Differential effect by chronic disease risk: A secondary analysis of the ChooseWell 365 randomized controlled trial.

Objective: Whether employees' health status is associated with the effectiveness of workplace health promotion programs is unknown. The objective of this study was to determine if the effect of a workplace healthy eating intervention differed by baseline chronic disease status. Methods: This was a secondary analysis of a randomized controlled trial conducted September 2016 to February 2018 among US hospital employees to test the effect of a 12-month behavioral intervention (personalized feedback, peer comparisons, and financial incentives) on diet and weight. Participants were classified as having chronic disease (yes/no) based on self-reported hypertension, hyperlipidemia, heart disease, stroke, pre-diabetes, diabetes, cancer or another serious illness. BMI was measured at study visits and calories purchased were measured from cafeteria sales data over 24 months. Mixed models with random effects assessed heterogeneity of treatment effects by chronic disease. Results: Participants (N = 548) were mostly female (79.7 %) and white (81.2 %); 224 (40.9 %) had chronic disease. Among those with chronic disease, intervention participants reduced caloric intake by 74.4 [22.3] kcal more than control, with a smaller difference between intervention and control (-1.9 [18.7] kcal) (three-way p-interaction = 0.02). The effect on BMI for those with chronic disease (0.47 [0.21] kg/m2) indicated weight stability among intervention participants and weight gain among controls while the effect (-0.56 [0.18] kg/m2) for those without chronic disease was the opposite (three-way p-interaction < 0.01). Conclusions: Those with chronic diseases had greater reductions in calories purchased and gained less weight. Employers with limited resources for health promotion might consider tailoring programs to employees at highest risk.

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Is the threatened land crab Cardisoma guanhumi conquering human-dominated systems?

Land use changes are heralded as a major driver of biodiversity loss. However, recent findings show that cities, perhaps the most radical habitat transformation, sustain increasing numbers of threatened species. This emerging trend has been mostly chronicled for vertebrates from landlocked cities, although loss of biodiversity and rates or urbanization are higher in coastal marine systems. To advance our understanding on how threatened species may conquer human-dominated systems, we studied the threatened edible crab Cardisoma guanhumi and assessed how it is proliferating in croplands and urban systems at different spatial scales and whether populations show consequences of long-term exploitation. We gathered the data on crab populations covering the whole distribution range, including three countries reporting this as a threatened species. The abundance, distribution, and size structure of crab populations among different land uses at local scales were compared and published data for populations thriving in different habitats throughout their distribution range were compiled. We found that at local scale this species is able to thrive in natural and human-disturbed habitats, where food sources are heavily altered. At larger scales, the species showed no differences in abundance and size structure among natural and anthropogenic habitats. In areas near the southern distribution edge, crab populations were more abundant and composed of larger animals in urban areas and croplands than those in natural habitats, suggesting that human-disturbed systems are stepping stones to extend the geographic range. However, we found a long-term reduction in maximum body size, exacerbated by land use changes, that likely reflects exploitation regimes consistently targeting larger crabs. Despite its status as a threatened species, the long history of human exploitation combined with livestock farming practices may explain the proliferation of this crab in human-dominated systems, which emphasize the need to consider conservation in human-dominated systems.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Position statement of the Latin American Dysphagia Society for the management of oropharyngeal and esophageal dysphagia during the COVID-19 pandemic.

INTRODUCTION: The SARS-CoV-2 virus that causes the COVID-19 disease is transmitted through the inhalation of droplets or aerosols and inoculation via the oronasal or ocular routes, transforming the management of swallowing disorders into a challenge for healthcare teams, given their proximity to the aerodigestive tract and the high probability of aerosol generation during patient evaluation and treatment. AIM: To provide essential guidance for Latin American multidisciplinary teams, regarding the evaluation and treatment of oropharyngeal and esophageal dysphagia, at the different levels of healthcare. The position statement was formulated for the purpose of maintaining medical service continuity, in the context of a pandemic, and minimizing the propagation and infection risks of the virus. METHODS: Thirteen experts in swallowing disorders were summoned by the Latin American Dysphagia Society to formulate a series of clinical suggestions, based on available evidence and clinical experience, for the management of dysphagia, taking the characteristics of Latin American healthcare systems into account. RESULTS: The position statement of the Latin American Dysphagia Society provides a series of clinical suggestions directed at the multidisciplinary teams that manage patients with oropharyngeal and esophageal dysphagia. It presents guidelines for evaluation and treatment in different contexts, from hospitalization to home care. CONCLUSIONS: The present statement should be analyzed by each team or healthcare professional, to reduce the risk for COVID-19 infection and achieve the best therapeutic results, while at the same time, being mindful of the reality of each Latin American country.

