Background and Aims: Using gaming to escape emotional difficulty has been suggested to be a candidate mechanism contributing to Internet gaming disorder (IGD). This study evaluated the associations among resilience, perceived stress, depression, and IGD. Methods: A total of 87 participants in an IGD group and 87 participants in a control group were recruited into this study. IGD was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. Stress levels, resilience, and depression were measured by a self-reported questionnaire. Results: The IGD group had a lower resilience, higher perceived stress, and depression than the control group. Hierarchical regression analysis demonstrated that resilience was associated with IGD when perceived stress was controlled. After depression was controlled, resilience and perceived stress were not associated with IGD. Among the IGD group, those with low resilience had higher depression. Furthermore, discipline was the resilience characteristic associated with IGD. Conclusions: Low resilience was associated with a higher risk of IGD. IGD individuals with low resilience had higher depression. Depression was more associated with IGD than resilience. Depression assessments and stress coping interventions should be provided for individuals with IGD who exhibit low resilience or high stress. Internet gaming disorder (IGD) has been identified as a potential psychiatric disorder because of its negative effects on multiple domains of functioning ,2,3. TheAddictive behaviors are often initiated as a maladaptive mechanism for coping with stress . Stress Convincing evidence indicates that stress is a risk factor for addiction and triggers relapses . The negNot all individuals who face stress develop addictions. Therefore, resilience factors may protect these mentally healthy individuals . For exaDepression is one of the most reported correlates of IGD . AlthougAccording to the aforementioned studies, resilience enables people to adapt successfully to stress or emotional difficulty and to avoid stress-related disorders . Thus, wOur participants comprised individuals who had IGD at the time of the study (the IGD group) and individuals who had never had IGD (the control group) based on a design of case-control study. All participants were recruited by advertisement from September 2012 to October 2013. The criteria for the IGD group specified that participants be: (1) young adults aged 20 to 30 years and with more than 9 years of education; (2) individuals spending either ≥40 h per week or ≥4 h per day on weekdays and ≥8 h per day on weekends engaged in Internet gaming; and (3) individuals who maintained a pattern of Internet gaming for more than 2 years. Participants who met all of three criteria underwent an additional interview with a psychiatrist using the criteria of the DSM-5 [For each participant in the IGD group, we matched a participant to be included in the control group by gender, education level, and age (within a range of 1 year). The recruitment criterion of participants in the control group was that their daily nonessential Internet use was less than 4 h. These participants were classified into the control group after a diagnostic interview with a psychiatrist.All participants underwent the interview, which comprised two steps: (1) a diagnostic interview based on the Mini-International Neuropsychiatric Interview (MINI) to assess psychotic disorders, bipolar I disorder, and substance-use disorders; and (2) a history-taking interview to evaluate psychotropic medication use, mental retardation, severe physical disorder, and brain injury. Those who had psychotic disorders, bipolar I disorder, substance-use disorders, mental retardation, severe physical disorder, or brain injury or used psychotropic medication were excluded.The diagnostic criteria of IGD were those of the DSM-5 . The ninWe conducted a diagnostic interview based on the psychotic disorder, bipolar I disorder, and substance-use disorder modules in the Chinese version of the MINI  to detecThe R14, which provides reliable internal consistency and external validity, was developed to evaluate the levels of resilience in the general population. Participants’ resilience was assessed using this scale , in whicThe Perceived Stress Scale (PSS) was designed to measure the extent to which situations in one’s life are perceived as stressful. The PSS score was correlated with life-event scores, depression, and physical symptomatology . It is sThe 20-item Mandarin Chinese version  of the CThe Clinical Global Impression (CGI) scale  asks “Cot-test. The associations between gender, lower resilience, and IGD were evaluated through Chi-squared analysis. A hierarchical logistic regression model was used to evaluate associations of resilience, perceived stress, and depression with IGD. Finally, we evaluated the associations of resilience, perceived stress, and depression with CGI score among participants with IGD. A logistic regression evaluated the association between items of R14 and IGD with gender, age, and educational level controlled. A value of p < 0.05 was considered significant for all analyses, which were performed using the SPSS package .We evaluated the associations of resilience, perceived stress, and depression with IGD using an independent A total of 87 participants in the IGD group and 87 in the control group were enrolled in the study after informed consent was obtained. This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUH-IRB-990380).A total of 87 participants from the IGD group and 87 participants from the control group were enrolled in this study. No significant differences were exhibited in gender, age, or education level between the IGD and control groups, as revealed in The hierarchical regression analysis in χ2 of perceived stress was higher than that of resilience, perceived stress was more associated with IGD than resilience was . Resilience and perceived stress exhibited no significant associations with IGD when depression was controlled for. This result demonstrated the mediating effect of depression in the associations of resilience and perceived stress with IGD. It also demonstrated that among resilience, stress, and depression, depression was the factor most associated with IGD.t-test in t = 0.023; p = 0.03). They also had a trend to have higher percieved stress ; however, this did not reach significance.The t = 2.15; p = 0.03), acceptance , drive , discipline , interest/engagement , self-efficacy , dependable , meaning , and resourcefulness . Then, we regressed IGD on these significant items in R14 with gender, age, and educational level controlled. The logistic regression in We firstly evaluated the difference in each item of R14 between IGD and the control group. It demonstrated that the IGD group had a lower score in ability to copy (This study demonstrated that participants with IGD experienced higher perceived stress. This result corresponds with those of other studies ,23. StreAs in the studies of Wu et al.  and CanaTwo studies have evaluated the buffering effect of resilience on the association between stress and IGD. Wu et al.  did not Individuals with IGD could experience the psychosocial distress results from excessive gaming . HoweverDepression is one of the most reported factors associated with IGD ,40. WithDiscipline was the only resilience characteristic associated with IGD when other items were controlled. Individuals with IGD had lower discipline than controls did. Self-regulation was reported to mediate the association between impulsivity and pathological video gaming among youth . IndividThis study had limitations that should be considered when interpreting the findings. First, IGD was evaluated only through a diagnostic interview with participants. Additional information from family members or partners could have increased the validity of the diagnosis. Second, the cross-sectional research design could not confirm causal relationships between resilience, perceived stress or escapist online gaming behaviors and IGD. Lastly, we excluded those take psychotropic medication from this study to prevent its effect on depression and perceived stress. However, it could limit the generation of this study’s results to populations with psychotropic medication.Individuals with IGD had lower resilience, higher perceived stress, and higher depression. Participants with low resilience exhibited 3.46 times odds ratio for IGD compared with those with adequate resilience. Further, depression was a more proximal factor to IGD than resilience and mediated the association between resilience and IGD. Interventions to promote coping strategies and treat depression should therefore be provided for individuals with IGD and concurrent high stress or depression. Finally, discipline is the resilience characteristic most associated with IGD. Its implications for IGD interventions deserve further study.


