Aerobic exercise is associated with decreased cancer incidence and cancer-associated mortality. However, little is known about the effects of exercise on pancreatic ductal adenocarcinoma (PDA), a ...disease for which current therapeutic options are limited. Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemic and intra-tumoral immunity. Mechanistically, exercise promotes immune mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8 T cells, which are responsible for the tumor-protective effects. In clinical samples, an exercise-dependent increase of intra-tumoral CD8 T cells is also observed. Underscoring the translational potential of the interleukin (IL)-15/IL-15Rα axis, IL-15 super-agonist (NIZ985) treatment attenuates tumor growth, prolongs survival, and enhances sensitivity to chemotherapy. Finally, exercise or NIZ985 both sensitize pancreatic tumors to αPD-1, with improved anti-tumor and survival benefits. Collectively, our findings highlight the therapeutic potential of an exercise-oncology axis and identify IL-15 activation as a promising treatment strategy for this deadly disease.
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•Aerobic exercise restricts pancreatic tumor growth by enhancing anti-tumor immunity•The anti-tumor effects of aerobic exercise are driven by IL-15Rα+ CD8 T cells•Pharmacological activation of IL-15/IL-15Rα promotes a durable anti-tumor response•Aerobic exercise and IL-15 activation sensitize pancreatic tumors to α-PD-1 therapy
Kurz. et al. discover that aerobic exercise slows pancreatic cancer growth in mice through activation of the immune system, particularly CD8+ T cells. The beneficial effects of exercise can be mimicked by treatment with an IL-15 super-agonist, NIZ985. Exercise or NIZ985 both improve the responsiveness of murine pancreatic tumors to immune- and non-immune- based therapeutics.
To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable.
In a 1-year randomized controlled trial, we compared ...usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings.
A total of 927 individuals indicated interest, 210 were enrolled, and 195 were randomized. Participants had recently seen a specialist (73%) and were largely college-educated (73%) and white (96%). Ninety-five (98% of the intervention group) completed at least one virtual visit, and 91% of 388 virtual visits were completed. Quality of life did not improve in those receiving virtual house calls (0.3 points worse on a 100-point scale; 95% confidence interval CI -2.0 to 2.7 points;
= 0.78) nor did quality of care or caregiver burden. Each virtual house call saved patients a median of 88 minutes (95% CI 70-120;
< 0.0001) and 38 miles per visit (95% CI 36-56;
< 0.0001).
Providing remote neurologic care directly into the homes of people with PD was feasible and was neither more nor less efficacious than usual in-person care. Virtual house calls generated great interest and provided substantial convenience.
NCT02038959.
This study provides Class III evidence that for patients with PD, virtual house calls from a neurologist are feasible and do not significantly change quality of life compared to in-person visits. The study is rated Class III because it was not possible to mask patients to visit type.
The latest Triassic was an interval of prolonged biotic extinction culminating in the end-Triassic Extinction (ETE). The ETE is now associated with a perturbation of the global carbon cycle just ...before the end of the Triassic that has been attributed to the extensive volcanism of the Circum-Atlantic Magmatic Province (CAMP). However, we attribute the onset of declining latest Triassic diversity to an older perturbation of the carbon cycle (δ13Corg) of global extent at or very close to the Norian/Rhaetian boundary (NRB). The NRB appears to be the culmination of stepwise biotic turnovers that characterize the latest Triassic and includes global extinctions of significant marine and terrestrial fossil groups. These biotic events across the NRB have been largely under-appreciated, yet together with a coeval disturbance of the carbon cycle were pivotal in the history of the Late Triassic. Here, we present new and published δ13Corg data from widespread sections (Italy, Greece, ODP, Australia, New Zealand, USA, Canada). These sections document a previously unknown perturbation in the carbon cycle of global extent that spanned the NRB. The disturbance extended across the Panthalassa Ocean to both sides of the Pangaean supercontinent and is recorded in both the Northern and Southern Hemispheres. The onset of stepwise Late Triassic extinctions coincides with carbon perturbation (δ13Corg) at the NRB, indicating that a combination of climatic and environmental changes impacted the biota at a global scale. The NRB event may have been triggered either by gas emissions from the eruption of a large igneous province pre-dating the NRB, by a bolide impact of significant size or by some alternative source of greenhouse gas emissions. As yet, it has not been possible to clearly determine which of these trigger scenarios was responsible; the evidence is insufficient to decisively identify the causal mechanism and merits further study.
