Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers : Two case reports

Digital ulcers (DUs) are a severe and frequent clinical feature of patients with systemic sclerosis (SSc). The presence of DUs may cause severe pain and often lead to impairment of patient\u2019s functional activities and health-related quality of life. Moreover, poor patient cooperation during the wound care procedure due to pain may be associated with a negative outcome of DU healing. Therefore, pain management has a key role in patients with SSc. These two case reports describe the effectiveness and safety of oxycodone/naloxone in patients with SSc complicated by painful chronic DUs. Such a therapy has provided pain relief and consequently an increased compliance during redressing wounds

Root Bacteria Recruited by Phragmites australis in Constructed Wetlands Have the Potential to Enhance Azo-Dye Phytodepuration

The microbiome associated with plants used in phytodepuration systems can boost plant growth and services, especially in ecosystems dealing with recalcitrant compounds, hardly removed via traditional wastewater (WW) treatments, such as azo-dyes used in textile industry. In this context, we aimed to study the cultivable microbiome selected by Phragmites australis plants in a Constructed Wetland (CW) in Morocco, in order to obtain candidate inoculants for the phytodepuration of azo-dye contaminated WW. A collection of 152 rhizospheric and endophytic bacteria was established. The strains were phylogenetically identified and characterized for traits of interest in the phytodepuration context. All strains showed Plant Growth Promotion potential in vitro and 67% of them significantly improved the growth of a model plant in vivo compared to the non bacterized control plants. Moreover, most of the isolates were able to grow in presence of several model micropollutants typically found in WW, indicating their potential use in phytodepuration of a wide spectrum of effluents. The six most promising strains of the collection were tested in CW microcosms alone or as consortium: the consortium and two single inocula demonstrated to significantly increase the removal of the model azo-dye Reactive Black 5 compared to the non bacterized controls

Fatal systemic toxoplasmosis in a 3-month-old young tibetan goat (Capra hircus)

Background: Toxoplasmosis is one of the most common parasitic infections in both humans and animals. It is a frequent cause of abortion and stillbirth in intermediate hosts, especially sheep and goats but rarely causes fatal clinical form in adult animals. Case presentation: In contrast, the study reports an unusual fatal case of toxoplasmosis in a young goat naturally infected with type II strain of Toxoplasma gondii. A three-month-old female goat was presented with dyspnea and died few days later. Grossly, lungs were firm, edematous and mottled with disseminated whitish areas. Generalized lymphadenopathy was found. The histopathological examination showed necrotic interstitial bronchopneumonia and necrotizing lymphadenitis with intralesional free and clustered within macrophages tachyzoites of T. gondii. DNA extracted from lungs and lymph nodes was positive for T. gondii by a fast qPCR. PCR-RFLP analysis and sequencing of GRA6 gene showed that the isolated strains belonged to type II genotype. Conclusions: This is an unusual report of acute systemic toxoplasmosis caused by the type II strain of T. gondii with a fatal outcome in a young goat

SOT-MRAM 300mm integration for low power and ultrafast embedded memories

We demonstrate for the first time full-scale integration of top-pinned perpendicular MTJ on 300 mm wafer using CMOS-compatible processes for spin-orbit torque (SOT)-MRAM architectures. We show that 62 nm devices with a W-based SOT underlayer have very large endurance (> 5x10^10), sub-ns switching time of 210 ps, and operate with power as low as 300 pJ.Comment: presented at VLSI2018 session C8-

The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β(3 )integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties

Correlation between cognitive functions and motor coordination in children with different cognitive levels

