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1.
Cancer J ; 30(4): 238-244, 2024.
Article in English | MEDLINE | ID: mdl-39042774

ABSTRACT

ABSTRACT: The treatment paradigm for rectal cancer has been shifting toward de-escalated approaches to preserve patient quality of life. Historically, the standard treatment in the United States for locally advanced rectal cancer has standardly comprised preoperative chemoradiotherapy coupled with total mesorectal excision. Recent data challenge this "one-size-fits-all" strategy, supporting the possibility of omitting surgery for certain patients who achieve a clinical complete response to neoadjuvant therapy. Consequently, patients and their physicians must navigate diverse neoadjuvant options, often in the context of pursuing organ preservation. Total neoadjuvant therapy, involving the administration of all chemotherapy and radiation before total mesorectal excision, is associated with the highest rates of clinical complete response. However, questions persist regarding the optimal sequencing of radiation and chemotherapy and the choice between short-course and long-course radiation. Additionally, meticulous response assessment and surveillance are critical for selecting patients for nonoperative management without compromising the excellent cure rates associated with trimodality therapy. As nonoperative management becomes increasingly recognized as a standard-of-care treatment option for patients with rectal cancer, ongoing research in patient selection and monitoring as well as patient-reported outcomes is critical to guide personalized rectal cancer management within a patient-centered framework.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Humans , Neoadjuvant Therapy/methods , Quality of Life , Chemoradiotherapy/methods , Treatment Outcome , Patient Selection , Disease Management
3.
JCO Clin Cancer Inform ; 5: 125-133, 2021 01.
Article in English | MEDLINE | ID: mdl-33492994

ABSTRACT

PURPOSE: Performance status (PS) is a subjective assessment of patients' overall health. Quantification of physical activity using a wearable tracker (Fitbit Charge [FC]) may provide an objective measure of patient's overall PS and treatment tolerance. MATERIALS AND METHODS: Patients with colorectal cancer were prospectively enrolled into two cohorts (medical and surgical) and asked to wear FC for 4 days at baseline (start of new chemotherapy [± 4 weeks] or prior to curative resection) and follow-up (4 weeks [± 2 weeks] after initial assessment in medical and postoperative discharge in surgical cohort). Primary end point was feasibility, defined as 75% of patients wearing FC for at least 12 hours/d, 3 of 4 assigned days. Mean steps per day (SPD) were correlated with toxicities of interest (postoperative complication or ≥ grade 3 toxicity). A cutoff of 5,000 SPD was selected to compare outcomes. RESULTS: Eighty patients were accrued over 3 years with 55% males and a median age of 59.5 years. Feasibility end point was met with 68 patients (85%) wearing FC more than predefined duration and majority (91%) finding its use acceptable. The mean SPD count for patients with PS 0 was 6,313, and for those with PS 1, it was 2,925 (122 and 54 active minutes, respectively) (P = .0003). Occurrence of toxicity of interest was lower among patients with SPD > 5,000 (7 of 33, 21%) compared with those with SPD < 5,000 (14 of 43, 32%), although not significant (P = .31). CONCLUSION: Assessment of physical activity with FC is feasible in patients with colorectal cancer and well-accepted. SPD may serve as an adjunct to PS assessment and a possible tool to help predict toxicities, regardless of type of therapy. Future studies incorporating FC can standardize patient assessment and help identify vulnerable population.


Subject(s)
Colorectal Neoplasms , Fitness Trackers , Colorectal Neoplasms/surgery , Exercise , Feasibility Studies , Female , Humans , Male , Middle Aged , Postoperative Complications
5.
Cell Rep ; 26(4): 996-1009.e4, 2019 01 22.
Article in English | MEDLINE | ID: mdl-30655224

ABSTRACT

Genetic and biochemical defects of mitochondrial function are a major cause of human disease, but their link to mitochondrial morphology in situ has not been defined. Here, we develop a quantitative three-dimensional approach to map mitochondrial network organization in human muscle at electron microscopy resolution. We establish morphological differences between human and mouse and among patients with mitochondrial DNA (mtDNA) diseases compared to healthy controls. We also define the ultrastructure and prevalence of mitochondrial nanotunnels, which exist as either free-ended or connecting membrane protrusions across non-adjacent mitochondria. A multivariate model integrating mitochondrial volume, morphological complexity, and branching anisotropy computed across individual mitochondria and mitochondrial populations identifies increased proportion of simple mitochondria and nanotunnels as a discriminant signature of mitochondrial stress. Overall, these data define the nature of the mitochondrial network in human muscle, quantify human-mouse differences, and suggest potential morphological markers of mitochondrial dysfunction in human tissues.