Background: Breast Cancer susceptibility genes 1 and 2 are implicated in hereditary breast and ovarian cancer and women can test for the presence of these genes prior to developing cancer. The goal of this study is to examine psychological distress, quality of life, and active coping mechanisms in a sample of women during the pre-test stage of the genetic counseling process, considering that pre-test distress can be an indicator of post-test distress. We also wanted to identify if subgroups of women, defined based on their health status, were more vulnerable to developing distress during the genetic counseling process.Methods: This study included 181 female participants who accessed a Cancer Genetic Counseling Clinic. The participants were subdivided into three groups on the basis of the presence of a cancer diagnosis: Affected patients, Ex-patients, and Unaffected participants. Following a self-report questionnaire, a battery of tests was administered to examine psychological symptomatology, quality of life, and coping mechanisms.Results: The results confirm that the genetic counseling procedure is not a source of psychological distress. Certain participants were identified as being more vulnerable than others; in the pre-test phase, they reported on average higher levels of distress and lower quality of life. These participants were predominantly Ex-patients and Affected patients, who may be at risk of distress during the counseling process.Conclusions: These findings highlight that individuals who take part in the genetic counseling process are not all the same regarding pre-test psychological distress. Attention should be paid particularly to Ex-patients and Affected patients by the multidisciplinary treating team. According to the Italian Register of Cancer, in 2016 in Italy 50,000 and 5,200 women received a diagnosis of breast and ovarian cancer, respectively AIOM. In womeWomen who have been identified as genetically at risk for developing HBOC have the choice of several interventions: surveillance, prophylactic mastectomy, prophylactic salpingo-oophorectomy, and chemoprevention via, for instance, the use of tamoxifen  evaluate each individual case and decide whether a patient should be subjected to the genetic testing procedure. (B) Pre-testing stage: during this stage, the individual learns about all the familial, hereditary, and sporadic forms of cancer and the chances of developing these. Often a genetic counselor or geneticist conducts a full pedigree construction to estimate the risk. This pre-test interview is also conducted to discuss potential uncertainties, informed consent, and future preventative options. An inability to process information secondary to active psychiatric or cognitive impairment could interfere with informed consent and this should be taken into consideration by the multidisciplinary team  Post-test stage: the multidisciplinary team then communicates the test results to the individual and helps them understand what these results mean and their implications are discussed. The test results can either be: positive, negative, or inconclusive. A positive test result indicates that the individual has a mutation that increases their chances of developing cancer. A negative test result can reassure a woman that there is no BRCA1/2 mutation, but this does not rule out other mutations in less common genes. An inconclusive test result indicates that there are variants of unknown significance and the individual may be advised to undergo further testing.Genetic counseling is an intervention aimed at informing and supporting individuals who must undertake a medical path that searches for and manages genetic defects or pathologies , patients with a history of cancer, hereinafter called Ex-patients (n = 69) and patients with no cancer diagnosis, Unaffected participants (n = 38). Eligibility criteria included: (1) being at least 18 years old; (2) being able to read and understand Italian; and (3) agreed to voluntarily participate in the research. No women with severe psychiatric or neurological disorders were excluded from the study as there were none that presented these symptoms. Furthermore, no participants refused to take part in the study and all women satisfied our inclusion criteria. Informed consent was obtained from all individual participants included in the study. The study was reviewed and approved by the Medical Ethical Committee of the IRCCS San Raffaele Hospital.This study included 181 female participants who accessed the Cancer Genetic Testing Service by the Medical Oncology, Breast Surgery, and Gynecology Units in a Hospital in the North of Italy between January 2012 and December 2016. The participants were subdivided into three groups on the basis of their health status: patients currently being treated for cancer, or Affected patients , the Coping Orientation to Problems Experienced questionnaire (COPE), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).socio-demographic data collected included questions regarding age, marital status, and presence of children. Regarding the medical information, the following were investigated: presence of a cancer diagnosis , treatments that were carried out, and the pedigree relationship to any relatives that may have been diagnosed with cancer. Lastly, we also asked patients if they had ever undergone any previous psychological or psychiatric treatments, or taken any psychopharmacological drugs.The Subsequently, patients completed the following standardized questionnaires:SCL-90-R , have been applied.To identify differences among Unaffected patients, Affected patients, and Ex-patients on the psychological constructs of interest and due to the non-normality of the examined psychometric scales, a Kruskal–Wallis test, the nonparametric counterpart to standard ANOVA, followed by PMCMR package, developed in R, was used to implement the Kruskal–Wallis test and post-hoc analysis for pairwise multiple comparisons , ranging from 21 to 80 years. As mentioned previously, the participants were divided into 3 groups on the basis of their health status: Affected patients , “Ex-patients” (38.12% n = 69), and Unaffected participants . In Table The mean age of the study participants was 48.54 years SD = 1.54, ranDescriptive statistics of variables of interest, along with group comparisons, are presented in Tables p < 0.0001), Anxiety (p = 0.0221), Somatization (p < 0.0001), and Depression (p = 0.0028).Focusing on the SCL-90-R, no group reported any scores of clinical relevance. Based on the Kruskal–Wallis test, groups of participants were significantly different in terms of GSI (p = 0.0012), Anxiety (p = 0.023), Somatization (p = 0.0023), and Depression (p = 0.0146). For both GSI and Somatization, the group of Affected patients significantly differed from those with no cancer diagnosis (p < 0.0001). Moreover, their scores significantly differed on the Depression scale (p = 0.0027).In particular, a significant difference emerged between Ex-patients and Unaffected participants in the mean scores of the GSI (p = 0.0045), Physical (p < 0.0001), Cognitive (p = 0.0156), Social (p = 0.0012), and Role Functioning (p = 0.0001). The scores of the Global health scale, Physical, Cognitive, Social, and Role Functioning are significantly different between the Affected patients and the Unaffected participants . The healthy group also differed from the group of Ex-patients regarding Physical, Cognitive, Social, and Role Functioning .Relatively good levels of health-related quality of life were reported by all groups in all functional domains. Overall, groups were significantly different in terms of their Global health (p = 0.0171). In detail, there was a significant difference between patients without cancer and those with cancer, both in the present or in the past . We did not find any significant differences between the Affected patients and Ex-patients on the considered constructs.The only coping strategy that revealed statistically significant differences among the subgroups was the social support coping mechanism  and live with a history of illness.The literature concerning coping mechanisms shows that people favor either a problem-focused approach or an emotional-focused one  and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All subjects gave written informed consent in accordance with the Declaration of Helsinki.VD was responsible for the conception, interpretation and design of the research project and approving the final copy. LC was responsible for drafting the work, revising it critically, drafting the study design and data acquisition. MB and RB were responsible for drafting the work, data collection, revising the manuscript and conducting research of the intellectual content. CB and FC were responsible for statistical analyses and data interpretation. ER and MZ were the oncologists responsible with organizing the project and helping with data collection and proof checking of the manuscript. MC, LS, and OG were responsible for the conception and design of the research project, critical analysis and approving the final copy. All authors are thus accountable for all aspects of the work, also with respect to the integrity and accuracy of it.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.


Maternal obesity is associated with metabolic changes in mothers and higher risk of obesity in the offspring. Obesity in breastfeeding mothers appears to influence human milk production as well as the quality of human milk. Maternal obesity is associated with alteration of immunological factors concentrations in the human milk, such as C-reactive protein (CRP), leptin, IL-6, insulin, TNF-Alpha, ghrelin, adiponectin, and obestatin. Human milk is considered a first choice for infant nutrition due to the complete profile of macro nutrients, micro nutrients, and immunological properties. It is essential to understand how maternal obesity influences immunological properties of human milk because alterations could impact the nutrition status and health of the infant. This review summarizes the literature regarding the impact of maternal obesity on the concentration of particular immunological properties in the human milk.  In 2014, the number of pregnant women with overweight and obesity were estimated at 38.9 million and 14.6 million, respectively, worldwide . AccordiHuman milk consists of nutrients and active factors. In addition to nutritive functions, some milk constituents also have bioactive properties such as whey proteins  and casein proteins (κ-casein and β-casein) . Other bMoreover, human milk composition, both over a single feeding and over the duration of lactation is unique and dynamic. Colostrum is the first milk produced 30 mL/24 h) from 30 to 40 h until a few days postpartum ,22. Tran h from 3The primary aim of this review is to describe the immunological functions of specific factors in human milk and the alterations that occur in conditions of overweight and obesity mothers. The secondary aim is to explore the other influential factors that stimulate alterations of specific immunological properties that also could influence their functions in human milk. Breast milk contains essential bioactive components that have been demonstrated by numerous studies. Many components studied have been found to provide a function, for example to prevent infections, heal diseases, and improve health status . Many biCandida albicans, Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus pneumoniae, and Vibrio cholerae [2) [Lactoferrin is one of the major iron-binding glycoproteins in colostrum that is immunomodulatory . Lactofecholerae . Lactofeerae [2) . Lactadherin is a glycoprotein associated with milk fat globules of human milk together with mucins, xanthine oxidase, and butyrophylin . The mai−). The concentration of lactoperoxidase of human milk at the first 6 months was found to be constant between 1–1.5 units/mL [2O2 both in the infant gut and mammary gland of mothers, with additional anti-microbial functions. Whether lactoperoxidase concentration in the human milk of obese mothers is altered has not yet been determined.The catalytic reactions of lactoperoxidase have bactericidal effects that kill Gram-positive and Gram-negative bacteria ,61. Thisunits/mL . LactopeAnother antimicrobial constituent of milk, lysozyme, is present at a concentration that is 3000-fold higher in human milk than cow’s milk. It is an active enzyme that works together with lactoferrin to effectively kill Gram-negative bacteria . A studyMucins, another antimicrobial factor, make up one of three major protein fractions of human milk, along with casein