In terms of lifestyle, the percentage of moderately and vigorously active children decreased  (p = 0.014). The percentage of children sleeping more than 9 h increased (p < 0.001). They watched more television programs (p < 0.001). Regarding oral hygiene, children did not change their brushing habits (p = 0.225). The percentage of children using non-fluoridated toothpaste was higher (6.4%), and no changes were observed (p > 0.05). In some cases, dental pain and abscesses were declared . This study confirms the need for campaigns to promote hygiene and dental care in combination with food education for a correct habit and promotion of a healthy and sustainable dietary style.The Severe Acute Respiratory Syndrome Coronavirus 2 disease COVID-19 pandemic caused several lifestyle changes, especially among younger people. The study aimed to describe the impact of eating habits, lifestyle, and home oral hygiene during the COVID-19 pandemic, on the cariogenic risk in the Italian paediatric population, by using an online survey. The survey was conducted through a virtual questionnaire divided into four parts: child personal and anthropometric data; oral health; child dietary habits (KIDMED test); and child lifestyle, before and during COVID-19 lockdown. During the lockdown, only 18.6% of the participants had high adherence to a Mediterranean diet, recording an increase in sweets consumption and the number of meals ( In the last year, our world has changed dramatically due to a new pandemic virus that spread all over the globe: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new form of coronavirus that has triggered a worldwide state of emergency, causing a strong impact on our lifestyles and eating habits. The lockdown has led to a rapid change in the habits and lifestyles of the population: physical distancing, reduction of socialization and relationship life, increase in time spent at home, digital education, smart working, and limitation of physical activity outdoors and in closed places .Since March 2020, several studies have been conducted to understand almost all of the changes in everyday life in different population categories and under precise circumstances .According to an Italian survey conducted on 3533 subjects between the ages of 12 and 86, changes in habits and lifestyles during the lockdown influenced eating habits and adherence to the Mediterranean diet model, particularly in the younger and older populations [Regarding Italy, the country has been subjected to several restriction laws that characterized different periods as part of a “hard” lockdown (from March to May 2020). During the tougher times, all non-necessary shops were closed, going out was banned, and people were encouraged to work online. At other times, people had the chance to go out and go to work, and almost all the shops had reopened . In all The lockdown has caused several health and psychological problems in different subjects, including young people and children . ChangesThis new situation compromised the maintenance of a healthy and varied diet and introduced incorrect habits that could increase cariogenic risk.Dental caries is one of the most common childhood diseases, and it continues into adulthood . GloballThe risk factors for pathological caries are frequently caused by the consumption of dietary sugars, inadequate fluoride, poor oral hygiene, and salivary dysfunction, whereas the protective factors are a healthy diet, brushing with fluoride toothpaste twice a day, professional topical fluoride, preventive and therapeutic sealants, and normal salivary function .Therefore, caries risk assessment is complex because a variety of social, cultural, behavioural, and socio-economic factors .In a study conducted in Southern Italy on a sample of non-migrant, economically disadvantaged children (age range: 12–14 years old), a Decayed, Missing, and Filled Teeth (DMFT) index of 3.29 ± 3.21 and caries prevalence of 55.9% were highlighted [Dental caries is a biofilm-mediated, sugar-driven, multifactorial, dynamic disease that is determined by the loss of the mineral homeostasis of tooth surfaces and by the imbalance between the demineralization and remineralization phases of the enamel. The pathological caries risk factors shift the balance in the direction of demineralization, dental caries, and lesion progression, whereas protective factors promote remineralization, lesion arrest, or regression .Although dental caries has a microbial aetiology, dietary sugar has been the most important risk factor .Healthy eating behaviours appear already in early childhood; in fact, the first months of life are crucial for the learning process of taste in humans and the subsequent acceptance of foods, especially healthy ones . A diet The total energy intake is the sum of all daily calories/kilojoules introduced with the diet, including macronutrients, such as fat, protein, carbohydrate-included total sugars (free sugars + intrinsic sugars + milk sugars), dietary fibers, and ethanol . Free sugars include monosaccharides and disaccharides added to foods and beverages by the manufacturer, cook, or consumer; and sugars naturally present in honey, syrups, fruit juices, and fruit-juice concentrates .The World Health Organization  recommends a reduced intake of free sugars throughout the life course (strong recommendation), with a reduction of free-sugar intake to less than 10% of the total energy intake (strong recommendation), and preferably below 5% of the total energy intake  in both adults and children .According to a systematic review of the literature to inform WHO guidelines, it appears that 42 out of 50 studies conducted on children reported a positive association between sugar intake and caries. According to the authors, there was moderate-quality evidence showing that caries is lower when free-sugar intake is <10% of the total energy