Cognitive development is related with central nervous system maturation and plays a crucial role for the definition of executive functions such as movement imagination, movement planning and problem-solving. In particular, executive functions are required during complex interactions between players/environment and are also fundamental for motor skills coordination. Although the complex interaction between cognitive and physical outcomes was recognized by several authors, few studies examined the magnitude of the relation between executive functions and motor development according to dif- ferent stages of cognitive maturation. Thus the aim was the assessment of the relationships between motor skills coordination and executive functions in children with different cognitive level. Ninety healthy male participants were involved in the study where children affected by Down syndrome were, also, recruited. The participants were divided into three groups according to classi- fication of Piaget: concrete, formal operational groups and Down syndrome individuals. Executive functions were assessed using a validated computerized battery tests while motor skills was evaluated using the K\uf6rperkoordinations Test f\ufcr Kinder. Analysis of variance by ranks (Kruskal-Wallis nonparametric test) and Mann-Whitney U pairwise comparisons with Dunn\u2019s correction for multiple contrasts were applied to assess the differences concerning the two kinds of outcome. The Pearson product-moment correlation coefficient was used to calculate the correlation between physical performance and the outcomes of the cognitive tests. A Spearman correlation was used to analyze the data when the assumption of normality was violated. The three groups showed differences in both executive functions and motor coordination outcomes. The highest number of significant correlations was found in the formal operational group (correlation coefficients ranging between 120.999 and 120.520, and between 0.970 and 0.759, all p values < 0.05) while a small number of correlations were found in the concrete operational group (correlation coefficients equal to 120.527, 120.461, 120.436 and 0.468, all p values < 0.05). No correlations between executive function and motor coordination were found in Down syndrome group. High executive function seems to affect the coordination skills

Outcomes, rates, and risk factors of transition of Raynaud&apos;s phenomenon to a connective tissue disease: systematic review and meta-analysis

Background: A number of observational studies were carried out in patients with isolated Raynaud's phenomenon (RP) to investigate the predictors of transition to RP secondary to connective tissue diseases (CTDs). Data from a meta-analysis, including studies until June 1996, highlighted the potential role of nailfold capillaroscopy and/or antinuclear antibodies (ANAs) in predicting such transition [1]. Objectives: To provide an updated comprehensive review and meta-analysis on the rates and the role of predictors of transition to CTDs and systemic sclerosis (SSc) in patients with RP. Methods: A systematic search of observational studies was undertaken using Medline and Embase (07/1996 to 08/2014). From the list of records retrieved, studies were screened by titles/abstracts and the full papers were sought where abstracts were felt to be relevant. Cohort studies reporting incidence and risk factors of transition from primary RP (pRP) or suspected secondary RP (ssRP) to CTDs were selected and data collected in ad hoc forms. pRP was defined according to Leroy and Medsger criteria (no history or physical findings suggestive of a secondary cause, normal capillaroscopy, negative serologic findings); ssRP was defined in presence of positive ANAs and/or abnormal capillaroscopy (even in association with symptoms or physical findings suggestive of a secondary cause without fulfilling criteria for a definite CTD). Relative risk (RR) and 95% confidence interval (CI) were extracted or calculated to present the association between risk factors and transition to CTDs. Random effects model was used to pool the results. Results: From 2.221 articles captured, 36 met the predefined criteria, 29 were excluded on full text, and 7 selected studies provided information on transition from pRP and/or ssRP to secondary RP: 5 prospective and 2 retrospective cohort studies. Six studies included a total of 4051 patients with pRP with a cumulative mean follow-up of 20241 person-years (mean follow-up 4.9\ub12 years); a total of 1220 transitions to overt CTDs were recorded (pooled incidence rate 2.5/100 person-years of observation, range 0\u20137.7); among these, 321 transitions were to SSc (pooled incidence rate 1.58/100 person-years, range 0\u20132.8). Five studies included 657 patients with ssRP with a cumulative mean follow-up of 2377 person-years (mean follow-up 3.6\ub11.1 years); a total of 188 transitions to CTDs were recorded (pooled incidence rate 7.9/100 person-years, range 3.3\u201326) and 135 to SSc (pooled incidence rate 5.7/100 person-years, range 2.1\u201313). With respect to the patients with pRP, having ANA without capillary abnormalities provided a modest risk to develop SSc (pooled RR 2.8, CI 2.1\u20133.8), even weaker resulted the association between capillary abnormalities without ANA and the risk of SSc transition (RR 1.3, CI 0.7\u20132.4). On the other hand, the coexistence of ANA and abnormal capillaroscopy significantly increased the risk of transition to SSc (RR 8.1, CI 6.9\u20139.7). Conclusions: A low incidence rate of transition from pRP to overt CTDs was confirmed. In patients with ssRP, whilst accepting the influence of selection bias of different studies, there appears to be a strong risk of transition toward a CTD regarding the concomitant presence of ANAs and abnormal capillaroscopy. References: Spencer - Green G. Arch Intern Med. 1998;158(6):595 \u2013 600

