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Although APOL1 gene variants are associated with nephropathy in African Americans, little is known about APOL1 protein synthesis, uptake, and localization in kidney cells. To address these questions, we examined APOL1 protein and mRNA localization in human kidney and human kidney-derived cell lines. Indirect immunofluorescence microscopy performed on nondiseased nephrectomy cryosections from persons with normal kidney function revealed that APOL1 protein was markedly enriched in podocytes (colocalized with synaptopodin and Wilms' tumor suppressor) and present in lower abundance in renal tubule cells. Fluorescence in situ hybridization detected APOL1 mRNA in glomeruli (podocytes and endothelial cells) and tubules, consistent with endogenous synthesis in these cell types. When these analyses were extended to renal-derived cell lines, quantitative RT-PCR did not detect APOL1 mRNA in human mesangial cells; however, abundant levels of APOL1 mRNA were observed in proximal tubule cells and glomerular endothelial cells, with lower expression in podocytes. Western blot analysis revealed corresponding levels of APOL1 protein in these cell lines. To explain the apparent discrepancy between the marked abundance of APOL1 protein in kidney podocytes observed in cryosections versus the lesser abundance in podocyte cell lines, we explored APOL1 cellular uptake. APOL1 protein was taken up readily by human podocytes in vitro but was not taken up efficiently by mesangial cells, glomerular endothelial cells, or proximal tubule cells. We hypothesize that the higher levels of APOL1 protein in human cryosectioned podocytes may reflect both endogenous protein synthesis and APOL1 uptake from the circulation or glomerular filtrate.
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Apolipoproteínas/metabolismo , Glomérulos Renales/metabolismo , Túbulos Renales Proximales/metabolismo , Riñón/metabolismo , Lipoproteínas HDL/metabolismo , Células Mesangiales/metabolismo , ARN Mensajero/metabolismo , Apolipoproteína L1 , Biopsia , Línea Celular , Células Cultivadas , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Técnicas In Vitro , Riñón/patología , Riñón/cirugía , Glomérulos Renales/patología , Túbulos Renales Proximales/patología , Células Mesangiales/patología , Microscopía Fluorescente , Nefrectomía , Podocitos/metabolismo , Podocitos/patologíaRESUMEN
Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.
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Nefropatía Asociada a SIDA/sangre , Apolipoproteínas/sangre , Lipoproteínas HDL/sangre , Insuficiencia Renal Crónica/sangre , Nefropatía Asociada a SIDA/genética , Adulto , Negro o Afroamericano/genética , Apolipoproteína L1 , Apolipoproteínas/genética , Estudios de Casos y Controles , Citocinas/sangre , Progresión de la Enfermedad , Dislipidemias/sangre , Femenino , Genotipo , Tasa de Filtración Glomerular , Humanos , Lipoproteínas HDL/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fenotipo , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal Crónica/genéticaRESUMEN
OBJECTIVE AND IMPORTANCE: The purpose of this report is to describe the clinical course of a patient referred to physiotherapy (PT) for the treatment of low back pain who was subsequently diagnosed with metastatic non-small cell carcinoma of the lung. CLINICAL PRESENTATION: A 48-year old woman was referred to PT for the evaluation and treatment of an insidious onset of low back pain of 2 month duration. The patient did not have a history of cancer, recent weight changes, or general health concerns. The patient's history and physical examination were consistent with a mechanical neuromusculoskeletal dysfunction and no red flag findings were present that warranted immediate medical referral. INTERVENTION: Short-term symptomatic improvements were achieved using the treatment-based classification approach. However, despite five PT sessions over the course of 5 weeks, the patient did not experience long-term symptomatic improvement. On the sixth session, the patient reported a 2-day history of left hand weakness and headaches. This prompted the physiotherapist to refer the patient to the emergency department where she was diagnosed with lung cancer. CONCLUSION: Differential diagnosis is a key component of PT practice. The ability to reproduce symptoms or achieve short-term symptomatic gains is not sufficient to rule out sinister pathology. This case demonstrates how extra caution should be taken in patients who are smokers with thoracolumbar region pain of unknown origin. The need for caution is magnified when one can achieve no more than short-term improvements in the patient's symptoms.
