Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

Human CD34+/dim neutrophil-committed progenitors do not differentiate into neutrophil-like CXCR1+CD14+CD16- monocytes in vitro.

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b-CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b-CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101-preNeus, and Lin-CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b-CD38+CD64dimCD115-, CD34+, and CD34dim/- cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/- neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34+CD45RA-/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/-CD45RA+/NCP3s, and CD34dim/-CD45RA-/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or "early neutrophil-committed progenitors," would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16- monocytes. Hence, presuming that neutrophil progenitors/"early neutrophil-committed progenitors" correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers' article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1+CD14+CD16- monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/"early neutrophil-committed progenitors" are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16- monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/"early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.

The slan antigen identifies the prototypical non-classical CD16+-monocytes in human blood.

Introduction: Peripheral monocytes in humans are conventionally divided into classical (CL, CD14++CD16-), intermediate (INT, CD14++CD16+) and non-classical (NC, CD14dim/-CD16++) cells, based on their expression levels of CD14 and CD16. A major fraction of the NC-monocytes has been shown to express the 6-sulfo LacNAc (slan) antigen, but whether these slan+/NC-monocytes represent the prototypical non-classical monocytes or whether they are simply a sub-fraction with identical features as the remainder of NC monocytes is still unclear. Methods: We analyzed transcriptome (by bulk and single cell RNA-seq), proteome, cell surface markers and production of discrete cytokines by peripheral slan+/NC- and slan-/NC-monocytes, in comparison to total NC-, CL- and INT- monocytes. Results: By bulk RNA-seq and proteomic analysis, we found that slan+/NC-monocytes express higher levels of genes and proteins specific of NC-monocytes than slan-/NC-monocytes do. Unsupervised clustering of scRNA-seq data generated one cluster of NC- and one of INT-monocytes, where all slan+/NC-monocytes were allocated to the NC-monocyte cluster, while slan-/NC-monocytes were found, in part (13.4%), within the INT-monocyte cluster. In addition, total NC- and slan-/NC-monocytes, but not slan+/NC-monocytes, were found by both bulk RNA-seq and scRNA-seq to contain a small percentage of natural killer cells. Conclusion: In addition to comparatively characterize total NC-, slan-/NC- and slan+/NC-monocyte transcriptomes and proteomes, our data prove that slan+/NC-, but not slan-/NC-, monocytes are more representative of prototypical NC-monocytes.

Clinical and transcriptomic characteristics of a novel SMARCD2 mutation that disrupts neutrophil maturation and function.

We report a novel case of SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2) mutation successfully treated with hematopoietic stem cell transplantation. The female patient presented delayed cord separation, chronic diarrhea, skin abscesses, skeletal dysmorphisms, and neutropenia with specific granule deficiency. Analysis of the transcriptomic profile of peripheral blood sorted mature and immature SMARCD2 neutrophils showed defective maturation process that associated with altered expression of genes related to specific, azurophilic, and gelatinase granules, such as LTF, CRISP3, PTX3, and CHI3L1. These abnormalities account for the prevalence of immature neutrophils in the peripheral blood, impaired function, and deregulated inflammatory responses.

CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer.

Patterns of receptors for chemotactic factors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represents a selective pathway for the homing of natural killer (NK) cells to the lung. C-C motif chemokine receptor-like 2 (CCRL2) is a nonsignaling seven-transmembrane domain receptor able to control lung tumor growth. CCRL2 constitutive or conditional endothelial cell targeted ablation, or deletion of its ligand chemerin, were found to promote tumor progression in a Kras/p53Flox lung cancer cell model. This phenotype was dependent on the reduced recruitment of CD27- CD11b+ mature NK cells. Other chemotactic receptors identified in lung-infiltrating NK cells by single-cell RNA sequencing (scRNA-seq), such as Cxcr3, Cx3cr1, and S1pr5, were found to be dispensable in the regulation of NK-cell infiltration of the lung and lung tumor growth. scRNA-seq identified CCRL2 as the hallmark of general alveolar lung capillary endothelial cells. CCRL2 expression was epigenetically regulated in lung endothelium and it was upregulated by the demethylating agent 5-aza-2'-deoxycytidine (5-Aza). In vivo administration of low doses of 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells, and reduced lung tumor growth. These results identify CCRL2 as an NK-cell lung homing molecule that has the potential to be exploited to promote NK cell-mediated lung immune surveillance.