Subject(s)
Mitochondria, Muscle/metabolism , Mitochondria, Muscle/pathology , Mitochondrial Diseases/metabolism , Mitochondrial Diseases/pathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Animals , DNA, Mitochondrial/metabolism , Humans , Mice , Mice, Transgenic , Species Specificity
6.
Cortex ; 111: 164-182, 2019 02.
Article in English | MEDLINE | ID: mdl-30502646

ABSTRACT

Facial expressions are described traditionally as monolithic or unitary entities. However, humans have the capacity to produce facial blends of emotion in which the upper and lower face simultaneously display different expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face in each hemisphere that, presumably, also occur in humans. Using high-speed videography, we began measuring the movement dynamics of spontaneous facial expressions, including facial blends, to develop a more complete understanding of the neurophysiology underlying facial expressions. In our part 1 publication in Cortex (2016), we found that hemispheric motor control of the upper and lower face is overwhelmingly independent; 242 (99%) of the expressions were classified as demonstrating independent hemispheric motor control whereas only 3 (1%) were classified as demonstrating dependent hemispheric motor control. In this companion paper (part 2), 251 unitary facial expressions that occurred on either the upper or lower face were analyzed. 164 (65%) expressions demonstrated dependent hemispheric motor control whereas 87 (35%) expressions demonstrated independent or dual hemispheric motor control, indicating that some expressions represent facial blends of emotion that occur across the vertical facial axis. These findings also support the concepts that 1) spontaneous facial expressions are organized predominantly across the horizontal facial axis and secondarily across the vertical facial axis and 2) facial expressions are complex, multi-component, motoric events. Based on the Emotion-type hypothesis of cerebral lateralization, we propose that facial expressions modulated by a primary-emotional response to an environmental event are initiated by the right hemisphere on the left side of the face whereas facial expressions modulated by a social-emotional response to an environmental event are initiated by the left hemisphere on the right side of the face.


Subject(s)
Face/physiology , Facial Expression , Functional Laterality/physiology , Motor Cortex/physiology , Adolescent , Adult , Emotions/physiology , Female , Humans , Male , Young Adult
7.
Cortex ; 76: 28-42, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26854960

ABSTRACT

Facial expressions are described traditionally as monolithic entities. However, humans have the capacity to produce facial blends, in which the upper and lower face simultaneously display different emotional expressions. This, in turn, has led to the Component Theory of facial expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face that, presumably, also occur in humans. The lower face is represented on the posterior ventrolateral surface of the frontal lobes in the primary motor and premotor cortices and the upper face is represented on the medial surface of the posterior frontal lobes in the supplementary motor and anterior cingulate cortices. Our laboratory has been engaged in a series of studies exploring the perception and production of facial blends. Using high-speed videography, we began measuring the temporal aspects of facial expressions to develop a more complete understanding of the neurophysiology underlying facial expressions and facial blends. The goal of the research presented here was to determine if spontaneous facial expressions in adults are predominantly monolithic or exhibit independent motor control of the upper and lower face. We found that spontaneous facial expressions are very complex and that the motor control of the upper and lower face is overwhelmingly independent, thus robustly supporting the Component Theory of facial expressions. Seemingly monolithic expressions, be they full facial or facial blends, are most likely the result of a timing coincident rather than a synchronous coordination between the ventrolateral and medial cortical motor areas responsible for controlling the lower and upper face, respectively. In addition, we found evidence that the right and left face may also exhibit independent motor control, thus supporting the concept that spontaneous facial expressions are organized predominantly across the horizontal facial axis and secondarily across the vertical axis.


