Ferroptosis: an iron-dependent form of nonapoptotic cell death.

Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration.

Pilot Study on the Impact of a Home-Based Exercise Program on Inflammatory Cytokines and Quality of Life in Men with Prostate Cancer Under Active Surveillance.

OBJECTIVES: This study aimed to demonstrate potential translation of pre-clinical studies to a home-based exercise intervention in mediating inflammatory cytokine markers and tumor progression in men under active surveillance for prostate cancer. METHODS: A 2-arm randomized control parallel group design was used. The exercise intervention consisted of 24 weeks of an aerobic and resistance home-based exercise program and results were compared to a waitlist control group. Data were collected at baseline and end of study for eotaxin, interferon-γ (INF-γ), interleukin-12 (IL-12), interleukin-1α (IL-1α), interleukin-5 (IL-5), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF), distanced walked during a 6-minute walk test (6MWT), body mass index, and health-related quality of life. RESULTS: Non-significant decreases were observed in all biomarkers, especially VEGF (pre: 125.16 ± 198.66, post: 80.29 ± 124.30, P = .06) and INF-γ (pre: 152.88 ± 312.71, post: 118.93 ± 158.79, P = .08), in the intervention group; only IL- α (pre: 332.15 ± 656.77, post: 255.12 ± 502.09, P = .20) decreased in the control group while all other biomarkers increased from baseline to end of study. A non-significant increase in 6MWT distance was observed in the intervention group, while a decrease was seen in the control group. Significant decreases in physical function, emotional wellbeing, and total composite scale on the FACIT-F were observed in the intervention group, possibly due to the isolation restrictions of COVID-19. Physical function on the SF-36 significantly increased in the control group. CONCLUSIONS: Future studies with powered samples are needed to confirm the trends observed for inflammatory biomarkers and functional fitness.

Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors.

INTRODUCTION: Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors. METHODS: Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified. RESULTS: Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/m2); majority were female (71%) and breast cancer survivors (65%), of which 44% were Hispanic. Marked reductions were observed in all cytokines except IL-4, with significant reductions (p < 0.05) found in IL-1b (- 13%) and IL-1ra (- 13%). No significant changes were observed in soluble cytokine receptors or CRP. CONCLUSIONS: TYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

Decline of Psychological Health Following the Designation of COVID-19 as a Pandemic: Descriptive Study.

BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020, and as of this writing, Texas, United States, has reported >675,000 cases with over 14,000 deaths. Many of the preventive measures implemented during the pandemic can increase sedentary lifestyles, which can lead to the development of chronic diseases, including obesity, among the general population and cause serious threats to people's physical health and overall quality of life. Individuals with pre-existing comorbidities are at an increased risk of COVID-19 and may hence have higher levels of stress. OBJECTIVE: This study aimed to investigate the relationship between physical activity levels and mental health status on an individual level and to compare them between those with and those without comorbidities in a cohort of Texas residents, before and after COVID-19 was declared a pandemic. METHODS: An electronic survey was disseminated throughout various regions of Texas. In total, 160 individuals were asked questions about their demographic characteristics, time spent on daily physical activities, and daily mental health status before and after COVID-19 was declared a pandemic. Frequency distributions and descriptive statistics were analyzed. RESULTS: Overall, 94 (58%) participants reported having ≥1 medical condition, and 31 (13.1%) had >3 medical conditions. Physical activity levels among participants with ≥1 pre-existing comorbidity drastically-but not significantly-decreased, as evident from a 10% increase in sedentary lifestyles after COVID-19 was declared a pandemic. On the contrary, we observed a 9% increase in the number of individuals without a pre-existing comorbidity who reported 30-60 min of physical activity per week. There was a 2-fold increase in the number of participants reporting more frequent feelings of nervousness, too much worry, trouble relaxing, and the fear of something awful happening after the pandemic. More specifically, individuals with pre-existing medical conditions reported, on average, a 10% higher incidence of feelings of stress, anxiety, and sadness compared to their healthy counterparts after COVID-19 was declared a pandemic. CONCLUSIONS: Stressful life conditions and chronic comorbidities are risk factors that can affect mental health and reduce the ability to perform activities of daily life. Therefore, when implementing pandemic protocols, municipalities should consider providing mental health support to their citizens to protect them from this rather inconspicuous adverse effect.