Titanium versus zirconia complete arch implant-supported fixed prostheses: A comparison of plaque accumulation.

STATEMENT OF PROBLEM: Complete arch implant-supported zirconia prostheses appear to have less plaque accumulation than titanium prostheses, but a comparison of the materials and the possible influence on the adjacent soft tissue is lacking. PURPOSE: The purpose of this clinical study was to compare the plaque accumulation and soft-tissue inflammation of complete arch implant-supported fixed maxillary prostheses fabricated with either a titanium framework or monolithic zirconia. MATERIAL AND METHODS: Twenty participants with a complete arch implant-supported fixed maxillary prosthesis were enrolled in the study. The participants were divided into 2 groups according to the prosthesis material, titanium (Ti) or zirconia (Zir). The prosthesis had to have been in function for at least 6 months, and participants were examined during at least 3 maintenance appointments at 3-month intervals. Clinical information collected in each appointment included standardized photographs to record the Plaque Area Index (PAI) of the intaglio surface of the prosthesis; clinical parameters including modified Plaque Index (mPI), modified Bleeding Index (mBI), implant mobility (MOB), probing depths ≥5 mm (PD), suppuration (SUP), keratinized tissue band ≥2 mm (KT), and an intraoral photograph of the maxillary arch without the prosthesis to evaluate the redness of the soft tissues. RESULTS: MOB was not present at any implant at any time point. SUP could not be analyzed because it was an infrequent finding. Both groups exhibited significant increases in mBI over time. No significant differences were observed for PD between the groups at any time point. Implants in the Ti group had significantly higher KT values than those in the Zir group; levels remained constant over time for both groups. Zirconia prostheses had slightly lower PAI levels than Ti prostheses. The PAI in the Zir group significantly decreased over time (P=.035); in the Ti group, they remained constant (P=.45). Higher PAI levels were correlated with increased levels of erythema; both groups had a significant decrease in erythema values over time (P=.04). CONCLUSIONS: Zirconia complete arch implant-supported fixed maxillary prostheses displayed a significant decrease in plaque accumulation in individuals who had received periodic maintenance and oral hygiene instructions. Ti prostheses had significantly higher plaque levels than zirconia prostheses at all time points, which was not reduced by maintenance and oral hygiene measures. The present study suggests that patients receiving zirconia prostheses respond well to plaque control measures, while plaque control for those with titanium prostheses may be more challenging.

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion.

COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease.

The Stereoscopic Anisotropy Is Smaller in Elderly Population.

Purpose: The stereoscopic anisotropy is one of the most intriguing phenomena of stereoscopic vision. It shows that the disparity thresholds to detect three-dimensional sinusoidal horizontal corrugations are much lower than for vertical corrugations for spatial frequencies lower than 1 cycles/deg. A recent study has shown that the anisotropy increases during childhood and that visual experience probably plays an important role in its development (Serrano-Pedraza et al., 2016). Here we want to determine the impact that the visual experience has throughout life in the stereoscopic anisotropy. Methods: We performed two experiments testing two age groups of 35 participants each: the young group aged 18 to 45 years and the old group aged 62 to 90 years. We measured disparity thresholds for three-dimensional sinusoidal corrugations of 0.1 cyc/deg, with either vertical or horizontal orientation. Detection thresholds were obtained using Bayesian adaptive staircases. For each participant we computed the anisotropy index by subtracting the thresholds in logarithmic units of the vertical minus the horizontal corrugation. Results: The analyses show that stereo thresholds for vertical corrugations are similar for both groups, however, for horizontal corrugations the thresholds are much lower for the young group. Therefore, the anisotropy was much stronger in the young group (mean, 0.67 ± 0.46) than for the old group (mean, 0.24 ± 0.3). Pearson correlation between the anisotropy index and age shows a negative and significant correlation (r = -0.49; P = 1.83 × 10-5; N = 70), that is, as age advances, the anisotropy decreases. Conclusions: Thus, visual experience plays an important role in the development of stereo vision. Although disparity thresholds for horizontal corrugations in the older group are higher, surprisingly, disparity thresholds for vertical corrugations remain stable and do not change. Therefore, the stereoscopic anisotropy decreases with aging.

CD66b-CD64dimCD115- cells in the human bone marrow represent neutrophil-committed progenitors.

