We found no significant difference between HF and no-HF groups regarding muscle performance, except for lower median gait speed in the HF group—0.53 m/s (0.35–0.89 m/s) versus 0.68 m/s (0.44–0.99 m/s), p = 0.02). HF patients significantly more often had low grip strength accompanied by slow gait, suggesting probable severe sarcopenia . In the regression analysis, significantly higher odds for HF were observed for lower mid-arm circumference (MAC) and dynapenia when controlling for age, sex, body mass index (BMI), calf circumference (CC), peripheral arterial disease, history of stroke, ischemic heart disease, atrial fibrillation, and diabetes mellitus. Conclusions: HF geriatric patients are often burdened with frailty, obesity, multimorbidity, and polypharmacy. As a result, they are more likely to present low muscle strength , which is frequently accompanied by functional limitations (suggestive of more advanced stages of sarcopenia). This tendency is evident mainly in older women. Nevertheless, sarcopenia can be independently associated with HF in older patients with multimorbidity and disability who are hospitalized in a geriatric department, as a multivariable logistic regression analysis demonstrated.The need to assess sarcopenia and frailty in patients with chronic heart failure (HF) has recently been raised. This cross-sectional study of 416 geriatric ward patients (median age (Me)—82  years, 77.4% female, 96.9% community dwelling) aimed to assess the prevalence of dynapenia, frailty syndrome, functional and nutritional health, and co-morbidity regarding their HF status. We collected data from comprehensive geriatric assessment. We observed HF in 162 (38.9%) patients, with 80 (49.4%) classified as New York Heart Association (NYHA) class III or IV. HF patients were significantly older, more frequently male, obese, hospitalized in the previous year, burdened with multimorbidity and polypharmacy, classified as frail, dependent on daily living activities, and physically non-active. Ischemic heart disease, atrial fibrillation, diabetes, peripheral arterial disease, anemia, chronic kidney disease, history of myocardial infarction, and stroke were found significantly more often in the HF group. A considerably higher percentage of HF patients had dynapenia (54.9% versus 41.9%,  The number of patients with heart failure (HF) is growing worldwide, mainly due to the aging of the population and the increasing prevalence of risk factors for cardiovascular diseases . Epidemiological data suggest that HF can affect about 1–2% of the adult population. In subsequent cohorts of adulthood, this percentage increases, and in the population over 70 years of age, the prevalence of HF is already 10% [Nevertheless, the burden of HF is rising . The incHeart failure is the cause of frequent hospitalizations and mortality . In studThe prevalence of sarcopenia in HF varies due to differences between study populations. However, it is the highest among those hospitalized for HF . NeverthWe performed a cross-sectional study of patients consecutively admitted to the geriatric ward of the Hospital of the Ministry of Interior in Bialystok, Poland between 1st September 2014 and 30th April 2015. Based on the comprehensive geriatric assessment (CGA)—a routine interdisciplinary procedure applied in the department—we collected information on the sociodemographic, medical, nutritional, and functional characteristics of patients with (HF+) and without (HF−) heart failure. The CGA is carried out by the ward’s doctors, nurses, the physiotherapist, and the psychologist using various assessment instruments and tests designed to assess these domains, as described below, to allow for a multidomain intervention and improve outcomes . We clas2DS2-VASc scale score > 3), and risk of bleeding .Sociodemographic characteristics included age, gender, place of residence , and way of living . Medical features included information on 15 chronic diseases  ; BMI; was ≤31 cm .Slowness and weakness were diagnosed according to the criteria proposed in the literature. Cut-off points were stratified by gender and height in the case of slowness and by gender and BMI quartiles in the case of weakness . The diaFrailty was diagnosed with the seven-item Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Patients were classified as frail if they belonged to category 5–7, pre-frail—category 4, and robust—category 1–3 score . The hanWe assessed the physical and mental abilities of an older person based on the results of the routine comprehensive geriatric assessment carried out in the geriatric ward: the ability to perform basic activities of daily life (with the Barthel Index), instrumental activities of daily living (with six items of the Duke Older American Resources and Services (OARS) I-ADL(IADL)) , the ris2 or Fisher’s exact test, the Mann–Whitney test, or the Student’s t-test. Missing values were omitted, and statistics were calculated for the adequately reduced groups. We performed a multivariable logistic regression analysis to determine the association between nutritional and sarcopenia predictors with HF, including predictors with a p-value less than 0.1, excluding those highly correlated (to avoid multicollinearity) and controlling for the influence of age, gender, and a number of chronic diseases. We reported odd ratios (ORs) with 95% confidence intervals (Cis) and p values for each model parameter. Finally, we evaluated the statistical significance of the model with the Hosmer–Lemeshow goodness-of-fit C-statistics . The results were considered statistically significant at two-tailed p < 0.05. The computed minimum number of a sample needed to have a confidence level of 95% with a real value of within ±5% of the measured/surveyed value of 385. The calculated margin of error here was 4.68% [The IBM SPSS Version 18 Software suite  was used to analyze the data collected. The Shapiro–Wilk test was used to assess the normality of the distribution of the quantitative variables. Descriptive statistics for continuous variables were expressed as mean (M) and standard deviation (SD) or median (Me) and interquartile range (IQR) as appropriate. Categorical variables were expressed as frequency (N) and percentage (%). As appropriate, differences between groups were expressed using χas 4.68% .The Ethics Committee approved the source study at the Medical University of Bialystok. All procedures performed in the study were under the ethical standards of the Medical University of Bialystok research committee and with the Helsinki declaration. The study can be classified as a study of ‘usual practice’. All study participants gave their informed written consent to participate in it.A total of 82 cases (50.6% of the HF group) were classified as NYHA class I or II and 80 cases (49.4%) as NYHA class III or IV. TTE examination was performed in only 35 patients (21.9% of the HF group) during their hospital stay. In addition, 35% of HF patients presented with swelling/peripheral edema, and 29.4% with pulmonary crepitation (in 23 cases (14.2%), both symptoms were present).p = 0.001) and more frequently belonged to the group of the more advanced age—75+ years old . In addition, more often, they were male  and less frequently lived alone. p < 0.001) and polypharmacy  and had been hospitalized in the previous year . They were more often diagnosed with ischemic heart disease, atrial fibrillation, diabetes, peripheral arterial disease, and a history of myocardial infarction and stroke. Significantly more often, they were diagnosed with anemia  and chronic kidney disease . The HF+ group could be classified as patients with an increased risk of thromboembolic complications according to the CHA2DS2-VASc score . Moreover, they significantly more often had a high risk of bleeding according to the HAS-BLED scale. Systolic and diastolic blood pressure in the HF+ group was considerably lower at admittance, and so was pulse pressure. The prevalence of high pulse pressure was similar in both groups, and the groups did not differ in the frequency of orthostatic hypotension. The HF+ group participants significantly more often received beta-blockers, alfa1-blockers (only by men), digoxin, ACEI/ARB, oral anticoagulants, and diuretics .HF+ patients were significantly more often burdened with multimorbidity  according to EWGSOP2 sarcopenia cut-off points. When analyzed in sex groups, the significant differences in these parameters were observed in women only. Weakness was diagnosed more frequently than low grip strength and was observed significantly more often in the HF+ group.The median value of gait speed was significantly lower in HF patients, but HF+ and HF- groups did not differ in the percentage of participants with a slow gait. Significantly more often, HF+ patients were classified as frail and severely frail, had higher POMA and TUG scores, and were more often classified as at falling risk. They had lower scores on the Barthel Index, the Duke OARS IADL scale, and the Norton scale, more often had pressure sores at admission and were physically non-active.We divided people assessed for muscle strength (based on hand grip strength) and fitness  into four groups depending on the results of these tests; see p = 0.046).In the first group, there were people categorized as fit and not suspected of sarcopenia—they did not have reduced muscle strength (no sarcopenia (SP) and no functional decline (FD)). In the second group, there were patients with reduced muscle strength but with the correct gait speed (SP but no FD); this was the smallest group of respondents. The third group included patients with a slow walking speed or a prolonged TUG time but with preserved muscle strength (no SP but FD). The fourth group included people with low grip strength accompanied by slow gait (SP and FD). The last group characteristic may be treated as the equivalent of ‘probable severe sarcopenia’. Patients with HF—2 = 0.200). In the next step, we added the number of chronic diseases (of 15 tested) to Model 2. The regression analysis confirmed the significance of three variables: CC, MAC, and the number of chronic diseases. The overall success rate for Model 3 was 77.5%, with a specificity of 74.8% and a sensitivity of 74.8% (Nagelkerk’s R2 = 0.421). The Hosmer–Lemeshow goodness-of-fit p-values for Models 1–3 were above 0.05, leading to the rejection of the null hypothesis of a lack of fit.In the first step, we performed a multivariable logistic regression analysis on HF as a dependent variable and a block of nine independent predictors: age, sex, MNA-SF score, gait speed, potential sarcopenia (dynapenia), MAC, CC, BMI, waist circumference, as shown in The study aimed to evaluate the prevalence of HF and its functional and nutritional correlates in geriatric ward patients, emphasizing parameters that may indicate