Engineered PROTAC-CID Systems for Mammalian Inducible Gene Regulation.

Gene regulation via chemically induced dimerization (CID) is useful for biomedical research. However, the number, type, versatility, and in vivo applications of CID tools remain limited. Here, we demonstrate the development of proteolysis-targeting chimera-based scalable CID (PROTAC-CID) platforms by systematically engineering the available PROTAC systems for inducible gene regulation and gene editing. Further, we show orthogonal PROTAC-CIDs that can fine-tune gene expression at gradient levels or multiplex biological signals with different logic gating operations. Coupling the PROTAC-CID platform with genetic circuits, we achieve digitally inducible expression of DNA recombinases, base- and prime-editors for transient genome manipulation. Finally, we package a compact PROTAC-CID system into adeno-associated viral vectors for inducible and reversible gene activation in vivo. This work provides a versatile molecular toolbox that expands the scope of chemically inducible gene regulation in human cells and mice.

Differential activation of innate and adaptive lymphocytes during latent or active infection with Mycobacterium tuberculosis.

Most individuals infected with Mycobacterium tuberculosis (Mtb) have latent tuberculosis (TB), which can be diagnosed with tests (such as the QuantiFERON-TB Gold test [QFT]) that detect the production of IFN-γ by memory T cells in response to the Mtb-specific antigens 6 kDa early secretory antigenic target EsxA (Rv3875) (ESAT-6), 10 kDa culture filtrate antigen EsxB (Rv3874) (CFP-10), and Mtb antigen of 7.7 kDa (Rv2654c) (TB7.7). However, the immunological mechanisms that determine if an individual will develop latent or active TB remain incompletely understood. Here we compared the response of innate and adaptive peripheral blood lymphocytes from healthy individuals without Mtb infection (QFT negative) and from individuals with latent (QFT positive) or active TB infection, to determine the characteristics of these cells that correlate with each condition. In active TB patients, the levels of IFN-γ that were produced in response to Mtb-specific antigens had high positive correlations with IL-1ß, TNF-α, MCP-1, IL-6, IL-12p70, and IL-23, while the proinflammatory cytokines had high positive correlations between themselves and with IL-12p70 and IL-23. These correlations were not observed in QFT-negative or QFT-positive healthy volunteers. Activation with Mtb-soluble extract (a mixture of Mtb antigens and pathogen-associated molecular patterns [PAMPs]) increased the percentage of IFN-γ-/IL-17-producing NK cells and of IL-17-producing innate lymphoid cell 3 (ILC3) in the peripheral blood of active TB patients, but not of QFT-negative or QFT-positive healthy volunteers. Thus, active TB patients have both adaptive and innate lymphocyte subsets that produce characteristic cytokine profiles in response to Mtb-specific antigens or PAMPs. These profiles are not observed in uninfected individuals or in individuals with latent TB, suggesting that they are a response to active TB infection.

Under-exposure to official matches is associated with muscle injury incidence in professional footballers.

External workload from matches is considered one of the most important muscle injury risk factors for football teams. However, there is scarce published evidence to support this belief. This study examined whether a particular profile of external match workload existed prior to a muscle injury. A total of 144 professional football players belonging to 2 teams were monitored over three seasons. For each muscle injury, a profile of external workload variables was determined for 5 to 8 games and expressed as: time playing exposure, total distance (TD) covered and high-speed running (HSR) covered. In addition, acute:chronic workload ratio (ACWR) was calculated. Sixty players (41.6%) reported a total of 86 muscle injuries during the three seasons. Muscle injuries occurred principally in matches (79.1%), the hamstring being the most affected muscle (44.1%). Injured players displayed substantially lower accumulated exposure time (ES = 0.45), TD (ES = 0.45) and HSR (ES = 0.39) in comparison with uninjured players in the last 5 games prior to injury. Compared to the uninjured players, ACWR for exposure (ES = -0.29/0.02) and running load (ES = -0.24/0.00) did not differ between match 5 and 2 prior to the injury, although uninjured players displayed a substantially greater ACWR in all 3 variables (ES = 0.31/0.35) than injured players in match 1 prior to the injury. Lower playing exposure (minutes played) and associated reduced running distances (TD and HSR) were observed in injured football players. Being under-loaded in official games could be a mediator for muscle injury in this cohort of elite football players.

