The use of equine chondrogenic‐induced mesenchymal stem cells as a treatment for osteoarthritis : a randomised, double‐blinded, placebo‐controlled proof‐of‐concept study

Background: There is a need to improve therapies for osteoarthritis in horses. Objectives To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses. Study design: Randomised, double-blinded, placebo-controlled experiment. Methods: In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically. Results: No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group. Main limitations: This study assessed the short-term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error. Conclusions: Equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses

Dark Matter from Minimal Flavor Violation

We consider theories of flavored dark matter, in which the dark matter particle is part of a multiplet transforming nontrivially under the flavor group of the Standard Model in a manner consistent with the principle of Minimal Flavor Violation (MFV). MFV automatically leads to the stability of the lightest state for a large number of flavor multiplets. If neutral, this particle is an excellent dark matter candidate. Furthermore, MFV implies specific patterns of mass splittings among the flavors of dark matter and governs the structure of the couplings between dark matter and ordinary particles, leading to a rich and predictive cosmology and phenomenology. We present an illustrative phenomenological study of an effective theory of a flavor SU(3)_Q triplet, gauge singlet scalar.Comment: 10 pages, 2 figures; v2: references added, minor changes to collider analysis, conclusions unchange

Evaluation of LHP® (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized, blinded control study

<p>Abstract</p> <p>Background</p> <p>Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine.</p> <p>Methods</p> <p>Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP^®or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16.</p> <p>Results</p> <p>Mean time to complete healing for LHP^®treated wounds was 32 days (95%CI = 26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI = 36.2-47.0) and 44.0 days (95%CI = 38.6-49.4) respectively. Wound healing occurred significantly faster in LHP^®wounds compared to both petrolatum (p = 0.0004) and untreated controls (p < 0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p < 0.0001) lower for LHP^®treated wounds compared to petrolatum from day 16 and onwards. <it>Staphylococcus aureus </it>and <it>Streptococcus zooepidemicus </it>were only found in cultures from petrolatum treated wounds and untreated controls.</p> <p>Conclusions</p> <p>Treatment with LHP^®reduced bacterial colonization and was associated with earlier complete wound healing. LHP^®cream appears to be safe and effective for topical wound treatment or wound protection.</p

Allele-Specific Gene Expression Is Widespread Across the Genome and Biological Processes

Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in- segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected

Vitamin D Status of Clinical Practice Populations at Higher Latitudes: Analysis and Applications

Background: Inadequate levels of vitamin D (VTD) throughout the life cycle from the fetal stage to adulthood have been correlated with elevated risk for assorted health afflictions. The purpose of this study was to ascertain VTD status and associated determinants in three clinical practice populationsliving in Edmonton, Alberta, Canada -a locale with latitude of 53°30\u27N, wheresun exposure from October through March is often inadequate to generate sufficient vitamin D. Methods: To determine VTD status, 1,433 patients from three independent medical offices in Edmonton had levels drawn for 25(OH)D as part of their medical assessment between Jun 2001 and Mar 2007. The relationship between demographic data and lifestyle parameters with VTD status was explored. 25(OH)D levels were categorized as follows: (1) Deficient

Vitamin D exposure and Risk of Breast Cancer: a meta-analysis

The relationship between vitamin D and breast cancer is still controversial. The present meta-analysis examines the effects of the 25(OH)D, 1,25(OH)2D and vitamin D intake on breast cancer risk. For this purpose, a PubMed, Scopus and Web of Science-databases search was conducted including all papers published with the keywords "breast cancer" and "vitamin D" with at least one reported relative risk (RR) or odds ratio (OR). In total sixty eight studies published between 1998 and 2018 were analyzed. Information about type of study, hormonal receptors and menopausal status was retrieved. Pooled OR or RR were estimated by weighting individual OR/RR by the inverse of their variance Our study showed a protective effect between 25 (OH) D and breast cancer in both cohort studies (RR?=?0.85, 95%CI:0.74-0.98) and case-control studies (OR?=?0.65, 95%CI: 0.56-0.76). However, analyzing by menopausal status, the protective vitamin D - breast cancer association persisted only in the premenopausal group (OR?=?0.67, 95%CI: 0.49-0.92) when restricting the analysis to nested case-control studies. No significant association was found for vitamin D intake or 1,25(OH)2D. CONCLUSION: This systematic review suggests a protective relationship between circulating vitamin D (measured as 25(OH) D) and breast cancer development in premenopausal women