and whey . Mucins The existence of lymphocytes in human milk was first discovered in colostrum . AnotherMacrophages and the mammary endothelium support the production of TNF-Alpha in human milk ,74. MacrStaphylococcus aureus [Neutrophils are another type of leukocyte that are abundant in the colostrum . The thrs aureus . This sts aureus . Stem cells have been found in human milk that differentiate into luminal, basal, and myoepithelial layers . These sChemokines are a type of cytokine that may stimulate cell movement . ChemokiG-CSF functions as a hematopoietic growth factor, to stimulate the proliferation of clonal and neutrophil progenitor differentiation . A studyThe production of macrophage migration inhibitory factor (MIF) is equivocal with some reports that MIF is not produced by specific human cells . AnotherCytokines interact with the other cells and cross the intestinal barrier to enhance or defend, and reduce inflammation . The cytBoth regulation and development of mammary gland function are mediated by IL-6 and TNF-Alpha . In addiThe main functions of IL-7 are to support lymphoid development, produce T-cells in the thymus, and assist in T-cell survival at secondary of peripheral lymphoid tissue . IL-7 fr2 and BMI >25 kg/m2 were 11.41 and 10.23 pg/mL, respectively. However, there was no statistically significant difference in the TNFα content of the milk in these mothers [In a study of mothers with varying BMI, the concentrations of TNFα in colostrum and 1-month milk of mothers with normal BMI were reported at 9.87 and 10.60 pg/mL, respectively . However mothers . The val mothers . Therefop = 0.013) than that of mothers with normal BMI (0.040 ng/mL). Furthermore, low concentration of EGF in the mother’s milk was significantly associated with higher infant body weight [Epidermal growth factor (EGF) is a growth modulator that can be found in amniotic fluid . The funy weight .HB-EGF is a growth factor that can be found in both amniotic fluid and human milk ,97. HB-Ep = 0.787). The Insulin-like Growth Factors (IGF)-I in human blood were found in 1968 by Jacobs et al. . IGF-1 hSpecific neurons of the peripheral nervous system need nerve growth factor (NGF) to survive . NGF hasHuman milk contains vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) at concentrations that are 100 times higher than blood of lactating mothers . The conThe role of adiponectin is to regulate metabolism of the body, specifically affecting satiety, tissue sensitivity to insulin, stimulate glucose uptake, and decrease energy expenditure ,110,111.Calcitonin has functions to inhibit gastric acid production, or regulate fluid balance, food intake, and gastrointestinal motility ,114,115.Ghrelin was identified by Kojima et al. 1999), as a 28-amino-acid-peptide. It was found to be predominantly expressed in the stomach , but it 99, as a Insulin in human milk functions as a hormone, and also influences the microbiome community in the lumen of the gastrointestinal tract . MothersLeptin is an adipocyte-derived hormone that was first found in 1994 . OpposinObestatin is a hormone that was found in 2005 in the gastrointestinal tract . ObestatResistin is a hormone in breast milk that regulates fetal growth, appetite, and metabolic development of the infant . The medSomatostatin functions to inhibit gastrin secretion . The higE. coli antigens, and is not destroyed by digestion [The major immunoglobulin found in human milk is Secretory IgA . This antibody is transferred from the milk to the infant, at the rate of 0.3 g/kg/day. About 10% is absorbed from the intestines and enters the infant blood . A deficigestion . A studyigestion . The staUnlike IgA, IgG and IgM are completely digested in the small intestine . Thus, iIgM concentration in the colostrum of human milk is the second highest of the immunoglobulins. The mean concentration of IgM is 0.47 ± 0.10 g/L . IgM proInsulin-like growth factor-binding proteins can be found in human milk and include insulin growth factor I (IGF-1) and insulin growth factor 2 (IGF-2). Colostrum contains the highest concentration of IGF compared to the later milks . IGF-1 fLipids contribute up to 44% of the total energy in human milk . Lipids Lactobacillus, Bacteroides, and Bifidobacteria. The proliferation of these microbiota stimulates the activation of T regulatory cells and transform intrauterine TH2 predominant to rebalance TH1/TH2 [Bifidobacterium and Lactobacillus are the primary probiotic in the gut that provide nutrients to the newborn intestine and protect it by establishing an acidic environment rich in short chain fatty acids (SCFAs) [Bifidobacterium and increasing number of Staphylococcus have been demonstrated in human milk of obese and overweight mothers [Lactobacillus and the lower of concentration of Bifidobacterium for 3 months may contribute to increased risk of overweight and obesity to the infant [Human milk supports proliferation of the milk microbiota by regulating the balance of specific microbiota such as,  TH1/TH2 . About 2 TH1/TH2 . Bifidob (SCFAs) ,149. Den (SCFAs) . A decre mothers ,44. Furte infant . Anothere infant . The alte infant ,157,158.The degradation of milk nucleic acid polymers (RNA) provides nucleotides, which have been found to improve immune function, enhance the bioavailability of iron, adjust the microflora in the intestine, alter plasma lipids, and support growth and maturation of the gut ,162,163.Human milk oligosaccharides (HMOs) protect infants from microbial infections, protect gut microbiota, prevent microbial adhesion, and invasion in the intestinal mucosa . HMOs arPrebiotics such as glycosaminoglycans, oligosaccharides, glycoprotein, and glycolipids are needed to support growth of the microbiota in the intestinal tract . GlycosaThe concentration of soluble CD14 (sCD14) in the colostrum is 20-fold greater than the concentration in maternal serum . A functOsteoprotegerin is part of the TNF super family components that inhibit the activation of TNF-induction to prevent proliferation process of T cells. The concentration of osteoprotegerin in epithelial cells of the human mammary gland and human milk is 1000 times higher than the concentration in human serum . OsteoprAlpha-lactalbumin of human milk is a bioactive protein that can be found in the whey fraction of milk . Alpha-lα1-Antitrypsin is a protease inhibitor in human milk. It has been shown to be an influential protein together with antichymotrypsin . α1-AntiAlpha-amylase is another significant bioactive protein in human milk . The newBile Salt Stimulated Lipase (BSSL) has been identified in human milk but not cow milk, where it contributes to 1%–2% of total milk protein. BSSL is influential as an active enzyme to digest lipid in the lumen of the infant gut. It hydrolyzes the esters of vitamin A and cholesterol, lyso-phospholipids, and other milk fats such as monoglycerides, diglycerides, and triglycerides . A studyHelicobacter pylori is prevented by κ-casein activity at the gastric mucosa. More specifically, κ-casein at the epithelial cell surface has role as a soluble receptor analogue which prevents the binding of mucosal epithelium to bacteria [Human milk proteins are often classified according the nature of how the colloids are distributed in milk, as either two components, whey or casein. Casein proteins are distinguished by their arrangement in micelles. Human milk contains 20%–40% caseins . MUC2 fubacteria . The ratbacteria . At the bacteria . C-reactive protein is an inflammatory protein marker that is primarily produced by the liver . MaternaFolate-binding protein regulates the metabolism of the vitamin folic acid, through distribution, absorption, and retention . The solE. coli and is stable against proteolytic digestive enzymes [12 in the newborn (acting as a vitamin B12-binding protein) [Haptocorrin is an anti-microbial substance that was found to reduce  enzymes . In addi enzymes . High coprotein) . There wThe composition of human milk is also influenced by other maternal factors, such as diet, age, ethnicity, metabolic health, type of delivery, smoking, amount of sleep, stress, and physical activity. Additionally, it is influenced by physiological factors such as diurnal variation, stage of lactation and stage of nursing, as well as factors related to the infant, including gender, birthweight, body composition, and behavioral factors, such as ad libitum feeding and time between feedings . The maiBased on literature that were collected and reviewed, obesity and overweight of mothers appears have a clear influence on the concentration of 29 immunological properties in human milk. An alteration of any of these immunological properties could influence the function of the human milk. An increase or decrease of immunological properties in human milk are predicted to influence the health status of infants in both the short term and long term. Further research is needed to study the correlation of high BMI with the 31 yet unstudied or unreported immunological properties in human milk and the risk of specific diseases to the infants.There are some limitations of this review. First, the range of years for publications of studies reviewed was not limited. Some current studies might have different results compared to older studies because of different number of participants, data collection methods, immunoassay methods and detection, and statistical analyses. Second, many studies did not classify the samples collected as to whether they were colostrum, hind milk, and fore milk. Differences in the composition of milk over the duration of lactation should have different concentration of immunological properties. Furthermore, these variations might influence the output of immunological actions related to their function as protectors and supporters for infant growth and development. 2 about the risk of obesity to mother and infant and suggest restricting excessive caloric intake outside of the recommended amounts needed for healthy infant growth. The health care professionals support the pregnant mother in obesity by providing weight management targets and the information about nutrient dense eating plans or menus.Medical practitioners, dietitian/nutritionists, and nurses should educate the pregnant mothers with BMI > 30 kg/mAfter delivery, exclusive breastfeeding can be promoted as another component of energy expenditure which will help prevent further weight gain by the obese mother. Breastfeeding mothers should not follow a weight loss program until 6–8 weeks after delivery because it may influence the quality and quantity of milk production. The overweight and obese mothers should be encouraged and supported to exclusively breastfeed for at least for 6 months.At 6–8 weeks postpartum, obese mothers should be encouraged to pursue healthy weight loss programs with nutrient dense eating plans after lactation is well established. Health professionals can emphasize that achieving a healthier BMI provides health benefits to both the infants  and to the mothers .Even though composition of some immunological factors in milk changes in obesity, there is not enough evidence at this time to suggest that the changes in the milk should preclude breastfeeding the infant, as the benefits of breastfeeding are well established. In fact, obese mothers in the US, Europe, Brazil, Latin America, Singapore, India, South Africa, and Australia, that cannot breastfeed, can consult with international board certified lactation consultants (IBCLC) and pediatricians to consider obtaining donor milk from a milk bank in one of these countries. Maternal overweight and obesity has been found to affect 29 immunological properties of human milk. While a complete understanding of the implications of these changes to the infant are not known, they add to the body of evidence supporting healthy weight management:The association of maternal obesity with immunological properties reported as unstudied in this review need investigation.The alteration of specific immunological properties and these effects on infant health condition (when breastfed by obese mothers) should be examined both in the short term and long term. A reduction of protective factors could have a negative impact on infant health. The differences in infant health status after exclusive breastfeeding by obese mothers should also be explored for obese mothers that practice nonexclusive breastfeeding. Exclusive breastfeeding has been widely encouraged due to the benefits for mothers and infants. It is conceivable that alterations in the immunological properties due to obesity may affect the usual advantages associated with exclusive breastfeeding.


