Background
Mucosal involvement is frequently seen in cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). There is no consensus regarding the prevalence, and a wide range of ...lesions has been reported. Its prognostic significance is currently unknown and a matter of controversy.
Objective
To classify oral lesions in lupus, evaluate their prevalence and assess their possible association with disease activity.
Methods
We conducted a descriptive study between 2016 and 2017. A total of 150 lupus patients were matched by sex, age and smoking status with 151 healthy individuals. All subjects underwent a careful evaluation of oral mucosa. On the same day of the clinical assessment, each patient underwent a peripheral venous blood and urine analysis. All patients underwent a full medical history, physical examination and a careful examination of the oral cavity. For each one, we obtained photographs of ten areas of the oral cavity. Two dermatologists of our group blindly recorded the presence and morphology of oral lesions. The disease activity of CLE patients was scored using the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index, and in SLE patients, activity was measured using the Systemic Lupus Erythematosus Disease Activity Index.
Results
In CLE patients, there was a statistically significant correlation between higher cutaneous disease activity and the following oral findings: discoid plaques, cobblestone and red/brown‐pigmented macules. In patients with CLE, red macules on jugal mucosa were statistically associated with anaemia and positive antinuclear antibodies titres; additionally, the presence of gingivitis was related to systemic inflammation. In SLE patients, gingival telangiectases were statistically significantly associated with leucopenia, hypocomplementemia and systemic inflammation.
Limitations
Biopsies on mucosal lesions were not performed.
Conclusion
Some specific oral lesions correlate with disease activity in CLE and SLE.
RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma ...concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder.
This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18–65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901.
From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41·3% (SD 39·7) for BUP-XR 300 mg/300 mg and 42·7% (38·5) for 300 mg/100 mg, compared with 5·0% (17·0) for placebo (p<0·0001 for both BUP-XR regimens). No compensatory non-opioid drug use was observed during BUP-XR treatment. The most common adverse events were headache (17 8% participants in the BUP-XR 300 mg/300 mg group vs 19 9% participants in the BUP-XR 300 mg/100 mg group vs six 6% participants in the placebo group), constipation (16 8% vs 19 9% vs 0), nausea (16 8% vs 18 9% vs five 5%), and injection-site pruritis (19 9% vs 13 6% vs four 4%). The BUP-XR safety profile was consistent with other buprenorphine products for treatment of opioid use disorder, except for injection-site reactions, which were reported in more than 5% of all participants who received BUP-XR, but were mostly mild and not treatment-limiting.
Participants' percentage abstinence was significantly higher in both BUP-XR groups than in the placebo group. Treatment with BUP-XR was also well tolerated. The availability of this monthly formulation, delivered by health-care providers, represents an advance in treatment for opioid use disorder that enhances the benefits of buprenorphine by delivering sustained, optimal exposure, while reducing risks of current buprenorphine products.
Indivior.
•cBM-MSCs and cAd-MSCs present similar immunophenotype, multilineage differentiation and immunomodulatory capacity.•Differences in proliferation and secretory profile are observed between both ...tissues.•Secretome from cBM-MSCs contains the highest concentration of soluble factors and exosomes.•Proteomic analysis reveals different exosomal cargo in each source related to regulation and metabolic processes.
The two main sources of mesenchymal stem cell (MSCs) in the canine species are bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). The secretion of multitude bioactive molecules, included under the concept of secretome and found in the cultured medium, play a predominant role in the mechanism of action of these cells on tissue regeneration. Although certain features of its characterization are well documented, their secretory profiles remain unknown. We described and compared, for the first time, the secretory profile and exosomes characterization in standard monolayer culture of MSCs from both sources of the same donor as well as its immunomodulatory potential. We found that despite the similarity in surface immunophenotyping and trilineage differentiation, there are several differences in terms of proliferation rate and secretory profile. cAd-MSCs have advantages in proliferative capacity, whereas cBM-MSCs showed a significantly higher secretory production of some soluble factors (IL-10, IL-2, IL-6, IL-8, IL-12p40, IFN-γ, VEGF-A, NGF-β, TGF-β, NO and PGE2) and exosomes under the same standard culture conditions. Proteomics analysis confirm that cBM-MSCs exosomes have a greater number of characterized proteins involved in metabolic processes and in the regulation of biological processes compared to cAd-MSCs. On the other hand, secretome from both sources demonstrate similar immunomodulatory capacity when tested in mitogen stimulated lymphocyte reaction, but not in their exosomes at the dose used. Considering that the use of secretome open as a new therapeutic strategy for different diseases, without the need to implant cells, those biological differences should be considered, when choosing the MSCs source, for either cellular implantation or direct use of secretome for a specific clinical application.
•RP/UHPLC–MS and HILIC/UHPLC–MS methods developed for metabolic analysis of CSF samples.•Altered metabolic fingerprints were related to AD progression in CSF samples.•The accuracy of the prediction ...model from MCI to AD was 98.7%.•Specificity and sensitivity of the prediction model from MCI to AD were above 95%.
Alzheimer's disease (AD) is the most prevalent cause of dementia among older people. Although AD probably starts 20–30 years before first clinical symptoms become noticeable, nowadays it cannot be diagnosed accurately in its early stages. In this work, we present a new MS-based metabolomic approach based on the use of ultra-high performance liquid chromatography–time-of-flight mass spectrometry (UHPLC–TOF MS) to investigate cerebrospinal fluid (CSF) samples from patients with different AD stages. With the aim to obtain wide metabolome coverage two different chromatographic separation modes, namely reversed phase (RP) and hydrophilic interaction chromatography (HILIC), were used. RP/UHPLC–MS and HILIC/UHPLC–MS methods were optimized and applied to analyze CSF samples from 75 patients related to AD progression. Significant metabolic differences in CSF samples from subjects with different cognitive status related to AD progression were detected using this methodology, obtaining a group of potential biomarkers together with a classification model by means of a multivariate statistical analysis. The proposed model predicted the development of AD with an accuracy of 98.7% and specificity and sensitivity values above of 95%.
