9 (4.9) years. Adherence to the current biologic therapy was high (79.3% and 57.5% according to the CQR5 questionnaire and the adherence question, respectively). Level of knowledge of self-care safety skills (median BIOSECURE score 71) was in the acceptable range. Level of adherence and level of knowledge of self-care safety skills for biologic therapy were not associated. Patients declared that the main sources of information were their rheumatologist (92.6%) and the rheumatology team (30.5%).

According to the patients’ estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).

According to the patients’ estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).

A central hallmark of osteoarthritis (OA) is cartilage destruction. Chondrocytes not only control cartilage metabolism, but are capable of immunogenic responses. The role of chondrocytes in the pathogenesis of OA is still unclear. In this study, we aimed to determine the immunological role of chondrocytes in response to proteoglycan aggrecan (PG) peptides.

Human chondrocytes were isolated from cartilage of knee OA patients undergoing knee arthroplasty and stimulated with proteoglycan aggrecan peptides in the presence of IFNγ. Antigen presentation markers, co-stimulatory molecules, cytokine production, gene expression and antigen presentation to T cells were evaluated.

Our results show that IFNγ was required for the expression of MHC class I and II. However, stimulation with PG peptides P16-31 and P263-280, but not P2379-2394, increased expression level of co-stimulatory molecules (CD80 and CD86) and IL-6, IL-8 and TNFα production. This upregulation was seen in chondrocytes to nearly comparable levels of professional antigen-presenting cells. A similar pattern of gene expression was observed between P16-31 and P263-280 peptide stimulation on chondrocytes and this was different from P2379-2394 peptide treatment. Co-culture with autologous T cells revealed signi cant proliferation of cells when stimulating with the P263-280 peptides.

Our study shows that human chondrocytes display unique features of antigen presentation. Their ability to process certain proteoglycan aggrecan peptides, in which these molecules are synthesised by the cartilage themselves render the possibility of a role for „self-antigens” in the immunopathogenesis of OA.

Our study shows that human chondrocytes display unique features of antigen presentation. Their ability to process certain proteoglycan aggrecan peptides, in which these molecules are synthesised by the cartilage themselves render the possibility of a role for „self-antigens” in the immunopathogenesis of OA.Osteopontin (OPN) is a phosphoglycoprotein involved in bone remodelling, wound healing, cell adhesion, tissue remodelling, and immune response that is distributed widely in normal adult tissues. OPN biological activity is regulated by thrombin and matrix metalloproteinases (MMPs) cleavage, where the full-length (OPN-FL) protein and the cleaved OPN-N are associated with autoimmune diseases such as systemic lupus erythematosus (SLE). OPN overexpression has been associated with a predisposition to SLE and bad prognosis since OPN could mediate a sustained polyclonal B cell activation that besides to intracellular OPN (iOPN) form, promote the T follicular helper (TFH) cells and enhance anti-nuclear antibody production. Currently, the role of OPN in lupus nephritis (LN) has been reported and extensively studied; however, no data are available about the potential mechanism of OPN in neuropsychiatric SLE (NPSLE). In this review, we highlighted the contribution of OPN and iOPN in LN and NPSLE immunopathology.

To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy.

We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE.

We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF’́s before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p<0.001; 95%CI -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed.

In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

To explore the association between serum S100A8/9 (calprotectin), clinical and ultrasound (US) assessment in juvenile idiopathic arthritis (JIA) patients.

A total of 30 well-characterised consecutive patients (18 female) with non-systemic JIA and 20 age-matched healthy controls were included. Serum and plasma samples obtained the same day of the clinical and sonographical assessment were tested for calprotectin levels by ELISA. Clinical status was defined using Wallace criteria. Ultrasonographic B-mode and power Doppler (PD) assessment of 44 joints for each subject was performed.

Clinically active disease was present in 14 patients, while 16 patients were active according to US evaluation. We found no differences in the serum/plasma calprotectin levels in clinically active disease group [29.6 (5.4-198.1) ng/ml; 12.6 (2.8-65.8) ng/ml] as compared with inactive disease group [24.8 (14.1-204.3); 12.7 (3.4-65.1)] (p=0.73; p=0.29). There was also no difference between US active disease [29.8 (5.4-204.3); 12.s to be extended with a larger number of patients.

In the present study we investigate the putative differences in pain catastrophising (PC), pain perception (PP), sexual functioning (SF), satisfaction (SS), and overall quality of life between fibromyalgia (FM) and rheumatoid arthritis (RA) patients as compared to healthy controls (HC).

Fifty-seven native Italian-speaking female individuals suffering either from FM or RA and thirty-eight healthy female controls (FM = 40; RA = 17; HC = 38) were submitted to a semi-structured interview aimed at assessing PP intensity (Visual Analog Scale; VAS), general health conditions (36-items Short-Form Health Survey; SF-36), PC (Pain Catastrophising Scale; PCS), SF and SS (Index of Sexual Satisfaction; ISS/ Female Sexual Function Index; FSFI).

