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Abstract Background Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. Methods This hypothesis‐generating analysis used biospecimens collected from a multi‐centre 2 × 2 factorial randomized design of 116 patients with stage I–III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log‐transformed, and main effects analyses were conducted using linear mixed‐effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. Results Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin‐15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (−2.69 pg/mL, 95% CI: −4.31, −1.07; adjusted P = 0.014) and interleukin‐15 (−1.74 pg/mL, 95% CI: −2.79, −0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. Conclusions This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis‐generating observation warrants further basic, translational and clinical investigation and replication.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a new disease entity occurring in the pediatric population two to six weeks after coronavirus exposure due to a systemic arteritis. We investigated post-hospital-discharge arterial function at short- and mid-term intervals using pulse wave velocity. We assessed associations between arterial function, left ventricular diastolic and systolic function and left ventricular mass. Materials and methods: Retrospective data collection was carried out on 28 patients with MIS-C with at least two outpatient pediatric cardiology clinic visits post hospital admission. The patients underwent assessment of systemic arterial function and cardiac function. Data included pulse wave velocity between carotid and femoral arteries and echocardiographic assessment of left ventricular systolic function (shortening and ejection fraction, longitudinal strain), diastolic function and left ventricular mass. Results: Pulse wave velocity significantly decreased from visit 1 to visit 2 (5.29 ± 1.34 m/s vs. 4.51 ± 0.91 m/s, p = 0.009). Left ventricular mass significantly decreased from visit 1 to visit 2 (42 ± 9 g/m2.7 vs. 38 ± 7 g/m2.7, p = 0.02). There was a significant negative correlation between the pulse wave velocity and E/A mitral inflow (−0.41, p < 0.05). Conclusions: Children have elevated pulse wave velocity and left ventricular mass in the short-term relative to mid-term values after hospital discharge. These results suggest that MIS-C is associated with transient systemic arterial dysfunction, which, in turn, may play a role in cardiac changes.

Objectives: This study aimed to analyze tobacco and marijuana use by middle and high school students identifying as bisexual, gay, lesbian, or heterosexual using data from the National Youth Tobacco Survey (NYTS) spanning from 2020 to 2022. By comparing substance use patterns among different sexual orientation groups, the study sought to identify disparities and potential socioeconomic factors influencing these behaviors. Methods: Data from the 2020 to 2022 NYTS were analyzed, focusing on responses regarding ever use of cigarettes, e-cigarettes, and marijuana by students of varying sexual orientations. Descriptive statistics and chi-square tests were employed to analyze differences in substance use and socioeconomic indicators between sexual orientation groups. Results: Of the 37 541 students included in the analysis, significant differences in substance use were observed among bisexual, gay, lesbian, and heterosexual students. Bisexual and gay/lesbian students exhibited higher rates of ever use of cigarettes, e-cigarettes, and marijuana compared to heterosexual students. In addition, socioeconomic differences, such as lower rates of family vehicle ownership and reduced access to vacations, were noted among bisexual and gay/lesbian students. Conclusions: The findings underscore significant differences in tobacco and marijuana use by adolescents based on sexual orientation, mirroring differences observed in LGBTQ adults. These results highlight the importance of targeted interventions, educational initiatives, and support systems tailored to the unique needs of LGBTQ youth. Addressing socioeconomic disparities and fostering inclusive environments are crucial steps in promoting the health and well-being of LGBTQ adolescents. Continued research and collaborative efforts are essential in mitigating health disparities and creating equitable environments for all adolescents.

Abstract Tennis elbow (lateral epicondylitis) typically responds well to conservative treatment, and few patients require surgical intervention. This study aimed to investigate the influence of lifestyle and clinical factors on the prognosis of tennis elbow. This prospective, multicenter, nested case–control study included patients diagnosed with lateral epicondylitis after excluding other conditions. Patients who required surgery because of inadequate improvement after 6 months of conservative treatment were defined as the case group; the remaining patients constituted the control group. Propensity score matching was performed to eliminate baseline differences. Univariate and multivariate analyses were performed using logistic regression. This study included 265 patients (53 in the case group, 212 in the control group). Multivariate analysis revealed that smoking, alcohol consumption, and frequent physical exercise were independent risk factors for surgical intervention, whereas combined treatment with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections was a protective factor against surgery. Subgroup analysis showed that heavy drinkers had a 3.74-fold higher risk of requiring surgical treatment within 1 year than occasional drinkers. Smoking and alcohol consumption were associated with non-operative treatment failure in patients with lateral epicondylitis. Combining oral NSAIDs and corticosteroid injections is a favorable conservative treatment option.

Abstract Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (−5.3 kg [SD:1.0]) and genotype-discordant diets (−4.8 kg [SD:1.1]; adjusted difference: −0.6 kg [95% CI: −2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.

