RESUMEN
In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that "explain" patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system.
Asunto(s)
Ratones , Atractivos Sexuales/orina , Órgano Vomeronasal/fisiología , Animales , Cromatografía Liquida , Femenino , Masculino , Ratones Endogámicos , Neuronas/citología , Neuronas/fisiología , Atractivos Sexuales/química , Conducta Sexual Animal , Olfato , Especificidad de la Especie , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Long-term treatment-related toxicity may substantially impact well-being, quality of life (QoL), and health of children/adolescents with brain tumors (CBTs). Strategies to reduce toxicity include pencil beam scanning (PBS) proton therapy (PT). This study aims to report clinical outcomes and QoL in PBS-treated CBTs. PROCEDURE: We retrospectively reviewed 221 PBS-treated CBTs aged <18 years. Overall-free (OS), disease-free (DFS), and late-toxicity-free survivals (TFS), local control (LC) and distant (DC) brain/spinal control were calculated using Kaplan-Meier estimates. Prospective QoL reports from 206 patients (proxies only ≤4 years old [yo], proxies and patients ≥5 yo) were descriptively analyzed. Median follow-up was 51 months (range, 4-222). RESULTS: Median age at diagnosis was 3.1 years (range, 0.3-17.7). The main histologies were ependymoma (n = 88; 39.8%), glioma (n = 37; 16.7%), craniopharyngioma (n = 22; 10.0%), atypical teratoid/rhabdoid tumor (ATRT) (n = 21; 9.5%) and medulloblastoma (n = 15; 6.8%). One hundred sixty (72.4%) patients received chemotherapy. Median PT dose was 54 Gy(relative biological effectiveness) (range, 18.0-64.8). The 5-year OS, DFS, LC, and DC (95% CI) were 79.9% (74-85.8), 65.2% (59.8-70.6), 72.1% (65.4-78.8), and 81.8% (76.3-87.3), respectively. Late PT-related ≥G3 toxicity occurred in 19 (8.6%) patients. The 5-year ≥G3 TFS was 91.0% (86.3-95.7). Three (1.4%) secondary malignancies were observed. Patients aged ≤3 years at PT (P = .044) or receiving chemotherapy (P = .043) experienced more ≥G3 toxicity. ATRT histology independently predicted distant brain failure (P = .046) and death (P = .01). Patients aged ≥5 years self-rated QoL higher than their parents (proxy assessment). Both reported lower social functioning and cognition after PT than at baseline, but near-normal long-term global well-being. QoL was well below normal before and after PT in children ≤4 years. CONCLUSIONS: The outcome of CBTs was excellent after PBS. Few patients had late ≥G3 toxicity. Patients aged <5 years showed worse QoL and toxicity outcomes.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Terapia de Protones/mortalidad , Calidad de Vida , Adolescente , Neoplasias Encefálicas/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Estudios Prospectivos , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The use of proton therapy (PT) in adolescents and young adults (AYAs) is becoming increasingly popular. This study aims to assess the outcomes and late toxicity consequences in AYAs (15-39 years) with brain/skull base tumors treated with pencil beam scanning proton therapy. METHODS: One hundred seventy six AYAs treated curatively at the Paul Scherrer Institute (PSI) were identified. Median age was 30 years (range 15-39) and median prescribed dose was 70.0 Gy (relative biological effectiveness [RBE]) (range 50.4-76.0). The most common tumors treated were chordomas/chondrosarcomas (61.4%), followed by gliomas (15.3%), and meningiomas (14.2%). RESULTS: After a median follow up of 66 months (range 12-236), 24 (13.6%) local only failures and one (0.6%) central nervous system (CNS) distant only failure were observed. The 6-year local control, distant progression-free survival, and overall survival were 83.2%, 97.4%, and 90.2%, respectively. The 6-year high-grade (≥grade [G] 3) PT-related late toxicity-free survival was 88.5%. Crude late toxicity rates were 26.2% G1, 37.8% G2, 12.2% G3, 0.6% G4, and 0.6% G5. The one G4 toxicity was a retinopathy and one G5 toxicity was a brainstem hemorrhage. The 6-year cumulative incidences for any late PT-related pituitary, ototoxicity, and neurotoxicity were 36.3%, 18.3%, and 25.6%; whilst high-grade (≥G3) ototoxicity and neurotoxicity were 3.4% and 2.9%, respectively. No secondary malignancies were observed. The rate of unemployment was 9.5% pre-PT, increasing to 23.8% post-PT. Sixty-two percent of survivors were working whilst 12.7% were in education post-PT. CONCLUSIONS: PT is an effective treatment for brain/skull base tumors in the AYA population with a reasonable late toxicity profile. Despite good clinical outcomes, around one in four AYA survivors are unemployed after treatment.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Terapia de Protones/mortalidad , Calidad de Vida , Neoplasias de la Base del Cráneo/radioterapia , Adolescente , Adulto , Neoplasias Encefálicas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/patología , Tasa de Supervivencia , Adulto JovenRESUMEN
