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T cell-mediated islet destruction is a hallmark of autoimmune diabetes. Here, we examined the dynamics and pathogenicity of CD4+ T cell responses to four different insulin-derived epitopes during diabetes initiation in non-obese diabetic (NOD) mice. Single-cell RNA sequencing of tetramer-sorted CD4+ T cells from the pancreas revealed that islet-antigen-specific T cells adopted a wide variety of fates and required XCR1+ dendritic cells for their activation. Hybrid-insulin C-chromogranin A (InsC-ChgA)-specific CD4+ T cells skewed toward a distinct T helper type 1 (Th1) effector phenotype, whereas the majority of insulin B chain and hybrid-insulin C-islet amyloid polypeptide-specific CD4+ T cells exhibited a regulatory phenotype and early or weak Th1 phenotype, respectively. InsC-ChgA-specific CD4+ T cells were uniquely pathogenic upon transfer, and an anti-InsC-ChgA:IAg7 antibody prevented spontaneous diabetes. Our findings highlight the heterogeneity of T cell responses to insulin-derived epitopes in diabetes and argue for the feasibility of antigen-specific therapies that blunts the response of pathogenic CD4+ T cells causing autoimmunity.
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Linfócitos T CD4-Positivos , Cromogranina A , Diabetes Mellitus Tipo 1 , Insulina , Camundongos Endogâmicos NOD , Animais , Diabetes Mellitus Tipo 1/imunologia , Cromogranina A/metabolismo , Cromogranina A/imunologia , Camundongos , Insulina/metabolismo , Insulina/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Células Th1/imunologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/metabolismo , Peptídeos/imunologia , Peptídeos/metabolismoRESUMO
Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the aortic arch are not DCs but instead specialized aortic intima resident macrophages (MacAIR) that depend upon colony-stimulating factor 1 and are sustained by local proliferation. Although MacAIR comprise the earliest foam cells in plaques, their proliferation during plaque progression is limited. After months of hypercholesterolemia, their presence in plaques is overtaken by recruited monocytes, which induce MacAIR-defining genes. These data redefine the lineage of intimal phagocytes and suggest that proliferation is insufficient to sustain generations of macrophages during plaque progression.
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Aorta/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Placa Aterosclerótica/imunologia , Túnica Íntima/imunologia , Animais , Diferenciação Celular , Linhagem da Célula , Movimento Celular , Proliferação de Células , Células Cultivadas , Colesterol/metabolismo , Progressão da Doença , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Parabiose , FagocitoseRESUMO
BACKGROUND: There has been a recent push to transition procedures previously performed at hospital-based outpatient surgical departments (HOPDs) to ambulatory surgery centers (ASCs). However, limited data regarding differences in early postoperative complications and care utilization (eg, emergency department visits and unplanned admissions) may drive increased overall costs or worse outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to examine differences in early 90-day adverse outcomes and postoperative emergency department visits associated with shoulder surgeries excluding arthroplasties that were performed in HOPDs and ASCs in a closed military health care system. We hypothesized that there would be no difference in outcomes between treatment settings. METHODS: We retrospectively evaluated the records for 1748 elective shoulder surgeries from 2015 to 2020. Patients were considered as 1 of 2 cohorts depending on whether they underwent surgery in an ASC or HOPD setting. We evaluated groups for differences incomplexity, surgical time, and medical risk. Outcome measures were emergency department visits, unplanned hospital admissions, and complications within the first 90 days after surgery. RESULTS: There was no difference in 90-day postoperative emergency department visits between procedures performed at HOPDs (n = 606) and ASCs (n = 1142). There was a slight increase in rate of unplanned hospital admission within 90 days after surgery in the HOPD cohort, most commonly for pain or overnight observation. The surgical time was significantly shorter (105 vs. 119 minutes, P < .01) at the ASC, but there was no difference in case complexity between the cohorts (P = .28). DISCUSSION/CONCLUSION: Our results suggest that in appropriate patients, surgery in ASCs can be safely leveraged for its costs savings, efficiency, patient satisfaction, decreases in operative time, and potentially decreased resource utilization both during surgery and in the early postoperative period.