Objective: Moderate physical activity (PA) is associated with a reduced risk to develop cardiovascular disease. However, junior athletes exercise between 10 and 20 h a week with intensities exceeding moderate levels by far. In this regard, the cardiovascular system has to increase its work five to six times compared to moderate intensities. This may result in potentially pathological adaptations of the cardiovascular system. The underlying process of vascular adaptations to exercise is yet not fully understood and hardly investigated in junior athletes. An increased blood pressure and pulse wave velocity, ventricular hypertrophy, arrhythmia, and even sudden cardiac death (SCD) has been reported in adult athletes. Studies, examining the cardiovascular system in children, its association to intensity and type of exercise, are rare. Therefore, we present the study protocol of a prospective cross-sectional study that investigates the influence of PA on the cardiovascular system in young athletes.Methods and Design: Children and adolescents, 7–18 years, presenting for their annual pre-participation screening at the Institute of Preventive Pediatrics, Faculty of Sports and Health Sciences, Technical University of Munich (TUM), are examined in this prospective cross-sectional study. Vascular parameters measured by ultrasound are carotid intima-media thickness (cIMT), vascular stiffness , and the vascular diameter (D) to calculate the IMT:Diameter-Ratio (IDR). Cardiac function is evaluated by a 12-lead ECG, and echocardiographic parameters . A cardiopulmonary exercise test is performed on a bicycle ergometer, muscular strength is assessed with the handgrip test, and physical activity with the MoMo questionnaire.Discussion: It is essential to follow young athletes over the course of their career in order to detect pathophysiological changes in the myocardium as soon as possible. If these changes are preceded or followed by changes in vascular structure and function is not known yet. Therefore, we present the study protocol of the Munich Cardiovascular adaptations in young athletes study (MuCAYA-Study) which investigates the association between vascular and cardiac adaptation to intensive exercise in junior athletes. There is no doubt about positive effects of physical activity (PA) on the human body. Physically active persons reduce their risk of developing type 2 diabetes mellitus, hypertension, and cardiovascular disease . PrevaleThe term “athlete's heart” describes a non-pathological electrophysiological, structural, and functional myocardial adaptation in response to continuous training stimuli in adults. Athletes present 10–15% increased left and right ventricles and a 10–20% increased left ventricular wall thickness. Functionally, an increased stroke volume and improved cardiac filling in diastole, improved capillary conductivity, and oxidative capacity of the skeletal muscle can be observed in athletes . MyocardContrary to positive effects of PA, maladaptations of the cardiovascular system may occur, sudden cardiac death (SCD) is the most severe one , 11, 12.Characteristic myocardial adaptations to intensive exercise training such as bradycardia, early repolarization, atrial dilatation, and ventricular hypertrophy are also seen in young athletes . In an AIn addition to cardiac adaptations to PA, there is evidence that PA also has an influence on the vascular system. Green, Spence, Rowley, Thijssen and Naylor  postulat2max, r = −0.21, p < 0.001) and PA. Denham et al. . In contrast, among competitive athletes, exercising at very high intensities, and control persons, negative adaptations to increased training intensities were found. Vlachopoulos et al. . Abergel et al.  and arterial stiffness are inversely correlated with cardiorespiratory fitness and physical activity –29. In cIn summary, there is no consensus on the effect of intensive exercise on the vascular system. Studies show an influence of aerobic endurance training to vascular properties , 32, 33.Therefore, this prospective cross-sectional study investigates the influence of PA on the cardiovascular system in young athletes. For this purpose, the structure and function of the vascular system and myocardium are examined as well as the association to intensive exercise training. Confounding variables are types of PA , cardiopulmonary fitness, muscular strength, and training stimuli (frequency and intensity).n = 250 children and adolescents are examined at the Institute of Preventive Pediatrics, Faculty of Sports and Health Sciences, Technical University of Munich (TUM).Children and adolescents, 7–18 years, presenting for their annual pre-participation screening, are enrolled in this prospective cross-sectional study over the course of two years. Each year, approximately Age 7–18 years.Informed consent by children and/or legal guardians.No acute infection.No acute orthopedic injury.Medical clearance for cardiopulmonary exercise testing.The following inclusion criteria are applied:The study is in compliance with the Declaration of Helsinki and is approved by the TUM ethics committee (project number: 301/18 S). Informed consent is contained of all children and/or their legal guardians.cIMT as structural vessel parameter is measured after 10–15 min rest in supine position at the far wall of the common carotid artery with the head turned 45° opposite to the site being investigated. cIMT is examined 1 cm proximal to the bifurcation at the end of diastole at two angles on the right side (120°/150°) and two angles on the left side (210°/240°). Measurements are performed in B-mode ultrasound according to the guidelines of the Association for European Paediatric and Congenital Cardiology (AEPC) . Using tVascular diameter (D) is measured at diastole, to calculate IMT:Diameter-Ratio (IDR) as parameter of functional adaptation (eccentric vs. concentric hypertrophy) of the vessel wall . cIMT anEnd-diastolic left ventricular diameter, left ventricular diastolic posterior wall thickness, and diastolic septal thickness are well-established parameters to describe myocardial morphology. They are examined via ultrasound  in a resting position with slightly lateral inclination by two-dimensional M-mode. Structural parameters are compared to reference values of Pettersen et al. . Left ve2) the body consumes sitting at rest. It equals 3.5 ml O2 per kg body mass per minute  at maximum strength, three times with the right and left hand, respectively .All participants undergo a 12-channel ECG at rest . Peripheral and central SBP and DBP, peripheral and central pulse pressure (PP), and aortic PWV are measured after a 5-min resting period using the Mobil-O-Graph . The cuff (size according to upper arm circumference) is placed on the left arm.2max is determined by cardiopulmonary exercise testing  on a bicycle ergometer  plus 12 lead ECG. Relative maximum load (W/kg) and relative VO2max (ml O2/min/kg) are calculated to determine participants' exercise capacity. Ventilation thresholds (VT1 and VT2) are defined by the V-slope method  defined at the 50th percentile and an abnormal increased cIMT (0.51 mm) above the 95th percentile.A sample of 2max and training stimuli  to changes of the cardiovascular system and to analyze a correlation between arterial and myocardial adaptations, relative to the type of exercise . Dependent parameters are arterial structure and function as well as myocardial structure and function. Independent parameters are VO2max and METs per week. Results are controlled for age, sex, BMI, BP, dietary behavior, blood cholesterol levels, and smoking.Differences between structural and functional parameters of the cardiovascular system will be compared to age- and sex-specific reference values –39. LineThis study aims to investigate the effect of PA on vascular and cardiac structure and function in young athletes. Furthermore, the influence of different types of PA , cardiopulmonary fitness, and training stimuli  on arterial structure and function are investigated, as well as the correlation of arterial structure and function to the structure and function of the heart.n = 720 athletes) and found an increased wall thickness in athletes compared to controls . In addition, 5% of participants had abnormal wall thickness values and showed an enlarged left ventricle (54.4 ± 2.1 mm). As highest values were observed in rowers, authors assumed a combination of intensive isometric and isotonic exercise that triggers hypertrophy of the left ventricle  and by biochemical mediators such as endothelin, cytokines, nitrogen, and oxidative stress by radical oxygen species . Hemodynentricle . In bothThe cardiovascular system is very sensitive to mechanical stimuli, such as an increased heart rate, increased ventricular filling, and increased arterial shear stress. This can also lead to adverse adaptations . In geneGreen et al.  suspect Increased inflammatory markers after intensive exercise could also have an impact on blood vessels. Increased leukocytes and CRP were found in athletes after a marathon race and associated with an increase in vascular stiffness , 56, 57.Positive adaptations due to exercise can be induced by increased shear stress and the associated release of vasoactive substances such as NO , 26, 59.In general, functional and structural changes are less pronounced in adolescent athletes due to their younger training history than in adults , 51. At In line with the definition of the athlete's heart, it is questionable in which way the vascular system adapts to training loads and whether there is a physiological relationship between cardiac and vascular adaptation , 67. BelSeveral studies demonstrate a U- or J-shaped curve of PA and health. Initially, physical activity is positively associated with better health status up to the vertex, which reflects the turning point with higher risk for cardiovascular events underneath and above a healthy threshold of PA in adults –71. The This study is a first step towards an analysis of cardiac and vascular structure and function in junior athletes. It will provide cross-sectional data as basic research for future longitudinal studies. The age-range covered is from 7 to 18 years and includes participants within different levels of their physiological, neurological, and mental development. It covers the age-range before, during, and after puberty which has an impact on hormonal status and thus on physical components. To account for this differences, participants will be compared to age- and sex-specific reference values and within their age-groups.We collect data on participants' training history to account for the time span they've been involved in competitive sports, to differentiate between shorter and longer exposure to physical training. What we cannot account for with this data is how participants respond to physical stimuli, as there will be athletes being predominantly disposed to muscular and cardiovascular adaptation than others. Genetic factors are not involved in the study at this point but could be one major aspect of future work as well as more laboratory parameters. Family history is assessed in the medical interview and will be reviewed for a history of cardiac disease or other health issues. This part could also be extended toward a family training history.The positive influence of physical activity on the cardiovascular system is affected by negative adaptations of intensive training stimuli and years of intensive endurance exercise in adults. This is reflected by changes in myocardial morphology and myocardial function as well as vascular structure and vascular function. In young athletes, increased wall thickness and increased lumen of the left ventricle were observed. Studies investigating the influence of intensive physical activity on the structure and function of the vascular system in young athletes do not yet exist. In children and adolescents studies show an association between moderate physical activity and positively altered structural and functional vascular parameters - however, these studies refer to athletes with normal levels of activity (according to the WHO recommendation). The role of type of sport, exercise frequency, and exercise intensity in the adaptation process is still unclear in adults and young athletes. Additionally, the long-term effects of this adaptation have not been sufficiently investigated , 72. ThiThe studies involving human participants were reviewed and approved by Ethics committee of the Technical University of Munich (project number: 301/18 S). Written informed consent to participate in this study was provided by the participants and/or legal guardian.LB and HW were involved in study conception and drafting the manuscript. TS and RO were involved in study conception and critically reviewed the manuscript. All authors have read and approved the final version of this manuscript.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.