Here we report the identification of human CD66b-CD64dimCD115- neutrophil-committed progenitor cells (NCPs) within the SSCloCD45dimCD34+ and CD34dim/- subsets in the bone marrow. NCPs were either CD45RA+ or CD45RA-, and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b+ neutrophils in both in vitro differentiation and in vivo adoptive transfer experiments. Single-cell RNA-sequencing analysis indicated NCPs fell into four clusters, characterized by different maturation stages and distributed along two differentiation routes. One of the clusters was characterized by an interferon-stimulated gene signature, consistent with the reported expansion of peripheral mature neutrophil subsets that express interferon-stimulated genes in diseased individuals. Finally, comparison of transcriptomic and phenotypic profiles indicated NCPs represented earlier neutrophil precursors than the previously described early neutrophil progenitors (eNePs), proNeus and COVID-19 proNeus. Altogether, our data shed light on the very early phases of neutrophil ontogeny.

Effects of Competitive ELISA-Positive Results of Piroplasmosis on the Performance of Endurance Horses.

Endurance is an increasingly popular equestrian sport. However, in southern Europe, there is a high prevalence of horses that are asymptomatic carriers of equine piroplasmosis (EP), a tick-borne disease that could affect their performance. This study aimed to evaluate the impact and influence of EP on the performance of endurance horses. Blood samples were collected from 40 horses in Extremadura, Spain, before and after a race, in different national elite horse endurance competitions. Hematological and biochemical parameters and EP seroprevalence were analysed by competitive enzyme-linked immunosorbent assay. The global seroprevalence of EP was 70%, with 27 horses testing positive for Theileria equi (67.5%) and three (7.5%) for Babesia caballi, with two of these horses (5%) positive for both. Approximately 82.5% of the horses (33 of 40) completed the competition, with no influence on performance or position achieved in those with subclinical parasitosis. There were also no significant differences in hematological or biochemical values between seropositive and seronegative horses. The data suggest that horses without clinical signs of EP can participate without performance impairment in competitions of up to 80 km. Although it is recommended that longer distance competitions should be further evaluated, this is the first step for decision-making by organizers and participants in this sport.

Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8.

The transcription factors (TFs) that regulate inducible genes in activated neutrophils are not yet completely characterized. Herein, we show that the genomic distribution of the histone modification H3K27Ac, as well as PU.1 and C/EBPß, two myeloid-lineage-determining TFs (LDTFs), significantly changes in human neutrophils treated with R848, a ligand of Toll-like receptor 8 (TLR8). Interestingly, differentially acetylated and LDTF-marked regions reveal an over-representation of OCT-binding motifs that are selectively bound by OCT2/POU2F2. Analysis of OCT2 genomic distribution in primary neutrophils and of OCT2-depletion in HL-60-differentiated neutrophils proves the requirement for OCT2 in contributing to promote, along with nuclear factor κB (NF-κB) and activator protein 1 (AP-1), the TLR8-induced gene expression program in neutrophils. Altogether, our data demonstrate that neutrophils, upon activation via TLR8, profoundly reprogram their chromatin status, ultimately displaying cell-specific, prolonged transcriptome changes. Data also show an unexpected role for OCT2 in amplifying the transcriptional response to TLR8-mediated activation.

Adaptation and transcultural translation into Spanish of the Patient-Rated Tennis Elbow Evaluation Questionnaire.

The purpose of this study was to perform the translation and cross-cultural adaptation of the Patient-Rated Tennis Elbow Evaluation Questionnaire to Spanish language and evaluate its reliability and validity. The translation and cultural adaptation into Spanish was done in accordance with the published guidelines. One-hundred fifty Spanish-speaking patients with unilateral chronic lateral epicondylalgia competed the questionnaire. Test-retest reliability was established by the intraclass correlation coefficient. Internal consistency was established with Cronbach's α. To establish convergent validity, we used the Disabilities of the Arm, Shoulder, and Hand Questionnaire using the Spearman's correlation coefficient. Error estimation in the measurements was calculated with the standard error of measurement. Our results showed a high internal consistency (Cronbach's α = .96) and high test-retest reliability (intraclass coefficient = .9; .89-.94; P < .001). The Spearman's correlation coefficient (r = .765; P < .001) showed a good relationship between the Spanish version of the Patient-Rated Tennis Elbow Evaluation Questionnaire and the Disabilities of the Arm, Shoulder, and Hand Questionnaire. The standard error of measurement (11.9%) showed little variability of measurements. In conclusion, the Spanish version of the Patient-Rated Tennis Elbow Evaluation Questionnaire is a valid and reliable tool that can be used to assess lateral epicondylalgia in Spanish-speaking individuals in order to implement the best treatment and reduce time with pain and disability.