The mammalian Y chromosome gene families in the ampliconic region are expressed predominantly or exclusively in the testis, and their copy number variations (CNV) are significantly associated with male reproductive traits, suggesting they have important roles in spermatogenesis and testicular development. ZNF280AY (zinc finger protein 280A, Y-linked) is a member of the zinc finger protein family and has been identified as a bovid-specific Y-chromosome gene. The current study applied a reliable quantitative real-time PCR method to estimate the CNV of ZNF280AY in 715 bulls across 21 cattle breeds and to further investigate the association of the CNV of ZNF280AY with bull reproductive traits and ZNF280AY mRNA expression levels in adult testis. The results revealed that the median copy number of ZNF280AY was 47, and the copy number varied from 11 to 154, showing significant CNV between and within the investigated cattle breeds. In addition, all 715 bulls were classified into Y1, Y2, and Y3 lineage groups based on a rapid genotyping method described previously. Pairwise comparisons indicated that bulls belonging to the Y1 lineage had a significantly lower median copy number (40) than bulls belonging to the Y2 (52) and Y3 lineages (57). Association analysis revealed that the CNV of ZNF280AY was correlated negatively with the percentage of normal sperm and sperm concentration in Holstein bulls, whereas no significant correlation was observed with ejaculation volume, total sperm count, sperm motility, postthaw motility (PTM), and scrotal circumference in Holstein and Simmental bulls. Furthermore, no correlation was observed between ZNF280AY copy number and ZNF280AY mRNA expression levels in the testis. The current study suggests that the CNV of the ZNF280AY gene family is associated with male reproductive traits and may serve as a valuable marker for early bull fertility selection in Holstein breeding programs.
Asunto(s)
Bovinos/genética , Variaciones en el Número de Copia de ADN , Fertilidad/genética , Regulación de la Expresión Génica , Genes Ligados a Y/genética , Reproducción/genética , Cromosoma Y/genética , Animales , Cruzamiento , Bovinos/fisiología , Marcadores Genéticos/genética , Genotipo , Masculino , Especificidad de Órganos , Fenotipo , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Especificidad de la Especie , Recuento de Espermatozoides/veterinaria , Motilidad Espermática/genética , Espermatogénesis/genética , Testículo/fisiología , Dedos de Zinc/genéticaRESUMEN
Okur-Chung syndrome is a neurodevelopmental condition attributed to germline CSNK2A1 pathogenic missense variants. We present 8 unreported subjects with the above syndrome, who have recognizable dysmorphism, varying degrees of developmental delay and multisystem involvement. Together with 6 previously reported cases, we present a case series of 7 female and 7 male subjects, highlighting the recognizable facial features of the syndrome (microcephaly, hypertelorism, epicanthic fold, ptosis, arched eyebrows, low set ears, ear fold abnormality, broad nasal bridge and round face) as well as frequently occurring clinical features including neurodevelopmental delay (93%), gastrointestinal (57%), musculoskeletal (57%) and immunological (43%) abnormalities. The variants reported in this study are evolutionary conserved and absent in the normal population. We observed that the CSNK2A1 gene is relatively intolerant to missense genetic changes, and most variants are within the protein kinase domain. All except 1 variant reported in this cohort are spatially located on the binding pocket of the holoenzyme. We further provide key recommendations on the management of Okur-Chung syndrome. To conclude, this is the second case series on Okur-Chung syndrome, and an in-depth review of the phenotypic features and genomic findings of the condition with suggestions on clinical management.