[Position statement of the Latin American Dysphagia Society for the management of oropharyngeal and esophageal dysphagia during the COVID-19 pandemic]. / Posicionamiento de la Sociedad Latinoamericana de Disfagia para el manejo de la disfagia orofaríngea y esofágica durante la pandemia COVID-19.

INTRODUCTION: The SARS-CoV-2 virus that causes the COVID-19 disease is transmitted through the inhalation of droplets or aerosols and inoculation via the oronasal or ocular routes, transforming the management of swallowing disorders into a challenge for healthcare teams, given their proximity to the aerodigestive tract and the high probability of aerosol generation during patient evaluation and treatment. AIM: To provide essential guidance for Latin American multidisciplinary teams, regarding the evaluation and treatment of oropharyngeal and esophageal dysphagia, at the different levels of healthcare. The position statement was formulated for the purpose of maintaining medical service continuity, in the context of a pandemic, and minimizing the propagation and infection risks of the virus. METHODS: Thirteen experts in swallowing disorders were summoned by the Latin American Dysphagia Society to formulate a series of clinical suggestions, based on available evidence and clinical experience, for the management of dysphagia, taking the characteristics of Latin American healthcare systems into account. RESULTS: The position statement of the Latin American Dysphagia Society provides a series of clinical suggestions directed at the multidisciplinary teams that manage patients with oropharyngeal and esophageal dysphagia. It presents guidelines for evaluation and treatment in different contexts, from hospitalization to home care. CONCLUSIONS: The present statement should be analyzed by each team or healthcare professional, to reduce the risk for COVID-19 infection and achieve the best therapeutic results, while at the same time, being mindful of the reality of each Latin American country.

A user-centered approach to developing a new tool measuring the behavioural and social drivers of vaccination.

BACKGROUND: Children around the world remain under-vaccinated for many reasons. To develop effective vaccine delivery programmes and monitor intervention impact, vaccine programme implementers need to understand reasons for under-vaccination within their local context. The World Health Organization (WHO) Working Group on the Behavioural and Social Drivers of Vaccination (BeSD) is developing standardised tools for assessing childhood vaccine acceptance and uptake that can be used across regions and countries. The tools will include: (1) a validated survey; (2) qualitative interview guides; and (3) corresponding user guidance. We report a user-centred needs assessment of key end-users of the BeSD tools. METHODS: Twenty qualitative interviews (Apr-Aug 2019) with purposively sampled vaccine programme managers, partners and stakeholders from UNICEF and WHO country and regional offices. The interviews assessed current systems, practices and challenges in data utilisation and reflections on how the BeSD tools might be optimised. Framework analysis was used to code the interviews. RESULTS: Regarding current practices, participants described a variety of settings, data systems, and frequencies of vaccination attitude measurement. They reported that the majority of data used is quantitative, and there is appetite for increased use of qualitative data. Capacity for conducting studies on social/behavioural drivers of vaccination was high in some jurisdictions and needed in others. Issues include barriers to collecting such data and variability in sources. Reflecting on the tools, participants described the need to explore the attitudes and practices of healthcare workers in addition to parents and caregivers. Participants were supportive of the proposed mixed-methods structure of the tools and training in their usage, and highlighted the need for balance between tool standardisation and flexibility to adapt locally. CONCLUSIONS: A user-centred approach in developing the BeSD tools has given valuable direction to their design, bringing the use of behavioural and social data to the heart of programme planning.

Depression in Ménière's disease: a systematic review and meta-analysis.

BACKGROUND: Ménière's disease is a debilitating chronic peripheral vestibular disorder associated with psychiatric co-morbidities, notably depression. METHODS: Database searches were performed to identify studies that assessed depression in Ménière's disease. Metrics used to diagnose depression were extracted, along with the prevalence of depression in each study. RESULTS: Fifteen studies from 8 different countries reported on 6587 patients. The weighted average age was 55.3 years (range, 21-88 years). Depression was measured by eight different scales, with Zung's Self-Rating Depression Scale used most often. A weighted proportion of 45.9 per cent of patients (confidence interval = 28.9-63.3) were depressed. Weighted averages (± standard deviations) of Beck's Depression Inventory and the Illness Behavior Questionnaire - Dysphoria were 8.5 ± 7.9 and 2.4 ± 1.7, respectively. CONCLUSION: The prevalence of depression in patients with Ménière's disease is nearly 50 per cent. Treating otolaryngologists should have a low threshold to screen and refer appropriately. Identifying and treating depression should allow for improvement of overall quality of life in patients with Ménière's disease.

Elevated serum complement levels and higher gene copy number of complement C4B are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE).

