While the arrival of combination antiretroviral therapy significantly decreased the prevalence of HIV-associated dementia, between 35 and 70% of all infected adults continue to develop some form of cognitive impairment. These deficits appears to affect multiple neural subsystems, but the mechanisms and extent of damage are not fully understood. In the current study, we utilized magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired-pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory processing in 43 HIV-infected adults and 28 demographically-matched uninfected controls. MEG responses were imaged using a beamformer, and time series data were extracted from the peak voxel in grand-averaged functional brain images to quantify the dynamics of sensory gating, oscillatory power, spontaneous power, and other neural indices. We found a significantly weakened response to the second stimulation compared to the first across groups, indicating significant sensory gating irrespective of HIV-infection. Interestingly, HIV-infected participants exhibited reduced neural responses in the 20-75 Hz gamma range to each somatosensory stimulation compared to uninfected controls, and exhibited significant alterations in peak gamma frequency in response to the second stimulation. Finally, HIV-infected participants also had significantly stronger spontaneous activity in the gamma range (i.e., 20-75 Hz) during the baseline period before stimulation onset. In conclusion, while HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency. We propose that this pattern of deficits suggests dysfunction in the somatosensory cortices, which is potentially secondary to accelerated aging.
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http://dx.doi.org/10.1016/j.nicl.2018.07.009 | DOI Listing |
Purpose: To better understand burnout in oncology and clinician well-being along the career continuum starting with training, we sought to characterize the professional well-being of physicians training in medical oncology in 2023 and to identify trends over time comparing to fellows from a decade prior.
Methods: All US medical oncology fellows taking the 2023 ASCO Medical Oncology In-Training Exam (ITE) were invited to complete an optional post-exam survey evaluating fatigue, satisfaction with work-life integration (WLI), emotional exhaustion and depersonalization. 2023 ITE survey responses were compared to the 2013 ASCO post-ITE survey (n=1345).
Sci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFPLoS One
January 2025
Alliance for Research in Exercise Nutrition and Activity (ARENA), Allied Health and Human Performance, University of South Australia, Adelaide, Australia.
Background: Cold-water immersion (CWI) has gained popularity as a health and wellbeing intervention among the general population.
Objective: This systematic review and meta-analysis aimed to evaluate the psychological, cognitive, and physiological effects of CWI in healthy adults.
Methods: Electronic databases were searched for randomized trials involving healthy adults aged ≥ 18 years undergoing acute or long-term CWI exposure via cold shower, ice bath, or plunge with water temperature ≤15°C for at least 30 seconds.
PLoS Biol
January 2025
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense.
View Article and Find Full Text PDFColorectal cancer (CRC) is the second leading cause of cancer-related mortality globally. While immunotherapeutic approaches are effective in a subset of CRC patients, the majority of CRC cases receive limited benefits from immunotherapy. This study developed an immune subtype classification system based on diverse immune cells and pathways.
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