Asunto(s)
Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Trastornos del Neurodesarrollo/genética , Adolescente , Quinasa de la Caseína II/química , Quinasa de la Caseína II/genética , Niño , Preescolar , Discapacidades del Desarrollo/fisiopatología , Cara/fisiopatología , Femenino , Genotipo , Humanos , Discapacidad Intelectual/fisiopatología , Masculino , Anomalías Musculoesqueléticas/genética , Anomalías Musculoesqueléticas/fisiopatología , Mutación Missense/genética , Trastornos del Neurodesarrollo/fisiopatología , Fenotipo , Conformación Proteica , Pliegue de Proteína , Secuenciación del Exoma/métodosRESUMEN
BACKGROUND: Thromboelastography (TEG) provides an integrated measurement of blood coagulation function and has been reported to be a useful tool for predicting clinical outcomes in patients with cardiovascular diseases. We aimed to investigate the application of TEG on admission for predicting early neurological deterioration (END) in patients with acute ischemic stroke and its potential correlation with the evolution of ischemic lesions. METHODS: Among patients consecutively admitted between January 1, 2016, and September 31, 2017, those presenting with mild and moderate acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤14) within 24 h of stroke onset were identified and included in this study. TEG was performed on the first day of admission. END was defined as an increase of ≥1 on subitems of the NIHSS or the emergence of new symptoms within 72 h of admission. Demographics, lab test results, and TEG values were compared according to whether END occurred. A multiple logistic regression model was then developed to investigate the predictive power of TEG for END. Receiver operating characteristic (ROC) curves were then plotted to evaluate the optimal cutoff values. RESULTS: Of the 246 eligible patients (mean age 65.3 ± 12.9 years, 73.6% male), END was identified in 72 (29.3%) patients. Patients with END corresponded to a higher proportion of females, a more prevalent history of diabetes mellitus (DM), higher baseline NIHSS scores, higher serum high-sensitivity C-reactive protein (hsCRP) levels, and significantly shorter R on TEG (4.0 ± 1.0 vs. 4.7 ± 1.2 min, p < 0.001). In further comparisons stratified by R tertiles, significant trends were found between shorter R and being female and older and being more likely to exhibit diffusion weighted imaging progression on follow-up MRI. After adjusting for female sex, baseline NIHSS score, DM, and hsCRP, the lower tertile of R (R ≤3.8 min) was strongly associated with END (OR 3.556, 95% CI 1.165-10.856, p < 0.001). ROC analysis demonstrated that R ≤3.45 min had the best predictive value for END with 87.9% sensitivity and 40.3% specificity. CONCLUSION: Decreased R time on admission TEG is associated with END within 3 days in patients with acute ischemic stroke.