Improving the Yield and Rate of Acid-Catalyzed Deconstruction of Lignin by Mechanochemical Activation.

Lignin is a potential biomass feedstock from plant material, but it is particularly difficult to economically process. Inspired by recent ball-milling results, state-of-the-art quantum mechanochemistry calculations have been performed to isolate and probe the purely mechanochemical stretching effect alone upon acid-catalyzed deconstruction of lignin. Effects upon cleavage of several exemplary simple ethers are examined first, and with low stretching force they all are predicted to cleave substantially faster, allowing for use of milder acids and lower temperatures. Effects upon an experimentally known lignin fragment model (containing the ubiquitous ß-O-4 linkage) are next examined; this first required a mechanism refinement (3-step indirect cleavage, 1-step side reaction) and identification of the rate-limiting step under zero-force (thermal) conditions. Mechanochemical activation using very low stretching forces improves at first only yield, by fully shutting off the ring-closure side reaction. At only somewhat larger forces, in stark contrast, a switch in mechanism is found to occur, from 3-step indirect cleavage to the direct cleavage mechanism of simple ethers, finally strongly enhancing the cleavage rate of lignin. It is concluded that mechanochemical activation of the common ß-O-4 link in lignin would improve the rate of its acidolysis via a mechanism switch past a low force threshold. Relevance to ball-milling experiments is discussed.

Semicontinuum (Cluster-Continuum) Modeling of Acid-Catalyzed Aqueous Reactions: Alkene Hydration.

An effort is made to reduce the errors of continuum solvation models (CSMs) with semicontinuum modeling to achieve 3 kcal mol-1 agreement with experiment for acid-catalysis activation Gibbs energies. First, two underappreciated CSM issues are reviewed: errors in the CSM solvation Gibbs energies grow beyond 5 kcal mol-1 (i) as ions are made smaller and (ii) as water clusters grow larger. Second, the computational reproduction of the known Gibbs energies (ΔrG and Δ‡G) of the paradigmatic reaction ethene + H2O + H3O+ → TS+ → ethanol + H3O+ is attempted. It is argued that, despite the >5 kcal mol-1 solvation errors for ions, it is possible to employ error cancellation strategies to reduce the errors in the reaction and activation Gibbs energies to 3 kcal mol-1 accuracy. A new 3 kcal mol-1 effect due to solvent-molecule "placement" (confinement from 1 M bulk concentration) was isolated and proved useful. Third, computational reproduction of the known entropies (ΔrS and Δ‡S) of the paradigmatic reaction is attempted using Trouton's constant and neglect of solvent structure reorganization effects (which must cancel well for this reaction); this worked well for ΔrS but needs empirical correction of ∼11 cal mol-1 K-1 for Δ‡S due to solvent disorientation when H3O+ is consumed. These entropy estimates allow for enthalpy (ΔrH and Δ‡H) estimation from the Gibbs energy values. Fourth, two recommended options, including A + H3O+·2W → [AHOH2+·2W]‡, are shown to also work well for the activations of propene and isobutene.

Understanding Self-regulation Behaviors in South Asians With Coronary Artery Disease: A Mixed-Methods Study.

