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1.
J Strength Cond Res ; 38(5): 825-834, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38595263

RESUMEN

ABSTRACT: Johansson, DG, Marchetti, PH, Stecyk, SD, and Flanagan, SP. A biomechanical comparison between the safety-squat bar and traditional barbell back squat. J Strength Cond Res 38(5): 825-834, 2024-The primary objectives for this investigation were to compare the kinematic and kinetic differences between performing a parallel back squat using a traditional barbell (TB) or a safety-squat bar (SSB). Fifteen healthy, recreationally trained male subjects (23 + 4 years of age) performed the back squat with a TB and an SSB at 85% of their respective 1 repetition maximum with each barbell while instrumented for biomechanical analysis. Standard inverse dynamics techniques were used to determine joint kinematic and kinetic measures. A 2 × 3 (exercise × joint) factorial analysis of variance with repeated measures was used to determine the kinetic and kinematic differences between the squats while using the different barbells. Fisher's least significant difference post hoc comparisons showed that the TB resulted in significantly greater maximum hip flexion angle (129.33 ± 11.8° vs. 122.11 ± 12.1°; p < 0.001; d = 1.80), peak hip net joint extensor torque (2.54 ± 0.4 Nm·kg -1 vs. 2.40 ± 0.4 Nm·kg -1 ; p = 0.001; d = 1.10), hip net extensor torque mechanical energy expenditure (MEE; 2.81 ± 0.5 Nm·kg -1 vs. 2.58 ± 0.6 Nm·kg -1 ; p = 0.002; d = 0.97), and ankle net joint plantar flexor torque MEE (0.32 ± 0.09 J·kg -1 vs. 0.28 ± 0.06 J·kg -1 ; p = 0.029; d = 0.63), while also lifting significantly (123.17 ± 20.8 kg vs. 117.17 ± 20.8 kg; p = 0.005; d = 0.858) more weight than the SSB. The SSB resulted in significantly higher maximum knee flexion angles (116.82 ± 5.8° vs. 115.65 ± 5.6°; p = 0.011; d = 0.75) than the TB, with no significant difference in kinetics at the knee. The TB may be preferred to the SSB for developing the hip extensors and lifting higher maximum loads. The SSB may be advantageous in situations where a more upright posture or a lower load is preferred while creating a similar demand for the knee joint.


Asunto(s)
Articulación de la Rodilla , Humanos , Masculino , Fenómenos Biomecánicos , Adulto Joven , Adulto , Articulación de la Rodilla/fisiología , Articulación de la Cadera/fisiología , Torque , Levantamiento de Peso/fisiología , Músculo Esquelético/fisiología , Articulación del Tobillo/fisiología , Entrenamiento de Fuerza/métodos , Rango del Movimiento Articular/fisiología
2.
Am J Community Psychol ; 65(3-4): 479-503, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31556467

RESUMEN

Comprehensive community initiatives (CCIs) represent a popular method for creating systemic change, yet there is a dearth of evidence on their effectiveness (Zaff, Pufall Jones, Donlan, Lin, & Anderson, 2016). This article presents a systematic review of the evidence on the population-level impact of CCIs, focusing specifically on documented effects from studies using an experimental or quasi-experimental design. Of 1,947 articles identified through a database and hand search, 25 articles examining six different CCIs-most of which employed prevention science frameworks-met the review inclusion criteria. The results of this review show that CCIs can strengthen protective factors and reduce risk factors, delay initiation of and reduce substance use, and reduce the likelihood of, and delay engagement in, violent and/or delinquent behaviors. Impacts have been documented as soon as one year after initial intervention, and as early as 7th grade, with effects sustained as long as seven years post-intervention, and as late as a year post-high school. However, relative to the prevalence of CCIs as a practical intervention, the evidence base is small, potentially dated, and focused on a narrow set of outcomes and populations. Recommendations for interpreting the evidence base are discussed, including methodological limitations and implications for future work.


