bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation and psychometric evaluation of the German version of the IcanSDM measure – a cross-sectional study among healthcare professionals
Authors: Lindig Anja , Hahlweg Pola , Christalle Eva , Giguere Anik , Härter Martin , von dem Knesebeck Olaf , Scholl Isabelle
Published: June 2021

Background

Shared decision-making (SDM) between patients and healthcare professionals (HCPs) is a key component of patient-centred care. To implement SDM in clinical practice and to evaluate its effects, it is helpful to know about HCPs’ perception of SDM barriers. The measure IcanSDM was developed in Canada and assesses the perception of SDM barriers. To our knowledge, no equivalent measure exists in German. Therefore, the aim of this study was to translate and adapt the IcanSDM measure to be used by a German speaking population and evaluate its psychometric properties.

Methods

This is a cross-sectional psychometric study based on a secondary analysis of baseline data from a SDM implementation study. The original 8-item IcanSDM was translated into German using a team translation protocol. We assessed comprehensibility via cognitive interviews with n = 11 HCPs. Based on results of cognitive interviews, the translated IcanSDM version was revised. Two hundred forty-two HCPs filled out the measure. Psychometric analysis included acceptance (completion rate), item characteristics (response distribution, skewness, item difficulties, corrected item-total correlations, inter-item correlations), factorial structure (confirmatory factor analysis (CFA), model fit), and internal consistency (Cronbach’s α).

Results

We translated and adapted the German IcanSDM successfully except for item 8, which had to be revised after the cognitive interviews. Completion rate was 98%. Skewness of the items ranged between −.797 and 1.25, item difficulties ranged between 21.63 and 70.85, corrected item-total-correlations ranged between .200 and .475, inter-item correlations ranged between .005 and .412. Different models based on CFA results did not provide a valid factorial structure. Cronbach’s α ranged between .563 and .651 for different factor models.

Conclusion

We provide the first German measure for assessing perception of SDM barriers by HCPs. The German IcanSDM is a brief measure with good acceptance. However, we found unsatisfying psychometric properties, which were comparable to results of the original scale. In a next step, the IcanSDM should be further developed and modified and predictive validity should be evaluated.
Protocol for a two-arm pragmatic stepped-wedge hybrid effectiveness-implementation trial evaluating Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship (ENCOMPASS)
Authors: Kowalkowski Marc , Eaton Tara , McWilliams Andrew , Tapp Hazel , Rios Aleta , Murphy Stephanie , Burns Ryan , Gutnik Bella , O’Hare Katherine , McCurdy Lewis , Dulin Michael , Blanchette Christopher , Chou Shih-Hsiung , Halpern Scott , Angus Derek C. , Taylor Stephanie P.
Published: June 2021

Background

Sepsis survivors experience high morbidity and mortality, and healthcare systems lack effective strategies to address patient needs after hospital discharge. The Sepsis Transition and Recovery (STAR) program is a navigator-led, telehealth-based multicomponent strategy to provide proactive care coordination and monitoring of high-risk patients using evidence-driven, post-sepsis care tasks. The purpose of this study is to evaluate the effectiveness of STAR to improve outcomes for sepsis patients and to examine contextual factors that influence STAR implementation.

Methods

This study uses a hybrid type I effectiveness-implementation design to concurrently test clinical effectiveness and gather implementation data. The effectiveness evaluation is a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial at eight hospitals in North Carolina comparing clinical outcomes between sepsis survivors who receive Usual Care versus care delivered through STAR. Each hospital begins in a Usual Care control phase and transitions to STAR in a randomly assigned sequence (one every 4 months). During months that a hospital is allocated to Usual Care, all eligible patients will receive usual care. Once a hospital transitions to STAR, all eligible patients will receive STAR during their hospitalization and extending through 90 days from discharge. STAR includes centrally located nurse navigators using telephonic counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted with suspected sepsis, defined by clinical criteria for infection and organ failure, are included. Planned enrollment is 4032 patients during a 36-month period. The primary effectiveness outcome is the composite of all-cause hospital readmission or mortality within 90 days of discharge. A mixed-methods implementation evaluation will be conducted before, during, and after STAR implementation.