Implant treatment in immunosuppressed renal transplant patients: A prospective case-controlled study.

OBJECTIVES: The aim of this clinical study was to evaluate long-term outcomes of implant therapy in a cohort of immunosuppressed renal transplant patients compared with a matched control group. MATERIAL AND METHODS: Pharmacologically immunosuppressed renal transplant patients received dental implant treatment between 2001 and 2011. Periodontal, clinical and radiographic parameters were prospectively measured with a mean follow-up of 116.8 months (range from 84 to 192 months). A matched controlled non-transplant sample receiving similar implant treatment in the same time was included as a control group. RESULTS: Implant survival rate was over 98% in both test and control groups (100% and 98.84%, respectively). Peri-implant mucositis was diagnosed in 46.80% of the implants in the study group and in 48.80% in the control group. Peri-implantitis occurred in 5.10% of the implants in the study group and in 8.10% of the controls. Wound healing and post-operative pain were similar in both groups. CONCLUSIONS: Despite the limitations of this study, pharmacological immunosuppression in renal transplant patients did not affect implant outcomes. Renal transplant patients should be carefully controlled periodically after implant treatment. CLINICAL IMPLICATIONS: The results from this investigation justify the use of dental implants for the dentalrehabilitation of immunosuppressed patients after renal transplantation provided they follow the necessarylong-term monitoring and regular maintenance of their oral and systemic health.

Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective-controlled study.

OBJECTIVES: The main objective of this prospective study was to evaluate the long-term outcome of implant therapy in liver transplant patients (LTP). The secondary goal was to assess several implant- and patient-dependent variables, such as peri-implantitis (PI), peri-implant mucositis (PIM), bone loss (BL), and immediate postoperative complications. MATERIAL AND METHODS: Two groups, including 16 pharmacologically immunosuppressed LTP and 16 matched controls, received 52 and 54 implants, respectively, between 1999 and 2008. After evaluating the postoperative healing, a mean follow-up of more than 8 years was carried out, and radiographic, clinical, and periodontal parameters were recorded to evaluate implant survival and implant- and patient-dependent outcomes. RESULTS: The early postsurgical complications were similar in both groups. Implant survival rate was 100% in the LTP group and 98.15% in the CG. PIM was diagnosed in 35.42% of the implants and 64.29% of the patients of LTP group (LTPG) and in 43.40% of the implants and 56.25% of the patients in the CG. PI was detected in 4.17% of the implants and 7.10% of the patients in the LTPG and in 9.43% of the implants and 18.80% of the patients in the CG. CONCLUSION: Pharmacologically immunosuppression in liver transplant patients was not a risk factor for implant failure, nor for the incidence of peri-implant diseases. Liver transplant is not a contraindication for dental implant treatment, although these patients should be carefully monitored during follow-up care.

Successful treatment of oral pemphigus vulgaris in an insulin-dependant geriatric patient.

OBJECTIVE: To present a clinical report of a patient treated with corticosteroids for oral pemphigus vulgaris (PV) lesions. BACKGROUND: PV is the type of pemphigus that most often affects the oral mucosa and tends not to appear in elderly people. METHODS: Two biopsies were needed for diagnosis. She was treated with oral prednisone and topically with 0.05% clobetasol propionate. CONCLUSION: An early diagnosis and treatment is needed for a good prognosis, especially in elderly patients with multiple systemic pathology.

"You Are Not Wrong About Getting Strong:" An Insight Into the Impact of Age Group and Level of Competition on Strength in Spanish Football Players.