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In this study, the influence of an amino silane (3-(2-aminoethylamino)-propyldimethoxymethylsilane, AEAPS) on the interfacial structure and adhesion of butyl acrylate/methyl methacrylate copolymers (BAMMAs) to silica was investigated by sum frequency generation vibrational spectroscopy (SFG). Small amounts of methacrylic acid, MAA, were included in the BAMMA polymerizations to assess the impact of carboxylic acid functionality on the glass interface. SFG was used to probe the O-H and CâO groups of incorporated MAA, ester CâO groups of BAMMA, and CH groups from all species at the silica interfaces. The addition of AEAPS resulted in a significant change in the molecular structure of the polymer at the buried interface with silica due to specific interactions between the BAMMA polymers and silane. SFG results were consistent with the formation of ionic bonds between the primary and secondary amines of the AEAPS tail group and the MAA component of the polymer, as evidenced by the loss of the MAA O-H and CâO signals at the interface. It is extensively reported in the literature that methoxy head groups of an amino silane chemically bind to the silanols of glass, leaving the amine groups available to react with various chemical functionalities. Our results are consistent with this scenario and support an adhesion promotion mechanism of amino silane with various aspects: (1) the ionic bond formation between the tail amine group and acid functionality on BAMMA, (2) the chemical coupling between the silane head group and glass, (3) migration of more ester CâO groups to the interface with order, and (4) disordering or reduced levels of CH groups at the interface. These results are important for better understanding of the mechanisms and effect of amino silanes on the adhesion between acrylate polymers and glass substrates in a variety of applications.
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Adesivos , Silanos , Adesivos/química , Aminas , Ésteres , Polímeros , Silanos/química , Dióxido de SilícioRESUMO
Optimal ex vivo expansion protocols of tumor-specific T cells followed by adoptive cell therapy must yield T cells able to home to tumors and effectively kill them. Our previous study demonstrated ex vivo activation in the presence of IL-12-induced optimal CD8+ T cell expansion and melanoma regression; however, adverse side effects, including autoimmunity, can occur. This may be due to transfer of high-avidity self-specific T cells. In this study, we compared mouse low- and high-avidity T cells targeting the tumor Ag tyrosinase-related protein 2 (TRP2). Not surprisingly, high-avidity T cells provide superior tumor control, yet low-avidity T cells can promote tumor regression. The addition of IL-12 during in vitro expansion boosts low-avidity T cell responsiveness, tumor regression, and prevents T cell exhaustion. In this study, we demonstrate that IL-12-primed T cells are resistant to PD-1/PD-L1-mediated suppression and retain effector function. Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while simultaneously increasing KLRG1. Using intravital imaging, we also determined that high-avidity T cells have sustained contacts with intratumoral dendritic cells and tumor targets compared with low-avidity T cells. However, with Ag overexpression, this defect is overcome, and low-avidity T cells control tumor growth. Taken together, these data illustrate that low-avidity T cells can be therapeutically beneficial if cocultured with IL-12 cytokine during in vitro expansion and highly effective in vivo if Ag is not limiting. Clinically, low-avidity T cells provide a safer alternative to high-avidity, TCR-engineered T cells, as IL-12-primed, low-avidity T cells cause less autoimmune vitiligo.
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Linfócitos T CD8-Positivos/imunologia , Interleucina-12/imunologia , Ativação Linfocitária/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Animais , Antígenos de Neoplasias/imunologia , Autoimunidade/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia Adotiva/métodos , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
PURPOSE OF REVIEW: Programmed death-1 (PD-1) is an inhibitory receptor that controls T and B cell proliferation and function through interacting with its ligand PD-L1 or PD-L2. PD-1/PD-L1 blockade reboots anti-tumor immunity and is currently used to treat > 15 different types of cancer. However, the response rate is not at 100% and some patients relapse. Importantly, up to 37% of patients treated with PD-1/PD-L1 blocking antibodies develop immune-related adverse events, including overt autoimmunity, such as type 1 diabetes (T1D). Herein, we discuss the role of PD-1, PD-L1, and PD-L2 signaling in pre-clinical models of T1D, including recent work from our laboratory. RECENT FINDINGS: We highlight ongoing efforts to harness PD-1/PD-L1 signaling and treat autoimmunity. We also evaluate studies aimed at defining biomarkers that could reliably predict the development of immune-related adverse events after clinical PD-1/PD-L1 blockade. With increasing use of PD-1 blockade in the clinic, onset of autoimmunity is a growing health concern. In this review, we discuss what is known about the role of PD-1 pathway signaling in T1D and comment on ongoing efforts to identify patients at risk of T1D development after PD-1 pathway blockade.