Discussion

This pragmatic evaluation will test the effectiveness of STAR to reduce combined hospital readmissions and mortality, while identifying key implementation factors. Results will provide practical information to advance understanding of how to integrate post-sepsis management across care settings and facilitate implementation, dissemination, and sustained utilization of best-practice post-sepsis management strategies in other heterogeneous healthcare delivery systems.

Trial registration

NCT04495946. Submitted July 7, 2020; Posted August 3, 2020.
Correction to: Exosomal miR-126 blocks the development of non-small cell lung cancer through the inhibition of ITGA6
Authors: Li Mingjun , Wang Qianqian , Zhang Xiaofei , Yan Ningning , Li Xingya
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
How muscle stiffness affects human body model behavior
Authors: Trube Niclas , Riedel Werner , Boljen Matthias
Published: June 2021

Background

Active human body models (AHBM) consider musculoskeletal movement and joint stiffness via active muscle truss elements in the finite element (FE) codes in dynamic application. In the latest models, such as THUMS™ Version 5, nearly all human muscle groups are modeled in form of one-dimensional truss elements connecting each joint. While a lot of work has been done to improve the active and passive behavior of this 1D muscle system in the past, the volumetric muscle system of THUMS was modeled in a much more simplified way based on Post Mortem Human Subject (PMHS) test data. The stiffness changing effect of isometric contraction was hardly considered for the volumetric muscle system of whole human body models so far. While previous works considered this aspect for single muscles, the effect of a change in stiffness due to isometric contraction of volumetric muscles on the AHBM behavior and computation time is yet unknown.

Methods

In this study, a simplified frontal impact using the THUMS Version 5 AM50 occupant model was simulated. Key parameters to regulate muscle tissue stiffness of solid elements in THUMS were identified for the material model MAT_SIMPLIFIED_FOAM and different stiffness states were predefined for the buttock and thigh.

Results

During frontal crash, changes in muscle stiffness had an effect on the overall AHBM behavior including expected injury outcome. Changes in muscle stiffness for the thigh and pelvis, as well as for the entire human body model and for strain-rate-dependent stiffness definitions based on literature data had no significant effect on the computation time.

Discussion

Kinematics, peak impact force and stiffness changes were in general compliance with the literature data. However, different experimental setups had to be considered for comparison, as this topic has not been fully investigated experimentally in automotive applications in the past. Therefore, this study has limitations regarding validation of the frontal impact results.

Conclusion

Variations of default THUMS material model parameters allow an efficient change in stiffness of volumetric muscles for whole AHBM applications. The computation time is unaffected by altering muscle stiffness using the method suggested in this work. Due to a lack of validation data, the results of this work can only be validated with certain limitations. In future works, the default material models of THUMS could be replaced with recently published models to achieve a possibly more biofidelic muscle behavior, which would even allow a functional dependency of the 1D and 3D muscle systems. However, the effect on calculation time and model stability of these models is yet unknown and should be considered in future studies for efficient AHBM applications.
Trajectories of antidepressant use before and after a suicide attempt among refugees and Swedish-born individuals: a cohort study
Authors: Amin Ridwanul , Rahman Syed , Helgesson Magnus , Björkenstam Emma , Runeson Bo , Tinghög Petter , Mehlum Lars , Qin Ping , Mittendorfer-Rutz Ellenor
Published: June 2021

Background

To identify key information regarding potential treatment differences in refugees and the host population, we aimed to investigate patterns (trajectories) of antidepressant use during 3 years before and after a suicide attempt in refugees, compared with Swedish-born. Association of the identified trajectory groups with individual characteristics were also investigated.

Methods

All 20–64-years-old refugees and Swedish-born individuals having specialised healthcare for suicide attempt during 2009–2015 (n = 62,442, 5.6% refugees) were followed 3 years before and after the index attempt. Trajectories of annual defined daily doses (DDDs) of antidepressants were analysed using group-based trajectory models. Associations between the identified trajectory groups and different covariates were estimated by chi2-tests and multinomial logistic regression.