Intron retention in the Drosophila melanogaster Rieske iron sulphur protein gene generated a new protein

Genomes can encode a variety of proteins with unrelated architectures and activities. It is known that protein-coding genes of de novo origin have significantly contributed to this diversity. However, the molecular mechanisms and evolutionary processes behind these originations are still poorly understood. Here we show that the last 102 codons of a novel gene, Noble, assembled directly from non-coding DNA following an intronic deletion that induced alternative intron retention at the Drosophila melanogaster Rieske Iron Sulphur Protein (RFeSP) locus. A systematic analysis of the evolutionary processes behind the origin of Noble showed that its emergence was strongly biased by natural selection on and around the RFeSP locus. Noble mRNA is shown to encode a bona fide protein that lacks an iron sulphur domain and localizes to mitochondria. Together, these results demonstrate the generation of a novel protein at a naturally selected site

Dark Matter Sees The Light

We construct a Dark Matter (DM) annihilation module that can encompass the predictions from a wide array of models built to explain the recently reported PAMELA and ATIC/PPB-BETS excesses. We present a detailed analysis of the injection spectrums for DM annihilation and quantitatively demonstrate effects that have previously not been included from the particle physics perspective. With this module we demonstrate the parameter space that can account for the aforementioned excesses and be compatible with existing high energy gamma ray and neutrino experiments. However, we find that it is relatively generic to have some tension between the results of the HESS experiment and the ATIC/PPB-BETS experiments within the context of annihilating DM. We discuss ways to alleviate this tension and how upcoming experiments will be able to differentiate amongst the various possible explanations of the purported excesses.Comment: 47 pages, 17 figure