intake. With a <5% energy cut-off, the risk of caries could be further reduced, but the evidence was judged to be not strong enough [The importance of the WHO Sugar Guidelines for Dental Health and Obesity Prevention was also shared in the joint European Organisation for Caries Research (ORCA)/ European Association of Dental Public Health (EADPH) symposium on sugar and oral health in 2016 .Studies in the literature often evaluated the frequency of intake of added sugars, rather than free sugars and their association with caries pathology in pediatric age . Added sA review of sugar consumption from national representative dietary surveys across the world reported that intakes of added sugars were higher in school-aged children and adolescents  compared to younger children or adults . In EuroThe purpose of this study was to analyze, in a pediatric population, the cariogenic risk related to changes in eating habits, lifestyle, and home oral hygiene during the COVID-19 lockdown.The Eating Habits and Lifestyle Changes in COVID-19 lockdown (EHLC-COVID-19) project  is direcThe survey was conducted for 6 months, from 15 July 2020 to 15 January 2021, among the Italian paediatric population by using an online platform accessible with an Internet connection through any device. The survey was diffused through institutional and private social networks , the “PATTO in Cucina Magazine” website , and insThe study was carried out in full agreement with national and international regulations, and the Declaration of Helsinki (2000). Parents were fully informed about the study requirements and were asked to accept the data-sharing and privacy policy before filling out the questionnaire, which was directly connected to the Google Form platform. The parents’ and child’s personal information, including names, were anonymized to maintain and protect confidentiality. The web survey was anonymous and did not allow us to trace sensitive personal data in any way. Moreover, the present web survey study did not need approval from the Ethics Committee. Once completed, each response was transmitted to the Google platform and the final database was downloaded as a Microsoft Excel sheet.The levels of adherence to the Mediterranean diet (MD) in our study were measured with the KIDMED index.The KIDMED test is the most used test in the literature to assess adherence to the MD in children and young people. KIDMED was devised by Serra-Majem et al. in subjects between the ages of 2 and 24, focusing on specific eating habits of the MD. The questionnaire could be self-administered or completed by interview .The 16 KIDMED questions ranged from 0 to 12 points. Most of the questions concerned the frequency of consumption of different food groups and their portions without specifying grams. The score was assigned as follows: positive adherence to the MD, +1; and negative adherence, −1. The sum of the values from the tests was divided into three levels: >8, excellent adherence to the MD; 4–7, need to improve daily intake according to MD models; ≤3, non-congruent quality with the MD model .The questionnaire on cariogenic risk during COVID-19 was specifically structured using Google Forms by the Section of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, of the University of Rome Tor Vergata, and by the Paediatric Dentistry Post-Graduate School of the University of Rome Tor Vergata. The questionnaire included 56 questions divided into 4 different sections: (1) child’s personal and anthropometric data ; (2) oral health before and during the COVID-19 lockdown ; (3) child dietary-habit information before and during the COVID-19 lockdown: (a) 8 questions , (b) 16 questions: adherence to the MD among children and adolescence (KIDMED) , (c) 4 qp-value < 0.05. Statistical analysis was performed using SPSS ver. 21.0 .Data are represented as numbers and percentages in parentheses (%) for categorical variables or mean and standard deviation (SD) for continuous variables. The Shapiro–Wilk test was performed to evaluate the distribution of variables. All the variables had a skewed distribution. The Spearman correlation coefficient was calculated to evaluate the correlation between continuous variables. A chi-squared test was employed to assess the association between categorical variables, while McNemar’s analysis was used to investigate the difference between categorical variables before and during the COVID-19 emergency. Mann–Whitney U and Kruskal–Wallis tests were performed to compare continuous variables among two or more groups, respectively. Finally, binary and multinomial logistic regression analyses were conducted to investigate the association between categorical variables (dependent) and continuous or categorical ones (independent). Results were significant for On 15 January 2021, the web survey was concluded and the collected data were analyzed. A total of 225 participants completed the questionnaire. Five interviewees did not give their consent for the data treatment; hence, 220 subjects, aged between 4 and 14 years old, were included in the data analysis. The age distribution of the sample is shown in The territorial coverage extended to the following Italian regions: Lazio (76.4%), Abruzzo (4.1%), Lombardy (2.7%), Calabria (5.9%), Apulia (4.5%), Emilia Romagna (0.9%), Veneto (1.4%), Campania (1.4%), Tuscany (0.5%), and Molise (2.3%). The majority of the interviewees lived in Rome (57.7%).To evaluate compliance with the MD recommendations during the COVID-19 lockdown, the KIDMED questionnaire was included in the survey. The KIDMED score showed that only 18.6% of the participants had high adherence to the MD during the lockdown .Regarding daily water consumption during the lockdown period, 46.4% of children drank between 1 and 2 L of water per day according to the reference intake levels for the Italian population . Table .p < 0.001). The number of meals before and during the lockdown also increased (p < 0.001) . No difference between the two periods was found concerning the use of probiotic supplements (p = 0.475) (14.5% before vs. 12.3% during).Concerning eating habits, half of the participants had not changed their eating habits (50.9%), but the data showed an increase in sweets consumption during the COVID-19 lockdown . Before p < 0.001). 