Asunto(s)
Participación de la Comunidad , Relaciones Comunidad-Institución , Relaciones Interinstitucionales , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Características de la Residencia , Conducta Social , Cambio Social , Adulto Joven
3.
Eur Arch Otorhinolaryngol ; 274(8): 3021-3028, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28540513

RESUMEN

With the advent of single-sided hearing loss increasingly being treated with cochlear implantation, bone conduction implants are reserved for cases of conductive and mixed hearing loss with greater complexity. The BoneBridge (BB, MED-EL, Innsbruck, Austria) is an active fully implantable device with no attenuation of sound energy through soft tissue. However, the floating mass transducer (FMT) part of the device is very bulky, which limits insertion in complicated ears. In this study, 3D printed temporal bones of patients were used to study its utility in preoperative planning on complicated cases. Computed tomography (CT) scans of 16 ears were used to 3D print their temporal bones. Three otologists graded the use of routine preoperative planning provided by MED-EL and that of operating on the 3D printed bone of the patient. Data were collated to assess the advantage and disadvantage of the technology. There was a statistically significant benefit in using 3D printed temporal bones to plan surgery for difficult cases of BoneBridge surgery compared to the current standard. Surgeons preferred to have the printed bones in theatre to plan their drill sites and make the transition of the planning to the patient's operation more precise. 3D printing is an innovative use of technology in the use of preoperative planning for complex ear surgery. Surgical planning can be done on the patient's own anatomy which may help to decrease operating time, reduce cost, increase surgical precision and thus reduce complications.


Asunto(s)
Implantación Coclear , Audífonos , Pérdida Auditiva Conductiva/cirugía , Complicaciones Posoperatorias/prevención & control , Impresión Tridimensional/estadística & datos numéricos , Hueso Temporal/diagnóstico por imagen , Adulto , Australia , Implantación Coclear/efectos adversos , Implantación Coclear/métodos , Femenino , Humanos , Masculino , Planificación de Atención al Paciente/normas , Diseño de Prótesis , Ajuste de Prótesis/métodos , Mejoramiento de la Calidad , Tomografía Computarizada por Rayos X/métodos
4.
J Vet Med Educ ; 44(1): 3-8, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28206849

RESUMEN

While existing literature suggests that professional students (e.g., medical, dental, law, nursing, etc.) experience high levels of stress and depression, the experiences of veterinary medical students have been less well examined. The purpose of this study was to explore the levels of stress and depression among veterinary medical students and to examine the relationship between these variables. Study participants were 1,245 veterinary medical students from North America. The findings provide support for the assertion that veterinary medical students experience high levels of stress and depression. Results also indicated that there is a correlation between stress and depression for veterinary medical students and that female students experience higher levels of stress and depression than their male counterparts.


Asunto(s)
Depresión/epidemiología , Salud Mental , Estrés Psicológico/epidemiología , Estudiantes de Medicina , Adolescente , Adulto , Canadá/epidemiología , Depresión/psicología , Educación en Veterinaria , Femenino , Humanos , Masculino , Salud Mental/estadística & datos numéricos , Facultades de Medicina Veterinaria/estadística & datos numéricos , Estrés Psicológico/psicología , Estudiantes de Medicina/estadística & datos numéricos , Estados Unidos/epidemiología , Adulto Joven
5.
Langmuir ; 31(5): 1776-83, 2015 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-25565379

RESUMEN

There has been a resurgence of interest in complex coacervation, a form of liquid-liquid phase separation (LLPS) in systems of oppositely charged macroions, but very few reports describe the somewhat anomalous coacervation between acidic and basic proteins, which occurs under very narrow ranges of conditions. We sought to identify the roles of equilibrium interprotein complexes during the coacervation of ß-lactoglobulin dimer (BLG2) with lactoferrin (LF) and found that this LLPS arises specifically from LF(BLG2)2. We followed the progress of complexation and coacervation as a function of r, the LF/BLG molar ratio, using turbidity to monitor the degree of coacervation and proton release and dynamic light scattering (DLS) to assess the stoichiometry and abundance of complexes. Isothermal titration calorimetry (ITC) showed that initial complex formation is endothermic, but a large exotherm related to coacervate formation obscured other regions. On the basis of turbidimetry, proton release, and DLS, we propose a speciation diagram that presents the abundance of various complexes as a function of r. Although multiple species could be simultaneously present, distinct regions could be identified corresponding to equilibria among particular protein pairs.


