Significant differences in favor of the intervention were found in other anthropometric variables and low-density lipoprotein cholesterol, but changes in triglycerides, high-density lipoprotein cholesterol, inflammation markers, blood pressure, and glucose metabolism were not observed. A family-based nutritional intervention based on the Atlantic diet showed beneficial effects on adiposity and the lipid profile.The Atlantic diet, the traditional dietary pattern in northern Portugal and northwest Spain, has been related to metabolic health and low ischemic heart disease mortality. The Galiat Study is a randomized controlled trial aimed to assess the effects of the Atlantic diet on anthropometric variables, metabolic profile, and nutritional habits. The dietary intervention was conducted in 250 families (720 adults and children) and performed at a primary care center. Over six months, families randomized to the intervention group received educational sessions, cooking classes, written supporting material, and foods that form part of the Atlantic diet, whereas those randomized to the control group followed their habitual lifestyle. 213 families (92.4%) completed the trial. Adults in the intervention group lost weight as opposed to controls who gained weight (adjusted mean difference −1.1 kg,  Suboptimal diet has been identified as an important risk factor for noncommunicable diseases (NCDs). In the Global Burden Disease Study 2017, 11 million deaths  were attributable to dietary risk factors, with non-optimal intake of whole grains, fruits, and sodium accounting for more than 50% of deaths . AlthougThe Atlantic diet, the traditional dietary pattern in northwestern Spain and Portugal, is composed, above all, of local, fresh, and seasonal products and involves home cooking and minimally processed foods ,12. It hA community-focused intervention based on the Atlantic diet and led by a primary health care center may help promoting beneficial changes in food behavior at the population level. The objective of this study was to assess the beneficial effects of such intervention on anthropometric variables, the lipid profile, markers of the metabolic syndrome, and nutrient intake.The GALIAT study , conducted between March 2014 and May 2015, was approved by the Galician Autonomic Committee for Research Ethics  and registered with clinicaltrials.gov (NCT02391701). The trial was run in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. Participants were informed of the aims of the study and provided their written consent to be included. For children, signed informed consent was obtained from parents and from children aged >12 years.The study was a randomized, controlled, parallel-arm, community-focused dietary intervention trial, the protocol of which has been previously reported . The stun = 720) accepted and gave written consent. Families were randomly allocated (1:1) to the intervention group  or to the control group  using a computer-generated table of random numbers. Finally, 120 families (n = 346) were in the intervention group and 111 (n = 315) completed the trial  from the A Estrada municipality, which constituted the index subjects. Participation in the study was offered to index subjects and their family members who lived in the same household unit. Inclusion criteria for the index subject  were age 18–85 years, and living in a family unit of at least two members. The other members of the family (either gender) had to be aged 3–85 years. Exclusion criteria for the index subjects were alcoholism, current lipid-lowering treatment, pregnancy, major cardiovascular disease , dementia, or having a predicted survival of less than one year. The exclusion criteria for the other members of the family were the same except for lipid-lowering treatment. A total of 662 families met the inclusion criteria and were invited to participate, 250 of which  the nutritionists explained the nutritional recommendations for adults and children, along with information on eating five meals per day without skipping breakfast, on preparing menus, recommended portion sizes, the Atlantic diet, and the food pyramid. They also explained the benefits of physical activity, how to limit sedentarism, and how to use the education material and the recipe book provided. At 3 months, the nutritional recommendations provided were reviewed, food behavior and action plans checked, barriers to progress identified, the changes experienced and the degree of compliance with the recommended diet examined, and doubts answered. At 6 months, a review of progress was made and final messages were given in a 2-h group session in which the researchers and nutritionists again explained the influence of lifestyle on health, how to change to a healthier diet, the importance of physical activity, the characteristics of the traditional Atlantic diet, patterns for designing a healthy diet, and general recommendations on portion sizes.Fieldwork was performed at a primary health care center, where 20 general practitioners, 3 pediatricians, and 20 nurses took part as collaborating researchers. A further physician, a nurse, and 4 nutritionists were employed to lead the field study at the health care center.The local city hall provided a van along with personnel to perform the weekly distribution of foodstuffs. A local business provided warehouse space for their storage. A local restaurant lent its facilities for the cooking lessons, and in collaboration with nutritionists, a local hostelry school developed a recipe book and also helped in the cooking lessons. Products included in the food basket were chosen for being part of the Atlantic diet and were donated for free by local food companies.All personnel involved in fieldwork received theoretical and practical training one month before the study started on how to normalize work procedures. A participatory research approach was followed (research-action-participation) with the aim of promoting mutual learning among researchers, health and city hall workers, and the community (the target).Outcomes were measured at the individual level. The primary outcome measures were changes at 6 months as compared with baseline of anthropometric variables (weight and body mass index [BMI]) and lipid profile . Secondary outcomes included changes in inflammation markers , glucose and insulin resistance levels (fasting plasma glucose [FPG] and HOMA-IR [homeostatic model assessment of insulin resistance]), and systolic (SBP) and diastolic (DBP) blood pressure.Participants were evaluated at baseline (visit 0) and at 3 and 6 months. Data collected at baseline included sociodemographic characteristics; medical history; tobacco and alcohol consumption; medication; anthropometric data; blood pressure; health-related quality of life; adherence to the Atlantic diet; a 3-day food record including two weekdays and either a Saturday or Sunday; and blood sampling for laboratory analysis. Participants in the intervention group received a nutrition education session, a recipe book, a diary with food delivery dates, and a food basket. At 3 months, anthropometric measurements, blood pressure, and laboratory analyses were performed, and the 3-day food record was completed. At 6 months (end of study), procedures were the same as those at baseline.® 701 model-class III, Digital display . Height was measured without shoes using a portable stadiometer SECA® 213 model , and recorded to the nearest 0.1 cm. Waist (narrowest point between the bottom of the rib and the top of the iliac crest) and hip  circumferences were measured using a Seca 201 model circumference measuring tape . Skinfold thickness was measured using a HOLTAIN Tanner/Whitehouse Skinfold caliper . Relative body fat was calculated according to the equation of Siri [All laboratory analyses were performed at the Santiago University Hospital. Blood was extracted in the morning following a 10–14 h fast. Total cholesterol, HDL-cholesterol and triglycerides were measured using an Advia 2400 Clinical Chemistry System , and LDL-cholesterol using the Friedewald formula , except  of Siri .Assessment of compliance with recommendations on the Atlantic diet was assessed using a previously validated 14-item Atlantic diet index .Dietary intake was measured using a 3-day food record. Information requested from participants included data on foods consumed (brand names) and characteristics of the methods used for preparation of foods and cooking. Moreover, they were advised to provide the weight of all foods consumed and, when this was not feasible, to use measurements available at home, such as cupfuls and spoonfuls. An equivalency table to assess hand size, household measurement, and weight was given to participants. Nutritionists checked all records completed by the participants. Dietary intake was analyzed using DIAL software . Health-https://glimmpse.samplesizeshop.org/ (accessed on 5 April 2021)). The intention-to-treat (ITT) and the per-protocol (PP) data set were analyzed. The ITT population included all subjects randomized for which data of at least one primary outcome measure was available. The PP population included subjects randomized who completed the study. Multivariate imputation by chained equations method was used to replace missing data. Differences between the intervention and the control group were analyzed using mixed linear models adjusted for age, gender, and baseline values, with the intervention condition deemed a fixed effect and clusters (family) as a random effect. The intraclass correlation coefficient (ICC) was used to assess the correlation of measurements made on individuals of the same cluster (family). Statistical significance was set at p < 0.05. The STATA 16 program was used for the analysis of data.Required sample size was calculated for specified serum cholesterol concentration  assuming that the dietary intervention would be associated with a reduction of 10 mg/dL. The sample size required ensuring a minimum predictive power of 80% with a 0.05 type 1 error assuming a 10% drop out rate, and was determined to be 250 families. Sample size and power estimates were calculated using the sample size shop’s GLIMMPSE 2.0 online tool for cluster data . Participation in the nutrition education program was high . A total of 81.7% (300/367) subjects in the intervention arm and 83.3% (294/353) in the control arm filled out completely the three-day food record at baseline at 3 and 6 months.Demographic and clinical data of the study subjects at baseline are shown in p < 0.001) in favor of the intervention arm , the hip/waist ratio, and percentage body in favor of the intervention arm. Results in the per-protocol (PP) dataset were similar  but subjects in the control arm gained weight . The mean difference after adjusting by baseline weight, age, gender, and family cluster was −1.1 kg  in favor of the intervention arm. This difference persisted in the PP analysis  in favor of the intervention group. Significant differences between the groups were also seen in the change in the intake of total fat, saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, and cholesterol. The intervention group subjects also showed a significant increase in their beta carotene and folic acid intakes  . The adj intakes .Adverse events did not occur in any of the study subjects.2, weight −1.04 kg), and total cholesterol (−2.85 mg/dL), but no evidence was found of any association between behavioral counseling interventions and improvements in HDL-C, triglycerides, or fasting glucose levels.A community-focused, primary health center-led intervention involving the Atlantic diet improved adiposity and the lipid profile through change induced in the family food behavior. The improvements achieved in anthropometric variables were the most relevant. Although the food intake and food composition of subjects in the intervention arm were recorded, the intervention itself placed no restrictions on energy intake. Compared to the control group, subjects in the intervention group experienced a significant reduction in bodyweight of −1.1 kg (−1.7 kg in men and −0.8 kg in women). At the end of the trial, 11% of the adult subjects in the intervention arm had lost 5% of their starting body weight, which is a common criterion for clinically meaningful weight loss ,26. A re2) in the intervention group as compared to controls is clinically relevant. In a collaborative analysis of 57 prospective studies, which included 894,576 participants from North America and Western Europe, with a BMI between 22.5 and 25 kg/m2, it was found that for each BMI increase of 5 kg/m2 there was an associated overall mortality 30% higher, ranging from 60–120% mortality for renal, diabetic, and hepatic diseases to 10% mortality for neoplasms [The reduction in BMI , and something that works in small communities may not work in large cities . HoweverIn conclusion, the present type of intervention may be useful for improving adiposity and the lipid profile in the general population, with the primary health care center as an appropriate setting for its implementation. The community focus increased the complexity of the intervention by including many non-health care professionals, but it strengthened the degree of social involvement achieved. Although the intervention was performed in a rural Spanish municipality, it might be quite easy to perform in other rural or urban settings.