53.6% of the whole sample declared to have followed a more sedentary lifestyle during the lockdown, compared to the 3.6% who were sedentary before; the percentage of moderately active children decreased from 64.5% to 41.4%; while the percentage of children who had vigorous physical activity before the lockdown changed from 31.8% to 5.0% (Lifestyle habits before and during lockdown changed significantly ( to 5.0% .p = 0.014)  .p < 0.001)  .p < 0.001) .Children also watched more television programs (TV) during the lockdown compared to before (p = 0.225). Results also showed that children had not changed their sleeping hygiene routines and continued to brush their teeth before going to sleep (p = 0.338). Conversely, there was a significant difference in terms of drinking or eating after tooth brushing, showing that children had increased this habit during lockdown . However, they had not changed their brushing habits, and they used their personal toothpaste  .Some of the subjects did not treat their caries during lockdown (7.3%).The results analysis showed that the COVID-19 lockdown led to substantial changes in the dietary and eating habits of families. Although the survey was disseminated on social networks or mailing lists and therefore covered the entire Italian territory, the majority of respondees (76.4%) were from Lazio. It is probable that parents belonging to our department or university responded more. However, being an anonymous survey, this remains a supposition.The KIDMED questionnaire results showed that most children’s diets during the pandemic were normally adherent to the MD model. According to MD adherence, children with a low, medium, or high score had an adequate consumption of extra virgin olive oil, fish, legumes, milk, yogurt, pasta, and rice. Following our results, some studies reported that dietary behaviours improved , while others worsened  in Italian children during the COVID-19 lockdown . Accordip < 0.001), and in eating behaviours between meals .Our results showed that during the lockdown, there was an increase in the consumption of sweet products, biscuits, and snacks, and reduced consumption of foods such as fruit, vegetables, and nuts. The consumption of sweets increased in 51.4% of the sample, with an additional change in the number of meals  in American children, which led to an increased risk of obesity, diabetes, and cardiovascular diseases . These dp < 0.001), which could be related to the increase in the frequency of eating between meals. According to a recent study, children aged 10–12 who watched TV (>90 min per day) were more likely to consume cariogenic foods and develop caries disease [In our results for Italian children, we observed that our interviewees changed their lifestyle habits during the lockdown, preferring a more sedentary behaviour compared to before. This aspect influenced sport decisions, because they suddenly stopped their workouts, preferring individual open-air sports . Changes in sports activity and lifestyle influenced sleeping quality and routines. Children tended to sleep more during lockdown compared to before. These data probably are connected to an increase in hours spent watching TV. Our data showed an increase in hours/day spent watching TV  .Jansen et al. showed an association between parental stress in the period of the COVID-19 lockdown, with children given foods particularly rich in kcals during snack times and more processed snacks with low nutrients  .The limited possibilities for daily shopping during the COVID-19 lockdown also led to changes in food choice that may have reduced the consumption of fresh foods  in favour of highly processed ones  rich in sugar, fats, and salt. These sugar-rich dietary habits and the intake of energy-dense, low-nutrient-dense snack foods may increase cariogenic risk.The intake of beverages and foods containing simple carbohydrates is not recommended between meals , and sevAn analysis of DMFT/DMFT and body fat mass, measured by DXA, demonstrated a specific correlation with dietary habits  .It is important to underline that even non-sweet snacks  are potentially cariogenic  due to tAccording to the pathogenesis model of caries based on the “ecological plaque hypothesis”, a greater role has been assigned to sugar intake in the aetiology. An increased frequency of fermentable sugar intake determined repeated conditions of low pH in biofilms, selecting an acid-tolerating bacterial community and cariogenic species . SpecifiThe goal of dental caries prevention is to preserve a strong tooth structure, prevent demineralization of enamel, and promote natural healing processes.p > 0.05). Moreover, 75% of them did not modify their tooth-brushing habits  (p > 0.05), or was not used at all  by a high percentage of subjects. The percentage of children using non-fluoridated toothpaste was higher than that observed (6.4%) in a cross-sectional study conducted in New Zealand on 4723 children [Good oral hygiene habits related to tooth brushing before going to sleep and toothpaste choice were also maintained by comparing the period before lockdown and during lockdown ( > 0.05) . Surprischildren . It is pchildren . They alchildren . We suppFluoride is safe and highly effective to prevent children’s dental caries  and reduFurthermore, 0.9% of the study subjects did not use toothpaste at all, and 32% did not have their own toothpaste but used their parents’. We cannot clarify to what extent these figures were influenced