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39.

The IL-12 family of cytokines plays crucial functions in innate and adaptive immunity. These cytokines include heterodimers sharing distinct α (IL-12A, IL-23A, and IL-27A) with two ß (IL-12B and Epstein-Barr virus induced gene 3 [EBI3]) chains, respectively, IL-12 (IL-12B plus IL-12A) and IL-23 (IL-12B plus IL-23A) sharing IL-12B, IL-27 (EBI3 plus IL-27A), IL-35 (EBI3 plus IL-12A), and IL-39 (EBI3 plus IL-23A) sharing EBI3. In this context, we have recently reported that highly pure neutrophils incubated with TLR8 agonists produce functional IL-23. Previously, we showed that neutrophils incubated with LPS plus IFNγ for 20 h produce IL-12. Herein, we investigated whether highly pure, TLR8-activated, neutrophils produce EBI3, and in turn IL-27, IL-35, and IL-39, the IL-12 members containing it. We report that neutrophils incubated with TLR8 ligands, TNFα and, to a lesser extent, LPS, produce and release remarkable amounts of EBI3, but not IL-27A, consequently excluding the possibility for an IL-27 production. We also report a series of unsuccessful experiments performed to investigate whether neutrophil-derived EBI3 associates with IL-23A to form IL-39. Furthermore, we show that neutrophils incubated with IFNγ in combination with either TLR8 or TLR4 ligands express/produce neither IL-12, nor IL-35, due to the inability of IFNγ, contrary to previous findings, to activate IL12A transcription. Even IL-27 was undetectable in supernatants harvested from IFNγ plus R848-treated neutrophils, although they were found to accumulate IL27A transcripts. Finally, by immunohistochemistry experiments, EBI3-positive neutrophils were found in discrete pathologies only, including diverticulitis, cholecystitis, Gorham disease, and Bartonella Henselae infection, implying a specific role of neutrophil-derived EBI3 in vivo.

Comparison of intradialytic versus home-based exercise programs on physical functioning, physical activity level, adherence, and health-related quality of life: pilot study.

Intradialytic exercise (ID) programs are effective and safe for hemodialysis (HD) patients to avoid functional deterioration. However, exercise is not routinely undertaken in most HD units, and we do not know if home-based (HB) programs are as effective as ID programs. The purpose of this study was to compare the effects of 16 weeks of ID exercise versus a HB exercise program for HD patients. A total of 46 patients were randomly assigned to the ID group (n = 24) or HB group (n = 22). They completed a 16-week combined exercise program 3 times/week. We measured physical activity level, physical functioning, depression level, and health-related quality of life at baseline and after 16 weeks. A significant time effect was found in both groups for the physical activity level (p = 0.012). There was also a significant group-time interaction effect for the one-leg standing test (OLST) (p = 0.049) and a significant time effect for the Short Physical Performance Battery (p = 0.013), timed up-and-go test (p = 0.005), sit-to-stand-10 (p = 0.027), right and left hand handgrip (p = 0.044, p < 0.001), one-heel left leg raise (p = 0.019), and 6-minute walking (p = 0.006), depression (p = 0.017). HRQoL remained unchanged. There was no difference between the two interventions on the tested outcomes (besides OLST). Both interventions were associated with positive changes of the physical activity levels and physical function.

Deciphering the fate of slan+ -monocytes in human tonsils by gene expression profiling.

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.

Benefits of adding stretching to a moderate-intensity aerobic exercise programme in women with fibromyalgia: a randomized controlled trial.

