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INTRODUCTION: Gene fusion identification by RNA-based next-generation sequencing (NGS) provides important information for cancer patients. NGS is commonly initiated by treating oncologists to identify therapeutic options. However, the implications of large fusion panels on tumor classification and diagnosis are underappreciated. We investigated the extent to which these tests aid diagnosis when ordered by pathologists. METHODS: We retrospectively reviewed the results of a validated Archer FusionPlex panel ordered by surgical pathologists at our institution, excluding cases tested for therapeutic targets. One hundred thirty-five cases of solid tumors from October 2020 and September 2021 were included. We compared the initial diagnosis to the final diagnosis, which incorporated fusion gene results. We classified the cases into groups based on the degree of contribution of the RNA fusion panel to the final diagnosis. RESULTS: Among 135 cases, a fusion event was identified in 47 cases, and no fusion event was identified in 88 cases. The results changed the diagnosis in 4 of 135 fusion positive cases (3%). Twenty-one cases (15%) provided a more specific diagnosis, and original diagnosis was confirmed in 17 cases (13%). In the remaining 5 cases (4%), the results identified fusion events of unknown clinical significance. CONCLUSIONS: RNA-based NGS provides significant benefit as an ancillary diagnostic tool. In our cohort, fusion analysis provided a more definitive diagnosis in 25 cases (19%). Our findings demonstrate an important role for pathologists in appropriate utilization of molecular testing, and diagnostic workflows integrating RNA-based NGS will lead to more accurate diagnosis and better patient care.
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Neoplasias , ARN , Fusión Génica , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Patólogos , Estudios RetrospectivosRESUMEN
OBJECTIVE: KRAS is a frequently mutated gene in cancers, and with recent FDA-approved targeted therapy for the G12C mutation, testing for KRAS variants is essential. We evaluated the performance of the Idylla KRAS assay on extracted DNA and cytology smears in order to expand the utility of the assay. METHODS: In total, fifty-seven human samples were analyzed. Idylla results from sixteen DNA extracted from formalin-fixed, paraffin-embedded tissues (FFPE DNA) and thirty cytology smears were compared to the reference method. We evaluated the performance of the Idylla assay using corresponding cytology smears to rescue cellblocks or surgical blocks that were quantity not sufficient (QNS) for next generation sequencing (NGS). RESULT: In the FFPE DNA cohort, 10 ng DNA input yielded valid results in all 16 samples, with 15 of 16 (93 %) concordant with NGS findings. In the cytology smear cohort, the Idylla KRAS assay demonstrated 100 % concordance with previous NGS results in 30 cases. In the QNS cohort, the assay was valid in all cases and KRAS mutations were identified in 3 of 11 cytology smears, including one G12C mutation. CONCLUSION: The Idylla KRAS assay is a high-performing, feasible, and convenient option for testing extracted DNA and cytology smears. It rescues QNS samples allowing it to be integrated into the molecular workflow as an initial screening test with remarkably quick turnaround times.
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Citodiagnóstico , Proteínas Proto-Oncogénicas p21(ras) , ADN , Análisis Mutacional de ADN/métodos , Formaldehído , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
OBJECTIVE: To examine the safety and efficacy of using a clitoral vacuum suction device (CVSD) versus vibratory stimulation (V) to treat orgasmic dysfunction in women with multiple sclerosis (MS) or spinal cord injury (SCI). DESIGN: Randomized clinical trial. SETTING: Two academic medical centers. PARTICIPANTS: Women (N=31) including 20 with MS and 11 with SCI. INTERVENTION: A 12-week trial of the use of a CVSD versus V. MAIN OUTCOME MEASURES: Female Sexual Function Inventory (FSFI) and Female Sexual Distress Scale (FSDS). RESULTS: Twenty-three women (18 MS, 5 SCI) completed the study including 13 of 16 randomized to CVSD and 10 of 15 randomized to V. There was a statistically significant increase in total FSFI score (P=.011), desire (P=.009), arousal (P=.009), lubrication (P=.008), orgasm (P=.012), and satisfaction (P=.049), and a significant decrease in distress as measured by FSDS (P=.020) in subjects using the CVSD. In subjects who used V, there was a statistically significant increase in the orgasm subscale of the FSFI (P=.028). Subjects using the CVSD maintained improvements 4 weeks after treatment. CONCLUSIONS: CVSD is safe and overall efficacious to treat female neurogenic sexual dysfunction related to MS and SCI. V is also safe and efficacious for female neurogenic orgasmic dysfunction; however, results were limited to the active treatment period. Because of ease of access and cost, clinicians can consider use of V for women with MS or SCI with orgasmic dysfunction. CVSD is recommended for women with multiple sexual dysfunctions or for whom V is ineffective.