BACKGROUND: South Asians (SAs) have a well-documented risk for mortality related to coronary artery disease (CAD). However, there is a lack of evidence to guide the implementation and dissemination of primary and secondary interventions to control and deter progression of CAD in SAs. OBJECTIVE: The aim of this study is to explore and describe self-regulation behaviors in SAs with CAD using Leventhal's Common Sense Model. METHODS: In this mixed-methods study, quantitative data were collected using 3 survey questionnaires (demographics, Illness Perception Questionnaire-Revised, and Coping/Self-Regulation Behaviors). Before completing the surveys, a subset of the sample (n = 20) participated in individual face-to-face or telephone interviews. RESULTS: A total of 102 SAs were enrolled (age, 53.5 ± 9.98 years). On average, participants rated themselves high (63 ± 3.06) on negative perceptions. In addition, they discussed desi diet, stress, a lack of physical activity, ignoring symptoms, and kismet (fate) as the most important perceived causes of their CAD. Most of the participants modified their lifestyle after their CAD event. Participants expressed regret for not having changed their lifestyle earlier when they were experiencing early symptoms of their CAD. CONCLUSION: Findings from this study enhance the understanding of self-regulation behaviors of SAs with CAD. Ultimately, these findings will inform the development and implementation of targeted interventions that address culture-specific lifestyle modification for SAs with CAD.

Simple and Complex Wheel Running Effect on Depression, Memory, Neuroinflammation, and Neurogenesis in Alzheimer's Rat Model.

INTRODUCTION: The aim of this study was to investigate 12 wk of simple and complex voluntary wheel running on Alzheimer's disease (AD), associated biomarkers, and behaviors. METHODS: Sixty male Wistar rats were randomly divided into six groups: healthy control (Con-Sed), AD only (AD-Sed), simple wheel control (SWC), complex wheel control (CWC), simple wheel AD (SWAD), and complex wheel AD (CWAD). Novelty-suppressed feeding test and the Morris water maze test were used to evaluate depression and memory, respectively. Ki67 was measured in the hippocampus, whereas interleukin (IL)-1ß and neural/glial antigen 2 (NG2) were measured in both the hippocampus and the prefrontal cortex. One-way ANOVA with Tukey's post hoc test was performed. RESULTS: AD-Sed group had significantly lower spacial memory ( P < 0.001) compared with Con-Sed. Simple and complex wheel running attenuated these deficits in the SWAD and CWAD groups, respectively ( P < 0.001). Only the CWAD group had significantly improved novelty-suppressed feeding test time compared with AD-Sed ( P < 0.001), equivalent to the healthy wheel running groups. AD-Sed has significantly higher hippocampal concentrations of Ki67 ( P = 0.01) compared with the Con-Sed. Both SWAD and CWAD had significantly reduced Ki67 with similar concentrations compared with the SWC and CWC groups ( P > 0.05). AD-Sed animals also presented with significantly higher hippocampal and prefrontal cortex concentrations of IL-1ß compared with Con-Sed ( P < 0.001). SWAD and CWAD had no effect in changing these concentrations. Complex wheel running significantly increased NG2 in the healthy control and AD models, whereas simple wheel running significantly increased NG2 in the AD model. CONCLUSIONS: The results of our study suggest that complex wheel running might be more advantageous in promoting memory and neuroplasticity while reducing depression that is associated with AD.

The Impact of Behavioral Lifestyle Intervention on Inflammatory Cytokines in Older Adults Living With Type 2 Diabetes: A Feasibility Study.

OBJECTIVE: This study investigates the effects of a behavioral lifestyle intervention on inflammatory cytokines and frailty in older adults (≥ 65 years) with type 2 diabetes (T2D). METHOD: We conducted a single-arm, 6-month intervention supplemented with diet and activity self-monitoring technology. We assessed frailty using Fried criteria and quantified inflammatory cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating-factor [GM-CSF], interferon [IFN-γ], tumor necrosis factor [TNF-α]) using a multiplex assay. We used paired t-tests with significance at P < .05. We calculated the Spearman correlation and evaluated the relationship between frailty, BMI, and inflammatory cytokines. RESULTS: Eighteen participants completed the study (mean ± SD: 71.5 ± 5.3 years; BMI: 34 ± 6 kg/m2). At baseline, we had 4 frail, 13 pre-frail, and 1 non-frail participant. At 6 months, we observed the therapeutic effects of the intervention on frailty score, BMI, IL-2, IFN-y, and GM-CSF. DISCUSSION: The study highlights the importance of behavioral lifestyle intervention in improving inflammatory cytokines and frailty in older adults.

Measurement of Cognitive Function in Exercise Oncology Studies in Patients Treated With Chemotherapy: A Scoping Review.

Cancer-associated cognitive deficits following chemotherapy have received increased attention in clinical research. Exercise has been shown to preserve cognitive function in cancer patients, though the overall effect is mixed. Here we present a scoping review of the published literature summarizing methods used to assess cognitive function in exercise oncology trials. Methods: PubMed, PsycINFO and CINAHL databases were searched using keywords "cognition," "cancer" OR "neoplasm" OR "tumor," "chemotherapy" and "exercise" OR "physical activity." Studies eligible for inclusion include prospective studies that were published in English in peer-reviewed journals that include a method of assessing cognitive function in adult cancer patients, in which an exercise modality or method of quantifying exercise habits was evident. Studies were excluded if they included a pediatric population, patients that were not diagnosed with cancer, or were systematic/narrative/scoping reviews, protocol papers or dissertation/theses. Results: A total of 29 studies met the inclusion criteria. In total, 29 unique assessments were used to evaluate cognitive function, including patient-reported outcomes (PROs; n = 8) and objective (n = 21) methods. More than half (n = 17) of included studies relied on PROs while 12 studies utilized objective measures of cognitive function Cognitive domains of the PROs were limited in scope, focusing on memory and attention/concentration while the objective measures were broader and inclusive of multiple domains. Conclusion: The results of this review indicate that mixed approaches to evaluating cognitive function in cancer patients pose a major limitation to understanding the role of exercise as an integrative approach. The evidence demonstrates a need for more uniform assessment of cognitive function in exercise oncology trials.

Tirzepatide and exercise training in obesity.

OBJECTIVES: The purpose of this study was to investigate the effects of 6 weeks of resistance training (RT) combined with aerobic training (AT) and Tirzepatide supplementation on lipid profiles, insulin resistance, anthropometric characteristics and physical fitness in prediabetic obese soldiers. METHODS: 61 obese men were randomly divided into six groups: Placebo; Tirzepatide 5 mg (T5); Tirzepatide 2.5 mg (T2.5); Hypertrophy, Strength, Power-Circuit Training+Placebo (Ex+P); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 5 mg (Ex+T5); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 2.5 mg (Ex+T2.5). All training groups performed aerobic training (AT) after resistance training. Subjects trained for six weeks, three sessions per week. Before and after the intervention period, the participants were evaluated for anthropometric measures, body composition [body weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM)], cardiorespiratory fitness (VO2max), and muscle strength (chest press 1RM and leg press 1RM). Blood biochemistry evaluations included triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), insulin level and insulin resistance (HOMA-IR). To evaluate the differences between the groups, ANCOVA statistical method was used along with Bonferroni's post hoc test, and the significance level was P <  0.05. RESULTS: Body weight, BMI, WC, FM, FBG, LDL-C, TC, TG and HOMA-IR were significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. WHR significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo group. HDL-C, chest press and leg press significantly increased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. VO2max significantly increased and insulin significantly decreased in Ex+P group compared to Placebo, T5 and T2.5 groups. FM, FBG and TG were significantly decreased in both the T2.5 and T5 groups compared to Placebo group. HOMA-IR, LDL-C and TC significantly decreased in the T5 group compared to Placebo group. Also, leg press significantly increased in Ex+P group compared to all other groups. CONCLUSIONS: Performing six weeks of combined resistance and aerobic training in the form of RT+AT alone is more effective than the simultaneous use of Tirzepatide on cardiorespiratory fitness, strength, and modulating insulin levels. Taking Tirzepatide in doses of 5 mg and 2.5 mg in combination with exercise training did not have a significant advantage over exercise training alone. Finally, taking Tirzepatide in doses of 5 mg or 2.5 mg in combination with exercise training is not significantly superior to each other.

Effectiveness of exercise interventions in animal models of multiple sclerosis.