Background: Neurobehavioral disability (NBD) has a major influence on long-term psychosocial outcome following acquired brain injury, as it affects not only the survivor of the brain injury, but the whole family.Objectives: To investigate (1) the frequency of NBD among survivors of severe brain injury measured by the Danish version of the St Andrew's-Swansea Neurobehavioural Outcome Scale (SASNOS) rated by patients and proxies, (2) factors associated with NBD, and (3) concordance between reports of NBD completed by patients and proxies.Methods: SASNOS was administered at an outpatient unit as a part of a follow-up assessment after discharge from intensive neurorehabilitation. SASNOS consists of five factors describing the following domains: Interpersonal Behavior, Cognition, Aggression, Inhibition and Communication, and both the patient and a proxy were asked to complete the questionnaire. Data collection was conducted over a period of 2 years, and 32 patients and 31 proxies completed the questionnaire. Mean time since injury was 19.4 months (10.0 SD). Most patients were male (68.8%), and most proxies were female (58.1%). Most of the patients had suffered a traumatic brain injury (68.8%).Results: A fourth of this patient group reported themselves below the normal range on the major domains of Interpersonal Behavior and Cognition. Significant associations between proxies' reports and time since injury, cohabitant status, and the patient's score on the Extended Glasgow Outcome Scale were found. Furthermore, significant differences were found between patient and proxy ratings. Proxies rated patients as having fewer problems on the Interpersonal Behavior domain, and more problems in relation to Cognition. Cognition was the only domain, where patients rated themselves higher indicating fewer problems, compared with their proxies. On both the Aggression and Communication domains, proxies rated patients higher indicating fewer problems than the patients themselves.Conclusion: Danish brain injury survivors experienced NBD as measured by SASNOS. Differences were found between patient and proxy ratings in relation to Cognition and Interpersonal Behavior. The NBDs identified can affect the survivor's ability to reintegrate and participate in activities of daily living, emphasizing how a systematic assessment is required. Survivors of acquired brain injury (ABI) often experience severe long-term consequences across physical, cognitive, social, behavioral, or psychological domains. Physical or cognitive disabilities can be devastating, but it has been argued that change in neurobehavioral functioning is one of the most distressing legacies of ABI , 2. NeurThe impact of cognitive disabilities in real life situations is not always paralleled by cognitive impairments captured by neuropsychological tests. The structure and composition of tests used in clinical testing mean that some important observations of neurobehavioral disabilities are missed , 19–21. One method of measuring NBD has been developed by Alderman, Wood and Williams, who introduced St Andrew's-Swansea Neurobehavioral Outcome Scale (SASNOS) . SASNOS The frequency of NBD among severe brain injury survivors measured by the Danish version of SASNOS as rated by patients and proxies.If NBD reports were associated with factors related to patient or proxy.Concordance between reports of NBD completed by patients and proxies.When survivors of severe ABI are seen for follow-up visits after intensive neurorehabilitation, subjective and qualitative reports of NBD by family members frequently occur . Due to Based on the existing international literature, we hypothesized that the majority of severe ABI survivors would report the presence of NBD in more than one domain, as would their proxies. We hypothesized that factors related to the injury would be associated with both proxies and patients reports of NBD. Furthermore, we hypothesized that discrepancies would be found between reports of patients and proxies, more specifically, that proxies would report more problems than patients in relation to emotional and behavioral disabilities.After discharge from sub-acute intensive neurorehabilitation in hospital, patients and their close family members were invited for a follow-up visit 1 to 3 years post injury at the outpatient clinic, Department of Neurorehabilitation, TBI Unit, Rigshospitalet, Denmark. During the study period, from December 2015 to December 2017, SASNOS was administered as a part of the standard follow-up assessment. The questionnaire was administered to both the patient and a proxy, in most cases a family member, by a neuropsychologist or a nurse working in the outpatient clinic. The participants were instructed to return the questionnaire when completed, and if the questionnaire was not completed immediately, they were asked to complete it at home and return it in a stamped address envelope.Patients were included if they met the following criteria:(1) severe traumatic or non-traumatic brain injury followed by intensive neurorehabilitation at Department of Neurorehabilitation, TBI Unit; (2) ≥18 years at time of follow-up; (3) ≥1year since time of injury; (4) intact ability to understand and read Danish; (5) ≥7 on the Rancho Los Amigos Scale (RLA) at follow-up indicating the resolution of post-traumatic amnesia (PTA) or similar state of confusion for patients with non-traumatic injuries.For the proxies, the following criteria had to be met: (1) close family member to the patient; (2) ≥18 years at time of follow-up; (3) able to understand and read Danish.Patients and proxies were excluded if they: (1) had an active substance abuse; (2) had severe aphasia; (3) had severe disorders of consciousness or cognitive disabilities that were too severe to complete the questionnaire.n = 5); not able to understand Danish (n = 1); severe cognitive disabilities or disorders of consciousness (n = 10); did not have any close proxy (n = 1); schizophrenia (n = 1). Of the remaining 58 patients who fulfilled our inclusion criteria, a few refused to complete the questionnaire (n = 2), but most never returned or received the questionnaire (n = 21). Consequently, we received 35 patient ratings. Of these ratings one patient questionnaire was returned anonymously, consequently this was excluded from further analyses. Two patients participated in the follow-up twice and completed the questionnaires both times. Only their first response was included in this study. One patient did not permit his proxy to complete SASNOS, and only the response of the patient was registered. Consequently, we ended up with a sample consisting of 63 questionnaires were included for the analyses, including 32 patient ratings and 31 ratings completed by proxies. This is equal to a response rate of 55.2%.When the study period was completed, 78 patients had been invited for a follow-up assessment at the outpatient clinic. Of these, 2 never showed up. Of the remaining eligible 76 patients, 18 were excluded due to: aphasia .Descriptive data, comprising age at injury, sex, type of injury, time since injury relationship to proxy, and cohabitant status, were collected from the clinic's local database . Furthermore, length of post-traumatic amnesia (PTA) or confusion was used as an indicator of the severity of the brain injury. A score on the Glasgow Outcome Scale Extended (GOSE) indicated level of global outcome at time of follow-up. If any demographic or injury related data were missing from the local database, the information were retrieved from the patient's file, thereby eliminating any missing data. All questionnaires were investigated for missing data. In case of missing data from one SASNOS subdomain, the mean value, based on the other items from that specific subdomain, was inserted.PTA/length of confusion: PTA is defined as a period of loss of consciousness and an inability to make consistently new memories after a brain injury. When a patient is consistently oriented and able to remember day to day and make new memories, the resolution of the PTA or confusional state is complete. The length of time a patient remains in PTA or confusional state is a method to assess the severity of the brain injury and is associated with outcome. A duration of PTA of >28 days is considered as a severe brain injury , 27.GOSE: GOSE is an 8-level scale assessing the global outcome after brain injury. The scores indicate: 1 (dead), 2 (vegetative state), 3 (lower severe disability and completely dependent on others), 4 , 5 , 6 (upper-moderate disability and returning to previous work with adjustments), 7 , 8  , 29. It SASNOS: The main outcome measure used in the study was SASNOS, which consists of five major domains measuring NBD following an acquired brain injury: Interpersonal Behavior, Cognition, Inhibition, Aggression, and Communication. Each of the major domains consist of a number of subdomains, which are shown in All 49 items are scored on a seven-point Likert-scale from “never” to “always.” Ratings are transformed to standard scores. T-scores with a mean of 50 and standard deviation of 10 is used. Higher scores reflect greater perception of ability and fewer symptoms of neurobehavioral disabilities. Transformation to T-scores allows for cross-scale comparisons and comparisons to neurological healthy individuals. If a patient receives a score of 2 SD  from meaThe questionnaire was translated into Danish following the recommendations for the cross-culture adaption of health status measures, a standardized procedure with back-translation  with pert-tests. All statistical analyses were conducted using SPSS version 22.0.Demographics are presented using means and standard deviations (SD) as well as frequencies as appropriate. Ratings on SASNOS were transformed into a standard distribution, and T-scores were calculated using the SASNOS scoring program available online . Based oA total of 32 patients and 31 proxies completed and returned SASNOS. The majority of the patients were male (68.8%), and the majority of proxies were female (58.1%). Most proxies were spouses (51.6%) and parents (29.0%) living with the patient (61.3%) .Most brain injury survivors