Results

Among the four identified trajectory groups, antidepressant use was constantly low (≤15 DDDs) for 64.9% of refugees. A ‘low increasing’ group comprised 5.9% of refugees (60–260 annual DDDs before and 510–685 DDDs after index attempt). Two other trajectory groups had constant use at medium (110–190 DDDs) and high (630–765 DDDs) levels (22.5 and 6.6% of refugees, respectively). Method of suicide attempt and any use of psychotropic drugs during the year before index attempt discriminated between refugees’ trajectory groups. The patterns and composition of the trajectory groups and their association, discriminated with different covariates, were fairly similar among refugees and Swedish-born, with the exception of previous hypnotic and sedative drug use being more important in refugees.

Conclusions

Despite previous reports on refugees being undertreated regarding psychiatric healthcare, no major differences in antidepressant treatment between refugees and Swedish-born suicide attempters were found.
Platelet adhesion in type 2 diabetes: impact of plasma albumin and mean platelet volume
Authors: Johansson Mona , Eriksson Andreas C. , Östgren Carl Johan , Whiss Per A.
Published: June 2021

Background

Altered mean platelet volume (MPV) and plasma albumin has been reported in type 2 diabetes (T2D). MPV is suggested to predict cardiovascular risk but there is a lack of evidence for associations between MPV and platelet adhesion. Plasma albumin and magnesium are other factors reported to influence thrombotic risk. The objectives of this study were to assess the association between platelet adhesion and plasma factors with a potential role to affect platelet activation.

Methods

Blood was collected from 60 T2D patients and 60 healthy controls. Platelet adhesion to different protein surfaces induced by various soluble activators were measured in microplates. MPV, albumin and magnesium were analysed together with additional routine tests.

Results

Despite normal levels, plasma albumin significantly correlated with adhesion of T2D platelets but not with controls. There was a significant association between MPV and platelet adhesion in both groups, but association was smaller in T2D. Levels of glucose, HbA1c or magnesium did not correlate with platelet adhesion.

Conclusions

Plasma albumin was associated with platelet adhesion in T2D suggesting that albumin may be a factor to consider upon cardiovascular risk assessment. MPV was more associated with the level of platelet adhesion in healthy individuals than in well-controlled T2D patients.
Interleukin-24 regulates mucosal remodeling in inflammatory bowel diseases
Authors: Ónody Anna , Veres-Székely Apor , Pap Domonkos , Rokonay Réka , Szebeni Beáta , Sziksz Erna , Oswald Franz , Veres Gábor , Cseh Áron , Szabó Attila J. , Vannay Ádám
Published: June 2021

Background

Recently, increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). However, the role of IL-24 in the pathomechanism of IBD is still largely unknown.

Methods

Presence of IL-24 was determined in the samples of children with IBD and in the colon of dextran sodium sulfate (DSS) treated mice. Effect of inflammatory factors on IL24 expression was determined in peripheral blood (PBMCs) and lamina propria mononuclear cells (LPMCs). Also, the impact of IL-24 was investigated on HT-29 epithelial cells and CCD-18Co colon fibroblasts. Expression of tissue remodeling related genes was investigated in the colon of wild type (WT) mice locally treated with IL-24 and in the colon of DSS treated WT and Il20rb knock out (KO) mice.

Results

 Increased amount of IL-24 was demonstrated in the serum and colon samples of children with IBD and DSS treated mice compared to that of controls. IL-1β, LPS or H2O2 treatment increased the expression of IL24 in PBMCs and LPMCs. IL-24 treatment resulted in increased amount of TGF-β and PDGF-B in HT-29 cells and enhanced the expression of extracellular matrix (ECM)-related genes and the motility of CCD-18Co cells. Similarly, local IL-24 treatment increased the colonic Tgfb1 and Pdgfb expression of WT mice. Moreover, expression of pro-fibrotic Tgfb1 and Pdgfb were lower in the colon of DSS treated Il20rb KO compared to that of WT mice. The disease activity index of colitis was less severe in DSS treated Il20rb KO compared to WT mice.