sarcopenia.2) were significantly more common in people with HF, as expected. Therefore, according to some authors, HF is one of the geriatric syndromes and a common pathophysiological pathway for several diseases [Our results confirmed HF as one of the most frequent conditions in this group; it was present in 38.9% of patients admitted to the geriatrics department. This appears to be a very high prevalence rate. In French studies on HF in people over 80 in geriatric facilities, the frequency of HF findings was lower—about 20%. Still, these studies included cases of patients with typical exacerbation symptoms or subjects hospitalized due to exacerbations of HF . We alsodiseases . Co-occudiseases . In addiThere were no significant differences in the prevalence of hypertension in our study, which may be due to the generally high prevalence of this disease in geriatric patients—hypertension was found in 78.6% of the study group. Moreover, systolic and diastolic blood pressure and pulse pressure on admission to the geriatrics department were significantly lower among people with HF than those without HF. This may result from the essence of the disease but also from more intensive therapy with drugs used in HF, which lowers blood pressure at the same time. People with HF were significantly more likely to take diuretics, ACEI / ARB, alpha1-blockers, and beta-blockers. This has also been described by other authors and results from the standards of therapeutic management in HF .The group of patients with HF showed a significantly more frequent occurrence of obesity diagnosed by BMI. This may indicate that sarcopenic obesity may be a more frequent clinical problem than sarcopenia among geriatric patients with HF . MalnutrIn regression models, with the controlled effects of age, sex, MNA-SF, walking speed, MAC, CC, BMI, and waist circumference, the association of sarcopenia (defined by dynapenia) with HF was statistically significant (Models 1 and 2). When chronic diseases that correlate significantly with HF  were included in the regression model (Model 3), dynapenia and the somatometric parameters—BMI, CC and MAC—retained their significance. The chance of HF occurrence increased with the prevalence of the probable sarcopenia (dynapenia): the higher the CC, the smaller the MAC, the latter being a more reliable indicator of lower muscle mass in HF than CC. In the group of people with edema on admission, the average CC value was significantly higher in our study (data not presented). In the absence of edema, CC and MAC may indicate low muscle mass. However, anthropometric measurements are not recommended in diagnosing sarcopenia because of many confounders as age-related changes in fat distribution. EGWSOP2 guidelines recommend BIA or DEXA, but these tests are unavailable in many medical settings. On the other hand, studies have shown their association with physical performance and poor nutritional status, and GLIM criteria for the diagnosis of malnutrition retain the possibility of using these measurements for low muscle mass if more reliable tests are unavailable . We usedp = 0.001. This is undoubtedly due to the age structure of the respondents but also to the specificity of their multiple diseases. The assessment of frailty occurrence in patients with HF is crucial, because the condition is associated with worse outcomes and poorer treatment tolerance [Frailty syndrome is a multi-dimensional, dynamic state in which a person becomes more susceptible to external and internal stressors. It results from the dysregulation and decreased efficiency of many systems, which limits the ability to maintain the body’s homeostasis and response to stress. The effect of frailty syndrome is an increased risk of disability, falls, institutionalization, hospitalization, and death. It is phenotypically manifested by weight loss, muscle weakness, slower gait, low physical activity, and mental exhaustion . Heart folerance ,36. Sarcopenia is defined as the loss of skeletal muscle mass and the weakening of the muscles’ function  . The incSome authors distinguish a ‘cardio-skeletal myopathy’ that develops in HF and ‘sarcopenia’ as a derivative of the aging process. The former consists of muscle fiber and capillary atrophy, conversion of type I fibers into type II ones, change in muscle structure and fiber orientation due to intra-fibular edema, and deposition of connective and adipose tissue—which consequently impairs the ability to generate strength and exercise tolerance. The latter is a result of selective denervation, the loss of fast motor units (with type II fibers being more susceptible to atrophy than type I fibers), and fat and connective tissue infiltration contributing to the decline in muscle quality. The frequent comorbidity of sarcopenia and HF may be explained by their common pathophysiological pathways, including altered nutrient intake and absorption , inflammatory processes and metabolic and autonomic disorders, humoral factors, the ubiquitin-proteasome system (UPS), myostatin signaling, apoptosis, and oxidative stress. These overlapping processes result in ultrastructural muscle abnormalities, mitochondrial structure and function changes, increased oxidative stress, and a shift in fiber distribution, ultimately leading to decreased exercise capacity .Our research confirmed the complexity of the clinical picture of HF in geriatric patients, indicating the fact that it is a multi-organ disease and not just a hemodynamic disorder. This means that the approach to diagnostics and therapy of HF in patients of advanced age should be multidirectional, as indicated by other authors . ConsideThe main limitation of this study was that it surveyed only one geriatric ward; therefore, the results cannot be generalized to the entire older adult population. In addition, we collected some information retrospectively from patients’ medical records after their discharge, resulting in missing data. Moreover, we can only talk about ‘potential sarcopenia’, because we rely on the results of the assessment of muscle strength while making a diagnosis. To confirm sarcopenia, we should assess the muscle mass. However, we did not perform this assessment in our research because of the need for the required measuring equipment. On the other hand, as confirmed recently by Blanquet et al., hand grip strength can be a valuable tool to screen for sarcopenia in older patients with chronic HF . UnfortuSignificantly higher odds for HF are observed for lower MAC (pointing to lower muscle mass) and for probable sarcopenia defined as dynapenia when controlling for age, sex, BMI, CC, and chronic diseases correlating with HF prevalence . This may confirm that sarcopenia (defined as a loss of muscle mass and muscle strength) is an independent predictor of heart failure in older patients with multimorbidity and disability who are hospitalized in a geriatric department.HF geriatric patients are often burdened with frailty, obesity, multimorbidity, and polypharmacy. As a result, they are more likely to present low muscle strength , which is frequently accompanied by functional limitations (suggestive of more advanced stages of sarcopenia). This tendency is evident mainly in older women. Nevertheless, sarcopenia can be independently associated with HF in older patients with multimorbidity and disability who are hospitalized in a geriatric department, as a multivariable logistic regression analysis has demonstrated.The study describes the prevalence and characteristics of HF among typical geriatric patients in a hospital ward (without excluded cases) in daily practice. HF occurred more frequently than in other studies on older populations, and the patients were burdened with numerous comorbidities and functional disabilities. The complex clinical picture of heart failure in geriatric patients confirms the need for a multidirectional and multidisciplinary approach that would correct hemodynamic disorders and prevent frailty, malnutrition, and sarcopenia.The study confirms the high occurrence of geriatric syndromes, such as dynapenia, inactivity, and frailty, in the HF group, indicating a need for comprehensive geriatric assessment in HF patients.Obesity and sarcopenic obesity seem to be more frequent clinical problems than sarcopenia alone among geriatric patients with HF.High levels of inactivity and dynapenia in geriatric HF patients may indicate a direction of prevention and therapeutic strategies.The clinical implications of this study are as follows:


The objective of this study was to investigate the relationship between dietary patterns and cognitive function in older adults (≥60 years old).Food intake was quantitatively assessed by the Food Frequency Questionnaire (FFQ), and cognitive function was assessed by the Chinese version of the Simple Mental State Examination Scale (MMSE). Four major dietary patterns were identified by the factor analysis (FA) method. The relationship between dietary patterns and cognitive function was evaluated by logistic regression.p-value = 0.033, OR (95% CI): 0.578  in Model III . In the ethnic stratification analysis, the scores of dietary pattern factors of the vegetable and mushroom among the Yao participants were 0.333 and 5.064. The Vegetable and mushroom diet pattern may be a protective factor for cognitive function, p-value = 0.012, OR (95% CI): 0.415 .A total of 884 participants were included in the study. Four dietary patterns  were extracted. In the total population, Model III results showed that the fourth quartile of dietary pattern factor scores for the vegetable and mushroom pattern was 0.399 and 7.056. The vegetable and mushroom dietary pattern may be a protective factor for cognitive function, with The fourth quartile of the vegetable and mushroom dietary pattern scores showed dose-dependent and a strong correlation with cognitive function. Currently, increasing vegetable and mushroom intake may be one of the effective ways to prevent and mitigate cognitive decline. It is recommended to increase the dietary intake of vegetables and mushroom foods. As global lifespan increases, there is a concern about diseases that significantly impact older adults, including those that cause chronic ailments, impact physical functioning, and lead to cognitive decline. Cognitive decline can have multiple causes, with Alzheimer's disease being the most common, with more than 46 million people worldwide suffering from dementia, which is impacted strongly , 2. It iThe implementation of healthy dietary patterns is a potential preventive strategy for declining cognitive function and can mitigate the cognitive decline that occurs with age . The effHowever, it has been found that one's entire diet should be considered and that there are synergistic effects between the nutrients consumed (stronger than their single components), meaning that