Multiple sclerosis (MS) is associated with an impaired immune system that severely affects the spinal cord and brain, and which is marked by progressive inflammatory demyelination. Patients with MS may benefit from exercise training as a suggested course of treatment. The most commonly used animal models of studies on MS are experimental autoimmune/allergic encephalomyelitis (EAE) models. The present review intends to concisely discuss the interventions using EAE models to understand the effectiveness of exercise as treatment for MS patients and thereby provide clear perspective for future research and MS management. For the present literature review, relevant published articles on EAE animal models that reported the impacts of exercise on MS, were extracted from various databases. Existing literature support the concept that an exercise regimen can reduce the severity of some of the clinical manifestations of EAE, including neurological signs, motor function, pain, and cognitive deficits. Further results demonstrate the mechanisms of EAE suppression with information relating to the immune system, demyelination, regeneration, and exercise in EAE. The role for neurotrophic factors has also been investigated. Analyzing the existing reports, this literature review infers that EAE is a suitable animal model that can help researchers develop further understanding and treatments for MS. Besides, findings from previous animal studies supports the contention that exercise assists in ameliorating MS progression.

Examining the Potential Effect of a Salt Sensitivity Biomarker in Korean American Immigrants: A Pilot Study.

The genetic factors involved with salt sensitivity (SS) have been studied using a genetic approach to identify individuals at high risk for developing hypertension and could benefit from a low sodium diet intervention, but this has not been well-studied in Korean American immigrants (KAIs). The purpose of this pilot study was to investigate the influence of SS that moderates blood pressure (BP) in KAIs (n = 34). KAIs were recruited from local communities and completed a blood draw, a 8-day food log, and BP testing. The dietary sodium intake was measured using the Fitbit mobile app, and an SS biomarker was assessed using targeted genotyping. out of five GNAI2 single nucleotide polymorphisms (SNPs) tested, rs4547694 significantly moderated the relationship of dietary sodium intake on BP in KAIs. Conclusions: Further studies are warranted to test the effect of a reduced sodium diet on BP while accounting for the moderating influence of an SS genotype.

Exercise and Creatine Supplementation to Augment the Adaptation of Exercise Training Among Breast Cancer Survivors Completing Chemotherapy: Protocol for an Open-label Randomized Controlled Trial (the THRIVE Study).

BACKGROUND: In breast cancer survivors, chemotherapy-induced muscle loss has been shown to be attenuated with structured resistance exercise. Creatine supplementation can increase bioenergetics in skeletal muscle, which helps to improve overall strength and endurance and reduce muscular fatigue. Therefore, we hypothesize that adding creatinine supplementation to exercise training will accelerate improvements in strength, endurance, and bioenergetics in breast cancer survivors. OBJECTIVE: The primary objective is to determine the effects of combining creatine supplementation with exercise on modulating strength and physical function in breast cancer survivors by comparing these effects to those of exercise alone. The secondary objectives are to determine if creatine supplementation and exercise can increase the intramuscular storage of creatine and improve body composition by comparing this intervention to exercise alone. METHODS: We aim to test our hypothesis by conducting an open-label randomized controlled trial of 30 breast cancer survivors who have completed chemotherapy within 6 months of enrollment. Eligible participants will be equally randomized (1:1) to either a creatine and exercise group or an exercise-only group for this 12-week intervention. Individuals who are randomized to receive creatine will be initially dosed at 20 g per day for 7 days to boost the availability of creatine systemically. Thereafter, the dose will be reduced to 5 g per day for maintenance throughout the duration of the 12-week protocol. All participants will engage in 3 center-based exercise sessions, which will involve completing 3 sets of 8 to 12 repetitions on chest press, leg press, seated row, shoulder press, leg extension, and leg curl machines. The primary outcomes will include changes in strength, body composition, and physical function in breast cancer survivors. The secondary outcomes will be intramuscular concentrations of creatine and adenosine triphosphate in the vastus lateralis, midthigh cross-sectional area, and quality of life. RESULTS: As of October 2021, a total of 9 patients have been enrolled into the study. No unexpected adverse events have been reported. CONCLUSIONS: Creatine is being studied as a potential agent for improving strength, endurance, and bioenergetics in breast cancer survivors following chemotherapy. The findings from our trial may have future implications for supporting breast cancer survivors in reversing the muscle loss experienced during chemotherapy and improving their physical function and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04207359; https://clinicaltrials.gov/ct2/show/NCT04207359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26827.