Asunto(s)
Coagulación Sanguínea , Isquemia Encefálica/diagnóstico , Sistema Nervioso Central/fisiopatología , Evaluación de la Discapacidad , Accidente Cerebrovascular/diagnóstico , Tromboelastografía , Trombofilia/diagnóstico , Anciano , Isquemia Encefálica/sangre , Isquemia Encefálica/fisiopatología , Angiografía Cerebral/métodos , Imagen de Difusión por Resonancia Magnética , Progresión de la Enfermedad , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Admisión del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/fisiopatología , Trombofilia/sangre , Factores de TiempoRESUMEN
Various studies have investigated laryngeal function and survival after induction chemotherapy in hypopharyngeal carcinoma, but potential factors to help predict response rates after induction chemotherapy remain unknown. This retro- spective study evaluated which factors are related to an ineffective response to two-cycle docetaxel, cisplatin, and 5-fluoro- uracil (TPF) induction chemotherapy in hypopharyngeal carcinoma to determine potential candidates for this treatment in clinical practice. From Jan 2005 to Dec 2015, 81 patients diagnosed with hypopharyngeal squamous cell carcinoma based on a pathological examination were analyzed. They were administered two-cycle TPF induction chemotherapy, and magnetic resonance imaging was performed before and after induction chemotherapy. The mean survival time was 5.7 years (95% confidence interval, 5.1-6.2 years). The 1, 3, 5 and 6-year survival rates were 98.8%, 80.1%, 64.5%, and 54.2%, respectively. TPF induction chemotherapy was well tolerated; the main adverse effects resolved with symptomatic treatment. A response to TPF induction chemotherapy was associated with lymph node size, tumor grade, invasion region, T stage, and primary tumor. The following issues were significantly associated with an increasing non-response rate to two-cycle induction chemotherapy: increasing lymph node size, moderately differentiated squamous cell carcinoma, invasion of the esophagus along with the thyroid cartilage, and primary tumor in the piriform sinus. Lymph nodes of ≥2.15 cm, moderately differenti- ated tumor grade, or thyroid cartilage invasion were the best cutoff values for patients who did not respond to induction chemotherapy. However, the initial cancer site, cancer stage, and degree of cancer differentiation were not closely related to the efficacy of induction chemotherapy.
Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Fluorouracilo/uso terapéutico , Quimioterapia de Inducción , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Tasa de SupervivenciaRESUMEN
AIM: Sodium pentosan polysulfate (Na-PPS) is a plant-based agent that has similar action with low-molecular-weight heparin. It inhibits factor Xa, preventing blood clot formation. To date, its use in clinical practice as thromboprophylaxis agent is still limited. In addition, the efficacy and safety profile of this agent was not robustly reported globally, especially for countries with major Muslim population. We hypothesized that Na-PPS was equally effective as the standard thromboprophylaxis. We aim to compare the efficacy and safety of Na-PPS against standard agent (fondaparinux or enoxaparin). METHODS: This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding. RESULTS: Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001). CONCLUSION: Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.
Asunto(s)
Anticoagulantes/farmacología , Procedimientos Quirúrgicos Ginecológicos , Evaluación de Resultado en la Atención de Salud , Poliéster Pentosan Sulfúrico/farmacología , Complicaciones Posoperatorias/prevención & control , Hemorragia Posoperatoria/inducido químicamente , Tromboembolia/prevención & control , Adulto , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Enoxaparina/farmacología , Femenino , Humanos , Persona de Mediana Edad , Poliéster Pentosan Sulfúrico/administración & dosificación , Poliéster Pentosan Sulfúrico/efectos adversosRESUMEN
Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line. As compared it to its parental cell line (CMT7364), CMT7364/5-FU showed different morphology, cross-resistant to other chemo-drugs and a prolonged population doubling time (PDT). The drug efflux pump proteins (ABCB1 and ABCG2) in CMT7364/5-FU were up-regulated. In vivo, the similar result revealed that CMT7364/5-FU cell line was more resistant to 5-FU. In conclusion, a 5-FU-resistant canine mammary tumor cell line (CMT7364/5-FU) was successfully established, it can serve as a good model for researching the mechanism of MDR and screening effective agents to reverse drug resistance.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Enfermedades de los Perros/patología , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Neoplasias Mamarias Animales/tratamiento farmacológico , Animales , Línea Celular Tumoral , Perros , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismoAsunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Personal de Salud , Enfermedades Profesionales/complicaciones , Neumonía Viral/complicaciones , Enfermedades de la Piel/complicaciones , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study aimed to determine whether phosphorylation of histone H2AX (γH2AX) is a predictive marker for neoadjuvant chemotherapy patients of cervical cancer. MATERIALS AND METHODS: The sections were divided into three sets. Set 1 consisted of 40 pre-treatment biopsies. Post-treatment tissues includes 38 patients in set 2 and 34 patients in set 3 who received cisplatin concurrent docetaxel treatment for one or two cycles, respectively. Formalin-fixed paraffin-embedded sections were analyzed after antigen retrieval and fluorescence antibody labeling for γH2AX staining. RESULTS: The expressions of γH2AX in cervical cancer tissues of post-neoadjuvant chemotherapy decreased to 22.94 ± 14.02% and 23.68 ± 13.55% (one and two cycles treatment, respectively) compared to preneoadjuvant chemotherapy (28.29 ± 15.67%), however there was no significant difference for γH2AX expression between pre- and post-neoadjuvant chemotherapy patients (F = 1.425, p = 0.245). There was no significant correlation between γH2AX expression and clinicopathologic parameters in patients of pre- and post-neoadjuvant chemotherapy. CONCLUSIONS: As a predictive marker for neoadjuvant chemotherapy of cervical cancer, more extensive research regarding γH2AX expression should be explored.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Histonas/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Docetaxel , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Taxoides/administración & dosificación , Resultado del Tratamiento , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Adulto JovenAsunto(s)
Unión Europea/organización & administración , Medicina Basada en la Evidencia/organización & administración , Neoplasias/radioterapia , Terapia de Protones/métodos , Oncología por Radiación/organización & administración , Ensayos Clínicos como Asunto , Fraccionamiento de la Dosis de Radiación , Europa (Continente) , Medicina Basada en la Evidencia/economía , Medicina Basada en la Evidencia/métodos , Humanos , Terapia de Protones/economía , Oncología por Radiación/economía , Oncología por Radiación/métodos , Sociedades Médicas/organización & administraciónRESUMEN
Many different malignancies occur in children, but overall, cancer in childhood is rare. Survival rates have improved appreciably and are higher compared with most adult tumour types. Treatment schedules evolve as a result of clinical trials and are typically complex and multi-modality, with radiotherapy an integral component of many. Risk stratification in paediatric oncology is increasingly refined, resulting in a more personalized use of radiation. Every available modality of radiation delivery: simple and advanced photon techniques, proton beam therapy, molecular radiotherapy, and brachytherapy, have their place in the treatment of children's cancers. Radiotherapy is rarely the sole treatment. As local therapy, it is often given before or after surgery, so the involvement of the surgeon is critically important, particularly when brachytherapy is used. Systemic treatment is the standard of care for most paediatric tumour types, concomitant administration of chemotherapy is typical, and immunotherapy has an increasing role. Delivery of radiotherapy is not done by clinical or radiation oncologists alone; play specialists and anaesthetists are required, together with mould room staff, to ensure compliance and immobilization. The support of clinical radiologists is needed to ensure the correct interpretation of imaging for target volume delineation. Physicists and dosimetrists ensure the optimal dose distribution, minimizing exposure of organs at risk. Paediatric oncology doctors, nurses, and a range of allied health professionals are needed for the holistic wrap-around care of the child and family. Radiographers are essential at every step of the way. With increasing complexity comes a need for greater centralization of services.