Conclusion

Our study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.
Perspectives in immunotherapy: meeting report from the immunotherapy bridge (December 2nd–3rd, 2020, Italy)
Authors: Ascierto Paolo A. , Bifulco Carlo , Ciardiello Fortunato , Demaria Sandra , Emens Leisha A. , Ferris Robert , Formenti Silvia C. , Galon Jerome , Khleif Samir N. , Kirchhoff Tomas , McQuade Jennifer , Odunsi Kunle , Patnaik Akash , Paulos Chrystal M. , Taube Janis M. , Timmerman John , Fox Bernard A. , Hwu Patrick , Puzanov Igor
Published: June 2021

Improved understanding of tumor immunology has enabled the development of therapies that harness the immune system and prevent immune escape. Numerous clinical trials and real-world experience has provided evidence of the potential for long-term survival with immunotherapy in various types of malignancy. Recurring observations with immuno-oncology agents include their potential for clinical application across a broad patient population with different tumor types, conventional and unconventional response patterns, durable responses, and immune-related adverse events. Despite the substantial achievements to date, a significant proportion of patients still fail to benefit from current immunotherapy options, and ongoing research is focused on transforming non-responders to responders through the development of novel treatments, new strategies to combination therapy, adjuvant and neoadjuvant approaches, and the identification of biomarkers of response. These topics were the focus of the virtual Immunotherapy Bridge (December 2nd–3rd, 2020), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer and are summarised in this report.
ECLS supported transport of ICU patients: does out-of -house implantation impact survival?
Authors: Fleissner Felix , Mogaldea Alexandru , Martens Andreas , Natanov Ruslan , Rümke Stefan , Salman Jawad , Kaufeld Tim , Ius Fabio , Beckmann Erik , Haverich Axel , Kühn Christian
Published: June 2021

Background

Extracorporeal life support (ECLS) is an established tool to stabilize severely ill patients with therapy-refractory hemodynamic or respiratory failure. Recently, we established a mobile ECLS retrieval service at our institution. However, data on the outcome of patients receiving ECLS at outside hospitals for transportation into tertiary hospitals is still sparse.

Methods

We have analyzed all patients receiving ECLS in outside hospitals (Transport group, TG) prior to transportation to our institution and compared the outcome to our in-house ECLS experience (Home Group, HG).

Results

Between 2012 and 2018, we performed 978 ECLS implantations, 243 of which were performed on-site in tertiary hospitals for ECLS supported transportation. Significantly more veno-venous systems were implanted in TG (n = 129 (53%) vs. n = 327 (45%), p = 0.012). Indication for ECLS support differed between the groups, with more pneumonia; acute respiratory distress syndromes in the TG group and of course, more postcardiotomy patients in HG. Mean age was 47 (± 20) (HG) vs. 48 (± 18) (TG) years, p = 0.477 with no change over time. No differences were seen in ECLS support time (8.03 days ±8.19 days HG vs 7.81 days ±6.71 days TG, p = 0.675). 30-day mortality (n = 379 (52%) (HG) vs. n = 119 (49%) (TG) p = 0.265) and death on ECLS support (n = 322 (44%) (HG) vs. n = 97 (40%) TG, p = 0.162) were comparable between the two groups, despite a more severe SAVE score in the v-a TG (HG: − 1.56 (± 4.73) vs. TG -3.93 (± 4.22) p < 0.001). Mortality rates did not change significantly over the years. Multivariate risk analysis revealed Influenza, Peak Insp. Pressure at implantation, pO2/FiO2 ratio and ECLS Score (SAVE/RESP) as well as ECLS support time to be independent risk factors for mortality.

Conclusion

Mobile ECLS support is a tremendous challenge. However, it is justified to offer 24 h/7d ECLS standby for secondary and primary hospitals as a tertiary hospital. Increasing indications and total numbers for ECLS support raise the need for further studies to evaluate outcome in these patients.
Blood volume and hemoglobin mass in long-term heart transplant recipients with and without Anemia
Authors: Seiler Florian , Ahlgrim Christoph , Birkner Philipp , Wrobel Nina , Rilinger Jonathan , Grundmann Sebastian , Bode Christoph , Pottgiesser Torben
Published: June 2021

Background

In systolic chronic heart failure, a heterogeneous blood volume (BV) regulation can be found with plasma volume expansion in many cases, possibly leading to pseudoanemia. Little is known about the volume status after heart transplantation (HTX). So far, anemia of HTX recipients was solely investigated using hemoglobin-concentration that may be misleading in a clinical context. The objective of the study was whether a difference in plasma volume and red cell volume can be observed in clinically stable heart transplant recipients compared to matched control subjects. Secondary, the aim was to describe anemia in the long-term after HTX based on quantitative data.

