combined method of white light tissue spectrometry and laser Doppler flowmetry under medical compression therapy (classes I and II), in different body positions (supine, sitting, standing and elevated position of the leg) and at different locations (great toe, lateral ankle and calf).

Results

During the entire study, no compression-related adverse events occurred. Evaluation of microcirculation parameters (oxygen saturation of hemoglobin and flow) at the different locations and in sitting and standing positions (patients with diabetes and PAD) under compression therapy classes I and II revealed no tendency for reduced microperfusion in both groups. In contrast, in the elevated leg position, all mean perfusion values decreased in the PAD and diabetes groups. However, the same effect was seen in the healthy subgroup.

Conclusions

In consideration of the present inclusion criteria, use of medical compression stockings is safe and feasible in patients with diabetes or PAD. This study did not find relevant impairment of microperfusion parameters under compression therapy in these patient subgroups in physiologic body positions.

Trial registration number

NCT03384758.
Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study
Authors: Wu Jianfeng , Huang Jianqiang , Zhu Guochao , Wang Qiongya , Lv Qingquan , Huang Ying , Yu Yang , Si Xiang , Yi Hui , Wang Cuiping , Liu Yihao , Xiao Han , Zhou Qian , Liu Xin , Yang Daya , Guan Xiangdong , Li Yanbing , Peng Sui , Sung Joseph , Xiao Haipeng
Published: June 2020

Introduction

With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19.

Research design and methods

We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes.

Results

Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes.

Conclusions

Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.
Understanding the structure of a country’s health service providers for defence health engagement
Authors: Bricknell Martin , Hinrichs-Krapels S , Ismail S , Sullivan R
Published: June 2020

There are a variety of structural and systems frameworks for describing the building blocks of country’s public health and health systems. In this paper, we propose a conceptual framework for a holistic view of a country’s health service providers in order to inform the plan for Defence Health Engagement activities with partner countries. This includes all potential government ministries involved in healthcare provision, the independent, private sector and the non-government organisation/charity sector. The framework provides a visualisation to support the analysis of a country’s health services providers. We propose that recognising and analysing the different contributions of all these national health providers is essential for understanding the wider political economy of a nation’s health systems. This can inform a plan of Defence Health Engagement for capacity building in crisis response, development and health systems strengthening.
Contextualised strategies to increase childhood and adolescent vaccination coverage in South Africa: a mixed-methods study
Authors: Wiysonge Charles Shey , Mahasha Phetole Walter , Ndwandwe Duduzile Edith , Ngcobo Ntombenhle , Grimmer Karen , Dizon Janine , Burnett Rosemary J , Cooper Sara
Published: June 2020

Introduction

Despite the unparalleled success of immunisation in the control of vaccine preventable diseases, immunisation coverage in South Africa remains suboptimal. While many evidence-based interventions have successfully improved vaccination coverage in other countries, they are not necessarily appropriate to the immunisation needs, barriers and facilitators of South Africa. The aim of this research is to investigate barriers and facilitators to optimal vaccination uptake, and develop contextualised strategies and implementation plans to increase childhood and adolescent vaccination coverage in South Africa.

Methods

The study will employ a mixed-methods research design. It will be conducted over three iterative phases and use the Adopt, Contextualise or Adapt (ACA) model as an overarching conceptual framework. Phase 1 will identify, and develop a sampling frame of, immunisation stakeholders involved in the design, planning and implementation of childhood and human papillomavirus immunisation programmes in South Africa. Phase 2 will identify the main barriers and facilitators to, and solutions for, increasing vaccination coverage. This phase will comprise exploratory qualitative research with stakeholders and a review of existing systematic reviews on interventions for improving vaccination coverage. Using the findings from Phase 2 and the ACA model, Phase 3 will develop a set of proposed interventions and implementation action plans for improving immunisation coverage in South Africa. These plans will be discussed, revised and finalised through a series of participatory stakeholder workshops and an online questionnaire, conducted as part of Phase 3.

Ethics

Ethical approval was obtained from the South African Medical Research Council (EC018-11/2018). No risks to participants are expected. Various steps will be taken to ensure the anonymity and confidentiality of participants.