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Clítoris , Esclerosis Múltiple/fisiopatología , Orgasmo , Disfunciones Sexuales Fisiológicas/fisiopatología , Disfunciones Sexuales Fisiológicas/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Succión/instrumentación , Vacio , Adulto , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, ß-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.
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Gastritis/patología , Infecciones por Helicobacter/patología , Helicobacter pylori , Enfermedades Intestinales/patología , Lesiones Precancerosas/patología , Antro Pilórico/patología , Adolescente , Anciano , Anciano de 80 o más Años , Atrofia/epidemiología , Atrofia/metabolismo , Atrofia/patología , Biomarcadores/metabolismo , Niño , Preescolar , Comorbilidad , Femenino , Gastritis/epidemiología , Gastritis/metabolismo , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/metabolismo , Humanos , Lactante , Enfermedades Intestinales/epidemiología , Enfermedades Intestinales/metabolismo , Masculino , México , Persona de Mediana Edad , Vigilancia de la Población , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/metabolismo , Antro Pilórico/metabolismoRESUMEN
BACKGROUND: American Indians face significant barriers to diagnosis and management of cardiovascular disease. We sought to develop a real-world implementation model for improving access to echocardiography within the Indian Health Service, the American Indian Structural Heart Disease Partnership. METHODS AND RESULTS: The American Indian Structural Heart Disease Partnership was implemented and evaluated via a 4-step process of characterizing the system where it would be instituted, building point-of-care echocardiography capacity, deploying active case finding for structural heart disease, and evaluating the approach from the perspective of the clinician and patient. Data were collected and analyzed using a parallel convergent mixed methods approach. Twelve health care providers successfully completed training in point-of-care echocardiography. While there was perceived usefulness of echocardiography, providers found it difficult to integrate screening point-of-care echocardiography into their workday given competing demands. By the end of 12 months, 6 providers continued to actively utilize point-of-care echocardiography. Patients who participated in the study felt it was an acceptable and effective approach. They also identified access to transportation as a notable challenge to accessing echocardiograms. Over the 12-month period, a total of 639 patients were screened, of which 36 (5.6%) had a new clinically significant abnormal finding. CONCLUSIONS: The American Indian Structural Heart Disease Partnership model exhibited several promising strategies to improve access to screening echocardiography for American Indian populations. However, competing priorities for Indian Health Service providers' time limited the amount of integration of screening echocardiography into outpatient practice. Future endeavors should explore community-based solutions to develop a more sustainable model with greater impact on case detection, disease management, and improved outcomes.
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Indio Americano o Nativo de Alaska , Cardiopatías , Sistemas de Atención de Punto , Humanos , Ecocardiografía , Cardiopatías/diagnóstico por imagen , Cardiopatías/terapia , Accesibilidad a los Servicios de SaludRESUMEN
CONTEXT.: Thyroid nodules with longitudinal nuclear grooves have been widely regarded as synonymous with papillary thyroid carcinoma (PTC). OBJECTIVE.: To study a series of cases of thyroid nodules that exhibited oncocytic (Hürthle cell) features and contained longitudinal nuclear grooves yet failed to display aggressive behavior or the full features of papillary thyroid carcinoma. DESIGN.: The clinicopathologic, immunohistochemical, and molecular genetic features of 15 patients with these features were studied. Next-generation sequencing was performed to examine 161 genes for oncogenic driver alterations associated with thyroid neoplasia. RESULTS.: The lesions occurred in 11 women and 4 men aged 27 to 80 years and measured 0.2 to 2.3 cm in diameter (mean, 1.1 cm). The tumors were well circumscribed and noninvasive and showed a proliferation of large cells with abundant granular cytoplasm and centrally placed nuclei displaying scattered longitudinal nuclear grooves. Immunohistochemical stains were negative for HBME-1, galectin-3, and CK19 in all cases. NRAS pQ61R was detected in 6 cases, KRAS p.Q61E in 1 case, and AKT2 p.E17K in 1 case. None of the genetic changes classically associated with conventional PTC or with high-grade thyroid malignant neoplasms were identified. Clinical follow-up in 9 patients showed no evidence of recurrence or metastases between 2 and 13 years (mean, 5.7 years). CONCLUSIONS.: Longitudinal nuclear grooves can be occasionally encountered in oncocytic (Hürthle cell) tumors and should not lead to a diagnosis of PTC in the absence of other features supporting that diagnosis.