Intermittent ethanol consumption changes the neuronal activity of the orbitofrontal cortex (OFC) in rodents, which has been attributed to important participation in the development of addiction, ...particularly alcoholism. The OFC participates in gustatory sensory integration. However, it is unknown whether this region can encode chemosensory elements of oral ethanol administration independently of the consumption movement (orofacial motor response) when administered for the first time (naïve mice). To answer this question, we used a sedated mouse model and a temporary analysis protocol to register extracellular neuronal responses during the oral administration of ethanol. Our results show an increase in neuronal frequency (in the first 500 ms) when low (0.6, 1, and 2.1 M) and high (3.2, 4.3, and 8.6 M) concentrations of ethanol are orally administered. The modulatory effect of ethanol was observed from low and high concentrations and differed from the tastants. There was consistent neuronal activity independent of the concentration of ethanol. Our results demonstrate a sensory representation of oral ethanol stimulation in the OFC neurons of naïve mice under sedation.
With additive manufacturing (AM) individual and biocompatible implants can be generated by using suitable materials. The aim of this study was to investigate the biological effects of polylactic acid ...(PLA) manufactured by Fused Deposition Modeling (FDM) on osteoblasts in vitro according to European Norm / International Organization for Standardization 10,993-5.
Human osteoblasts (hFOB 1.19) were seeded onto PLA samples produced by FDM and investigated for cell viability by fluorescence staining after 24 h. Cell proliferation was measured after 1, 3, 7 and 10 days by cell-counting and cell morphology was evaluated by scanning electron microscopy. For control, we used titanium samples and polystyrene (PS).
Cell viability showed higher viability on PLA (95,3% ± 2.1%) than in control (91,7% ±2,7%). Cell proliferation was highest in the control group (polystyrene) and higher on PLA samples compared to the titanium samples. Scanning electron microscopy revealed homogenous covering of sample surface with regularly spread cells on PLA as well as on titanium.
The manufacturing of PLA discs from polylactic acid using FDM was successful. The in vitro investigation with human fetal osteoblasts showed no cytotoxic effects. Furthermore, FDM does not seem to alter biocompatibility of PLA. Nonetheless osteoblasts showed reduced growth on PLA compared to the polystyrene control within the cell experiments. This could be attributed to surface roughness and possible release of residual monomers. Those influences could be investigated in further studies and thus lead to improvement in the additive manufacturing process. In addition, further research focused on the effect of PLA on bone growth should follow. In summary, PLA processed in Fused Deposition Modelling seems to be an attractive material and method for reconstructive surgery because of their biocompatibility and the possibility to produce individually shaped scaffolds.
In this work, concretes with high levels of fly ash replacing portland cement were elaborated. The concretes 'properties in the fresh state (consistency, workability, and heat of hydration) and in ...the hardened state (compressive strength, modulus of elasticity, conductivity, void index, water absorption, and density) were measured. Microstructural and thermal characterization were performed. Numerical simulations were performed to analyze the heat exchange during the cement hydration process. Statistical analysis was adequate, and a proposed regression model was validated for the high-volume fly ash concrete, with 60% replacing the portland cement. This concrete presented values of mechanical strength (33.38 + or - 3.99 MPa) and modulus of elasticity (38.58 + or - 0.81 GPa) which confirms its use as structural concrete. This concrete showed low heat of hydration, a reduction of 23% in relation to the reference concrete (without fly ash) during its curing process, and its microstructure presented a lower level of cracking. Keywords: concrete with high levels fly ash; factorial planning; micro-structure; numerical simulation; thermal and mechanical properties.
The Covid-19 pandemic is an unprecedented shock that has tested the responsiveness of education systems around the world. The international literature that has studied the Covid-19 pandemic and ...school performance is still limited. Colombia presents an interesting scenario for the analysis due to the prolonged school closures and long lockdowns it experienced in 2020, and the availability of a rich dataset on the results of a high school exit examination (Saber11) that was administered even during the pandemic. Using this data, we estimate whether the COVID-19 pandemic is associated to lower levels of performance amongst graduating high school students using a school and time fixed effects model, finding a negative relation. Due to the significant reduction in the number of students taking the national standardized high school exit exam in 2020, we use inverse probability weighting (IPW) regressions to control for possible selection bias. The results of these regressions show that the Covid-19 pandemic has a negative and statistically significant relation with the scores obtained by students on the Saber11 exam. These results are relevant because they provide evidence to motivate the design of public policies that mitigate the side effects of the pandemic on educational outcomes.
•Literature on the effects of Covid-19 on school performance is still limited.•Colombia presents an interesting scenario for the analysis due to prolonged school closures.•The Covid-19 pandemic had a negative and significant association with students’ performance.•Access to a computer and internet connection at home is associated with a better performance in the examination.
Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective ...cohort of an H pylori eradication trial in a Hispanic population.
A total of 800 adults with precancerous lesions were randomized to anti–H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location.
Overall, 356 individuals completed 20 years of follow-up. Anti–H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio OR, 0.59; 95% confidence interval CI, 0.38–0.93). H pylori–negative status had a beneficial effect on the score over time (P = .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85–1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06–0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8–103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7–6.6) for GC.
In a high-GC-risk Hispanic population, anti–H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.
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