OBJECTIVE: Systemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between complement and CVD in cSLE. METHODS: Gene copy numbers (GCNs) for total C4, C4A and C4B were measured by TaqMan-based real-time PCR and Southern blotting, and analysed with laboratory and clinical parameters through Student's t-test and χ2 analyses. Effects of total C4, C4A and C4B GCNs on the response to placebo or atorvastatin treatment and progression of CIMT were examined by regression analyses. RESULTS: At baseline, C4 protein levels strongly correlated with GCNs of total C4 (p=1.8×10-6). Each copy of C4 gene increased mean serum C4 by 3.28 mg/dL. Compared with those without hypertension (N=142), individuals with hypertension demonstrated significantly elevated serum levels for C4 and C3 at baseline and serially (C4: P=5.0×10-25; C3: P=5.84×10-20). Individuals with ≥2 C4B genes had 2.5 times the odds of having hypertension (p=0.016) and higher diastolic blood pressure (p=0.015) compared with those with C4B deficiency. At the study end, subjects with ≥2 C4B and atorvastatin treatment had significantly slower increase in CIMT compared with those treated with placebo (p=0.018). CONCLUSIONS: cSLE with hypertension had elevated serum levels of C4 and C3 and higher GCN of C4B; cSLE with ≥2 C4B genes would benefit from statins therapy to prevent atherosclerosis.

Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein.

Radiotherapy is a cornerstone of cancer management. The improvement of spatial dose distribution in the tumor volume by minimizing the dose deposited in the healthy tissues have been a major concern during the last decades. Temporal aspects of dose deposition are yet to be investigated. Laser-plasma-based particle accelerators are able to emit pulsed-proton beams at extremely high peak dose rates (~109 Gy/s) during several nanoseconds. The impact of such dose rates on resistant glioblastoma cell lines, SF763 and U87-MG, was compared to conventionally accelerated protons and X-rays. No difference was observed in DNA double-strand breaks generation and cells killing. The variation of the repetition rate of the proton bunches produced an oscillation of the radio-induced cell susceptibility in human colon carcinoma HCT116 cells, which appeared to be related to the presence of the PARP1 protein and an efficient parylation process. Interestingly, when laser-driven proton bunches were applied at 0.5 Hz, survival of the radioresistant HCT116 p53-/- cells equaled that of its radiosensitive counterpart, HCT116 WT, which was also similar to cells treated with the PARP1 inhibitor Olaparib. Altogether, these results suggest that the application modality of ultrashort bunches of particles could provide a great therapeutic potential in radiotherapy.

Functional disconnection between the visual cortex and right fusiform face area in schizophrenia.

Patients with schizophrenia show impairment in processing faces, including facial affect and face detection, but the underlying mechanisms are unknown. We used functional magnetic resonance imaging (fMRI) to characterize resting state functional connectivity between an independent component analysis (ICA)-defined early visual cortical network (corresponding to regions in V1, V2, V3) and a priori defined face-processing regions (fusiform face area [FFA], occipital face area [OFA], superior temporal sulcus [STS] and amygdala) using dual regression in 20 schizophrenia patients and 26 healthy controls. We also investigated the association between resting functional connectivity and neural responses (fMRI) elicited by a face detection paradigm in a partially overlapping sample (Maher et al., 2016) that used stimuli equated for lower-level perceptual abilities. Group differences in functional connectivity were found in right FFA only; controls showed significantly stronger functional connectivity to an early visual cortical network. Functional connectivity in right FFA was associated with (a) neural responses during face detection in controls only, and (b) perceptual detection thresholds for faces in patients only. The finding of impaired functional connectivity for right FFA (but not other queried domain-specific regions) converges with findings investigating face detection in an overlapping sample in which dysfunction was found exclusively for right FFA in schizophrenia during face detection.

Modeling the chemotherapy-induced selection of drug-resistant traits during tumor growth.

The emergence of drug-resistance is a major challenge in chemotherapy. In this paper we develop a mathematical model to study the dynamics of drug-resistance in solid tumors. Our model follows the dynamics of the tumor, assuming that the cancer cell population depends on a phenotype variable that corresponds to the resistance level to a cytotoxic drug. The equation for the tumor density is written as a reaction-diffusion equation with a pressure term that depends on the local cell density. The model incorporates the dynamics of nutrients and two different types of drugs: a cytotoxic drug, which directly impacts the death rate of the cancer cells, and a cytostatic drug that reduces the proliferation rate. This model successfully integrates the phenotype structured drug-resistance approach with an asymmetric tumor growth model in space. Through analysis and simulations we study the impact of spatial and phenotypic heterogeneity on the tumor growth under chemotherapy. We demonstrate that heterogeneous cancer cells may emerge due to the selection dynamics of the environment. Our model predicts that under certain conditions, multiple resistant traits emerge at different locations within the tumor. We show that a higher dosage of the cytotoxic drug may delay a relapse, yet, when this happens, a more resistant trait emerges. Moreover, we estimate the expansion rate of the tumor boundary as well as the time of relapse, in terms of the resistance trait, the level of the nutrient, and the drug concentration. Finally, we propose an efficient drug schedule aiming at minimizing the growth rate of the most resistant trait. By combining the cytotoxic and cytostatic drugs, we demonstrate that the resistant cells can be eliminated.