Asunto(s)
Lactoferrina/química , Lactoferrina/aislamiento & purificación , Lactoglobulinas/química , Lactoglobulinas/aislamiento & purificación , Electricidad Estática , Animales , Bovinos , Concentración de Iones de Hidrógeno , Modelos Moleculares , Conformación Proteica , Protones
6.
J Strength Cond Res ; 29(11): 3143-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25932990

RESUMEN

Athletes often need to both jump high and get off the ground quickly, but getting off the ground quickly can decrease the vertical ground reaction force (VGRF) impulse, impeding jump height. Energy stored in the muscle-tendon complex during the stretch-shortening cycle (SSC) may mitigate the effects of short ground contact times (GCTs). To take advantage of the SSC, several coaches recommend "attacking" the ground with the foot in a dorsiflexed (DF) position at contact. However, the efficacy of this technique has not been tested. This investigation tested the hypotheses that shorter GCTs would lead to smaller vertical depth jump heights (VDJH), and that this difference could be mitigated by instructing the athletes to land in a DF as opposed to a plantar flexed (PF) foot position. Eighteen healthy junior college athletes performed depth jumps from a 45-cm box onto force platforms under instruction to achieve one of the 2 objectives (maximum jump height [hmax] or minimal GCT [tmin]), with one of the 2 foot conditions (DF or PF). These variations created 4 distinct jump conditions: DF-hmax, DF-tmin, PF-hmax, and PF-tmin. For all variables examined, there were no significant interactions. For all 4 conditions, the ankle was PF during landing, but the DF condition was 28.87% less PF than the PF condition. The tmin conditions had a 23.48% shorter GCT than hmax. There were no significant main effects for jump height. The peak impact force for tmin was 22.14% greater than hmax and 19.11% greater for DF compared with PF conditions. A shorter GCT did not necessitate a smaller jump height, and a less PF foot did not lead to improvements in jump height or contact time during a depth jump from a 45-cm box. The same jump height was attained in less PF and shorter GCT conditions by larger impact forces. To decrease contact time while maintaining jump height, athletes should be instructed to "get off the ground as fast as possible." This cue seems to be more important than foot position. However, it should be acknowledged that this technique leads to larger impact forces, which should be considered when prescribing the number of foot contacts in a plyometrics program. The ability of athletes to truly land in a DF position during depth jumps is questioned and needs further investigation.


Asunto(s)
Articulación del Tobillo/fisiología , Ejercicio Pliométrico , Humanos , Extremidad Inferior/fisiología , Masculino , Movimiento/fisiología , Factores de Tiempo , Adulto Joven
7.
J Strength Cond Res ; 29(11): 3134-42, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25932989

RESUMEN

This investigation examined the characteristics of a failed back squat. Subjects were instructed to perform 3 repetitions of a barbell squat with a 3 repetition maximum load while instrumented for biomechanical analyses and standing atop force platforms. Inverse dynamics calculations were used to determine the net joint moment (NJM) power, work, and energy of the hip, knee, and ankle. Five subjects failed to complete all 3 repetitions, allowing for comparisons between a successful and the failed repetition. Although the NJM power and work were lower at all 3 joints during the failed attempt, the only statistically significant differences were at the hip. These findings suggest that the energy generated by the hip joint NJM limited performance of the task. However, examination of the NJM energy generation over time on an individual basis uncovered some features that were masked by the aggregated group mean data. For some subjects, the knee NJM limited the movement. Additionally, negligible to modest compensations occurred between the hip and knee NJM: a decreased energy generated by one NJM was often accompanied by an increase in energy generated at the other. A limiting joint, or "weak link," may explain the failure to complete a lift. Interventions should address the limiting joint on an individual-specific basis and incorporate assistive exercises that target these deficiencies.


Asunto(s)
Articulaciones/fisiología , Extremidad Inferior/fisiología , Levantamiento de Peso/fisiología , Adulto , Fenómenos Biomecánicos/fisiología , Femenino , Humanos , Masculino , Adulto Joven
8.
Otol Neurotol ; 45(1): 65-74, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37853785