had suffered a traumatic brain injury  and had a mean age of 44.9 (SD 16.8) at time of the follow-up assessment. Most had sustained a severe injury indicated by length of PTA or period of confusion .The mean time since injury was 19.4 months (SD 10.0), and at time of follow-up, only a fourth of the patients were rated as having “good recovery” indicated by GOSE score of 7 or 8.Scores outside normal range: Raw scores on SASNOS were transformed to T-scores, and number of patients scoring outside the normal range were investigated. Based on the recommendations by the original authors, normal range was defined as more than 1 SD below the mean , and conThe highest frequencies of patients outside the normal range were found on two major domains of Interpersonal Behavior and Cognition. Ratings are depicted in p = 0.006) the longer the time since injury. Furthermore, proxies living with the patient rated the patient's Interpersonal Behavior (p = 0.036) and Aggression (0.044) domains higher, indicating fewer problems, than proxies not living with the patient. Another finding was that there was a significant association between proxies' ratings on the Cognition domain and the patients' scores on GOSE (p = 0.001) (Differences were found in relation to time since injury and cohabitant status. Proxies rated the patients' cognition as significantly lower (= 0.001) . No difft = −2.17, df = 30, p = 0.040) and on the following domains; Cognition , Aggression , and Communication . The mean scores are depicted in Differences between ratings completed by proxies and patients were investigated and significant differences were found, both on the Total Sum , Irritability , Overt aggression , Speech and language , and Mental state . On the Executive functioning, patients gave significantly higher ratings than proxies . These differences are depicted in On a number of subdomains, proxies gave significantly higher ratings; Engagement , and most studies have been conducted in America. Despite differences between the SASNOS and NFI, some of the subscales are similar. NFI also investigates aggression, but where the present study found lower ratings for proxies than patients using SASNOS, Seel et al. found no significant differences on this scale . By compCognition was the only domain, where patients reported fewer problems than their proxies. In both the Hart and Seel studies, no significant discrepancies were found between reports on cognition , 24. HowIt is important to address the long-term impact of NBD and be aware of potential changes in the pattern or degree of disabilities over time. It has become evident that brain injury survivors spend more time at home, have fewer friends and social contacts than prior to the injury . ChangesThe present study has some limitations. First of all, it is based on a relatively small sample. Over a period of two years, 32 patients met the inclusion criteria and agreed to participate in the study. The patients included had been hospitalized for specialized neurorehabilitation in the sub-acute phase. A criterion for this type of rehabilitation is that the injury is severe, which was supported by the patients' long period of confusion or PTA. This partly explains why it was not possible to include a larger number of participants. Some of the patients seen for the follow-up assessment in the outpatient clinic had severe cognitive disabilities, disorders of consciousness or severe aphasia. Patients with such disabilities were not able to complete the questionnaire and were consequently excluded. This affects the generalizability of the study, as patients with the most severe injuries might have been excluded. Using data from a cohort at a later stage post injury (> 2 years) could offer a larger sample size. Another reason for the small number of participants could also be a consequence of fatigue, which is common after ABI , 44. If Second, the validity of patient ratings can be challenged if patients with severe brain injury lack the ability to recognize their disabilities. Furthermore, proxy ratings can be biased due to a high level of stress or emotional impact. However, SASNOS has shown good psychometric properties regarding reliability and validity and SASNOS is one way to measure NBD containing the subjective aspect of consequences after ABI.Third, the single-center design is also a limitation, which warrants caution with respect to generalizing the results. However, as Department of Neurorehabilitation, TBI Unit, covers the Eastern part of Denmark that fact does expand the representativeness of the sample.The use of SASNOS in this study has indicated areas of potential research. First of all, it could be interesting to explore the impact of the severity of injury in relation to concordance of reports on the SASNOS questionnaires. Second, it could also be of clinical interest to compare SASNOS profiles in cases who have or have not received rehabilitation after ABI. Third, a study exploring if a SASNOS profile at an early stage of recovery can predict psychosocial outcome at a later stage, e.g., 2 to 5 years after injury, would be of clinical interest. If it is possible to identify factors continuously influencing the patient's ability for community reintegration in long-term, it would be possible to focus early or medium-term clinical interventions to help the patient and the family adapt, accommodate, and minimize the social handicap consequent upon NBD. This would be a fruitful area for future research studies, from which both patients and their families would benefit.All authors contributed to conception and design of the study; PS organized the database. AN performed the statistical analysis. PS and AN wrote the first draft of the manuscript. All authors wrote sections of the manuscript and contributed to manuscript revision, read 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.


Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases. However, complicated subdural empyema rarely occurs after trepanation and drainage of chronic subdural hematoma.A male patient (77 years old) was admitted to the hospital on the 2nd day of fever after an undergoing a “trepanation and drainage of chronic subdural hematoma” operation at a local hospital. After admission, the patient was treated with an emergency operation in which a subdural abscess was diagnosed and then administered antibiotics after the operation.According to the clinical manifestations, intraoperative findings of imaging examination and the results of pus culture, the diagnosis was subdural empyema.We surgically removed the subdural empyema. Postoperative antibiotics were administered according to the results of bacterial culture.At 3 months after the operation, the patient returned to the hospital for reexamination and was found to have achieved a good recovery and good self-care.Subdural empyema after trepanation and drainage of chronic subdural hematoma is a very rare and severe disease. Early diagnosis and operative intervention as well as the intravenous administration of antibiotics can improve the prognosis of patients and enhance their quality of life. After we contacted the ethics committee of The First Hospital of Jilin University, ethical approval was not required for this case report article. Informed consent was obtained from the patient for the publication of this case report.Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases.[2A male patient (77 years old) presented 3 days after an operation for “trepanation and drainage of chronic subdural hematoma” at a local hospital. The patient run a fever for 2 days and was admitted to the hospital on July 15, 2018. In his past medical history, the patient had suffered from diabetes for 25 years and had achieved mediocre effect by controlling his blood glucose levels with insulin. Admission PE: His Glasgow Coma Scale score was E3V5M6. On the right side of the wound, redness and swelling were observed at 1 operative incision, and there was a pink purulent secretion spilling out of the incision. The bilateral pupils were 2.0 mm in diameter and showed slow direct and indirect reactions to light. The limbs showed low muscle tension. The muscle strength of the left upper limbs was grade I, while that of the lower limbs was grade II, and that of the right limbs was grade V. Hyperreflexia was observed in the deep and superficial reflex in the right limbs, and the Babinski sign was positive. The patient's neck was stiff at a position of 3 transverse fingers. Findings on cranial CT showed a localized defect of the right parietal bone, a low density area in the right subdural space of the frontal, parietal, and temporal regions. The right brain tissues were compressed, and the cerebral sulcus was shallow and had disappeared. The right ventricle was compressed and decreased in size. The median line had shifted toward the left side (Fig. Klebsiella oxytoca” (Table During the operation, a drainage tube was placed subdurally through the original drill hole, and a large amount of purulent liquid and a small amount of bloody liquid were collected. The patient was diagnosed with “subdural empyema”, and craniotomy was performed. The dura mater was cut open at the site of the defect, a large amount of purulent yellow-white fluid was found subdurally in the frontotemporal part of the wound, and local separation had occurred Fig. C, D. Thea” Table . Third-ga” Table  E, F. Wh3Streptococcus milleri group, which is followed by other pathogenic bacteria, including β-hemolytic Streptococcus, Staphylococcus aureus, Haemophilus influenzae, Streptococcus mutans, and Pseudomonas. Escherichia coli,Propionibacterium acnes,Campylobacter fetusKlebsiella,[Klebsiella, a gram-negative bacillus that generally occurs in immunocompromised hosts.Chronic subdural hematoma is one of the most common neurosurgical diseases.[Conceptualization: Hongfa Yang.Data curation: Hang Xue, Weitao Zhang, Hongfa Yang.Funding acquisition: Hongfa Yang.Investigation: Weitao Zhang, Lin Shi, Yiming Zhang.Resources: Weitao Zhang, Bing Yu, Hongfa Yang.Software: Lin Shi.Visualization: Lin Shi.Writing – original draft: Hang Xue.Writing – review & editing: Hang Xue.