Presence of t(14;18) translocation in healthy individuals varies according to ethnic background in the Brazilian population.

Several groups have demonstrated that healthy individuals can present the t(14;18) translocation. In this report, the presence of the translocation was examined in healthy blood donors in Brazil, a country considered an ethnic melting pot. The translocation was detected by nested PCR in 227 peripheral blood samples from individuals with different ethnic backgrounds. The t(14;18) translocation was found in 45 of 85 White individuals (52.94%); in 57 of 72 Black individuals (79.17%); and in 68 of 70 individuals (97.14%) of Japanese-descent. In conclusion, the frequency of the t(14;18) translocation in the Brazilian population varies according to the ethnic background.

CircosVCF: circos visualization of whole-genome sequence variations stored in VCF files.

Summary: Visualization of whole-genomic variations in a meaningful manner assists researchers in gaining new insights into the underlying data, especially when it comes in the context of whole genome comparisons. CircosVCF is a web based visualization tool for genome-wide variant data described in VCF files, using circos plots. The user friendly interface of CircosVCF supports an interactive design of the circles in the plot, and the integration of additional information such as experimental data or annotations. The provided visualization capabilities give a broad overview of the genomic relationships between genomes, and allow identification of specific meaningful SNPs regions. Availability and Implementation: CircosVCF was implemented in JavaScript and is available at http://www.ariel.ac.il/research/fbl/software. Contact: malisa@ariel.ac.il. Supplementary information: Supplementary data are available at Bioinformatics online.

Cell-free reconstitution reveals centriole cartwheel assembly mechanisms.

How cellular organelles assemble is a fundamental question in biology. The centriole organelle organizes around a nine-fold symmetrical cartwheel structure typically ∼100 nm high comprising a stack of rings that each accommodates nine homodimers of SAS-6 proteins. Whether nine-fold symmetrical ring-like assemblies of SAS-6 proteins harbour more peripheral cartwheel elements is unclear. Furthermore, the mechanisms governing ring stacking are not known. Here we develop a cell-free reconstitution system for core cartwheel assembly. Using cryo-electron tomography, we uncover that the Chlamydomonas reinhardtii proteins CrSAS-6 and Bld10p together drive assembly of the core cartwheel. Moreover, we discover that CrSAS-6 possesses autonomous properties that ensure self-organized ring stacking. Mathematical fitting of reconstituted cartwheel height distribution suggests a mechanism whereby preferential addition of pairs of SAS-6 rings governs cartwheel growth. In conclusion, we have developed a cell-free reconstitution system that reveals fundamental assembly principles at the root of centriole biogenesis.

Potential immunological markers for diagnosis of human strongyloidiasis using heterologous antigens.

Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently used to obtain heterologous antigens for immunological diagnosis of human strongyloidiasis. The aim of this study was to identify antigens from filariform larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from filariform larvae of S. venezuelensis were obtained in phosphate saline (SS and SM) and in Tris-HCl buffer (TS and TM), and were analysed by Western blotting. Different antigenic components were recognized by IgG antibodies from the sera of strongyloidiasis patients. Highest recognition was observed for a 30-40 kDa mass range present in all antigenic fractions. The band encompassing this mass range was then excised and subjected to mass spectrometry for protein identification. Immunoreactive proteins identified in the soluble fractions corresponded to metabolic enzymes, whereas cytoskeletal proteins and galectins were more abundant in the membrane fractions. These results represent the first approach towards identification of S. venezuelensis antigens for use in immunodiagnostic assays for human strongyloidiasis.

Presence of t(14; 18) translocation in healthy individuals varies according to ethnic background in the Brazilian population

Several groups have demonstrated that healthy individuals can present the t(14;18) translocation. In this report, the presence of the translocation was examined in healthy blood donors in Brazil, a country considered an ethnic melting pot. The translocation was detected by nested PCR in 227 peripheral blood samples from individuals with different ethnic backgrounds. The t(14;18) translocation was found in 45 of 85 White individuals (52.94%); in 57 of 72 Black individuals (79.17%); and in 68 of 70 individuals (97.14%) of Japanese-descent. In conclusion, the frequency of the t(14;18) translocation in the Brazilian population varies according to the ethnic background.