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INTRODUCTION: The Burley Readiness Examination (BRE) for Musculoskeletal (MSK) Imaging Competency assesses physical therapists' baseline MSK imaging competency. Establishing its reliability is essential to its value in determining MSK imaging competency. The purpose of this study was to test the reliability of the BRE for MSK Imaging Competency among physical therapists (PTs) with varying levels of training and education. REVIEW OF LITERATURE: Previous literature supports PTs' utility concerning diagnostic imaging; however, no studies directly measure their competency. With PTs expanding their practice scope and professional PT education programs, increasing their MSK imaging instruction, assessing competency becomes strategic in determining the future of MSK education and training. SUBJECTS: One hundred twenty-three United States licensed PTs completed the BRE. METHODS: Physical therapists completed the BRE through an online survey platform. Point biserial correlation (rpb) was calculated for each examination question. Final analyses were based on 140 examination questions. Examination scores were compared using independent sample t-test and one-way analysis of variance. Chi-square tests and odds ratios (ORs) assessed the relationship of a passing examination score (≥75%) and the type of training. Reliability of the BRE was assessed using Cronbach's alpha (α). RESULTS: Mean overall examination score was 75.89 ± 8.56%. Seventy PTs (56.9%) obtained a passing score. Physical therapists with additional MSK imaging training, board certification, and residency or fellowship training scored significantly higher (P < .001) compared with those with only entry-level PT program education. Physical therapists with additional MSK imaging training scored significantly higher (xÌ = 81.07% ± 8.93%) and were almost 5 times (OR = 4.74, 95% CI [1.95-11.50]) as likely to achieve a passing score than those without. The BRE demonstrated strong internal consistency (Cronbach's α = 0.874). DISCUSSION AND CONCLUSIONS: The BRE was reliable, consistently identifying higher examination scores among those with increased MSK imaging training. Training in MSK imaging influenced competency more than other factors. The BRE may be of analytical value to PT professional and postprofessional programs.
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Competencia Clínica , Evaluación Educacional , Fisioterapeutas , Humanos , Competencia Clínica/normas , Reproducibilidad de los Resultados , Fisioterapeutas/educación , Evaluación Educacional/métodos , Estados Unidos , Femenino , Masculino , Enfermedades Musculoesqueléticas/diagnóstico por imagen , Encuestas y Cuestionarios , Adulto , Diagnóstico por Imagen/normasRESUMEN
OBJECTIVES: To examine physical therapist awareness and utilization of imaging referral privileges in the United States (US) and how it relates to direct access frequency. METHODS: This study utilized survey data collected in 2020-2021 from US physical therapists. Subjects were asked about imaging referral jurisdictional authority in their state. Responses were analyzed for accuracy and compared to the level of jurisdictional authority and its impact on imaging referral. Analysis of imaging skills performance and imaging referral practices were compared to direct access frequency. RESULTS: Only 42.0% of physical therapists practicing in states that allow imaging referral were aware of this privilege. Those practicing where imaging referral was allowed via state legislation were significantly more likely (p < 0.01) to be aware of this privilege (71.4%) compared to those granted by the state board (25.2%). Those aware of their imaging referral scope were more likely (p < 0.01) to practice imaging referral (44.5%) compared to those who were unaware (3.2%). Direct access frequency was positively associated with imaging skill performance and imaging referral practice (p < 0.01). Doctors of Physical Therapy, residency/fellowship-trained physical therapists, and board-certified physical therapists all reported practicing greater frequency of direct access (p < 0.01). DISCUSSION/CONCLUSION: There is a striking lack of awareness of imaging privileges among physical therapists as influenced by the level of jurisdictional scope. These results suggest that the lack of awareness may have a dampening effect on diagnostic imaging referrals. The American Physical Therapy Association should consider engaging with state boards to raise imaging privilege awareness.