OBJECTIVE: This study aimed to compare the maximum and rapid force production of Spanish football players and explore the differences between age group and level of competition. METHODS: A cross-sectional study was developed to evaluate the peak force (PF), relative PF, and rate of force development over 250 ms (RFD0-250) during the isometric midthigh pull between groups of football players based on age group (senior vs junior) and level of competition (national vs regional). Using a portable isometric rig, 111 football players performed 2 isometric midthigh-pull trials on a force plate. Two-way analysis of variance with Bonferroni post hoc correction was applied, and statistical significance was set at P ≤ .05. The PF, relative PF, and RFD0-250 0, 25, 50, 75, and 100 percentiles were also calculated and descriptively reported, separated by age group and level of competition. RESULTS: The analysis of variance revealed a significant main effect of the level of competition for the PF (P < .001), relative PF (P = .003), and RFD0-250 (P < .001). There was a significant main effect of age group for the PF (P < .001). There was a significant interaction effect of the age group × level of competition for relative PF (P = .014). National players were stronger than regional players on the PF and RFD0-250 (P < .001). Senior players were stronger than junior players for the PF (P < .001). CONCLUSIONS: Maximum and rapid force production are crucial for Spanish football players as they progress in both level of competition and age group. Practitioners should encourage young football players to prioritize strength development to improve their athletic performance.

Dental treatment under general anesthesia in patients with severe intellectual disability at the Gregorio Marañón General University Hospital: a 10-year retrospective study.

OBJECTIVES: There is a high demand for dental treatment in a hospital setting for patients with severe intellectual disability (ID), due to their inability to cooperate. The objective was to determine the types of dental treatment carried out on patients with severe ID, as well as the possibility of performing clinical and radiographic examinations prior to treatment and to identify their characteristics. METHOD AND MATERIALS: A retrospective observational study was performed, based on the medical histories of patients with severe ID or a disability included in the portfolio of dental services of Community of Madrid, who underwent dental treatment at the Stomatology Service of the Gregorio Marañón General University Hospital from the year 2009 to 2019. Data on age, sex, etiology of disability, and dental treatment were obtained. RESULTS: A total of 1,845 patients were included. The type of disability in the majority of cases was unknown, followed by encephalopathy, cerebral paralysis, and Down syndrome. In total, 8,439 dental extractions were performed on 1,548 patients (83.9%). Clinical and radiographic exploration were carried out on 874 patients (47.4%). CONCLUSIONS: Ultrasonic scaling was the most frequently performed treatment in patients. Dental extractions were the next most common treatment. An increase in age showed a higher demand for surgical procedures and extractions. Over half of the patients (52.6%) did not tolerate clinical or radiographic examinations.

Modulation of Monocyte Response by MicroRNA-15b/106a/374a During Antibody-mediated Rejection in Kidney Transplantation.

BACKGROUND: Increasing evidence suggest that microRNAs are involved in the physiopathology of acute or chronic renal disease. In kidney transplantation, as key regulators of cellular homeostasis, microRNAs may be involved in the regulation of immune cell function and the allograft response. Here, we investigated the change in circulating microRNA expression profile and their involvement in the profound transcriptional changes associated with antibody-mediated rejection (AMR). METHODS: Blood samples were collected at the time of the 710 kidney allograft biopsies at 4 European transplant centers. Messenger RNA and microRNA profiling analyses were performed in a discovery-to-validation study within 3 independent cohorts encompassing N = 126, N = 135, and N = 416 patients, respectively. RESULTS: Compared with samples with no AMR, 14 microRNAs were significantly decreased in AMR samples. Among them, expression levels of microRNA-15b, microRNA-106a, and microRNA-374a gradually decreased with the severity of AMR lesions. From their in silico-predicted target genes, a high proportion proved to be significantly upregulated in the paired transcriptomic analysis. Gene ontology analyses of microRNA-15b/-106a/-374a suggested enrichment in myeloid-related pathways, which was further refined by in silico and ex vivo transcriptomic analyses, showing a specific origin from classical CD14 + monocytes. Finally, human CD14 + monocytes were subjected to transduction by antago-microRNAs to mimic AMR pathology. MicroRNA-15b/-106a/-374a impairment resulted in cellular activation with an increased expression of CD69, CRIM1, IPO7, and CAAP1, direct and common targets of the 3 microRNAs. CONCLUSIONS: Together, our data provide new insights into circulating microRNAs as markers and key players in AMR, and they suggest monocyte involvement in this process.

Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response.