RESUMEN

OBJECTIVE: To investigate ictal nystagmus and audiovestibular characteristics in episodic spontaneous vertigo after cochlear implantation (CI). STUDY DESIGN: Retrospective and prospective case series. PATIENTS: Twenty-one CI patients with episodic spontaneous vertigo after implantation were recruited. INTERVENTIONS: Patient-initiated home video-oculography recordings were performed during one or more attacks of vertigo, using miniature portable home video-glasses. To assess canal and otolith function, video head-impulse tests (vHITs) and vestibular-evoked myogenic potential tests were conducted. MAIN OUTCOME MEASURES: Nystagmus slow-phase velocities (SPVs), the presence of horizontal direction-changing nystagmus, and post-CI audiovestibular tests. RESULTS: Main final diagnoses were post-CI secondary endolymphatic hydrops (48%) and exacerbation of existing Ménière's disease (29%). Symptomatic patients demonstrated high-velocity horizontal ictal-nystagmus (SPV, 44.2°/s and 68.2°/s in post-CI secondary endolymphatic hydrop and Ménière's disease). Direction-changing nystagmus was observed in 80 and 75%. Two were diagnosed with presumed autoimmune inner ear disease (SPV, 6.6°/s and 172.9°/s). One patient was diagnosed with probable vestibular migraine (15.1°/s).VHIT gains were 0.80 ± 0.20 (lateral), 0.70 ± 0.17 (anterior), and 0.62 ± 0.27 (posterior) in the implanted ear, with abnormal values in 33, 35, and 35% of each canal. Bone-conducted cervical and ocular vestibular-evoked myogenic potentials were asymmetric in 52 and 29% of patients (all lateralized to the implanted ear) with mean asymmetry ratios of 51.2 and 35.7%. Reversible reduction in vHIT gain was recorded in three acutely symptomatic patients. CONCLUSION: High-velocity, direction-changing nystagmus time-locked with vertigo attacks may be observed in post-CI implant vertigo and may indicate endolymphatic hydrops. Fluctuating vHIT gain may be an additional marker of a recurrent peripheral vestibulopathy.


Asunto(s)
Implantación Coclear , Hidropesía Endolinfática , Enfermedad de Meniere , Nistagmo Patológico , Neuronitis Vestibular , Humanos , Enfermedad de Meniere/complicaciones , Estudios Retrospectivos , Vértigo/diagnóstico , Vértigo/complicaciones , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/etiología , Neuronitis Vestibular/complicaciones
9.
Langmuir ; 29(50): 15614-23, 2013 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-24164315

RESUMEN

Lactoferrin (LF) and ß-lactoglobulin (BLG), strongly basic and weakly acidic bovine milk proteins, form optically clear coacervates under highly limited conditions of pH, ionic strength I, total protein concentration C(P), and BLG:LF stoichiometry. At 1:1 weight ratio, the coacervate composition has the same stoichiometry as its supernatant, which along with DLS measurements is consistent with an average structure LF(BLG2)2. In contrast to coacervation involving polyelectrolytes here, coacervates only form at I < 20 mM. The range of pH at which coacervation occurs is similarly narrow, ca. 5.7-6.2. On the other hand, suppression of coacervation is observed at high C(P), similar to the behavior of some polyelectrolyte-colloid systems. It is proposed that the structural homogeneity of complexes versus coacervates with polyelectrolytes greatly reduces the entropy of coacervation (both chain configuration and counterion loss) so that a very precise balance of repulsive and attractive forces is required for phase separation of the coacervate equilibrium state. The liquid-liquid phase transition can however be obscured by the kinetics of BLG aggregation which can compete with coacervation by depletion of BLG.


Asunto(s)
Lactoferrina/química , Lactoglobulinas/química , Animales , Bovinos , Concentración de Iones de Hidrógeno , Concentración Osmolar
10.
Clin Neurophysiol ; 152: 1-10, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37257318