OBJECTIVE: To investigate the effects of adding stretching to a moderate-intensity aerobic exercise programme in women with fibromyalgia. DESIGN: Randomized controlled trial. SUBJECTS: Sixty-four female patients who were diagnosed with fibromyalgia syndrome based on the American College of Rheumatology criteria were recruited (mean age: 54.27 ± 6.94 years). INTERVENTIONS: The control group (n = 32) underwent supervised moderate-intensity cycling (50%-70% of the age-predicted maximum heart rate) three times per week for 12 weeks. The experimental group (n = 32) underwent the same exercise programme plus a stretching programme once per week for 12 weeks. MAIN MEASURES: The main measures of this study were sleep quality assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, the impact of fibromyalgia on quality of life assessed by the Fibromyalgia Impact Questionnaire, and pain perception assessed by the visual analogue scale at baseline, after 4 weeks, and after 12 weeks. RESULTS: The experimental group experienced significant improvements at 4-week measure compared with control group: Pittsburgh Sleep Quality Index (P < 0.001); Epworth Sleepiness Scale (P = 0.002); Fibromyalgia Impact Questionnaire (0.93 ± 7.39, P < 0.001); and visual analogue scale (0.52 ± 0.05, P < 0.001). Also at 12-week measure, experimental group experienced significant improvements compared with control group: Pittsburgh Sleep Quality Index (P < 0.001), Epworth Sleepiness Scale (P < 0.001); Fibromyalgia Impact Questionnaire (1.15 ± 9.11, P < 0.001); and visual analogue scale (0.81 ± 0.62, P < 0.001). CONCLUSION: Adding stretching to a moderate-intensity aerobic exercise programme increased sleep quality, decreased the impact of fibromyalgia on the quality of life, and reduced pain compared with just a moderate-intensity aerobic exercise programme in our sample of women with fibromyalgia.

Short-Term Effects of Kinesio Taping in the Treatment of Latent and Active Upper Trapezius Trigger Points: two Prospective, Randomized, Sham-Controlled Trials.

The presence of myofascial trigger points (MTrPs) is one of the most common causes of musculoskeletal problems and may lead to limited professional activity. Among the various treatment methods proposed for MTrPs, Kinesio Taping (KT) is a non-invasive, painless, and less time-consuming method with fewer side effects that has become widely used as a therapeutic tool in a variety of prevention and rehabilitation protocols. The aim of the study was to evaluate the immediate and short-term efficacy of the space correction KT technique in patients with latent or active MTrPs in the upper trapezius muscle. Two parallel randomized sham-controlled trials were simultaneously executed: in trial A, ninety-seven participants with latent MTrPs were randomly assigned to either the KT (n = 51) or sham (n = 46) group; in trial B, thirty-seven participants with active MTrPs were assigned to the KT (n = 20) or sham (n = 17) group. The primary outcome was pressure pain threshold (PPT) in the upper trapezius muscle, measured with algometry. Secondary outcomes included the active range of motion (ROM) of the cervical spine (lateral flexion and rotation), measured with a cervical ROM goniometer. In each trial, two-way ANOVA tests were used to compare the study effects on the outcome measures between the groups, with time serving as the intra-group factor (baseline, immediately, and 72 h after the application) and the intervention type (KT and sham) as the between-group factor. At 72 h, participants receiving KT did not show significant differences in PPT (trial A: mean difference -1.8 N; 95% CI: [-8.1, 4.4], trial B: mean difference -1.2 N; 95% CI: [-7.4, 5.1]), cervical lateral flexion (trial A: mean difference 0.2 degrees; 95% CI: [-2.7, 3.1], trial B: mean difference -2.4 degrees; 95% CI: [-8.4, 3.6]), and cervical rotation (trial A: mean difference 3.7 degrees; 95% CI: [-0.1, 7.5], trial B: mean difference 1.4 degrees; 95% CI: [-5.7, 8.4]), compared to the sham groups. Thus, the results of this study do not support the use of the space correction KT technique to treat patients with latent or active myofascial trigger points in the upper trapezius muscle.

Asociación de las conductas de riesgo en adolescentes. Estrategias para su prevención / Association of adolescent risk behaviors. Prevention strategies

OBJETIVO PRINCIPAL: Analizar la asociación de conductas de riesgo para la salud en el marco de la Teoría de la Conducta Problema. METODOLOGÍA: 524 adolescentes (Medad=16,7; DT = 1,6) cumplimentaron un cuestionario online. Mediante Análisis Factorial Exploratorio se estudiaron seis conductas: borracheras, consumos de tabaco y hachís, búsqueda de sensaciones, sexo sin protección y comportamiento vial inseguro. RESULTADOS PRINCIPALES: En la adolescencia intermedia (edades 16-17) la agrupación resultó compatible con la dimensión "no convencionalidad" identificada por Jessor. Su prevalencia aumentó al finalizar la educación obligatoria. CONCLUSIÓN: Esta agrupación aconseja la prevención simultánea de dichas conductas. Dado que estos comportamientos ayudan a los adolescentes a ganar autonomía personal y relacionarse con sus iguales, su prevención no debe limitarse a informar sobre los riesgos que ocasionan. Promover conductas prosociales (p.ej., participar en la vida escolar y comunitaria) puede ayudar a los adolescentes a vivir de manera saludable su transición evolutiva