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Diabetes Mellitus Tipo 1 , Neoplasias , Autoimunidade , Humanos , Ativação Linfocitária , Transdução de SinaisRESUMO
The performance of nonionic surfactants is mediated by the interfacial interactions at the solid-liquid interface. Here we applied sum frequency generation (SFG) vibrational spectroscopy to probe the molecular structure of the silica-nonionic surfactant solution interface in situ, supplemented by quartz crystal microbalance with dissipation monitoring (QCM-D) and molecular dynamics (MD) simulations. The combined studies elucidated the effects of nonionic surfactant solution concentration, surfactant composition, and rinsing on the silica-surfactant solution interfacial structure. The nonionic surfactants studied include ethylene-oxide (EO) and butylene oxide (BO) components with different ratios. It was found that the CH groups of the surfactants at the silica-surfactant solution interfaces are disordered, but the interfacial water molecules are ordered, generating strong SFG OH signals. Solutions with higher concentrations of surfactant lead to a slightly higher amount of adsorbed surfactant at the silica interface, resulting in more water molecules being ordered at the interface, or a higher ordering of water molecules at the interface, or both. MD simulation results indicated that the nonionic surface molecules preferentially adsorb onto silanol sites on silica. A surfactant with a higher EO/BO ratio leads to more water molecules being ordered and a higher degree of ordering of water molecules at the silica-surfactant solution interface, exhibiting stronger SFG OH signal, although less material is adsorbed according to the QCM-D data. A thin layer of surfactants remained on the silica surface after multiple water rinses. To the best of our knowledge, this is the first time the combined approaches of SFG, QCM-D and MD simulation techniques have been applied to study nonionic surfactants at the silica-solution interface, which enhances our understanding on the interfacial interactions between nonionic surfactants, water and silica. The knowledge obtained from this study can be helpful to design the optimal surfactant concentration and composition for future applications.
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Programmed death-1 (PD-1) inhibits T and B cell function upon ligand binding. PD-1 blockade revolutionized cancer treatment, and although numerous patients respond, some develop autoimmune-like symptoms or overt autoimmunity characterized by autoantibody production. PD-1 inhibition accelerates autoimmunity in mice, but its role in regulating germinal centers (GC) is controversial. To address the role of PD-1 in the GC reaction in type 1 diabetes, we used tetramers to phenotype insulin-specific CD4+ T and B cells in NOD mice. PD-1 or PD-L1 deficiency, and PD-1 but not PD-L2 blockade, unleashed insulin-specific T follicular helper CD4+ T cells and enhanced their survival. This was concomitant with an increase in GC B cells and augmented insulin autoantibody production. The effect of PD-1 blockade on the GC was reduced when mice were treated with a mAb targeting the insulin peptide:MHC class II complex. This work provides an explanation for autoimmune side effects following PD-1 pathway inhibition and suggests that targeting the self-peptide:MHC class II complex might limit autoimmunity arising from checkpoint blockade.
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Autoimunidade/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Antígeno B7-H1/imunologia , Diabetes Mellitus Experimental/imunologia , Feminino , Centro Germinativo/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos NODRESUMO
Chemical reactions are the most important phenomena in chemistry. However, chemical reactions at buried solid/solid interfaces are very difficult to study in situ. In this research, the chemical reaction between two solid polymer materials, a nylon film and a maleic anhydride (MAH) grafted poly(ethylene-octene) (MAHgEO) sample, was directly analyzed at the buried nylon/MAHgEO interface at the molecular level in real time and in situ, using surface and interface sensitive sum-frequency generation (SFG) vibrational spectroscopy. Disappearance of nylon signals indicated a chemical reaction between amine and hydrolyzed amide groups of nylon and MAH groups on the MAHgEO at the buried interface. The appearance of SFG signals from reaction products was also observed at the buried nylon/MAHgEO interface. The mechanism of the observed interfacial reaction was further analyzed. Temperature-dependent SFG experiments were performed to measure the activation energy of the interfacial reaction, enabling a comparison with that reported for the bulk materials. The interfacial chemical reaction between nylon and MAHgEO greatly improved the adhesion of these dissimilar materials. The detailed analysis of a chemical reaction between two polymers at the polymer/polymer buried interface underscores the utility of SFG as a powerful analytical tool to build understanding of buried interfaces and to accelerate the design of interfacial structures with desired properties.