Outcomes, rates and predictors of transition of isolated Raynaud&apos;s phenomenon : a systematic review and meta-analysis

QUESTIONS: Published studies lack clear indicators of risk and predictors of transition from Raynaud's phenomenon (Rp) to connective tissue diseases (CTDs). Therefore, we aimed to study the outcomes, rates and predictors of transition to CTDs in patients with Rp. METHODS: A sensitive search was developed in Medline and Embase. Observational studies reporting incidence and risk factors of transition from Rp to a CTD were analysed by two independent reviewers. The main outcome was the rate of transition to a CTD; the secondary outcome was the evaluation of predictors. RESULTS: Of 856 articles captured, 7 selected studies met the inclusion criteria. A total of 4051 patients with primary Rp (pRp) and 1220 transitions to overt CTDs were recorded. The mean incidence rate of transition from pRp to a CTD was 2.65/100 person-years (standard error [SE] 1.2, 95% confidence interval [CI] 0.44-5.73). A total of 657 patients with suspected secondary Rp (ssRp) had antinuclear antibodies (ANAs) and/or capillary abnormalities; 188 transitions to CTDs were recorded, the mean incidence rate of transition from ssRp to CTD was 11.01/100 person-years (SE 4.0, 95% CI 0.11-22.12), and 135 transitions to systemic sclerosis (SSc), giving a mean incidence rate of transition from ssRp to SSc of 5.7/100 person-years (SE 2.19, 95% CI 1.02-13.19). With respect to patients with pRp, having ANAs without capillary abnormalities was associated with a risk for developing a CTD (pooled relative risks [RR] 7.63, 95% CI 2.87-20.29), whereas capillary abnormalities without ANAs resulted in a weaker risk of CTD transition (RR 5.53, 95% CI 1.45-21.06). The coexistence of ANAs and abnormal capillaroscopy significantly increased the risk of transition to CTD (RR 16.96, 95% CI 6.61-43.55). CONCLUSIONS: A low incidence rate of transition from pRp to overt CTD was found. In spite of a possible study selection bias, ssRp appears to have a strong risk of transition to a CTD when there is concomitant presence of ANAs and abnormal capillaroscopy

Recurrent and Founder Mutations in the Netherlands: the Long-QT Syndrome

Background and objective The long-QT syndrome (LQTS) is associated with premature sudden cardiac deaths affecting whole families and is caused by mutations in genes encoding for cardiac proteins. When the same mutation is found in different families (recurrent mutations), this may imply either a common ancestor (founder) or multiple de novo mutations. We aimed to review recurrent mutations in patients with LQTS. Methods By use of our databases, we investigated the number of mutations that were found recurrently (at least three times) in LQT type 1-3 patients in the Netherlands. We studied familial links in the apparently unrelated probands, and we visualised the geographical distribution of these probands. Our results were compared with published literature of founder effects in LQTS outside the Netherlands. Results We counted 14 recurrent LQT mutations in the Netherlands. There are 326 identified carriers of one of these mutations. For three of these mutations, familial links were found between apparently unrelated probands. Conclusion Whereas true LQT founder mutations are described elsewhere in the world, we cannot yet demonstrate a real founder effect of these recurrent mutations in the Netherlands. Further studies on the prevalence of these mutations are indicated, and haplotype-sharing of the mutation carriers is pertinent to provide more evidence for founder mutation-based LQTS pathology in our countr

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study

Introduction: Several studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19. Method: This prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (&lt;20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis. Results: Two Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86–1.62; p = 0.29). Discussion: The prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients