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OBJECTIVES: Fluorescent in situ hybridization has been the definitive modality in testing for overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2) for decades to guide the appropriate treatment for cancer patients. In more recent years innovation and new techniques have been developed to supplant or even replace FISH as a standard method for biomarker testing. Alternative testing methods such polymerase chain reaction (PCR), next-generation sequencing (NGS), and other in situ hybridization (ISH)-derived techniques such as chromogenic-ISH (CISH) have been shown in multiple publications to have high concordance with FISH in addition to advantages in economics, logistics and practicality to the point where CISH and derived methods appear to have eclipsed FISH as a testing method of choice after immunohistochemistry (IHC). This review assesses the status of FISH compared to other diagnostic techniques such as IHC, CISH, and less common and/or experimental methods. Also addressed are the updates to the guidelines from the American Society of Clinical Oncology (ASCO), College of American Pathologists (CAP), and National Comprehensive Cancer Network (NCCN) regarding FISH and IHC for HER2 testing with the updates reducing the number of equivocal diagnoses in the latest iteration. Though our findings show a constantly changing technological landscape, FISH remains an important primary tool to guide medical treatment and as a solid foundation to build upon for innovation in cancer research.
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-The theoretical explanations used to explain changes in performance during motor imagery and physical practice conditions are inconsistent when memory retrieval is and is not required. This study measured performance time and workload during acquisition, a retention test requiring memory retrieval, and a retention test not requiring memory retrieval using a key-pressing task. The participants were assigned to physical practice with or without instructions to learn or motor imagery with or without instructions to learn. A diagram of the keys was presented during the practice trials and the first retention test, but was not presented during the second test. The results revealed no effect for the learning instructions or performance changes during the practice phases. However, during both retention tests participants in the physical practice conditions performed significantly faster than those in the motor imagery conditions. Also, higher levels of workload were reported for the motor imagery conditions when the retention test required memory retrieval compared to the other phases. A discussion of the implications of workload on performance is presented with respect to varying practice conditions.
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Imaginación/fisiología , Memoria/fisiología , Destreza Motora/fisiología , Práctica Psicológica , Desempeño Psicomotor/fisiología , Adulto , Femenino , Humanos , Aprendizaje , Masculino , Resistencia Física , Retención en Psicología/fisiología , Adulto JovenRESUMEN
Identifying potential modifiable determinants of functional movement ability and fatigue may inform efforts to maintain constant physical readiness, especially in active duty military over 40 years of age, who are largely sedentary throughout their work day. The primary aim of this study was to determine the associations among conventional fitness measures (body composition, flexibility, and strength), sedentary behavior (sitting time), functional movement ability, and fatigue in military personnel. Volunteer active duty personnel 40 years of age and older (n = 569 males; n = 121 females; mean ± SD for total sample = 44.5 ± 4.1 years) were assessed for adiposity (%Fat), strength, flexibility, self-reported sitting time, perceived fatigue using the fatigue severity scale, and functional movement ability using the functional movement screening criteria. Greater flexibility was associated with better functional movement screening scores (r = 0.34, p < 0.05), and waist circumference and %Fat were inversely related to function (r = -0.26 and -0.21, p < 0.05). Furthermore, less sitting time (p < 0.001) was associated with less fatigue. Our data suggest that exercise training, reductions in daily sitting time, and weight management may be viable intervention targets to enhance functional movement ability and reduce fatigue in 40+ year old active duty military personnel.