The woodland lost (deforestation) and woodland gained (afforestation) were collocated with intensive forest practices in the past 27 years. The conversions from woodland to cropland and from woodland to grassland were the dominant processes of deforestation and afforestation, respectively. Steep slope cropland was one of the major conversion patterns of afforestation after 2000. This result is mainly explained by the implementation of the “Grain for Green Program” policy and the large-scale development of eucalyptus plantations. Further efforts should be made to control deforestation in this area. These findings can also be used as a reference in the formulation and implementation of sustainable woodland management policies.It is increasingly acknowledged that land-use and land-cover change has become a key subject that urgently needs to be addressed in the study of global environmental change. In the present study, supported by the long-time-series of land-use and land-cover data from 1990, 2000, and 2017, we used the land-use transition matrix, Markov chain model and Moran’s I to derive detailed information of the spatial patterns and temporal variation of the land-use and land-cover change; additionally, we highlight the deforestation/afforestation conversion process during the period of 1990–2017. The results show that a total of 4708 km As an important part of worldwide sustainable development, LUCC and deforestation in China has attracted great attention8. Land cover refers to the biophysical attributes of the Earth’s surface, while land use refers to the human purpose or intent applied to these attributes9. Many previous studies have focused on revealing the effects of LUCC, e.g., the significant effects on resource production and the influence on climate change10, soil erosion11, biodiversity4, food security4, and even threats to public health12, while also concentrating on determining the drivers of LUCC14. However, examining the process and trends of LUCC via quantitative analysis is a prerequisite to gain a deeper understanding of LUCC and help policy makers set improvement targets in specific areas and adopt appropriate practices while also keeping in line with other fields of sustainability16. However, land-use data are also a prerequisite issue for the evaluation of LUCC in a specific region18. Based on this, we used land-use and land-cover datasets due to their high accuracy and long time scale features, which were produced by Chinese academics, to identify the patterns and processes of LUCC in the study region21.Land-use and land-cover change (LUCC) has been considered an important research topic for global environmental change and sustainable development10, and it is also a factor that provides feedback for the drivers of land-use change22. Many previous studies have reported that deforestation has a close relationship with climate change24, biodiversity loss and increases in CO2 and other greenhouse gases25, soil degradation26, flooding27, ecosystem services28, and human livelihood29. The effects of LUCC can even threaten economic development and food security31. Therefore, understanding the deforestation process and the related drivers in a quantitative way is necessary to provide appropriate policy intervention. The International Panel on Climate Change (IPCC) emphasized that the conversion between forest and other land-use types  is frequently referred to as deforestation. In contrast, afforestation “occurs when forest cover expands through the planting of trees on lands without trees”32. Thus, in the present study, deforestation is defined as woodland being converted into other land-use types, while afforestation is defined as other land-use types being changed into forested areas. The drivers of deforestation have significant regional characteristics, with the most common drivers of deforestation summarized as logging for timber, commercial agricultural development, urban and mining expansion, and grazing in Asia33. The implementation of a set of forest protection policies has contributed significantly to the growth of forest cover in China during the last 20 years34. Severe deforestation previously occurred in China, and the temporal and spatial characteristics of deforestation35, the drivers of deforestation36, and the conservation policies37 have been reported in several past studies39. However, there is a distinct lack of studies examining the transition between other land-use types and deforestation/afforestation based on a long-time-series of land-use data.Deforestation is an important process of LUCC40. An LUCC analysis using long-time-scale land-use data is effective for determining the major land-use conversion and provides useful information for planners and policymakers. Guangxi was chosen as a case study, as the southern area of China has experienced conflict between urbanisation and basic arable land protection as well as conflict between basic arable land protection and woodland protection in the past several decades42. The acceleration of urbanisation and industrialisation has led to serious ecological destruction, such as a decrease in ecological carrying capacity, vast coverage and intensity of water and soil loss, desertification, soil erosion, vegetation degradation, biodiversity losses, invasion of alien species, environmental pollution, natural hazards, geological hazards, and forest hazards44. Considering these conditions, the objectives of this research are as follows: (1) to identify the land-use change process in Guangxi during the periods of 1990–2000 and 2000–2017; (2) to evaluate the deforestation patterns based on LUCC analysis, and (3) to discuss the relationship between deforestation/afforestation patterns and possible drivers from a policy perspective.Since the economic reformation in China, land use has changed significantly, with various patterns and driving forces found at different spatial scales2 , including the six investigated land-use types, underwent changes in Guangxi. As seen in Fig. 2  and 197 km2 , respectively, since 1990. Every municipality expanded during the past 27 years  and 686 km2 (0.29%), respectively, in the study area; additionally, cropland gains (703 km2) occurred in Qinzhou. This decrease was followed by woodland areas, which decreased by 418 km2. Unused land was only altered slightly, with a change of less than 0.01% in the total area (8.6 km2), and woodland gains (1362 km2) occurred mostly in Guigang, Wuzhou, and Yulin. The results suggest that the area of land types with higher ecological values  decreased. Water bodies showed a slight increase in this region, and the major driver can be summarised as the national water sources/river protection polices that were implemented in the 1990s. However, because most remote sensing images were obtained from similar seasons (July–October), which includes the flood season in the southern region, this can also lead to interpolation errors for water bodies.The land use net change and spatial patterns are presented in Figs The land-use change processes and patterns are presented with the transition matrix and TPs    converted from woodland. Figure 2 increase in the woodland area, which mostly occurred in Guigang, Yulin, and Laibin  was converted into woodland. Figure 2 of water bodies were transformed from other land-use types. At the same time, 47 km2 of water bodies were changed into other land-use types. There was a slight decrease in unused land in this area.There were four major land-use changes that progressed as follows: built-up land expansion, deforestation, afforestation and decreased grassland. First, there was an expansion of built-up land (421 kmin) Fig. . Second,bin Fig. . Affores2 of woodland was lost or gained, respectively, in Guangxi.During 2000–2017, land-use activities became slightly stronger, with the lowest TPs of 0.97  was changed into built-up land. The greatest decrease in cropland occurred in Nanning, Baise, Guilin, and Guigang  and built-up land (400 km2). Deforestation mostly occurred in Wuzhou, Hezhou, Nanning, and Baise. In contrast, woodland increased significantly by 640 km2, with approximately 65.5% (419 km2) transformed from grassland. Figure 2, with 109 km2 of the water body area having changed into other land-use types and 165 km2 having been converted to water bodies from other land-use types , the map of slope in the study area was processed by ArcGis software. The slope was classified into four levels by thresholds of 2, 6, 15, and 25 degrees46. The converted cropland and the total areas of deforestation and afforestation were identified by different slope degrees.The feature of the “Grain for Green Program” (GFGP)  is the conversion of steep-slope or degraded cropland into forest or grassland2 of cropland in Guangxi in 2000 , we used the land-use matrix method, Markov chain model and Moran’s I to derive detailed LUCC information and analyse the deforestation and afforestation conversion patterns between two periods (1990–2000 and 2000–2017).49. In China, approximately 50% of cropland expansion resulted from deforestation in the past 300 years50, and this global value is 60%10. In China, the Economic Reform began at the end of the 1970s, in which cropland demand increased dramatically to feed the large population and support the agricultural industries51. Since 1979, the Household Production Responsibility System (HPRS) has been in effect, and in 1992, the market-directed economic system launched in China. All of these policies have led to specific land-use conversion, such as the conversion of woodland into cropland and built-up land52.During the past 27 years, woodland has experienced several conversion patterns in Guangxi. In the period of 1990–2000, woodland changed into cropland (deforestation), and grassland was converted into woodland (afforestation)  (FAPCA)54, the China Ecological Environment Conservation Plan (1998) (CEECP), the China Wetland Protection Action Plan (2000) (CWPAP), the China Mangrove Protection Management (CMPM), and the Utilization Plan (2002) (UP)52. All of these regulations and policies promoted afforestation throughout this period. During this period, approximately 20% of converted woodland was changed into grassland, and