by the limited shopping possibilities during the lockdown.p < 0.001). This erroneous habit was linked to ECC with the administration of bottles filled with fermentable liquids containing carbohydrates, rather than soothers dipped in honey or sugar [Moreover, the data analysis related to eating frequency  or drinking habits  before going to sleep and after brushing teeth highlighted a significant increase, from 0.77 ± 1.41 to 1.08 ± 1.70 times per week during the COVID-19 lockdown (or sugar ,13. Thesor sugar . In a reor sugar . Thus, aor sugar . Even inor sugar , it is eor sugar .According to the data of the study, 7.3% of the subjects had already been diagnosed with caries pathologies before the lockdown. During the lockdown, 10% experienced painful dental symptoms, and 2.7% experienced abscess pathologies.Unfortunately, the COVID-19 lockdown initially limited routine oral care and prevention except for emergency and urgent interventions, but according to Brian and Weintraub, the pandemic offered an opportunity for the dental profession to shift more toward non-aerosolizing and prevention-focused approaches . AttendiOur results confirmed previous data on risk factors for early childhood caries .As recently reported, applying a 25% AgNO3 solution followed by a commercially available 5% NaF containing functionalized tricalcium phosphate could be a solution for the prevention and control of dental caries .The limitations of this study concern the poor sample size, as well as the lack of clinical data on oral health status and hygiene index.This survey showed that during the COVID-19 lockdown, there was an increased risk factor of caries compared to protective factors. This was due to an increased intake of fermentable sugars, frequent consumption of dietary sugars, frequent intake of snacks between meals, incorrect oral-habit hygiene, and inadequate topical fluor prophylaxis caused by an occasional use of fluoride toothpaste. It was concluded that in this pandemic period, a caries-prevention program aimed at parents and children is essential to intercept caries pathology risk factors and encourage protective behaviors, while also considering the prolongation of the emergency period.


N = 1531 participants  between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescent Version, and Interpersonal Needs Questionnaire. Moderation analyses were performed. Results: No statistically significant differences were found in the frequency of lifetime NSSI in the adolescents based on gender. Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of lifetime NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of lifetime NSSI, and between perceived burdensomeness and the frequency of lifetime NSSI. Conclusions: Thwarted belongingness and perceived burdensomeness might be positively associated with the frequency of lifetime NSSI, and MIL might be negatively associated with the frequency of lifetime NSSI. Thus, adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve assessment and treatment protocols for adolescents with NSSI.Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) might be negatively associated with thwarted belongingness and perceived burdensomeness. To date, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of lifetime NSSI in Spanish adolescents. Aims: (a) To test whether thwarted belongingness and perceived burdensomeness are associated with frequency of lifetime NSSI; (b) to test whether MIL moderates the association between thwarted belongingness and frequency of lifetime NSSI; and (c) to test whether MIL moderates the association between perceived burdensomeness and frequency of lifetime NSSI. Method: The sample consisted of  Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI) ,2. In faSeveral authors  suggest In an effort to better understand NSSI, the Interpersonal-Psychological Theory of Suicide (IPTS)  could prHowever, although the IPTS does not suggest that thwarted belongingness and perceived burdensomeness are associated with NSSI, participants who engage in NSSI may have difficulties with emotional deregulation, interpersonal relationships, or impulsivity, which may lead to feelings of being a burden to their families . FurtherIn the same way, individuals with a history of NSSI can lack meaningful social connections with others and feel that they are a burden to others. Previous studies found that people with NSSI had less interpersonal support than people without NSSI , and thaWhen people feel that they are a burden to other family members or that they do not belong, they experience deep emotional distress, which can lead to increased emotional deregulation and psychopathology. Performing NSSI would lead them to escape emotionally from this emotional distress, and NSSI would have the function of trying to bring emotional deregulation through emotional escape . Thus, tTo date, two previous studies have analyzed the association between thwarted belongingness and NSSI frequency. In a previous study with non-clinical adolescents found that lifetime NSSI frequency was moderately and positively associated with perceived burdensomeness and thwarted belongingness . In the Nevertheless, the aforementioned studies focused on analyzing risk factors for NSSI, and no studies have analyzed protective factors between perceived burdensomeness and thwarted belongingness and the frequency of lifetime NSSI in adolescents. In this regard, the construct of thwarted belongingness could be negatively associated with the construct of meaning in life (MIL) . MIL couIn adolescents, MIL has been positively associated with health, stress reduction ,25,26, aRegarding the association between MIL and NSSI frequency, several studies found that MIL was negatively associated with NSSI frequency in participants with borderline personality disorders ,31 and eIn sum, taking the aforementioned studies into