dietary patterns may have a more significant impact on cognitive function , 14. In The most commonly used method to explore dietary patterns is factor analysis (FA) using a data-driven approach. This method is not limited by theory but reflects dietary intake in a specific population. For example, adherence to a “grain” pattern may be a risk factor for cognitive function and a “plant” pattern may be a protective factor for cognitive function . GongcheThe study site was Gongcheng Yao Autonomous County, Guilin, Guangxi, China. According to the cross-sectional sampling survey, the sample size calculation formula is as follows:N is the sample size, Z is the statistic, α = 0.05, Z = 1.96, p is the expected prevalence, q = 1-p, and d is the allowable error (d = 0.1p). The prevalence of cognitive dysfunction in rural Chinese older adults was 42.9%  and women (n = 514).Inclusion criteria were as follows: older adults who (a) resided in the study area; (b) were over 60 years of age; (c) had blood sample, height, weight, and questionnaire information; and (d) had a reasonable energy intake of 500–6000 kcal . FinallyThis research was conducted in accordance with the guidelines set forth in the Declaration of Helsinki, and all procedures involving human participants were approved by the Ethics Committee of Guilin Medical College. Written informed consent was obtained from each participant (No. 20180702-3).The MMSE questionnaire has high reliability and validity for the assessment of cognitive function. The questionnaire has the advantage of being easily applied and implemented in a short period. To assess the relationship between dietary patterns and the risk of cognitive dysfunction, MMSE scores have been classified according to the level of literacy: illiterate group ≤17, primary group ≤20, secondary and higher group ≤24 as the cutoff point, regarded as the cognitive impairment group (CI), compared to the non-CI group, and the rest are classified as the non-cognitive impairment (non-CI) group , 28.The main food intake during the previous year was determined by reference to the food frequency questionnaire (FFQ), which included the frequency and quantity of food consumed . The intFeature values of >1 and scree plots were used to determine the number of dietary patterns. Furthermore, by using orthogonal transformations of rotation factors, the results were easier to interpret. Food groups with absolute factor loadings of >0.3 were significant in the dietary pattern because the food items in these food groups appeared to be strongly associated with the identified factors. Factor scores were calculated by weighting each participant's intake of the 14 food groups by factor loadings. We named dietary patterns based on food groups with factor loadings of >0.6.Diabetes was defined as fasting blood glucose (FBG) of ≥7.0 mmol/L or a regimen of glucose-lowering medications . Hypertet-test were applied for continuous and categorical variables, respectively, and the Wilcoxon rank-sum test was used for comparisons between groups of nonnormally distributed information. The energy and nutrient contents of food were obtained from the Chinese Food Composition Table (2009 version)  . Nutrienversion)  were empN = 663) and CI  (N = 221). The jitter scatter plot and the histogram of the propensity value distribution show good results (The propensity score matching (PSM) results were as follows: non-CI (non-cognitive impairment) , hypertension , MMSE scores, orientation, memory, attention calculation, language skills, and visuospatial skills  of the non-CI and CI groups, as shown in P-values = 0.009) and agricultural activities , as shown in Statistically significant differences occurred between the sex , protein , carbohydrate , dietary fiber , fruit , soybeans and nuts , poultry , aquaculture , eggs , mushrooms , and vegetables and mushrooms  of the non-CI and CI groups, as shown in P-values = 0.008), soybeans and nuts , oil tea , oil and salt , and seafood and alcohol  significantly varied among different ethnic groups, as shown in Significant differences were observed in the dietary pattern scores of SFAs (Kaiser–Meyer–Olkin (KMO) factor adequacy is equal to 0.81, Bartlett's test of sphericity is less than 0.001, and the cumulative variance explained is 44.64%, all of which meet the conditions for the use of factor analysis. The left side of the Scree plots shows the characteristic roots, and the slope for 4–5 factors becomes flatter, with the first four factors already covering most of the information, as shown in P-values of p = 0.009, p = 0.01, and p = 0.024, respectively  to flexibly model and visualize the relationship between dietary pattern scores and cognitive function. The seafood and alcohol dietary pattern showed a non-linear relationship with cognitive function, with a trend consisting of an initial decline, a brief increase, and a final flattening off,  = 0.003 .P-values = 0.017) and oil tea  dietary patterns, as shown in In Model I, after adjusting for sex and ethnicity, the score of the vegetable and mushroom dietary pattern factor was in the fourth quartile ; the vegetable and mushroom dietary pattern may be a protective factor for cognitive function, with an OR (95% CI) of 0.484 . Other dietary patterns were not associated with cognitive function. In Model II, after adjusting for sex, ethnicity, marital status, agricultural activities, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, and BMI, when the score of the vegetable and mushroom dietary pattern factor was in the fourth quartile (0.399 and 7.056), it was found that the vegetable and mushroom dietary pattern may be a protective factor of cognitive function, with an OR (95% CI) of 0.517 . Other dietary patterns were not associated with cognitive function. In Model III, after adjusting for sex, ethnicity, marital status, agricultural activities, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, BMI, and dietary fiber, when the score of the vegetable and mushroom dietary pattern factor was in the fourth quartile , it was found that the vegetable and mushroom dietary pattern may be a protective factor of cognitive function, with an OR (95% CI) of 0.578 . Other dietary patterns were not associated with cognitive function. A linear trend was noted between the quartiles of the dietary scores of the vegetable and mushroom (N = 884). In a study of elderly people in Gongcheng County, female participants had a higher prevalence of cognitive impairment than other rural Chinese populations. There is substantial variation when considering the beneficial effects of diet in studies of the association of diet and cognitive impairment with age, and one potential reason for this variation in dietary pattern-cognitive function association may be sex  were extracted. The vegetable and mushroom dietary pattern (a) showed significant outcomes when the dietary pattern scores were at the fourth quartile after different levels of adjustment for potential confounders and (b) may be a protective factor for cognitive function. Among the Yao respondents, the vegetable and mushroom dietary pattern showed strong correlations with cognitive health when the dietary pattern scores were at the fourth quartile and after adjusting for different degrees of potential confounding factors. It is suggested that vegetable and mushroom dietary pattern may be a protective factor for cognitive function. After reviewing the previous literature, we made even more surprising findings. The Mediterranean dietary pattern includes various vegetables and mushrooms. Strict adherence to the Mediterranean diet (MD) may result in better cognitive status , 41. In Oil and salt were not correlated with cognitive function. This finding is inconsistent with previous studies, which suggest that the oil and salt dietary pattern may be a risk factor for cognitive function . DietaryThe seafood and alcohol dietary pattern may not be associated with cognitive function. Previous reports suggest that the dietary patterns of older adult French people may be beneficial for cognitive function  . HoweverOil tea dietary patterns were not associated with decreased cognitive function. Previous studies have reported that high doses of oil tea intake may be associated with a low risk of abnormal HDL cholesterol . This stThis study also has some limitations that must be carefully considered. First, this study is a cross-sectional study, consisting mainly of older Chinese adults, and therefore, it is not possible to establish a clear chronological order or to exclude the possibility of reverse causality and the existence of Neyman bias. Second, the dietary intake assessment was not performed before the cognitive function measures, and we cannot infer the existence of the resulting causality. Third, the dependence of the FFQ method on memory or cognitive performance in this study did not allow for a precise estimation of nutrient intake. Fourth, we controlled for the effects of nutrient dietary intake in the model using the residual method and VIF. Fifth, we were unable to adjust for genetically related lipoprotein E status, but we controlled for a wide range of health-related factors as potential confounders. Sixth, because we conducted a large cross-sectional epidemiological survey, the MMSE questionnaire is not clinically adequate to accurately classify cognitive impairment, and our data do not adequately support studies with a detailed classification of patients with cognitive impairment. The MMSE questionnaire can only be used to initially assess the status of cognitive function. Therefore, to obtain more precise findings, longer follow-up and larger prospective studies are necessary to explore the relationship between dietary patterns and cognitive function.In this population-based study, the vegetable and mushroom dietary pattern showed a strong correlation with cognitive function, and this association was dose-dependent. Therefore, the vegetable and mushroom dietary pattern is the safest choice at this time. Finally, the vegetable and mushroom dietary pattern may be a protective factor for cognitive function, suggesting that more vegetables and mushroom foods should be consumed in the diet to prevent cognitive impairment.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of Guilin Medical College. The patients/participants provided their written informed consent to participate in this study.RG and ZZ had full access to all of the data in the study, took responsibility for the integrity of the data, and the accuracy of the data analysis. RG drafted the manuscript and performed the statistical analysis. WP, JC, TL, KH, SX, and XT critically revised the manuscript for important intellectual content. YL obtained funding. YL and JQ supervised the study. All authors contributed to the article and approved the submitted version.


This study investigated levels of anxiety and sleep quality and their association with physical activity in junior high school students under quarantine during the COVID-19 pandemic. It also tests the effectiveness of physical activity and psychological nursing interventions in alleviating anxiety ‘and improving sleep quality.In July 2021, 14,000 home-quarantined junior high school students in Yangzhou City (China) were selected by random cluster sampling to complete an online survey. We then selected 95 junior high school students for an 8-week longitudinal experiment exploring whether the two types of intervention made positive contributions to students' anxiety, sleep quality, and physical activity.The cross-sectional study revealed that physical activity was significantly related to anxiety and sleep quality. In the longitudinal study, students who underwent the exercise intervention or the psychological nursing intervention experienced significant improvement in their anxiety levels. The exercise intervention also promoted improved sleep quality. Overall, the exercise intervention was more effective than the psychological nursing intervention in reducing levels of anxiety and sleep disorders.During the epidemic period, junior high school students should be encouraged to spend more time engaging in physical activity, and their sleep quality and anxiety shouldbe focused on. Against the background of the normalization of the COVID-19 epidemic in China, the rapid spread of virus mutations necessitates a range of prevention and control measures, including closing workplaces and schools. Residents in affected areas have been required to follow quarantine measures, resulting in negative impacts on their daily life and physical and mental health. One group particularly vulnerable to the detrimental effects of home or hotel quarantine, especially with respect to psychology, sleep, and learning, is junior high school students , psychological nursing group (25 people), and exercise group (25 people). The experimental process was divided into pre-test and post-test. All participants took part voluntarily and were free to withdraw at any time. Before the start of the study, we obtained informed consent from the school teachers, participating junior high school students, and their parents. The study design was approved by the Ethics Committee of the Nursing School of Yangzhou University (Batch number: YXYLL-2020-106).2 (kg/m2). Overweightness and obesity were defined according to gender and age BMI thresholds in the national health standard Screening for Overweight and Obesity of School-age Children and Adolescents (WS/T 568-2018) , only-child status, urban–rural residence, living mode, and family structure. BMI was calculated by dividing weight by heightWS/T 568-  to evaluate participants' anxiety symptoms. The scale comprises seven items, each scored from 0 to 3. Total scores of 0–4 indicate minimal anxiety, 5–9 points represent mild anxiety, 10–14 denote moderate anxiety, and 15–21 suggest severe anxiety. Cronbach's α coefficient of the GAD-7 in this study was 0.932.The revised Physical Activity Rating Scale (PARS-3) by Liang Deqing was employed to assess the amount of physical activity of junior high school students , as translated by Zou et al. . The sca1) and 1/10 (threshold for accepting H0). Specifically, to test whether moral valence impacts on matching attempts in perceptual matching, this study focused on the difference in response time under different conditions and adopted Bayesian factor sequence design to test the BF values corresponding to three key effects: (1) the interaction between moral titer and matching degree; (2) the reaction time of the moral positive matching condition is faster than that of the neutral matching condition; and (3) the reaction time of the moral negative matching condition is slower than that of the neutral matching condition. The three key effects will be analyzed using Bayesian repeated-measures ANOVA and Bayesian paired-samples t-test , respectively, which both use JASP built-in priors. Considering the practical factors of this study, the minimum sample size was set at 18 and the maximum sample size at 25 participants.The sample size for the longitudinal experiment was determined using Bayesian factor analysis, and the Bayesian factor threshold BF10 for stopping data collection was set at 10  with regular exercise. The HIIT activities comprised 10 movements: 10 burpees, 30 opening and closing jumps, 10 kneeling push-ups, 20 alternating knee lifts, 20 squats, 20 bench bends, 10 squat jumps, 20 supine tummy rolls, 10 lunge squats, and 20 supine hip straightens on both sides. These exercises were performed at a medium intensity for 20 min, and completed 3 times per week. To ensure that exercise intensity was at the desired (safe) level, we randomly selected six participants to wear Polar heart rate monitors; their heart rates were recorded at quiet time and 3, 6, and 15 min into the exercise. Before the experiment, the research purpose and the exercise regime were clearly explained to all participants. They were forbidden to drink alcohol, coffee, tea, or any other drinks affecting sleep for 48 h before the experiment and instructed not to engage in strenuous exercise for 24 h before the experiment. No participants had any major life events.In the psychological nursing group, quarantined students with elevated anxiety received remote online support from the nursing staff of Yangzhong People's Hospital. During the 8-week intervention, each student met remotely with a nurse once per week for 30–40 min. The intervention was designed to create a quiet and comfortable environment for dialogue, conducive to good communication; nurses maintained a cordial and warm attitude toward students and used technical language where appropriate, aiming to help students express their innermost thoughts and reduce their resistance to psychological intervention. Nurses explained to students the adverse effects of anxiety and how lack of physical activity is detrimental to physical and mental health, as well as providing information on the main causes of anxiety among junior high school students, such as learning pressure, change of environment, and separation. They also paid close attention to emotional variations in students, and gave targeted guidance based on each student's anxiety level, seeking to reduce their psychological burden and affirm their efforts in the intervention process. In addition, the nurses gave timely examples to illustrate the radical and fluctuating nature of anxiety, thereby aiming to lessen students' fear and concerns and promote their confidence. Students also received training in relaxation methods, such as listening to soft music to relax their minds and reduce both psychological tension and anxiety. Finally, the nurses also encouraged students to actively exercise at home.Participants in the anxiety control group and the normal control group lived a normal home life and engaged in study as usual.p-values for anxiety, sleep quality, and total questionnaire all exceeded 0.05. At the test level of α = 0.05, we can conclude that the survey results of each dimension and the total questionnaire did not significantly differ, indicating bivariate normal distributions suitable for Pearson correlation analysis. As p-value of the attitude dimension was < 0.001, Spearman correlation analysis was used.The Kolmogorov–Smirnov normality test was conducted on the questionnaire results. t-tests were used to compare the data before and after the intervention, and independent-samples t-tests and one-way ANOVAs were used to test the different groups.The data were analyzed using SPSS 26.0 software. For MPAI, total scores of 34–50 represent mild cell phone addiction, 51–68 denote moderate addiction, and 69–85 indicate severe addiction. Paired-samples p < 0.05) and sleep quality (p < 0.01) significantly differed among participants of different grades during the quarantine period. Anxiety also significantly differed between urban and rural dwellers, while sleep quality significantly differed between male and female students. No other significant differences were found. The full results are shown in Chi-square tests were performed to identify any significant differences in the levels of anxiety and sleep quality within demographic categories. The results indicate that anxiety  and sleep quality . Next, we used a simple linear regression model to analyze the impact of physical activity (independent variable) on anxiety and sleep quality (dependent variables). The model formulas were as follows:As shown in R2 values of 0.030 and 0.066, indicating that physical activity explains the reasons of 3.0 and 6.6% changes in anxiety and sleep quality. Both regressions have overall significance . The regression results are presented in with respective t-tests revealed significant differences in anxiety, physical activity, and sleep quality between the normal control group and the anxiety control group. The results illustrate that levels of anxiety, physical activity, and sleep quality significantly improved after the exercise intervention and psychological nursing during the quarantine period.As shown in A one-way ANOVA was performed to reveal differences between the anxiety control group, exercise group, and nursing group in levels of anxiety, physical activity, and sleep quality. As reported in t-tests to compare levels of anxiety, physical activity, and sleep quality in each group before and after the intervention. After the exercise intervention, there were significant improvements in student's levels of anxiety (p = 0.000), physical activity (p = 0.000), and sleep quality (p = 0.019). After the psychological nursing intervention, there was no significant difference in anxiety (p > 0.05), but there were significant differences in physical activity and sleep quality (p < 0.01). In both the anxiety control group and the normal control group, anxiety, sleep quality, and physical activity all significantly declined over the 8-week period. The full results are shown in We carried out paired-samples The results demonstrated that, during the quarantine period, the incidence of anxiety among junior high school students was 43.0%, while 55.7% had sleep quality disorders. These levels are consistent with those reported by and Xu et al.  and ChenModerate exercise plays an important role in the physical and mental health development of adolescents . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.PC and YC contributed to study conception and design, and to manuscript polishing, and revision. SJ and PL organized the database, performed statistical analysis, and wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.


Conclusions: cirrhotic LT candidates with a prior history of HE rifaximin treatment are associated with a lower risk of time-dependent all-cause hospitalization, likely due to its unique effect on gut microbiome composition/function. In cirrhotic patients listed for liver transplantation (LT) with a history of hepatic encephalopathy (HE), rifaximin reduces the number of hospitalizations, but whether it influences the time to first hospitalization is unknown. Aims: to evaluate the time-dependent impact of rifaximin on the risk of all-cause hospitalization and dropout in patients on the LT waiting list. Methods: Consecutive patients listed for LT were retrospectively enrolled. After balancing populations with and without rifaximin treatment using the inverse probability therapy weighting analysis, Fine–Gray multivariable competing risk analyses were run to explore risk factors for the first episode of hospitalization and dropout. Results: When comparing 92 patients taking rifaximin to the untreated group of 152, rifaximin treatment was not associated with any of the study outcomes. In the subset of patients with a history of HE at waitlist entry (N = 81 rifaximin-treated and N = 39 untreated), rifaximin intake was independently associated with a lower risk of hospitalization for all causes (SHR 0.638; 95.0% CI 0.418–0.973;  Cirrhosis caused 1.32 million deaths worldwide in 2017 and, in 2019, cirrhosis mortality was associated with 2.4% of global deaths ,6,7. It This was a retrospective monocenter observational study investigating data of cirrhotic patients listed for LT who received rifaximin or did not. The present study was conducted in accordance with the Declaration of Helsinki and was approved by the Local Ethics Board of Sapienza University of Rome (Ref. N. 3420. 27 November 2014). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed to create this study.Clinical records of 244 consecutive cirrhotic patients at the time of entry on the waiting list for LT at Sapienza University of Rome were retrospectively selected and evaluated (time period 2011–2018). Patients were divided into two groups based on whether they were on chronic treatment with rifaximin or not. All patients were ≥18 years old and cirrhosis diagnosis was made based on the presence of at least 2 of the following conditions: (a) history of cirrhosis complications: HE, variceal gastrointestinal bleeding, ascites; (b) blood test consistent with cirrhosis: hyperbilirubinemia, hypoalbuminemia, prolonged international normalized ratio, low platelet count; (c) signs of advanced chronic liver disease and/or portal hypertension at diagnostic examinations: nodular-appearing liver at abdominal imaging (ultrasound/computed tomography), reduced portal vein flow at ultrasound, increased liver stiffness, gastroesophageal varices at upper endoscopy; (d) fibrosis stage 4 according to Metavir classification at liver biopsy . ExclusiThe primary outcome of this study was the risk of first-episode hospitalization, either for all causes or for HE. Secondary outcomes were the risk of dropout for deterioration and for first episode of gastrointestinal (GI) bleeding and of spontaneous bacterial peritonitis (SBP). Dropout was considered an event in cases of (a) death; (b) clinical worsening; (c) tumor progression. In the cases of delisting for liver function improvement, change of LT center, and poor compliance, the cases were censored. The first episode of GI bleeding and that of SBP could be the cause of hospitalization or arise during hospitalization. Competitive risk analyses were performed for all outcomes, considering LT as the competitive event. 2; (2) Type 2 Diabetes Mellitus (T2DM); (3) metabolic dysregulation, established by the presence of at least two of the following characteristics: (a) triglycerides ≥ 150 mg/dL or being on treatment for hypertriglyceridemia; (b) fasting serum glucose value of 100–125 mg/dL; (c) hypertension with median arterial blood pressure values ≥ 130/85 mmHg or being on treatment with antihypertensive drugs; (d) high-density lipoprotein cholesterol (HDL) less than 40 mg/dL in men or less than 50 mg/dL in women or being on treatment for low HDL [Data were retrospectively extracted from hospitalization and outpatient follow-up records. Data errors and missingness were identified across the database and solved, when possible, with specific queries. Baseline information was collected at the time of the waitlist and included patient demographics, comorbidities, and cirrhosis etiology, including Metabolic-Associated Fatty Liver Disease (MAFLD)  and rifa low HDL . Stage o low HDL . The pos low HDL . From thContinuous variables are reported as medians and interquartile ranges (IQRs). Categorical variables are described as numbers and percentages. The Mann–Whitney U test and Fisher’s exact test compared continuous and categorical variables, respectively.Missing data relative to study covariates always involved less than 10% of patients. In all the cases, missing data were handled with a single imputation method. In detail, a median of nearby points imputation was adopted. The median instead of the mean was adopted due to the skewed distribution of the managed variables.p is the probability of cause without considering covariates, and PS is the propensity score.To compensate for the nonrandomized design of this study, we balanced  the populations using the inverse probability therapy weighting (IPTW) analysis. To compare the rifaximin group with the no-rifaximin group, we express continuous data as means (SDs) based on categorical data on the frequency distribution. Eight potential confounders were included in the boosted models: age, male sex, waiting time duration, Model for End-stage Liver Disease (MELD), BMI, T2DM, chronic kidney disease (CKD), and MAFLD. To reduce the artificial increase in the sample size, and therefore the type I error rate  associated with the inflated sample size in the pseudo-data, we used stabilized weights (SWs) according to the following formula:p values can be biased from population size, results from the comparisons between covariate subgroups are reported as effect size . The Cohen d values that were lower than 0.1 indicated very small differences between means, values between 0.1 and 0.3 indicated small differences, values between 0.3 and 0.5 indicated moderate differences, and values greater than 0.5 indicated large differences.Because Different Fine–Gray multivariable competing risk analyses were run in the post-IPTW population to explore the risk factors for all-cause hospitalization, GI bleeding, SBP, and dropout. The variables to use for constructing the models were preliminarily selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression (stepwise regression with backward elimination), with the intent to create a parsimonious model in terms of number of covariates. Only variables present at the time of waiting list inscription were introduced in the models with the intent to avoid the risk of immortal time bias. The variables tested for each model were male sex, BMI, CKD, MELD, T2DM, age, cirrhosis etiology , HCC, ascites, and varices. The models were constructed using “liver transplantation” as the competing event. Sub-hazard ratios (SHRs) and 95.0% CIs were reported for significant variables. A sub-analysis only focusing on patients with HE at the time of waiting list inscription was also performed. p < 0.05 were considered statistically significant. Statistical analyses were run using the SPSS statistical package version 27.0 . Variables with p = 0.007) and MELDNa (p < 0.0001) and were more commonly affected by ascites (p = 0.02), esophageal varices (p = 0.04), and overt HE (p < 0.0001). In the rifaximin group, 12% of patients had no history of overt HE. In these patients, rifaximin was prescribed for a diagnosis of minimal HE. In patients in the rifaximin group, the diagnosis of T2DM (p = 0.02) and MAFLD (p = 0.004) was more frequent. Ninety-two patients were enrolled in the rifaximin group and one hundred fifty-two patients were enrolled in the no-rifaximin group. The median follow-up time was 239 days (IQR = 83–500). At enrollment, patients in the rifaximin group had been on rifaximin treatment for a median time of 145.5 days (IQR = 93.75–357) and the minimum treatment duration was 31 days. During the follow-up, no differences were observed between the two groups in terms of dropout rates for worsening or LT . From waWith the intent to minimize the potential biases connected to the presence of confounders, the rifaximin-treated and untreated groups were artificially balanced using an IPTW. Before the balancing, the two groups showed small to moderate differences in the potential confounders investigated. After the IPTW, all the Cohen’s D-values declined, showing only very small differences after the balancing . Risk factors for the first episode of hospitalization for all causes or for HE, for the first episode of GI bleeding and of SBP, and for dropout were studied using a competitive risk analysis in the post-IPTW population ; rifaximThe long recruitment period (2011–2018) allowed us to carry out a sub-analysis in the subgroup of patients with HE by dividing them into treated and not treated with rifaximin. In this sub-analysis, 36 patients were not on rifaximin treatment, while 81 were on rifaximin treatment. This difference in treatment choice was due to the different time period of inscription on the waiting list compared to the date of publication of the recommendation on the management of HE and the related prescriptive policy of rifaximin. Both before and after IPTW, no significant differences were observed between the rifaximin and untreated groups in terms of demographic and clinical characteristics . After Ip = 0.04), and for the risk of HE-related hospitalization   . In contWe explored the potential clinical benefits of rifaximin treatment in cirrhotic patients entering the waiting list for LT.In our retrospective cohort, more than one third (37.7%) of cirrhotic patients undergoing LT were on rifaximin treatment since entering the waiting list and most of them (88%) had a history of overt HE. MAFLD represents, as expected, the main etiology of liver cirrhosis and was more common in the rifaximin-treated group than in the untreated group. For a better comparison between the rifaximin-treated and untreated group and in order to compensate for differences due to the nonrandomized design of our study, we balanced the two populations using the IPTW analysis. This statistical method is considered a good tool to compare differences between groups for all baseline characteristics, both before and after confounder weighting, and to estimate the treatment effect in observational studies. Compared to other statistical methods, the main advantages of IPTW are that of increasing the effective size of the sample, retaining most of individuals in the analysis, and of showing less bias in the estimation of hazard ratios . In our The benefit of rifaximin on all-cause hospitalization in patients with advanced cirrhosis such as LT candidates and with a prior history of HE is relevant for several reasons. Indeed, for patients on the LT waiting list, avoiding hospitalization improves the chances of accessing the transplant, as hospitalization in these patients has been associated with worst outcomes. In fact, patients who are hospitalized often have a temporary or definitive contraindication to LT due to the complication/s or nosocomial infections that delay or prevent access to the transplant . Our resOur result that rifaximin is of benefit only in the subgroup of patients with a prior history of HE deserves specific comments. It has been shown, in fact, that the gut microbiota characteristics are different in patients with and without a history of HE and it is likely that the effects of rifaximin may differ in the two types of patients ,38. IndeLimitations of our study are the monocentric and retrospective nature. This study was observational in a heterogeneous population and not rigorously designed to study the effect of treatment with rifaximin versus no rifaximin. Especially regarding the analysis in the entire study population, the rifaximin-treated and untreated groups were unbalanced in terms of disease severity, comorbidity, and etiology. It is possible that this imbalance was not completely corrected by the statistical analysis with IPTW and by the fact of having tested, as potential confounders for the multivariate analyses, some disease severity indices such as the MELD score; the presence of HCC, ascites, and varices; and different demographic variables and comorbidities. Furthermore, we did not collect data regarding GI bleeding and SBP prophylaxis, which may have influenced the results. Finally, we cannot say what, in addition to HE, are the other types of complications that cause hospital admissions for all causes on which Rifaximin has a beneficial effect in the subgroup with previous HE. However, the strengths of our study are the long recruitment period (ten years), during which all cirrhotic patients underwent the same waitlist and dropout criteria, and the long median follow-up (>7.5 months).In summary, our study found that a large percentage of cirrhotic patients on the waiting list for LT are treated with rifaximin and that, among the latter, MAFLD is the prevalent etiology. Our study demonstrated that, in cirrhotic patients with a history of established HE at the time of the liver transplant waiting list, rifaximin has a significant beneficial impact on the risk of hospitalization related to HE and all causes.