Methods

Blood volume and its constituents red cell volume and plasma volume were quantified using an abbreviated carbon monoxide rebreathing method (aCORM) with focus on its primary measure total hemoglobin mass (Hbmass) and coincidental anemia in 36 (7 women) heart transplant recipients. For comparison, a matched control group of 46 (5 women) healthy subjects was selected.

Results

Neither Hbmass nor blood volumes were significantly different in HTX patients compared to matched healthy control group subjects. The prevalence of anemia 6.3 ± 4.3 years after transplantation was 19%. Hbmass and red cell volume were significantly lower in anemic HTX patients compared to non-anemic patients while plasma volume was not expanded. Various immunosuppressant regimens did not have an effect on Hbmass, plasma volume or red cell volume.

Conclusions

There was no difference in blood volumes and Hbmass between HTX patients and control subjects. The pathophysiologic blood volume regulation in chronic heart failure does not seem to be longer active in long-term HTX recipients. However, in the long-term after HTX, anemia occurs in a considerable number of patients as true anemia without a clear association with immunosuppression.

Trial registration

German registry for clinical studies, DRKS00006078. Registered 09 May 2014,https://www.drks.de/drks_web/navigate.do?navigationId=trial. HTML&TRIAL_ID=DRKS00006078.
Parkinson mice show functional and molecular changes in the gut long before motoric disease onset
Authors: Gries Manuela , Christmann Anne , Schulte Steven , Weyland Maximilian , Rommel Stephanie , Martin Monika , Baller Marko , Röth Ralph , Schmitteckert Stefanie , Unger Marcus , Liu Yang , Sommer Frederik , Mühlhaus Timo , Schroda Michael , Timmermans Jean-Pierre , Pintelon Isabel , Rappold Gudrun A. , Britschgi Markus , Lashuel Hilal , Menger Michael D. , Laschke Matthias W. , Niesler Beate , Schäfer Karl-Herbert
Published: June 2021

Background

There is increasing evidence that Parkinson’s disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain is already destroyed, so that the lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use a transgenic A30P-α-synuclein-overexpressing PD mouse model to identify appropriate candidate markers in the gut before hallmark symptoms begin to manifest.

Methods

Based on a gait analysis and striatal dopamine levels, we defined 2-month-old A30P mice as pre-symptomatic (psA30P), since they are not showing any motoric impairments of the skeletal neuromuscular system and no reduced dopamine levels, but an intestinal α-synuclein pathology. Mice at this particular age were further used to analyze functional and molecular alterations in both, the gastrointestinal tract and the ENS, to identify early pathological changes. We examined the gastrointestinal motility, the molecular composition of the ENS, as well as the expression of regulating miRNAs. Moreover, we applied A30P-α-synuclein challenges in vitro to simulate PD in the ENS.

Results

A retarded gut motility and early molecular dysregulations were found in the myenteric plexus of psA30P mice. We found that i.e. neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are significantly altered in the psA30P, thus representing potential biomarkers for early PD. Many of the dysregulated miRNAs found in the psA30P mice are reported to be changed in PD patients as well, either in blood, cerebrospinal fluid or brain tissue. Interestingly, the in vitro approaches delivered similar changes in the ENS cultures as seen in the transgenic animals, thus confirming the data from the mouse model.

Conclusions

These findings provide an interesting and novel approach for the identification of appropriate biomarkers in men.
Why and how to open intensive care units to family visits during the pandemic
Authors: Mistraletti Giovanni , Giannini Alberto , Gristina Giuseppe , Malacarne Paolo , Mazzon Davide , Cerutti Elisabetta , Galazzi Alessandro , Giubbilo Ilaria , Vergano Marco , Zagrebelsky Vladimiro , Riccioni Luigi , Grasselli Giacomo , Scelsi Silvia , Cecconi Maurizio , Petrini Flavia
Published: June 2021