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The surfactant properties of amphiphilic hyperbranched polyglycerols (HPGs) were investigated. The HPGs were prepared by ring-opening multibranching polymerization of glycidol using hydrophobic initiators of varying size and structure. The cloud points for all HPG surfactants were found to be >80 °C in deionized water with >1 wt % NaCl. The HPG surfactants with hydrophilic-lipophilic balance values between 16 and 18 were found to form stable octanol/water (o/w) emulsions within a 24 h period. Several surface properties, including critical micelle concentration (CMC), efficiency of surface tension reduction (pC20), effectiveness of surface tension reduction (γCMC), surface excess concentration at the CMC (Γmax), minimum area/molecule at the interface (Amin), and the CMC/C20 ratio of the HPG surfactants were measured in deionized water at 22.6 °C. In general, increasing HPG size was marked by an increase in minimum surface area per molecule (Amin) at the aqueous liquid/air interface. This increase in size also led to lower CMC and greater pC20 values of HPG surfactants prepared with Tergitol 15-S-7 initiator (HPG 5a-5d), a commercially available ethylene glycol oligomer with a branched hydrophobic tail.
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Nylon and maleic anhydride (MAH)-grafted polyolefin-based thin co-extruded multilayer films are widely used in packaging applications encountered in daily life. The molecular structure of the nylon/MAH-grafted polyolefin buried interface and molecular bonding between these two chemically dissimilar layers are thought to play an important role in achieving packaging structures with good adhesion. Here, the molecular bonds present at a nylon/maleic anhydride (MAH)-grafted polyethylene buried interface were systematically examined in situ for the first time using sum frequency generation (SFG) vibrational spectroscopy. The carbonyl stretching frequency region of the SFG spectra of a nylon/MAH-grafted polyethylene buried interface showed the presence of hydrolyzed MAH groups grafted to the polyethylene chain and very low levels of unreacted MAH enriched at the buried interface. The ability of SFG to detect these molecular species at the buried interface yields important understanding of the interfacial molecular structure and provides the basis for subsequent in situ studies of the bonding reaction between the grafted MAH and nylon directly at the interface. This understanding may guide the design of multilayer films with improved properties such as enhanced adhesion between polymer layers. The approach used in this study is general and is applicable to study the molecular characteristics of other buried interfaces of significance, such as buried interfaces involving polymers in solar cells, polymer semiconductors, and batteries. Nylon impact modification is another area of interest where the interaction between the MAH-grafted elastomer and the continuous phase of nylon is important.
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Subpectoral biceps tenodesis of the shoulder may be a useful tool that can address a wide range of disorders in the setting of pathology of the long head of the biceps tendon. Primary indications include (1) zone 2 or zone 3 tendon pathology and (2) failed previous proximal tendon tenodesis. Secondary indications include (1) an overhead athlete or thrower, (2) chronic tendinopathy, and (3) surgeon preference. A subpectoral technique allows tendon fixation directly posterior (deep) to the pectoralis tendon high in the bicipital fossa or in the mid fossa or fixation low in the fossa inferior to the pectoralis tendon (infrapectoral). Fixation technique options include an onlay suture anchor, onlay unicortical button, inlay bicortical button, or inlay interference screw. Potential surgical complications include humeral fracture, loss of fixation, tendon pullout or rupture, and neurovascular injury. Regardless of the specific location or technique used, subpectoral tenodesis is a valuable tool for the treatment of proximal biceps tendon pathology.
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Músculo Esquelético/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Ombro/cirurgia , Tendões/cirurgia , Tenodese/métodos , Braço/cirurgia , Parafusos Ósseos/efeitos adversos , Cadáver , Humanos , Fraturas do Úmero/cirurgia , Âncoras de Sutura , Tendinopatia/cirurgiaRESUMO
Asphaltenes are surface-active molecules that exist naturally in crude oil. They adsorb at the water-oil interface and form viscoelastic interfacial films that stabilize emulsion droplets, making water-oil separation extremely challenging. There is, thus, a need for chemical demulsifiers to disrupt the interfacial asphaltene films, and, thereby, facilitate water-oil separation. Here, we examine ethylcellulose (EC) as a model demulsifier and measure its impact on the interfacial properties of asphaltene films using interfacial shear microrheology. When EC is mixed with an oil and asphaltene solution, it retards the interfacial stiffening that occurs between the oil phase in contact with a water phase. Moreover, EC introduces relatively weak regions within the film. When EC is introduced to a pre-existing asphaltene film, the stiffness of the films decreases abruptly and significantly. Direct visualization of interfacial dynamics further reveals that EC acts inhomogeneously, and that relatively soft regions in the initial film are seen to expand. This mechanism likely impacts emulsion destabilization and provides new insight to the process of demulsification.