An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography–tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their values seen with human StAR. Conversely, these cells carrying K111R and K253R deacetylation mutants diminished E2 biosynthesis. These findings provide novel and mechanistic insights into intra-tumoral E2 regulation by elucidating the functional importance of this uncovered StAR post-translational modification (PTM), involving acetylation and deacetylation events, underscoring the potential of StAR as a therapeutic target for hormone-sensitive BC.

BackgroundPhysical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer.MethodsIn this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage.ResultsIn the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P

Abstract Introduction People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self‐reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI +0.15%) HGI subgroups. Results The prevalence of prediabetes was 42.4% based on FPG, 27.2% based on HbA1c and 17.2% based on 2hOGTT. FPG and HbA1c thus overdiagnosed prediabetes by 25.2% and 10.0%, respectively, compared to the OGTT gold standard. Prevalence was (1) similar in low, moderate and high HGI participants based on 2hOGTT, (2) highest in low HGI participants based on FPG, and (3) highest in high HGI participants based on HbA1c. Among participants with mismatched FPG and HbA1c, OGTT was normal in (1) 79.5% of participants with normal FPG but prediabetic HbA1c (mean HGI = +0.53%), and (2) 75.2% of participants with normal HbA1c but prediabetic FPG (mean HGI = −0.30%). Conclusions FPG overdiagnosed prediabetes in people with low HGI. HbA1c overdiagnosed prediabetes in people with high HGI. Clinical use of HGI could improve prediabetes diagnosis and help health care providers avoid inappropriate or delayed treatment of people with extremes of HGI.

Abstract The most common site of metastasis of prostate cancer (PCa) is bone. Skeletal-related events can increase the risk of death in patients with PCa by 28%. Due to the low detection rate of lesions in patients with low prostate-specific antigen (PSA) levels, the value of 99mTc methylene diphosphonate (99mTc-MDP) bone scintigraphy is limited. Prostate-specific membrane antigen (PSMA) is a small molecular probe that can efficiently and specifically detect PCa lesions. This prospective study aimed to evaluate the difference between 99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and 99mTc-MDP SPECT/CT in the detection of bone metastasis in PCa. A total of 74 men with pathologically confirmed PCa from October 2019 to November 2021 were prospectively enrolled in this study. The median age was 70 (range, 55–87) years. All patients underwent both 99mTc-PSMA SPECT/CT and 99mTc-MDP SPECT/CT at an average interval of 12.1 (range, 1–14) days. The detected imaging-positive bone lesions were scored as “typical metastasis” or “equivocal metastasis” by a standard reporting schema. Subsequent therapy modality details were observed through follow-up. Twenty-five of the 74 patients were diagnosed with bone metastases. 99mTc-PSMA SPECT/CT and 99mTc-MDP SPECT/CT detected 20 and 18 bone metastases, with sensitivities of 80.0% (20/25) and 72.0% (18/25), specificities of 100.0% (49/49) and 81.3% (40/49), and AUCs of 88.0% and 84.9%, respectively. There was a significant difference in the AUC between the two imaging methods (P

BackgroundRelative energy deficiency in sport (RED-S) as a consequence of athlete malnutrition remains a prominent issue. However, it remains underrecognized, in part due to the perceived outward health of athletes. The Eat2Win app was designed to combat RED-S and athlete malnutrition by providing education, behavior modification, and direct communication with expert sports dietitians to athletes and sport professionals (professionals who work with athletes, eg, sport coaches and athletic trainers). ObjectiveThe purpose of this formative research was to gain critical insight on motivators and barriers to optimal nutritional intake from both the athletes’ and sport professionals’ perspectives. Additionally, since these 2 groups represent the primary end users of an app aimed at improving athlete nutrition and reducing the risk of RED-S, a secondary objective was to gain insight on the preferences and perceptions of app-based educational content and functionality. MethodsAn electronic survey was developed by an interdisciplinary team of experts. Survey questions were established based upon prevailing literature, professional dietetic field experience, and app design considerations to obtain respondent knowledge on key sports nutrition topics along with motivations and barriers to meal choices. Additionally, the survey included questions about the development of an integrative, clinician-support app aimed at addressing RED-S. These questions included preferences for educational content, modes of in-app information, and communication delivery for the target population (app end users: athletes and sport professionals). The survey was distributed through Research Electronic Data Capture (REDCap) to athletes and sport professionals using targeted email, social media, and community engagement campaigns. The electronic survey was available from May 4 to August 2, 2022. ResultsSurvey respondents (n=1352) included athletes and professionals who work with athletes from a variety of settings, like high school, collegiate, professional, and club sports. Respondents reported high interest in 8 core sports nutrition topics. The preferred modes of information and communication delivery were visual formats (eg, videos and infographics) and in-app alerts (eg, direct messaging and meal reminders). Only athlete respondents were asked about motivators and barriers that influence meal choices. “Health” and “sports performance” were the highest scoring motivators, while the highest scoring barriers were “cost of food,” “easy access to unhealthy food,” and “time to cook or prepare food.” Notably, survey respondents provided positive feedback and interest using a novel function of the app: real-time meal feedback through food photography. ConclusionsThe Eat2Win app is designed to combat RED-S and athlete malnutrition. Results from this study provide critical information on end-user opinions and preferences and will be used to further develop the Eat2Win app. Future research will aim to determine whether the Eat2Win app can prevent RED-S and the risk of athlete malnutrition to improve both health and performance.