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Adenoma Oxifílico , Carcinoma Papilar , Neoplasias de la Tiroides , Nódulo Tiroideo , Masculino , Humanos , Femenino , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología , Células Oxífilas/patología , Neoplasias de la Tiroides/patología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Carcinoma Papilar/patología , Adenoma Oxifílico/genética , Adenoma Oxifílico/patología , Biología MolecularRESUMEN
Background: Gaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors. Methods: This retrospective study evaluated individuals with Fontan circulation followed at our center since 2010. A gap in care was defined as an absence of any formal cardiology provider-patient contact (clinic visit or telehealth) for >15 months. Results: Over a third of 308 patients with Fontan circulation experienced at least one gap in care between 2010 and 2022, and 77 experienced a gap in care during the COVID-19 pandemic. Of this latter group, 27 (35%) had never experienced a prior gap in cardiology care until the pandemic. Those who experienced gaps in care during the pandemic were on average older (18.0 [IQR 9.6-25.6] vs. 14.2 [7.2-21.2] years, p = 0.01), more likely to be of Black/African American race (23.4% vs 7.4%, p = 0.001), and less likely to have a diagnosis of protein-losing enteropathy or plastic bronchitis (0% vs. 8.6%, p = 0.005). Those without a gap in care during the pandemic were more likely to have utilized telehealth visits (13% vs 3%, p = 0.02). Conclusion: Gaps in care are common and appear to have been exacerbated by the COVID-19 pandemic in those with a Fontan circulation. Such gaps are particularly common among African American and adult patients, and may potentially be mitigated by expanding telehealth access.
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The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.
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Neoplasias Colorrectales , Neoplasias Endometriales , Femenino , Humanos , Inestabilidad de Microsatélites , Neoplasias Endometriales/genética , Neoplasias Endometriales/cirugía , Repeticiones de Microsatélite , Fenotipo , Inmunohistoquímica , Reparación de la Incompatibilidad de ADN , Neoplasias Colorrectales/genéticaRESUMEN
Objective The purpose of this study was to evaluate pituitary tumor patient satisfaction with telemedicine, patient preference for telemedicine, potential socioeconomic benefit of telemedicine, and patients' willingness to proceed with surgery based on a telemedicine visit alone. Method In total, 134 patients who had pituitary surgery and a telemedicine visit during the coronavirus disease 2019 (COVID-19) pandemic (April 23, 2020-March 4, 2021) were called to participate in a 13-part questionnaire. Chi-square, ANOVA, and Wilcoxon Rank Sum tests were used to determine significance. Result Of 134 patients contacted, 90 responded (67%). Ninety-five percent were "satisfied" or "very satisfied" with their telemedicine visit, with 62% stating their visit was "the same" or "better" than previous in-person appointments. Eighty-two percent of the patients rated their telemedicine visit as "easy" or "very easy." On average, patients saved 150 minutes by using telemedicine compared with patient reported in-person visit times. Seventy-seven percent of patients reported the need to take off from work for in-person visits, compared with just 12% when using telemedicine. Forty-nine percent of patients preferred in-person visits, 34% preferred telemedicine, and 17% had no preference. Fifty percent of patients said they would feel comfortable proceeding with surgery based on a telemedicine visit alone. Patients with both initial evaluation and follow-up conducted via telemedicine were more likely to feel comfortable proceeding with surgery based on a telemedicine visit alone compared with patients who had only follow-up telemedicine visits ( p = 0.051). Conclusion Many patients are satisfied with telemedicine visits and feel comfortable proceeding with surgery based on a telemedicine visit alone. Telemedicine is an important adjunct to increase access to care at a Pituitary Center of Excellence.