account, to date, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of lifetime NSSI. Therefore, research is needed to better understand the possible association between perceived burdensomeness and thwarted belongingness and the frequency of NSSI , and it Thus, the aims of this study are: (a) to test whether thwarted belongingness and perceived burdensomeness are associated with the frequency of lifetime NSSI; (b) to test whether meaning in life moderates the association between thwarted belongingness and the frequency of lifetime NSSI; and (c) to test whether meaning in life moderates the association between perceived burdensomeness and the frequency of lifetime NSSI.Therefore, based on the studies mentioned above, we hypothesize that: (a) thwarted belongingness and perceived burdensomeness will be associated with the frequency of lifetime NSSI; (b) MIL will be a moderator between thwarted belongingness and the frequency of lifetime NSSI; and (c) MIL will be a moderator between perceived burdensomeness and the frequency of lifetime NSSI in Spanish adolescents.N = 1531 participants between 12 and 18 years old from Spain. The mean age was 14.85 years (SD = 1.56). Regarding gender, n = 736 (48.1%) were men, and n = 795 (51.9%) were women.The study sample consisted of The convenience sample was composed of adolescents between 12 and 18 years of age who were invited to participate in the research voluntarily through the schools. Participants and parents were given appropriate instructions to complete the assessment protocol. Parents were asked for written informed consent and a commitment to participate in the study, as well as the corresponding written authorizations for the minors’ participation, which were administered through the tutors of each course. An email address and a telephone number were provided to answer parents’ questions and help the participants. Only two participants contacted the researchers and were offered the resources they might need, and four parents were interested in knowing what questionnaires would be used and their possible risks. Participation was voluntary and anonymous, and no compensation was given for participating in this study. The inclusion criteria were that participants had to be adolescents between 12 and 18 years old, and the adolescents and their parents had to give their informed consent.To recruit the convenience sample, 22 schools in Spain were contacted by mail or telephone. Eight of these schools finally decided to participate in the study. There are no differences between the schools that decided to participate and the ones that did not in terms of economic, cultural, and social characteristics. The participants were studying Compulsory Secondary Education or pre-university courses in Spanish schools: 25% of the participants came from the Valencian Community, 22% from the Basque Country, 17% from La Rioja, 20% from the Community of Madrid, 6% from Castilla la Mancha, 6% from Castilla-León, and 4% from Aragon.The participants answered the questionnaires through an online platform on an ordinary school day in their own classes. The time period for answering the questionnaires was approximately 30–40 min. After the evaluation, a contact email was provided in case any of the participants required more information or needed to talk with a clinical psychologist. None of the participants made use of this service.We followed the World Health Organization definition of adolescents as people from 10 to 18 years old. The study procedure was approved by the Ethical Committee of the Catholic University of Valencia Saint Vincent Martyr (Project Identification code UCV 2015-2016-25-V2).Inventory of Statements about Self-Injury (ISAS) [ISAS-I) asks about the lifetime frequency of 12 different NSSI behaviors performed intentionally and without suicidal intent: banging/hitting self, biting, burning, carving, cutting, wound picking, needle-sticking, pinching, hair pulling, rubbing skin against rough surfaces, severe scratching, and swallowing chemicals. Adolescents were asked to indicate how many times they had injured themselves.y (ISAS) . The prePurpose-In-Life Test-Adolescents Version (PIL-A) [PIL-A are answered on a Likert scale ranging from 1 to 7, with a specific anchor for each item, and they assess two factors: satisfaction and meaning in life and purposes and goals in life. The total score ranges between 10 and 63. Higher scores represent higher meaning in life. The PIL-A assesses general beliefs about meaning in life, for example: “In life I have: from 1 = No goals or aims at all to 7 = Very clear goals and aims”; “I have discovered: from 1 = No mission or purpose in life to 7 = Clear-cut goals and a satisfying life purpose”. In the present study, the PIL-A showed high internal consistency (α = 0.89). (PIL-A) . This sc (PIL-A)  for asseInterpersonal Needs Questionnaire (INQ) [INQ is a self-report measure composed of 15 items that evaluate the main constructs of interpersonal suicide theory , which predicts the desire to commit suicide through two factors: thwarted belongingness and perceived burdensomeness. The items are answered on a Likert scale. Higher scores represent higher thwarted belongingness and higher perceived burdensomeness. Representative items from the INQ are: “These days, the people in my life would be better off if I were gone”; “These days, I feel disconnected from other people” . The subscales showed good internal consistency for thwarted belongingness (α = 0.83) and perceived burdensomeness (α = 0.88) in our sample.re (INQ) . The INQISAS-I into a 5-range scale: 1 = no presence of NSSI; 2 = between 1 and 4 times; 3 = between 5 and 50 times; 4 = between 51 and 100 times; 5 = more than 100 times. To test differences in the presence and frequency of lifetime NSSI between genders, we performed t tests and we used the Welch test when there was