Since the lockdown because of the pandemic, family members have been prohibited from visiting their loved ones in hospital. While it is clearly complicated to implement protocols for the admission of family members, we believe precise strategic goals are essential and operational guidance is needed on how to achieve them. Even during the pandemic, we consider it a priority to share strategies adapted to every local setting to allow family members to enter intensive care units and all the other hospital wards.
Seropositivity to canine tick-borne pathogens in a population of sick dogs in Italy
Authors: Mendoza-Roldan Jairo Alfonso , Benelli Giovanni , Bezerra-Santos Marcos Antonio , Nguyen Viet-Linh , Conte Giuseppe , Iatta Roberta , Furlanello Tommaso , Otranto Domenico
Published: June 2021

Background

Canine vector-borne diseases (CVBDs) associated to ticks are among the most important health issues affecting dogs. In Italy, Ehrlichia canis, Anaplasma spp., Rickettsia conorii and Borrelia burgdorferi (s.l.) have been studied in both healthy canine populations and those clinically ill with suspected CVBDs. However, little information is currently available on the overall prevalence and distribution of these pathogens in the country. The aim of this study was to assess the prevalence and distribution of tick-borne pathogens (TBPs) in clinically suspect dogs from three Italian macro areas during a 15-year period (2006–2020).

Methods

A large dataset (n = 21,992) of serological test results for selected TBPs in three macro areas in Italy was analysed using a Chi-square test to evaluate the associations between the categorical factors (i.e. macro area, region, year, sex and age) and a standard logistic regression model (significance set at P = 0.05). Serological data were presented as annual and cumulative prevalence, and distribution maps of cumulative positive cases for TBPs were generated.

Results

Of the tested serum samples, 86.9% originated from northern (43.9%) and central (43%) Italy. The majority of the tests was requested for the diagnosis of E. canis (47%; n = 10,334), followed by Rickettsia spp. (35.1%; n = 7725), B. burgdorferi (s.l.) (11.6%; n = 2560) and Anaplasma spp. (6.2%; n = 1373). The highest serological exposure was recorded for B. burgdorferi (s.l.) (83.5%), followed by Rickettsia spp. (64.9%), Anaplasma spp. (39.8%) and E. canis (28.7%). The highest number of cumulative cases of Borrelia burgdorferi (s.l.) was recorded in samples from Tuscany, central Italy. Rickettsia spp. was more prevalent in the south and on the islands, particularly in dogs on Sicily older than 6 years, whereas Anaplasma spp. was more prevalent in the north and E. canis more prevalent in the south and on the islands.

Conclusions

The results of this study highlight the high seroprevalence and wide distribution of the four TBPs in dogs with clinically suspected CVBDs from the studied regions of Italy. The very high seroprevalence of B. burgdorferi (s.l.) exemplifies a limitation of this study, given the use of clinically suspect dogs and the possibility of cross-reactions when using serological tests. The present research provides updated and illustrative information on the seroprevalence and distribution of four key TBPs, and advocates for integrative control strategies for their prevention.

Graphical Abstract
Prevalence of ultrasound-detected knee synovial abnormalities in a middle-aged and older general population—the Xiangya Osteoarthritis Study
Authors: Jiang Ting , Yang Tuo , Zhang Weiya , Doherty Michael , Zhang Yuqing , Wei Jie , Sarmanova Aliya , Hall Michelle , Yang Zidan , Li Jiatian , Fernandes Gwen S. , Obotiba Abasiama D. , Gohir Sameer A. , Courtney Philip , Zeng Chao , Lei Guanghua
Published: June 2021

Background

There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample.

Methods

Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA.

Results

There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval [CI] 2.00–2.86) for synovial hypertrophy, 1.58 (95%CI 1.39–1.80) for effusion, and 4.36 (95%CI 3.09–6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38–4.82), 2.01 (95%CI 1.76–2.29), and 6.49 (95%CI 4.51–9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding P for interaction were 0.004 and 0.067, respectively.

Conclusions

Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.
Cross-cultural translation and validation of the Spanish version of the patellofemoral pain and osteoarthritis subscale of the KOOS (KOOS-PF)
Authors: Martinez-Cano Juan Pablo , Vernaza-Obando Daniel , Chica Julián , Castro Andrés Mauricio
Published: June 2021

Objective

The aim of this study was to translate to Spanish the patellofemoral pain and osteoarthritis subscale of the knee injury and osteoarthritis outcome score (KOOS-PF) and validate this Spanish version of a disease-specific patient-reported outcome measure (PROM) for patellofemoral pain.