ObjectivesPost-stroke dysphagia is the most common neurological impairment after stroke. The swallowing process is controlled by a network made up of the cerebral cortex, subcortical area, and brainstem structure. The disruption of the swallowing network after stroke leads to dysphagia. The affected swallowing muscles after stroke mainly include the laryngeal muscles (suprahyoid muscle and thyrohyoid muscle) and infrahyoid muscle. These muscles experience kinematic effects and muscle strength weakens, resulting in reduced movement in the swallowing process. Acupuncture can change the excitability of cerebral cortical nerve cells, promote the recovery of neurological function, and enhance neuromuscular excitability, ultimately improving the control of swallowing-related nerves and muscles and promoting swallowing functional recovery. In this meta-analysis, we systematically evaluate the clinical efficacy of acupuncture in the treatment of post-stroke dysphagia.MethodsRandomized controlled trials of tongue acupuncture therapy for post-stroke dysphagia were searched and selected from seven electronic databases (PubMed, CBM, Cochrane, Embase, CNKI, VPCS, and Wan fang). The Cochrane Collaboration tool was used to conduct methodological quality assessment. Rev. Man 5.4 software was utilized to perform data analysis.ResultsA total of 15 studies with 1,094 patients were included. Meta-analysis Showed that WST score WST score (MD = −0.56, 95% CI (−1.23, 0.12), Z = 1.62, p

Objectives: The use of alternative nicotine products by middle and high school students is a growing concern due to industry marketing techniques, availability, and popularity of new products, and ambiguous nicotine concentrations. The 2021 National Youth Tobacco Survey (NYTS) provides information about the frequency, and characteristics of middle, and high school students who have used nicotine pouches. Methods: The National Youth Tobacco Surveys provide important information about the frequency of use of tobacco and alternative nicotine products by a representative sample of students in schools in the United States. The 2021 survey included questions about the use of nicotine pouches/dissolvable tobacco products. The results from the survey were analysis using descriptive statistics, and logistic regression to model the association between the use of these alternative nicotine products, and the use of electronic cigarettes or the use of conventional cigarettes. Results: A total of 20 413 students participated in the survey year 2021; 17 842 were included in the final data analysis. Their ages ranged from 9 to 18+. Identified risk factors for the use of alternative nicotine products included race, and age. The adjusted odds ratio (OR) was lower in non-Hispanic Black and Hispanic students, as compared to non-Hispanic White students. Older students had a substantially higher risk of using nicotine/dissolvable tobacco products, specifically, compared to students less than or equal to 13 years old. The OR increased 174% (OR: 2.74; 1.70-4.41) in 17-year-old students. The perception of harm associated with electronic cigarettes increased the likelihood of using alternative nicotine products. Students who did not smoke cigarettes (OR: 0.39; 0.27-0.56) or did not smoke electronic cigarettes (OR: 0.20; 0.18-0.40) had significantly lower OR for using alternative nicotine products. Conclusions: The 2021 National Youth Tobacco Survey indicates that a relatively small percentage of middle school and high school student have used nicotine pouches. However, with the increase in new, alternative tobacco products, understanding adolescent use in comparison to other tobacco products is an important trend to monitor.

Abstract Background Body mass is the primary metabolic compartment related to a vast number of clinical indices and predictions. The extent to which skeletal muscle (SM), a major body mass component, varies between people of the same sex, weight, height, and age is largely unknown. The current study aimed to explore the magnitude of muscularity variation present in adults and to examine if variation in muscularity associates with other body composition and metabolic measures. Methods Muscularity was defined as the difference (residual) between a person's actual and model‐predicted SM mass after controlling for their weight, height, and age. SM prediction models were developed using data from a convenience sample of 492 healthy non‐Hispanic (NH) White adults (ages 18–80 years) who had total body SM and SM surrogate, appendicular lean soft tissue (ALST), measured with magnetic resonance imaging and dual‐energy X‐ray absorptiometry, respectively; residual SM (SMR) and ALST were expressed in kilograms and kilograms per square meter. ALST mass was also evaluated in a population sample of 8623 NH‐White adults in the 1999–2006 National Health and Nutrition Examination Survey. Associations between muscularity and variation in the residual mass of other major organs and tissues and resting energy expenditure were evaluated in the convenience sample. Results The SM, on average, constituted the largest fraction of body weight in men and women up to respective BMIs of 35 and 25 kg/m2. SM in the convenience sample varied widely with a median of 31.2 kg and an SMR inter‐quartile range/min/max of 3.35 kg/−10.1 kg/9.0 kg in men and 21.1 kg and 2.59 kg/−7.2 kg/7.5 kg in women; per cent of body weight as SM at 25th and 75th percentiles for men were 33.1% and 39.6%; corresponding values in women were 24.2% and 30.8%; results were similar for SMR indices and for ALST measures in the convenience and population samples. Greater muscularity in the convenience sample was accompanied by a smaller waist circumference (men/women: P

