Assessment of the Composition and Biologic Activity of Platelet Rich Plasma and its Relationship to Clinical Outcomes in Patients with Knee Osteoarthritis

Recent studies suggest positive clinical outcomes associated with platelet-rich-plasma (PRP) administration to treat knee osteoarthritis (OA). However, the results remain inconclusive in part because of the high variability in PRP preparations and the limited information regarding the relevant biologically active components of PRP. We hypothesize that the variability in clinical response is driven by the heterogeneous composition of PRP. In this study we evaluated the composition and biological activity of PRP and further correlated our findings to clinical outcomes in patients receiving intra-articular injections for knee OA. After IRB approval and patient consent, we enrolled 51 patients (mean age: 57.9 ± 10.1; mean BMI: 26.0 ± 4.1) with mild-moderate knee OA (Kellgren Lawrence grades 1-3), eligible for intra-articular PRP injection. We obtained MRI at baseline and outcome measures (KOOS JR and PNS) at baseline, 6 weeks, 6 months, and 12 months after PRP injection. Patients were categorized as “good” and “poor” responders based on the outcome measures, corrected using published Minimally Clinically Important Difference (MCID) values. Aliquots of PRP and whole blood from the same patients were used to evaluate composition (CBC with differential and multiplex ELISA) and biologic activity, using a co-culture system of macrophages and fibroblast incubated with TNFa with and without PRP (10% v:v) for 24 hours. Total RNA from cells was used for RNAseq, Nanostring, and RTqPCR analysis. On average, we collected 4.07 ± 01.05 mL of PRP, and 3.24 ± 0.85 mL of PRP were injected intra-articularly. PRP preparations yielded mean fold-changes of 1.60 ± 0.37 platelets and 0.19 ± 0.08v leukocytes, relative to whole-blood from the same patients (set as 1). On average, all patients that reached the 6-month time-point (N = 32) reported improved outcomes at 6-weeks and 6-months after PRP administration (KOOS and PNS p\u3c0.05 vs. baseline). After MCID corrections, we identified “good” (N=17, positive response using both measures) and “poor” responders (N=15, poor response in one or both measures). RNAseq analyses showed PRP-dependent changes in the TNFa-induced modulation of a number of genes, including CXCL7 and CCL5. NanoString and RTqPCR analyses confirmed the RNAseq results. Comparisons of PRP from good and poor responders identified changes in the composition and biologic activity between these groups. This pilot study integrated clinical data with genomic approaches to evaluate variability in the composition and activity of PRP, and how this may influence outcomes in patients with knee OA. We uncovered subsets of genes differentially modulated by co-treatment of PRP with TNFa, in agreement with the concept that the reduced knee OA pain in patients treated with PRP is driven by the ability of PRP to modulate inflammation. Furthermore, we identified changes in the composition and biologic activity of PRP between “good” and “poor” responders

RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins

The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning

Opportunities and challenges of Web 2.0 for vaccination decisions.

A growing number of people use the Internet to obtain health information, including information about vaccines. Websites that allow and promote interaction among users are an increasingly popular source of health information. Users of such so-called Web 2.0 applications (e.g. social media), while still in the minority, represent a growing proportion of online communicators, including vocal and active anti-vaccination groups as well as public health communicators. In this paper, the authors: define Web 2.0 and examine how it may influence vaccination decisions; discuss how anti-vaccination movements use Web 2.0 as well as the challenges Web 2.0 holds for public health communicators; describe the types of information used in these different settings; introduce the theoretical background that can be used to design effective vaccination communication in a Web 2.0 environment; make recommendations for practice and pose open questions for future research. The authors conclude that, as a result of the Internet and Web 2.0, private and public concerns surrounding vaccinations have the potential to virally spread across the globe in a quick, efficient and vivid manner. Web 2.0 may influence vaccination decisions by delivering information that alters the perceived personal risk of vaccine-preventable diseases or vaccination side-effects. It appears useful for public health officials to put effort into increasing the effectiveness of existing communication by implementing interactive, customized communication. A key step to providing successful public health communication is to identify those who are particularly vulnerable to finding and using unreliable and misleading information. Thus, it appears worthwhile that public health websites strive to be easy to find, easy to use, attractive in its presentation and readily provide the information, support and advice that the searcher is looking for. This holds especially when less knowledgeable individuals are in need of reliable information about vaccination risks and benefits

Compartmentation of photosynthesis gene expression in C4 maize depends on time of day

Compared with the ancestral C3 state, C4 photosynthesis occurs at higher rates with improved water and nitrogen use efficiencies. In both C3 and C4 plants, rates of photosynthesis increase with light intensity and are maximal around midday. We determined that in the absence of light or temperature fluctuations, photosynthesis in maize (Zea mays) peaks in the middle of the subjective photoperiod. To investigate the molecular processes associated with these temporal changes, we performed RNA sequencing of maize mesophyll and bundle sheath strands over a 24-h time course. Preferential expression of C4 cycle genes in these cell types was strongest between 6 and 10 h after dawn when rates of photosynthesis were highest. For the bundle sheath, DNA motif enrichment and gene coexpression analyses suggested members of the DNA binding with one finger (DOF) and MADS (MINICHROMOSOME MAINTENANCE FACTOR 1/AGAMOUS/DEFICIENS/Serum Response Factor)-domain transcription factor families mediate diurnal fluctuations in C4 gene expression, while trans-activation assays in planta confirmed their ability to activate promoter fragments from bundle sheath expressed genes. The work thus identifies transcriptional regulators and peaks in cell-specific C4 gene expression coincident with maximum rates of photosynthesis in the maize leaf at midday.This work was supported by the European Commission project 3to4 (grant agreement no: 289582), by Fundação para a Ciência e Tecnologia (FCT) through research unit GREEN-it “Bioresources for Sustainability” (UID/Multi/04551/2013, UIDB/04551/2020), by POPH-QREN to A.R.B. (SFRH/BD/105739/2014), A.M.G. (SFRH/BD/89743/2012), and N.J.M.S. (IF/01126/2012), by ERACAPS grant C4BREED and BBSRC grants BB/L014130, BBP0031171, and BB/S006370/1, and by European Research Council Grant Revolution RG80867

Neurocognitive bases of emotion regulation development in adolescence

Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. However, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe