ResearchPad - medical-sciences https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Falls Risk in Relation to Activity Exposure in High-Risk Older Adults]]> https://www.researchpad.co/article/elastic_article_10135 Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME).MethodsOne hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson’s disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken.ResultsAt baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035).ConclusionsThis work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs. ]]> <![CDATA[Unraveling the Association Between Gait and Mortality—One Step at a Time]]> https://www.researchpad.co/article/elastic_article_10129 Slowness of walking is one of the very first signs of aging and is considered a marker for overall health that is strongly associated with mortality risk. In this study, we sought to disentangle the clinical drivers of the association between gait and mortality.MethodsWe included 4,490 participants of the Rotterdam Study who underwent a gait assessment between 2009 and 2015 and were followed-up for mortality until 2018. Gait was assessed with an electronic walkway and summarized into the domains Rhythm, Phases, Variability, Pace, Tandem, Turning, and Base of Support. Cox models adjusted for age, sex, and height were built and consecutively adjusted for six categories of health indicators (lifestyle, musculoskeletal, cardiovascular, pulmonary, metabolic, and neurological). Analyses were repeated in comorbidity-free individuals.ResultsMultiple gait domains were associated with an increased risk of mortality, including Pace (hazard ratio (HR) per SD worse gait, adjusted for other domains: 1.34 [1.19–1.50]), Rhythm (HR: 1.12 [1.02–1.23]) and Phases (HR: 1.12 [1.03–1.21]). Similarly, a 0.1 m/s decrease in gait speed was associated with a 1.21 (1.15–1.27) times higher hazard of mortality (HR fully adjusted: 1.14 [1.08–1.20]). In a comorbidity-free subsample, the HR per 0.1 m/s decrease in gait speed was 1.25 (1.09–1.44). Cause-specific mortality analyses revealed an association between gait speed and multiple causes of death.ConclusionsSeveral gait domains were associated with mortality risk, including Pace which primarily represents gait speed. The association between gait speed and mortality persisted after an extensive adjustment for covariates, suggesting that gait is a marker for overall health. ]]> <![CDATA[Evaluation of Clinically Meaningful Changes in Measures of Frailty]]> https://www.researchpad.co/article/elastic_article_10128 To determine the clinically meaningful changes and responsiveness of widely used frailty measures.MethodsWe analyzed data from a prospective cohort study of 1,135 community-dwelling older adults who underwent assessments of frailty and health-related quality of life using the EuroQol-5D at baseline and 1 year later. Frailty measures included deficit-accumulation frailty index (FI); frailty phenotype; Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale; and the Study of Osteoporotic Fracture (SOF) index. We determined the clinically meaningful changes by the distribution-based method and the anchor-based method using the EuroQol-5D score and responsiveness indices.ResultsFrailty measures were available in 925 participants at 1 year (81.5%). Based on the distribution-based method, small and large clinically meaningful changes were 0.019 and 0.057 for FI, 0.249 and 0.623 for frailty phenotype, 0.235 and 0.587 for FRAIL scale, and 0.116 and 0.289 for SOF index, respectively. The anchor-based estimates of small and large changes were 0.028 and 0.076 for FI, 0.097 and 0.607 for frailty phenotype, 0.269 and 0.368 for FRAIL scale, and 0.023 and 0.287 for SOF index, respectively. Based on the responsiveness index, per-group sample sizes to achieve 80% power in clinical trials, ranged from 51 (FI) to 7,272 (SOF index) for a small change and 9 (FI) to 133 (FRAIL scale) for a large change.ConclusionsThe estimates of clinically meaningful change of frailty measures can inform the choice of frailty measures to track longitudinal changes of frailty in clinical trials and clinical care of community-dwelling older adults. ]]> <![CDATA[Uncontrolled Diabetes as an Associated Factor with Dynapenia in Adults Aged 50 Years or Older: Sex Differences]]> https://www.researchpad.co/article/elastic_article_10127 Epidemiological studies demonstrate an association between diabetes and low neuromuscular strength (NMS). However, none have grouped participants into nondiabetics (ND), undiagnosed diabetics (UDD), controlled diabetics (CD), and uncontrolled diabetics (UCD) or investigated what glycated hemoglobin levels (HbA1c) are associated with low NMS (dynapenia) by sex.MethodsWe analyzed the association between UDD, CD, and UCD and dynapenia, the extent to which the different groupings of these individuals modifies this association and the association between HbA1c levels and NMS, by sex, in a cross-sectional study involving 5,290 participants ≥50 years from the ELSA study. In the first two analyses, logistic regression models were used with dynapenia (grip strength <26 kg in men and <16 kg in women) as outcome and diabetes (ND, UDD, CD, and UCD) as exposure. Next, linear regression was performed with grip strength as the outcome, and the participants were classified based on HbA1c level as exposure. The models were adjusted by sociodemographic, behavioral, and clinical characteristics.ResultsCompared to ND, only UCD was associated with dynapenia (men OR = 2.37 95% CI 1.36–4.14; women OR = 1.67 95% CI 1.01–2.79). This association was less clear, particularly in women, when CD and UCD groups were merged. HbA1c ≥6.5% in men and ≥8.0% in women were associated with lower NMS.ConclusionsUCD increases the chance of dynapenia in both sexes. The different groupings based on diabetes status modify the association between UCD and dynapenia. The threshold of HbA1c associated with reduced NMS is lower in men compared to women. ]]> <![CDATA[Spread and dynamics of the COVID-19 epidemic in Italy: Effects of emergency containment measures]]> https://www.researchpad.co/article/elastic_article_8299 The spread of coronavirus disease 2019 (COVID-19) in Italy prompted drastic measures for transmission containment. We examine the effects of these interventions, based on modeling of the unfolding epidemic. We test modeling options of the spatially explicit type, suggested by the wave of infections spreading from the initial foci to the rest of Italy. We estimate parameters of a metacommunity Susceptible–Exposed–Infected–Recovered (SEIR)-like transmission model that includes a network of 107 provinces connected by mobility at high resolution, and the critical contribution of presymptomatic and asymptomatic transmission. We estimate a generalized reproduction number (R0 = 3.60 [3.49 to 3.84]), the spectral radius of a suitable next-generation matrix that measures the potential spread in the absence of containment interventions. The model includes the implementation of progressive restrictions after the first case confirmed in Italy (February 21, 2020) and runs until March 25, 2020. We account for uncertainty in epidemiological reporting, and time dependence of human mobility matrices and awareness-dependent exposure probabilities. We draw scenarios of different containment measures and their impact. Results suggest that the sequence of restrictions posed to mobility and human-to-human interactions have reduced transmission by 45% (42 to 49%). Averted hospitalizations are measured by running scenarios obtained by selectively relaxing the imposed restrictions and total about 200,000 individuals (as of March 25, 2020). Although a number of assumptions need to be reexamined, like age structure in social mixing patterns and in the distribution of mobility, hospitalization, and fatality, we conclude that verifiable evidence exists to support the planning of emergency measures.