RESUMEN

OBJECTIVE: To examine the relationship between widely used otolith function tests: the Subjective Visual Horizontal (SVH) and Vestibular Evoked Myogenic Potentials (VEMP). METHODS: A retrospective analysis was performed on 301 patients who underwent SVH, ocular and cervical VEMP (oVEMP and cVEMP) tests on the same day. Correlations between the mean SVH tilt and amplitude asymmetry ratios for bone-conducted (BC) oVEMP and air-conducted (AC) cVEMP were examined. Diagnoses included vestibular neuritis, stroke, vestibular migraine, Meniere's disease, sudden sensorineural hearing loss (SSNHL) and vestibular schwannoma. RESULTS: SVH results were concordant with the oVEMP in 64% of cases and the cVEMP in 51%. Across all patients, SVH demonstrated a significant moderate correlation with BC oVEMP amplitude asymmetry ratios (r = 0.55, p < 0.001) and a weak correlation with AC cVEMP amplitude asymmetry ratios (r = 0.35, p < 0.001). A stronger correlation between SVH and oVEMPs was observed in patients with vestibular neuritis (r = 0.67, p < 0.001) and SSNHL (r = 0.76, p = 0.001). CONCLUSIONS: SVH correlates better with oVEMP than cVEMP symmetry. SIGNIFICANCE: This finding reinforces the hypothesis of a common utricular origin for both SVH and oVEMPs which is distinct from the saccular origin of cVEMPs.


Asunto(s)
Pérdida Auditiva Sensorineural , Enfermedad de Meniere , Potenciales Vestibulares Miogénicos Evocados , Neuronitis Vestibular , Humanos , Potenciales Vestibulares Miogénicos Evocados/fisiología , Neuronitis Vestibular/diagnóstico , Estudios Retrospectivos , Enfermedad de Meniere/diagnóstico , Ojo
11.
J Histotechnol ; 45(2): 85-91, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34787535

RESUMEN

Cryopreserving tissues for histology requires the use of coolants to buffer the sample from liquid nitrogen (LN2) and to control the rate of temperature decline. Several coolants sharing similar physical characteristics are available on the market; however, commonly used coolants are variably flammable and/or toxic and pose risks to personnel and facilities. The purpose of this study was to compare the performance of three commercially available coolants: hexane, 2-methylbutane (2 M), and 1-methoxyheptafluoropropane (N7000). Fresh mouse tissues were frozen by each method, for their ability to preserve microscopic architecture and to protect RNA from degradation were evaluated and compared to tissue characteristics obtained by direct immersion in LN2. Our results show that for most tissues, the N7000 freezing coolant provides equal or improved preservation of microscopic architecture. While snap-freezing tissues in LN2 provides superior RNA protection, no significant differences in RNA quality were seen between tissues frozen in hexane, 2 M, and N7000.


Asunto(s)
Criopreservación , Hexanos , Animales , Criopreservación/métodos , Congelación , Ratones , ARN , Temperatura
12.
Clin Neurophysiol ; 138: 197-213, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35370080

RESUMEN

OBJECTIVE: To examine the vestibulo-ocular reflex (VOR) and compensatory-saccades before and after complete unilateral vestibular deafferentation (UVD). METHODS: Forty patients were studied before and after surgery for vestibular or facial schwannoma using the video head-impulse test (vHIT) and multivariable regression. RESULTS: Prior to UVD (median(IQR), 14(58.4) days), the average VOR-gain towards the lesioned-ear was lower than in normal for all semicircular canals (lateral, anterior, posterior: 0.69, 0.72, 0.49). One-week after UVD (5(3.0) days) VOR gains were further reduced (0.22, 0.37, 0.27), however, within one-year after UVD (171(125.0) days) the lesioned-ear VOR gains had slightly increased (+0.08, +0.11, +0.03), maximally for the anterior-canal. After UVD, the VOR gain asymmetry (gain towards minus away from intact-ear) was lower for the intact posterior-canal plane (0.56, 0.56, 0.22). For the lesioned canals, the frequency and amplitude of the first compensatory-saccade increased from 61-93% and 1.9-3.6° pre-surgery, to 98-99% and to 3.1-5.9° one-week post-surgery and remained unchanged over one-year; second saccade frequency and amplitude decreased over the same timespan. CONCLUSIONS: After UVD the high-acceleration VOR for the intact posterior-canal plane is more symmetrical than the other canals. First compensatory-saccades adapt within one week and subsequently change only marginally. SIGNIFICANCE: Saccade compensation from surgical UVD is near complete by one-week.