Results

The KOOS-PF was translated to Spanish and sixty patients with patellofemoral pain and/or osteoarthritis accepted to complete the questionnaire. 1-week later 58 patients answered the questions again for the test–retest reliability validation and finally 55 patients completed 1-month later for the responsiveness assessment. The Spanish version showed very good internal consistency (Cronbach’s alpha: 0.93) and test–retest reliability (intraclass correlation coefficient: 0.82). Responsiveness was confirmed, showing a strong correlation with the global rating of change (GROC) score (r 0.64). The minimal detectable change was 11.1 points, the minimal important change was 17.2 points, and there were no floor or ceiling effects for the score.
Screening of potential vaccine candidates against pathogenic Brucella spp. using compositive reverse vaccinology
Authors: Zai Xiaodong , Yin Ying , Guo Fengyu , Yang Qiaoling , Li Ruihua , Li Yaohui , Zhang Jun , Xu Junjie , Chen Wei
Published: June 2021

Brucellaspp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains ofBrucellaspp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load ofB. abortusS19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens againstBrucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenicBrucellaspecies challenge.
A newly identified Hippo homologue from the oriental river prawn Macrobrachium nipponense is involved in the antimicrobial immune response
Authors: Huang Ying , Ren Qian
Published: June 2021

The Hippo signalling pathway plays a vital role in organ size control, cell proliferation, apoptosis, and immune regulation. In this study, a Hippo homologue with three isoforms (named MnHippo-a, MnHippo-b, and MnHippo-c) was isolated and characterized for the first time from the freshwater prawn Macrobrachium nipponense. The deduced amino acid sequences of MnHippo-a (698 aa), MnHippo-b (688 aa), and MnHippo-c (656 aa) were highly similar, and they all contained an N-terminal S_TKc (serine/threonine protein kinase catalytic) domain and a C-terminal Mst1_SARAH (Sav/Rassf/Hpo) domain. MnHippo-a and MnHippo-c were derived from alternative splicing. Phylogenetic analysis was performed, and the results revealed that MnHippo was a member of the clade containing STPK4 and Hippo of Penaeus vannamei. The expression distribution showed that MnHippo was constitutively expressed in various tissues of uninfected prawns and highly expressed in the hepatopancreas and intestine. In prawns challenged with Vibrio parahaemolyticus and Staphylococcus aureus, the expression of MnHippo in haemocytes was significantly upregulated. Furthermore, in MnHippo-knockdown prawns injected with V. parahaemolyticus or S. aureus, the transcription levels of five antimicrobial peptides were downregulated. MnHippo silencing weakened the clearance of V. parahaemolyticus and S. aureus in prawns. The survival rate of the MnHippo-dsRNA group was obviously decreased from 2 to 6 days post-injection with V. parahaemolyticus or S. aureus. Hence, MnHippo might be involved in the antibacterial immune defence of M. nipponense.
Mammary gland 3D cell culture systems in farm animals
Authors: Finot Laurence , Chanat Eric , Dessauge Frederic
Published: June 2021

In vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.
Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan
Authors: Duan Li-Yao , Liang Yan , Gong Wen-Ping , Xue Yong , Mi Jie , Wang Jie , Wang Lan , Jia Zai-Xing , Lei Hong , Liang Yu-Mei , Liu Jun , Zheng Yue , Wu Xue-Qiong
Published: June 2021

Background

The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH.

Methods

BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing.

Results

After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model.