Vasovagal reactions (VVRs) are common but complex donor adverse reactions (DAEs) in blood donations. VVRs have been extensively studied with a multitude of risk factors identified including young age, female gender and first-time donor status. How they may interplay remains obscure.A total of 1,984,116 blood donations and 27,952 immediate VVRs (iVVRs) and 1,365 delayed VVRs (dVVRs) reported between 2011 and 2021 in NZ were used in multivariate logistic regression analyses each concerning donations with iVVRs as cases and those free of DAEs as controls. For each analysis stepwise selection was used to identify the best model and risk factors carrying significant main effects and/or interactions. Identified interactions informed further in-depth regression analyses to dissect iVVR risk patterns.p = 6.2e-07) in first-time donations only and with age group in repeat donations only (p < 2.2e-16), together indicating young female donors at the highest risk of iVVRs. Our results also revealed that donation policy changes contributed to the year effects; donors had a lower iVVR risk at mobile sites than well-medicalized donation centers probably because of under-reporting.Over 95% of VVRs were iVVRs that had lower female preponderance and deferrals than dVVRs. iVVRs had a school seasonal pattern in whole blood donations driven by first-time donors from schools/colleges, and interactions between gender and age group differentiating the first-time from repeat donations. Subsequent regression analyses identified the known and novel risk factors of year and mobile collection sites and their interactions. iVVR rates were roundly elevated in 2020 and 2021 probably because of COVID-19 restrictions like facemask wearing. Exclusion of the 2020 and 2021 data removed the interactions with year, but confirmed interactions of gender with mobile collection sites (Modeling statistical interactions is valuable in identifying odds and revealing novel iVVR risk patterns and insights into blood donations. Vasovagal reactions (VVRs) are the most common but complex donor adverse events (DAEs) in blood donations , 2. DuriVVR incidence rates per 1,000 donations vary widely, e.g., from 10 to 125 in whole blood (WB) donations and 1.6 to 41.7 in apheresis collections (A VVR can be further classified as immediate (iVVR) if it happens at a collection site or delayed (dVVR) if it happens beyond the collection site and within 24 h following donation. Although dVVRs account for only a small proportion (~10%) of the total VVRs reported, this could be an under-estimate as donors might not necessarily report symptoms after leaving the collection site , 9.VVRs have been extensively studied globally, with a multitude of risk factors identified , 8, 10. Further research is needed to address a few shortfalls. Firstly, major donation environmental changes like implementation of interventions  and the Here we used a comprehensive dataset of blood donations and DAEs collated by the New Zealand Blood Service (NZBS) to study VVR risk patterns in NZ blood donors. We first characterized blood donations and VVRs by known risk factors, as well as by year and type of collection sites. Concentrating on iVVRs, we then performed multivariate logistic regression analyses, modeling main effects and interactions together for first-time and repeat donations separately. Identified interactions were examined closely and used to inform in-depth analyses to dissect risk patterns of iVVRs and identify the most vulnerable donors.This is a retrospective study of blood donations and DAEs between 2011 and 2021 in NZ. NZBS is the sole provider of blood and blood products in NZ and is responsible for the collection of blood from volunteer non-remunerated donors and to the provision of blood products within the hospital environment. NZBS has collected DAE data reported by nurses in charge using a standard form based on guidance and definitions for complications related to blood donation by the International Society of Blood Transfusion.n = 28), or with a wrong flag of “Citrate Reaction” in WB donations (n = 26), or with a duplicate entry of red cells not returned , giving a rate of exclusion of initial data of 18.9%. Further, entries of the first-time donation flag of each DAE were checked against that recorded in the database of blood donations and corrected accordingly if a mismatch was detected. In total, nearly 2 million  blood donations and 60,028 DAEs  during the study period were analyzed.Data from blood donations between 2011 and 2021, including donor gender, donation type , donation date, age at donation, donation site and site type , first-time donor status, were extracted from dedicated NZBS databases. DAEs reported between 2011 and 2021 were extracted from a NZBS Haemovigilance database, including the same fields for blood donations above plus fields storing DAE categories, symptoms and donor outcome. Only DAEs related to either WB donations, or plasmapheresis or plateletpheresis were concerned in this study. Data quality control of DAEs removed records with missing entries of symptoms  of NZBS. All research has conformed to the principles embodied in the Declaration of Helsinki.Blood donation and DAE data were first characterized by known risk factors of VVR such as gender, age, first-time donation status, type of blood donations, and type of collection sites. Seasonal and yearly impact were also explored. Chi-square tests were used for group comparisons between iVVR and dVVR. DAE or iVVR rates were calculated as per 1,000 donations as appropriate. Following previous studies  and donoMASS, stats, DescTools, ggplot2, and questionr. Multivariate logistic regression analyses were performed for first-time donations and repeat donations separately. The regression models concerned gender, age group, type of donation site, year, and their interactions for convenience of comparisons, with donation site and donation type excluded because of data sparsity at certain levels of either of the two variables. For each set of logistic regression analyses, a three-step approach was taken using the glm function with the regression family parameter set as binomial and the stepAIC function:  with significant effects in the regression, and was further analyzed using the anova function to quantify variance explained by each covariate and examine significance using the built-in Chi-square test. The odds. Ratio function of the questionr package was used to calculate odds ratios and test statistical significance using a built-in Fisher’s exact test.The blood donation data were merged with the DAE data into a combined list with additional fields storing whether each donation was associated with a DAE and what type of DAEs if yes. In the combined list, donations associated with DAEs other than iVVRs were first excluded, and then donations associated with iVVRs were set as cases and those free of DAEs were set as controls. The resultant list was further split into a list of only first-time donations with/without iVVR and a list of the remaining donations by repeat donors. Statistical analyses were performed using R  v4.1.1).1MASS, sunction:  the resuNZ blood donations and DAEs reported between 2011 and 2021 are summarized in p = 0.01), permanent deferral (p = 4.2e-07), and female preponderance (p = 7.1e-10)  . About 27.1e-10) . FurtherConcentrating on iVVRs hereafter, we first observed clear gender and school seasonal patterns . CompariWe then observed statistical interactions between age group and gender in iVVR rates in both the first-time and repeat donations . ClearlyConsidering donations with iVVRs as cases and those free from DAEs as controls, multivariate logistic regression analyses detected significant interactions for both the first-time and repeat donations . ConsideMonthly iVVR rates in 2020 and 2021 were therefore compared against the historic counterparts calculated using data between 2011 and 2019 . In WB dp = 6.2e-07, We further computed odd ratios of iVVRs using data between 2011 and 2019 in the first-time and repeat donations, respectively, . ClearlyEmpowered by comprehensive data of NZ-wide blood donations, we closely examined key risk factors for iVVR and characterized their interactions for the first time. In addition to the well-known risk factors of first-time donation status, young age and female gender , 13, 28,The association of mobile sites with reduced iVVR risk appeared as a surprise initially as by a conventional perception it would the other way around. Since impact of type of collection sites on risk of iVVRs has been underexplored , it is np = 6.2e-07) and between gender and age group in repeat donations (p < 2.2e-16)  . The for2.2e-16) , suggest2.2e-16) , where y2.2e-16) , 26. Mar2.2e-16) , which mOur results raised a couple of concerns about donor vigilance in NZ blood donations. First, only a small proportion of the total iVVR variance were explained by the risk factors identified in either the first-time donation model  or the repeat donation model (<7%), suggesting that some important variables might have been missed out from the current donor vigilance. Monitoring additional factors such as donor blood volume, fear and pain , 16 and In addition to the operational issues above, major changes to donation environment and operation policies could contribute to the significant year effects identified in both the first-time and the repeat donation models. One good example was the implementation of COVID-19 restriction measures in blood donation settings, of which facemask wearing could influence breathing, effective communication, and ability to detect early signs of adverse reactions , 30, genOur study also highlighted a couple of research issues. First, fear and/or pain related psychological factors , 16, altThis study was limited by data available for comprehensive investigation. For example, we characterized that dVVRs were featured by female preponderance and high probability of permanent deferral , but werhaemo.vigilance@nzblood.co.nz.The data analyzed in this study is subject to the following licenses/restrictions: Applications for access to the de-identified data will be reviewed by the Clinical Advisory Group of NZ Blood Service. Requests to access these datasets should be directed to MS, Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.W-HW, MS, RC, and AC conceived the idea of the study. W-HW, AC, MS, DS, and DW contributed to the design of the study and the acquisition, analysis or interpretation of the data. AV, KM, JH, LR, LS, AB, and SK contributed to interpretation of the results and discussion of clinical insights. W-HW performed the statistical analysis and prepared the first draft of the manuscript. AC, DW, DS, MS, RC, and SK revised it critically for important clinical content. W-HW and MS had full access to all the data in the study. All authors contributed to the content of the paper, reviewed and approved the final version and had responsibility for the decision to submit for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Brain radiotherapy often results in impairment of hypothalamic–pituitary (HT-P) function, which in turn causes secretory dysfunction of related hormones. In this paper, the frequency of metastasis in the HT-P area and its high-risk factors in patients with brain metastasis were retrospectively analyzed, and thus provide experimental evidence for protecting HT-P area during whole brain radiotherapy (WBRT).A retrospective analysis was performed on the data of patients with brain metastasis diagnosed by cranial magnetic resonance imaging (MRI) at the First Hospital of Lanzhou University from 2017 to 2020. The anatomical positions of the hypothalamus and pituitary were delineated, followed by their expansion by 5 mm