Asunto(s)
Neurilemoma , Reflejo Vestibuloocular , Prueba de Impulso Cefálico , Humanos , Reflejo Vestibuloocular/fisiología , Movimientos Sacádicos , Canales Semicirculares , Nervio Vestibular
13.
Otol Neurotol ; 43(4): e489-e496, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35085109

RESUMEN

OBJECTIVE: Menière's disease (MD) is characterized by recurrent vertigo and fluctuating aural symptoms. Diagnosis is straightforward in typical presentations, but a proportion of patients present with atypical symptoms. Our aim is to profile the array of symptoms patients may initially present with and to analyze the vestibular and audiological test results of patients with a diagnosis of MD. DESIGN: A retrospective study of patient files. SETTING: A tertiary, neuro-otology clinic Royal Prince Alfred Hospital, Sydney, Australia. METHOD: We identified 375 patients. Their history, examination, vestibular-evoked myogenic potentials (VEMP), video head-impulse test, canal-paresis on caloric testing, subjective visual horizontal (SVH), electrocochleography, ictal nystagmus, and audiometry were assessed. RESULTS: Atypical presenting symptoms were disequilibrium (n = 49), imbalance (n = 13), drop-attacks (n = 12), rocking vertigo (n = 2), and unexplained vomiting (n = 3), nonspontaneous vestibular symptoms in 21.6%, fluctuation of aural symptoms only (46%), and headaches (31.2%). Low velocity, interictal spontaneous-nystagmus in 13.3% and persistent positional-nystagmus in 12.5%. Nystagmus recorded ictally in 90 patients was mostly horizontal (93%) and of high velocity (48 ±â€Š34°/s). Testing yielded abnormal caloric responses in 69.6% and abnormal video head impulse test 12.7%. Air-conducted cervical VEMPs were abnormal in 32.2% (mean asymmetry ratio [AR] 30.2 ±â€Š46.5%) and bone-conducted ocular VEMPs abnormal in 8.8% (AR 11.2 ±â€Š26.8%). Abnormal interictal SVH was in 30.6%, (ipsiversive n = 46 and contraversive n = 19). Mean pure-tone averages 50 dB ±â€Š23.5 and 20 dB ±â€Š13 for affected and unaffected ears. CONCLUSION: Menière's disease has a distinctive history, but atypical presentations with normal vestibular function and hearing are a diagnostic challenge delaying treatment initiation.


Asunto(s)
Enfermedad de Meniere , Nistagmo Patológico , Potenciales Vestibulares Miogénicos Evocados , Pruebas Calóricas , Audición , Humanos , Enfermedad de Meniere/diagnóstico , Nistagmo Patológico/diagnóstico , Estudios Retrospectivos , Vértigo/diagnóstico
14.
PLoS One ; 17(9): e0274582, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36107926

RESUMEN

Non-alcoholic fatty liver disease (NAFLD), represents an unmet medical need that can progress to non-alcoholic steatohepatitis (NASH), which, without intervention, can result in the development of cirrhosis and hepatocellular carcinoma (HCC). Inflammation is a pathological hallmark of NASH, and targeting key inflammatory mediators of NASH may lead to potential therapeutics for the disease. Herein, we aimed to investigate the role of IL-23 signaling in NASH progression in murine models. We showed that recombinant IL-23 can promote IL-17 producing cell expansion in the liver and that these cells are predominately γδ T cells and Mucosal Associated Invariant T cells (MAITs). Reciprocally, we found that IL-23 signaling is necessary for the expansion of γδ T cells and MAIT cells in the western diet (WD) diet induced NASH model. However, we did not observe any significant differences in liver inflammation and fibrosis between wild type and Il23r-/- mice in the same NASH model. Furthermore, we found that Il23r deletion does not impact liver inflammation and fibrosis in the choline-deficient, L-amino acid-defined and high-fat diet (CDA-HFD) induced NASH model. Based on these findings, we therefore propose that IL-23 signaling is not necessary for NASH pathogenesis in preclinical models and targeting this pathway alone may not be an effective therapeutic approach to ameliorate the disease progression in NASH patients.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Aminoácidos/uso terapéutico , Animales , Carcinoma Hepatocelular/patología , Colina , Modelos Animales de Enfermedad , Hepatitis/complicaciones , Mediadores de Inflamación , Interleucina-17/genética , Interleucina-23 , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/patología
15.
Sci Transl Med ; 14(641): eabl8146, 2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35442706

RESUMEN

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2-driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.


