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.

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]. / 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.

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.

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.

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.

Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons.

Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20-104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥ 60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength.

Structural analysis and optical properties of the Bi2-x Y x WO6 system.

Photocatalytic conversion of solar energy into chemical energy has attracted considerable interest for several decades. One compound already reported as a visible-light-active photocatalyst for water splitting is BiYWO6, a member of the Bi2-x Y x WO6 family of compounds. The structural and optical properties of other members of this family have not been reported to date. In this work, we synthesized various compositions of Bi2-x Y x WO6, studied their optical properties, and report their structural parameters obtained by utilizing powder diffraction coupled with Rietveld refinement.

A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.

STUDY QUESTION: Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day? SUMMARY ANSWER: In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG. WHAT IS KNOWN ALREADY: UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA. STUDY DESIGN, SIZE, DURATION: A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU). PARTICIPANTS/MATERIAL, SETTING, METHODS: A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL). MAIN RESULTS AND THE ROLE OF CHANCE: Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles. LIMITATIONS, REASONS FOR CAUTION: This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images. WIDER IMPLICATIONS OF THE FINDINGS: Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.

Rituximab therapy has a rapid and durable response for refractory cytopenia in childhood-onset systemic lupus erythematosus.

OBJECTIVES: Autoimmune thrombocytopenia (AITP) and hemolytic anemia (AIHA) are common in childhood-onset systemic lupus erythematosus (cSLE) and may be refractory to conventional therapies. Our objectives were to: (a) examine our experience; (b) determine the rate and durability of response to rituximab; and (c) evaluate its safety in our cSLE population with refractory cytopenias. METHODS: We performed a single-center retrospective cohort study of cSLE patients with refractory AITP or AIHA treated with rituximab between 2003 and 2012. Outcomes included the time to complete clinical response, time to B-cell depletion, duration of response and time to flare. Adverse events were also analyzed. RESULTS: Twenty-four (6%) of 394 cSLE patients received rituximab for refractory cytopenia. The indication was AITP in 16 (67%), AIHA in five (21%) and both in three (13%) patients. The median (interquartile range (IQR)) time from cytopenia onset to rituximab therapy was 16 (7-27) months for AITP and 10 (2-29) months for AIHA. Complete response following the first course of rituximab occurred at a median (IQR) of 48 (14-103) days, only one patient failed to respond. Five (21%) patients had one or more flare episodes at 22 (15-27) months. Infusion reactions were rare and one infection with herpes zoster required hospitalization in the first 12 months. Three of four patients with low IgG levels prior to the first rituximab course developed persistent hypogammaglobulinemia, and three patients have required intravenous immunoglobulin replacement. CONCLUSION: Rituximab appears to be a well-tolerated, safe and long-lasting therapy for cSLE patients with refractory AITP and/or AIHA. Caution should be exercised when considering rituximab for patients with preexisting hypogammaglobulinemia.

Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and clinical manifestations.

UNLABELLED: Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. OBJECTIVES: Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. METHODS: A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. RESULTS: CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. CONCLUSIONS: There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE.

Effects of obesity on health-related quality of life in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE). METHODS: Obesity was defined as a body mass index (BMI) ≥ 95 th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures. RESULTS: Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains. CONCLUSION: Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE.

Seasonal variability in environmental tobacco smoke exposure in public housing developments.

The risk of tobacco smoking and second-hand smoke (SHS) exposure combined are the leading contributors to disease burden in high-income countries. Recent studies and policies are focusing on reducing exposure to SHS in multiunit housing (MUH), especially public housing. We examined seasonal patterns of SHS levels within indoor common areas located on Boston Housing Authority (BHA) properties. We measured weekly integrated and continuous fine particulate matter (PM2.5) and passive airborne nicotine in six buildings of varying building and occupant characteristics in summer 2012 and winter 2013. The average weekly indoor PM2.5 concentration across all six developments was 9.2 µg/m3, higher during winter monitoring period (10.3 µg/m3) compared with summer (8.0 µg/m3). Airborne nicotine concentrations ranged from no detection to about 5000 ng/m3 (mean 311 ng/m3). Nicotine levels were significantly higher in the winter compared with summer (620 vs. 85 ng/m3; 95% CI: 72-998). Smoking-related exposures within Boston public housing vary by season, building types, and resident smoking policy. Our results represent exposure disparities that may contribute to health disparities in low-income communities and highlight the potential importance of efforts to mitigate SHS exposures during winter when outdoor-indoor exchange rates are low and smokers may tend to stay indoors. Our findings support the use of smoke-free policy as an effective tool to eliminate SHS exposure and protect non-smokers, especially residents of MUH.

Left ventricular assist device exchange for persistent infection: a case series and review of the literature.

Left ventricular assist device (LVAD) exchange for control of infection may be an option for the treatment of persistent and severe infections of the LVAD. Data are limited regarding the indications for device exchange, methods for exchanging infected devices, post-exchange antimicrobial management, and outcomes of such patients. We report a series of cases in which an exchange was performed for persistent LVAD infection, review the literature on LVAD exchange and surgical techniques for these infectious complications, and suggest management strategies from a multidisciplinary perspective.

First Report of Recombinant Potato virus Y Strains Infecting Potato in Jordan.