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A study of 80 cases of spindle cell thymoma in which the spindle cell component was overshadowed by massive numbers of stromal lymphocytes is presented. The patients were 38 women and 42 men, aged 8 to 81 years (mean=54 y). All tumors presented as an anterior mediastinal mass; 5 patients had myasthenia gravis and one had Good syndrome. The tumors were well-circumscribed, encapsulated, and measured 2.9 to 26.0 cm in greatest diameter (mean=7.3 cm). Using modified Masaoka staging, 66 tumors were stage I, 10 were stage IIa, 2 were stage III and 1 was stage IV. Histologically the tumors were characterized by a predominant lymphocytic population admixed with scattered small spindle epithelial cells. The neoplastic spindle cells in these tumors demonstrated 2 major growth patterns: in 33 cases, the tumors were exclusively composed of dense sheets of lymphocytes containing scattered spindle cells resembling a lymphocyte-rich thymoma (WHO type B1); in the remaining cases the tumors showed admixtures of a predominantly lymphocytic component with areas that were lymphocyte-poor and contained a pure spindle cell population similar to WHO type A. Immunohistochemical stains and electron microscopy corroborated the spindle cell morphology in both types. The GTF2I p.L424H variant was identified in 53 of 63 (84%) cases analyzed. Clinical follow-up in 27 cases showed that most of the tumors behaved in an indolent manner. Our study expands the spectrum of spindle cell thymoma by demonstrating the existence of cases that are predominantly composed of lymphocyte-rich elements and lack areas with a pure (lymphocyte poor) spindle cell morphology.
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Timoma , Neoplasias del Timo , Femenino , Humanos , Inmunohistoquímica , Linfocitos/patología , Masculino , Biología Molecular , Timoma/genética , Neoplasias del Timo/genéticaRESUMEN
OBJECTIVES: To provide an overview of the challenges encountered during the interpretation of sequence variants detected by next-generation sequencing (NGS) in myeloid neoplasms, as well as the limitations of the technology with the goal of preventing the over- or undercalling of alterations that may have a significant effect on patient management. METHODS: Review of the peer-reviewed literature on the interpretation, reporting, and technical challenges of NGS assays for myeloid neoplasms. RESULTS: NGS has been integrated widely and rapidly into the standard evaluating of myeloid neoplasms. Review of the literature reveals that myeloid sequence variants are challenging to detect and interpret. Large insertions and guanine-cytosine-heavy areas prove technically challenging while frameshift and truncating alterations may be classified as variants of uncertain significance by tertiary analysis informatics pipelines due to their absence in the literature and databases. CONCLUSIONS: The analysis and interpretation of NGS results in myeloid neoplasia are challenging due to the varied number of detectable gene alterations. Familiarity with the genomic landscape of myeloid malignancies and knowledge of the tools available for the interpretation of sequence variants are essential to facilitate translation into clinical and therapy decisions.
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Neoplasias Hematológicas/genética , Trastornos Mieloproliferativos/genética , Neoplasias Hematológicas/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Trastornos Mieloproliferativos/diagnóstico , Análisis de Secuencia de ADN/métodosRESUMEN
Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8-34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P<0.0001), low-density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P<0.0001), and high-density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P<0.0001) than controls. In those with a Fontan, high-density lipoprotein cholesterol was inversely correlated with body mass index (r=-0.30, P<0.0001), high-sensitivity C-reactive protein (r=-0.27, P=0.0006), and alanine aminotransferase (r=-0.18, P=0.02) but not with other liver disease markers. Lower high-density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04-1.81 [P=0.03]). This relationship was attenuated when log high-sensitivity C-reactive protein was added to the model (HR, 1.26; 95% CI, 0.95-1.67 [P=0.10]). Total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high-density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan-associated liver disease and lipid metabolism.