FM patients had a significantly higher PP both as compared to RA and HC (p<0.002 for both), and higher PC as compared to HC but not as compared to RA patients (p<0.03 and p<0.64). When compared to RA patients and HC, they showed a lower quality of life (p<0.002 for both comparisons), a compromised SF (p<0.003 and p<0.002, respectively) and a lower index of SS with respect to HC (p<0.002). RA patients had higher PP (VAS; p<0.002), lower quality of life and SF as compared to HC (p<0.002 and p<0.003, respectively).

FM and RA patients showed a significantly lower quality of life, SF and SS as compared to HC. PC was significantly related to PP and low quality of life in FM patients while in RA patients it negatively affected quality of life and especially the sexual sphere both when considering SF and SS.

FM and RA patients showed a significantly lower quality of life, SF and SS as compared to HC. PC was significantly related to PP and low quality of life in FM patients while in RA patients it negatively affected quality of life and especially the sexual sphere both when considering SF and SS.The risk of herpes zoster (HZ) and HZ-related complications is increased in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) relative to the general population; therefore, HZ vaccination is recommended in these patient groups. In this literature-based review, we summarise the available evidence on the use of HZ vaccines in patients with RA and PsA, and discuss strategies for managing breakthrough infection. Currently available data show suboptimal rates of HZ vaccination among these patients and highlight a need for strategies to improve HZ vaccination programmes in clinical practice. Further clinical studies are also required to optimise the use of HZ vaccines in patients with RA and PsA, particularly with regard to determining the impact of different immunosuppressive therapy regimens on vaccine immunogenicity and, ultimately, efficacy, as well as the impact of vaccination on disease activity and safety.The bacterial genotoxin colibactin interferes with the eukaryotic cell cycle by causing dsDNA breaks. It has been linked to bacterially induced colorectal cancer in humans. Colibactin is encoded by a 54 kb genomic region in Enterobacteriaceae. The colibactin genes commonly co-occur with the yersiniabactin biosynthetic determinant. Investigating the prevalence and sequence diversity of the colibactin determinant and its linkage to the yersiniabactin operon in prokaryotic genomes, we discovered mainly species-specific lineages of the colibactin determinant and classified three main structural settings of the colibactin-yersiniabactin genomic region in Enterobacteriaceae. The colibactin gene cluster has a similar but not identical evolutionary track to that of the yersiniabactin operon. Both determinants could have been acquired on several occasions and/or exchanged independently between enterobacteria by horizontal gene transfer. Integrative and conjugative elements play(ed) a central role in the evolution and structural diversity of the colibactin-yersiniabactin genomic region. Addition of an activating and regulating module (clbAR) to the biosynthesis and transport module (clbB-S) represents the most recent step in the evolution of the colibactin determinant. In a first attempt to correlate colibactin expression with individual lineages of colibactin determinants and different bacterial genetic backgrounds, we compared colibactin expression of selected enterobacterial isolates in vitro. Colibactin production in the tested Klebsiella species and Citrobacter koseri strains was more homogeneous and generally higher than that in most of the Escherichia coli isolates studied. Our results improve the understanding of the diversity of colibactin determinants and its expression level, and may contribute to risk assessment of colibactin-producing enterobacteria.Strain HNM0947T, representing a novel actinobacterium, was isolated from the coral Galaxea astreata collected from the coast of Wenchang, Hainan, China. The strain was found to have morphological and chemotaxonomic characteristics consistent with the genus Nocardiopsis. The organism formed abundant fragmented substrate mycelia and aerial mycelia which differentiated into non-motile, rod-shaped spores. Whole-cell hydrolysates contained meso-diaminopimelic acid and no diagnostic sugars. The major menaquinones were MK-10(H8), MK-10(H6) and MK-10(H4). The major phospholipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. The major fatty acids were iso-C160, anteiso-C170, C180, C180 10-methyl (TBSA) and anteiso-C150. The G+C content was 71.3 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HNM0947T belonged to the genus Nocardiopsis and shared highest sequence similarity to Nocardiopsis salina YIM 90010T (98.8%), Nocardiopsis xinjiangensis YIM 90004T(98.5%) and Nocardiopsis kunsanensis DSM 44524T (98.3%). The strain HNM0947T was distinguished from its closest type strain by low average nucleotide identity (90.8%) and dDDH values (60.4%) respectively. Based on genotypic, chemotaxonomic and phenotypic characteristics, it was concluded that strain HNM0947T represents a novel species of the genus Nocardiopsis whose name was proposed as Nocardiopsis coralli sp. nov. The type strain was HNM0947T (=CCTCC AA 2020015 T=KCTC 49525 T).The Journal of Medical Microbiology has a global presence with an international Editorial Board. Asian countries such as PR China, India and Iran are prolific in the submission of manuscripts. Overall, the acceptance rate has been highest for European countries, the USA, Canada and Australia, and lowest for African, Asian and Latin American (LATAM) countries. The creation of regional Editors to assist the authors from these countries would serve the scientific community.A novel strain of a member of the genus Acinetobacter, strain PS-1T, was isolated from the skin of fresh water pufferfish (Tetraodon cutcutia) collected from Mahanadi River, India. Cells were Gram-stain-negative, aerobic, coccoid and non-motile. The predominant polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and phospholipid (PL) and the cell wall sugars were glucose, galactose and ribose. The major cellular fatty acids of PS-1T were C18  1ω9c (30.67 %), C16  1ω7c (19.54 %), C16  0 (15.87 %), C12  0 (7.35 %) and C12  0 3-OH (6.77 %). The genome size was 3.5 Mbp and the DNA G+C content was 41.97 %. Gene ontology study revealed that the major fraction of genes were associated with biological processes (53.99 %) followed by molecular function (30.42 %) and cellular components (15.58 %). Comparisons of 16S rRNA gene sequences revealed 97.94-97.05 % sequence similarity with the closely related type strains of species of the genus Acinetobacter. The average nucleotide identity (ANI) and average amino acid identity (AAI) of PS-1T with reference strains of species of the genus Acinetobacter with validly published names were bellow 95-96 and the corresponding in-silico DNA-DNA