Subject(s)
Behavior/physiology , Emotions/physiology , Face/physiology , Facial Expression , Functional Laterality/physiology , Motor Cortex/physiology , Adolescent , Adult , Female , Humans , Male , Young Adult
8.
Neuropharmacology ; 60(5): 748-56, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21185314

ABSTRACT

Group I metabotropic glutamate receptors (mGluRs) are expressed by many interneurons of the hippocampus. Although they have been implicated in short- and long-term synaptic plasticity of glutamatergic transmission, their roles in modulating transmission to interneurons are incompletely understood. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) acutely depressed transmission at synapses in the feed-forward inhibitory pathway made by Schaffer collaterals on interneurons in the rat hippocampal CA1 sub-field. DHPG elicited a qualitatively similar depression at synapses made by pyramidal neuron axon collaterals on interneurons in the feedback circuit in stratum oriens. Selective blockers revealed a link from mGluR1 to reversible, and mGluR5 to long-lasting, depression. The acute DHPG-induced depression was consistently accompanied by an elevation in paired-pulse ratio, implying a presynaptic decrease in release probability. However, it was also attenuated by blocking G-protein and Ca(2+) signalling within the postsynaptic neuron, arguing for a retrograde signalling cascade. The DHPG-evoked depression was unaffected by antagonists of CB1 and GABA(B) receptors but was occluded when presynaptic P/Q-type Ca(2+) channels were blocked. Finally, high-frequency stimulation delivered to an independent conditioning pathway evoked a heterosynaptic reversible depression, which was sensitive to group I mGluR antagonists. Group I mGluRs thus powerfully modulate synaptic excitation of hippocampal interneurons and mediate inter-synaptic cross-talk. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.


Subject(s)
Excitatory Amino Acid Agonists/pharmacology , Glycine/analogs & derivatives , Hippocampus/physiology , Interneurons/physiology , Methoxyhydroxyphenylglycol/analogs & derivatives , Receptors, Metabotropic Glutamate/agonists , Resorcinols/pharmacology , Synaptic Transmission/drug effects , Animals , Calcium Channels/drug effects , Calcium Channels/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Glycine/pharmacology , Methoxyhydroxyphenylglycol/pharmacology , Neuronal Plasticity , Rats , Rats, Sprague-Dawley , Receptors, Metabotropic Glutamate/physiology , Signal Transduction/physiology , Synapses/physiology
9.
J Safety Res ; 34(2): 175-81, 2003.
Article in English | MEDLINE | ID: mdl-12737956

ABSTRACT

PROBLEM: An average of three workers a year are killed in surface mining operations when a piece of haulage equipment collides with another smaller vehicle or a worker on foot. Another three workers are killed each year when haulage equipment backs over the edge of a dump point or stockpile. Devices to monitor the blind areas of mining equipment are needed to provide a warning to operators when a vehicle, person, or change in terrain is near the equipment. METHOD: A proximity warning system (PWS) based on the global positioning system (GPS) and peer-to-peer communication has been developed to prevent collisions between mining equipment, small vehicles, and stationary structures. RESULTS: A final system was demonstrated using one off-highway haul truck, three smaller vehicles, and various stationary structures at a surface mining operation. The system successfully displayed the location of nearby vehicles and stationary structures and provided visual and audible warnings to the equipment operator when they were within a preset distance. SUMMARY: Many surface mining operations already use GPS technology on their mobile equipment for tracking and dispatch. Our tests have shown that it is feasible to add proximity warning to these existing systems as a safety feature. Larger scale and long-term tests are needed to prove the technology adequately. IMPACT ON INDUSTRY: A PWSs that incorporates a combination of technologies could significantly reduce accidents that involve collisions or driving over an edge at surface mining operations.


Subject(s)
Accidents, Traffic/prevention & control , Geographic Information Systems , Mining/instrumentation , Occupational Health , Accidents, Traffic/mortality , Communication , Humans , United States , Workforce
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