a violation of variance equality on Levene’s test. Next, we tested the moderation role of meaning in life (PIL) in the association between thwarted belongingness (PIL) and NSSI frequency. Finally, we tested the moderation role of meaning in life (PIL) in the association between perceived burdensomeness (INQ) and NSSI frequency. Moderation analyses were conducted using the PROCESS macro for SPSS32 [First, means, standard deviations, and correlations between continuous variables were calculated. Second, we turned the r SPSS32 . To avoir SPSS32 .n = 1115, 72.8% participants did not report any lifetime episodes of NSSI; n = 207, 13.5% between 5 and 50 episodes; 146, 9.5% more than 100 episodes; 32, 2.1% between 51 and 100 episodes; and 31, 2% between 1 and 4 episodes of lifetime NSSI. In the subsample of women participants, n = 587, 73.8% participants did not report any lifetime episodes of NSSI; n = 106, 13.3% between 5 and 50 episodes; 65, 8.2% more than 100 episodes; 22, 2.8% between 1 and 4 episodes; and 15, 1.9% between 51 and 100 episodes of lifetime NSSI. In the subsample of men participants, n = 528, 71.7% participants did not report any lifetime episodes of NSSI; n = 101, 13.7% between 5 and 50 episodes; 81, 11% more than 100 episodes; 17, 2.3% between 51 and 100 episodes; and 9, 1.2% between 1 and 4 episodes of lifetime NSSI. There were no differences in the frequency of lifetime NSSI by gender, t = 1.749, p = 0.08.Regarding the frequency of lifetime NSSI in the overall sample, r = 0.62, p < 0.01), and it had a low association with NSSI frequency . Perceived burdensomeness had a positive and low association with NSSI frequency . Finally, MIL was highly and negatively correlated with thwarted belongingness  and perceived burdensomeness , and it had a low and negative association with NSSI frequency .t = 4.53; p < 0.001; adjusted R2 = 0.09) and perceived burdensomeness  predicted the frequency of NSSI in adolescents. Moreover, MIL moderated the association between thwarted belongingness and NSSI frequency  = 39.90, p < 0.001, adjusted R2 = 0.12). After entering thwarted belongingness, MIL predicted NSSI frequency, both in addition to thwarted belongingness and when interacting with thwarted belongingness, thus supporting a moderating impact of MIL on the association between thwarted belongingness and NSSI frequency  = 9.39, p < 0.001). As F = 36.28, p < 0.001, adjusted R2 = 0.10). After entering perceived burdensomeness, MIL predicted NSSI frequency, both in addition to perceived burdensomeness and when interacting with perceived burdensomeness, thus supporting a moderating impact of MIL on the association between perceived burdensomeness and NSSI frequency  = 3.88, p < 0.001). Finally, MIL moderated the association between perceived burdensomeness and NSSI frequency . Thus, our hypothesis was confirmed. Our results are similar to those found in other studies with adolescents, showing that the relationship between thwarted belongingness and perceived burdensomeness was associated with NSSI frequency , sheddinR2 adjusted range 10–12%). Our results might be explained by the fact that adolescents with low MIL could develop a greater number of interpersonal and behavioral problems in the family, such as substance use, eating disorders, and risk behaviors [Regarding the second and third aims, our results suggest that MIL was a moderating variable between thwarted belongingness and the frequency of lifetime NSSI, as well as between perceived burdensomeness and the frequency of lifetime NSSI, confirming our hypotheses. However, although meaning in life was a moderator variable, the amount of variance explained by the models was small , whiehaviors . These fehaviors . Howeverehaviors , good inehaviors , loving ehaviors  2006), tehaviors .Moreover, our results are consistent with studies showing that connectedness was inversely associated with NSSI . KlonskyAlthough there is consensus about the moderating role of MIL in the risk factors for suicide in previous research with adults , we shouRegarding the frequency of lifetime NSSI, we found that 27.2% of the participants had carried out lifetime NSSI. Although there is high variability across studies regarding the frequency of NSSI , our perOur results have important theoretical and practical implications. Based on our results, thwarted belongingness and perceived burdensomeness could be positively associated with the frequency of lifetime NSSI, and MIL could be negatively associated with the frequency of lifetime NSSI. Based on the theory of the functionality of NSSI , an adolINQ refers to participants’ recent perceived burdensomeness or thwarted belongingness. This is a key limitation given the lack of temporal ordering, and it is possible that the perceived burdensomeness or thwarted belongingness was a consequence of NSSI, and not the other way around. Previous studies suggested that people with NSSI had difficulties with emotional deregulation, interpersonal relationships, or impulsivity, which lead to feelings of being a burden to their caregivers [Our study has some limitations that should be taken into account when interpreting the results. An important limitation is that the outcome measure was the frequency of lifetime NSSI, whereas the predictor variable regivers . In addiregivers . This isIn conclusion, based on previous studies ,17 and t


Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental brain disorders in childhood. Despite extensive researches, the neurobiological mechanism underlying ADHD is still left unveiled. Since the deficit functions, such as attention, have been demonstrated in ADHD, in our present study, based on the oddball P3 task, the corresponding electroencephalogram (EEG) of both healthy controls (HCs) and ADHD children was first collected. And we then not only focused on the event-related potential (ERP) evoked during tasks but also investigated related brain networks. Although an insignificant difference in behavior was found between the HCs and ADHD children, significant electrophysiological differences were found in both ERPs and brain networks. In detail, the dysfunctional attention occurred during the early stage of the designed task; as compared to HCs, the reduced P2 and N2 amplitudes in ADHD children were found, and the atypical information interaction might further underpin such a deficit. On the one hand, when investigating the cortical activity, HCs recruited much stronger brain activity mainly in the temporal and frontal regions, compared to ADHD children; on the other hand, the brain network showed atypical enhanced long-range connectivity between the frontal and occipital lobes but attenuated connectivity among frontal, parietal, and temporal lobes in ADHD children. We hope that the findings in this study may be instructive for the understanding of cognitive processing in children with ADHD. Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders, characterized by age-inappropriate symptoms of inattention, hyperactivity, and impulsivity . It arisThe brain is not only a dynamic system but also a complex network . Of noteIn this study, we hypothesized that the differences in ERP components could reflect on which stage the cognitive deficits in ADHD occurred, and brain network analysis might further uncover the potential network mechanism underlying the task behaviors of ADHD during the designed P3 tasks. Therefore, to better understand how ADHD children recruit cognitive resources to complete the tasks, the ERP and complex network analyses were adopted to investigate the potential differences between HCs and ADHD children.Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria of ADHD diagnosis. Two psychiatrists made these diagnoses independently based on DSM-5 and needed to assess the children in two or more situations. For the control group, age-matched children did not have ADHD or any other psychiatric disorders. Exclusion criteria were neurological disorder, a history of brain injury, mental retardation, comorbid current psychiatric diagnosis, and other neurodevelopmental disorders.A total of 71 children, including 40 ADHD children  = 2.11 years) and 31 HCs  were recruited from Shenzhen Luohu District Maternity and Child Healthcare Hospital, China. ADHD children needed to meet the Our experiment complied with a standard oddball paradigm, as shown in Ω.The EEG data were recorded with a 16-channel Ag/AgCl  electrode cap . All electrodes were positioned according to the 10-20 international system. During online data recording, electrode AFz served as the reference. EEG signals were sampled at 1000 Hz and online bandpass filtered at 0.05-100 Hz. During recording, the impedances of all electrodes were kept below 5 kt-test.Reaction accuracy (RA) was the ratio of the number of correct responses to the total number of stimuli. Reaction time (RT) was measured from the onset of the stimulus to the time for response (pressing the “1” key) as indicated in the recordings. Any potential differences in RA and RT between the HCs and ADHD children were investigated by an independent μV were implemented to preprocess the EEG datasets. In fact, to evoke the clear P3, subjects have to pay all of their attention to the target stimuli, by mentally counting the target number or physically pressing the required button [Multiple preprocessing procedures, including References Electrode Standardization Technique (REST) referencing –29, [1, d button , which wd button . After cd button .t-test.After preprocessing, all artifact-free trials were trial-averaged for each subject. Then, according to previous studies , 33, theThe phase lock value (PLV) was proposed to estimate the phase synchronization among each pair of signals  and has ϕx(t) and ϕy(t), of two given signals, x(t) and y(t), the analytical signal H(t) is defined by the Hilbert transform (HT) as follows:t) and t) are the HT of x(t) and y(t), which are defined as follows:ϕx(t) and ϕy(t), can be computed as follows:To estimate the corresponding instantaneous phases, wplv is the connection weight estimated by PLV, Δt is the sampling interval, and N denotes the sample number.Finally, the PLV value can be estimated as follows:t-test was used to investigate the potential difference in brain architecture between the two groups.Based on the PLV, the adjacency matrix per trial per subject was first calculated. Afterwards, for each subject, the final weighted network, a 16 × 16 adjacency matrix, was acquired by averaging matrices across all trials. Based on these constructed brain networks, an independent t-test.In our present study, when estimating the cortical current density of P2 and N2, the sLORETA (v20171101) was adopted. The cortex has been modeled as a collection of volume elements (voxels) in the digitized atlas provided by the Brain Imaging Center, Montreal Neurological Institute (MNI) . The sLONo significant differences in RA and RT between the two groups were first found in this study, as shown in p < 0.05), as displayed in Thereafter, when investigating the concerned ERP components on electrodes P3 and P4, similar results on both electrodes were found. In detail, no significant difference in P3 was found between the HCs and ADHD children. On the contrary, the amplitudes of both P2 and N2 were reduced in ADHD children, when compared to HCs (p < 0.01) and in temporal, frontal, and occipital regions for N2 (p < 0.01), whose MNI coordinates, T-value, and voxel number are listed in Tables Given the differences in N2 and P2, the differences corresponding to the cortical activity between the two groups were statistically investigated, which are shown in p < 0.05) between the two groups. In detail, relatively stronger functional connectivity  among frontal and