hybridization (DDH) values were below 70 %. A phylogenomic tree based on core genome analysis supported these results. Genotypic and phenotypic characteristics of PS-1T indicate that the strain represents a novel species of the genus Acinetobacter and the name Acinetobacter kanungonis sp. nov. is proposed. The type strain is PS-1T (=JCM 34131T=NCIMB 15260T).Objective The objective of this study was to analyze the long-term effects of a personalized cognitive stimulation (PCS) program on the global cognition, cognitive aspects, activities of daily living (ADLs), anxiety, and depression in older adults with possible mild cognitive impairment (MCI).Methods A 12-month follow-up analysis was carried out in a single-blind, randomized clinical trial to research the long-term effects of a 10-week PCS program evaluating the cognitive level, depression, and anxiety of older adults with possible MCI.Results Fifty older adults were assessed 12 months after the CS program, 23 in the intervention group and 27 in the control group. There were significant differences between the groups at 12 months in the global cognition (p = .002), in global orientation (p less then .001), and in spatial orientation (p = .004) in favor of the intervention group, measured with the Spanish version of the Mini-Mental Status Examination (MEC-35).Conclusions A PCS program could be effective in improving global cognition and global and spatial orientation.Clinical implications A PCS program based on cognitive levels in older adults with possible MCI achieves improvements in global cognition and global and spatial orientation. PCS programs can be applied successfully by trained occupational therapists.Sexual minority college students are disproportionately impacted by sexual assault in college, however, there is a paucity of research exploring the role of the college environment in victimization. This study explores the relationship of campus climate with sexual assault victimization for these students. This sample included 1,110 current college students in the United States who identified as a sexual minority. Logistic regression results indicated that the more observations of harassment and discrimination of sexual minority students by participants, the more likely they were to experience sexual assault victimization in college. Also, the more out a participant was on campus, and the stronger sense of belonging they had to their college, the less likely they were to experience sexual assault victimization. Sexual assault prevention efforts on college campuses would benefit from programming and policies that support belonging and address discrimination and harassment.Neural Architecture Search (NAS), which aims at automatically designing neural architectures, recently draw a growing research interest. Different from conventional NAS methods, in which a large number of neural architectures need to be trained for evaluation, the one-shot NAS methods only have to train one supernet which synthesizes all the possible candidate architectures. As a result, the search efficiency could be significantly improved by sharing the supernet’s weights during the candidate architectures’ evaluation. This strategy could greatly speed up the search process but suffer a challenge that the evaluation based on sharing weights is not predictive enough. Recently, pruning the supernet during the search has been proven to be an efficient way to alleviate this problem. However, the pruning direction in complex-structured search space remains unexplored. In this paper, we revisited the role of path dropout strategy, which drops the neural operations instead of the neurons, in supernet training, and several interesting characters of the supernet trained with dropout are found. Based on the observations, a Hierarchically-Ordered Pruning Neural Architecture Search (HOPNAS) algorithm is proposed by dynamically pruning the supernet with a proper pruning direction. Experimental results indicate that our method is competitive with state-of-the-art approaches on CIFAR10 and ImageNet.The occurrence and emissions of methane (CH4) from above-ground urban natural gas infrastructure is poorly understood. Compared to below-ground infrastructure, these facilities are relatively easy to monitor and maintain and present an opportunity for cost-effective CH4 reductions. We present a case study and methodology for detecting, attributing, and quantifying CH4 emissions from fence line measurements at above-ground natural gas facilities in the City of Calgary, Alberta, Canada. We produced bounding-box concentration maps by walking around the outer fence of 33 facilities with a backpack-configured trace gas analyzer and a tablet with integrated GPS. Wind measurements were acquired simultaneously from a fixed location on site with a 3D sonic anemometer. We fused geolocation, CH4 concentration, and wind data to determine the likelihood each facility was emitting. We found one definitive leak by carrying out measurements directly alongside an exposed section of pipe. Based on the presence of methyl mercaptan (CH3SH) odor, peak ΔCH4, and the difference between downwind and upwind ΔCH4, we interpret a high plausibility that 22 facilities were emitting CH4, followed by 2 with a medium plausibility, and 8 with a low plausibility. Once verified to plausibly emit, these data were used to estimate emissions flux at six facilities where near-field obstructions were limited. The estimated emissions flux for six facilities was 66.31 mg CH4 s-1, or 2.1 tonnes CH4 yr-1 if this flux remained constant. Overall, this study indicates most above-ground natural gas facilities surveyed in Calgary were emitting CH4. These facilities represent easy mitigation targets for reducing CH4 emissions and improving environmental performance. To our knowledge, this is the first study to integrate qualitative and quantitative information to predict detection plausibility in a complex measurement setting.Due to comprehensive social distancing measures related to the COVID-19 pandemic, medical faculties worldwide have made a virtue of necessity in resorting to online teaching. Medical faculties grapple with how to convey clinical competencies to students in this context. There is a need for research not only to map but also to explain the effect of these secondary measures on students’ learning and mental wellbeing. During a period of ongoing comprehensive social distancing measures in Germany, we translated a competency-based curriculum including obstetrics, paediatrics, and human genetics to an e-learning course based on online patient and teacher encounters. In our qualitative study on students’ and teachers’ views, we identify potential enablers and drivers as well as barriers and challenges to undergraduate medical education under lockdown. In summer 2020, we conducted six focus group interviews to investigate medical students’ and teachers’ perspectives, experiences and attitudes. All focus groups were vcial distancing measures.