Dissemination

The study findings will be shared at stakeholder workshops, the website of Cochrane South Africa and academic publications and conferences.
Cholesterol and triglyceride levels in midlife and risk of heart failure in women, a longitudinal study: the prospective population study of women in Gothenburg
Authors: Halldin Anna-Karin , Lissner Lauren , Lernfelt Bodil , Björkelund Cecilia
Published: June 2020

Objective

To examine the association between triglycerides and cholesterol serum values and risk of developing heart failure in women.

Design

Longitudinal observational study of four cohorts 50-year-old women examined in 1968–1969, 1980–1981, 1992–1993 and 2004–2005, and followed until 2012. S-triglycerides and s-cholesterol were measured at baseline and heart failure morbidity and mortality data collected from 1980 to 2012.

Setting

Prospective population study Gothenburg, Sweden. Primary care.

Participants

1143 women 50 year old without history of heart failure or myocardial infarction.

Main outcome measure

Association among s-triglycerides, s-cholesterol and heart failure expressed as HR for heart failure, adjusted for smoking, body mass index (BMI), physical activity and age.

Results

For 50-year-old women examined in 1968–1969, there was an independent association between level of s-triglycerides and heart failure and a significantly higher risk of developing heart failure (HR 1.8; CI 1.16 to 2.80, for each increment of 1.0 mmol/L in s-triglycerides), adjusted for smoking, BMI, physical activity and age. There was no significant association between s-cholesterol and risk of heart failure (HR 0.9; CI 0.77 to 1.15). In the cohorts of 50-year-old women examined in 1980 and 1992, there were no significant associations between neither s-triglycerides or s-cholesterol and the risk of heart failure. In the pooled analyses of the cohorts examined in 1968, 1980 and 1992, a significantly increased risk of heart failure was found (HR 1.49; CI 1.10 to 2.03) for s-triglycerides independently, but not for s-cholesterol. None of the 50-year-old women examined in 2004–2005 developed heart failure by 2012 and were excluded from further analyses.

Conclusions

High levels of s-triglycerides but not s-cholesterol may be a risk marker for later development of heart failure in 50-year-old women.
Restoration of miR-340 controls pancreatic cancer cellCD47expression to promote macrophage phagocytosis and enhance antitumor immunity
Authors: Xi Qing , Zhang Jieyou , Yang Guangze , Zhang Lijuan , Chen Ying , Wang Chengzhi , Zhang Zimu , Guo Xiangdong , Zhao Jingyi , Xue Zhenyi , Li Yan , Zhang Qi , Da Yurong , Liu Li , Yao Zhi , Zhang Rongxin
Published: June 2020

Background

Immune checkpoint blockade has emerged as a potential cancer immunotherapy. The “don’t eat me” signalCD47in cancer cells binds signal regulatory protein-α on macrophages and prevents their phagocytosis. The role of miR-340 in pancreatic ductal adenocarcinoma (PDAC), especially in tumor immunity, has not been explored. Here, we examined the clinical and biological relevance of miR-340 and the molecular pathways regulated by miR-340 in PDAC.

Methods

CD47and miR-340 expression and the relationship with cancer patient survival were analyzed by bioinformatics. The mechanism of miR-340 action was explored through bioinformatics, luciferase reporter, qRT-PCR and western blot analyses. The effects of miR-340 on cancer cells were analyzed in terms of apoptosis, proliferation, migration and phagocytosis by macrophages.In vivotumorigenesis was studied in orthotopic and subcutaneous models, and immune cells from the peripheral and tumor immune microenvironments were analyzed by flow cytometry. Depletion of macrophages was used to verify the role of macrophages in impacting the function of miR-340 in tumor progression.

Results

miR-340 directly regulates and inversely correlates withCD47,and it predicts patient survival in PDAC. The restoration of miR-340 expression in pancreatic cancer cells was sufficient to downregulateCD47and promote phagocytosis of macrophages, further inhibiting tumor growth. The overexpression of miR-340 promoted macrophages to become M1-like phenotype polarized in peripheral and tumor immune microenvironments and increased T cells, especially CD8+T cells, contributing to the antitumor effect of miR-340.