Potato (Solanum tuberosum L.) is an important vegetable crop in Jordan, occupying second position after olives. In 2012, potatoes were planted on about 6,000 ha with a production of about 141,000 t (2). Potato virus Y (PVY) is a serious problem for potato production worldwide. Recombinant strains of the virus were reported to cause tuber necrotic ringspot disease (PTNRD) in many potato-growing regions of the world. In the last few years, a new recombinant PVYNTN-NW that belongs to PVYZ (3) has been reported in the neighboring Syria. It included three recombination patterns, SYR-I, SYR-II, and SYR-III, and caused severe PTNRD (1). Since PVY is easily transmitted from one region to another by aphid vectors and infected potato seeds, this study was initiated to investigate the possible occurrence of PVY strains in Jordan. In October 2013, 33 leaf samples were collected from symptomatic potato plants cv. Spunta from Wadi Rum, Jordan (GPS coordinates 29°31'37.76″ N, 35°42'48.75″ E), the largest potato-producing area in Jordan. Sampled plants displayed leaf mottling and yellowing, symptoms similar to those caused by PVY. All samples were tested for PVY by DAS-ELISA using the ELISA kit (monoclonal cocktail) developed by BIOREBA (Reinach, Switzerland) to detect all PVY isolates. Twenty-nine samples were found positive for PVY by ELISA. To confirm virus infection, total RNA was extracted from all ELISA-positive samples and used as template in uniplex RT-PCR using strain-specific primers (1). The band pattern of PCR amplicons showed that 12 samples were infected with PVYNTN-NW genotype SYR-III and produced bands of 1,085, 441, and 278 bp. One sample was infected with PVYNTN (A) and produced bands of 1,307, 633, and 441 bp, and one other sample was infected with PVYNTN-NW genotype SYR-II and produced bands of 1,085 and 441 bp. Mixed infection with PVYNTN-NW genotype SYR-III and PVYNTN (B) was also detected in one sample producing bands of 278, 441, 1,085, and 1,307 bp. To confirm infection with the recombinant strains, PCR fragments of 278 bp amplified from three samples and 1,085 bp obtained from another three samples were directly sequenced and sequences were deposited in GenBank under accession numbers KJ159968, KJ159969, and KJ159970 for the 278-bp fragment and KJ159974, KJ159975, and KJ159976 for the 1,085-bp fragment. Sequence comparison with other PVY strains available in the NCBI database showed that the 278-bp fragment had the highest nucleotide sequence identity (100%) with PVY isolates SYR-III-A26 (AB461467) and SYR-III-2-4 (AB461457) from Syria. BLAST searches also showed that the 1,085-bp fragment shared 99% nucleotide identities with PVY isolates SYR-II-L3 (AB461482) and SYR-II-Be4 (AB461474) from Aleppo, Syria. To our knowledge, this is the first report of PVY recombinants in Jordan, and the first report of PVYNTN-NW recombinants infecting potato crop outside Syria. Since Europe is the main supplier of potato seeds for farmers in Jordan and Syria, the introduction of PVYNTN-NW to the region could have happened through infected potato seeds. Results of this study create new challenges for potato growers in Jordan as well as other countries in the region. References: (1) M. Chikh Ali et al. J. Virol. Methods 165:15, 2010. (2) FAO. http://faostat.fao.org/ (3) A. V. Karasev and S. M. Gray. Ann. Rev. Phytopathol. 51:571, 2013.

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.

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.

Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices.

BACKGROUND: Because follicular lymphoma (FL) patients have heterogeneous outcomes, the FL international prognostic index (FLIPI) was developed to risk-stratify patients and to predict survival. However, limited data exist regarding the role of FLIPI in the era of routine first-line rituximab (R) and R-chemotherapy regimens and in the setting of community oncology practices. PATIENTS AND METHODS: We evaluated the outcome data from the National LymphoCare Study (NLCS), a prospective, observational cohort study, which collects data on patients with FL in the United States (US) community practices. RESULTS: Among 1068 male and 1124 female patients with FLIPI data, most were treated in US community practices (79%); 35% were FLIPI good risk, 30% intermediate risk, and 35% poor risk. FLIPI risk groups were significant predictors of overall survival (OS) and progression-free survival (PFS) for patients who undergo watchful waiting (WW), and those who receive non-R-containing regimens, R-alone, and R-chemotherapy combinations. CONCLUSIONS: In the setting of contemporary practice with routine R use, stratifying patients into good, intermediate, and poor FLIPI risk groups predicts distinct outcomes in terms of OS and PFS. FLIPI remains an important prognostic index in the R era and should be used in clinical practices to support discussions about prognosis.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

Depressive symptoms are prevalent in childhood-onset systemic lupus erythematosus (cSLE).

BACKGROUND: Depressive symptoms are common in adolescence and young adulthood; however, their prevalence in childhood-onset systemic lupus erythematosus (cSLE) is unknown. OBJECTIVE: The objective of this study was to examine the prevalence of depressive symptoms and their association with disease characteristics in children, adolescents, and young adults with cSLE. METHODS: A cross-sectional sample of patients with cSLE between 10 to 24 years old completed standardized depression inventories. Demographics and disease characteristics were collected. RESULTS: Total depression inventory scores reported were below standard cut-off values for depression. However, 26% (10/38) of children and adolescents, and 44% (seven of 16) of young adults had scores at or above established cut-offs for elevated depression symptoms. Physical symptoms of depression were endorsed most frequently. There were no differences in depressive symptoms by disease characteristics including disease duration, health-related quality of life inventory scores, antiphospholipid antibody status, and a history of renal involvement or neuropsychiatric SLE (NPSLE). However, two patients had a history of depression as an NPSLE manifestation of their SLE. In the children and adolescents, prednisone dose was associated with negative self-esteem (r = 0.37, p = 0.04) and somatic depressive symptoms (r = 0.39, p = 0.02), but we did not observe a significant association in the young adults. CONCLUSION: Depressive symptoms in cSLE are frequent, although similar to the high prevalence rates in the general population. Physical symptoms are most frequently endorsed. Further study will determine if serial evaluations are recommended for early detection in this at-risk population.