To investigate biomechanics, muscle performance, and disability of the craniocervical region in temporomandibular disorder (TMD) patients and compare them with controls.

Craniocervical posture was evaluated using lateral photography and radiography. Range of motion, muscle performance, disability, and TMD severity were assessed using an inclinometer, Functional Strength Testing of Cervical Spine, Neck Disability Index, and Fonseca Anamnestic Index, respectively.

Compared to the control group, the TMD group demonstrated higher cervical flexion angle (

=0.005) and neck disability (

<0.001) as well as lower cervical extension (

=0.040), right cervical rotation (

=0.005), left cervical rotation (

<0.001), and tragus-C7-horizontal (

=0.048) angles, and reduced muscle performances (

≤0.001). Most patients had higher than normal craniocervical angle (

<0.001). Muscle performance in each cervical motion (

<0.005) and disability (

<0.001) were associated with TMD severity in the TMD group.

Biomechanics, muscle performance, and disability of craniocervical region were altered in the TMD group.

Biomechanics, muscle performance, and disability of craniocervical region were altered in the TMD group.Anthropogenic emissions of greenhouse gases are warming the Earth. It is likely that the greatest impacts of climate change on human and natural systems will come from increasingly frequent and severe extreme weather and climate events. Some increases in such extremes are already being detected, and this trend is projected to continue as Earth warms. Here we review the overarching climate drivers of increases in extreme weather and address the context in which extremes occur and the challenges of projecting future changes. The observational evidence for climate-driven increases in extremes and the implications of model projections are reviewed for heat and drought and several types of storms tropical cyclones, midlatitude storms, and severe local weather, focusing on those changes most relevant to the continental United States. We emphasize the overall observed and modeled trends in extreme weather in which we have the greatest confidence, because they are consistent with our fundamental understanding of weather and climate. Despite remaining uncertainty about many details, especially in model-based projections, the signal of increasing extremes is sufficiently clear that it demands a robust human response, in limiting future emissions of greenhouse gases and in making our human systems more resilient to further changes that are inevitable as Earth continues to warm.Objectives The perspectives of professionals involved in behavioral health (BH) services with short-stay residents in skilled nursing facilities (SNFs) are rarely captured in the literature. This study examines the real-world experiences of BH clinicians and administrators in post-acute/subacute care units in SNFs.Methods This qualitative study used semi-structured interviews with 18 clinicians (e.g., psychologists and social workers) and five administrators (e.g., directors of social services or BH company executives) involved in BH services with short-stay SNF residents. Interviews were recorded, transcribed, and analyzed by two independent coders using conventional thematic content analysis.Results Three themes emerged from the data (1) BH needs are high among short-stay residents and families during post-acute care transitions; (2) BH services offer multiple unique opportunities to enhance post-acute/subacute care in SNFs; and (3) barriers to providing optimal BH care exist at multiple levels and require action from BH clinicians and stakeholders.Conclusions Variability in clinician roles and barriers to optimized care suggest the need for future research targeting best practices and implementation strategies for BH services with short-stay SNF residents.Clinical Implications Results identified multiple ways in which BH services may enhance resident, family, and staff outcomes, as well as the milieu in SNFs.Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is unclear. We reviewed published literature for evidence of an association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.Methods Articles were retrieved until April 29th, 2021 by searching in seven databases. Data were combined using the general-variance-based method.Results A total of 25 cohort studies (N=41,339 patients) and 11 randomized clinical trials (RCTs; N=8,709) were found. The use of HCQ was not associated with mortality in meta-analysis of RCTs (pooled risk ratio (PRR) 1.08, 95%CI 0.97-1.20; I2=0%), but it was associated with 20% lower mortality risk (PRR=0.80, 95%CI 0.69-0.93; I2=80%) in pooling of cohort studies. The negative association with mortality was mainly apparent by pooling cohort studies that used lower doses of HCQ (≤400 mg/day; PRR=0.69, 95%CI 0.57-0.87). Use of HCQ+AZM (11 studies) was associated with 25% non-statistically significant lower mortality risk (PPR=0.75; 0.51-1.10; P=0.15). Use of HCQ was not associated with severe adverse events (PRR=1.12, 95%CI 0.88-1.44; I2=0%).Conclusions HCQ use was not associated with mortality in COVID-19 patients