Gain-of-function mutations in stimulator of interferon gene 1 (STING1) result in STING-associated vasculopathy with onset in infancy (SAVI), a severe autoinflammatory disease. Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which have roles in the onset and severity of SAVI and remain to be elucidated. To this end, we performed a multi-omics comparative analysis of peripheral blood mononuclear cells (PBMCs) and plasma from SAVI patients and healthy controls, combined with a dataset of healthy PBMCs treated with IFN-ß. Our data reveal a subset of disease-associated monocyte, expressing elevated CCL3, CCL4, and IL-6, as well as a strong integrated stress response, which we suggest is the result of direct PERK activation by STING. Cell-to-cell communication inference indicates that these monocytes lead to T cell early activation, resulting in their senescence and apoptosis. Last, we propose a transcriptomic signature of STING activation, independent of type I IFN response.

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. METHODS: To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. FINDINGS: The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. CONCLUSIONS: These results provide potential for a better understanding of disease pathophysiology. FUNDING: Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d'Excellence ''Milieu Intérieur," grant ANR-10-LABX-69-01; ANR-flash Covid19 "AIROCovid" and "CoVarImm"), Institut National de la Santé et de la Recherche Médicale (INSERM), and the "URGENCE COVID-19" fundraising campaign of Institut Pasteur.

Effects of muscular injuries on the technical and physical performance of professional soccer players.

Introduction: The aim of this study was to determine the effects of muscular injuries in the lower limbs on the technical and physical performance of professional soccer players when they return to the league competition. Methods: Seventy-six muscular injuries incurred by Spanish male professional soccer players (Age: 27.5 ± 3.5 years) were analyzed during two consecutive competitive seasons: 2014-2015 and 2015-2016. The players' performance was studied during Spanish First Division competitive matches using a multi-camera computerized tracking system (Mediacoach Desktop). Results: After muscular injury relative total distance covered in sprints decreased by 8.6 ± 30.2% (P = 0.013) in the first half and 7.7 ± 36.6% (P = 0.038) in the second half. Similarly, maximal running speed decreased by 2.78 ± 6.91 km.h-1 (pre: 27.3 ± 6.4 km.h-1vs. post: 24.5 ± 6.6 km.h-1, P = 0.013) in the first half, and 1.50 ± 5.68 km.h-1 (29.1 ± 3.9 km.h-1vs. 27.6 ± 5.3 km.h-1, P = 0.043) in the second half. Muscle injury also affected technical performance significantly decreasing successful passes (P = 0.045). There were no differences in the number of possession gains (P = 0.277), and possession losses (P = 0.178). Conclusions: After a moderate or severe muscular injury (causing >8 days lay off), player performance is significantly lower in high-intensity efforts and technical skills such as sprints, maximal running speed, or successful passes.

Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4+ T Lymphocytes.

Dendritic cells (DCs) serve a key function in host defense, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. DCs express cell surface receptors for HIV-1 entry, but are relatively resistant to productive viral replication. They do, however, facilitate infection of co-cultured T-helper cells through a process referred to as trans-infection. We previously showed that tetraspanin 7 (TSPAN7), a transmembrane protein, is involved, through positive regulation of actin nucleation, in the transfer of HIV-1 from the dendrites of immature monocyte-derived DCs (iMDDCs) to activated CD4+ T lymphocytes. Various molecular mechanisms have been described regarding HIV-1 trans-infection and seem to depend on DC maturation status. We sought to investigate the crosstalk between DC maturation status, TSPAN7 expression and trans-infection. We followed trans-infection through co-culture of iMDDCs with CD4+ T lymphocytes, in the presence of CXCR4-tropic replicative-competent HIV-1 expressing GFP. T cell infection, DC maturation status and dendrite morphogenesis were assessed through time both by flow cytometry and confocal microscopy. Our previously described TSPAN7/actin nucleation-dependent mechanism of HIV-1 transfer appeared to be mostly observed during the first 20 h of co-culture experiments and to be independent of HIV replication. In the course of co-culture experiments, we observed a progressive maturation of MDDCs, correlated with a decrease in TSPAN7 expression, a drastic loss of dendrites and a change in the shape of DCs. A TSPAN7 and actin nucleation-independent mechanism of trans-infection, relying on HIV-1 replication, was then at play. We discovered that TSPAN7 expression is downregulated in response to different innate immune stimuli driving DC maturation, explaining the requirement for a TSPAN7/actin nucleation-independent mechanism of HIV transfer from mature MDDCs (mMDDCs) to T lymphocytes. As previously described, this mechanism relies on the capture of HIV-1 by the I-type lectin CD169/Siglec-1 on mMDDCs and the formation of a "big invaginated pocket" at the surface of DCs, both events being tightly regulated by DC maturation. Interestingly, in iMDDCs, although CD169/Siglec-1 can capture HIV-1, this capture does not lead to HIV-1 transfer to T lymphocytes.