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The molecular structures of buried interfaces of maleic anhydride grafted and ungrafted polyethylene films with silica and nylon surfaces were studied in situ using sum-frequency generation (SFG) vibrational spectroscopy. Grafting maleic anhydride to polyethylene altered the molecular structures at buried interfaces, including changing the orientation of polymer methylene groups and resulting in the presence of CâO groups at silica interfaces. These molecular level changes are correlated with enhanced adhesion properties, with ordered CâO groups and in-plane orientation of the methylene groups associated with higher levels of adhesion. While improved adhesion was observed for grafted polyethylene at the nylon interface, no CâO groups were detected at the interface using SFG, for films thermally treated at 185 °C. In this case, either no CâO groups are present at the interface or they are disordered; the latter explanation is more likely, considering the observed improvement in adhesion.
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Foam and emulsion stability has long been believed to correlate with the surface shear viscosity of the surfactant used to stabilize them. Many subtleties arise in interpreting surface shear viscosity measurements, however, and correlations do not necessarily indicate causation. Using a sensitive technique designed to excite purely surface shear deformations, we make the most sensitive and precise measurements to date of the surface shear viscosity of a variety of soluble surfactants, focusing on SDS in particular. Our measurements reveal the surface shear viscosity of SDS to be below the sensitivity limit of our technique, giving an upper bound of order 0.01 µN·s/m. This conflicts directly with almost all previous studies, which reported values up to 10(3)-10(4) times higher. Multiple control and complementary measurements confirm this result, including direct visualization of monolayer deformation, for SDS and a wide variety of soluble polymeric, ionic, and nonionic surfactants of high- and low-foaming character. No soluble, small-molecule surfactant was found to have a measurable surface shear viscosity, which seriously undermines most support for any correlation between foam stability and surface shear rheology of soluble surfactants.
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Modelos Químicos , Dodecilsulfato de Sódio/química , Tensoativos/química , Imãs , Reologia , Resistência ao Cisalhamento , ViscosidadeRESUMO
It was an honor to be selected to participate in the 2017 Arthroscopy Association of North America Advanced Arthroscopy Traveling Fellowship. This year's group included Michael J. Alaia, M.D., Assistant Professor and Associate Sports Medicine Fellowship Director at NYU Hospital for Joint Diseases; Nathan K. Endres, M.D., Associate Professor at the University of Vermont; LCDR Patrick W. Joyner, M.D., Assistant Professor at Naval Medical Center Portsmouth, and Head Physician East Coast Navy Seals; and LTC Christopher J. Tucker, M.D., Assistant Professor at the Uniformed Services University and Chief of Sports Service at Fort Belvoir Community Hospital. This year, we were honored to have a true pioneer in sports medicine and arthroscopic surgery, Dr. Jack M. Bert, Past President of Arthroscopy Association of North America and Adjunct Clinical Professor at the University of Minnesota, serve as our Godfather.
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Bolsas de Estudo , Cirurgiões Ortopédicos , Viagem , Humanos , América do Norte , Sociedades MédicasRESUMO
BACKGROUND: Little is known about the incidence and characteristics of primary, or external, shoulder impingement in an occupationally and physically active population. A longitudinal, prospective epidemiologic database was used to determine the incidence and risk factors for shoulder subacromial impingement in the United States (U.S.) military. Our hypothesis was that shoulder impingement is influenced by age, sex, race, military rank, and branch of service. METHODS: The Defense Medical Epidemiology Database was queried for all shoulder impingement injuries using International Classification of Disease, Ninth Addition, Clinical Modification code 726.10 within a 10-year period from 1999 through 2008. An overall injury incidence was calculated, and a multivariate analysis performed among demographic groups. RESULTS: In an at-risk population of 13,768,534 person-years, we identified 106,940 cases of shoulder impingement resulting in an incidence of 7.77/1000 person-years in the U.S. military. The incidence of shoulder impingement increased with age and was highest in the group aged ≥40 years (incidence rate ratio [IRR], 4.90; 95% confidence interval [CI], 4.61-5.21), was 9.5% higher among men (IRR, 1.10, 95% CI, 1.06-1.13), and compared with service members in the Navy, those in the Air Force, Army, and Marine Corps were associated with higher rates of shoulder impingement (IRR, 1.46 [95% CI, 1.42-1.50], 1.42 [95% CI, 1.39-1.46], and 1.31 [95% CI, 1.26-1.36], respectively). CONCLUSIONS: The incidence of shoulder impingement among U.S. military personnel is 7.77/1000 person-years. An age of ≥40 years was a significant independent risk factor for injury.