in pooling results from RCTs (high level of certainty of evidence), but it was associated with 20% mortality reduction when findings from observational studies were combined (low level of certainty of evidence). The reduction of mortality was mainly apparent in observational studies where lower doses of HCQ were used. These findings might help disentangling the debate on HCQ use in COVID-19.Both natural and anthropogenic fugitive dust can cause serious hazards to the environment and human health. In this study, the development of biodegradable dust suppressants and their environmental impacts were evaluated. Biodegradable dust suppressants were prepared using various biomass-based polymeric materials such as crude glycerol (a by-product of biodiesel manufacturing), biodiesel, palm oil, cooking oil, seaweed mixtures, wakame (Undaria pinnatifida), and red algae. The results of wind-tunnel tests with Korean standard sand demonstrated that spraying diluted mixtures of crude glycerol and biomass materials can significantly reduce the generation of dust. The optimal molar mixing ratio of crude glycerol and the biomass materials was 11, and the optimal dilution concentration was determined to be 100 times for the mixture of crude glycerol and biodiesel, palm oil, and cooking oil and 50 times for the mixture of crude glycerol with a seaweed mixture, wakame, and red algae. The suppression ability was 83.r, due to their toxic effects, it is necessary to develop a new eco-friendly suppressant that can be biodegraded in the soil and that is not hazardous to human health or the environment. In this study, we try to develop an eco-friendly dust suppressant with low toxicity, to evaluate various potential dust suppressants, and to propose promising candidate products for commercialization and mass production. Ingredients and by-products of biodiesel production, marine biomass, and commercial vegetable oils were selected for the synthesis of suppressants. The optimal mixing ratio was determined, and the suppression ability was evaluated via wind tunnel tests. Considering biodegradability, the most effective suppressants were determined.The hyperdiverse genus Trichoderma is one of most useful groups of microbes for a number of human activities, and their accurate identification is crucial. The structural simplicity and lack of distinctive phenotypic variation in this group enable the use of DNA-based species delimitation methods in combination with phylogenies (and morphology when feasible) to establish well-supported boundaries among species. Our study employed a multilocus phylogeny and four DNA-based methods (automated barcode gap discovery [ABGD], statistical parsimony [SPN], generalized mixed Yule coalescent [GMYC], and Bayesian phylogenetics and phylogeography [BPP]) for four molecular markers (acl1, act, rpb2, and tef1) to delimit species of two lineages of Trichoderma. Although incongruence among these methods was observed in our analyses, the genetic distance (ABGD) and coalescence (BPP) methods and the multilocus phylogeny strongly supported and confirmed recognition of 108 and 39 different species in the Harzianum and Longibrachiatum lineages, including three new species associated with cacao farms in northern Peru, namely, T.awajun, sp. nov., T. jaklitschii, sp. nov., and T. peruvianum, sp. nov. Morphological distinctions between the new species and their close relatives are primarily related to growth rates, colony appearance, and size of phialides and conidia. This study confirmed that an integrative approach (DNA-based methods, multilocus phylogeny, and phenotype) is more likely to reliably verify supported species boundaries in Trichoderma.Marla Sokolowski is a true pioneer in behavioral genetics, having made the first molecular delineation of a naturally occurring behavioral polymorphism in her work on the foraging locus in Drosophila melanogaster. The gene was subsequently found to be responsible for behavioral variants and types in many other species, both invertebrate and mammal (human). The path to get there is a paradigmatic example of how to use the power of genetic analysis, including some rather esoteric techniques, to zero in on a gene and delineate its molecular identity and its pleiotropic roles.The psychological consequences of the global COVID-19 pandemic are just now starting to be understood; however, the behavioral consequences are less understood. Thus, the current report examined whether cyberbullying processes and frequency are affected by the COVID-19 pandemic. We compared US adult participant data from six months before the start of the pandemic (July 2019; n = 181) to data collected in the middle of the pandemic (May, 2020; n = 173) to determine if there are any significant differences in anonymity perceptions, belief in the irrelevance of muscularity for online bullying (BIMOB), cyberbullying attitudes, and cyberbullying perpetration. Results showed that there were significant increases in BIMOB, cyberbullying attitudes, and cyberbullying perpetration during the pandemic, but no significant change for anonymity perceptions. Further, the relationships between several