A Comprehensive Map of the Monocyte-Derived Dendritic Cell Transcriptional Network Engaged upon Innate Sensing of HIV.

Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During HIV-1 infection, human dendritic cells (DCs) can detect the virus through an innate sensing pathway, leading to antiviral interferon and DC maturation. Here, we develop an iterative experimental and computational approach to map the HIV-1 innate response circuitry in monocyte-derived DCs (MDDCs). By integrating genome-wide chromatin accessibility with expression kinetics, we infer a gene regulatory network that links 542 transcription factors with 21,862 target genes. We observe that an interferon response is required, yet insufficient, to drive MDDC maturation and identify PRDM1 and RARA as essential regulators of the interferon response and MDDC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting complexity and cooperativity in the regulatory circuit controlling the response to infection.

Data on spatio-temporal patterns of wild fruit harvest from the economically important palm Mauritia flexuosa in the Peruvian Amazon.

These data are the foundation of the analyses and results published in the article "Spatio-temporal patterns of Mauritia flexuosa fruit extraction in the Peruvian Amazon: Implications for conservation and sustainability" (Horn et al., 2018) [1]. Here we include data on the volume of M. flexuosa fruit arriving in the city of Iquitos, Peru from the surrounding region. This includes the amount of fruit (in sacks and kg), the date of entry into Iquitos, the point of embarkation (watershed and coordinates), the method of transportation and the point of entry into Iquitos. Data is provided in a number of formats, including data tables, Google Earth KML files and summary tables by watershed and/or month.

Coincidencia de Rhupus y embarazo. Reporte de caso / Coincidence of Rhupus and pregnancy. Case report

Resumen ANTECEDENTES: Si bien el lupus eritematoso sistémico y la artritis reumatoide son enfermedades suficientemente descritas, no lo es la asociación de estas, que se denomina rhupus, que hace referencia a la manifestación clínica resultante de ambas enfermedades enmascaradas que dificulta el diagnóstico y tratamiento. CASO CLÍNICO: Paciente de 37 años que inició con un cuadro con características de lupus eritematoso sistémico y artritis reumatoide hacía 16 años. Se encontró con alteraciones en los estudios de laboratorio y con hallazgos radiológicos que apoyaron el cuadro de rhupus. Por lo anterior se documenta la evolución de este padecimiento, que coincide con su embarazo y después de éste. CONCLUSIONES: La aparición simultánea de lupus eritematoso sistémico y artritis reumatoide, aun cuando fue reportada desde hace décadas, es una enfermedad rara en frecuencia, por lo que hay escasa información del rhupus solo y más aún en coincidencia con el embarazo.

Abstract BACKGROUND: Although systemic lupus erythematosus and rheumatoid arthritis are sufficiently described diseases, the association of these is not, and is called rhupus, which refers to the clinical manifestation resulting from both diseases masked, making diagnosis and treatment difficult. CLINICAL CASE: 37-year-old patient who started with a clinical picture with features of systemic lupus erythematosus and rheumatoid arthritis 16 years ago. She was found to have alterations in laboratory studies and radiological findings that supported the diagnosis of rheupus. Therefore, the evolution of this condition is documented, which coincides with and after her pregnancy. CONCLUSIONS: The simultaneous occurrence of systemic lupus erythematosus and rheumatoid arthritis, even though it was reported decades ago, is a rare disease in frequency, so there is scarce information on rhupus alone and even more so in coincidence with pregnancy.