P < 0.001). Global spatial autocorrelation showed a positive spatial correlation distribution for the prevalence of the third multimorbidity pattern in China (P = 0.032). The status of chronic diseases and multimorbidity among the elderly with a spatial correlation is a significant health issue in China.This study aimed to investigate the spatial distribution and patterns of multimorbidity among the elderly in China. Data on the occurrence of 14 chronic diseases were collected for 9710 elderly participants in the 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Web graph, Apriori algorithm, age-adjusted Charlson comorbidity index (AAC), and Spatial autocorrelation were used to perform the multimorbidity analysis. The multimorbidity prevalence rate was estimated as 49.64% in the elderly in China. Three major multimorbidity patterns were identified: [Asthma/Chronic lungs diseases]: (Support (S) = 6.17%, Confidence (C) = 63.77%, Lift (L) = 5.15); : ; : . Results of the AAC analysis showed that the more chronic diseases an elderly has, the lower is the 10-year survival rate ( Despite many unpredictable hygiene challenges can be life threatening and cause the population decline, such as climate change caused by the extreme weather, emerging infectious diseases such as SARS, COVID-19, and superbugs, the population is aging at an accelerating rate and most people will live beyond the age of 60, with far-reaching impact on health systems, health workers, and health budget in China and around the world.Aging is often accompanied by multimorbidity or contemporaneous occurrence of a variety of chronic diseases . The WorInternational study of multimorbidity, for its definition generally agree with the WHO, just a few research defined as people with three or more chronic diseases at the same time, the study population are usually derived from the general population or primary care clinical practice, with a large sample size and strong representativeness –10. HoweThe pathogenesis of chronic disease is complicated, and researchers have gradually realized that the occurrence of chronic diseases is not only related to heredity and unhealthy lifestyle, but also to the human environment in terms of geographical location, environment, and climate, as well as the levels of pollution caused by various harmful substances , 19. TheIn this study, the 2015 waves of China Health and Retirement Longitudinal Study (CHARLS) database were adopted, and methods such as Apriori algorithm and spatial autocorrelation were used to explore the prevalence and patterns of multimorbidity among the elderly in China, as well as the spatial distribution of multimorbidity. Additionally, we aimed to further promote the prevention and control of chronic diseases and provide data for the implementation of effective management of multimorbidity in the future.Relevant data for 9786 participants aged 60 year and above were selected from the 2015 waves of CHARLS (See http://charls.pku.edu.cn/zh-CN). The data are publicly available. They can be downloaded with personal information removed.Raw data were obtained free of charge from the website of the CHARLS (http://bzdt.ch.mnr.gov.cn/browse.html?picId=%224o28b0625501ad13015501ad2bfc0240%22), ArcGIS 10.2  software was used to correlate the prevalence of chronic diseases and multimorbidity of the elderly in China with the electronic map, and to establish the database.Based on the China province  electronic map of 1:1,000,000  index was used to assess the impact of multimorbidity in elderly. Finally, we used spatial autocorrelation to explore the spatial distribution characteristics of multimorbidity.In the web graph, each chronic disease is shown as a dot. If the patient has two chronic diseases at the same time, the dots of the two chronic diseases are connected by line segments. The thickness of the line segment is determined by the frequency of the two chronic diseases being affected at the same time. The thicker the line is, the stronger the link strength will be. Thus, the correlation strength can be roughly reflected by different types of lines. Dotted lines represent weak correlation; normal thin lines and thick lines represent moderate and strong correlations, respectively.P(A∩B). Confidence (C): is the percentage of B contained in D when A is also contained in D, that is, the probability of P(B│A). Lift (A): is the ratio of the conditional probability of the occurrence of B to the unconditional probability of occurrence of B in the case of A, that is, P(B│A)│P(B)*P(A). The Lift is divided by 1. When the Lift >1, it indicates that there is a positive correlation between A and B and that there is multiple possibility of the occurrence of B under the condition of A. When Lift = 1, it means that the association rule reflects a common phenomenon. These three indices are indispensable, and single use of any one of them will result in wrong conclusions.There are many effective algorithms of association rules, among which the most classical one is Apriori algorithm. Indexes of evaluation include Support, Confidence, and Lift. Support (S): A→B represents the percentage of A∩B that is contained in transaction database D, that is, the probability of Based on the characteristics of the current survey of chronic diseases, the existence of antecedent and association rules cannot prove the causal relationship; thus, it is called Left-hand-side and Right-hand-side to avoid confusion. In this study, the screening conditions of association rules were set as follows: the min-support was 3.0%, the min-confidence was 50.0%, and the left-hand-side was 1. In combination with the research sample, this study further analysed the left-hand-side for 2 and 3 , to explore the correlation between a variety of chronic diseases.AAC included 19 diseases, which were weighted 1, 2, 3, and 6 points according to their severity. The age-adjusted score is 1 point for the age of 50 to 59 years, and 1 point is added for every 10 years. Finally, the 10-year survival rate was calculated according to the corresponding formula.Spatial autocorrelation mainly includes global spatial autocorrelation and local spatial autocorrelation.Global spatial autocorrelation analysis mainly uses Moran’s I coefficient to reflect the degree of spatial aggregation of attribute variables in the whole area. Moran’s I >0 indicates that the attribute variables have positive correlation in the study area; Moran’s I <0 indicates that the attribute variables have negative correlation in the study area, and Moran’s I = 0 suggests that the attribute variables are randomly distributed in the study area and there is no autocorrelation.Local spatial autocorrelation is used to analyse the spatial relationship between adjacent regions, and Moran’s I along with LISA  is used to reflect the spatial aggregation degree of attribute variables in local regions. For the case of area unit I, Ii >0 indicates high-high type  or low-low type , Ii <0 indicates high-low type  or low-high type .Stata 13.0 was used for sorting and screening data. Descriptive statistics analyses and chi-square test were performed by using SPSS 19.0. IBM. SPSS Clementine 12.0 was used to prepare the web graph, and Apriori algorithm. Spatial autocorrelation analysis was performed in OpenGeoDa9.5.As shown in The Chi-square test was used to compare the prevalence of chronic diseases and multimorbidity between urban and rural and between genders. Except for cancer and other malignant tumors and memory-related diseases, the differences of prevalence of chronic diseases and multimorbidity was statistically significant between genders, and the prevalence of female was generally higher than that of male. The prevalence of chronic lung diseases, stroke, kidney disease, and asthma of male was higher than that of female. In addition to liver disease, kidney disease, emotional, nervous, or psychiatric problems, there were significant differences in chronic diseases and multimorbidity between urban and rural, and the prevalence urban is generally higher than that in rural, and the prevalence of stomach or other digestive disease, emotional, nervous, or psychiatric problems, arthritis or rheumatism and asthma is higher in rural than in urban.The web graph analysis showed strong association between [Stomach or other digestive disease/Arthritis or rheumatism], [Hypertension/Arthritis or rheumatism] and [Hypertension/Heart attack] . A totalApriori algorithm was used to analyse the association among the chronic diseases. Under the conditions of min-support = 3%, min-confidence = 50%, and lift >1, and 11 association rules were selected . The supWith two left-hand-side, min-support, and min-confidence unchanged, 39 association rules were obtained, among which, 11 association rules with the one left-hand-side were excluded and nine association rules with confidence ≥ 60% and lift≥ 1.6 were selected .With three left-hand-side, min-support, and min-confidence unchanged, 42 association rules were obtained, among which, 39 association rules with the two left-hand-side were excluded and four association rules were selected .Based on the AAC scores, the severity of multimorbidity was categorized into three grades: mild, with AAC score of 0–1; moderate, with AAC scores of 2–4; severe, with AAC scores of ≥5. The AAC in 5186 (53.41%) elderly individuals of the sample was mild, in 3775 (38.88%) was moderate, and in 749 (7.71%) was severe. The survival rates of the three groups were evaluated by rank-sum test and revealed that higher comorbidity score was significantly associated with lower 10-year survival rate (p < 0.001).Moran’s I value is a weighted correlation coefficient similar to Pearson’s coefficient, which is obtained through the covariance of spatial units and requires the data to be normal. In this study, the prevalences of multimorbidity and chronic diseases were tested for normality and showed a normal distribution (p > 0.05).On spatial analysis of multimorbidity, the following three most relevant multimorbidity patterns of association rules were selected: [Asthma/Chronic lung diseases],  and . Results show that the prevalence of multimorbidity patterns for  followed a distinctly positive correlation distribution in China, while the prevalence of the other two multimorbidity patterns showed random distributions without spatial correlation distribution in China .Subsequently, we further analysed the spatial correlation of the prevalence of the three multimorbidity patterns in different regions, and the results are shown in An Analysis Report of National Health Services Survey in China” released in 2016. The possible reasons for this observation include higher life expectancy in females that results in longer period of illness, and also that among the elderly, the proportion of females who are widowed and live alone is higher than that of males, which may be associated with prominent psychological problems . This may be because patients with arthritis take non-steroidal anti-inflammatory drugs, which can lead to gastrorrhagia and other diseases . The secThe top three most relevant patterns from the association rule: [Asthma/Chronic lung diseases], ,  that were identified in this study have also been reported by other researchers. A study those participants from Beijing Medical Claim Data for Employees showed that the most prevalent disease pair was that of osteoarthritis and rheumatoid arthritis with hypertension. Ischaemic heart disease, hypertension, and osteoarthritis and rheumatoid arthritis constituted the most common triad combination . A NetheThe [Asthma/Chronic lung diseases] pattern has been noticed by many scholars in recent year , 31. In  pattern is of great concern to researchers. Vered Bieber et al.  showed tThe risk of coronary artery disease complications in patients with RA is 1.5–2.0 times higher than that of the general population . This stResults of the AAC analysis showed a lower 10-year survival rate in the elderly with more chronic diseases, further highlighting the harmful impact of multimorbidity.Finally, we conducted spatial autocorrelation analysis on the three selected multimorbidity patterns, which was helpful in observing the characteristics of multimorbidity in spatial distribution. The prevalence of the multimorbidity pattern [Asthma/Chronic lung diseases] was randomly distributed both globally and locally, indicating that the pattern was less affected by the cultural environment and more affected by the interaction between the two diseases. The prevalence of multimorbidity pattern  had “high-high” type in Shanxi and its surroundings, which may be related to the air quality in Shanxi province, where the dust-haze is severe. The prevalence of multimorbidity pattern  had “high-high” type in Heilongjiang province, a municipality of Beijing and its surroundings, and “low-low” type in Hunan province, in Guangdong province and its surroundings, which was roughly the same as the clustering area when the prevalences of hypertension, heart attack, and dyslipidemia were analysed separately. These results suggest that the environment, economy, and lifestyle factors have significant influence on this pattern.In addition, in this study, the spatial analysis of chronic diseases and multimorbidity did not combine the economy, population and climate, so the spatial distribution could only be observed, but the reason for such distribution was difficult to be found. In the following studies, we will further analyze and explain the spatial distribution of chronic diseases and multimorbidity based on specific factors.In conclusion, the prevalence of chronic diseases and multimorbidity is high among the elderly population in China, and is higher in elderly women. The negative effects of multimorbidity are serious. Health departments should determine the characteristics of different multimorbidity patterns and develop corresponding treatment and medication guidelines in accordance with this information. In prevention and treatment of chronic diseases and multimorbidity, regional factors should be taken into consideration, and corresponding measures should be formulated more comprehensively according to the specific cultural and environmental factors in the area.S1 File(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.


Conclusions: Once nurses have improved their knowledge, education, and beliefs/attitudes, SSC implementation may concomitantly increase. A continuing education program and clear guidelines are needed to promote SSC adoption in practice.Skin-to-skin, or chest-to-chest, contact (SSC) between newborns and their mothers is known as kangaroo mother care. The physiological and psychological benefits of SSC for infants and mothers are well established. The World Health Organization (WHO) recommends practicing SSC for term and preterm newborns. However, in Saudi Arabia, SSC is not practiced as widely as recommended. There is insufficient evidence of the nurses’ knowledge and attitudes regarding SSC in Saudi Arabia. The aims of this study were to describe and determine relationships between knowledge, education, beliefs/attitudes, and the implementation of SSC in Jeddah, Saudi Arabia. Thank You for Your Time and Kind Suggestion Methods: Cross-sectional descriptive data were collected from 40 nurses using an English-language version of a knowledge, beliefs/attitudes, education, and implementation questionnaire used by others. Results: The mean age of the nurses was 42.4 years (SD = 3.2), with a mean experience of 12 years (SD = 2.1). The mean total score of SSC knowledge was 13.6 (SD = 2.3), the mean of total score of attitudes/beliefs was 12.3 (SD = 3.1), the SSC education mean score was 17.1 (SD = 3.4), and the SSC implementation mean score was 17.0 (SD = 4.1). In total, 55% of the nurses were not sure of the impact of SSC on brain development in neonates, 45% could not interpret infants’ responses during SSC; 67% disagreed that it was the nurses’ responsibility to facilitate SSC, 37.5% were not aware of SSC guidelines, and 47% of the nurses had not received any continuing education on SSC in their units. Pearson correlations revealed a significant association between SSC implementation and nurses’ knowledge level (r = 0.297,  Skin-to-skin contact (SSC) between mothers and newborns, or kangaroo mother care (KMC), is defined as “placing the naked baby prone on the mother’s bare chest at birth or soon afterwards” . The WorThere have been several studies of nurses’ knowledge, beliefs/attitudes, education, and implementation of SSC. National studies conducted in the USA began in 2002 with Engler et al.’s study showing that 82% of 637 responding hospitals offered SSC to mothers who requested it and that the nurses’ knowledge of the benefits of SSC was poor, in which inadequate knowledge negatively impacted the nurses’ attitudes toward SSC . In the To facilitate SSC practice in Saudi Arabia, the knowledge and attitudes of the nurses across the country must be studied; however, to the best of our knowledge, no studies on SSC practices have been conducted in the city of Jeddah, which represents the western region of the kingdom.Objectives: The objectives of this study were to describe the nurses’ knowledge, education, beliefs/attitudes, and implementation of SSC, and to determine any relationships between them.Design: A cross-sectional correlational descriptive study was used to describe the nurses’ knowledge, education, beliefs/attitudes, and implementation of SSC and to determine the relationships between them.Setting: All nurses were recruited from an obstetric and pediatric department (NICU), labor room, and postpartum care unit at a university hospital. Period of recruitment was from 20 March 2018 to 5 April 2018.Participants: The participant population included nurses working in obstetric and pediatric units, which are units in a hospital where SSC between mothers and newborns is applied. A convenience sampling method was used to gain access to study participants. Data collectors were responsible for handing the surveys to nurses who agreed to fill in the survey and then collecting the surveys from them when they had completed it; alternatively, they could leave the completed survey in the head nurse’s office in their unit after completion. Consent was implied if the participants agreed to complete the survey and handed it back to the data collectors or head nurse of the unit. All nurses were English speakers.Variables and Measurement: The study variables were SSC knowledge, attitudes and beliefs, SSC education, and SSC implementation. The predictor variables were SSC knowledge, attitudes and beliefs, and SSC education, and the outcome variable was SSC implementation. The tool was a shortened (20 items) version of Engler et al.’s 2002 SSC survey of nurses’ knowledge, attitudes, and practices of SSC  by Vittner et al. The 20 items were divided into four dimensions: SSC Knowledge (five items), Attitudes and Beliefs (four items), SSC Education (five items), and SSC Implementation (six items). The five-point Likert scale responses ranged from Strongly Disagree (SD) to Disagree (D), to Neither Agree nor Disagree (N), to Agree (A), to Strongly Agree (SA). The Likert data were treated as continuous data in which 1 = SD, 2 = D, 3 = N, 4 = A, and 5 = SA. Thus, the possible range of scores for Knowledge was 5–25, for Attitudes and Beliefs 4–20, for Education 5–25, and for Implementation 6–30. The tool’s construct validity was established by conducting a principal component analysis, and the reliability of the subscales ranged between 0.79 and 0.90 ,17.Ethical Consideration: The study was reviewed and approved by the biomedical ethics research committee at the university hospital. Reference# 131-18.Bias: We controlled the non-response bias by choosing a short, simple survey that helped us to increase the participants’ response rate in a tertiary setting where nurses have a heavy workload. We chose a cross-sectional design, which allowed us to collect all responses at once to control any events that might affect the nurses’ responses. We controlled data collection bias by recruiting data collectors who were responsible for collecting the data and entering the data into the Statistical Package for Social Sciences (SPSS) program, then checking the entry with research assistance to avoid any potential bias from the researcher’s knowledge.Study size: A total of 44 nurses working in