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Fisioterapeutas , Derivación y Consulta , Alcance de la Práctica , Humanos , Estados Unidos , Diagnóstico por Imagen , Femenino , Masculino , Competencia Clínica , Adulto , Encuestas y CuestionariosRESUMEN
STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the diagnostic accuracy of lumbar movement restrictions and pain in patients with metastatic bone cancer. BACKGROUND: When evaluating patients with low back pain, physical therapists have used the presence of nonmechanical findings during a spinal movement screen as 1 factor in determining whether physician referral is necessary. There are no studies that have investigated the accuracy of this strategy in a situation of diagnostic uncertainty. METHODS: This study included 1,109 patients (655 women) with low back pain (mean age=54.8±16.3 years) seen at a spine surgery center who received a clinical movement screen and an imaging-supported diagnosis by an orthopedic surgeon. No report of pain during movement and no limitation of movement were considered the 2 targeted findings as these are associated with nonmechanical findings. RESULTS: Sixty-six patients were diagnosed with metastatic cancer, 61 with metastatic bone cancer and concomitant diagnoses. Pain-free lumbar movements in all directions for patients with metastatic bone cancer without concomitant diagnoses were associated with a posttest probability of 0.00 (+likelihood ratio=2.4; -likelihood ratio=0.0), which may be useful in ruling out spinal cancer. In situations where a concomitant diagnosis was present with cancer, the value of a movement screen was poor. CONCLUSION: Nonmechanical findings during a traditional movement screen are not specific to sinister conditions such as metastatic spinal cancer. Clinicians should expect concomitant conditions to exhibit painful or limited findings in patients with and without cancer.
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Dolor de Espalda/etiología , Movimiento , Examen Físico/métodos , Rango del Movimiento Articular , Neoplasias de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/secundario , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/complicacionesRESUMEN
OBJECTIVES: To explore if physical therapists are practicing skills necessary to refer patients for musculoskeletal imaging. METHODS: An expert panel established a list of nine requisite skills to refer for musculoskeletal imaging. A blinded expert panel validated the list using a 5-point Likert scale. The skills list was examined via an electronic survey distributed to United States physical therapists. RESULTS: 4,796 respondents were included. Each of the nine skills were routinely performed by a majority of the respondents (range: 54.52-94.72%). Respondents routinely performed 6.95 (± 0.06) skills, with 67.41% routinely performing seven or more skills. Doctors of physical therapy routinely performed more imaging skills (7.15 ± 0.06) compared to their masters- (6.44 ± 0.19) and bachelors-trained (5.95 ± 0.21) counterparts (p < 0.001). Residency/fellowship-trained physical therapists were more likely to routinely perform more imaging skills (7.60 ± 0.11 vs. 6.79 ± 0.07, p < 0.001). Imaging skill performance was greater among board-certified physical therapists (7.39 ± 0.09 vs. 6.71 ± 0.08, p < 0.001) and APTA members (7.06 ± 0.07 vs. 6.65 ± 0.12, p < 0.001). CONCLUSION: Physical therapists are routinely practicing the requisite imaging skills to directly refer to a radiologist for musculoskeletal imaging.
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Internado y Residencia , Fisioterapeutas , Becas , Humanos , Modalidades de Fisioterapia , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Podocyte structural and transcriptional phenotype plasticity characterizes glomerular injury. Transcriptional activity of WT1 (Wilm's tumor 1) is required for normal podocyte structure and is repressed by the podocyte adherens junction protein, WTIP (WT1 interacting protein). Here we show that WTIP translocated into podocyte nuclei in lipopolysaccharide (LPS)-treated mice, a model of transient nephrotic syndrome. Cultured podocytes, which stably expressed an epitope-tagged WTIP, were treated with LPS. Imaging and cellular fractionation studies demonstrated that WTIP translocated from podocyte cell contacts into nuclei within 6 h and relocalized to cell contacts within 24 h after LPS treatment. LPS-stimulated WTIP nuclear translocation required JNK activity, which assembled a multiprotein complex of the scaffolding protein JNK-interacting protein 3 and the molecular motor dynein. Intact microtubule networks and dynein activity were necessary for LPS-stimulated WTIP translocation. Podocytes expressing sh-Wtip change morphology and demonstrate altered actin assembly in cell spreading assays. Stress signaling pathways initiate WTIP nuclear translocation, and the concomitant loss of WTIP from cell contacts changes podocyte morphology and dynamic actin assembly, suggesting a mechanism that transmits changes in podocyte morphology to the nucleus.