Interventions for improving oral health in people after stroke

BACKGROUND: For people with physical, sensory and cognitive limitations due to stroke, the routine practice of oral health care (OHC) may become a challenge. Evidence‐based supported oral care intervention is essential for this patient group. OBJECTIVES: To compare the effectiveness of OHC interventions with usual care or other treatment options for ensuring oral health in people after a stroke. SEARCH METHODS: We searched the Cochrane Stroke Group and Cochrane Oral Health Group trials registers, CENTRAL, MEDLINE, Embase, and six other databases in February 2019. We scanned reference lists from relevant papers and contacted authors and researchers in the field. We handsearched the reference lists of relevant articles and contacted other researchers. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated one or more interventions designed to improve the cleanliness and health of the mouth, tongue and teeth in people with a stroke who received assisted OHC led by healthcare staff. We included trials with a mixed population provided we could extract the stroke‐specific data. The primary outcomes were dental plaque or denture plaque. Secondary outcomes included presence of oral disease, presence of related infection and oral opportunistic pathogens related to OHC and pneumonia, stroke survivor and providers' knowledge and attitudes to OHC, and patient satisfaction and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full‐text articles according to prespecified selection criteria, extracted data and assessed the methodological quality using the Cochrane 'Risk of bias' tool. We sought clarification from investigators when required. Where suitable statistical data were available, we combined the selected outcome data in pooled meta‐analyses. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: Fifteen RCTs (22 randomised comparisons) involving 3631 participants with data for 1546 people with stroke met the selection criteria. OHC interventions compared with usual care Seven trials (2865 participants, with data for 903 participants with stroke, 1028 healthcare providers, 94 informal carers) investigated OHC interventions compared with usual care. Multi‐component OHC interventions showed no evidence of a difference in the mean score (DMS) of dental plaque one month after the intervention was delivered (DMS –0.66, 95% CI –1.40 to 0.09; 2 trials, 83 participants; I(2) = 83%; P = 0.08; very low‐quality evidence). Stroke survivors had less plaque on their dentures when staff had access to the multi‐component OHC intervention (DMS –1.31, 95% CI –1.96 to –0.66; 1 trial, 38 participants; P < 0.0001; low‐quality evidence). There was no evidence of a difference in gingivitis (DMS –0.60, 95% CI –1.66 to 0.45; 2 trials, 83 participants; I(2) = 93%; P = 0.26: very low‐quality evidence) or denture‐induced stomatitis (DMS –0.33, 95% CI –0.92 to 0.26; 1 trial, 38 participants; P = 0.69; low‐quality evidence) among participants receiving the multi‐component OHC protocol compared with usual care one month after the intervention. There was no difference in the incidence of pneumonia in participants receiving a multi‐component OHC intervention (99 participants; 5 incidents of pneumonia) compared with those receiving usual care (105 participants; 1 incident of pneumonia) (OR 4.17, CI 95% 0.82 to 21.11; 1 trial, 204 participants; P = 0.08; low‐quality evidence). OHC training for stroke survivors and healthcare providers significantly improved their OHC knowledge at one month after training (SMD 0.70, 95% CI 0.06 to 1.35; 3 trials, 728 participants; I(2) = 94%; P = 0.03; very low‐quality evidence). Pooled data one month after training also showed evidence of a difference between stroke survivor and providers' oral health attitudes (SMD 0.28, 95% CI 0.01 to 0.54; 3 trials, 728 participants; I(2) = 65%; P = 0.06; very low‐quality evidence). OHC interventions compared with placebo Three trials (394 participants, with data for 271 participants with stroke) compared an OHC intervention with placebo. There were no data for primary outcomes. There was no evidence of a difference in the incidence of pneumonia in participants receiving an OHC intervention compared with placebo (OR 0.39, CI 95% 0.14 to 1.09; 2 trials, 242 participants; I(2) = 42%; P = 0.07; low‐quality evidence). However, decontamination gel reduced the incidence of pneumonia among the intervention group compared with placebo gel group (OR 0.20, 95% CI 0.05 to 0.84; 1 trial, 203 participants; P = 0.028). There was no difference in the incidence of pneumonia in participants treated with povidone‐iodine compared with a placebo (OR 0.81, 95% CI 0.18 to 3.51; 1 trial, 39 participants; P = 0.77). One OHC intervention compared with another OHC intervention Twelve trials (372 participants with stroke) compared one OHC intervention with another OHC intervention. There was no difference in dental plaque scores between those participants that received an enhanced multi‐component OHC intervention compared with conventional OHC interventions at three months (MD –0.04, 95% CI –0.33 to 0.25; 1 trial, 61 participants; P = 0.78; low‐quality evidence). There were no data for denture plaque. AUTHORS' CONCLUSIONS: We found low‐ to very low‐quality evidence suggesting that OHC interventions can improve the cleanliness of patient's dentures and stroke survivor and providers' knowledge and attitudes. There is limited low‐quality evidence that selective decontamination gel may be more beneficial than placebo at reducing the incidence of pneumonia. Improvements in the cleanliness of a patient's own teeth was limited. We judged the quality of the evidence included within meta‐analyses to be low or very low quality, and this limits our confidence in the results. We still lack high‐quality evidence of the optimal approach to providing OHC to people after stroke

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E-2, and tumor necrosis factor alpha in the canine osteoarthritic joint

Background: Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E-2 (PGE(2)), and tumor necrosis factor alpha (TNF-alpha) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE(2) between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE(2), osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE(2) concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE(2) concentration was compared between osteoarthritic and control joints. Associations between SP, PGE(2), osteoarthritic pain, and the signalment of dogs were evaluated. Results: There was no significant change from baseline in SP or PGE(2) after IA BoNT A. Synovial fluid PGE(2) was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE(2) correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-alpha remained under the detection limit of the assay in all samples. Conclusions: The results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE(2). Synovial fluid PGE(2,) but not SP, could be a marker for chronic osteoarthritis and pain in dogs.Peer reviewe