Breast cancer (BC) is a heterogeneous condition and comprises molecularly distinct subtypes. An imbalance in the levels of epigenetic histone deacetylases (HDACs), modulating estrogen accumulation, especially 17β-estradiol (E2), promotes breast tumorigenesis. In the present study, analyses of The Cancer Genome Atlas (TCGA) pan-cancer normalized RNA-Seq datasets revealed the dysregulation of 16 epigenetic enzymes (among a total of 18 members) in luminal BC subtypes, in comparison to their non-cancerous counterparts. Explicitly, genomic profiling of these epigenetic enzymes displayed increases in HDAC1, 2, 8, 10, 11, and Sirtuins (SIRTs) 6 and 7, and decreases in HDAC4–7, –9, and SIRT1–4 levels, respectively, in TCGA breast tumors. Kaplan–Meier plot analyses showed that these HDACs, with the exception of HDAC2 and SIRT2, were not correlated with the overall survival of BC patients. Additionally, disruption of the epigenetic signaling in TCGA BC subtypes, as assessed using both heatmaps and boxplots, was associated with the genomic expression of factors that are instrumental for cholesterol trafficking/utilization for accelerating estrogen/E2 levels, in which steroidogenic acute regulatory protein (STAR) mediates the rate-limiting step in steroid biosynthesis. TCGA breast samples showed diverse expression patterns of a variety of key steroidogenic markers and hormone receptors, including LIPE, CYP27A1, STAR, STARD3, CYP11A1, CYP19A1, ER, PGR, and ERBB2. Moreover, regulation of STAR-governed steroidogenic machinery was found to be influenced by various transcription factors, i.e., CREB1, CREM, SF1, NR4A1, CEBPB, SREBF1, SREBF2, SP1, FOS, JUN, NR0B1, and YY1. Along these lines, ingenuity pathway analysis (IPA) recognized a number of new targets and downstream effectors influencing BCs. Of note, genomic, epigenomic, transcriptional, and hormonal anomalies observed in human primary breast tumors were qualitatively similar in pertinent BC cell lines. These findings identify the functional correlation between dysregulated epigenetic enzymes and estrogen/E2 accumulation in human breast tumors, providing the molecular insights into more targeted therapeutic approaches involving the inhibition of HDACs for combating this life-threatening disease.

ObjectiveTo explore the use of 99mTc-rituximab tracer injection for internal mammary sentinel lymph node (IM-SLN) detection in patients with primary breast cancer.MethodsThis prospective observational study enrolled female patients with primary breast cancer between September 2017 and June 2022 at Fujian Provincial Hospital. The participants were divided into the peritumoral group (two subcutaneous injection points on the surface of the tumor), two-site group (injections into the glands at 6 and 12 o’clock around the areola area), and four-site group (injections into the gland at 3, 6, 9, and 12 o’clock around the areola area). The outcomes were the detection rates of the IM-SLNs and axillary sentinel lymph nodes (A-SLNs).ResultsFinally, 133 patients were enrolled, including 53 in the peritumoral group, 60 in the two-site group, and 20 in the four-site group. The detection rate of the IM-SLNs in the peritumoral group (9.4% [5/53]) was significantly lower than in the two-site (61.7% [37/60], P

Objectives: The current guidelines for managing patients with sepsis include the early cultures, administration of antibiotics, and fluid resuscitation. Several clinical trials have tried to determine whether or not the administration of corticosteroids improves outcomes in these patients. This study analyzed the characteristics of a large group of critically ill patients who either had cortisol levels drawn during their intensive care unit management or had hydrocortisone administered during their management. Methods: A list of patients who had cortisol levels measured or who had hydrocortisone administered empirically for the treatment of sepsis was identified by the medical record department at University Medical Center in Lubbock, Texas. The primary outcome was in-hospital mortality. Secondary outcomes included the need for mechanical ventilation, the need for renal replacement therapy, the need for vasopressors, length of stay, and the development of nosocomial infections. Results: This study included 351 patients, including 194 women (55.3%). The mean age was 62.9 ± 16.1 years. The mean admission SOFA score was 9.3 ± 3.63, the mean APACHE 2 score was 18.15 ± 7.7, and the mean lactic acid level was 3.8 ± 4.0 mmol/L. One hundred sixty-two patients required intubation, 262 required vasopressors, 215 developed acute kidney injury, and 319 had cortisol levels measured. The mean length of stay was 11.5 ± 13.7 days; the mortality rate was 32.2%. Multiple variable analysis demonstrated that higher cortisol levels were associated with increased mortality (44.1% if cortisol ⩾20 µg/dL versus 17.5% if cortisol

