Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) for Locally Advanced Pancreatic Cancer: A Promising Approach.

Locally advanced pancreatic cancer (LAPC) is characterized by poor prognosis and low response durability with standard-of-care chemotherapy or chemoradiotherapy treatment. Stereotactic body radiation therapy (SBRT), which has a shorter treatment course than conventionally fractionated radiotherapy and allows for better integration with systemic therapy, may confer a survival benefit but is limited by gastrointestinal toxicity. Stereotactic MRI-guided adaptive radiation therapy (SMART) has recently gained attention for its potential to increase treatment precision and thus minimize this toxicity through continuous real-time soft-tissue imaging during radiotherapy. The case presented here illustrates the promising outcome of a 69-year-old male patient with LAPC treated with SMART with daily adaptive planning and respiratory-gated technique

Leukocyte Subset Changes in Response to a 164-km Road Cycle Ride in a Hot Environment

International Journal of Exercise Science 9(1): 34-46, 2016. The purpose of this observational study was to determine the circulating leukocyte subset response to completing the 2013 Hotter’N Hell Hundred recreational 164-km road cycle event in a hot and humid environmental condition. Twenty-eight men and four women were included in this study. Whole blood samples were obtained 1-2 hours before (PRE) and immediately after (POST) the event. Electronic sizing/sorting and cytometry were used to determine complete blood counts (CBC) including neutrophil, monocyte, and lymphocyte subsets. The concentration of circulating total leukocytes (103·µL-1) increased 134% from PRE to POST with the greatest increase in neutrophils (319%, p\u3c0.0001). Circulating monocytes (including macrophages) increased 24% (p=0.004) and circulating lymphocytes including B and T cells increased 53% (p\u3c0.0001). No association was observed between rolling time or relative intensity and leukocyte subset. Completing the Hotter n’ Hell Hundred (HHH), a 100 mile recreational cycling race in extreme (hot and humid) environmental conditions, induces a substantial increase in total leukocytes in circulation. The contribution of increases in specific immune cell subsets is not equal, with neutrophils increasing to greater than 4-fold starting values from PRE to POST race. It is likely that exercise in stressful environmental conditions affects the complement of circulating immune cells, although activational state and characterization of specific leukocyte subsets remains unclear. The observed increase in circulating cell sub-populations suggests that the circulating immune surveillance system may be acutely affected by exercise in hot and humid conditions

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

Systematic review on the instruments used for measuring the association of the level of multimorbidity and clinically important outcomes

Objectives There are multiple instruments for measuring multimorbidity. The main objective of this systematic review was to provide a list of instruments that are suitable for use in studies aiming to measure the association of a specific outcome with different levels of multimorbidity as the main independent variable in community-dwelling individuals. The secondary objective was to provide details of the requirements, strengths and limitations of these instruments, and the chosen outcomes. Methods We conducted the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42018105297). We searched MEDLINE, Embase and CINAHL electronic databases published in English and manually searched the Journal of Comorbidity between 1 January 2010 and 23 October 2020 inclusive. Studies also had to select adult patients from primary care or general population and had at least one specified outcome variable. Two authors screened the titles, abstracts and full texts independently. Disagreements were resolved with a third author. The modified Newcastle-Ottawa Scale was used for quality assessment. Results Ninety-six studies were identified, with 69 of them rated to have a low risk of bias. In total, 33 unique instruments were described. Disease Count and weighted indices like Charlson Comorbidity Index were commonly used. Other approaches included pharmaceutical-based instruments. Disease Count was the common instrument used for measuring all three essential core outcomes of multimorbidity research: Mortality, mental health and quality of life. There was a rise in the development of novel weighted indices by using prognostic models. The data obtained for measuring multimorbidity were from sources including medical records, patient self-reports and large administrative databases. Conclusions We listed the details of 33 instruments for measuring the level of multimorbidity as a resource for investigators interested in the measurement of multimorbidity for its association with or prediction of a specific outcome. © 2021 Author(s). Published by BMJ

Ergogenic effects of betaine supplementation on strength and power performance

<p>Abstract</p> <p>Background</p> <p>We investigated the ergogenic effects of betaine (B) supplementation on strength and power performance.</p> <p>Methods</p> <p>Twelve men (mean ± SD age, 21 ± 3 yr; mass, 79.1 ± 10.7 kg) with a minimum of 3 months resistance training completed two 14-day experimental trials separated by a 14-day washout period, in a balanced, randomized, double-blind, repeated measures, crossover design. Prior to and following 14 days of twice daily B or placebo (P) supplementation, subjects completed two consecutive days (D1 and D2) of a standardized high intensity strength/power resistance exercise challenge (REC). Performance included bench, squat, and jump tests.</p> <p>Results</p> <p>Following 14-days of B supplementation, D1 and D2 bench throw power (1779 ± 90 and 1788 ± 34 W, respectively) and isometric bench press force (2922 ± 297 and 2503 ± 28 N, respectively) were increased (p < 0.05) during REC compared to pre-supplementation values (1534 ± 30 and 1498 ± 29 W, respectively; 2345 ± 64 and 2423 ± 84 N, respectively) and corresponding P values (1374 ± 128 and 1523 ± 39 W; 2175 ± 92 and 2128 ± 56 N, respectively). Compared to pre-supplementation, vertical jump power and isometric squat force increased (p < 0.05) on D1 and D2 following B supplementation. However, there were no differences in jump squat power or the number of bench press or squat repetitions.</p> <p>Conclusion</p> <p>B supplementation increased power, force and maintenance of these measures in selected performance measures, and these were more apparent in the smaller upper-body muscle groups.</p