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Transporte Activo de Núcleo Celular , Proteínas Portadoras/metabolismo , Núcleo Celular/metabolismo , Microtúbulos/metabolismo , Podocitos/metabolismo , Actinas/química , Animales , Transporte Biológico , Línea Celular , Proteínas Co-Represoras , Proteínas del Citoesqueleto , Humanos , Lipopolisacáridos/metabolismo , Ratones , Fenotipo , Transducción de SeñalRESUMEN
HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.
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Infecciones por VIH/complicaciones , VIH-1/fisiología , Enfermedades Renales/virología , Riñón/virología , Urotelio/virología , Replicación Viral , Secuencia de Bases , Biopsia , Cartilla de ADN , Productos del Gen env/genética , Infecciones por VIH/patología , VIH-1/clasificación , VIH-1/genética , Humanos , Riñón/patología , Enfermedades Renales/patología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Urotelio/patologíaRESUMEN
BACKGROUND: Isolated medial cuneiform fracture is a rare but diagnostically challenging condition. Diagnostic delay in these cases may lead to delays in ideal treatment approaches and prolonged symptoms. An understanding of clinical presentation is needed to expedite diagnosis, facilitate decision making, and guide treatment approach. METHODS: Case studies/series were searched in four databases until September 2019. Included studies had participants with a history of traumatic closed medial cuneiform fracture. Studies were excluded if the medial cuneiform fractures were open fractures, associated with multitrauma, or associated with dislocation/Lisfranc injury. Three blinded reviewers assessed the methodological quality of the studies, and a qualitative synthesis was performed. RESULTS: Ten studies comprising 15 patients were identified. Mean ± SD patient age was 38.0 ± 12.8 years, with 86.7% of reported participants being men. The overall methodological quality was moderate to high, and reporting of the patient selection criteria was poor overall. The most commonly reported clinical symptoms were localized tenderness (60.0%) and edema (53.3%). Direct blow was the most common inciting trauma (46.2%), followed by axial load (30.8%) and avulsion injuries (23.1%). Baseline radiographs were occult in 72.7% of patients; magnetic resonance imaging and computed tomography were the most common diagnostic modalities. Mean ± SD diagnostic delay was 64.7 ± 89.6 days. Conservative management was pursued in 54.5% of patients, with reported resolution of symptoms in 3 to 6 months. Surgical intervention occurred in 45.5% of patients and resulted in functional restoration in 3 to 6 months in all but one patient. CONCLUSIONS: Initial radiographs for isolated medial cuneiform fractures are frequently occult. Due to expedience and relatively low cost, radiographs are still a viable first-line imaging modality. If clinical concern remains, magnetic resonance imaging may be pursued to minimize diagnostic delay. Conservative management is a viable treatment method, with expected return to full function in 3 to 6 months.
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Fracturas Óseas , Huesos Tarsianos , Adulto , Diagnóstico Tardío , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Radiografía , Huesos Tarsianos/diagnóstico por imagenRESUMEN
BACKGROUND: Diagnosing patients with cervical cord compressive myelopathy in a timely manner can be challenging due to varying clinical presentations, the absence of pathognomonic findings, and symptoms that are usually insidious in nature. OBJECTIVE: To describe the clinical course of a patient with primary complaint of left medial knee pain that was nonresponsive to surgical and conservative measures; the patient was subsequently diagnosed with cervical cord compressive myelopathy. DESIGN: Case report. SUBJECT: A 63-year-old man with a primary complaint of left medial knee pain. FINDINGS: Physical examination of the left knee was normal except for slight palpable tenderness over the medial joint line. During treatment, he noted loss of balance during activities of daily living. Reassessment revealed bilateral upper extremity hyperreflexia, bilateral Babinski reflex, and positive bilateral Hoffman reflex. Magnetic resonance imaging of the cervical spine demonstrated moderately severe spinal stenosis at the C3-C4, C5-C6, and C6-C7 levels. After C3-C7 laminoplasty for cervical cord compressive myelopathy, he reported substantial improvement of his left medial knee. Three years later, he had no complaint of knee pain. CONCLUSION: Appropriate diagnosis and treatment of cervical cord compressive myelopathy may avoid unnecessary diagnostic imaging, medical evaluations, invasive procedures, and potential neurologic complications.