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Militares/estatística & dados numéricos , Síndrome de Colisão do Ombro/epidemiologia , Adulto , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Dor de Ombro/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
We investigated the effects of dietary nitrate (NO3 (-)) supplementation on the concentration of plasma nitrite ([NO2 (-)]), oxygen uptake (VÌo2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a double-blind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO3 (-)-rich beetroot juice (8.4 mmol NO3; BR) or NO3 (-)-depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO2 (-)] was significantly elevated in H-BR and N-BR compared with H-PL (P < 0.01) and N-PL (P < 0.01). The rate of decline in plasma [NO2 (-)] was greater during severe-intensity exercise in H-BR [-30 ± 22 nM/min, 95% confidence interval (CI); -44, -16] compared with H-PL (-7 ± 10 nM/min, 95% CI; -13, -1; P < 0.01) and in N-BR (-26 ± 19 nM/min, 95% CI; -38, -14) compared with N-PL (-1 ± 6 nM/min, 95% CI; -5, 2; P < 0.01). During moderate-intensity exercise, steady-state pulmonary VÌo2 was lower in H-BR (1.91 ± 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 ± 0.25 l/min, 95% CI; 1.93, 2.26; P = 0.02), and VÌo2 kinetics was faster in H-BR (τ: 24 ± 13 s, 95% CI; 15, 32) compared with H-PL (31 ± 11 s, 95% CI; 23, 38; P = 0.04). NO3 (-) supplementation had no significant effect on VÌo2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO3 (-) in hypoxia (H-PL: 197 ± 28; 95% CI; 173, 220 vs. H-BR: 214 ± 43 s, 95% CI; 177, 249; P = 0.04) but not normoxia. The metabolism of NO2 (-) during exercise is altered by NO3 (-) supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO3 (-) supplementation enhances VÌo2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude.
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Exercício Físico/fisiologia , Nitratos/farmacologia , Nitritos/sangue , Oxigênio/metabolismo , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Suplementos Nutricionais , Método Duplo-Cego , Tolerância ao Exercício/fisiologia , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Adulto JovemRESUMO
Purpose: To determine whether activity on Twitter was correlated with increasing impact factor (IF) among 6 orthopaedic sports medicine journals. Methods: Twitonomy software was used to collect account activity for the American Journal of Sports Medicine; Arthroscopy: The Journal of Arthroscopic and Related Surgery; Knee Surgery, Sports Traumatology, Arthroscopy; Journal of Shoulder and Elbow Surgery; Orthopaedic Journal of Sports Medicine; and Sports Health. Data from 2000 to 2020 were collected. Each journal's annual IF score was collected via scijournal.org. A multivariate regression model was used to predict the influence of different Twitter metrics on IF from 2012 to 2019. The journal name, number of tweets, and interaction of the two were used to predict IF. Additionally, Pearson correlation was used to assess correlations between Twitter account metrics and IF. Results: Over the study period, all IFs increased, with the exception of that for American Journal of Sports Medicine. The effect size between number of tweets and IF was not the same for each journal. For every additional tweet, American Journal of Sports Medicine increased its IF by 0.001 (P = .18). Sports Health and Orthopaedic Journal of Sports Medicine increased their IF by 0.01 (P = .002) and 0.022 (P < .001), respectively. Knee Surgery, Sports Traumatology, Arthroscopy would expect a decrease in its IF by 0.004 (P = .55) and Journal of Shoulder and Elbow Surgery and Arthroscopy would increase its IF by 0.002 (P = .71) and 0.001 (P = .99), but this was not significant. There was a statistically significant positive correlation between annual tweets and IF across all journals. Conclusions: Markers of Twitter account activity, specifically the number of annual tweets, were predictive of an increase in IF among the orthopedic sports medicine journals included in this study. Clinical Relevance: The findings of this study may allow orthopaedic sports medicine journals to make more effective, targeted, and productive use of their social media accounts to reach a broader audience, increase their influence, and increase the IF of their journal.
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Meniscal injury is common, and despite modern techniques, the failure rate following repair remains high. While there are recent treatment advances in the form of biologics, there is limited evidence and agreement on these emerging therapies and their role in meniscal healing. Amniotic tissue (umbilical cord allograft) is a biologic augmentation therapy that has been utilized in other musculoskeletal applications but has not been reported for use in meniscal repair. We describe a technique to deliver an allograft amniotic membrane into a meniscus tear repair site, potentially optimizing healing.