Conclusions

miR-340 is a key regulator of phagocytosis and antitumor immunity, and it could offer a new opportunity for immunotherapy for PDAC.
Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity
Authors: Reches Adi , Ophir Yael , Stein Natan , Kol Inbal , Isaacson Batya , Charpak Amikam Yoav , Elnekave Afek , Tsukerman Pinchas , Kucan Brlic Paola , Lenac Tihana , Seliger Barbara , Jonjic Stipan , Mandelboim Ofer
Published: June 2020

Background

The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.

Methods

We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo.

Results

We identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo.

Conclusion

We discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.
Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma
Authors: Ascierto Paolo Antonio , Del Vecchio Michele , Mackiewicz Andrzej , Robert Caroline , Chiarion-Sileni Vanna , Arance Ana , Lebbé Céleste , Svane Inge Marie , McNeil Catriona , Rutkowski Piotr , Loquai Carmen , Mortier Laurent , Hamid Omid , Bastholt Lars , Dreno Brigitte , Schadendorf Dirk , Garbe Claus , Nyakas Marta , Grob Jean-Jacques , Thomas Luc , Liszkay Gabriella , Smylie Michael , Hoeller Christoph , Ferraresi Virginia , Grange Florent , Gutzmer Ralf , Pikiel Joanna , Hosein Fareeda , Simsek Burcin , Maio Michele
Published: June 2020

Background

We have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.

Methods

This randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.

Results

At a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutantBRAFtumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively.

Conclusions

This 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies.

Trial registration number

NCT01515189.
Effects of bird feeder density on the foraging behaviors of a backyard songbird (the House Finch, Haemorhous mexicanus) subject to seasonal disease outbreaks
Authors: Aberle M.A. , Langwig K.E. , Adelman J.S. , Hawley D.M.
Published: June 2020

Provisioning of wildlife, such as backyard bird feeding, can alter animal behavior and ecology in diverse ways. For species that are highly dependent on supplemental resources, it is critical to understand how variation in the degree of provisioning, as occurs naturally across backyards, alters wildlife behavior and ecology in ways potentially relevant to disease spread. We experimentally manipulated feeder density at suburban sites and tracked local abundance, foraging behaviors, body mass, and movement in House Finches (Haemorhous mexicanus (P.L. Statius Müller, 1776)), the primary host of a pathogen commonly spread at feeders. Sites with high feeder density harbored higher local House Finch abundance, and birds at these sites had longer feeding bouts and total time on feeders relative to sites with low feeder density. House Finches at high-density feeder sites had lower residual body mass despite greater apparent feeder access. Finally, birds first recorded at low-density feeder sites were more likely to move to neighboring high-density feeder sites than vice versa. Because local abundance and time spent on feeders have both been linked with disease risk in this species, the effects of heterogeneity in bird feeder density on these traits may have important consequences for disease dynamics in this system and more broadly.
High-precision limits on W–$$W'$$ and Z–$$Z'$$ mixing from diboson production using the full LHC Run 2 ATLAS data set
Authors: Pankov A. A. , Osland P. , Serenkova I. A. , Bednyakov V. A.
Published: June 2020

The full ATLAS Run 2 data set with time-integrated luminosity of $$139 \, {\text {fb}}^{-1}$$139fb-1 in the diboson channels in hadronic final states is used to probe a simple model with an extended gauge sector (EGM), proposed by Altarelli et al., and often taken as a convenient benchmark by experimentalists. This model accommodates new charged $$W'$$W′ and neutral $$Z'$$Z′ vector bosons with modified trilinear Standard Model gauge couplings, decaying into electroweak gauge boson pairs WZ or WW, where W/Z decay hadronically. Exclusion limits at the 95% CL on the $$Z'$$Z′ and $$W'$$W′ resonance production cross section times branching ratio to electroweak gauge boson pairs in the mass range of $$\sim $$∼ 1–5 TeV are here converted to constraints on W–$$W'$$W′ and Z–$$Z'$$Z′ mixing parameters and masses for the EGM. We present exclusion regions on the parameter space of the $$W'$$W′ and $$Z'$$Z′ by using the full Run 2 data set comprised of pp collisions at $$\sqrt{s}=13 \, \hbox {TeV}$$s=13TeV and recorded by the ATLAS detector at the CERN LHC. The obtained exclusion regions are significantly extended compared to those obtained from the previous analysis performed with Tevatron data as well as with LHC data collected at 7 and 8 TeV in Run 1 and are the most stringent bounds to date.