outwards, respectively, in the three-dimensional direction, and the hypothalamus +5 mm and pituitary +5 mm were obtained as the avoidance area, in which the frequency of brain metastasis was evaluated. Univariate and multivariate logistic regression models were used to analyze the high risk factors of brain metastasis in HT-P area.p < 0.001), and the occurrence of brain metastasis in the pituitary  were related to brain metastasis in the hypothalamus, and that the only relevant factor for brain metastasis in the pituitary was the occurrence of that in the hypothalamus . There was no correlation between tumor pathological types, the maximum diameter, the total volume of brain metastatic lesions and the risk of brain metastasis in hypothalamus and pituitary.A total of 3,375 brain metastatic lesions from 411 patients were included in the analysis. The rates of brain metastasis in the hypothalamus +5 mm and pituitary +5 mm in the whole group of cases were 2.9% (12/411) and 1.5% (6/411) respectively; the frequency of lesions was 0.4% (13/3375) and 0.2% (6/3375) respectively. Univariate and multivariate analyses showed that the number of brain metastases (OR = 14.946; 95% CI = 4.071–54.880; The frequency of brain metastasis in the HT-P area is extremely low. The risk of brain metastases in the hypothalamus is correlated with their number. The larger the number of metastatic lesions, the higher the frequency of brain metastasis. Protection of the HT-P area during WBRT may be unlikely to compromise the tumor recurrence rate for patients with a relatively small number of brain metastases. It has been reported in studies that up to 40% of tumor patients will develop brain metastasis . RadiothThe data on 411 patients with brain metastasis admitted to the First Hospital of Lanzhou University from 2017 to 2020 were retrospectively collected. The screening criteria for them were as follows: eligibility criteria , T1-weighted enhanced sequences, etc.) and exclusion criteria .The cranial MRI images of patients at initial diagnosis were accessed and viewed through the hospital PACS system. The number and distribution of brain metastases were observed on T1, T2 weighted plain scanned and T1 weighted enhanced images. The MRI T1-weighted enhanced sequence images were imported into Varian eclipse planning system for target delineation to delineate the anatomical boundaries of all brain metastasis, hypothalamus and pituitary, which were expanded by 5 mm outwards in the three-dimensional direction to obtain the boundary contours of hypothalamus +5 mm and pituitary +5 mm, respectively. The boundary distance of brain metastatic lesions and the shortest distance between the boundaries of the two areas was measured. The schematic diagram of the location of brain metastatic lesions, hypothalamus and pituitary is shown in The frequency of brain metastasis was calculated in the hypothalamus +5 mm and pituitary +5 mm. The relationship between brain metastasis in the hypothalamus and pituitary and various clinical features was analyzed by statistical methods, and the high-risk factors for brain metastasis in this area were explored.p < 0.05).Logistic regression method was adopted to analyze the correlation between brain metastasis in HT-P area and clinical factors such as age, sex, pathological type, as well as the number, the maximum diameter and the total volume of brain metastatic lesions by SPSS 21 software. The optimal cut-off value for the number of brain metastases was obtained by calculating the area under the receiver operating characteristic (AUROC) curve. The difference was statistically significant (p < 0.001) and the occurrence of brain metastasis in the pituitary  were correlated with the risk of brain metastasis in the hypothalamus (p = 0.006)  and about 10.0% (41/411), respectively. There were 341 cases (83.0%) of lung cancer, 30 cases (7.3%) of breast cancer, and 40 cases (9.7%) of other tumors . Per patthalamus . The res= 0.006) . There wIt has been reported in many studies that the probability of functional impairment of endocrine organs such as hypothalamus and pituitary after radiotherapy can be as high as 20–90% , 17, 18.Similar to the problem of hippocampal protection, if the frequency of brain metastasis in HT-P area is extremely low, the possibility of tumor recurrence in this area will be relatively low. Therefore, this area can be protected during WBRT. In other words, when the location of brain metastatic lesions in patients is relatively far from the HT-P area, the avoidance of these two areas can be considered in delineating the target area for WBRT, or stricter dose restrictions can be imposed on these two organs in evaluating the radiotherapy plan, thus making them receiving as low a radiation dose as possible. Therefore, there is a need to understand the frequency of brain metastasis in the HT-P area. However, there were few reports on the frequency of brain metastasis in HT-P area in the past, with the scarcity of relevant data. Therefore, the data on patients with brain metastasis at our unit were retrospectively analyzed.In 2010, Marsh analyzed a total of 935 brain metastasis in 155 patients in a study, and found only one case of brain metastasis in the pituitary . A largeHowever, similar to Janssen’s findings in 2019 , our stuIn the retrieval of the literature, it was found that there were almost no reports on the frequency of brain metastasis in the HT-P area in Chinese population. As a data analysis of a large sample of patients with brain metastasis, this study provides a scientific basis for investigating the risk of brain metastasis in the HT-P area in Chinese population, with a certain reference value. Also, it has been pointed out in studies that it is feasible to protect the HT-P area during WBRT with the help of current advanced radiotherapy technology , 32. If In conclusion, the frequency of brain metastasis in the HT-P area is extremely low. There is a correlation between the number of brain metastases and the risk of brain metastasis in the hypothalamus. In other words, the larger the number of metastatic lesions, the higher the frequency of brain metastasis in the hypothalamus. It needs to be further verified by more studies whether there is a correlation between the risk of brain metastasis in the hypothalamus and that in the pituitary. Therefore, for patients with a relatively small number of brain metastases, this data suggests that protection of the HT-P area during WBRT may be unlikely to compromise the tumor recurrence rate; clinical applications should be explored.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants or patients/participants legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.PX: Writing – original draft. HH: Investigation, Writing – review & editing. XC: Investigation, Writing – review & editing. NL: Data curation, Formal analysis, Writing – review & editing. HZ: Data curation, Writing – review & editing. RY: Investigation, Writing – review & editing. PY: Data curation, Investigation, Writing – review & editing. WH: Data curation, Investigation, Writing – review & editing. HQ: Writing – review & editing.


Microcephaly is a neurological condition characterized by anomalies in the growth of the cranial circumference. This study aims to examine the association between sociodemographic and clinical variables and the occurrence of secondary microcephaly in newborns in Brazil. It also aims to investigate the association between this congenital anomaly and teratogenic infections. This research adopts an observational approach with an ecological, descriptive, and analytical design. The sample includes infants aged ≤28 days and registered in the country’s Live Births Information System from January 2015 to December 2021. Newborns were categorized into G1, consisting of newborns with one of the three infections , and G2, consisting of newborns with two of the three infections. A total of 1513 samples were analyzed and divided into two groups: one infection  and two infections (n = 56). The northeastern region of Brazil has the highest prevalence of microcephaly. Regarding the population profile, the Zika virus infection is more common among white mothers, while the syphilis infection is more common among black mothers. Among newborns with microcephaly, boys have a lower prevalence of toxoplasmosis infection, while girls have a lower prevalence of Zika virus infection. This study provides pertinent information on each infection and contributes to the epidemiologic understanding of the association between teratogenic infections and microcephaly. Microcephaly is a neurological condition characterized by anomalies in the growth of the cranial circumference, which can be identified by abnormalities in the reduction of measurements used to estimate this growth . These cThe major congenital infections associated with the clinical presentation studied in this study are collectively referred to as TORCH, an acronym for toxoplasmosis, rubella, cytomegalovirus, herpes simplex infection, syphilis, and acquired immunodeficiency syndrome (AIDS) ,7,8. TraStrengthening the health system to control and prevent congenital infections through public health strategies can help prevent the occurrence of microcephaly associated with these infections. However, this problem persists in some developing and underdeveloped countries, resulting in high rates of morbidity in the population .In Brazil, after identifying an increase in microcephaly cases in Pernambuco, the government launched an epidemiological investigation in October 2015 to analyze whether the increase was a fluctuation in numbers or a potential outbreak. A preliminary analysis of the Live Birth Information System (SINASC) showed that the numbers observed in Pernambuco in October 2015 were significantly higher than usual. In response, the WHO and the Brazilian government declared the microcephaly epidemic a national and international public health emergency in November 2015 ,17,18.ZIKV is transmitted by Aedes mosquitoes and can cause severe central nervous system complications, including microcephaly. Microcephaly is a condition in which a baby’s head is smaller than normal. It can cause a range of health problems, including developmental delays, seizures, and intellectual disabilities ,20.In addition to ZIKV, other infections can cause microcephaly, including syphilis and toxoplasmosis. Syphilis is a sexually transmitted infection that can be passed from mother to fetus during pregnancy. Toxoplasmosis is an infection caused by a parasite that can be transmitted by eating raw or undercooked meat or by contact with the urine of infected cats ,22,23,24This scenario should also be studied in the context of the sociodemographic characteristics of each locality and their association with microcephaly, especially in developing countries. Therefore, the aim of this study is to investigate the association between sociodemographic and clinical variables and the occurrence of secondary microcephaly in newborns in Brazil. It is also intended to investigate the association between this congenital anomaly and teratogenic infections. The study hypothesis is whether there are significant differences in sociodemographic and clinical variables related to microcephaly caused by teratogenic infections alone or in co-infection in Brazil.The data used are limited to secondary variables and do not reveal the personal data of the patients, therefore, in compliance with the National Health Council (CNS) Resolution No. 510 of 7 April 2016, the study was exempted from the mandatory evaluation by the corresponding research ethics committee .This observational study with an ecological design includes descriptive and inferential analyzes of live births of