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Colesterol/sangre , Dislipidemias/etiología , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Biomarcadores/sangre , Dislipidemias/sangre , Dislipidemias/epidemiología , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/sangre , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Prospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Secreted Protein Acid and Rich in Cysteine (SPARC) is an extracellular glycoprotein secreted by fibroblasts and osteoblasts in normal tissues. SPARC overexpression occurs in multiple tumors including pancreatic ductal adenocarcinoma (PDAC) and may predict favorable response to nab-paclitaxel. The prognostic significance of SPARC expression in PDAC is unclear - some reports indicate SPARC overexpression associates with poor outcomes and others find no correlation. Considering neoadjuvant therapy enhances the stromal fibrosis of PDAC and taking into account that SPARC is a component of PDAC stromal fibrosis, we hypothesized that SPARC expression would be greater in neoadjuvant-treated versus treatment-naive PDAC. Quantitative immunohistochemistry was used to measure SPARC expression in resected PDAC in 74 cases of neoadjuvant treated PDAC and 95 cases of treatment-naïve PDAC. SPARC expression was increased 54% in neoadjuvant treated PDAC compared to treatment-naïve PDAC. These data indicate that increased SPARC expression correlates with neoadjuvant therapy in PDAC.
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The archaeological site of Lepenski Vir is widely known after its remarkable stone art sculptures that represent a unique and unprecedented case of Holocene hunter-gatherer creativity. These artworks were found largely associated with equally unique trapezoidal limestone building floors around their centrally located rectangular stone-lined hearths. A debate has raged since the discovery of the site about the chronological place of various discovered features. While over years different views from that of the excavator about the stratigraphy and chronology of the site have been put forward, some major disagreements about the chronological position of the features that make this site a key point of reference in European Prehistory persist. Despite challenges of re-analyzing the site's stratigraphy from the original excavation records, taphonomic problems, and issues of reservoir offsets when providing radiocarbon measurements on human and dog bones, our targeted AMS (Accelerator Mass Spectrometry) dating of various contexts from this site with the application of Bayesian statistical modelling allows us to propose with confidence a new and sound chronological framework and provide formal estimates for several key developments represented in the archaeological record of Lepenski Vir that help us in understanding the transition of last foragers to first farmers in southeast Europe as a whole.
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Estrogen receptor-beta (ERß) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERß agonists (SERBAs) with in vivo efficacy that are A-C estrogens, lacking the B and D estrogen rings. The most potent and selective A-C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the ß over α isoform and with EC50s of 20-30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound's ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A-C estrogen is selective, brain penetrant, and facilitates memory consolidation.
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Receptor beta de Estrógeno/agonistas , Estrógenos/química , Estrógenos/farmacología , Consolidación de la Memoria/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Receptor beta de Estrógeno/química , Receptor beta de Estrógeno/metabolismo , Estrógenos/metabolismo , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Conformación Proteica , Relación Estructura-ActividadRESUMEN
BACKGROUND/OBJECTIVE: To review the literature and provide a framework for sex education for the child, adolescent, or adult with a spinal cord injury (SCI) or disorder. METHODS: Discussion and review of the literature. RESULTS: There is a paucity of research available regarding the impact of SCIs and disorders on sexuality in children and adolescents; however, there is a significant body of literature on this topic in adults. Recommendations based on these findings are presented. Guidelines regarding sexuality in children and adolescents with general disabilities may be adapted for the education of children and adolescents with SCIs and disorders. CONCLUSIONS: Parents, partners, and persons with SCIs and disorders should be provided with age-appropriate information about sexuality that includes specific information with respect to SCIs and disorders. Although there has been a significant increase in information that is available about the impact of sexuality in adults after SCI, more information is needed about the effects of SCIs and disorders on the healthy sexual development of children and adolescents.