Understanding Questions and Concerns Regarding COVID-19 and the COVID-19 Vaccine Among Populations Presenting at a COVID-19 Vaccine Clinic Hub: A Qualitative Study.

BACKGROUND: Skepticism among the public surrounding the COVID-19 vaccine is still prevalent despite vaccine-positive communication and many Americans having already received the vaccine. Side effects of the vaccine, as well as its expeditious research and development, are among the top concerns among those hesitant to receive the coronavirus vaccine. Moreover, there is additional concern regarding the association between comorbidities and severity of illness due to the coronavirus pandemic. OBJECTIVE: We aimed to describe the pandemic- and vaccine-related concerns of South Texas residents who attended the UT Health San Antonio School of Nursing's vaccine clinic with the goal of better understanding vaccine-related misconceptions and hesitancy for subsequent vaccination campaigns and boosters. METHODS: An electronic survey accessible via a QR code on printed flyers was distributed throughout the waiting areas and post-vaccine observation rooms within the COVID-19 vaccine clinic at UT Health San Antonio School of Nursing from April 5 to 16, 2021. The survey contained a primary open-ended question designed to obtain information on concerns of the clinic attendees regarding the COVID-19 pandemic and COVID-19 vaccine. A thematic analysis was performed on the qualitative data to identify major themes to better understand concerns of vaccine clinic visitors. RESULTS: During the 11-day period, 510 attendees received vaccinations through the vaccination clinic and completed the survey. Five areas of concern were identified by the 277 attendees: immunity, future vaccinations, vaccine symptoms and safety, protocol post-vaccination, and child vaccinations. Post-hoc sentiment analysis showed that responses were generally neutral or negative. CONCLUSION: This study provides a perspective regarding questions and concerns of South Texas residents regarding the COVID-19 pandemic, the vaccine, and their general health status within a vaccinated population. Vaccine recipients were found to still have questions even after receiving the vaccine, suggesting that eliminating uncertainty surrounding the COVID-19 vaccine is not necessary to motivate individuals to receive the vaccine. Instead, addressing concerns through public health messaging could be a useful strategy to address vaccine-related concerns and increase subsequent vaccine uptake in future vaccination campaigns and boosters.

A technology assisted precision ketogenic diet intervention for cardio-renal-metabolic health in overweight or obese adults: Protocol for a randomized controlled trial.

BACKGROUND: The obesity epidemic is a public health concern, as it is associated with a variety of chronic conditions. The ketogenic diet has drawn much scientific and public attention. However, implementation is challenging and its effect on cardio-renal-metabolic health is inconclusive. This study will assess the feasibility, acceptability, and preliminary efficacy of a technology-assisted ketogenic diet on cardio-renal-metabolic health. METHODS: This is a single center, 6-month, stratified, randomized controlled trial. A total of 60 overweight/obese adults (18+ years old) will be enrolled, including 20 without type 2 diabetes (T2D) and without chronic kidney disease (CKD); 20 with T2D, but without CKD; and 20 with early-stage CKD. Participants will be stratified based on health conditions and randomized into a ketogenic diet (n = 30) or a low-fat diet group (n = 30). Health education involving diet and physical activity will be delivered both digitally and in-person. Mobile and connected health technologies will be used to track lifestyle behaviors and health indicators, as well as provide weekly feedback. The primary outcome (weight) and the secondary outcomes (e.g., blood pressure, glycemic control, renal health) will be assessed with traditional measurements and metabolomics. DISCUSSION: Mobile and connected health technologies provide new opportunities to improve chronic condition management, health education attendance, planned lifestyle changes and engagement, and health outcomes. The advancement of bioinformatics technology offers the possibility to profile and analyze omics data which may advance our understanding of the underlying mechanisms of intervention effects on health outcomes at the molecular level for personalized and precision lifestyle interventions.