Abstract Background Enhanced metabolic plasticity and diversification of energy production is a hallmark of highly proliferative breast cancers. This contributes to poor pharmacotherapy efficacy, recurrence, and metastases. We have previously identified a mitochondrial-targeted furazano[3,4-b]pyrazine named BAM15 that selectively reduces bioenergetic coupling efficiency and is orally available. Here, we evaluated the antineoplastic properties of uncoupling oxidative phosphorylation from ATP production in breast cancer using BAM15. Methods The anticancer effects of BAM15 were evaluated in human triple-negative MDA-MB-231 and murine luminal B, ERα-negative EO771 cells as well as in an orthotopic allograft model of highly proliferative mammary cancer in mice fed a standard or high fat diet (HFD). Untargeted transcriptomic profiling of MDA-MB-231 cells was conducted after 16-h exposure to BAM15. Additionally, oxidative phosphorylation and electron transfer capacity was determined in permeabilized cells and excised tumor homogenates after treatment with BAM15. Results BAM15 increased proton leak and over time, diminished cell proliferation, migration, and ATP production in both MDA-MB-231 and EO771 cells. Additionally, BAM15 decreased mitochondrial membrane potential, while inducing apoptosis and reactive oxygen species accumulation in MDA-MB-231 and EO771 cells. Untargeted transcriptomic profiling of MDA-MB-231 cells further revealed inhibition of signatures associated with cell survival and energy production by BAM15. In lean mice, BAM15 lowered body weight independent of food intake and slowed tumor progression compared to vehicle-treated controls. In HFD mice, BAM15 reduced tumor growth relative to vehicle and calorie-restricted weight-matched controls mediated in part by impaired cell proliferation, mitochondrial respiratory function, and ATP production. LC-MS/MS profiling of plasma and tissues from BAM15-treated animals revealed distribution of BAM15 in adipose, liver, and tumor tissue with low abundance in skeletal muscle. Conclusions Collectively, these data indicate that mitochondrial uncoupling may be an effective strategy to limit proliferation of aggressive forms of breast cancer. More broadly, these findings highlight the metabolic vulnerabilities of highly proliferative breast cancers which may be leveraged in overcoming poor responsiveness to existing therapies.

Summary: Background: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. Methods: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose–response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. Findings: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]). Interpretation: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. Funding: US Centers for Disease Control and Prevention.

Vaccinations against COVID-19 infection have become a contentious issue in the United States. Multiple segments of society, including healthcare workers, have expressed concerns regarding the need for vaccination and the safety of current vaccines. Many hospital-based nurses have helped care for patients with severe COVID-19 infections. An anonymous online survey was sent to the nursing staff at University Medical Center in Lubbock, TX, USA, through a hospital-based email system to determine vaccination status and attitudes towards the COVID-19 vaccine and other routine vaccines. Multivariable regression analysis was used to determine factors associated with vaccination. A total of 251 nurses responded to this survey; 211 nurses (83.7%) had received the vaccine. Almost all nurses (242, 96%) had received all childhood vaccinations, and 231 (91.7%) had received an influenza vaccination in the prior year. A minority of nurses (75, 29.8%) supported mandatory vaccination for healthcare workers. The reasons for declining vaccination included the possibility that diet and alternative medications provided better protection against COVID-19. This survey demonstrates that over 80% of nurses working in a hospital managing very sick patients with COVID-19 infection had been vaccinated. However, nurses who did not take the annual influenza vaccine and did not consider other protective measures useful (such as mask-wearing) were significantly less likely to vaccinate. Nurses can provide an important resource for conversations with the public and patients about vaccine initiatives.

The purpose of this study was to examine whether a 9-month intensive lifestyle intervention could lead to weight loss and improve cardiovascular risk factors among young women with both gestational diabetes mellitus (GDM) and newly diagnosed diabetes. A total of 83 young women, who had GDM and were subsequently diagnosed as type 2 diabetes at an average of 2.6 years after delivery, participated in a 9-month intensive lifestyle intervention and a follow-up survey at 6–9 years postintervention. After the 9-month intervention, these women had a weight loss of 2.90 kg (−4.02% of initial weight), decreased waist circumference (−3.12 cm), body fat (−1.75%), diastolic blood pressure (−3.49 mmHg), fasting glucose (−0.98 mmol/L) and HbA1c (−0.72%). During the 6–9 years postintervention period, they still had lower weight (−3.71 kg; −4.62% of initial weight), decreased waist circumference (−4.56 cm) and body fat (−2.10%), but showed a slight increase in HbA1c (0.22%). The prevalence of using glucose-lowering agents increased from 2.4% at baseline to 34.6% after the 9-month lifestyle intervention, and to 48.4% at 6–9 years postintervention. A 9-month intensive lifestyle intervention can produce beneficial effects on body weight, HbA1c and other cardiovascular risk factors among young women with previous GDM who subsequently developed new diabetes.

Abstract Aims A high haemoglobin glycation index (HGI) is associated with greater risk for hypoglycaemia and chronic vascular disease. Standardizing how the HGI is calculated would normalize results between research studies and hospital laboratories and facilitate the clinical use of HGI for assessing risk. Methods The HGI is the difference between an observed HbA1c and a predicted HbA1c obtained by inserting fasting plasma glucose (FPG) into a regression equation describing the linear relationship between FPG and HbA1c in a reference population. We used data from the 2005–2016 U.S. National Health and Nutrition Examination Survey (NHANES) to identify a reference population of 18,675 diabetes treatment–naïve adults without self‐reported diabetes. The reference population regression equation (predicted HbA1c = 0.024 FPG + 3.1) was then used to calculate the HGI and divide participants into low (

Background: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. Methods: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. Results: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). Conclusions: Among patients with colon cancer, these results do not support homebased RT as an adjunct to chemotherapy specifically to improve planned treatment intensity. [ABSTRACT FROM AUTHOR]

Study design: A systematic review and meta-analysis. Objective: The objective of this meta-analysis was to evaluate the association between calcium-phosphorus balance and adolescent idiopathic scoliosis (AIS). Methods: Databases, including PubMed, OVID database, Web of Science, CBM database and CNKI database were searched for the relevant case control studies and cross-sectional studies. Two authors selected studies and extracted data independently. Data analysis was performed by Review Manager Software 5.0. Subgroup analysis was performed on the serum level of vitamin D according to gender and menstruation. Results: Five studies were included, with a total of 646 cases of AIS and 791 controls. AIS group had a lower serum level of vitamin D compared to control group [MD = −6.74, 95% CI (−9.47, −4.00)]. Gender and menstruation condition were thought to have no effect on the primary outcome of vitamin D level by subgroup analysis [MD = −5.97, 95% CI (7.61, −4.34)]. The AIS group had a lower calcium level [SMD= −0.77, 95% CI (−1.51, −0.02)] and calcitonin level compared to control group. There was no statistical difference in phosphorus level [SMD=0.5, 95% CI (−0.46, 0.57)] and parathyroid hormone level [SMD = −0.11, 95% CI (−0.54, −0.31)]. Meanwhile, the observational indexes, including serum levels of calcium, phosphorus, parathyroid hormone and calcitonin were within normal limits. Conclusion: Vitamin D deficiency may be involved in the pathogenesis of AIS by influencing the regulation of calcium-phosphors metabolism on human bone. Therefore, we suggest to screen vitamin D level in AIS patients. Level of Evidence: Level III, Therapeutic Study Keywords: Systematic review, Metabolism, Vitamin D, Scoliosis, Etiology, Adolescent

Background: Hyperglycemia at the time of hospital admission has been associated with poor outcomes in several patient groups, but there is little information about this association in hospitalized patients with diverse diagnoses. Methods: We identified all adult patients admitted between 10/1/2015 and 9/30/2016 who had glucose levels measured during the first 24 h after admission to the hospital. Clinical information included age, gender, glucose levels, diagnoses based on ICD 10 discharge coding, length of stay (LOS), and mortality. Patients were classified into quartiles based on glucose levels and into clinically relevant glucose categories. Results: This study included 18,478 adult patients admitted to a tertiary care hospital. The median age was 53 years, the median LOS was 4 days, and the overall in-hospital mortality was 3.8%. The median admission glucose level was 117 mg/dL. Mortality increased in each glucose quartile; it was also highest in patients admitted with a glucose 200 mg/dL. The LOS was significantly shorter in patients in glucose quartiles 1 and 2. Conclusions: Admission glucose levels were associated with in-hospital mortality and LOS in this cohort of hospitalized patients. Attention to glucose levels can help identify patients at risk for poor outcomes.

Background: Pressures measured during mechanical ventilation provide important information about the respiratory system mechanics and can help predict outcomes. Methods: The electronic medical records of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic information, clinical information, management requirements, and outcomes, such as mortality, ICU length of stay, and hospital length of stay. Mechanical ventilation pressures were recorded on the second full day of hospitalization. Results: This study included 312 adult patients. The mean age is 59.1 ± 16.3 years; 57.4% were men. The mean BMI was 29.3 ± 10.7. Some patients had pulmonary infections (46.2%), and some patients had extrapulmonary infections (34.9%). The overall mortality was 42.6%. In a multi-variable model that included age, gender, number of comorbidities, APACHE 2 score, and PaO 2 /FiO 2 ratio, peak pressure, plateau pressure, driving pressure, and PEEP all predicted mortality when entered into the model separately. There was an increase in peak pressure, plateau pressure, and driving pressure across BMI categories ranging from underweight to obese. Conclusions: This study demonstrates that ventilator pressure measurements made early during the management of patients with acute respiratory failure requiring mechanical ventilation provide prognostic information regarding outcomes, including mortality. Patients with high mechanical ventilator pressures during the early course of their acute respiratory failure require more attention to identify reversible disease processes when possible. In addition, increased BMIs are associated with increased ventilator pressures, and this increases the complexity of the clinical evaluation in the management of obese patients.

To investigate the productions of biogenic amines (BAs) in Pacific white shrimp treated by compound preservatives (P, 0.05 g/L quercetin, 0.025 g/L 4-hexylresorcinol, and 0.025 g/L cinnamic acid) in combination with modified atmosphere packaging (M, 80% CO2/10% O2/10% N2), four groups of samples treated with or without preservatives and alone or in combination with modified atmosphere packaging (A, A+P, M, M+P) during storage at 4 °C for 12 days were analyzed. Most BAs increased in all samples, especially, putrescine and cadaverine. MAP inhibited the increase of most BAs (except for tyramine) and psychrotrophic bacterial counts. The inhibitory effect of the compound preservatives on bacterial growth and BAs was limited in aerobically- and MAP-stored samples, but they retarded the production of tyramine, which accumulated more rapidly in MAP. Lowest total BAs and bacterial counts were found in sample M+P (78.3 mg/kg and 5.82 log cfu/g, day 12), indicating that the combined treatment of the preservatives and MAP could reduce the risk of disorders caused by BAs. Keywords: Pacific white shrimp, Biogenic amines, Tyramine, Quercetin-containing preservatives

Background: Indwelling pleural catheters (IPC) have been used increasingly in patients with recurrent pleural effusions. However, data about mortality after IPC use are limited. Objectives: We sought to determine the natural history following IPC placement in Lubbock, Texas, in terms of life expectancy and pleurodesis rates in patients with both malignant and benign effusions. Methods: A retrospective review of patients who had IPC insertion from March 2014 through December 2016 at University Medical Center in Lubbock, Texas, was performed. Patients 18 years and older who had IPC placement for recurrent pleural effusions were included. The duration of IPC placement, the type of pleural effusion, the volume of fluid, pleurodesis, complications, and mortality after IPC placement were retrieved from electronic medical records. Results: There were 45 patients included in the study; 20 patients (44%) were male, and 25 patients (56%) were female. The mean age was 63.5 years old. There were 33 patients with malignant pleural effusion and 12 patients with benign pleural effusion. No patients with malignant effusion were known to be alive at the time of mortality calculation, whereas two patients with benign effusion were known to be alive. Median survival was 468 days in the benign effusion group and 115 days in the malignant effusion group. The 30-day mortality was not significantly different between the two groups (malignant 34.5% vs. benign 25.0%). However, 1-year mortality was significantly higher in the malignant effusion group (89.7%) than in the benign effusion group (41.7%) (p < 0.005). Conclusion: The use of indwelling pleural catheters in Lubbock, Texas, has comparable results to published studies. These catheters should be considered as a bridge to a long-term treatment rather than a definitive therapy.

Abstract Background Evidence suggests that tocotrienols may benefit bone health in osteopenic women. However, their safety in this population has never been investigated. This study was to evaluate the safety of a 12-week supplementation of annato tocotrienol in postmenopausal osteopenic women, along with effects of the supplementation on quality of life, body composition, physical activity, and nutrient intake in this population. Methods Eighty nine postmenopausal osteopenic women were randomly assigned to 3 treatment arms: (1) Placebo (430 mg olive oil/day), (2) Low tocotrientol (Low TT) (430 mg tocotrienol/day from DeltaGold 70 containing 300 mg tocotrienol) and (3) High tocotrienol (High TT) (860 mg tocotrienol/day from DeltaGold 70 containing 600 mg tocotrienol) for 12 weeks. DeltaGold 70 is an extract from annatto seed with 70% tocotrienol consisting of 90% delta-tocotrienol and 10% gamma-tocotrienol. Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, bilirubin, kidney function (blood urea nitrogen and creatinine), electrolytes, glucose, protein, albumin, and globulin at 0, 6, and 12 weeks. Serum tocotrienol and tocopherol concentrations were assessed and pills counted at 0, 6, and 12 weeks. Quality of life, body composition, physical activity, and dietary macro- and micro-nutrient intake were evaluated at 0 and 12 weeks. A mixed model of repeated measures ANOVA was applied for analysis. Results Eighty seven subjects completed the study. Tocotrienol supplementation did not affect liver or kidney function parameters throughout the study. No adverse event due to treatments was reported by the participants. Tocotrienol supplementation for 6 weeks significantly increased serum delta-tocotrienol level and this high concentration was sustained to the end of study. There was no difference in serum delta-tocotrienol levels between the Low TT and the High TT groups. No effects of tocotrienol supplementation were observed on quality of life, body composition, physical activity, and nutrient intake. Conclusions Annatto-derived tocotrienol up to 600 mg per day for 12 weeks appeared to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. Tocotrienol supplementation for 12 weeks did not affect body composition, physical activity, quality of life, or intake of macro- and micro-nutrients in these subjects. Trial registration ClinicalTrials.gov identifier: NCT02058420. Title: Tocotrienols and bone health of postmenopausal women.

Clinical research using routine laboratory tests can provide important opportunities to investigators, especially those with limited resources, and can improve patient care, especially if the result improves clinical decision making without the use of more sophisticated or expensive tests. Laboratory analysis of biological parameters can be used for screening, diagnostic testing, predicting prognosis, and measuring treatment responses. Often the same parameter can be used for several purposes, depending on the clinical scenario and the patient population. For example, several studies have suggested the mean platelet volume (MPV) is different in patients with acute coronary syndrome compared to patients with coronary disease but no acute syndrome. Given this information it might seem relatively easy to start studies using this laboratory test. However, multiple questions need to be considered before starting any research using MPV measurements. We will discuss some of these considerations in this review article. This approach applies to most research projects based on laboratory tests.

Background: Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods: In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFaR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. Results: In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFaR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P<0.001) but not sTNFaR2 (P=0.39). In stage I-II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI: -70.1, -0.7) and IL6: -29.6% (95% CI: -58.4, -0.8) but not sTNFaR2: 2.7% (95% CI: sTNFaR2: -15.7, 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. Conclusion: This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype with limited treatment options. Obesity and insulin resistance are associated with a worse prognosis in those with TNBC. Moringa oleifera (moringa) is a tropical edible plant used for both food and medicinal purposes and found to have anti-obesity and anti-cancer effects in vitro and in preclinical models. The anti-cancer effects of moringa seed extract alone and in combination with chemotherapy were evaluated in immunocompromised female mice with diet-induced obesity bearing MDA-MB-231-derived xenograft tumors. Moringa supplementation protected against high-fat diet- and chemotherapy-induced increases in fasting glucose and improved insulin sensitivity. Moringa supplementation alone did not attenuate tumor growth relative to chemotherapy alone, and in combination worsened tumor progression. Moringa supplementation alone reduced angiogenesis, but this effect was abrogated in combination with chemotherapy. Moringa supplementation may be an effective strategy to improve metabolic health in mice with obesity and TNBC and reduce angiogenesis in tumors, but may have a negative interaction when used as a concurrent complementary therapy. Caution should be taken when considering the consumption of moringa seed extracts while receiving chemotherapy for breast cancer treatment. Further investigations of alternative timings of moringa therapy are warranted.

Objective: The aim of this study was to compare the unilateral and bilateral approaches in treating osteoporotic vertebral compression fractures. Methods: Based on the principles and methods of the Cochrane systematic reviews, the records of the Cochrane Library, PubMed, Web of Science, Chinese Bio-medicine database, China Journal Full-text Database, VIP database, and Wanfang database were reviewed until October 2014. The randomized controlled trials on unilateral and bilateral approaches to percutaneous vertebroplasty (PVP)/percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures were included. The risk of bias of included trials was assessed based on the Cochrane Handbook for Systematic Reviews of Interventions Version. The RevMan Software 5.0 was used for meta-analysis. Results: Fifteen randomized controlled trials with a total of 850 patients were included. Risk of bias in the included studies was inevitable. There was no statistically significant difference in visual analog scale, vertebral height, kyphotic angular, and quality of life. The main operative complications were bone cement leakage and adjacent vertebral fracture, without difference between the two groups. Conclusions: In view of the current evidence, there is insufficient evidence to show any difference between the unilateral and bilateral approaches in both the PVP and PKP treatment in osteoporotic vertebral compression fractures. Level of Evidence: Level I, Therapeutic study. Keywords: Minimally invasive surgery, Osteoporotic vertebral compression fracture, Percutaneous kyphoplasty, Percutaneous vertebroplasty, Systematic review

Background: Acute kidney injury (AKI) is often one component of multiple organ failure (MOF) in the intensive care unit (ICU). However, not all patients with MOF develop AKI, and AKI may develop in the absence of MOF. We compared the impact of AKI alone and in combination with MOF on the survival of patients admitted to a large tertiary care medical intensive care unit (MICU). Methods: We abstracted data from the electronic medical records of patients admitted to the MICU from April 2012 through June 2013 and categorized patients as either high-risk or low- risk status based on use of vasopressor support or mechanical ventilation during the ICU stay. The outcomes we considered were in-hospital, 30-day, 90-day, 180-day, and 1-year mortality. Results: Of the 834 critically ill patients, 743 (89%) developed some degree of AKI. Ninety-one percent of the high-risk cohort developed AKI and 87% of the low-risk cohort developed AKI. Patients with AKI had higher mortality at 1-year than patients without AKI (adjusted odds ratio [OR], 2.5; 95% confidence interval [CI], 1.38 to 4.53); P interaction 0.0026). Hospital mortality was greater for high-risk patients without AKI than for low-risk patients with AKI. Conclusion: Acute kidney injury occurs at similar frequency in high and low-risk ICU patients and has significant impact on survival in both groups. Cardiovascular collapse or respiratory failure has greater impact on short term mortality than AKI, but this effect diminishes over time. Conversely, the impact of AKI on mortality increased over time and remained an independent risk factor for mortality.