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Background Aging affects immunity, potentially altering fever response to infection. We assess effects of biological variables on basal temperature, and during COVID-19 infection, proposing an updated temperature threshold for older adults ≥65 years. Methods Participants were from 4 cohorts: 1 089 unaffected adult TwinsUK volunteers; 520 adults with emergency admission to a London hospital with RT-PCR confirmed SARS-CoV-2 infection; 757 adults with emergency admission to a Birmingham hospital with RT-PCR confirmed SARS-CoV-2 infection and 3 972 adult community-based COVID Symptom Study participants self-reporting a positive RT-PCR test. Heritability was assessed using saturated and univariate ACE models; mixed-effect and multivariable linear regression examined associations between temperature, age, sex, and body mass index (BMI); multivariable logistic regression examined associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis was used to identify temperature threshold for adults ≥ 65 years. Results Among unaffected volunteers, lower BMI (p = .001), and increasing age (p < .001) was associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% confidence interval 18%–57%). In COVID-19+ participants, increasing age was associated with lower temperatures in Birmingham and community-based cohorts (p < .001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p < .001). Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults Conclusions Aging affects temperature in health and acute infection, with significant heritability, indicating genetic factors contribute to temperature regulation. Our observations suggest a lower threshold (37.4°C/97.3°F) for identifying fever in older adults ≥65 years.

Background: High meat consumption might play a role in promoting low-grade systemic inflammation, but evidence is limited. Objectives: We examined cross-sectional associations of habitual meat consumption with serum C-reactive protein (CRP) and total white blood cell count (WBCC) in British adults. Methods: We included 403,886 men and women (aged 38–73 y) participating in the UK Biobank who provided information on meat intake (via touchscreen questionnaire) and a nonfasting blood sample at recruitment (2006–2010). For a subset of participants (∼5%), an additional blood sample was collected (median 4.4 y later). We used multivariable linear regression models to estimate associations of meat intake (total meat, unprocessed red meat, processed meat, and poultry) with logCRP and logWBCC. Results: The difference in the serum CRP (mg/L) for each 50-g/d higher intake for total meat was 11.6% (95% CI: 11.1, 12.0%), for processed meat was 38.3% (95% CI: 36.0, 40.7%), for unprocessed red meat was 14.4% (95% CI: 13.6, 15.1%), and for poultry was 12.8% (95% CI: 12.0, 13.5%). The difference in the WBCC (×10–9L) for each 50 g/d higher intake of total meat was 1.5% (95% CI: 1.4, 1.6%), for processed meat was 6.5% (95% CI: 6.1, 6.9%), for unprocessed red meat was 1.6% (95% CI: 1.4, 1.7%), and for poultry was 1.6% (95% CI: 1.4, 1.7%). All associations were attenuated after adjustment for adiposity; by 67% with BMI (in kg/m2) and by 58% with waist circumference for total meat and CRP, and by 53% and 47%, respectively, for WBCC, although associations remained statistically significant. Findings of sensitivity analyses in 15,420 participants were similar prospectively, except there were no associations between unprocessed red meat and WBCC. Conclusions: Higher meat consumption, particularly of processed meat, was positively associated with inflammatory markers in these British adults; however, the magnitudes of associations are small and predominantly due to higher adiposity.

Background: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. Objectives: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. Methods: Twelve young (18–35 y old) and 12 older (60–75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. Results: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). Conclusions: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems. This trial was registered at www.isrctn.com as ISRCTN86706442.

Background Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty. Objective To examine this hypothesis using a Mendelian randomization (MR) analysis. Methods We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean [SD] age of 56.7 [8.0] years. The association between serum protein measures and FI was mainly analyzed by the inverse variance weighted method. Results A genetically predicted serum albumin level was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (beta = -0.172 per g/L; 95% confidence interval = -0.336 to -0.007; P = 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (beta = -0.153 per g/L; 95% confidence interval = -0.251 to -0.056; P = 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% confidence interval = -0.287 to -0.009; P = 0.037) for women, -0.154 per g/L (95% confidence interval = -0.290 to -0.018; P = 0.027) for men. Conclusions The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.

Background Coverage of iron folic-acid (IFA) supplementation is a key indicator for tracking programmatic progress within and across countries. However, the validity of maternal report of this information during household surveys has yet to be determined. Objective This study aimed to examine the validity of maternal recall of receipt of IFA supplementation during antenatal care and factors associated with accuracy of maternal recall. Methods A longitudinal cohort design was employed. The direct observation of the IFA received during all antenatal care visits at the five study health posts served as the "gold standard" to the maternal report of IFA received during the postpartum interview. Individual-level validity was assessed by calculating indicator sensitivity, specificity and area under the operating curve (AUC). The inflation factor (IF) measured population-level bias. A multivariable log-binomial model was used to assess factors associated with accurate recall. Results The majority (95.8%) of women were observed receiving IFA during pregnancy. Women overreported the number IFA tablets received compared to what was observed during ANC visits (mean difference = 45 tablets). Maternal report of any IFA receipt was moderate (AUC = 0.60, 95% CI: 0.50, 0.71) and population bias was low (IF = 1.01). However, the individual-level validity was poor across the seven IFA tablet count categories; the AUC for categories ranged from misleading to moderate. Driven by the trend of maternal overreport, the inflation factor indicated that maternal report drastically underestimated the coverage of lower tablet categories and overestimated the coverage of higher tablet counts. Accuracy of maternal report was not associated with months since last ANC observation nor any maternal characteristics. Conclusions Maternal report of the amount of IFA supplementation received during pregnancy produced extremely biased population coverage and performed poorly to moderately for individual level validity. It is imperative to improve this indicator, as it is used in global frameworks and national program planning.

Background: Observational studies have reported associations between serum phosphate and BMI in specific clinical settings, but the nature of this relation in the general population is unclear. Objectives: The aim of this study was twofold: to investigate the association between serum phosphate and BMI and body composition, as well as to explore evidence of causality through a bidirectional one-sample Mendelian randomization (MR) in the population-based Rotterdam Study (RS). Methods: Observational associations between phosphate (mg/dL) and BMI, lean mass, and fat percentage (fat%), estimated by DXA, were analyzed using multivariable regression models in 9202 participants aged 45-100 y from 3 RS cohorts. The role of serum leptin was examined in a subgroup of 1089 participants. For MR analyses, allele scores with 6 single-nucleotide polymorphisms (SNPs) for phosphate and 905 SNPs for BMI were constructed in 7983 participants. Results: Phosphate was inversely associated with BMI in the total population (β: -0.89; 95% CI: -1.17, -0.62), and stronger in women (β: -1.92; 95% CI: -2.20, -1.65) than in men (β: -0.37; 95% CI: -0.68, -0.06) (P-interaction < 0.05). Adjustment for leptin did not change results in men. In women, adjustment for leptin attenuated the association, but it was not abolished (β: -0.94; 95% CI: -1.45, -0.42). Phosphate was inversely associated with fat%, but not with lean mass, in both sexes. MR analyses suggested a causal effect of BMI on serum phosphate (β: -0.01; 95% CI: -0.02, 0.00) but not vice versa. Conclusions: Serum phosphate was inversely associated with BMI and fat% in a population-based study of middle-aged and older adults, with a stronger effect in women than in men. Adjusting for leptin attenuated this relation in women only. MR results suggest a causal effect of BMI on phosphate but not vice versa. An underlying sex dimorphism in phosphate homeostasis should be further explored.

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan–Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer.

Background: Measurement of the 24-h urinary iodine concentration or urinary iodine excretion (UIE) is the gold standard to determine iodine status; however, this method is inconvenient. The use of salivary iodine could be a possible alternative since salivary glands express the sodium-iodine symporter.Objectives: We aimed to establish the correlation between the salivary iodine secretion and UIE, to evaluate the clinical applicability of the iodine saliva measurement.Methods: We collected 24-h urine and saliva samples from 40 participants >= 18 y: 20 healthy volunteers with no specific diet (group 1), 10 patients with differentiated thyroid cancer with a low dietary intake (

The present study aimed to reduce the parotid gland dose in the hippocampus avoidance with whole-brain radiotherapy (HA-WBRT) using the helical tomotherapy (HT). Ten patients who had previously undergone WBRT were randomly selected and enrolled in this study. During the treatment planning, two different techniques to the jaw were applied for each patient, namely, 1.0 cm fixed jaw and 2.5 cm dynamic jaw. To efficiently reduce the dose in the bilateral parotid glands, directional block (DB) mode was set. The DB is a function of a treatment planning system for the dose reduction in organs at risk. The standard HA-WBRT plan which did not reduce the parotid gland dose was also designed to compare the plan quality. Compared with the standard HA-WBRT plan, the parotid gland dose could be reduced by approximately 70% without extending the delivery time by adding the parotid gland on the DB mode to the dose constraint. In addition, the differences in dosimetric parameters observed between the plans employing the 1.0 cm fixed jaw and 2.5 cm dynamic jaw were almost negligible. Moreover, delivery time in the 2.5 cm dynamic jaw could be greatly reduced by 60% compared with that in the 1.0 cm fixed jaw.

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V15 Gy)

According to guidelines, carbon-ion beam therapy is considered to carry a high safety risk for patients with cardiac implantable electronic devices (CIEDs), although the actual impacts remain unclear. In this study, we investigated the safety of carbon-ion beam therapy in patients with CIEDs. Patients with CIEDs who underwent carbon-ion therapy at Gunma University Heavy Ion Medical Center between June 2010 and December 2019 were identified and investigated for abnormalities in the operation of their CIEDs, such as oversensing and resetting during irradiation, and abnormalities in operation after treatment. In addition, the risk of irradiation from carbon-ion beam therapy was evaluated by model simulations. Twenty patients (22 sites) with CIEDs were identified, 19 with pacemakers and one with an implantable cardioverter-defibrillator (ICD). Treatments were completed without any problems, except for one case in which the treatment was discontinued because of worsening of the primary disease. Monte Carlo simulation indicated that the carbon beam irradiation produced neutrons at a constant and high level in the irradiation field. Nevertheless, with the distances between the CIEDs and the irradiation fields in the analyzed cases, the quantity of neutrons at the CIEDs was lower than that within the irradiation. Although carbon-ion beam therapy can be safely administered to patients with CIEDs, it is advisable to perform the therapy with sufficient preparation and backup devices because of the risks involved.

Renal cell carcinoma (RCC) is the third most common genitourinary cancer in the USA. Despite recent advances in the treatment for advanced and metastatic clear cell RCC (ccRCC), the 5-year relative survival rate for the distant disease remains at 12%. Cabozantinib, a tyrosine kinase inhibitor (TKI), which is one of the first-line therapies approved to treat advanced ccRCC as a single agent, is now being investigated as a combination therapy with newer immunotherapeutic agents. However, not much is known about how cabozantinib modulates the immune system. Here, we present a high throughput tri-culture model that incorporates cancer cells, endothelial cells, and patient-derived immune cells to study the effect of immune cells from patients with ccRCC on angiogenesis and cabozantinib resistance. We show that circulating immune cells from patients with ccRCC induce cabozantinib resistance via increased secretion of a set of pro-angiogenic factors. Using multivariate partial least square regression modeling, we identified CD4+ T cell subsets that are correlated with cabozantinib resistance and report the changes in the frequency of these populations in ccRCC patients who are undergoing cabozantinib therapy. These findings provide a potential set of biomarkers that should be further investigated in the current TKI-immunotherapy combination clinical trials to improve personalized treatments for patients with ccRCC.

Background Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment. Objectives The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance. Methods This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function). Results Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): −9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [−1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate

Although the health effects of exposure to low-dose ionizing radiation have been the focus of many studies, the affected biological functions and underlying regulatory mechanisms are not well-understood. In particular, the influence of radiation exposure at doses of less than 200 mGy on the regulation of genes and pathways remains unclear. To investigate the molecular alterations induced by varying doses of low-dose radiation (LDR), transcriptomic analysis was conducted based on ribonucleic acid (RNA) sequencing following exposure to 50 and 150 mGy doses. Human peripheral blood was collected, and the samples were divided into three groups, including two treatments and one control (no radiation). A total of 876 (318 upregulated and 558 downregulated) and 486 (202 upregulated and 284 downregulated) differentially expressed genes (DEGs) were identified after exposure to 50 mGy and 150 mGy, respectively. Most upregulated genes in both the 50 mGy and 150 mGy groups were associated with ‘antigen processing and presentation,’ which appeared to be the major targets affected by LDR exposure. Several interacting genes, including HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRB1, and HLA-DRB5 were mapped to ‘antigen processing and presentation,’ ‘immune system-related diseases’ and the ‘cytokine-mediated signaling pathway,’ suggesting that these genes might drive the downstream transmission of these signal transduction pathways. Our results suggest that exposure to LDR may elicit changes in key genes and associated pathways, probably helping further explore the biological processes and molecular mechanism responsible for low-dose occupational or environmental exposures in humans.

Background Higher flavonoid intakes are hypothesised to confer protection against type 2 diabetes mellitus. Objective We aimed to 1) investigate associations between flavonoid intakes and diabetes, 2) examine the mediating impact of body fat, and 3) identify subpopulations that may receive the greatest benefit from higher flavonoid intakes in participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years. Design Cross-sectional associations between baseline flavonoid intake, estimated using food frequency questionnaires and the Phenol Explorer database, and body fat estimated by bioelectrical impedance, were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines with multivariable-adjusted Cox proportional hazards models. Results Among 54,787 participants (median [IQR] age of 56 [52-60] years; (47.3%) men), 6700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95%CI: -1.74, -1.30) and a 19% lower risk of diabetes [hazard ratio (95%CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 57% (95% CI: 42%, 83%) of the association between flavonoid intake and incident diabetes. Of the flavonoid subclasses, moderate to high intakes of flavonols, flavanol monomers, flavanol oligo + polymers, and anthocyanins were significantly associated with a lower risk of diabetes. While associations were not modified by sex, smoking status, BMI or physical activity (pinteraction > 0.05 for all), findings on an absolute scale suggest that those at a higher risk (those with obesity) may benefit the most from a higher flavonoid intake. Conclusions These findings suggest that a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.

The purpose of this study is to investigate the frequency of education, knowledge of radiation and workplace anxiety of Fukushima Daiichi Nuclear Power Plant (FDNPP) workers and to analyze what type of words are used for anxiety with a text mining method. An original questionnaire survey was given to FDNPP workers, and a text mining method was used to extract information from free-entry fields. The questionnaires were collected from 1135 workers (response rate: 70.8%). It was found that when workers receive education on radiation, the increased knowledge helps to reduce their anxiety. Among the 1135 workers, 92 of 127 completed the free-entry field with valid entries. Seventy-one words were extracted by the text mining method. The words used differed depending on the degree of anxiety. The text mining method revealed information about the presence or absence of radiation anxiety and the subjects’ working environment and background.

This study aimed to quantitatively clarify the baseline drift for each respiratory cycle in two respiratory-gating methods using the intra-beam respiratory motion data of lung cancer patients. The residual motion and dose distribution were calculated based on intra-beam respiratory motion data with the baseline drift. To quantify the baseline drift \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\Delta$\end{document} during irradiation, it was defined as the inclination between the detected expiration point and the expiration point in the next cycle in the anterior–posterior (AP), cranial–caudal (CC) and left–right (LR) directions obtained using an in-house programme. The baseline drift value reached up to 0.74 mm/s in the CC direction as per the respiratory motion data of 10 patients. The homogeneity index (HI) of the phase-gating method tended to increase because the target was irradiated even when the amplitude position of the target differed from period to period. In contrast, the amplitude-gating method enabled irradiation considering the amplitude position of the target because the gating window was set considering the amplitude position of the respiratory motion. The respiratory-gating methods and respiratory phase in respiratory-gating lung stereotactic body radiation therapy (SBRT) must be determined based on the respiratory motion of the patients.

Oral administration of a water-soluble iodine contrast agent (gastrografin) was reported to assist in the appropriate contouring of the small intestine on computed tomography (CT)-based radiotherapy (RT) planning. The efficacy and optimal dose of gastrografin in CT-based image-guided brachytherapy (IGBT) for cervical cancer remain unknown. This study aimed to investigate the efficacy of pretreatment oral administration of gastrografin at a small dose of 50 ml in CT-based IGBT for cervical cancer. A total of 422 sessions in 137 patients who underwent CT-based IGBT with 50 ml of oral gastrografin (concentration, 3% or 4%) were analyzed. Preparation of gastrografin was judged as effective when the small intestine was contrast-enhanced at the area where the small intestine was in contact with the uterus/adnexa. About 287 out of 422 sessions (68%) were judged as effective with gastrografin preparation. The 135 ineffective sessions were considered as follows: (i) the contrast enhancement of the small intestine was not confirmed (n = 36), (ii) the small intestine was not in contact with the uterus/adnexa despite the confirmation of the contrast enhancement of the small intestine (n = 34), and (iii) gastrografin was absent in the small intestine at the area in contact with the uterus/adnexa, even when gastrografin was observed in the small intestine at the area not in contact with the uterus/adnexa (n = 65). In conclusion, pretreatment oral administration of a small dose gastrografin achieved moderate efficacy for accurate contouring of the small intestine close to the uterus/adnexa in CT-based IGBT for cervical cancer.

We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.

BACKGROUND Reservoir-wave analysis (RWA) separates the arterial waveform into reservoir and excess pressure (XSP) components, where XSP is analogous to flow and related to left ventricular workload. RWA provides more detailed information about the arterial tree than traditional blood pressure (BP) parameters. In end-stage renal disease (ESRD), we have previously shown that XSP is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). In this study, we examined whether XSP increases after creation of an AVF in ESRD. METHODS Before and after a mean of 3.9 ± 1.2 months following creation of AVF, carotid pressure waves were recorded using arterial tonometry. XSP and its integral (XSPI) were derived using RWA through pressure wave analysis alone. Aortic stiffness was assessed by carotid–femoral pulse wave velocity (CF-PWV). RESURLTS In 38 patients (63% male, age 59 ± 15 years), after AVF creation, brachial diastolic BP decreased (79 ± 10 vs. 72 ± 12 mm Hg, P = 0.002), but the reduction in systolic BP, was not statistically significant (133 ± 20 vs. 127 ± 26 mm Hg, P = 0.137). However, carotid XSP (14 [12–19] to 17 [12–22] mm Hg, P = 0.031) and XSPI increased significantly (275 [212–335] to 334 [241–439] kPa∙s, P = 0.015), despite a reduction in CF-PWV (13 ± 3.6 vs. 12 ± 3.5 m/s, P = 0.025). CONCLUSIONS Creation of an AVF resulted in increased XSP in this population, despite improvement in diastolic BP and aortic stiffness. These findings underline the complex hemodynamic impact of AVF on the cardiovascular system., Graphical Abstract Graphical Abstract

Background We have developed a simple and globally applicable tool, the Global Diet Quality Score (GDQS), to measure diet quality. Objectives To test the utility of the GDQS, we examined the associations of the GDQS with weight change and risk of obesity in US women. Methods Health, lifestyle, and diet information were collected from women (n = 68,336) in the Nurses’ Health Study II (aged 27–44 y in 1991) through repeated questionnaires (1991–2015). The GDQS has 25 food groups (maximum = 49 points) and scoring higher points reflects a healthier diet. The association between GDQS change in 4-y intervals and concurrent weight change was computed with linear models adjusted for confounders. Results Mean ± SD weight gain across 4-y periods was 1.68 ± 6.26 kg. A >5-point improvement in GDQS was associated with −1.13 kg (95% CI: −1.19, −0.77 kg) weight gain compared with a score change of 5-point score decrease was associated with 1.13 kg (95% CI: 1.04, 1.22 kg) more weight gain in women aged 5-point increase and 1.32 (95% CI: 1.26, 1.37) for a >5-point decrease. Risk of obesity did not differ by age. Compared with other diet quality scores, the Alternate Healthy Eating Index-2010 had somewhat stronger associations than the GDQS (P

Background The global diet quality score (GDQS) is a simple, standardized metric appropriate for population-based measurement of diet quality globally. Objectives We aimed to operationalize data collection by modifying the quantity of consumption cutoffs originally developed for the GDQS food groups and to statistically evaluate the performance of the operationalized GDQS relative to the original GDQS against nutrient adequacy and noncommunicable disease (NCD)-related outcomes. Methods The GDQS application uses a 24-h open-recall to collect a full list of all foods consumed during the previous day or night, and automatically classifies them into corresponding GDQS food group. Respondents use a set of 10 cubes in a range of predetermined sizes to determine if the quantity consumed per GDQS food group was below, or equal to or above food group-specific cutoffs established in grams. Because there is only a total of 10 cubes but as many as 54 cutoffs for the GDQS food groups, the operationalized cutoffs differ slightly from the original GDQS cutoffs. Results A secondary analysis using 5 cross-sectional datasets comparing the GDQS with the original and operationalized cutoffs showed that the operationalized GDQS remained strongly correlated with nutrient adequacy and was equally sensitive to anthropometric and other clinical measures of NCD risk. In a secondary analysis of a longitudinal cohort study of Mexican teachers, there were no differences between the 2 modalities with the beta coefficients per 1 SD change in the original and operationalized GDQS scores being nearly identical for weight gain (-0.37 and -0.36, respectively, P

BACKGROUND Obstructive sleep apnea (OSA) is a risk factor of several cardiovascular diseases. We investigated the association between aortic root diameter and hypoxia-related parameters in hypertensive patients with OSA. METHODS Our study included 242 hypertensive patients with OSA (52 mild, 71 moderate, and 119 severe). All the patients underwent echocardiography for measuring aortic root diameter and polysomnography for measuring apnea–hypopnea index (AHI), oxygen desaturation index, and time spent with oxygen desaturation less than 90%. RESULTS The study patients included 19.8% women and had a mean (±SD) age of 49.9 ± 12.9 years, a mean aortic root diameter of 33.4 ± 2.6 mm, and a prevalence of echocardiographic aortic root dilation of 3.7%. Patients with mild, moderate, and severe OSA had similar echocardiographic left ventricular structure. However, patients with severe OSA had a significantly (P < 0.05) greater aortic root diameter (33.9 ± 2.4 mm vs. 32.4 ± 2.2 and 33.4 ± 2.9 mm, respectively) and higher prevalence of aortic root dilatation (5% vs. 1% and 3%, respectively) than those with mild and moderate OSA. Aortic root diameter corrected by body height was significantly (P < 0.001) associated with AHI, oxygen desaturation index and time spent with oxygen desaturation less than 90% (r = 0.23–0.33). After adjustment for various confounding factors, the associations between aortic root diameter and polysomnography parameters remained statistically significant (P < 0.05). CONCLUSIONS The severity of OSA was associated with the aortic root diameter. Patients with severe OSA had a greater aortic root diameter.

Background The prevalence of type 2 diabetes has increased substantially in India over the past 3 decades. Undiagnosed diabetes presents a public health challenge, especially in rural areas, where access to laboratory testing for diagnosis may not be readily available. Objectives The present work explores the use of several machine learning and statistical methods in the development of a predictive tool to screen for prediabetes using survey data from an FFQ to compute the Global Diet Quality Score (GDQS). Methods The outcome variable prediabetes status (yes/no) used throughout this study was determined based upon a fasting blood glucose measurement ≥100 mg/dL. The algorithms utilized included the generalized linear model (GLM), random forest, least absolute shrinkage and selection operator (LASSO), elastic net (EN), and generalized linear mixed model (GLMM) with family unit as a (cluster) random (intercept) effect to account for intrafamily correlation. Model performance was assessed on held-out test data, and comparisons made with respect to area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results The GLMM, GLM, LASSO, and random forest modeling techniques each performed quite well (AUCs >0.70) and included the GDQS food groups and age, among other predictors. The fully adjusted GLMM, which included a random intercept for family unit, achieved slightly superior results (AUC of 0.72) in classifying the prediabetes outcome in these cluster-correlated data. Conclusions The models presented in the current work show promise in identifying individuals at risk of developing diabetes, although further studies are necessary to assess other potentially impactful predictors, as well as the consistency and generalizability of model performance. In addition, future studies to examine the utility of the GDQS in screening for other noncommunicable diseases are recommended.

Background Key nutrient deficits remain widespread throughout sub-Saharan Africa (SSA) whereas noncommunicable diseases (NCDs) now cause one-third of deaths. Easy-to-use metrics are needed to track contributions of diet quality to this double burden. Objectives We evaluated comparative performance of a novel food-based Global Diet Quality Score (GDQS) against other diet metrics in capturing nutrient adequacy and undernutrition in rural SSA adults. Methods We scored the GDQS, Minimum Dietary Diversity–Women (MDD-W), and Alternative Healthy Eating Index–2010 (AHEI-2010) using FFQ data from rural men and nonpregnant, nonlactating women of reproductive age (15–49 y) in 10 SSA countries. We evaluated Spearman correlations between metrics and energy-adjusted nutrient intakes, and age-adjusted associations with BMI, midupper arm circumference (MUAC), and hemoglobin in regression models. Results Correlations between the GDQS and an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B-12 adequacy were 0.34 (95% CI: 0.30, 0.38) in men and 0.37 (95% CI: 0.32, 0.41) in women. The GDQS was associated (P

Background The double burdens of under- and overnutrition are changing the health of individuals and the economic and disease burdens in China. Poor diet plays an important role; however, a valid and easily operationalized metric that could capture the full range of characteristics of the diet that are relevant to both under- and overnutrition is lacking in China. Objectives We aimed to examine the application of the Global Diet Quality Score (GDQS) to evaluate nutrient inadequacy and metabolic syndrome in different demographic groups of Chinese adults. Methods A total of 35,146 individuals (men 14,978, women 20,168) aged >18 y from the 2010–2012 China National Nutrition and Health Survey were included. We scored the GDQS using average intakes of 25 food groups from 3 d of 24-h dietary recalls. Double burden was defined as coexisting metabolic syndrome and nutrient inadequacy. Results Diet quality assessed by GDQS was significantly higher in urban than in rural residents (20.8 compared with 18.7), and increased with both educational level and household income (P-trends < 0.0001). A higher GDQS score was inversely associated with metabolic syndrome and nutrient inadequacy, or both (P-trends < 0.0001): multivariate adjusted ORs comparing extreme quintiles of GDQS were 0.79 (95% CI: 0.69, 0.91) for metabolic syndrome, 0.17 (95% CI: 0.14, 0.20) for nutrient inadequacy, and 0.59 (95% CI: 0.50, 0.69) for the double burden. These associations were consistent across different household income levels (P-interaction = 0.26), suggestively stronger in younger (

Background Evidence on concurrent changes in overall diet quality and weight and waist circumference in women of reproductive age from low- and middle-income countries is limited. Objectives We examined the associations of changes in the Global Diet Quality Score (GDQS) and each GDQS food group with concurrent weight and waist circumference change in Mexican women. Methods We followed prospectively 8967 nonpregnant nonlactating women aged 25–49 y in the Mexican Teachers’ Cohort between 2006 and 2008. We assessed diet using an FFQ of the previous year and anthropometric measures were self-reported. Regression models were used to examine 2-y changes in the GDQS and each food group (servings/d) with weight and waist circumference changes within the same period, adjusting for demographic and lifestyle factors. Results Compared with those with little change in the GDQS (−2 to 2 points), women with the largest increase in the GDQS (>5 points) had less weight (β: −0.81 kg/2 y; 95% CI: −1.11, −0.51 kg/2 y) and waist circumference gain (β: −1.05 cm/2 y; 95% CI: −1.62, −0.48 cm/2 y); likewise, women with the largest decrease in the GDQS (

Background We have developed a diet quality metric intended for global use. To assess its utility in high-income settings, an evaluation of its ability to predict chronic disease is needed. Objectives We aimed to prospectively examine the ability of the Global Diet Quality Score (GDQS) to predict the risk of type 2 diabetes in the United States, examine potential differences of association by age, and compare the GDQS with other diet quality scores. Methods Health, lifestyle, and diet information was collected from women (n = 88,520) in the Nurses’ Health Study II aged 27–44 y at baseline through repeated questionnaires between 1991 and 2017. The overall GDQS consists of 25 food groups. Points are awarded for higher intake of healthy groups and lower intake of unhealthy groups (maximum of 49 points). Multivariable HRs were computed for confirmed type 2 diabetes using proportional hazards models. We also compared the GDQS with the Minimum Diet Diversity score for Women (MDD-W) and the Alternate Healthy Eating Index-2010 (AHEI-2010). Results We ascertained 6305 incident cases of type 2 diabetes during follow-up. We observed a lower risk of diabetes with higher GDQS; the multivariable HR comparing extreme quintiles of the GDQS was 0.83 (95% CI: 0.76, 0.91; P-trend

Background Poor diet quality is a major driver of both classical malnutrition and noncommunicable disease (NCD) and was responsible for 22% of adult deaths in 2017. Most countries face dual burdens of undernutrition and NCDs, yet no simple global standard metric exists for monitoring diet quality in populations and population subgroups. Objectives We aimed to develop an easy-to-use metric for nutrient adequacy and diet related NCD risk in diverse settings. Methods Using cross-sectional and cohort data from nonpregnant, nonlactating women of reproductive age in 10 African countries as well as China, India, Mexico, and the United States, we undertook secondary analyses to develop novel metrics of diet quality and to evaluate associations between metrics and nutrient intakes and adequacy, anthropometry, biomarkers, type 2 diabetes, and iteratively modified metric design to improve performance and to compare novel metric performance to that of existing metrics. Results We developed the Global Diet Quality Score (GDQS), a food-based metric incorporating a more comprehensive list of food groups than most existing diet metrics, and a simple means of scoring consumed amounts. In secondary analyses, the GDQS performed comparably with the Minimum Dietary Diversity - Women indicator in predicting an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy and with anthropometric and biochemical indicators of undernutrition (including underweight, anemia, and serum folate deficiency), and the GDQS also performed comparably or better than the Alternative Healthy Eating Index - 2010 in capturing NCD-related outcomes (including metabolic syndrome, change in weight and waist circumference, and incident type 2 diabetes). Conclusions The simplicity of the GDQS and its ability to capture both nutrient adequacy and diet-related NCD risk render it a promising candidate for global monitoring platforms. Research is warranted to validate methods to operationalize GDQS assessment in population surveys, including a novel application–based 24-h recall system developed as part of this project.

BACKGROUND The majority of postoperative events in patients undergoing carotid endarterectomy (CEA) are of hemodynamic origin, requiring preventive strict postoperative arterial blood pressure (BP) control. This study aimed to assess whether BP monitoring with noninvasive beat-to-beat ClearSight finger BP (BPCS) can replace invasive beat-to-beat radial artery BP (BPRAD) in the postoperative phase. METHODS This study was a single-center clinical validation study using a prespecified study protocol. In 48 patients with symptomatic carotid artery stenosis, BPCS and BPRAD were monitored ipsilateral in a simultaneous manner during a 6-hour period on the recovery unit following CEA. Primary endpoints were accuracy and precision of BP derived by ClearSight (Edward Lifesciences, Irvine, CA) vs. the reference standard (Arbocath 20 G, Hospira, Lake Forest, IL) to investigate if BPCS is a reliable noninvasive alternative for BP monitoring postoperatively in CEA patients. Validation was guided by the standard set by the Association for Advancement of Medical Instrumentation (AAMI), considering a BP-monitor adequate when bias (precision) is, Graphical Abstract Graphical Abstract

The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers’ positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior–inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

BACKGROUND Adherence to study medications is crucial to evaluating treatment effects in clinical trials. To assess whether in the SPRINT trial, adherence and cardiovascular outcomes are associated regardless of intervention assignment. METHODS This study included 9,361 participants aged ≥50 years, recruited from 102 clinics. Participants were randomized to a Standard Treatment Group (targeted systolic blood pressure [SBP], Graphical Abstract Graphical Abstract

Background Greater whole grain (WG) consumption is associated with reduced risk of cardiovascular disease (CVD); however, few prospective studies have examined WG or refined grain (RG) intake and intermediate cardiometabolic risk factors. Objectives We examined the longitudinal association between WG and RG intake on changes in waist circumference (WC); fasting HDL cholesterol, triglyceride, and glucose concentrations; and blood pressure. Methods Subjects were participants in the Framingham Offspring cohort study [n = 3121; mean ± SD baseline age: 54.9 ± 0.2 y; BMI (kg/m2) 27.2 ± 0.1]. FFQ, health, and lifestyle data were collected approximately every 4 y over a median 18-y follow-up. Repeated measure mixed models were used to estimate adjusted mean changes per 4-y interval in risk factors across increasing categories of WG or RG intake. Results Greater WG intake was associated with smaller increases in WC (1.4 ± 0.2 compared with 3.0 ± 0.1 cm in the highest compared with the lowest category, respectively; P-trend

Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These data point to low plasma hippuric acid as a plausible hallmark of frailty status, associated with lower fruit–vegetable intakes.

In cervical cancer treatment, radiation therapy is selected based on the degree of tumor progression, and radiation oncologists are required to delineate tumor contours. To reduce the burden on radiation oncologists, an automatic segmentation of the tumor contours would prove useful. To the best of our knowledge, automatic tumor contour segmentation has rarely been applied to cervical cancer treatment. In this study, diffusion-weighted images (DWI) of 98 patients with cervical cancer were acquired. We trained an automatic tumor contour segmentation model using 2D U-Net and 3D U-Net to investigate the possibility of applying such a model to clinical practice. A total of 98 cases were employed for the training, and they were then predicted by swapping the training and test images. To predict tumor contours, six prediction images were obtained after six training sessions for one case. The six images were then summed and binarized to output a final image through automatic contour segmentation. For the evaluation, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) was applied to analyze the difference between tumor contour delineation by radiation oncologists and the output image. The DSC ranged from 0.13 to 0.93 (median 0.83, mean 0.77). The cases with DSC

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.

Graphical Abstract Graphical Abstract

Background Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. Objective The objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI). Methods A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. Results A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). Conclusions Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.

Background Emerging evidence links underhydration and habitual low water intake to higher cardiometabolic risk, but evidence is limited in community-dwelling older adults. Objectives The objective is to examine if higher water intake and better hydration are associated with better cardiometabolic health. Methods This cross-sectional analysis using general linear models included 2238 participants from the Framingham Heart Study Second Generation and First Generation Omni cohorts with an estimated glomerular filtration rate >30 mL·min–1·1.73 m–2 and a valid FFQ for assessment of water intake. Of these participants, 2219 had fasting spot urinary creatinine data and 950 had 24-h urine creatinine data to assess hydration. Cardiometabolic risk factors included fasting glucose, triglycerides (TGs), total cholesterol (TC), HDL cholesterol, and calculated LDL cholesterol; glycated hemoglobin (HbA1c); C-reactive protein (CRP); and systolic (SBP) and diastolic (DBP) blood pressure. Results The combined cohorts were on average aged 70 y; 55% were women. Mean (95% CI) daily total water intakes were 2098 (2048, 2150) mL for men and 2109 (2063, 2156) mL for women. Total daily water, beverage (including plain water), and plain water intakes demonstrated significant positive trends with HDL cholesterol (P 0.05). Conclusions Our findings of a consistent pattern between circulating lipid concentrations and different water sources and hydration markers support an association between hydration and lipid metabolism in older adults and add to the growing evidence that inadequate water intake and underhydration may lead to higher cardiometabolic risk.

Background: Biomarkers such as omega-3 (n-3) PUFAs, urinary iodine concentration (UIC), 1-methylhistidine (1-MH), and trimethylamine N-oxide (TMAO) have been associated with fish intake in observational studies, but data from children in randomized controlled trials are limited. Objectives: The objective of this exploratory analysis was to investigate the effects of fatty fish intake compared with meat intake on various biomarkers in preschool children. Methods: We randomly allocated (1:1) 232 children, aged 4 to 6 y, from 13 kindergartens. The children received lunch meals of either fatty fish (herring/mackerel) or meat (chicken/lamb/beef) 3 times a week for 16 wk. We analyzed 86 biomarkers in plasma (n = 207), serum (n = 195), RBCs (n = 211), urine (n = 200), and hair samples (n = 210). We measured the effects of the intervention on the normalized biomarker concentrations in linear mixed-effect regression models taking the clustering within the kindergartens into account. The results are presented as standardized effect sizes. Results: We found significant effects of the intervention on the following biomarkers: RBC EPA (20:5n-3), 0.61 (95% CI: 0.36, 0.86); DHA (22:6n-3), 0.43 (95% CI: 0.21, 0.66); total n-3 PUFAs, 0.41 (95% CI: 0.20, 0.64); n-3/n-6 ratio, 0.48 (95% CI: 0.24, 0.71); adrenic acid (22:4n-6, -0.65 (95% CI: -0.91, -0.40), arachidonic acid (20:4n-6), -0.54 (95% CI: -0.79, -0.28); total n-6 PUFAs, -0.31 (95% CI: -0.56, -0.06); UIC, 0.32 (95% CI: 0.052, 0.59); hair mercury, 0.83 (95% CI: 0.05, 1.05); and plasma 1-MH, -0.35 (95% CI: -0.61, -0.094). Conclusions: Of the 86 biomarkers, the strongest effect of fatty fish intake was on n-3 PUFAs, UIC, hair mercury, and plasma 1-MH. We observed no or limited effects on biomarkers related to micronutrient status, inflammation, or essential amino acid, choline oxidation, and tryptophan pathways.The trial was registered at clinicaltrials.gov (NCT02331667). Keywords: 1-methylhistidine; biomarkers; fatty fish; mercury; omega-3; polyunsaturated fatty acids; preschool children; targeted metabolomics. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Background: \ud COVID-19 has been associated with cases of severe respiratory illness, admissions to intensive therapy units (ITUs), and high mortality rates.\ud \ud Objectives: \ud The aim of the present study was to examine the relation between computed tomography- body composition (CT-BC) measurements, systemic inflammation, and clinical outcomes in those with COVID-19.\ud \ud Methods: \ud Patients who presented to our institution between March 17 and May 1, 2020, with a positive PCR test for COVID-19 or characteristic radiological changes, were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, poGPS, NLR , CT-BC measurements, and clinical outcomes including ITU admission and 30-d mortality, of those admitted.\ud \ud Results: \ud Sixty-three patients met the study inclusion criteria. Forty-two patients (67%) were aged ≥70 y, 30 (47.6%) were male and 34.9% ( n = 22) had a poGPS ≥1. ITU admission was significantly associated with a high VFA ( P < 0.05). Thirty-day mortality was associated with high VFA (P < 0.05) and low SMI (P < 0.05).\ud \ud Conclusions: \ud Sarcopenia in the presence of obesity was associated with clinical outcomes including greater 30-d mortality.

Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients’ ovaries were shielded with cylinder-type lead blocks. The dose–volume parameters (D98% and Dmean) in the ovaries and the pelvic bones were extracted from the dose–volume histogram (DVH). The mean ovary Dmean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary Dmean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis Dmean and pelvis D98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.

Background Maternal nutrition interventions are inadequately integrated into antenatal care (ANC). Alive & Thrive aimed to strengthen delivery of micronutrient supplements and intensify interpersonal counseling and community mobilization through government ANC services. Objectives We compared nutrition-intensified ANC (I-ANC) with standard ANC (S-ANC) on coverage of nutrition interventions and maternal nutrition practices. Methods We used a cluster-randomized design with cross-sectional baseline (2017) and endline (2019) surveys (n ∼660 pregnant and 1800 recently delivered women per survey) and a repeated-measures longitudinal study in 2018–2019 (n = 400). We derived difference-in-difference effect estimates (DIDs) for diet diversity, consumption of micronutrient supplements, weight monitoring, and early breastfeeding practices. Results Despite substantial secular improvements in service coverage from India's national nutrition program, women in the I-ANC arm received more home visits [DID: 7–14 percentage points (pp)] and counseling on core nutrition messages (DID: 10–23 pp) than in the S-ANC arm. One-third of women got ≥3 home visits and one-fourth received ≥4 ANC check-ups in the I-ANC arm. Improvements were greater in the I-ANC arm than in the S-ANC arm for any receipt and consumption of iron–folic acid (DID: 7.5 pp and 9.5 pp, respectively) and calcium supplements (DID: 14.1 pp and 11.5 pp, respectively). Exclusive breastfeeding improved (DID: 7.5 pp) but early initiation of breastfeeding did not. Maternal food group consumption (∼4 food groups) and probability of adequacy of micronutrients (∼20%) remained low in both arms. Repeated-measures longitudinal analyses showed similar results, with additional impact on consumption of vitamin A–rich foods (10 pp, 11 g/d), other vegetables and fruits (22–29 g/d), and gestational weight gain (0.4 kg). Conclusions Intensifying nutrition in government ANC services improved maternal nutrition practices even with strong secular trends in service coverage. Dietary diversity, supplement consumption, and breastfeeding practices remained suboptimal. Achieving greater behavior changes will require strengthening the delivery and use of maternal nutrition services integrated into ANC services in the health system. This trial was registered at clinicaltrials.gov as NCT03378141.

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.

Background The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression. Methods Patients were enrolled in this trial between April and September 2020. They were randomized in two groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units. Other outcomes include mechanical ventilation, non-invasive ventilation, readmission, and COVID-19 symptoms after discharge. Results We randomized 64 patients with COVID-19 into two groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of intensive care unit or ward admission, the discharge rate, or readmission rates between the two groups. Conclusions This randomized triple-blind multi-centric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients., Graphical Abstract Graphical Abstract

Background Cardiometabolic risk (CMR) is a key indicator of physiological decline with age, but age-related declines in a nationally representative older US population have not been previously examined. Methods We examined the trajectory of CMR over 8 years of aging, from 2006/2008 to 2014/2016, among 3528 people older than age 50 in the Health and Retirement Study. We used growth curve models to examine change in total CMR as well as in individual cardiometabolic biomarkers to understand how baseline differences and rates of change vary across sociodemographic characteristics, by smoking status, and medication use. Results Total CMR did not change among respondents who survived over 8 years. Despite significant differences in CMR across demographic and education groups at baseline, the pace of change with age did not differ by these characteristics. Among individual biomarkers, risk levels of diastolic blood pressure, resting heart rate, and total cholesterol decreased over 8 years while glycosylated hemoglobin, waist circumference, and pulse pressure increased over that time. Both the statistical significance levels and the magnitudes of the reduction over time with age in diastolic blood pressure, resting heart rate, and total cholesterol in models adjusted for age, race/ethnicity, gender, smoking, and education were reduced after controlling for blood pressure and cholesterol medication. Conclusions The relatively constant total CMR level over 8 years occurred because some indicators improved with age while some deteriorated in this period. Medication use contributed to the improvement in blood pressure, resting heart rate, and total cholesterol.

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups’ backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve.

To the best of our knowledge there have been no randomized controlled trials comparing lobectomy—a standard treatment for patients with early-stage non-small cell lung cancer (NSCLC)—and particle beam therapy (PBT), the best performing existing radiotherapy. We conducted a virtual randomized trial in medically operable patients with stage IA NSCLC to compare lobectomy and PBT effectiveness. A Markov model was developed to predict life expectancy after lobectomy and PBT in a cohort of patients with stage IA NSCLC. Ten thousand virtual patients were randomly assigned to each group. Sensitivity analyses were performed as model variables and scenarios changed to determine which treatment strategy was best for improving life expectancy. All estimated model parameters were determined using variables extracted from a systematic literature review of previously published articles. The preferred strategy differed depending on patient age. In young patients, lobectomy showed better life expectancy than that of PBT. The difference in life expectancy between lobectomy and PBT was statistically insignificant in older patients. Our model predicted lobectomy as the preferred strategy when operative mortality was under 5%. However, the preferred strategy changed to PBT if operative mortality post lobectomy was over 5%. For medically operable patients with stage IA NSCLC, our Markov model revealed the preferred strategy of lobectomy or PBT regarding operative mortality changed with varying age and comorbidity. Until randomized controlled trial results become available, we hope the current results will provide a rationale background for clinicians to decide treatment modalities for patients with stage IA NSCLC.

X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules’ excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.