Asunto(s)
Asma , Factores de Crecimiento de Fibroblastos , Corticoesteroides/farmacología , Corticoesteroides/uso terapéutico , Animales , Fluticasona/farmacología , Fluticasona/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Ácido Hialurónico , Inflamación/tratamiento farmacológico , Ratones
16.
Sci Transl Med ; 14(627): eabf8188, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-35020406

RESUMEN

Exacerbations of symptoms represent an unmet need for people with asthma. Bacterial dysbiosis and opportunistic bacterial infections have been observed in, and may contribute to, more severe asthma. However, the molecular mechanisms driving these exacerbations remain unclear. We show here that bacterial lipopolysaccharide (LPS) induces oncostatin M (OSM) and that airway biopsies from patients with severe asthma present with an OSM-driven transcriptional profile. This profile correlates with activation of inflammatory and mucus-producing pathways. Using primary human lung tissue or human epithelial and mesenchymal cells, we demonstrate that OSM is necessary and sufficient to drive pathophysiological features observed in severe asthma after exposure to LPS or Klebsiella pneumoniae. These findings were further supported through blockade of OSM with an OSM-specific antibody. Single-cell RNA sequencing from human lung biopsies identified macrophages as a source of OSM. Additional studies using Osm-deficient murine macrophages demonstrated that macrophage-derived OSM translates LPS signals into asthma-associated pathologies. Together, these data provide rationale for inhibiting OSM to prevent bacterial-associated progression and exacerbation of severe asthma.


Asunto(s)
Asma , Oncostatina M/metabolismo , Animales , Asma/patología , Humanos , Pulmón/patología , Macrófagos/metabolismo , Ratones , Moco , Oncostatina M/genética
17.
Sports Biomech ; : 1-19, 2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34730473

RESUMEN

During elite-level hammer throws, the vertical displacement of the centre of mass (COM) of the thrower and hammer are approximately 180° out of phase (the hammer's COM is at its high point when the thrower's COM is at its low point, and vice versa) prior to the hammer's release. This out-of-phase coordination pattern contributes to the velocity of the hammer, which ultimately contributes to the distance thrown. Several drills are used to improve coordination between the thrower's and hammer's COM, but it is not currently known if the out-of-phase pattern is present during these drills. This study examined the relative phase between the COM of the hammer and thrower during two different rotational drills: The Double Hammer Head and Single Arm drills. Using a 12-camera motion analysis system, COM kinematics for both the hammer and thrower were examined for seven NCAA Division I throwers during the two drills. Contrary to their purported purpose, the phase angles between thrower's and hammer's COM were significantly different from 180° during both drills. Further research should be conducted to examine the mechanical factors of hammer throwing drills, as well as the effect such drills have when implemented within training programs.

18.
Res Social Adm Pharm ; 17(7): 1321-1326, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33153913

RESUMEN

BACKGROUND: A pharmacist-physician covisit model in which patients see both a pharmacist and physician on the same day was established in a primary care practice. Previously, patients were seen in a referrals-based model in which providers referred patients for clinical pharmacy services on a different day. OBJECTIVE: To assess access to clinical pharmacy services in a pharmacist-physician covisit model compared to a referrals-based model. METHODS: A retrospective chart review was completed for patients who were seen by physicians on pre-specified half-days of clinic before and after implementation of the covisit model. Covisit model half-days between June 29, 2018 and September 30, 2018 and matched half-days from 2015 were included. Charts were reviewed to determine if patients scheduled to see the physician would benefit from clinical pharmacy services, including being seen for chronic disease management, eligible for a Medicare Annual Wellness Visit (AWV), prescribed medications that required counseling, had an adverse medication-related event, or had adherence concerns. Those eligible for clinical pharmacy services were further reviewed to determine if the patient interacted with a pharmacist within three months of their visit. RESULTS: Prior to implementation of the covisit model, 123 patient visits were completed on the pre-specified half-days. Of these, 61 patients (49.6%) were deemed eligible for clinical pharmacy services. In the covisit model, 149 patients were seen by the physician, of which 69 patients (46%) were eligible for clinical pharmacy services. More patients in the covisit cohort went on to interact with a pharmacist (56 patients, 81% vs. 10 patients, 16%, adjusted OR = 32.98, 95% CI [8.89-122.39]). The most common reasons patients were identified for clinical pharmacy services were eligibility for AWV, hypertension, and diabetes. CONCLUSIONS: A pharmacist-physician covisit model significantly increased accessibility to clinical pharmacy services compared to a referrals-based model.