Three-dimensional covalent connectors are valuable synthons for accessing crystalline or amorphous networks. Currently, fused polycyclic alkanes are employed as connectors in this context. We debut ...phosphorus-nitrogen (PN) cages as new 3-dimensional (3-D) inorganic connectors that yield crystalline and amorphous networks, including examples with gas porosity. We show that the high tunability of PN cages accelerates network diversification and the presence of a responsive
31
P NMR spectroscopic handle provides structural insight. Collectively, this work unlocks a new and convenient 3-D synthon for reticular chemistry.
We debut phosphorus nitrogen cages as a new family of convenient and tunable 3-dimensional connectors for reticular chemistry (crystalline or amorphous).
Experience impacts learning and perception. Familiarity with stimuli that later become the conditioned stimulus (CS) in a learning paradigm, for instance, reduces the strength of that learning-a fact ...well documented in studies of conditioned taste aversion (CTA; De la Casa & Lubow, 1995; Lubow, 1973; Lubow & Moore, 1959). Recently, we have demonstrated that even experience with "incidental" (i.e., non-CS) stimuli influences CTA learning: Long Evans rats pre-exposed to salty and/or sour tastes later learn unusually strong aversions to novel sucrose (Flores et al., 2016), and exhibit enhanced sucrose-responsiveness after learning in gustatory cortex (GC; Flores et al., 2018). These findings suggest that incidental taste exposure (TE) may change spiking responses that have been shown to underlie the processing of tastes in GC. Here, we test this hypothesis, evaluating whether GC neuron spiking responses change across 3 days of taste exposure. Our results demonstrate that the discriminability of GC ensemble taste responses increases with this familiarization. Analysis of single-neuron responses recorded across multiple sessions reveals that taste exposure not only enriches identity and palatability information in taste-evoked activity but also enhances the discriminability of even novel tastes. These findings demonstrate that "mere" familiarization with incidental episodes of tasting changes the neural spiking responses of taste processing and provides specific insight into how such TE may impact later learning.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Although caloric restriction in numerous models extends life, longevity in humans is suggested to be limited by the increased prevalence of obesity. Adiponectin, a fat-derived peptide, has a ...protective role against age-related disease, and thus is an excellent candidate gene for longevity. We studied adiponectin levels in centenarians (n = 118), their offspring (n = 228), and unrelated participants <95 (n = 78). Adiponectin levels were significantly greater in participants older than 95 years (p =.01), an effect that was independent of sex and body mass index (BMI). Adiponectin levels in the offspring were higher (following adjustment for age, sex, and BMI) compared to controls (p =.02), suggesting that inherited factors play a role in determining adiponectin levels. Over-representation of two common variants in Adiponectin gene (ADIPOQ) in male long-lived individuals combined with their independent association with elevated plasma adiponectin levels (in men and women) suggests that their presence may promote increased life span through the regulation of adiponectin production and/or secretion.
Purpose of Review
Advances in technology have expanded telemedicine opportunities covering medical practice, research, and education. This is of particular importance in movement disorders (MDs), ...where the combination of disease progression, mobility limitations, and the sparse distribution of MD specialists increase the difficulty to access. In this review, we discuss the prospects, challenges, and strategies for telemedicine in MDs.
Recent Findings
Telemedicine for MDs has been mainly evaluated in Parkinson’s disease (PD) and compared to in-office care is cost-effective with similar clinical care, despite the barriers to engagement. However, particular groups including pediatric patients, rare MDs, and the use of telemedicine in underserved areas need further research.
Summary
Interdisciplinary telemedicine and tele-education for MDs are feasible, provide similar care, and reduce travel costs and travel time compared to in-person visits. These benefits have been mainly demonstrated for PD but serve as a model for further validation in other movement disorders.
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