Lack of neuroinflammation in the HIV-1 transgenic rat: An [18 F]-DPA714 PET imaging study

BACKGROUND: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. METHODS: Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. RESULTS: [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. CONCLUSION: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0390-9) contains supplementary material, which is available to authorized users

Resistance Training and Milk-Substitution Enhance Body Composition and Bone Health in Adolescent Girls

Background: Increased soft-drink consumption has contributed to poor calcium intake with 90% of adolescent girls consuming less than the RDA for calcium. Purpose/objectives: The purpose of this investigation was to determine the independent and additive effects of two interventions (milk and resistance training) on nutrient adequacy, body composition, and bone health in adolescent girls. Methods: The experimental design consisted of four experimental groups of adolescent girls 14–17 years of age: (1) Milk + resistance training [MRT]; n = 15; (2) Resistance training only [RT]; n = 15; (3) Milk only [M] n = 20; (4) Control [C] n = 16. A few significant differences were observed at baseline between the groups for subject characteristics. Testing was performed pre and post-12 week training period for all groups. Milk was provided (3, 8 oz servings) for both the MRT and the M groups. The MRT group and the RT groups performed a supervised periodized resistance training program consisting of supervised one-hour exercise sessions 3 d/wk (M, W, F) for 12 wk. Baseline dietary data was collected utilizing the NUT-P-FFQ and/or a 120 item FFQ developed by the Fred Hutchinson Cancer Research Center (Seattle, Washington). Body composition was measured in the morning after an overnight fast using dual-energy X-ray absorptiometry (DXA) with a total body scanner (ProdigyTM, Lunar Corporation, Madison, WI). A whole body scan for bone density and lumbar spine scans were performed on all subjects. Maximal strength of the upper and lower body was assessed via a one-repetition maximum (1-RM) squat and bench press exercise protocols. Significance was set at P ≤ 0.05. Results: Significant differences in nutrient intakes between groups generally reflected the nutrient composition of milk with greater intakes of protein and improved nutrient adequacy for several B vitamins, vitamin A, vitamin D, calcium, magnesium, phosphorus, potassium, and zinc. Mean calcium intake was 758 and 1581 mg/d, in the non-milk and milk groups, respectively, with 100% of girls in the milk groups consuming \u3e RDA of 1300 mg/d. There were no effects of milk on body composition or muscle performance, but resistance training had a main effect and significantly increased body mass, lean body mass, muscle strength, and muscle endurance. There was a main effect of milk and resistance training on several measures of bone mineral density (BMD). Changes in whole body BMD in the M, RT, MRT, and CON were 0.45, 0.52, 1.32, and −0.19%, respectively (P \u3c 0.01). Conclusions: Over the course of 12 weeks the effects of 1300 mg/d of calcium in the form of fluid milk combined with a heavy resistance training program resulted in the additive effects of greater nutrient adequacy and BMD in adolescent girls. While further studies are needed, combining increased milk consumption with resistance training appears to optimize bone health in adolescent girls

Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation

Introduction The History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain. Methods In a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days. Results Between November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone. Conclusions A HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone. https://emj.bmj.com/content/40/7/474 This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0

Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors

AbstractOBJECTIVES: The full potential of stereotactic body radiation therapy (SBRT), in the treatment of unresectable intrahepatic malignancies, has yet to be realized as our experience is still limited. Thus, we evaluated SBRT outcomes for primary and metastatic liver tumors, with the goal of identifying factors that may aid in optimization of therapy. METHODS: From2005 to 2010, 62 patients with 106 primary and metastatic liver tumors were treated with SBRT to a median biologic effective dose (BED) of 100 Gy (42.6-180). The majority of patients received either three (47%) or five fractions (48%). Median gross tumor volume (GTV) was 8.8 cm3 (0.2-222.4). RESULTS: With a median followup of 18 months (0.46-46.8), freedom from local progression (FFLP) was observed in 97 of 106 treated tumors, with 1- and 2-year FFLP rates of 93% and 82%. Median overall survival (OS) for all patients was 25.2 months, with 1- and 2-year OS of 81%and 52%. Neither BED nor GTV significantly predicted for FFLP. Local failure was associated with a higher risk of death [hazard ratio (HR) = 5.1, P = .0007]. One Child-Pugh Class B patient developed radiationinduced liver disease. There were no other significant toxicities. CONCLUSIONS: SBRT provides excellent local control for both primary and metastatic liver lesions with minimal toxicity. Future studies should focus on appropriate selection of patients and on careful assessment of liver function to maximize both the safety and efficacy of treatment