variables germane to cyberbullying perpetration prediction were stronger during the pandemic than before. Overall, these findings add to our understanding of the behavioral impact the COVID-19 pandemic has on US adults.Corticobasal syndrome (CBS) is associated with diverse pathological substrates such as tau, prion protein, transactive response and, rarely, alpha synuclein. We report the case of a54-year-old man, who presented with asymmetric levodopa-poor-responsive parkinsonism, frontal lobe signs and behavioral changes. He was diagnosed with CBS, and postmortem analyses revealed Lewy body disease Braak stage VI without comorbid pathologies. Retrospectively, the clinical course of our patient and previous reports indicate that CBS plus mood changes and autonomic dysfunction, including reduced uptake of metaiodobenzylguanidine, are predictive factors of Lewy body pathology, even if the clinical picture is atypical.Currently, most licensed vaccines against SARS-CoV-2 infection are approved for adults and not for children. We conducted a test negative case-control study to assess the effectiveness of Measles Containing Vaccines (MCVs) against SARS-CoV-2 infection in Pune, India, in children who were ≥1 year and less then 18 years of age and were tested for SARS-CoV-2 infection by Reverse transcription polymerase chain reaction (RT-PCR). The enrolled participants included 274 SARS-CoV-2 positive cases (216 vaccinated and 58 unvaccinated) along with 274 SARS-CoV-2 negative controls (265 vaccinated and 9 unvaccinated). Of the 274 cases, 180 (65.7%) were asymptomatic while 94 (34.3%) were symptomatic, all with mild severity. The number of participants with symptomatic SARS-CoV-2 infection was significantly lower in the vaccinated group compared to the unvaccinated group (p less then .0001). The unadjusted overall Vaccine Effectiveness (VE) in the vaccinated group compared to unvaccinated group was 87.4% (OR = 0.126, 95% CI of VE 73.9-93.9) while the adjusted overall VE after adjusting for age and sex was 87.5% (OR = 0.125, 95% CI of VE 74.2-94.0). MCVs reduced incidence of laboratory confirmed SARS-CoV-2 infection in children. Number of symptomatic cases were also lower in the vaccinated group compared to the unvaccinated group. Results of our study have provided strong preliminary evidence that MCVs have a good effectiveness against SARS-CoV-2 infection in the pediatric population, which needs to be confirmed further through prospective randomized clinical trials.Background There are no data on circulating concentrations of sFas (proapoptotic protein of extrinsic pathway) and Bcl2 (antiapoptotic protein of intrinsic pathway) in COVID-19 patients. Thus, our objective study was to determine whether an association exists between serum concentrations of sFas and Bcl2 and COVID-19 patient mortality.Methods This observational and prospective study of COVID-19 patients was performed in eight Intensive Care Units (ICU) from Canary Islands (Spain). Serum levels of sFas and Bcl2 at ICU admission were determined. Mortality at 30 days was the end-point study.Results Surviving patients (n = 42) compared to non-surviving (n = 11) had lower APACHE-II (p less then 0.001), lower SOFA (p = 0.004), lower serum sFas levels (p = 0.001) and higher serum Bcl2 levels (p less then 0.001). Logistic regression showed an association between high serum sFas levels and mortality after controlling for APACHE-II (OR = 1.004; 95% CI = 1.101-1.007; p = 0.01) or SOFA (OR = 1.003; 95% CI = 1.101-1.106; p = 0.004), and between low serum Bcl2 levels and mortality after controlling for APACHE-II (OR = 0.927; 95% CI = 0.873-0.984; p = 0.01) or SOFA (OR = 0.949; 95% CI = 0.913-0.987; p = 0.01).Conclusions Thus, to the best of our knowledge, this is the first study reporting blood levels of sFas and Bcl2 in COVID-19 patients and its association with mortality.Background Results of randomized clinical trials may not be entirely applicable to clinical practice. The present manuscript aims to explore the pragmatism and robustness of the evidence that supports the European Society for Medical Oncology (ESMO) follicular lymphoma (FL) guidelines.Methods & design Analysis of all trials used to support positive, therapeutic, oncological recommendations in the 2020 ESMO FL guidelines. Predefined data points were extracted from each trial. Pragmatism was assessed by means of the PRECIS-2 tool, the difference in overall survival in the interventions compared and the source of funding. Robustness was assessed by means of the fragility index and the p value.Results 28 trials were included. The full protocol or a protocol summary was provided for 12 (43%). Based on the PRECIS-2 domains, trials were considered pragmatic in organization, analysis and flexibility and explanatory in eligibility. Robustness was high, with 4/24 (17%) trials with p values between 0.05 and 0.005 and a median fragility index of 18.Conclusions Results of trials to support ESMO recommendations in FL were robust. Pragmatism was high in some domains but modest to low in others and the pattern was similar across trials. Transparency in the publication of trial protocols was suboptimal.