OBJECTIVE: To analyze the association of health risk behaviors in the framework of the Problem Behavior Theory. METHODS: 524 adolescents (Mage= 16.7, SD = 1.6) completed an online questionnaire. Through Exploratory Factor Analysis, six behaviors were studied: drunkenness, tobacco and hashish use, sensation-seeking, unsafe sex andunsafe road behavior. RESULTS: From middle adolescence (ages 16-17), behavioral grouping was consistent with "unconventionality" dimension identified by Jessor. Its prevalence increased at the end of compulsory education. CONCLUSION: This grouping suggests the simultaneous prevention of such behaviors. Since these behaviors help adolescents gain personal autonomy and relate to their friends, their prevention should not be limited to reporting the risks that cause. Promoting prosocial behaviors (eg, participating in school and community life) can help adolescents to live their development stage in a healthy way

Accuracy of 3-dimensional-printed Endodontic Surgical Guide: A Human Cadaver Study.

INTRODUCTION: Cone-beam computed tomographic (CBCT)-based 3-dimensional-printed surgical guides, such as those used in implant placement and orofacial surgery, allow for accurate planning and performance of surgical procedures. The objective of this study was to evaluate the accuracy of CBCT-designed surgical guides for use during endodontic surgery. METHODS: A split-mouth design was conducted using 48 roots in a cadaver model. In the experimental group, using information from the preoperative CBCT scans and digital impressions, surgical guides were designed using Blue Sky Bio (Grayslake, IL) planning software and printed using a Form 2 3-dimensional printer (Formlabs, Somerville, MA). The guides were designed to allow for surgical access at 3 mm from the apex of each root with depth control to the lingual or palatal surface of the root. In the control group, surgical access was completed "freehand" by visually approximating measurements from the CBCT scan only. The planned and postoperative CBCT images were superimposed, and the deviation of the surgical access point from the planned target was measured using Invivo software (Anatomage, San Jose, CA). A 2-tailed t test and the Fisher exact test were conducted to compare the deviation in the experimental CBCT-guided group versus the control CBCT-approximated freehand group. RESULTS: The mean deviation for the guided group (1.743 mm) was significantly less than that of the approximated freehand group (2.638 mm, P < .001). Only in 11 of the 24 samples of the control group was surgical access considered clinically successful (within the apical area of the root), whereas all 24 of the experimental samples were considered clinically successful. CONCLUSIONS: Using a CBCT-designed printed surgical guide is a more accurate method for access to the apical portion of the root during surgical endodontics compared with a "freehand" CBCT-approximated method.

Human neutrophils activated via TLR8 promote Th17 polarization through IL-23.

Human neutrophils contribute to the regulation of inflammation via the generation of a range of cytokines that affect all elements of the immune system. Here, we investigated their ability to express some of the members of the IL-12 family after incubation with TLR8 agonists. Highly pure human neutrophils were thus incubated for up to 48 h with or without R848, or other TLR8 agonists, to then measure the expression levels of transcripts and proteins for IL-12 family member subunits by RNA-seq, reverse transcription quantitative PCR, and ELISA. We show a TLR8-mediated inducible expression of IL-12B and IL-23A, but not IL-12A, mRNA, which occurs via chromatin remodeling (as assessed by ChIP-seq), and subsequent production of IL-23 and IL-12B, but no IL-12, proteins. Induction of IL-23 requires endogenous TNF-α, as both mRNA and protein levels were blocked in TLR8-activated neutrophils via a TNF-α-neutralizing Ab. We also show that supernatants from TLR8-activated neutrophils, but not autologous monocytes, induce the differentiation of Th17 cells from naïve T cells in an IL-23-dependent fashion. This study unequivocally demonstrates that highly pure human neutrophils express and produce IL-23, further supporting the key roles played by these cells in the important IL-17/IL-23 network and Th17 responses.