Asunto(s)
Servicio de Farmacia en Hospital , Médicos , Anciano , Humanos , Medicare , Farmacéuticos , Estudios Retrospectivos , Estados Unidos
19.
Mucosal Immunol ; 14(4): 912-922, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33846533

RESUMEN

Acute exacerbations (AE) of asthma, remain one of the biggest concerns for patients living with asthma. As such, identifying the causes, the molecular mechanisms involved and new therapeutic interventions to prevent AE is a high priority. Immunity to intestinal helminths involves the reactivation of type-2 immune responses leading to smooth muscle contraction and mucus hypersecretion-physiological processes very similar to acute exacerbations in the airways following allergen exposure. In this study, we employed a murine model of intestinal helminth infection, using Heligmosomoides polygyrus, to identify miRNAs during active expulsion, as a system for the identification of miRNAs that may contribute to AE in the airways. Concomitant with type-2 immunity and expulsion of H. polygyrus, we identified miR-99a-5p, miR-148a-3p and miR-155-5p that were differentially regulated. Systemic inhibition of these miRNAs, alone or in combination, had minimal impact on expulsion of H. polygyrus, but inhibition of miR-99a-5p or miR-155-5p significantly reduced house dust mite (HDM)-driven acute inflammation, modelling human acute exacerbations. Immunological, pathological and transcriptional analysis identified that miR-155-5p or miR-99a-5p contribute significantly to HDM-driven AE and that transient inhibition of these miRNAs may provide relief from allergen-driven AE, without compromising anti-helminth immunity in the gut.


Asunto(s)
Alérgenos/inmunología , Asma/etiología , Memoria Inmunológica , MicroARNs/genética , Animales , Asma/metabolismo , Asma/patología , Biomarcadores , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Helmintiasis Animal/complicaciones , Helmintiasis Animal/inmunología , Helmintiasis Animal/parasitología , Interacciones Huésped-Parásitos , Inmunidad Innata , Ratones
20.
J Orthop Sports Phys Ther ; 40(6): 336-44, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20479532

RESUMEN

STUDY DESIGN: Longitudinal single-cohort study. OBJECTIVE: To characterize the time course of performance adaptations during a postsurgical exercise intervention following a single-level microdiscectomy. BACKGROUND: Patients with a recent history of lumbar microdiscectomy are functionally limited, weak, have compromised paraspinal musculature, and benefit from an exercise program. METHODS: Patients (n = 48) with a single-level microdiscectomy participated in a 12-week (36 sessions) comprehensive strength and endurance exercise program starting 4 to 6 weeks postsurgery. Lumbar extensor strength was quantified as the degree from horizontal on a modified Sorensen test procedure. Patients unable to assume the horizontal position were assumed to have strength deficits. Lumbar muscular endurance performance was quantified by the amount of time patients could hold the Sorensen test position at the horizontal. The time rate of lumbar muscular endurance adaptations were analyzed using longitudinal growth curve modeling. RESULTS: The adherence rate of this program was low (67%). Twenty percent of the patients were identified as having strength deficits. These deficits were corrected in all patients within 3 to 9 weeks. Linear mixed-model results suggest an improvement of 5.6 seconds in hold time per week of exercise. Both the initial level of endurance and the rates of improvements were highly individualized. CONCLUSION: The time course of musculoskeletal performance adaptations in persons with a history of lumbar surgery is highly individualized. When compared to normative endurance times, the results of this study indicate that the number of sessions and duration of therapy needed to generate meaningful adaptations of the paraspinal musculature is longer than what is typically provided in the clinic postsurgery. LEVEL OF EVIDENCE: Therapy, level 4.J Orthop Sports Phys Ther 2010;40(6):336-344, Epub 13 May 2010. doi:10.2519/jospt.2010.3141.


Asunto(s)
Adaptación Fisiológica , Discectomía , Terapia por Ejercicio/métodos , Vértebras Lumbares/cirugía , Debilidad Muscular/rehabilitación , Adulto , Estudios de Cohortes , Terapia por Ejercicio/instrumentación , Femenino , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fuerza Muscular , Resistencia Física , Cuidados Posoperatorios
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