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<![CDATA[Machine learning predicts the functional composition of the protein corona and the cellular recognition of nanoparticles]]> https://www.researchpad.co/article/elastic_article_8275 Protein corona formation is critical for the design of ideal and safe nanoparticles (NPs) for nanomedicine, biosensing, organ targeting, and other applications, but methods to quantitatively predict the formation of the protein corona, especially for functional compositions, remain unavailable. The traditional linear regression model performs poorly for the protein corona, as measured by R2 (less than 0.40). Here, the performance with R2 over 0.75 in the prediction of the protein corona was achieved by integrating a machine learning model and meta-analysis. NPs without modification and surface modification were identified as the two most important factors determining protein corona formation. According to experimental verification, the functional protein compositions (e.g., immune proteins, complement proteins, and apolipoproteins) in complex coronas were precisely predicted with good R2 (most over 0.80). Moreover, the method successfully predicted the cellular recognition (e.g., cellular uptake by macrophages and cytokine release) mediated by functional corona proteins. This workflow provides a method to accurately and quantitatively predict the functional composition of the protein corona that determines cellular recognition and nanotoxicity to guide the synthesis and applications of a wide range of NPs by overcoming limitations and uncertainty.

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<![CDATA[Effectiveness of convalescent plasma therapy in severe COVID-19 patients]]> https://www.researchpad.co/article/N1f6f671d-8823-406a-b910-0c222f4b76c0 Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

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<![CDATA[Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility]]> https://www.researchpad.co/article/N9d2f2704-807b-4c99-8081-8db95ab9e2fa As human society ages globally, age-related disorders are becoming increasingly common. Due to decreasing physiological reserves and increasing organ system dysfunction associated with age, frailty affects many elderly people, compromising their ability to cope with acute stressors. Frail elderly people commonly manifest complex clinical symptoms, including cognitive dysfunction, hypomobility, and impaired daily activity, the metabolic basis of which remains poorly understood. We applied untargeted, comprehensive LC-MS metabolomic analysis to human blood from 19 frail and nonfrail elderly patients who were clinically evaluated using the Edmonton Frail Scale, the MoCA-J for cognition, and the TUG for mobility. Among 131 metabolites assayed, we identified 22 markers for frailty, cognition, and hypomobility, most of which were abundant in blood. Frailty markers included 5 of 6 markers specifically related to cognition and 6 of 12 markers associated with hypomobility. These overlapping sets of markers included metabolites related to antioxidation, muscle or nitrogen metabolism, and amino acids, most of which are decreased in frail elderly people. Five frailty-related metabolites that decreased—1,5-anhydroglucitol, acetyl-carnosine, ophthalmic acid, leucine, and isoleucine—have been previously reported as markers of aging, providing a metabolic link between human aging and frailty. Our findings clearly indicate that metabolite profiles efficiently distinguish frailty from nonfrailty. Importantly, the antioxidant ergothioneine, which decreases in frailty, is neuroprotective. Oxidative stress resulting from diminished antioxidant levels could be a key vulnerability for the pathogenesis of frailty, exacerbating illnesses related to human aging.

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<![CDATA[Dawn of the Visible Monkey: Segmentation of the Rhesus Monkey for 2D and 3D Applications]]> https://www.researchpad.co/article/Nb040dc3b-d1d9-40f4-bbae-8f72cab9c1fe

Background

To properly utilize the sectioned images in a Visible Monkey dataset, it is essential to segment the images into distinct structures. This segmentation allows the sectioned images to be compiled into two-dimensional or three-dimensional software packages to facilitate anatomy and radiology education, and allows them to be used in experiments involving electromagnetic radiation. The purpose of the present study was to demonstrate the potential of the sectioned images using the segmented images.

Methods

Using sectioned images of a monkey's entire body, 167 structures were segmented using Adobe Photoshop. The segmented images and sectioned images were packaged into the browsing software. Surface models were made from the segmented images using Mimics. Volume models were made from the sectioned images and segmented images using MRIcroGL.

Results

In total, 839 segmented images of 167 structures in the entire body of a monkey were produced at 0.5-mm intervals (pixel size, 0.024 mm; resolution, 8,688 × 5,792; color depth, 24-bit color; BMP format). Using the browsing software, the sectioned images and segmented images were able to be observed continuously and magnified along with the names of the structures. The surface models of PDF file were able to be handled freely using Adobe Reader. In the surface models, the space information of all segmented structures was able to be identified using Sim4Life. On MRIcroGL, the volume model was able to be browsed and sectioned at any angle with real color.

Conclusion

Browsing software, surface models, and volume models are able to be produced based on the segmentation of the sectioned images. These will be helpful for students and researchers studying monkey anatomy and radiology, as well as for biophysicists examining the effects of electromagnetic radiation.

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<![CDATA[Virtual Anatomical and Endoscopic Exploration Method of Internal Human Body for Training Simulator]]> https://www.researchpad.co/article/Nd80b2ce9-c597-4293-839f-6b3cfdeffdcc

Background

Virtual environments have brought the use of realistic training closer to many different fields of education. In medical education, several visualization methods for studying inside the human body have been introduced as a way to verify the structure of internal organs. However, these methods are insufficient for realistic training simulators because they do not provide photorealistic scenes or offer an intuitive perception to the user. In addition, they are used in limited environments within a classroom setting.

Methods

We have developed a virtual dissection exploration system that provides realistic three-dimensional images and a virtual endoscopic experience. This system enables the user to manipulate a virtual camera through a human organ, using gesture-sensing technology. We can make a virtual dissection image of the human body using a virtual dissection simulator and then navigate inside an organ using a virtual endoscope. To improve the navigation performance during virtual endoscopy, our system warns the user about any potential collisions that may occur against the organ's wall by taking the virtual control sphere at the virtual camera position into consideration.

Results

Experimental results show that our system efficiently provides high-quality anatomical visualization. We can simulate anatomic training using virtual dissection and endoscopic images.

Conclusion

Our training simulator would be helpful in training medical students because it provides an immersive environment.

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<![CDATA[Previous Hepatitis A Virus Infection Is Related to Slower Psychomotor Speed in Elderly Adults]]> https://www.researchpad.co/article/N3ed142e4-2b1e-46fd-9e48-f10f5588e07f

Abstract

Background

Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function.