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Rodilla/fisiopatología , Dolor/etiología , Compresión de la Médula Espinal/complicaciones , Vértebras Cervicales , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dolor/patologíaRESUMEN
BACKGROUND: the purpose of this study is to assess the relationship between functional levels in activities of daily living and sports and fear-avoidance beliefs in patients with a history of anterior cruciate ligament reconstruction (ACLR), after controlling for injury-related variables and physical impairment measures. PATIENTS AND METHODS: forty-eight subjects (34 men, 14 women; age 20.6 ± 1.2 years), at a mean of 31.7 ± 16.2 months following ACLR, participated in this study. Functional levels in activities of daily living and sports were assessed with the Knee Outcome Survey (KOS) Activities of Daily Living Scale (ADLS) and Sports Activity Scale (SAS). Fear-avoidance beliefs were assessed with the physical activity subscale of the fear-avoidance beliefs questionnaire (FABQ), which was adapted for use in patients with knee pathology. Injury-related variables included whether or not additional knee surgery was performed after the initial ACLR and the number of months from the most recent ACLR to participation in this study. Physical impairment measures included single-leg hop capabilities, quadriceps strength, and anterior knee joint laxity. RESULTS: hierarchical linear regression analysis revealed that scores on the physical activity subscale of the FABQ contributed significantly to KOS ADLS and SAS scores after accounting for injury-related variables and physical impairment measures. The final regression model accounted for 61% of the variance in KOS ADLS and SAS scores (P < 0.001). CONCLUSION: these results suggest that fear-avoidance beliefs following ACLR can potentially adversely influence functional levels in activities of daily living and sports.
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Actividades Cotidianas , Ligamento Cruzado Anterior/cirugía , Miedo , Procedimientos de Cirugía Plástica/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The number of physical therapists with imaging ordering privileges is increasing; however, a known level of competency and knowledge is generally lacking within the profession, as is a method to determine practitioner competency. The purpose of this study was to develop a valid musculoskeletal (MSK) imaging competency examination for physical therapists. METHODS: This 3-round Delphi method study utilized experts to reach consensus on examination content and development. Round 1 was completed by 37 experts. The last 2 rounds were completed by 35 experts. Experts rated questions on a 5-point Likert rating scale of importance (1 = not at all important, 5 = very important). Consensus was achieved with an a priori decision of (1) >75% agreement of the expert panel rating and ≥4 on the Likert scale, and (2) ≥.90 on Cronbach alpha and intraclass correlation coefficients. Experts recommended a passing score of 75%. The examination was subsequently reviewed by a panel of 5 radiologists. RESULTS: The Delphi method and radiologist panel review resulted in the 151-question Burley Readiness Examination (BRE) for MSK Imaging Competency. Interrater agreement and internal consistency of the Delphi panel were excellent, with an average intraclass correlation coefficient and Cronbach alpha of .928 and .950, respectively. CONCLUSIONS: The BRE is a tool that has the potential to demonstrate practitioners' level of baseline competency with MSK imaging. Additional testing among physical therapists will provide further validation and reliability of the examination. IMPACT: The use and application of diagnostic imaging is becoming more widespread in physical therapist practice throughout the United States. The BRE could potentially have broader implications for health care utilization and cost in the area of MSK imaging.
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Competencia Clínica/normas , Técnica Delphi , Sistema Musculoesquelético/diagnóstico por imagen , Fisioterapeutas/normas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiólogos/educación , Radiólogos/normasRESUMEN
BACKGROUND: Little is known about medical screening and differential diagnosis (MSDD) preparation of physical therapist students. METHODS: Professional degree physical therapist programs in the U.S. were surveyed regarding MSDD content and faculty perception of graduate competence. RESULTS: Fifty-five of 226 programs responded for a 24.3% response rate. Sixty-six percent strongly agreed that students were adequately prepared to perform MSDD with patients who are referred, whereas 47.3% strongly agreed for patients who are direct access. Faculty board specialty certification status affected perception of student competence (p=0.04). Increased emphasis during clinical affiliations was the most beneficial way to increase student knowledge of MSDD skills. Non-response bias assessment was non-significant. CONCLUSION: Increasing clinical exposure was the top recommendation for expanding both faculty and student knowledge and skills. Factors potentially impacting student preparation in MSDD content have been identified and require further study.