Convalescent plasma (CP) containing antibodies derived from coronavirus disease 2019 (COVID-19) survivors has been proposed as a promising therapeutic option for severe COVID-19.

In our intensive care unit (ICU), 55 patients (46 male, median age 61 years) with PCR-confirmed COVID-19 (35 = 63.6% on mechanical ventilation, 7 = 14.5% on high-flow nasal oxygen, 12 = 20% on non-invasive ventilation, 1 = 1.8% without respiratory support) were treated with high-titre CP (200 mL per dose, range 1-6 doses, median 3 doses per patient, minimum titre > 1100, Wantai test). 139 COVID-19 patients treated in the same ICU who did not receive CP served as control group. In 27 patients, the effect of CP on the individual levels of SARS-CoV-2 IgG antibodies was assessed by ELISA in serum sample pairs collected before and after CP transfusion.

The first CP dose was administered at a median of 8 days after symptom onset. 13 patients in the plasma cohort died (28-day mortality 24.1%), compared to 42 (30.2%) in the cohort who did not receive CP (

 = 0.5, Pearson Chi-squared test). Out of the 27 individuals investigated for the presence of IgG antibodies, 8 did not have detectable IgG levels before the first CP transfusion. In this subpopulation, 3 patients (37.5%) died. Not a single confirmed adverse reaction to CP was noted.

While adjunctive treatment with CP for severe and life-threatening COVID-19 was a very safe intervention, we did not observe any effect on mortality.

While adjunctive treatment with CP for severe and life-threatening COVID-19 was a very safe intervention, we did not observe any effect on mortality.Introduction Candida species have been regarded as global health threats due to their ability to cause invasive infections. It is challenging to treat Candida bloodstream infections, which are associated with high mortality levels. Monotherapy with antifungals is sometimes not effective against severe Candida infections, and combination therapy is needed in clinical practice.Areas covered This review was undertaken based on data from a PubMed search for English language reports published before March 2021 by using the terms 'caspofungin,’ 'Candida species,’ 'combination therapy,’ 'antifungal effect,’ and 'novel antifungal agent.’Expert opinion Combination therapy is an empirical strategy for treating refractory Candida infections. Caspofungin has been recommended to treat candidaemia. Caspofungin in combination therapy has some applications, while the efficacy of combination therapy in the treatment of refractory Candida infections needs more study, such as randomized controlled trials. In addition, novel compounds or drugs with potential antifungal activities have been examined, and some of them exhibit synergistic interactions with caspofungin. Thus, the antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy is summarized.

Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of this pathway gives rise to many diseased conditions like cancer, Alzheimer’s, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting the Wnt pathway can be a potential approach to design and develop novel therapeutic classes.

Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized.

The scientific community is working extensively to bring first in the class molecule to the market which targets the Wnt pathway. Lorecivivint, Wnt inhibitor, for the treatment of knee osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules like LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical develfor metastatic breast cancer. Ongoing preclinical and clinical trials will define the role of the Wnt pathway in different therapeutic areas and have opened new opportunities.M-M-R®II (M-M-R II) is routinely used in many countries at 12-15 months with a second dose at 4 to 6 years of age. However, the vaccine may need to be administered at other ages due to delays in the immunization schedule or in certain situations such as outbreaks or international travel. A systematic literature review was conducted to evaluate efficacy, immunogenicity and safety of M-M-R II among 6- to 11-month-olds and persons ≥7 years of age. A search for randomized controlled trials (RCTs) was conducted in 2019 including Medline, Embase and Cochrane CENTRAL. Only one study reported seroconversion rates after one dose in infants at 9 months of age 87.4% (measles), 92.3% (mumps), and 91.2% (rubella); no safety data were reported. Seven studies reported immunogenicity and safety data for M-M-R II at ≥7 years of age. Seroconversion rates ranged from 96%-100% (measles), 65%-100% (mumps), and 91%-100% (rubella). Rates of selected adverse events ranged from 5.2%-8.7% for fever (≥38°C or ≥38.1°C), 2%-33.3% for injection site reactions, and 0.4% for measles/rubella-like rash (one study). No efficacy studies were found. This literature review identified RCTs with evidence to support that M-M-R II is immunogenic and well tolerated in individuals ≥7 years of age.

Many patients sensitized to mites remain symptomatic and uncontrolled despite traditional treatment. Sublingual immunotherapy (SLIT) has demonstrated to reduce the symptoms of allergic rhinitis, the need for additional drug treatments, and to reduce the number of moderate and severe exacerbations in patients with allergic asthma caused by mites that had not been adequately controlled.

After reviewing the most recent literature, a scientific committee composed by 5 pneumologists experts in asthma proposed 41 items that addressed the diagnosis of allergic asthma caused by mites, the role of house dust mite (HDM) SLIT tablet in the therapeutic plan and in the control of the disease, and the profile of patients with asthma candidates for this therapy. Through a modified Delphi method, the items were send to 106 pneumologists involved in asthma to be agreed.

The high degree of consensus reached by the panel of pneumologists shows the importance of HDM SLIT tablet in the treatment of allergic asthma caused by mites, particularly taking into account that they barely use this therapy because until now they did not have a registered treatment with solid evidence of efficacy and safety.

The high degree of consensus reached by the panel of pneumologists shows the importance of HDM SLIT tablet in the treatment of allergic asthma caused by mites, particularly taking into account that they barely use this therapy because until now they did not have a registered treatment with solid evidence of efficacy and safety.Introduction The efficacy and safety of trabectedin/pegylated liposomal doxorubicin (trabectedin/PLD) in patients with recurrent ovarian cancer have been demonstrated in randomized clinical studies. Real-world evidence is a subsequent necessary step for completing information from clinical practice. In the case of trabectedin/PLD, this evidence derives from prospective studies, retrospective analyses, and case series.Areas covered The present narrative review provides the most relevant data about efficacy and safety of trabectedin/PLD in real-world studies, and the interpretation of the experience with trabectedin/PLD in clinical practice for patients with recurrent ovarian cancer.Expert opinion Trabectedin/PLD has a proven antitumor activity that is maintained when administered in advanced lines. Trabectedin/PLD in patients who have relapsed between 6 and 12 months have showed comparable survival outcomes than platinum-based regimens. Moreover, the administration of trabectedin/PLD was associated with a positive survival trend after two previous platinum lines and a significantly superior PFS after subsequent platinum-based therapy. Additionally, the activity of trabectedin seems to be increased in patients with BRCA-mutated ovarian cancer. Overall, real-word evidence has confirmed that trabectedin/PLD is an effective and safe non-platinum combination for advanced lines of chemotherapy in patients with platinum-sensitive recurrent ovarian cancer.