Methods

From the National Health and Nutrition Examination Survey, 1999–2002, we selected study participants (≥60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST).

Results

HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted β coefficient of DSST score was −9.55 (95% confidence interval [CI] −9.57 to −9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted β coefficient of DSST score was −2.48 (95% CI −2.49 to −2.46, p < .001) for the HAV-seropositive participants.

Conclusion

HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.

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<![CDATA[Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target]]> https://www.researchpad.co/article/N034db990-6cbd-43a1-ad39-f38bffd3935c

Significance

An explanation has been lacking for the suppressive action of antagonists of growth hormone-releasing hormone receptors (GHRH-Rs) on cancers that do not express GHRH-Rs, an established target of the antagonists. We demonstrate here that esophageal squamous cell carcinoma (ESCC), a representative cancer type that barely expresses GHRH-Rs, responds to GHRH-R antagonists. Hypoxia induces GHRH-R splice variant 1 (SV1) and activates a key glycolytic enzyme. Glycolytic metabolism and tumor progression are promoted by activation of SV1 and reversed by the GHRH-R antagonist MIA-602. A high expression of SV1 in ESCC patients predicts a poor prognosis. These findings document the importance of SV1 as a target of GHRH-R antagonists and underline the therapeutic potential of GHRH-R antagonists against SV1-expressing cancers.

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<![CDATA[The Effect of Exercise Training on Insulin Resistance in Sedentary Year Old Rats1]]> https://www.researchpad.co/article/N88dffe30-8e38-4f12-a33b-bf456baf88e2

Abstract

The purpose of this study was to determine if exercise training of 12-month-old Sprague-Dawley rats could reverse the resistance to insulin-induced glucose uptake that has been shown to occur in these animals. Twelve-month-old rats were trained to run 1½ miles/day in motorized exercise wheel cages, and the ability of insulin to stimulate glucose uptake in these rats was compared with values observed in two groups of similar aged sedentary rats — one fed rat chow ad libitum and the other a calorie-restricted diet for 4 months. Body weight increased and insulin-stimulated glucose uptake decreased as rats fed chow ad libitum grew from 12 to 16 months of age. In contrast, 4 months of either exercise training or calorie restriction prevented weight gain and loss of insulin-stimulated glucose uptake. Thus, the intensity of exercise training attained in this study did not result in an improvement in insulin action in older rats above and beyond that related to the reduction in rate of body weight gain

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<![CDATA[HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy]]> https://www.researchpad.co/article/N6b5777e2-9867-471a-8b60-18a64e948b6e

Significance

Myotonic dystrophy type 1 (DM1) is a model for RNA-mediated disease in microsatellite expansion disorders. DM1 is caused by CTG expansions (CTGexp) and expression of CUGexp RNAs that sequester muscleblind-like (MBNL) proteins, while also triggering hyperphosphorylation of CUGBP1/ETR3-like factor 1 (CELF1). These proteins regulate developmental transitions in RNA processing, so DM1 is characterized by retention of fetal RNA processing patterns in adults. Although current evidence indicates that CELF1 is a specific antagonist of MBNL activity, this study reveals that another protein, HNRNPA1, is also downregulated during normal development but upregulated in DM1, where it also induces fetal splicing shifts. Thus, DM1 disease results from an imbalance in the expression of multiple RNA processing factors important for both proliferation and differentiation.

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<![CDATA[Imaging breast cancer using hyperpolarized carbon-13 MRI]]> https://www.researchpad.co/article/N5127102a-7ddd-4753-a3b5-5bc5a72231e6

Significance

Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group.

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<![CDATA[RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci]]> https://www.researchpad.co/article/Nbd79c58a-6966-4001-9e97-30a4a1cde16f

Significance

Normally, BRCA1 promotes physiological, error-free homologous recombination repair (HRR) of damaged DNA and genome stability. In contrast, excessive, deregulated HRR can lead to genome instability. The BRCA1-binding protein RAP80 restricts HRR amplitude and genome instability, at least in part by manifesting polyubiquitin and poly-ADP-ribose binding activities in postdamage nuclear foci. Although how these processes operate in detail remains unknown, we find that simultaneous defects in RAP80/BRCA1 complex formation and in BRCA1 poly-ADP-ribosylation result in the persistent accumulation of BRCA1-containing complexes in nuclear foci that also contain CtIP and BACH1. These effects lead to excessive HRR, chromosomal hyper-recombination, and gross chromosomal abnormalities.