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Patients with cancer experience a higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the first and second dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in US and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of two vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months before vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody groups.

A randomized controlled trial of a home-based exercise program on prognostic biomarkers in men with prostate cancer: A study protocol.

BACKGROUND: Herein, we propose a novel RCT study to collect preliminary data on the impact of a 24-week home-based exercise program that can improve prognosis, physical function, and quality of life (QoL) in men with prostate cancer (PCa). This study will provide data on the feasibility of conducting a home-based exercise study and pilot data on the impact of exercise on circulating concentrations of biomarkers reported in the literature to be beneficial for the prognostication of PCa. METHODS/DESIGN: Thirty male patients, clinically-diagnosed with prostate cancer under active surveillance, will be recruited to participate in a 2-arm, 24-week home-based program. Random allocation to each arm - intervention, and control - will be performed in a 1:1 ratio. Participants assigned to the intervention group will perform 30 min of light-to-moderate intensity walking five days a week (40-60% heart rate reserve) and three sets of 15 repetitions of light callisthenic exercises (bodyweight squats, incline push-ups, and hip thrusts) 3 days a week. Participants randomized to the control group will maintain normal activity throughout the 24 weeks. Four visits occurring at baseline, 12-, 18-, and 24-weeks will be used to assess QoL, body composition, prognostic biomarker concentrations, and overall physical function. Primary endpoints include significant changes in prognostic biomarkers. Secondary endpoints include changes in quality of life, physical function and body composition. DISCUSSION: This study should demonstrate preliminary evidence that a home-based exercise intervention can impact biomarkers of progression while improving quality of life, physical function and body composition. Results from this study have the potential to promote health and wellness while minimizing cancer progression in men with PCa.

Myasthenia gravis presentation and treatment variations: A case study approach.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that can affect the ocular, bulbar, neck, proximal limb, and respiratory muscles. This case study presents two similar individuals diagnosed with MG that presented with varying symptomatology and also with a different response to therapy. These two patients represent a unique patient group that represents only 10% of patients diagnosed with MG.

Comparing the effects of progressive and mild intensity treadmill running protocols on neuroprotection of parkinsonian rats.

AIMS: Parkinson's disease (PD) is characterized by progressive loss of dopamine cells. It is suggested that exercise could be employed as a non-pharmacological approach for reducing the risk of PD incidence. The purpose of this study was to compare the effects of 4-week Mild-intensity (MIEx) and progressive exercise (PEx) protocols on rotational behavior, GFAP, DA, TH, MANF, CDNF and NGF levels in striatum of parkinsonian rats induced by 6-hydroxydopamine. METHODS: 42 Wistar male rats were divided into 6 groups including, healthy and PD controls, MIEx, PEx, healthy MIEx, and healthy PEx. MIEx protocol was performed as follows: 5 days a week, 2 sessions a day of 15 min at a speed of 15 m/min. PEx protocol encompassed a training regimen of 5 days a week initiating by 20 min in the first day reaching 50 min on the fifth day and 60 min in the next 3 weeks. PD was induced after training protocol by injection of 6-OHDA into the striatum of rats. For confirming PD, apomorphine rotational test was employed. KEY FINDINGS: The MIEx protocol did not have any positive impacts on the variables except for CDNF (P < 0.0001). Levels of DA (P < 0.0001) and TH (P = 0.0004) increased significantly after performing PEx protocol. Moreover, PEx protocol considerably reduced rotational behavior of rats (P = 0.0244). SIGNIFICANCE: The findings of this research confirm positive effects of PEx in protecting against PD. This progressive training protocol has explicitly shown a neuroprotective effect against PD-inducing nervous toxin through increasing neurotrophins.