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Envejecimiento/psicología , Educación del Paciente como Asunto , Sexualidad/psicología , Traumatismos de la Médula Espinal/psicología , Femenino , Humanos , Masculino , Literatura de Revisión como AsuntoRESUMEN
BACKGROUND: Adequate range of knee motion is critical for successful total knee arthroplasty. While aggressive physical therapy is an important component, manipulation may be a necessary supplement. There seems to be a lack of consensus with variable practices existing in managing stiff postoperative knees following arthroplasty. Hence we aim to determine the current practice and trend among knee surgeons throughout the United Kingdom. MATERIALS AND METHODS: Postal questionnaires were sent out to 100 knee surgeons registered with British Association of Knee Surgeons, ensuring that the whole of United Kingdom was well represented. The questions included whether the surgeon used Manipulation Under Anaesthaesia (MUA) as an option for stiff postoperative knees; timing of MUA; use of Continuous Passive Motion (CPM) post-manipulation. RESULTS: We received 82 responses. 46% of respondents performed MUA routinely, 43% sometimes, and 11 never. Majority (71.23%) performed MUA within 3 months of the index procedure. 68% routinely used CPM post-manipulation while 7% of the respondents applied splints or serial cast post MUA. 41% of the surgeons routinely used Patient Controlled Analgaesia ± Regional blocks. Majority (55%) never performed open/arthroscopic debridement of fibrous tissue for adhesiolysis. CONCLUSIONS: Knee manipulation requires an additional anaesthetic and may result in complications such as: supracondylar femur fractures, wound dehiscence, patellar tendon avulsions, haemarthrosis, and heterotopic ossification. Moreover studies have shown that manipulation while being an important therapeutic adjunct does not increase the ultimate flexion achieved. Manipulation should be reserved for the patient with difficult and painful flexion in the early postoperative period.
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We have recently shown that a study population of patients with at least 1 sessile serrated adenoma (SSA) are 4 times more likely to harbor synchronous serrated polyps [SSAs, traditional serrated adenomas (TSAs) and right sided hyperplastic polyps] than a unselected population of patients. However, 35% of the polyps in the study patients were conventional adenomas (CAds). We hypothesized that the CAds in these study patients would have histologic and molecular differences compared with CAds from a control population without sessile serrated adenomas. To this end, 104 study and 79 control CAds were analyzed according to 9 histologic criteria. A subset of these polyps was also screened for BRAF mutations, KRAS mutations, CpG island methylation, and MUC6 expression. A total of 31 study CAds and 2 control CAds had atypical histologic features (bright cytoplasmic eosinophilia +/- focal serrations and crypt dilatation). None of the adenomas tested had mutations in BRAF or KRAS. Evidence of low levels of CpG island methylation was seen in 35% of the atypical CAds and in only 4.5% of the typical CAds. In addition, these atypical CAds were more likely to express MUC6. Thus, the presence of cytoplasmic eosinophilia with or without focal serrations and crypt dilatation identifies a subset of CAds with characteristics of the serrated neoplasia pathway. These atypical CAds occur more commonly in patients predisposed to developing SSAs and suggest the presence of a mucosal field defect in these patients.
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Adenoma/patología , Neoplasias del Colon/patología , Pólipos del Colon/patología , Lesiones Precancerosas/patología , Adenoma/química , Adenoma/clasificación , Adenoma/genética , Anciano , Estudios de Casos y Controles , Neoplasias del Colon/química , Neoplasias del Colon/clasificación , Neoplasias del Colon/genética , Pólipos del Colon/química , Pólipos del Colon/clasificación , Pólipos del Colon/genética , Islas de CpG , Metilación de ADN , Análisis Mutacional de ADN , Dilatación Patológica , Eosinofilia/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hiperplasia , Inmunohistoquímica , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Mucina 6/análisis , Mutación , Lesiones Precancerosas/química , Lesiones Precancerosas/clasificación , Lesiones Precancerosas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas ras/genéticaRESUMEN
PURPOSE: We determined if the degree of preservation of sensory function in the T11-L2 dermatomes could be used to determine the potential for psychogenic erectile responses in men with spinal cord injury. MATERIALS AND METHODS: Subjects included 45 men with spinal cord injury and 16 able-bodied control subjects. A 78-minute laboratory based analysis was done of subject subjective arousal, penile circumference, blood pressure, and heart rate responses to audiovisual erotic and audiovisual erotic combined with manual penile stimulation. RESULTS: Able-bodied subjects generally had significantly greater penile circumferences than spinal cord injured subjects during the stimulation periods. The degree of preservation of combined pinprick and light touch sensation in the T11-L2 dermatomes distinguished those who did and did not have a significant increase in penile circumference with audiovisual stimulation. Blood pressure and heart rate readings were generally higher in able-bodied than spinal cord injured subjects throughout the experimental protocol. However, all readings were within normal limits. CONCLUSIONS: Results support the hypothesis that psychogenic erection depends on the sympathetic nervous system. Findings underscore a possible parallel in neurological control of sexual responses between the sexes.