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Competencia Clínica/normas , Docentes/psicología , Especialidad de Fisioterapia/educación , Adulto , Anciano , Curriculum , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , PercepciónRESUMEN
HIV-associated nephropathy (HIVAN) is characterized by collapsing FSGS. Because transgenic mice with podocyte-specific overexpression of the vascular endothelial growth factor 164 (VEGF164) isoform also develop collapsing FSGS, we sought to determine whether VEGF plays a role in HIVAN. Compared with controls, immunohistochemistry revealed that kidneys from HIV-1-transgenic mice (Tg26) and from patients with HIVAN had greater expression of both VEGF and its transcriptional regulator, hypoxia-inducible factor 2alpha (HIF-2alpha). Similarly, mRNA and protein levels of VEGF and HIF-2alpha were increased in HIV-infected podocytes in vitro, and this transcriptional upregulation was found to be stimulated by the HIV viral protein Nef in a Src kinase-and Stat3-dependent manner. HIV-1 also upregulated VEGFR2 and its co-receptor neuropilin-1 and suppressed the expression of semaphorin 3a in the podocyte. Exogenous VEGF stimulated proliferation and de-differentiation of podocytes, which are features of collapsing FSGS, and VEGFR2 neutralizing antibodies reversed these features in podocytes infected with HIV-1 or isolated from Tg26 mice. In conclusion, HIV-1 induces VEGF and VEGFR2 expression in podocytes, and this may be a critical step in the pathogenesis of HIVAN.
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Nefropatía Asociada a SIDA/metabolismo , VIH-1 , Podocitos/fisiología , Podocitos/virología , Factor A de Crecimiento Endotelial Vascular/genética , Nefropatía Asociada a SIDA/patología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Biopsia , Línea Celular Transformada , Regulación Viral de la Expresión Génica , Humanos , Ratones , Ratones Transgénicos , Podocitos/citología , ARN Mensajero/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The patient was a 64-year-old woman who reported a sudden onset of neck pain and headaches following a fall 2.5 months prior to her initial physical therapy visit. Cervical spine radiographs, which were ordered by the referring physician, revealed extensive degenerative disc disease of the lower cervical spine. At her initial physical therapy evaluation, cervical spine range of motion was within functional limits except for bilateral rotation, which was limited to 45 degrees due to pain and stiffness. The patient's headache symptoms were abolished with the Sharp-Purser test. Although assessment of symptoms was not the intent of the Sharp-Purser test, a reduction of symptoms during the test would warrant further evaluation. Therefore, the physical therapist ordered cervical spine flexion-extension radiographic views to assess for atlantoaxial instability. The radiologist's report noted a stable atlantodens interval that did not change with cervical flexion and extension and a course of physical therapy was initiated. At the time of discharge from physical therapy, the patient reported no neck pain and only very mild occasional headaches, which she believed she could manage on her own.
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Accidentes por Caídas , Vértebras Cervicales/diagnóstico por imagen , Cefalea/etiología , Degeneración del Disco Intervertebral/diagnóstico por imagen , Dolor de Cuello/etiología , Articulación Atlantoaxoidea , Diagnóstico Diferencial , Femenino , Cefalea/rehabilitación , Humanos , Inestabilidad de la Articulación/complicaciones , Inestabilidad de la Articulación/diagnóstico , Persona de Mediana Edad , Dolor de Cuello/rehabilitación , Modalidades de Fisioterapia , RadiografíaRESUMEN
PURPOSE: To determine the effects of cryotherapy on quadriceps electromyographic (EMG) activity and isometric strength in early postoperative knee surgery patients. METHODS: Twenty-two volunteers with recent knee surgeries were included. EMG readings of the vastus medialis (VM), rectus femoris (RF), and vastus lateralis (VL) from the surgical leg were collected during a maximal voluntary quadriceps setting (QS) activity. Maximum isometric knee extension force measurements were also recorded. Subjects were randomly assigned to receive an ice bag or a sham room-temperature bag to the front of their postsurgical knee for 20 min. After treatment, the subjects repeated the above mentioned maximum QS and isometric knee extension force measurements. The subjects returned 24 h later to conduct the same test protocol but received the treatment (ice or sham) not applied during their first test session. RESULTS: A 38% increase in VM EMG activity during QS and a 30% increase in maximum isometric knee extension strength were found after cryotherapy treatment. No significant differences were found in RF or VL EMG activity during QS after cryotherapy. No significant differences were found in any measurements after the sham treatment. CONCLUSION: Clinicians should consider applying ice to knee joints prior to exercise for patients following knee surgery with inhibited quadriceps.
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Crioterapia , Rodilla/cirugía , Fuerza Muscular/fisiología , Procedimientos Ortopédicos/rehabilitación , Músculo Cuádriceps/fisiopatología , Adulto , Electromiografía , Femenino , Humanos , Contracción Isométrica , Masculino , Cuidados PosoperatoriosRESUMEN
BACKGROUND AND PURPOSE: This case report describes a patient referred for physical therapy treatment of neck pain who had an underlying hangman's fracture that precluded physical therapy intervention. CASE DESCRIPTION: This case involved a 61-year-old man who had a sudden onset of neck pain after a motor vehicle accident 8 weeks before his initial physical therapy visit. Conventional radiographs of his cervical spine taken on the day of the accident did not reveal any abnormalities. Based on the findings at his initial physical therapy visit, the physical therapist ordered conventional radiographs of the cervical spine to rule out the possibility of an undetected fracture. OUTCOMES: The radiographs revealed bilateral C2 pars interarticularis defects consistent with a hangman's fracture. The patient was referred to a neurosurgeon for immediate review. Based on a normal neurological examination, a relatively low level of pain, and the results of radiographic flexion and extension views of the cervical spine (which revealed no evidence of instability), the neurosurgeon recommended that the patient continue with nonsurgical management. DISCUSSION: In patients with neck pain caused by trauma, physical therapists should be alert for the presence of cervical spine fractures. Even if the initial radiographs are negative for a fracture, additional diagnostic imaging may be necessary for a small number of patients, because they may have undetected injuries that would necessitate medical referral and preclude physical therapy intervention.
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Vértebras Cervicales/lesiones , Errores Diagnósticos , Dolor de Cuello/etiología , Fracturas de la Columna Vertebral/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Dolor de Cuello/terapia , Modalidades de Fisioterapia , Derivación y Consulta , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/terapiaRESUMEN
A 55-year-old man was referred to physical therapy because of constant mid-back pain of 1 month's duration. Because of the strong suspicion for a fracture, thoracic spine anterior-posterior and lateral radiographs were ordered, which revealed compression deformities of the T6, T8, T9, and T12 vertebral bodies. An interventional radiologist ordered magnetic resonance imaging and believed the patient was a candidate for vertebroplasty, a technique in which medical grade cement is injected into a painful fractured vertebral body in an effort to stabilize the fracture. At 1 week following his vertebroplasty the patient was pain free. Further medical evaluation indicated that the patient had underlying osteoporosis, and treatment was initiated. At 1 and 2 years after vertebroplasty, the patient reported being symptom free. However, a history of osteoporosis and multiple compression fractures led to further medical evaluation 2 years after vertebroplasty and the patient was eventually diagnosed with multiple myeloma for which treated was initiated.
Asunto(s)
Dolor de Espalda/etiología , Fracturas por Compresión/fisiopatología , Vértebras Torácicas/fisiopatología , Fracturas por Compresión/diagnóstico , Fracturas por Compresión/patología , Humanos , Masculino , Persona de Mediana Edad , Especialidad de Fisioterapia , Radiografía , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/patologíaRESUMEN
The radiographs of this patient, an 11-year-old female with progressively worsening right knee pain, were significant for a right slipped capital femoral epiphysis (SCFE). The patient was referred to the orthopaedic surgeon on-call and underwent surgical fixation of her SCFE on the day of diagnosis.