Extracellular Vesicles Released from Mycobacterium tuberculosis-Infected Neutrophils Promote Macrophage Autophagy and Decrease Intracellular Mycobacterial Survival.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100-1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication. We previously demonstrated that human neutrophils infected in vitro with Mtb H37Rv release EVs (EV-TB), but the effect of these EVs on other cells relevant for the control of Mtb infection, such as macrophages, has not been completely analyzed. In this study, we characterized the EVs produced by non-stimulated human neutrophils (EV-NS), and the EVs produced by neutrophils stimulated with an activator (PMA), a peptide derived from bacterial proteins (fMLF) or Mtb, and observed that the four EVs differed in their size. Ligands for toll-like receptor (TLR) 2/6 were detected in EV-TB, and these EVs favored a modest increase in the expression of the co-stimulatory molecules CD80, a higher expression of CD86, and the production of higher amounts of TNF-α and IL-6, and of lower amounts of TGF-ß, in autologous human macrophages, compared with the other EVs. EV-TB reduced the amount of intracellular Mtb in macrophages, and increased superoxide anion production in these cells. TLR2/6 ligation and superoxide anion production are known inducers of autophagy; accordingly, we found that EV-TB induced higher expression of the autophagy-related marker LC3-II in macrophages, and the co-localization of LC3-II with Mtb inside infected macrophages. The intracellular mycobacterial load increased when autophagy was inhibited with wortmannin in these cells. In conclusion, our results demonstrate that neutrophils produce different EVs in response to diverse activators, and that EV-TB activate macrophages and promote the clearance of intracellular Mtb through early superoxide anion production and autophagy induction, which is a novel role for neutrophil-derived EVs in the immune response to Mtb.

Neurodynamic mobilization and foam rolling improved delayed-onset muscle soreness in a healthy adult population: a randomized controlled clinical trial.

OBJECTIVES: Compare the immediate effects of a Neurodynamic Mobilization (NM) treatment or foam roller (FR) treatment after DOMS. DESIGN: Double blind randomised clinical trial. SETTING: The participants performed 100 drop jumps (5 sets of 20 repetitions, separated by 2 min rests) from a 0.5-m high box in a University biomechanics laboratory to induce muscle soreness. The participants were randomly assigned in a counter-balanced fashion to either a FR or NM treatment group. PARTICIPANTS: Thirty-two healthy subjects (21 males and 11 females, mean age 22.6 ± 2.2 years) were randomly assigned into the NM group (n = 16) or the FR group (n = 16). MAIN OUTCOME MEASURES: The numeric pain rating scale (NPRS; 0-10), isometric leg strength with dynamometry, surface electromyography at maximum voluntary isometric contraction (MVIC) and muscle peak activation (MPA) upon landing after a test jump were measured at baseline, 48 h after baseline before treatment, and immediately after treatment. RESULTS: Both groups showed significant reduction in NPRS scores after treatment (NM: 59%, p < .01; FR: 45%, p < .01), but no difference was found between them (p > .05). The percentage change improvement in the MVIC for the rectus femoris was the only significant difference between the groups (p < 0.05) at post-treatment. After treatment, only the FR group had a statistically significant improvement (p < 0.01) in strength compared to pre-treatment. CONCLUSION: Our results illustrate that both treatments are effective in reducing pain perception after DOMS whereas only FR application showed differences for the MVIC in the rectus femoris and strength.

Surgical Treatment of a Peripheral Ossifying Fibroma and Reconstruction with a Porcine Collagen Matrix: A Case Report.

A 35-year-old woman was referred to the Department of Oral Medicine and Orofacial Surgery after several recurrences of an ossifying fibroma (OF) that affected the free and attached gingiva of the maxillary right central incisor. Surgery was performed with a complete excision of the lesion together with the surrounding healthy tissue up to the bone. To guide the healing of the anterior esthetic framework and the excised tissues, a porcine collagen matrix as an alternative to connective tissue graft was used. After an 18-month follow-up, the lesion had not recurred and keratinized gingiva had formed around the area.

Prevalence of multiple sclerosis in Latin America and its relationship with European migration.

Multiple sclerosis (MS) is a chronic, degenerative autoimmune inflammatory disease of the central nervous system. The prevalence is different in every continent, changing according to geographical and environmental characteristics. The areas with the highest prevalence in the world are Europe and North America. In Latin America, the prevalence is higher in areas where there was greater European migration, as in the case of Argentina, Chile, Brazil, Uruguay and Mexico, and there have been no identified cases amongst native Indian populations. It should be considered that environmental factors may influence the prevalence of MS in Latin America, and it seems as if there are protective factors such as exposure to ultraviolet radiation and the presence of parasitosis.