The understanding of antimicrobial utilization patterns is pertinent to successful implementation of the National Action Plans on Antimicrobial Resistance (AMR). There is, however, limited information on antibiotics utilization in Nigeria. This study was undertaken to build on existing information and provide direction for appropriate interventions including Antibiotics Stewardship Programs (ASP).

A Point Prevalence Study (PPS) was conducted in two public urban health facilities in Lagos, Nigeria using a design adapted from the European Center for Disease Prevention and Control (ECDC) and Global-PPS surveys.

The prevalence of antibiotics use was 80.6% administered mostly parenterally (83.1% of total prescriptions) with concerns with extended surgical antibiotics prophylaxis. The mostly used antibiotics in the secondary hospital were parenteral metronidazole (32.4%), ceftriaxone (27.5%), and amoxicillin + clavulanate (8.2%) while the mostly used in the tertiary hospital were ceftriaxone (25.3%), parenteral metronidazole (19.1%), and amoxicillin + clavulanate (9.3%). There was an appreciable lack of specific functional capacities, policies, and processes to promote appropriate antimicrobial use in both hospitals.

There is high rate of antibiotics utilization in these facilities with lack of institutional frameworks and processes for ensuring appropriate antibiotic use. The study provides the information needed to improve future antimicrobial use in hospitals and reduce AMR.

There is high rate of antibiotics utilization in these facilities with lack of institutional frameworks and processes for ensuring appropriate antibiotic use. The study provides the information needed to improve future antimicrobial use in hospitals and reduce AMR.Introduction Disturbances in myocardial lipid metabolism are increasingly being recognized as drivers of the development and progression of heart disease. Therefore, there is a need for treatments that can directly target lipid metabolic defects in heart failure. The membrane-associated glycoprotein CD36 plays a pivotal role in governing myocardial lipid metabolism by mediating lipid signaling and facilitating the cellular uptake of long-chain fatty acids. Emerging evidence suggests that CD36 is a prominent target in the treatment of heart failure.Areas covered This article provides an overview of the key role of CD36 for proper contractile functioning of a healthy heart, its implications in the development of cardiac disease (ischemia/reperfusion, cardiac hypertrophy, and diabetic cardiomyopathy), and its application as a target to normalize cardiac metabolism as part of so-called metabolic modulation therapy.Expert opinion CD36 appears a promising and effective therapeutic target in the treatment of heart failure. Natural compounds and chemical agents known to alter the amount or subcellular distribution of CD36 or inhibit its functioning, should be evaluated for their potency to correct cardiac metabolism and cure heart disease.Research on how to promote vaccination among victims of conflict is scarce. In this study, we conducted an experiment to determine how an artistic illustration communication intervention delivered alongside counseling will influence the behavior intention toward COVID-19 vaccination. The study involved 470 respondents (n = 235 control) and (n = 235 treatment). Variables from social cognitive theory and theory of planned behavior were used to develop the study hypotheses. The result of the study showed that victims of conflict who are exposed to visual messages on COVID-19 vaccination reported greater self-efficacy than those who are not. Also, victims of conflict who are exposed to visual messages on COVID-19 vaccination reported greater task efficacy than those who are not. Furthermore, victims of conflict who are exposed to visual arts on COVID-19 vaccination reported more positive outcome expectancy from the vaccine than those who are not. Finally, the result showed that victims of conflict who are exposed to visual messages on COVID-19 vaccination reported intention to make themselves available for vaccination than those who are not. We discussed these findings and highlighted the nexus between insecurity and health promotion.The combined effects of HLA-allele matching at six-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and CD34+ cell dose on clinical outcomes were analyzed in 1,226 adult cases with single-unit unrelated cord blood transplantation. In the six-loci analysis, low HLA-allele matches did not significantly increase the overall mortality compared to higher matches, whereas in the five-loci analysis excluding HLA-DPB1, they caused a higher overall mortality (HR 1.42, p = .002), possibly due to the graft-versus-leukemia effect of HLA-DPB1 mismatches. A lower CD34+ cell dose ( less then .50 × 105/kg) resulted in higher mortality and lower engraftment; these inferior outcomes were offset by high HLA-allele matches (7-10/10 match), while the inferior outcomes of low HLA-allele matches were improved by increasing the CD34+ cell dose. Consideration of the combined effects of the CD34+ cell dose and HLA matching may expand the options for transplantable units when HLA matching or the CD34+ cell dose is inadequate.