Asunto(s)
Braquiterapia , Neoplasias , Oncología por Radiación , Adulto , Humanos , Niño , Oncología Médica , Reino UnidoRESUMEN
Background: Patients with primary brain tumors (PBT) face significant mobility issues related to their disease and/or treatment. Here, the authors describe the preliminary utility and feasibility of two established mobility measures, the Timed-Up-and-Go (TUG) and Five-Times Sit-to-Stand (TSS) tests, in quickly and objectively assessing the mobility status of PBT patients at a single institution's neuro-oncology clinic. Methods: Adult patients undergoing routine PBT care completed the TUG/TSS tests and MD Anderson Symptom Inventory-Brain Tumor module (MDASI-BT), which assessed symptom burden and interference with daily life, during clinic visits over a 6-month period. Research staff assessed feasibility metrics, including test completion times/rates, and collected demographic, clinical, and treatment data. Mann-Whitney tests, Kruskal-Wallis tests, and Spearman's rho correlations were used to interrogate relationships between TUG/TSS test completion times and patient characteristics. Results: The study cohort included 66 PBT patients, 59% male, with a median age of 47 years (range: 20-77). TUG/TSS tests were completed by 62 (94%) patients. Older patients (P < .001) and those who were newly diagnosed (P = .024), on corticosteroids (P = .025), or had poor (≤80) KPS (P < .01) took longer to complete the TUG/TSS tests. Worse activity-related (work, activity, and walking) interference was associated with longer TUG/TSS test completion times (P < .001). Conclusions: The TUG/TSS tests are feasible for use among PBT patients and may aid in clinical care. Older age, being newly diagnosed, using corticosteroids, poor (≤80) KPS, and high activity-related interference were associated with significant mobility impairment, highlighting the tests' potential clinical utility. Future investigations are warranted to longitudinally explore feasibility and utility in other practice and disease settings.
RESUMEN
The two-dimensional (2D) nonseparable linear canonical transform (NSLCT) is a generalization of the fractional Fourier transform (FRFT) and the LCT. It is useful in signal analysis and optics. The eigenfunctions of both the FRFT and the LCT have been derived. In this paper, we extend the previous work and derive the eigenfunctions of the 2D NSLCT. Although the 2D NSLCT is very complicated and has 16 parameters, with the proposed methods, we can successfully find the eigenfunctions of the 2D NSLCT in all cases. Since many optical systems can be represented by the 2D NSLCT, our results are useful for analyzing the self-imaging phenomena of optical systems.
RESUMEN
BACKGROUND: Headache accounts for a significant number of cases presenting to the Emergency Department (ED) and has a high societal cost, contributed by recurrent ED and clinic visits, and unnecessary diagnostic tests. OBJECTIVE: This review article covers the important clinical tools needed to evaluate headaches in both adults and children in the ED. METHODS: Medline/PubMed was searched using the keywords "Emergency department", "headache", "adult", "pediatric", "clinical assessment", "diagnosis" and "treatment", in the title or abstract. The search covers the period from 1 January 1990 to 31 December 2019. RESULTS: The articles selected were based on their relevancy to the objective of this review article. Additional relevant publications were identified from article references lists. CONCLUSION: The emergency physician plays a key role in differentiating between primary and secondary headaches. Within the limited ED resources, appropriate diagnostic testing should be used to identify the life-threatening headaches. This will ensure patients are given the appropriate evidence-based pharmacological therapy and holistic management.
Asunto(s)
Servicio de Urgencia en Hospital , Cefalea , Adulto , Atención Ambulatoria , Niño , Cefalea/diagnóstico , Cefalea/terapia , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Patients with high-grade glioma (HGG) face unique challenges toward the end of life (EoL), given their aggressive trajectory and neurologic deterioration. Aggressiveness of medical care at EoL has been identified as an important quality metric for oncology patients. At this time, limited data exist around the nature of EoL care of patients with HGG. METHODS: Patients with HGG and palliative care (PC) referral seen between 2010 and 2015 were identified (N = 80). Of these, N = 52 met inclusion criteria. Random selections of patients with (1) HGG not referred to PC (n = 80), and (2) non-CNS cancers with PC referral (n = 80) were identified for comparison. A composite score of aggressiveness of medical care at EoL was calculated for each patient from predetermined variables. A time of eligibility for PC was defined for each patient when predetermined criteria based on symptom burden, functional status, and prognosis were met. RESULTS: Among the patients analyzed with HGG referred to PC, 59.6% (N = 31) were referred as inpatients, and 53.8% (N = 28) were referred within the last 12 weeks of life. Patients with HGG had similar aggressiveness of care at EoL regardless of PC referral, and HGG patients had less aggressive care at EoL than patients with non-CNS cancers (p = 0.007). Care was more aggressive at EoL in HGG patients who received late versus early PC referrals (p = 0.012). Motor weakness at time of eligibility (OR = 2.55, p = 0.002) and more disease progressions (OR = 1.25, p = 0.043) were associated with less aggressive care at EoL. CONCLUSIONS: Early clinical- and disease-related features predict the aggressiveness of medical care at EoL in patients with HGG. Formal PC consultation is used infrequently and suboptimally in patients with HGG. Our data suggest that the role of PC in improving EoL outcomes in HGG warrants further evaluation.
Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Cuidado Terminal/métodos , Neoplasias Encefálicas/patología , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Indicadores de Calidad de la Atención de SaludRESUMEN
Microendoscopic calcium imaging with one-photon miniature microscopes enables unprecedented readout of neural circuit dynamics during active behavior in rodents. In this study, we describe successful application of this technology in the rhesus macaque, demonstrating plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from large populations of neurons simultaneously in bilateral dorsal premotor cortices during performance of a naturalistic motor reach task. Imaging is stable over several months, allowing us to longitudinally track individual neurons and monitor their relationship to motor behavior over time. We observe neuronal calcium dynamics selective for reach direction, which we could use to decode the animal's trial-by-trial motor behavior. This work establishes head-mounted microendoscopic calcium imaging in macaques as a powerful approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and it promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.
Asunto(s)
Conducta Animal/fisiología , Calcio/metabolismo , Endoscopía , Imagenología Tridimensional , Corteza Motora/diagnóstico por imagen , Animales , Cabeza , Macaca mulatta , Masculino , Corteza Motora/cirugía , Neuronas/fisiología , Factores de TiempoRESUMEN
ADVANCES IN KNOWLEDGE: This review details the indication of brain tumors for proton therapy and give a list of the open prospective trials for these challenging tumors.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Medicina Basada en la Evidencia , Terapia de Protones/métodos , Adulto , Factores de Edad , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/radioterapia , Cordoma/diagnóstico por imagen , Cordoma/radioterapia , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Humanos , Estudios Prospectivos , Terapia de Protones/economía , Terapia de Protones/tendencias , Dosificación Radioterapéutica , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/radioterapiaRESUMEN
BACKGROUND: It is estimated only 8-11% of patients with glioblastoma (GBM) enrol in clinical trials, limiting treatment development. We analysed the clinical and demographic features of patients with GBM enroled in clinical trials at the University of Texas MD Anderson Cancer Center (MDACC). METHODS: We reviewed the records of adult patients treated for primary GBM between 2007 and 2012 at the MDACC. A total of 755 patients were identified: 133 were deemed non-eligible, 111 were deemed trial eligible but received standard care and 511 participated in a clinical trial (311 for newly diagnosed glioblastoma [nGBM] and 200 for recurrent glioblastoma [rGBM]). Population characteristics were analysed using descriptive statistics, and survival end-points were evaluated with the Kaplan-Meier method. RESULTS: The median age of clinical trial participants and trial eligible patients was 53.2 years (standard deviation 12.1). Most patients (49.4%) were enroled in a clinical trial protocol for nGBM. The majority of nGBM trial participants were male patients (65.1%), white (86.3%), married (84.4%) and in state (59.9%). Employment status, education, symptoms, tumour location, performance status, extent of resection and treatment facility differed between nGBM trial participants and non-participants. Patients who were eligible but did not enrol tended to be older, have worse performance status and live farther away from the MDACC. CONCLUSION: Numerous disease and demographic barriers exist in trial enrolment in patients with GBM. This study highlights some of these obstacles, which require attention to improve patient enrolment to clinical trials. Patient and physician engagement in novel therapeutic strategies is essential to improving outcomes in this disease.