Conclusions

NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.
Anti-NMDAR encephalitis for psychiatrists: the essentials
Authors: Beattie Matthew , Goodfellow John , Oto Maria , Krishnadas Rajeev
Published: June 2021

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly presents with psychiatric symptoms. Psychiatrists need to be alert to this diagnostic possibility, especially in female adolescents and young adults, as exemplified by the real (de-identified) case outlined below. Earlier diagnosis and immunotherapy improves long-term outcomes. Collaboration with neurology colleagues is essential for optimal care. ‘Red flags’ for autoimmune encephalitis and ‘diagnostic clues’ act as helpful aide memoires for this uncommon condition. The gold standard for testing is the detection of NMDAR antibodies in cerebrospinal fluid, but serum can be tested as a more accessible (but less reliable) preliminary step. The results of routine blood tests, magnetic resonance imaging of the head and electroencephalograms can be normal or show non-specific changes. Diagnostic criteria exist to define probable and definite cases. Immunotherapy for anti-NMDAR encephalitis is effective for many patients, but recovery is prolonged and relapses can occur.
Racial disparities in pediatric cancer care in the United States: An analysis of the Kids' Inpatient Database.
Authors: Baliga Sujith , Blakaj Dukagjin , Yildiz Vedat , Puri Pranav , Palmer Joshua David
Published: June 2021

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Background: The impact of race and socioeconomic status (SES) on cancer mortality has been elucidated in adult patients, but is not well described in pediatric oncology. We hypothesize that racial and socioeconomic disparities exist in pediatric cancer patients, resulting in higher rates of hospitalization and mortality. Methods: We analyzed the Kids’ Inpatient Database (KID) which shows national estimates of inpatient stays for pediatric patients. Inclusion criteria included patients who were ≤20 with a cancer diagnosis identified through the Clinical Classifications Software (CCS). Variables analyzed were discharge status, patient demographics, hospital characteristics, expected payment source, total visit charge, and length of stay. Initial comparisons between cancer and non-cancer related discharges were performed using a chi-square test. To estimate disparities by race, clinical comparisons were performed across five racial groups: White, Black, Hispanic, Asian/Pacific Islander, and Native American/Other. A multivariable logistic regression model was used to examine predictors of hospitalization and mortality. Results: From 2006-2012, there were 9,488,477 non-cancer related pediatric inpatient stays and 242,489 cancer related stays. Patients with cancer related visits were more likely to be white, male (54.9% vs 46.1%, p < 0.0001), older at admission, have private insurance (52.5% vs 41.7%), and were from a higher income quartile (76th-100th percentile, 25.2% vs 19.9%, p < 0.001). These patients also had a higher rate of death during admission (1.2% vs 0.5%, p < 0.0001), higher cost of visit charge ($25,097 vs $8,267, p < 0.001), longer length of stay (4 vs 2 days), and were less likely to be discharged (85.5% vs 92.0%, p < 0.0001).The four most frequent cancer diagnoses associated with hospital admission were leukemia (n = 75,807), Other and Unspecified Primary (n = 50,076), bone/connective tissue tumor (n = 42,477), and central nervous system tumor (n = 27,958). Patients who were non-white were more likely to die during their inpatient stay (1.5% Non-white versus 0.9% White, p < 0.001). On multivariate logistic regression, Black (OR: 1.61, 95% CI: 1.57-1.66, p < 0.0001) and Native American (OR: 1.39, 95% CI: 1.34-1.44, p < 0.0001) race, as well as lower income quartile (OR: 1.24, 95% CI: 1.19-1.28, p < 0.001) were associated with increased odds of death during admission. Conclusions: This is the largest observational study to date to identify the impact of race and SES on pediatric cancer hospitalization and mortality in the United States. Non-white race and lower SES was associated with significantly increased odds of death during admission. Given the significant difference in mortality by race, healthcare policy makers and insurance companies should investigate the specific drivers of increased admission and mortality and develop strategies to address inequity in cancer care.
Disparities in cardiovascular risk factors by race/ethnicity among adult survivors of childhood cancer: A report from the Childhood Cancer Survivorship Study (CCSS).
Authors: Noyd David H , Yasui Yutaka , Li Nan , Chow Eric Jessen , Bhatia Smita , Landstrom Andrew , Gilchrist Susan , Tonorezos Emily S. , Zullig Leah L. , Casillas Jacqueline N. , Berkman Amy Madelon , Ness Kirsten K. , Mulrooney Daniel A. , Leisenring Wendy M. , Howell Carrie R. , Shoag Jamie Michelle , Kirchhoff Anne C. , Howell Rebecca M. , Armstrong Gregory T. , Oeffinger Kevin C.
Published: June 2021

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Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade >2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (>2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]