at the same time, approximately 41% of converted woodland was changed from grassland in Guangxi  (CBCAP)see Fig. . One pos56. Above all, urbanisation and industrialisation should be considered as important challenges leading to deforestation in Guangxi.After 2000, the deforestation pattern involved the conversion of woodland into built-up land  and degraded cropland and barren land into forest and grassland60. The GFGP is renowned as the largest ecological policy in the world and is closely related to LUCC61. Many previous studies have reported that the GFGP has worked effectively in China, as woodland has been restored60, ecosystem services have improved62, soil organic carbon levels have increased45, and biodiversity has been enhanced61. In addition, the afforestation process, including the conversion between grassland and woodland in Guangxi, can mostly be explained by the rapid growth of eucalyptus logging.Since 1999, in a bid to combat serious ecological issues, such as droughts and floods, the Chinese government launched the “GFGP” program in 25 provinces, which covers 82% of the total land area of China63. Hansen et al.63 stated that a collocation of gains and loss of forest can be found in China, indicating that intensive forest practices are executed in this region. This result is mainly due to the large-scale development of eucalyptus plantations in China. Eucalyptus is planted not only in Guangxi but also in most of southern China, such as Guangdong, Yunnan, Hainan, Sichuan and Fujian provinces, of which approximately 1.4 million ha are in Guangxi64. Eucalyptus plantations provide a large amount of timber and, due to their adaptability and stable rapid growth, have caused a set of potential ecological issues, such as water deprivation, biodiversity loss, desertification, and fertilizer consumption65. In addition, our study also indicates that the conversion of steep-slope  land is the primary conversion process in Guangxi, but the converted cropland accounts for 1.18% of the total steep-sloping cropland. As previous studies and GFGP regulations suggest, all steep-sloping cropland  should be converted to forest47. Thus, in terms of sustainable development in Guangxi, reducing the ecological issues of water and fertilizer related to eucalyptus plantations and implementing the GFGP are important features for the future.Although the conversion from cropland to woodland has been effectively stopped, especially since 2000, the area of deforestation has decreased but is still larger than the area of afforestation. At the same time, deforestation and afforestation have co-existed in Guangxi in all periods, and this is in accordance with the results of previous studieshttps://earthenginepartners.appspot.com/science-2013-global-forest/download_v1.5.html) to analyse the deforestation and afforestation in Guangxi; the major result found that deforestation and afforestation are collocated in Guangxi, which is in agreement with the results of a previous study63. However, due to the different interpolation methods, classification systems and definitions of forest , there are also some different results that can be extracted from these two datasets (GFCD and CNLCD). Overall, this study analysed deforestation and afforestation based on land-use change analysis and indicated the different patterns of deforestation and afforestation. We then analysed the relationships with major policies and major forest practices, providing useful information for decision-makers.As a comparison, we also used the Global Forest Change data (GFCD) , which included the six investigated land-use types. The general pattern of LUCC in this region included an expansion of built-up land and water bodies as well as a reduction in woodland, cropland, and grassland areas. The transition from cropland and forest to built-up land in addition to the transition from cropland and grassland to forest have been the dominant LUCC patterns over the past 27 years. Woodland is the dominant land-use type in Guangxi. From 1990 to 2017, deforestation and afforestation have both occurred, with deforestation being the major ecological problem during the past 27 years. After the implementation of the GFGP in 1999, the conversion from woodland to cropland was effectively curbed in this region. At the same time, the large-scale development of eucalyptus plantations has accelerated the afforestation and deforestation processes in Guangxi. Eucalyptus plantations have also led to serious ecological issues in Guangxi. Sustainable woodland management under new economic development plans should remain high on the political agenda.LUCC analysis can provide important information for global environment change and sustainable development studies, which can also be useful for decision-makers. In this research, using a long-time-series of  remote sensing images with high resolution (30 m and 8 m), we obtained detailed information of LUCC and highlighted the woodland conversion process in Guangxi during the periods of 1990–2000 and 2000–2017. Our findings show that the area of land use and land cover transition in Guangxi was 4708 kmThis paper found the major trends of historical land-use conversions in Guangxi and indicated the related policy framework for woodland transition processes. We have provided an understanding of the national policy aspect; however, the LUCC resulted from land-use change and feedbacks on the drivers of land-use change. Therefore, a further study focused on the “cause-response” of LUCC is needed in this region.43. It includes fourteen municipalities  was 20,396.25 billion Yuan (CNY), with an annual increase of 7.3%69.Guangxi, located in southern China, is a typical area that faces many ecological problems and challengesies Fig. . GuangxiThe major land-use type in Guangxi is woodland, with the proportion of woodland being over 65.5% of the total area in 2017. This is followed by cropland and grassland, which cover proportions of 21.5% and 8.8% of the total area, respectively. Most of the woodland is distributed in Baise, Hechi, and Guilin, followed by Liuzhou, Nanning, Chongzuo, and Wuzhou, with approximately 26.1% of the total woodland distributed over these seven municipalities. Beihai is the smallest woodland city, contributing only 0.7% of the total area of woodland in 2017. The total area covered by water bodies, built-up land, and unused land accounts for less than 10% of the land area in Guangxi.70. Computer-assisted visual interpretation of satellite images was used to create a digital LUCC map at a spatial scale of 1:100,0003. More technological details can be found in previous studies21. Then, the interpretations of the satellite images were validated against a number of field surveys. Many previous studies reported that the overall accuracy was over 95%; specifically, accuracy was 98% for grassland, forest, and built-up land and 99% for cropland71. In the present study, we created 299 random points and using Google Earth (https://www.google.com/earth/) to validate land-use data from 2017, and the overall accuracy in the first class was 89%.The long-time-series land-use data were obtained from Chinese National Land use/Land Cover Database (CNLCD), which was developed by the Chinese Academy of Sciences (CAS). The database spans from 1990 to 2015 and is updated at 5-year intervals. This database was produced via long-time-series remote sensing data. More than 500 TM/ETM+/OLI scenes from satellite images were used to map all of China for each period72 and to identify the drivers of LUCC70, through which optimal land-use strategies can be modelled73.These datasets have been widely used to identify the detailed information of LUCChttps://www.usgs.gov/) for 2015 and Gaofen-1 (GF-1) (http://www.cresda.com/EN/satellite/7155.shtml) for 2017 were used as the key information sources. Most of the image data were acquired during similar seasons (July–October) and were selected on the grounds of being cloud-free. Above all, the land-use data in this research covered three time periods: 1989/1990, 2000, and 2017 , and in an effort to create a uniform spatial scale, we interpolated based on different minimum patches. Specifically, in 1990 and 2000, 8 × 8 pixels (approximately 240 × 240 m on the ground) were employed, and in 2017, 30 × 30 pixels (240 × 240 m) were employed. For more details, refer to previous studies75. The classification used in this study was based on 25 land-use types defined by Liu et al.3, which were then grouped into six land-use types, including cropland, woodland, grassland, water body, unused land, and built-up land  between different states are recorded in a transition matrix that originates from the land-use transition matrix79. The transition possibilities (TPs) matrix can be expressed as follows77:Land-use change is not a unidirectional process, and a specific land-use type is theoretically changed into or from other land-use typesThe Markov chain model is a random process; the state of one land-use type at time t + 1 only depends on the current time t and is not related to any time before t. The state of the land-use type (St) at beginning time t and end time t + 1 (St + 1) can be expressed as follows:80. The basic principle of Moran’s I is as follows80:This study used Moran’s I to analyse the global spatial autocorrelation of each land-use type in Guangxi since 1990. Spatial autocorrelation is generally used to describe and compare the spatial structure of data81. In this study, Geoda was used to calculate the global spatial autocorrelation82.The value of Moran’s I is between . When I = 0, there is no autocorrelation between the data; when I > 0, there is a positive relation between observations; when I < 0, the relation is positivek) and mapping the spatial patterns of woodland losses and gains. The deforestation and afforestation rates were calculated using the following formula:Sa and Sb are the areas of the land-use type at the beginning and end of a period, respectively.To highlight the features of deforestation and afforestation over time, we analysed the deforestation and afforestation rates by calculating the change rate for woodland (The land use conversion process between 1980s and 2000 (left), between 2000 and 2017 (right)