obstetric and pediatric units in the selected setting. We calculated our sample size using power analysis with 95 CI, margin error 5%, and population proportion of 50.p-values of <0.05 were considered significant. The dimension scores  were used for the correlations.Quantitative variables and statistical methods The statistical analysis involved descriptive statistics and Pearson product–moment correlations using SPSS, version 16.0. Frequency and percentage were used to describe the distribution of responses across the Likert scale for each item, and the score for each item was reported as an interval number. The mean ± SD was used to describe Likert data treated as continuous data. The Pearson correlation was used to identify the relationship between the study variables. Participants/descriptive data: A total of 40 nurses responded completely: 12 were from NICU, 13 from the labor room, and 15 from the postpartum care unit. In total, 50% of the nurses were Pilipino and the remaining were Indian, Saudi, and Egyptian, representing 30%, 15%, and 5%, respectively. All nurses were female with a mean age of 42.4 (SD = 3.2) years old, and average years of experience of 12 (SD = 2.1). Most participants held a Bachelor’s degree in Nursing (75%) and 25% had a diploma.of Likert-based responses on the nurses’ knowledge of SSC are shown in mean of the total score of the SSC knowledge dimension was 13.6 (SD = 2.3), the mean of the total score of attitudes/beliefs was 12.3 (SD = 3.1), SSC education mean score was 17.1 (SD = 3.4), and SSC implementation mean score was 17.0 (SD = 4.1).Main results: The number and percentage p-value = 0.03), SSC implementation and nurse’s attitudes , and SSC implementation and nurse’s education . A significant association was found between nurse’s knowledge, attitudes, and education ). Moreover, a significant association was found between nurse’s attitudes/beliefs and their education , as shown in To determine relationships between nurses’ knowledge, education, beliefs/attitudes, and implementation of SSC, Pearson correlation findings revealed a significant positive association between implementation of SSC and the level of nurse’s knowledge (r = 0.297, Key results: The findings showed that nurses had a moderate level of knowledge, positive attitudes/beliefs, moderate education, and moderate implementation levels. The findings also revealed a significant association between nurse’s knowledge, attitudes/beliefs, SSC education about SSC, and nurses’ perceptions toward SSC implementation in a tertiary hospital.Limitations: There are several limitations to this study. A relatively small sample size of participants was used, which was due to the selection being limited to pediatric and obstetric units, which have a smaller number of staff compared to other units. Furthermore, the participants were selected from only one setting in the city of Jeddah, which will affect the generalizability of the findings. Finally, based on the study design, a causal relationship cannot be inferred. However, the results are consistent with other studies conducted in different cities in Saudi Arabia.Interpretation of the nurses’ SSC Knowledge: The results indicate a very low knowledge level of SSC in obstetric and pediatric unit nurses. Nurses demonstrated uncertainty about their information regarding infants’ physiological and psychological responses during SSC and how they assessed or interpreted these responses. Moreover, most of them were not aware of the neurological benefits of SSC for infants’ brain maturation. The study results are comparable to Al-Shehri and Binmanee in Riyadh, Saudi Arabia, who found that nurses were uncertain about physiological responses for low-weight infants . The stuInterpretation of nurses’ attitudes/beliefs toward SSC: Nurses have a relatively positive attitude toward SSC benefits for the newborn, which is comparable to several studies that showed a positive attitude toward SSC benefits in mother–infant bonding ,20,22,24Interpretation of Nurse’s SSC Education: Nurses showed a moderate level of education, awareness of guidelines in their units, regular assessment, the measurement of SSC responses, and attending educational courses or conferences on SSC. However, most of the nurses’ responses indicated a lack of SSC continuing education in their units, which is comparable to findings of a perinatal nurses survey, which showed that most of the nurses did not have continuing-education services in their units regarding SSC practices . A lack Interpretation of nurses’ perceptions toward SSC implementation. Nurses demonstrated moderate implementation of SSC in their units. Obstetric and pediatric units use SSC regularly with eligible neonates with good management of SSC practices, but there are no clear guidelines and protocols updated with current evidence. This finding is in agreement with several previous studies conducted worldwide and clearly shows the importance of having clear guidelines and protocols to facilitate SSC adoption and implementation of the practices ,19,24,28The association of nurses’ knowledge, education, and attitudes/beliefs with SSC implementation aligned with several previous studies, which found that confidence increases when the level of knowledge increases  and posiThere are conflicting responses regarding SSC implementation, while guidelines and protocols were unclear, not enough training and education was received, and the physician did not support SSC in their unit’s SSC practices regularly with eligible neonates. This might be explained by the Saudi Ministry of Health’s initiation toward practicing SSC through a baby-friendly hospital policy that encourages hospital representatives to implement SSC in each hospital, but without the complete application of the policy by setting up a training and education plan for the staff and providing a clearly written policy with details of procedures for staff to follow and make it relevant to them in each unit policy and procedure book.Generalizability: This study’s findings cannot be generalized for all obstetric and pediatric unit nurses because the study was conducted in one setting with a very small number of nurses working there. We cannot generalize the findings because of the nature of the setting; the study setting was a university hospital, which always has an educational role that affects its services. Moreover, 50% of the participants were Pilipino, which might also affect the generalizability, because heterogenicity of the sample was not met. However, our findings are highly applicable to nursing settings characterized by the large presence of Pilipino staff and teaching hospital.Recommendation: Based on the findings, we recommend providing staff with continuing education on the updated evidence of SSC and a training lab to support the nurses’ skills in the implementation of SSC for term/preterm and NICU newborns. This study also recommends establishing clear policy and guidelines for the use of SSC in the policy and procedure handbooks in each pediatric and obstetric unit. During the staff orientation period, we recommend using SSC workshops to enhance the nurses’ level of knowledge and review the policy and guidelines to foster SSC adoption appropriately in practice. Regarding future studies, it is recommended that a quasi-experimental study is conducted to measure the changes in knowledge level and beliefs on SSC after intensive educational courses or workshops. Furthermore, this study should be conducted with a larger sample size in multi-settings in Jeddah City.Skin-to-skin contact between newborns and mothers is evidence-based practice that should be adopted optimally according to the recommendations from the WHO and other national and international organizations. Nurses’ knowledge, education, and beliefs are important facilitators for optimal use of SSC, however, until now, many studies in Saudi Arabia have shown inadequate levels of knowledge and unclear policy and guidelines in the health care setting that impede the adoption of SSC and also have negative effects on the nurses’ beliefs and attitudes. This study provides updated information regarding the nurses’ knowledge, beliefs, and education that have a direct influence on the implementation of SSC in Jeddah, Saudi Arabia.


Randomly selected samples  were studied according to the ESSE-RF protocol. Lipoprotein parameters were estimated by routine methods. Statistical analyses were performed using R software (v.3.5.1). The overall dyslipidemia prevalence was 76.1% (76.9/75.3% for men/women). In women, total cholesterol (TC) and low-density lipoprotein (LDL)-C levels gradually increased with age ; in men, they reached a maximum by 45–54  and then decreased. No differences in high-density lipoprotein (HDL)-C in men of different ages were found, but slight decreases in HDL-C and apo AI were observed in women by 55–64 years. No pronounced associations between education and lipid levels in men were observed; higher-educated women showed significantly better lipoprotein profiles. Similar associations between lipids and income level were detected. Women from rural areas had higher TC and triglycerides than urban residents. Regardless of sex, rural residents had higher HDL-C and apo AI, and reduced apo B/apo AI. Conclusion: Information on the peculiarities of dyslipidemia prevalence and lipoprotein profile depending on sex, age, residential place, and socioeconomic status is useful for assessing the global ASCVD risk, and for risk modeling based on national data.This study aimed to describe the dyslipidemia prevalence and pattern among adult populations from different regions ( Atherosclerosis-related cardiovascular diseases (ASCVDs) are the leading cause of death: about 17.9 million people died from these diseases in 2019, representing 32% of all global deaths  . Apo AI and apo B concentrations were measured by an immunoturbidimetric assay; Lp(a) level was determined with a latex particle-enhanced turbidimetric immunoassay, which does not depend on the apo(a) isoform size.Blood was drawn at the regional polyclinics after patients’ overnight fasting using the standard technique. Serum was obtained by low-speed centrifugation  level ≥ 30 mg/dL were regarded as elevated ones.n (%). The Mann–Whitney U test was used to compare the distributions of continuous variables and the two-sided Fisher’s exact test was used to compare categorical variables. For pairwise comparisons, when there were more than two samples, Holm’s correction for multiple comparisons was applied. The prevalence of dyslipidemia was standardized by sex and age, where 2010 All-Russian Population Census data were used as a reference. We considered outcomes statistically significant if the p value was <0.05.Statistical analyses were performed using R software (version 3.5.1). Continuous variables are presented as mean (M) and standard deviation (SD) if Pearson’s nonparametric skewness coefficient was <0.2. Skewed parameters are presented as median (Me) and interquartile range . Categorical variables are presented as p < 0.001).The most prevalent type of dyslipidemia was hypercholesterolemia (TC level ≥ 5.0 mmol/L), which, on average, was 58.2% and varied from 50 to 67% depending on the region . Atherogp < 0.0001).Variations in the TC level were largely due to the content of cholesterol transported within LDL . At the p = 0.013).Both in men and women, a significant increase with age was also observed in the level of TG . Women hThe level of HDL-C in women in the entire age range was significantly higher than in men . No diffp = 0.004).There were no differences in TG level between men and women with primary education; in women, a higher level of education was associated with a reduced TG level. At the same time, men with secondary education were characterized by the highest TG level, whereas in women, it decreased with the level of education.The highest level of Lp(a), regardless of sex, was found in subjects with primary education (higher in women than in men); at the same time, there were no differences in men differing by the level of education, whereas in women with higher education, the level of Lp(a) was significantly lower than in those with primary education.p < 0.0001 for HDL-C, and 1.65 ± 0.39 vs. 1.60 ± 0.39 g/L; p = 0.032 for apo AI).Regardless of the education level, women had an expectedly higher level of HDL-C and HDL major protein apo AI. There were no differences in HDL-C level between men with different education levels, but serum apo AI concentration appeared to be highest in the group having secondary education. On the contrary, in women, both HDL-C level and apo AI concentrations were significantly higher in subjects with higher education compared to those who had primary education .p = 0.037). The results of the analysis of the relationship of Lp(a) level with the income showed its gradual decrease with the level of income for men, with differences only between low- and high-income subjects for women.Women from the low-income group had the highest levels of TC, LDL-C, TG, and apo B as compared with the high-income participants . In the No differences in HDL-C level were detected between men with different income levels. On the contrary, the HDL-C level in women increased with their well-being. Apo AI showed an increase with income regardless of gender, and these changes were realized at lower values of apo B/apo AI ratio in high-income individuals regardless of gender .This study was undertaken to compare the blood lipids levels in subjects of different sex and age in the representative population samples from 13 regions of the Russian Federation. It should be noted that these regions do not represent the Russian population as a whole; however, they have been selected to reflect different climates, geographical locations, levels of industrial development, and ethnic diversity, and were representative for each particular region.Numerous papers have reported the data on lipid profile and dyslipidemia prevalence in different countries and regions worldwide, indicating the real need and importance of having data on the national characteristics of these disorders, including socioeconomic, behavioral, metabolic, and hereditary peculiarities ,16,17,18The prevalence of elevated levels of TC and LDL-C levels and their mean levels in the regions of Russia turned out to be higher than in the USA ,20. A coThere are accumulating data showing that the burden of ASCVD and dyslipidemia is increasing across developing countries: while age-specific ASCVD in many high-income countries is declining, the prevalence of plasma lipid disorders in the Asia-Pacific region is rising ,17; simiThe multidirectional trends in the lipid profile parameters between industrially developed and developing countries have been revealed. In the United Arab Emirates, men had higher mean levels of TC and LDL-C than women did, which decreased with age in both groups. Similarly, men had higher mean TG levels than women did, which decreased sharply after 50 years of age but increased after the same age in women. The mean HDL-C level also varied depending on sex and age .In the analysis of trends in serum TC levels for adults aged 25+ in 199 countries and regions from 1980 to 2008, it was demonstrated that in 2008, serum TC was highest in the high-income region including Australasia, North America, and Western Europe, whereas the lowest TC levels were detected in sub-Saharan Africa ,19 showeBesides lipid parameters, in several regions included in the ESSE-RF study, we were able to measure the levels of major apolipoproteins apo AI and apo B and to calculate the apo B/apo AI ratio. In men, there was a uniform increase in the prevalence of a high apo B/apo AI ratio with increasing age, while in women, the prevalence did not change up to 44 years, with a sharp increase in people over 45 years; at the same time, if, in men, the prevalence of apo B/apo AI ≥ 1.0 increased by 2 times by 55 years, then in women at this age, the prevalence of a high apo B/apo AI ratio was already 4 times higher than in young people. There was no clear correlation between the level of education and the level of income for either men or women. At the same time, in both men and women, the frequency of increased apo B/apo AI ratio (≥1.0) in urban residents was 1.5–2 times higher than in rural ones . Case-coLp(a) is a strong cardiovascular risk predictor, and an elevation in its level  is a hereditary condition associated with increases in atherogenic, inflammation, and prothrombotic risk, for what should be considered as an independent ASCVD risk factor. Using ESSE-RF data, a significant association of Lp(a) serum level exceeding 9 mg/dL with the presence of myocardial infarction and coronary artery disease in adults aged 25–64 years has recently been shown . A prospSanto et al. (2019) showed that, in men, the higher the socioeconomic or educational status, the higher the TC, LDL-C, and TG levels and the lower the HDL-C levels, even after controlling for age, body mass index, arterial hypertension, smoking habits, and physical activity. In women, higher socioeconomic strata were associated with higher levels of TC and HDL-C, whereas lower levels of TC, LDL-C, and TG were found in individuals with higher education. In addition, individuals from the upper socioeconomic strata had higher levels of TC and LDL-C and were more than twice as likely to have multiple blood lipid changes .Lara and Amigo  performeIn our study, we did not obtain any pronounced associations between educational status and lipoprotein parameters in men, while women with higher education showed a significantly better lipid profile; the same trends were found when analyzing associations between lipids and prosperity. The influence of socioeconomic factors on lipid levels has been shown in epidemiological studies performed in developed American and European countries, also with different results in men and women: TC levels decreased in a gradient fashion with increasing socioeconomic and educational level; in women, these changes manifested to a greater extent. Thus, it is still not entirely clear whether there are differences in blood lipid levels in adults based on education status. Indeed, if, in Russia, there is a certain consistency between the level of education and income—the higher the education, the higher the well-being of people, in developing countries—there is some discrepancy between a low level of education and growing incomes allowing the purchase of unhealthy food . NonetheTaken together, our and the literature data indicate that every country or region has its own characteristics that determine the magnitude of epidemiological burden due to dyslipidemia and its atherosclerotic consequences. Wide variations in the levels of lipoproteins and in different types of dyslipidemia prevalence, which depend on sex, age, race/ethnicity, level of education and income, country, and place of residence, have been found. This means the need for specific information reflecting these features that could be obtained from population-based epidemiological studies, both cross-sectional and prospective ones. Thus, strategies aimed at correcting dyslipidemia should be developed by taking into account sex and age variations, as well as socioeconomic and regional differences.As a strength of our study, the possibility of measurement and analysis of the protein compounds of lipoproteins in several regions included in the ESSE-RF study should be pointed out, which sets our study apart from almost from all abovementioned.Among the limitations of this study, we should indicate that the sample from 13 regions was not representative for the male and female population of the whole country, but for each region participating in the ESSE-RF study. In addition, our cohort did not include seriously ill patients, because data collection at home was not provided. In addition, persons leading an antisocial lifestyle were not included.To conclude, in this paper based on the ESSE-RF study, we analyzed and found some peculiarities on lipids and lipoprotein profiles and the prevalence of atherogenic dyslipidemias in the general population from several Russian regions differing in climate and geography, taking into account sex, age, education and income level, as well as settlement . These data indicate the need to develop ASCVD preventive strategies based on our own data.


Internet gaming disorder (IGD) has become a serious public health problem in East Asia, and studies have reported IGD to be significantly associated with anxiety, but no causal relationship between the two has yet been demonstrated. Children are at high risk of developing IGD, however, previous studies have principally focused on the condition in adults and adolescents and reported non-clinical samples. A large-scale survey is needed to research and evaluate IGD and anxiety in children and adolescents to understand the current situation of IGD in children and explore the impact of IGD on anxiety.A cross-sectional study using an online questionnaire was conducted between March 1 and July 31, 2021. A total of 10,479 school children and adolescents in the western provinces of China were selected by convenience sampling. A questionnaire was used to collect data anonymously. The questionnaire covered IGD and the Revised Children's Manifest Anxiety Scale (RCMAS). Welch's ANOVA Test and Games-Howell test were used to test for differences in anxiety levels between IGD groups. Poisson regression analysis was used to further investigate the key predictors of IGD.n = 334) (95% CI: 2.9–3.2%) were classified as at high risk of presenting with IGD, 71.1%  (95% CI: 70.3–72.0%) were classified as low-risk players, and 25.7%  (95% CI: 24.9–26.5%) were classified as non-gaming. The average RCMAS score was (7.18 ± 7.534). The high-risk group had a higher total score RCMAS, as well as scoring higher in its three dimensions. Regression analysis using gender, age, and total RCMAS score as independent variables, and risk of IGD as a dependent variable showed that the odds ratio (OR) for gender was 2.864 (95% CI: 2.267–3.618), and the OR for total RCMAS score was 1.101 (95% CI: 1.087–1.114). The OR for age was not statistically significant.3.2% of participants (Anxiety was a predictor of IGD, with statistically significant group differences in total anxiety, as well as the dimensions of physiological anxiety, social correlation, and sensitivity. The timely assessment of anxiety in children and adolescents, training social skills, and facilitating effective integration into society could be effective ways of reducing the incidence and impact of IGD. With the rapid development of the Internet, the internet gaming market has also grown rapidly, bringing China US$12 billion in revenue in 2013 alone . HoweverPrevious studies reporting the evaluation of IGD have used self-reported continuous scales to determine the level of addiction. Few studies report the use of cut-off values or diagnostic criteria to determine the true clinical significance of IGD. Any IGD score that does not reach clinical diagnostic significance may not be representative of the detrimental impact of clinical symptoms. Further, the number of online gamers is huge, and many have a normal level of social function. This may in part be due to the lack of a clinical diagnosis for IGD.Anxiety is one of the most common mental health disorders treated in primary care , with anChildren are at high risk of IGD. Previous studies have mostly focused on adults and adolescents and studied non-clinical populations. Few studies have investigated IGD in both children and adolescents simultaneously –28, and The study inclusion criteria were: (1) children aged between 9 and 18 years; (2) children whose parents and themselves agreed to participate in the study; and (3) children who were able to complete the questionnaire independently. The study exclusion criteria were: (1) children with a medical diagnosis of a learning disability, developmental delay, or dyslexia; or (2) children who did not want to participate in the study. The samples for this study are from 12 primary and middle schools. The researchers contacted the principal of each school, and after obtaining the principal's approval, we went to the school to recruit samples.Demographic data collected included the participant's gender, age, family structure, whether they were an only child, the education level of their parents, and their household monthly income.The nine-item Internet Gaming Disorder Scale Short Form (IGDS-SF9), developed by Pontes and Griffiths, is a short self-report scale that is used to measure the severity of IGD based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria , 30. ConThe Revised Child Manifest Anxiety Scale (RCMAS), published by Reynolds and Richmond , was basThe study was conducted over a large geographical area, between March and May, 2021. A total of 12 primary and middle schools from the region participated in the survey. Before collecting data, study information was sent to students, asking them to participate after obtaining written informed consent from their parents or themselves. The survey was predominantly conducted online survey, with some paper copies of the questionnaire provided to those who requested this format.All procedures were conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Biomedical Ethics Committee of West China Hospital of Sichuan University (Ethics Number: 2019907). All participants were informed about the study and written informed consent was provided by the parents or legal guardians. In addition, participants and their parents were informed that participation was anonymous, all data was to be used only for scientific research, and they had the right to withdraw from the study at any time.Incomplete questionnaires were excluded from the analysis. The results of the electronic questionnaire were directly exported. Data from the questionnaires completed on paper were entered into Epidata 3.1 using a two-person entry method. These two repositories were then merged into a single spreadsheet in SPSS 24.0 for statistical analysis. Frequencies were used to report participants' sociodemographic characteristics and IGD scores. RCAMS scores were reported using the mean, standard deviation, and interquartile range. For unordered categories data, such as gender, family structure and whether one-child or not, Mann—Whitney U was used to compare the differences in rates between groups, while for ordinal categorical data, such as age, family income, and parents' education level, the Spearman correlation test was used to compare the differences in game addiction among the subjects under different demographic characteristics. The average scores of anxiety levels between different IGD groups are tested for homogeneity of variance. If the variances are uniform, analysis of variance is used to compare the differences in anxiety levels between different groups. If the variances are not uniform, Welch's ANOVA Test is used to compare different gaming addiction groups. If the difference in anxiety levels between the groups is significant, the Games-Howell test  will be A total of 10,501 participants completed part of the survey. After excluding invalid questionnaires, the remaining 10,479 respondents were included in the analysis. Invalid questionnaires were defined as those having the same responses for more than 90% of the answers except for basic demographic data. The age range of participants was 9 to 18 years, most of whom were in the 13–15 years group (54.19%), with uniform gender distribution , and most of them were the only child in the household (60.21%). See Harman's single factor test was used to test for common method bias . The pron = 334) (95% CI: 2.9–3.2%) were classified as high risk, 71.1%  (95% CI: 70.3–72.0%) were classified as low risk, and 25.7%  (95% CI: 24.9–26.5%) were classified as non-gamers.The prevalence of IGD was estimated based on the IGDS9-SF results. 3.2% of participants . The worry and oversensitivity subscale was the highest-scoring subscale see .post-hoc testing, and the results reported in P < 0.001).Due to there being unequal variance across groups, Welch's ANOVA was used, and the Games-Howell test was used for 2 = 1,285.823, p = 0.001) and parallelism test , indicating that the model did not pass the parallelism test. Informed by the clinically significant distinction made by the IGD score, the combination of non-gamer and low-risk groups were defined as a “non-high-risk group” and assigned a value of 0, and the high-risk group alone was assigned a value of 1. Poisson regression was used with all dependent variables to investigate group differences in gender, age, and total anxiety score, and the results are reported in 2 of 293.261 (P < 0.001). These results show that gender and total anxiety score were predictive of IGD.As the dependent variable had three levels , an ordered categorical logistic regression was performed, whereby the non-gamers group was assigned a value of 0, the low-risk group assigned a value of 1, and the high-risk group assigned a value of 2. Simultaneous forced entry was used to include all variables that showed group differences in the previous analysis. No collinearity was found between variables (VIF <10). The results of the model fitting were as follows: model fitting information  compared to female 2.0%) respondents. This is consistent with the results of previous work  reportin.0% respoG = 0.068) correlation between age and IGD. However, when participants were divided into non-high-risk and high-risk groups for multiple regression, age did not show any effect on IGD. Previous work  The results of our study showed that gender and anxiety predicted IGD, but we did not examine any potential sex-specific interactions with types of anxiety, which limits our discussion of our results; (2) A self-report tool was used, which may be affected by social desirability bias causing participants to underestimate their own gaming addiction. There are few objective measures of gaming addiction, and their use may not be feasible on the scale of this study.Anxiety was a predictor of IGD, with statistically significant group differences in total anxiety, as well as the dimensions of physiological anxiety, social correlation, and sensitivity. The timely assessment of anxiety in children and adolescents, training social skills, and facilitating effective integration into society could be effective ways of reducing the incidence and impact of IGD. Future researches can explore sex-specific pathways to IGD, for example, if IGD prevalence in males and females could be predicted by different types of anxiety?The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Biomedical Ethics Committee of West China Hospital of Sichuan University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.XH and H-xS: conceptualization, methodology, writing—reviewing and editing, and writing original draft. H-qL: data collection, data analyses, and writing—reviewing and editing. W-jG: data collection, data analyses, and writing–reviewing. DL: methodology, data analyses, and writing—reviewing. J-jX: conceptualization, methodology, writing-reviewing, and supervision. All authors contributed to the article and approved the submitted version.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.