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Fatiga/fisiopatología , Personal Militar , Movimiento/fisiología , Aptitud Física/fisiología , Conducta Sedentaria , Adiposidad , Adulto , Fatiga/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fuerza Muscular , Rango del Movimiento Articular , Factores de Tiempo , Estados Unidos , Circunferencia de la CinturaRESUMEN
Mitotic progression in eukaryotic cells depends upon the activation of cyclin-dependent kinase 1 (CDK1), followed by its inactivation through the anaphase-promoting complex (APC)/cyclosome-mediated degradation of M-phase cyclins. Previous work revealed that expression of a constitutively active CDK1 (CDK1AF) in HeLa cells permitted their division, but yielded G1 daughter cells that underwent premature S-phase and early mitotic events. While CDK1AF was found to impede the sustained activity of APC-Cdh1, it was unknown if this defect improperly stabilized mitotic substrates and contributed to the occurrence of these premature M phases. Here, we show that CDK1AF expression in HeLa cells improperly stabilized APC-Cdh1 substrates in G1-phase daughter cells, including mitotic kinases and the APC adaptor, Cdc20. Division of CDK1AF-expressing cells produced G1 daughters with an accelerated S-phase onset, interrupted by the formation of premature bipolar spindles capable of spindle assembly checkpoint function. Further characterization of these phenotypes induced by CDK1AF expression revealed that this early spindle formation depended upon premature CDK1 and Aurora B activities, and their inhibition induced rapid spindle disassembly. Following its normal M-phase degradation, we found that the absence of Wee1 in these prematurely cycling daughter cells permitted the endogenous CDK1 to contribute to these premature mitotic events, since expression of a non-degradable Wee1 reduced the number of cells that exhibited premature cyclin B1oscillations. Lastly, we discovered that Cdh1-ablated cells could not be forced into a premature M phase, despite cyclin B1 overexpression and proteasome inhibition. Together, these results demonstrate that expression of constitutively active CDK1AF hampers the destruction of critical APC-Cdh1 targets, and that this type of condition could prevent newly divided cells from properly maintaining a prolonged interphase state. We propose that this more subtle type of defect in activity of the APC-driven negative-feedback loop may have implications for triggering genome instability and tumorigenesis.
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Proteína Quinasa CDC2/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/fisiología , Huso Acromático/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Ciclosoma-Complejo Promotor de la Anafase , Aurora Quinasa B , Aurora Quinasas , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Ensamble y Desensamble de Cromatina , Ciclina B1/genética , Ciclina B1/metabolismo , Replicación del ADN , Estabilidad de Enzimas , Expresión Génica , Silenciador del Gen , Inestabilidad Genómica , Células HeLa , Humanos , Puntos de Control de la Fase M del Ciclo Celular , Proteínas Mad2 , Mitosis , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Inhibidores de Proteasoma , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
The authors investigated the underlying processing structures for mental and physical practice. Participants mentally or physically performed 4 tasks during practice. Halfway through practice, 2 tasks were switched from mental to physical practice, or vice versa. After completing practice trials, participants performed 2 retention tests. The first retention test required memory retrieval and the second retention test reinstated the practice context and did not require memory retrieval. Measures of response initiation and execution showed discrepant findings suggesting that different processing structures underlie response initiation and execution during mental and physical practice. Findings for the switch conditions supported this interpretation suggesting that different neural structures may facilitate processing related to mental and physical practice.
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Recuerdo Mental , Práctica Psicológica , Retención en Psicología , Adulto , Femenino , Humanos , Masculino , Desempeño Psicomotor , Tiempo de ReacciónRESUMEN
The purpose of the present experiment was to investigate the role of auditory feedback and its impact on movement time in a standard Fitts task. Feedback was given at the moment of target acquisition. A 2-way analysis of variance found significant differences between feedback groups at all three indexes of difficulty (F(2, 40) = 156.02, p < .001). Results from a mixed-model multivariate analysis of variance for kinematic factors show significant differences in peak velocity and the location of peak velocity when comparing feedback groups. In general, the addition of auditory feedback decreased the task ID by .5.
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Estimulación Acústica/métodos , Retroalimentación Sensorial , Movimiento , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Desempeño Psicomotor , Factores de Tiempo , Adulto JovenRESUMEN
The myelodysplastic syndromes (MDS) are a clinically heterogeneous group of hematologic disorders. Cytogenetic analysis is crucial as it can provide both diagnostic and prognostic information. Herein, 32 cytogenetically normal patients with primary MDS were analyzed both by multiple FISH probes on interphase nuclei (FISH panel testing) and by M-FISH (metaphase nuclei). One patient had a chromosome 13q-arm deletion, while the remaining 31 patients had normal results. These findings confirm standard cytogenetics as an excellent technique in identifying the common chromosomal abnormalities associated with MDS and suggest limited utility for either a FISH panel test or M-FISH in primary MDS.