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<![CDATA[Expansion, in vivo–ex vivo cycling, and genetic manipulation of primary human hepatocytes]]> https://www.researchpad.co/article/N89fc4848-86db-4892-a0b3-0bf1f857d203

Significance

The ability to study human liver disease is limited by available hepatocyte models. Primary human hepatocytes (PHH) and xenograft models suffer from limited availability, donor-to-donor variability, and high cost. Here we report two transformative advances. First, the alkaloid retrorsine improves humanization of the murine liver, which allows routine production of highly humanized mice and high-quality mouse-passaged PHH. Second, the ability to genetically modify PHH cultures and retransplant to create highly humanized mice with genetically altered grafts. When combined, these two advances open new frontiers for creating disease-specific PHH models and for performing genetic and other screens in PHH.

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<![CDATA[Identification and characterization of extrachromosomal circular DNA in maternal plasma]]> https://www.researchpad.co/article/N4ed35f2e-40b9-47c5-b9fd-d0864aea5c4d

Significance

We observed the presence of extrachromosomal circular DNA (eccDNA) in the plasma of pregnant women. We found that the plasma eccDNA molecules were longer than their linear counterparts. Among such eccDNA molecules, those of fetal origin were shorter than those of maternal origin. Characteristic dual-repeat patterns of eccDNA junctions might shed light on their possible generation mechanisms and provide them with distinctive signatures over linear cell-free DNA. Furthermore, the closed circular structure of eccDNA might allow resistance to exonucleases and thus higher stability of these molecules over their linear counterparts. These features of eccDNA provide opportunities for research and biomarker development. This work represents an example in the nascent field of plasma DNA topologics.

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<![CDATA[High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model]]> https://www.researchpad.co/article/N067c0cd7-7024-49bd-b55e-878a8ea0a198

Significance

New strategies are needed to improve efficacy of anti-PD1 therapy in cancer treatment. Ascorbic acid (AA, vitamin C) has been previously shown to cause genome-wide demethylation in multiple malignancies by enhancing the activity of the Ten-Eleven Translocation (TET) enzymes. This study shows that AA treatment 1) increases immunogenicity of lymphoma cells; 2) enhances intratumoral infiltration of CD8+ T cells and macrophages; and 3) synergizes with anti-PD1 checkpoint inhibition in a syngeneic lymphoma mouse model via marked activation of cytotoxic cells (cytotoxic T cells and NK cells) and antigen presenting cells. The data provide a compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma and in preclinical models of other malignancies.

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<![CDATA[Protein Intake and Functional Integrity in Aging: The Framingham Heart Study Offspring]]> https://www.researchpad.co/article/Nacad2205-9355-4837-a940-c5bff4e3e97c

Abstract

Background

Higher protein intake is linked to maintenance of muscle mass and strength, but few studies have related protein to physical function and disability in aging.

Methods

In participants of the Framingham Heart Study Offspring, we examined associations between protein intake (g/d), estimated from food frequency questionnaires, and maintenance of functional integrity, as a functional integrity score based on responses to 17 questions from Katz Activities of Daily Living, Nagi, and Rosow-Breslau questionnaires, repeated up to five times (1991/1995–2011/2014) over 23 years of follow-up. Cox proportional hazard models were used to estimate risk of incident loss of functional integrity (functional integrity score ≤ 15th percentile).

Results

In 2,917 participants (age 54.5 [9.8] years), baseline protein intake was 77.2 (15.6) g/d. The functional integrity score (baseline, mean 98.9, range 82.4–100.0) was associated with objective performance (gait speed, grip strength) and lower odds of falls, fractures, and frailty. Across follow-up, there were 731 incident cases of loss of functional integrity. In fully adjusted models, participants in the highest category of protein intake (median 92.2 g/d) had 30% lower risk of loss of functional integrity (hazard ratio [95% confidence interval] 0.70 [0.52, 0.95], p trend = .03), versus those with the lowest intake (median 64.4 g/d). However, sex-stratified analyses indicated the association was driven by the association in women alone (hazard ratio [95% confidence interval] 0.49 [0.32, 0.74], p trend = .002) and was nonsignificant in men (hazard ratio [95% confidence interval] 1.14 [0.70, 1.86], p trend = .59).

Conclusions

Higher protein intake was beneficially associated with maintenance of physical function in middle-aged, high-functioning U.S. adults over the span of two decades. This association was particularly evident in women.

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