Dietary polyphenol exposure is known to change protein saliva composition in rodents, but less is known in humans. The present study aimed to assess the relationship between saliva protein composition and adherence to Mediterranean Diet (MD) and polyphenol intake levels. Participants were assessed for their dietary habits, which were converted in Mediterranean adherence level, according to Mediterranean Diet Adherence Score (MEDAS) score. Total polyphenol and total flavanol intakes were extrapolated from dietary data, using Phenol explorer database. Whole saliva was collected, and proteins were separated by SDS-PAGE. Salivary S-type cystatins were highly expressed in the group with medium adherence to MD, being positively correlated with wine intake in overweight individuals. The association between salivary amylase and MD adherence also depended on Body Mass Index (BMI), with a positive association only in normal weight individuals. Polyphenol intake was positively associated with S-type cystatins levels, particularly when flavanols were considered separately. These results show that saliva relationship with MD adherence depend on BMI, suggesting that normal weight and overweight individuals may have different salivary responses to diet. Moreover, these results reinforce the link between saliva and dietary polyphenols (flavanols) levels, leading to the hypothesis that salivary proteome can have a role in polyphenol-rich foods acceptance. Mediterranean Diet (MD) is accepted as one of the most healthy and sustainable dietary patterns. High adherence to MD has been shown to relate with several different health benefits, such as obesity reduction, diabetes, and cardiovascular protection, among many others ,2. DespiThe MD dietary pattern is characterized by the intake of considerable amounts of vegetables, fresh fruits, and whole grain cereals, with moderate to low amounts of products of animal origin, having extra-virgin olive oil as the main source of fat. In addition, low to moderate consumption of wine, at main meals, is also present in MD dietary pattern. Altogether, this makes MD a polyphenol rich diet . PolypheSaliva is a biological fluid that plays numerous roles in the oral cavity, participating in oral food perception . The intBesides the potential effect of saliva on acceptance and intake of polyphenol rich foods, it should also be simultaneously considered the potential effect of polyphenols ingestion in salivary protein composition. In different animal studies, it was observed that increasing the levels of dietary tannins, a particular type of polyphenols, results in changes in salivary proteome ,14. AlthFor all that was stated above, namely the potential influence of saliva protein composition in the acceptance of polyphenol rich diets, on one hand, and the possible effect of polyphenol intake in saliva protein composition, we hypothesize that the adherence to a Mediterranean dietary pattern is associated with polyphenol intake and with saliva composition. This study was performed with the general objective of assessing how MD adherence is related with saliva protein composition. Since MD food products are rich in polyphenols, two specific objectives were considered: (1) to assess the differences in salivary protein profile among groups with different adherence levels to MD; and (2) to investigate if salivary protein profiles relate with the levels of total polyphenols and flavanols in diet.One hundred twenty-two adult individuals  participated in this study. Only individuals not reporting oral or nasal health problems, nor taking medication, were considered. Participants were instructed to arrive at test room between 10:00 a.m. and 11:00 a.m., at least 1 h and 30 min after breakfast intake, and without eating or drinking anything other than water, after that.2) was used to classify individuals in underweight, normal weight, pre-obese, and obese, accordingly: BMI < 18.5; 18.5 < BMI < 24.99; 25 < BMI < 29.99; and BMI > 30 [Height and weight were measured according to the European Health Examination Survey procedures, with participants evaluated in a stand position wearing light cloths and barefoot. Height and weight were accessed using a portable stadiometer (Seca 214) and a digital scale accurate to the nearest 0.1 kg (Seca 803), respectively. Body mass index (BMI) . Frequency of food consumption, over the previous 12 months, was assessed using a self-administered, semi-quantitative food frequency questionnaire (FFQ), validated for Portuguese adults . For catSince the FFQ does not access polyphenols consumption, an extra questionnaire, developed using the same model of the validated FFQ was applied, in which 50 fruits and vegetables were presented individually. The amount (per day) of each food item was calculated by multiplying the frequency of consumption (number of days per month/week) by the weight of the standard portion size of the food-item, as previously described for FFQ. The amounts of polyphenol and flavanol of each food considered  were extracted from a polyphenol database . Daily ig for 30 min at 4 °C. The supernatant was recovered and stored at −80 °C until subsequent analysis.Unstimulated saliva was collected, from each participant, by accumulating all saliva produced in the mouth and spitting it to a tube, maintained on ice, at regular intervals, for 3 min. Before saliva collection, individuals were asked to rinse their mouth with water to remove residual saliva and/or any food debris. After collection, saliva was transported, on ice, to laboratory, where it was frozen at −28 °C. With the aim of removing mucins, cells and other solid material, saliva samples were thawed on ice and centrifuged at 13,000 Saliva flow rate was calculated by assuming a density of 1.0 g/mL for saliva. Tubes containing saliva were weighed and the weight of the empty tube was subtracted. In order to calculate flow rate, the final volume was divided by the number of minutes of saliva collection. Saliva pH was measured using a calibrated pH meter  and recording to two decimal places. The Bradford method was used for total protein concentration determination. Bovine serum albumin (BSA) was used as standard, and the method was carried out in microplates of 96-weels, which were read at 600 nm in a microplate reader .www.gelanalyzer.com, accessed on 1 May 2019) and values of volume for each band were normalized for analysis of the volume percentage of each protein band. Molecular masses were determined in accordance with molecular mass standards  run with protein samples.Each saliva sample was run in 14% polyacrylamide gels in duplicate. The volume of each sample used corresponded to 7.5 µg total protein. Samples were mixed with sample buffer and run on each lane of a mini-gel  using a Laemmli buffer system, as described before . Protein® kit was used to determine the enzymatic activity of salivary amylase according to the manufacturer’s recommendations and following the procedure described before [A Salimetricsd before .Exploratory analysis consisted of means, standard deviation, medians and quartiles. Age, BMI and the total amount of polyphenol intake were compared among MD adherence groups using One-way ANOVA. The relationship between the adherence to MD diet and total polyphenol consumption was accessed using the Spearman correlation test between total Med scores and total polyphenol daily intake. The differences between sexes in MD adherence was compared using the Chi-squared test.Salivary bands A-H, I1, I2, J, and K, and amylase/protein (U/mg) concentration were compared between MD groups and BMI groups using the Two-way ANOVA test, as well the interaction effect MD groups*BMI groups. The results of Levene’s equality of variance and normality tests were evaluated as ANOVA assumptions. A Bonferroni-type adjustment was made to prevent alpha inflation; the effect size and power of the test were also examined for interpretability purposes.Principal component analysis was used to estimate the number of latent variables emerging from the salivary SDS-PAGE bands , amylase/protein (U/mg), and flavonoids and polyphenol intake, to derive optimal non-correlated components among the parameters. As the variables showed moderate correlations, the Oblimin rotation was performed. The overall Kaiser-Meyer-Olkin (KMO) measure and Bartlett’s test of sphericity were examined which are required for a good principal component analysis, and the decision of the number of components to be retained was based on eigenvalues, total of explained variance and Scree plot examination. Statistical analysis was performed using SPSS 27.0 software.The higher percentage of individuals participating in this study presented medium adherence to MD pattern (62.3%), with 14.8% of the individuals having poor and only 22.9% high adherence, respectively.p = 0.0005)  .p = 0.006; Chi-squared test).When the three groups of MD adherence were compared for age or BMI, no differences were observed. Concerning sex, a higher adherence was observed in women , comparatively to men  , with a medium effect size , with a medium effect size.According to the results of the Two-way ANOVA test, a significant effect of MD adherence groups was observed on band K (previously identified to contain cystatins ): Group ect size . Additiop = 0.036; N = 70 and rho = 0.231; p = 0.053; N = 70 for non-olive oil fat and wine, respectively). Considering only obese individuals the strength of the correlation increases and in the case of wine, it becomes statistically significant .To better understand the reason for higher levels of band K in the group with medium MD adherence, an association between the levels of this band and the consumption of foods, considered in each of the 14 items of MEDAS scale, was assessed. Correlations were observed for non-olive oil fats and wine, but only considering overweight individuals  = 273.4; p < 0.0001). PCA retained five components that had eigenvalues greater than one and which explained 57% of the total variance, as confirmed by visual inspection of the scree plot , total polyphenol, and flavonoids intake. The suitability was assessed prior to analysis, and the inspection of the correlation matrix indicated those variables that had at least one correlation coefficient greater than 0.30. The KMO measure was 0.56, and the Bartlett’s test of sphericity was statistically significant  individuals. Cystatins are cysteine protease inhibitors, for which an association with diet and oral food perception has already been observed in different studies cyanidins, which are responsible for bitterness and astringency , reinforThe relationship between MD adherence and saliva was observed also at the level of salivary amylase. As in the case of cystatins, this relationship was also influenced by BMI, with increasing levels of the protein observed only in normal weight individuals. It could be hypothesized that such increase with higher levels of MD adherence could be related with the increased levels of polyphenols associated, since salivary amylase was one of the proteins induced by polyphenol (tannin) intake ,32. HoweThe effect of BMI in salivary amylase is particularly interesting. Some controversy exists if overweight/obese and normal weight individuals differ in salivary amylase amounts. Whereas some studies observed higher levels of amylase in the whole saliva of obese ,37, otheFrom our knowledge, this is the first time that saliva is studied in the context of MD diet. The results of this study show association between saliva protein composition and this dietary food pattern, but this appears to differ in function of the food items contributing to that adherence level, showing that different salivary proteins can better indicate the intake level of particular foods or food groups, rather than indicate the total level of adherence.It seems to be the flavanol group that mostly contribute to the relationship between saliva and polyphenol intake. Salivary cystatins appear to have potential as biomarkers of these bitter/astringent compounds intake. Nevertheless, it is important to highlight that the unbalanced number of individuals belonging to each MD adherence group, due to different distribution by each group, is a limitation, due to the reduced number of participants from the high and low adherence groups.One interesting observation, in this study, is the influence that BMI has in the relationship between saliva and diet. This is particularly relevant, not only because it shows that overweight individuals can respond to diet differently than normal weight ones but also because it reinforces the need of considering BMI when studying saliva.


Nivolumab and pembrolizumab are the standard treatments for patients with advanced non-small-cell lung cancer (NSCLC). While there are reports on several inflammatory indices and the prognosis of patients with cancer, no study has combined baseline medication with the neutrophil-to-lymphocyte ratio (NLR) to predict clinical outcomes. This study investigated the efficacy of baseline medications plus NLR to predict the effectiveness of nivolumab and pembrolizumab in a real-world clinical setting.We conducted a single-center retrospective observational study of consecutive patients with advanced NSCLC who received nivolumab or pembrolizumab as first-line, second-line, or beyond treatment between December 2015 and November 2018 at the National Cancer Center Hospital in Japan. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The drug-based prognostic score for baseline medications plus NLR was weighed based on the regression β coefficients. The multivariable Cox proportional hazard model was used to assess the association between the prognostic score-stratified groups and survival outcomes.P = 0.031). In contrast, no association between these prognosis groups and PFS was observed.In total, 259 patients were evaluated in this study. A prognostic score calculated from the baseline medications plus NLR was used to categorize the patients into good (score 0), intermediate (scores 1–2), and poor (scores 3–6) -prognosis groups. The multivariable Cox proportional hazard model revealed a significant association between the poor-prognosis group and reduced OS. The hazard ratio of OS was 1.75 (95% confidence interval: 1.07–2.99; The findings suggest that the baseline medications with nivolumab or pembrolizumab plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC and could be used as a prognostic index for poor outcomes. However, to ascertain the clinical application of these findings, these concomitant medications need further validation in a large-scale multicenter study. The Global Burden of Disease 2016 study estimated the burden of tracheal, bronchial, and lung cancers at ~36.4 million  consecutive patients aged ≥ 20 years who were diagnosed with postoperative relapse or unresectable stage III and IV NSCLC; 2) patients who had received at least one course of nivolumab monotherapy  or pembrolizumab monotherapy (200 mg/kg bodyweight every 3 weeks) administered as first-line, second-line, or beyond treatment between December 2015 and November 2018; and 3) patients without complications or prior history of chronic or recurrent autoimmune disease and interstitial pulmonary disease. The treatment schedule and follow-up were modified at the clinician’s discretion according to the toxicity profile of each patient. Clinic visits and imaging evaluations were conducted every 6–8 weeks, starting at treatment initiation, according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria .The exclusion criteria were as follows: 1) history of prior administration of any ICIs and/or investigational drugs as part of a clinical trial or at a previous hospital before the investigation period; 2) discontinuation of treatment due to death or hospital transfer during the first 6 weeks after ICI treatment initiation, or only the first cycle of ICI because of disease progression or adverse events; 3) lack of baseline laboratory data (within 1 week before ICI treatment initiation), and 4) study participation shorter than 6 weeks .The study protocol was approved by the National Cancer Center Institutional Review Board  in Japan. The study was conducted in accordance with the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research involving Human Subjects by the Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labour, and Welfare of Japan. Acquiring written or oral informed consent from participants was waived because of the retrospective nature of the study. Accordingly, we used an opt-out method through the official website of the National Cancer Center Hospital.Research members from Keio University retrieved the patients’ data from electronic medical records held at the National Cancer Center Hospital. Patients’ baseline age, sex, cancer stage, Eastern Cooperative Oncology Group performance status (ECOG PS), chemotherapy regimen, treatment line, and medication history were extracted from physician and pharmacist records within 30 days of oral or intravenous administration before the initiation of ICI treatment. In addition, the routinely available laboratory data before ICI treatment initiation and the date of progression and death at the time of ICI treatment initiation were also collected. Patient records were then anonymized prior to data analysis by three investigators. In the present study, baseline concomitant medications were categorized as follows: corticosteroids , PPIs (yes or no), antibiotics (yes or no), metformin (yes or no), fibrates (yes or no), statins (yes or no), and NSAIDs (yes or no). We focused on the NLR at baseline (defined as the most recent blood count within one week before ICI treatment initiation) as routinely available blood cell counts. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. The end of the follow-up period was August 31, 2020.Progression-free survival (PFS) was defined as the period from the date of the first administration of ICIs to the date of documentation of disease progression or death from any cause. Overall survival (OS) was defined as the period from the date of the first ICI administration to the date of death from any cause. Patients without documented radiographic progression or who were still alive were censored on the date of the last follow-up.P-values were two-sided, and the statistical significance was set at P < 0.05.The Kaplan–Meier method was used to estimate the PFS and OS. The log-rank test was used to compare the differences among the three groups. The drug-based prognostic score for baseline concomitant medication plus NLR at baseline was weighed based on the regression β coefficients according to a previous study by Buti et al. . Univari3 and 1316 (IQR: 914–1697) cells/mm3, respectively. Thus, the median value of the NLR was 3.7 (IQR: 2.5–6.2).The patient flowchart is shown in P = 0.009), but not with PFS. As shown in P = 0.031). In contrast, no association between these prognosis groups and PFS was observed. The hazard ratios of PFS of the poor- and intermediate-prognosis groups were 0.97  and 0.81 , respectively. Furthermore, the multivariable Cox proportional hazard model revealed that ECOG PS 2 and later-line treatment were significantly associated with a reduced OS. The hazard ratios of OS were 2.36  and 1.60 , respectively. Similarly, the multivariable Cox proportional hazard model revealed that later-line treatment was significantly associated with a reduced PFS. The hazard ratio of PFS was 1.45 . Applying the computed score to this population, the Harrell’s concordance statistic for OS was 0.634.Overall, 188 events of disease progression and 142 deaths occurred. As shown in The present study tested the hypothesis that baseline medications plus NLR could predict the clinical efficacy of nivolumab and pembrolizumab in clinical practice. Accordingly, the findings demonstrated that baseline medications plus NLR could reduce the effectiveness of nivolumab and pembrolizumab as first-line, second-line, or beyond treatment in patients with advanced NSCLC in a clinical setting. We showed that the poor-and intermediate-prognosis groups had reduced OS  compared with the good-prognosis group. To our knowledge, this is the first study to report the association between baseline medications and routinely available blood cell counts at baseline and clinical outcomes of ICI treatment in the Japanese population using real-world data.n = 217) and validation (n = 1012) cohorts. In another study, Buti et al. (n = 950) as a first-line treatment, a drug-based prognostic score of baseline medication showed a predictive ability for survival outcome. Concordant with these studies, the present study demonstrated that NLR complimented the predictive ability of a drug-based prognostic score. In this population, baseline medications plus NLR had a higher predictive value than did the Buti’s scoring system and NLR  as a second-and further-line setting, the Meet-URO prognostic score of baseline NLR and clinical factors showed a predictive ability for survival outcome. However, when we categorized patients into three prognosis groups as follows: score 0 (good-prognosis), score 1–3 (intermediate-prognosis), and score 4–6 (poor-prognosis), the poor and intermediate-prognosis groups demonstrated reduced OS  compared with the good-prognosis group. These findings suggest that baseline medications and NLR are key prognostic parameters. Once validated, these parameters could be used in the clinical setting, as they are easily available and do not require additional costs or setup. Hence, NLR was selected for the development of the prognostic score, based on Rebuzzi et al. . The present study combined baseline medications with the routinely available NLR at baseline as a novel prognostic score, and an NLR ≥ 3 was assigned 2 points as in previous studies  as a first- and later-line treatment, baseline corticosteroids, PPIs, and antibiotics were associated with worse clinical outcomes. In another study, Cortellini et al. (n = 950) as a first-line treatment, baseline corticosteroids, PPIs, and antibiotics were associated with worse clinical outcomes. In the present study, six patients received metformin, two patients received fibrates, and eighteen patients received statins, and these medications were not analyzed because of the small number of patients. In contrast, 97 patients received NSAIDs. A sub-analysis to evaluate the association between co-administration of NSAIDs and survival outcomes revealed a significant association between NSAIDs and OS . However, there was multicollinearity between PPIs and NSAIDs because PPIs were prescribed for prophylaxis of NSAID-induced gastric ulcers. Additionally, there have been no reports on the relationship between baseline concomitant NSAIDs and survival outcomes of ICIs , baseline medications were not significantly associated with the onset of irAEs. Fourth, the present study did not evaluate the smoking status because of its retrospective nature. Finally, the present study mainly evaluated second- or later-line treatments. The current standard first-line treatment for advanced NSCLC is a combination of ICI and platinum doublet; therefore, the clinical significance of this study is relatively weak. Overall, the findings of this study should be validated in a large-scale multicenter study with an adequate sample size of patients treated with a variety of baseline medications that affect the gut microbiota.This study has some limitations. First, this was a retrospective observational study; therefore, the presence of an information bias cannot be excluded. In addition, medical records used in this study were heterogeneous between physicians and may not have been recorded completely, especially those of the baseline medications—we concomitantly used medical records written by pharmacists. Methodologically, the three groups did not match, and the sample size was unequal; therefore, to reduce the effect of potential confounding factors associated with observational studies and clinical differences in patient characteristics, we used multivariable analyses. Nevertheless, unmeasured confounders such as other baseline medications, PD-L1 expression, and post-treatment of ICI were not controlled during the multivariable analyses, which is a major limitation of our study since controlling these could have affected the results. Second, our data were derived from a single-center, and the sample size was relatively small compared with those of previous studies that created a drug-based prognostic score for the first time , 17. ThiIn conclusion, the findings suggest that baseline medications plus NLR could lead to progressively shorter survival outcomes in patients with advanced NSCLC treated with nivolumab or pembrolizumab in clinical practice. Our data provide preliminary evidence for prognostic score-driven baseline medication and routinely available blood cell counts at baseline in Japanese patients with advanced NSCLC and suggest that the prognostic scores could be used as a prognostic index for predicting survival outcomes in clinical practice. These findings are likely to be translated to other Asian populations, highlighting the need for additional research in this field. Finally, since the present study only employed a training cohort, our prognostic score-driven baseline medications and NLR should be confirmed using a large sample size as a validation cohort.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by National Cancer Center Institutional Review Board . The ethics committee waived the requirement of written informed consent for participation.HK: Concept and design. TO, HK, and SE: acquisition of data (acquired data and managed patients). TO, HK, and AH: Data analysis and interpretation. TO and HK: Writing, reviewing, and revising the manuscript. TN: Supervision of the study. All authors contributed to manuscript revision and read and approved the submitted version.This work was supported in part by the Foundation for Promotion of Cancer Research in Japan and the Research Foundation for Pharmaceutical Sciences in Japan. The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.YO received research funding from Kissei, Dainippon-Sumitomo, Ignyta, LOXO, AstraZeneca, Taiho Pharmaceutical, Chugai, Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, MSD, Kyorin, Takeda, and Novartis and received honoraria from AstraZeneca, Taiho Pharmaceutical, Chugai, Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, MSD, Kyorin, Takeda, Novartis, Celltrion, Amgen, and Boehringer Ingelheim. TN received research funding from Astellas Pharma, Chugai, Daiichi Sankyo, Otsuka Pharmaceutical, Sanofi, and Shionogi.The remaining 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.