both sexes diagnosed with microcephaly between 2015 and 2021 in Brazil.The study used data from the SINASC , in this2, composed of 5570 municipalities, and an estimated population of 213,317,639 inhabitants in 2021, corresponding to a population density of 22.43 inhabitants per km2, an average fertility rate of 1.76 children per woman, and an infant mortality rate of 11.56 deaths per thousand live births, one of the highest rates in Latin America [The study was conducted in Brazil, divided into five macroregions: north, northeast, midwest, southeast, and south. According to the Brazilian Institute of Geography and Statistics (IBGE), the country has a total area of 8,510,345.540 km America .Live newborns were identified according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10), which are selected newborns with ICD-10 code Q02, corresponding to microcephaly within the neonatal period defined as 28 days of age or less. The time frame for this study was set from 2015 to 2021. This time frame is justified by the World Health Organization’s confirmation of congenital Zika syndrome (CZS) in the northeastern region of Brazil, the identification of its association with Guillain-Barré syndrome and central nervous system malformations at birth, and the start of international reporting in other countries in the Americas in 2015 . The selThe variables were divided into two categories: sociodemographic and clinical factors . Accordingly, the sociodemographic context in this study was examined through the description of maternal race/ethnicity, neonatal sex, birth year, and live birth classification. Maternal clinical factors were assessed based on maternal age, type of pregnancy, gestational fever, exanthema, pruritus, conjunctivitis, joint pain, muscle pain, edema, headache, ganglionic hypertrophy, and nerve damage. On the other hand, neonatal clinical factors were determined by weight, head circumference, neurological impairment, visual impairment, hearing impairment, type of evidence, and imaging findings .t-test (parametric) for independent samples were used. Statistical significance was defined as a p-value of <0.05.Data were organized in Microsoft Excel 2016 and then transferred to the Statistical Package for Social Science for Windows (IBM SPSS) software (version 21). The normality of the data was assessed using the Kolmogorov–Smirnov test, considering that all samples had representative values greater than 50. Descriptive analysis was performed to obtain frequency values (absolute and relative), mean and standard deviation (for parametric variables), and median with interquartile range  for the groups. For parametric variables with more than two groups, a one-way analysis of variance (ANOVA) was used, followed by Tukey’s post-test for significance analysis. For nonparametric independent sample data with more than two groups, the Kruskal–Wallis one-factor test was used, along with a pairwise comparison  and a Pearson’s chi-squared or Fisher’s exact test for categorical variables. Values were adjusted using Bonferroni’s method for comparing proportions to identify significant differences between variables within each group. For segments with two or fewer groups, the Mann–Whitney test (nonparametric) and the p < 0.050). Among male newborns, the prevalence of toxoplasmosis (37.9%) was lower than that of the Zika virus (47.9%), but among female newborns, the prevalence of toxoplasmosis (62.1%) was higher than that of the Zika virus (52.1%) (p = 0.006). A total of 1457 cases were analyzed, divided into three different infection groups: syphilis (423), toxoplasmosis (295), and Zika virus (739). In the sociodemographic analysis , self-rep < 0.001). From 2018 to 2021, the prevalence of Zika virus infections became lower compared to the other years . When classifying live births by gestational age, preterm deliveries were more common with toxoplasmosis infections (29.1%) compared to Zika virus infections (20.0%) (p = 0.025).Considering the year of birth of the newborns, the years 2015 and 2016 showed a higher prevalence of Zika virus infections  compared to the other years (p = 0.019), with a higher prevalence of live births with one infection (20.9%) compared to two infections (9.1%) in 2015 (p = 0.019). The average incidence rate of newborns younger than 28 days diagnosed with microcephaly per 100,000 live births by Brazilian region and state between 2015 and 2021 is shown in p < 0.001). Pregnancy fever (p < 0.001) was most common with Zika virus infections (48.8%) compared to syphilis (14.7%) and toxoplasmosis (14.9%). Exanthema during pregnancy (p < 0.001) was more common with Zika virus infections in the first (41.4%), second (18.2%), and third (8.8%) trimesters compared to other infections. Other pregnancy manifestations also showed statistical significance. Among them, pruritus (p < 0.001), conjunctivitis (p < 0.001), arthralgia (p < 0.001), myalgia (p < 0.001), edema (p = 0.034), headache (p < 0.001), and ganglionic hypertrophy (p = 0.032) were more common with Zika virus infections compared to the others. From another perspective, p = 0.012) was higher in mothers with one infection  than in mothers with two infections .p = 0.001), and the head circumference was lower  in those with the Zika virus infection. Diagnosis during pregnancy was more common with the Zika virus infection (43.5%) and postpartum in the syphilis infection (82.7%) (p < 0.001). MRI findings suggestive of congenital infection were more common with the Zika virus infection (84.2%) compared to toxoplasmosis (0%), while findings suggestive of other changes were more common with the toxoplasmosis infection (100%) compared to the Zika virus infection (0%) (p = 0.002). With regard to trans-fontanel ultrasonography (p < 0.001), normal results were more common with toxoplasmosis (83.3%) and Zika virus (76.9%) infections than with syphilis (41.9%) infections. Among altered results suggestive of congenital infections, the prevalence was lower for the toxoplasmosis (11.7%) and Zika virus (15.6%) infections than for syphilis (46.5%) infections. In computed tomography scan analyzes (p < 0.001), normal results (23.1%) were less frequent, while altered results suggestive of congenital infection (71.4%) were more frequent in the syphilis infections compared to the others. Among altered results with other abnormalities, a higher prevalence was observed for the Zika virus (11.8%) compared to syphilis (4.5%).p = 0.007). Abnormal results suggested infection was more common for syphilis (37.6%) than for toxoplasmosis (12.8%) (According to the results presented, this study accepts the alternative hypothesis, since there are significant differences in sociodemographic and clinical variables related to microcephaly caused by teratogenic infections alone or in co-infection in Brazil.Regarding the geo-referenced socio-demographic factors in the study, it was observed that the highest frequency of these diseases occurred in the northeastern region during the period analyzed. This may be partly due to the fact that it is a tourist region, which contributes to a significant influx of people from different parts of the country and the world, making these populations more vulnerable to transmission; as a result, public health authorities have initiated epidemiological investigations to identify the emergence and possible links .The incidence of microcephaly was higher among non-white mothers compared to black mothers. This finding regarding race/color may be attributed to factors such as low education, inadequate income, living in disadvantaged areas, and poor neighborhoods . These fWe did not uncover pertinent findings that elucidate the exact association between maternal age and birth year; however, it is plausible that these variables are important in the epidemiology of microcephaly, especially in the context of Brazil. This speculation stems from the declaration of a public health emergency in November 2015, which triggered a notable increase in disease surveillance and prevention efforts between 2010 and 2017 .Male newborns had a higher prevalence of toxoplasmosis, while female newborns had a lower prevalence. It has been observed that the toxoplasma gondii infection can affect male viability and survival in humans, which may be related to hormone levels . TherefoIn 2015 and 2016, Brazil experienced an outbreak of microcephaly cases associated with ZIKV , as confToxoplasmosis infection has been associated with higher rates of preterm birth. Acute gestational toxoplasmosis can lead to a miscarriage or severe damage to the eyes, brain, and other structures of the fetus. Although the impact of toxoplasmosis on prematurity is not fully understood, it has been suggested that it may be related to the cascade of inflammatory events in the placenta and fetus . ChildreWomen in later stages of pregnancy presented with isolated Zika virus infection. A previous study  also fouAs a strength of this research, it highlights the national perspective on sociodemographic and clinical factors associated with one or more teratogenic infections associated with microcephaly in Brazil, while previous studies have focused on specific regions or states. As inherent limitations of an observational approach that incorporates an ecological design, we first emphasize that this specific design prevents the establishment of causal relationships between exposures and outcomes and instead provides associations and trends within the confines of the population level . In addiThe results of this study showed that the Zika virus infection was more common among white mothers, while the syphilis infection was more common among black mothers. These ethnic/racial differences should be interpreted with the understanding that in Brazil, the classification of race/ethnicity by the Brazilian Institute of Geography and Statistics is based on self-report. This means that ethnic categories may not be accurate due to the lack of clear definitions of ethnic, linguistic, cultural, or historical characteristics . The scientific literature also shows heterogeneity of associated sociodemographic factors , but socThe present study investigated the sociodemographic and clinical factors associated with microcephaly in live births in northeastern Brazil. The results showed that the northeastern region of Brazil had the highest incidence of microcephaly. Self-reported white mothers were more likely to have the Zika virus infection, while black mothers were more likely to have the syphilis infection. Toxoplasmosis had a lower prevalence in male newborns, while Zika virus had a lower prevalence in female newborns. In 2015 and 2016, the Zika virus was the main teratogenic factor, while syphilis predominated in 2018 and 2019, and toxoplasmosis emerged as the main factor in 2020. The toxoplasmosis infection was associated with higher rates of preterm birth. In 2015, there were more cases of a single infection. Women in later stages of pregnancy had isolated Zika virus infection. Symptoms such as gestational fever, exanthema, pruritus, conjunctivitis, arthralgia, myalgia, edema, headache, and ganglion hypertrophy were more common in mothers with the Zika virus. Children with microcephaly had weight loss, with the Zika virus having the least effect. Most cases of all infections were detected postpartum. CT scan, plain ultrasound, and trans fontanel examination were more accurate in diagnosing microcephaly in syphilis cases. The results of this study suggest that sociodemographic and clinical factors show variation among live births with microcephaly resulting from teratogenic infections caused by different microorganisms. The results also highlight the importance of early diagnosis and intervention for children with microcephaly.