occipital lobes but weaker linkages  among frontal, parietal, and temporal regions were found for ADHD children, when compared to HCs.As previously illustrated, ADHD patients usually showed the task deficits in varied substage information processing, such as information integration and neuronal response stages, rather than the whole task period . HoweverBeing exposed to external stimuli, to achieve satisfying task performance, the brain has to receive, integrate, process, and respond to their perceived target stimuli. P3 is the neuronal response to target stimuli after the decision process . Li et aP2 is regarded as the exogenous response, as it is automatically produced regardless of the task or attention variables but is amenable to attentive manipulations, and its latency and amplitude may covary with aspects of selective attention or stimulus encoding processes . TherefoMore evidence underlying these differences would be acquired, when considering the cortical N2 and P2 activity. On the one hand, compared to ADHD children, HCs showed much stronger activity in frontal, cingulate, and central areas for P2. And these cortexes involved in the generation of P2  and abnoGiven that only EEG datasets of several ADHD girls were collected, one possible limitation was that our present study did not take the gender effect into consideration; in the future, the gender-matched ADHD children will be recruited to validate if the gender could affect our present findings. Another might be that the task behaviors were not taken into consideration when selecting reliable task trials; in our future, more detailed individual behaviors would be recorded and then analyzed during preprocessing to further validate our current findings.Although no significant differences in task behavior between the HCs and ADHD children were found, electrophysiological ERP and functional network did uncover the potential cognitive deficits in ADHD children, especially in the early task stage. In particular, significant differences in both N2 and P2 amplitudes and cortical activity, but not in P3, between the two groups were first found. And further, the topological differences showed the attenuated functional connectivity among frontal, parietal, and temporal lobes in ADHD children, which might be compensated by the enhanced long-range frontal-occipital connectivity to accomplish the required tasks.


Following the fourth Industrial Revolution, electronic and data-based technology is becoming increasingly developed. However, current research on enhancing electromagnetic interference (EMI) shielding and the physical protection performance of structures incorporating these technologies is insufficient. Therefore, in this study aiming for the improvement of EMI shielding and structural performance of structures, twelve concrete walls were fabricated and tested to determine their shielding effectiveness and drop-weight impact resistance. Concrete walls strengthened by three thickness types of high-strength, high-ductility concrete (HSDC) have been considered. The test results showed that the shielding effectiveness with strengthening thickness increased by approximately 35.6–46.2%. Specimens strengthened by more than 40% and 10% of the strengthening area ratio of single- and double-layer, respectively, exhibited more than 20 dB of shielding effectiveness. Moreover, the relationship between the damaged area ratio and shielding effectiveness was evaluated by means of the drop-weight impact test. The structural performance and EMI shielding effectiveness improved as the HSDC thickness increased. The fourth Industrial Revolution Industry 4.0) has brought the importance of data-based industries to the forefront; as a result, the need for electromagnetic interference (EMI) shielding has increased to maintain the circuitry of electric devices in a normal state. EMI shielding is achieved via the loss of electric field strength when electromagnetic waves are reflected or absorbed by conductive materials. EMI shielding is generally achieved using heavy metal plates, conductive paints/spraying, or conductive mesh, which require a high initial investment and continuous maintenance, assuming that they are even effective. Few studies have been conducted on the shielding- and structural performance of undamaged structures ,3,4,5,6..0 has brThere are many types of metallic powder employed as conductive constituents, such as metal oxides, steel furnace slag, and iron. This powder needs to be incorporated into the matrix of manufactured materials at a certain volume fraction to achieve effective shielding properties; this represents the percolation threshold ,2,3,5. FIt is important not only to build new buildings using the developed conductive cementitious materials or metallic grid/mesh but also to protect existing buildings from EMI. There is little research published on SE tests of existing buildings in which normal concrete has a little EMI resistance ,2,3. A gckf > 120 MPa) and published [The compressive and flexural strength properties of developed hybrid fiber-reinforced HSDC have already been evaluated , the strengthening thickness of HSDC , and the layer type of HSDC (single or double). Hence, this study aims to contribute basic data regarding the EMI SE and impact resistance of reinforced concrete through fiber-reinforced cementitious composites.3 and specific surface area of 3413 cm2/g), crushed fine aggregate (density of 2.60 g/cm3 and fineness modulus 2.88), and coarse aggregate (density of 2.67 g/cm3 and fineness modulus 6.63) were used in this study, with a maximum aggregate size of 18 mm. The sieve analysis of the aggregates used is exhibited in 3 and specific surface area of 200,000 cm2/g), and silica filler (density 0.75g/cm3 and specific surface area of 2.65 cm2/g) were used as binder materials, as shown in The normal concrete (NC) mix proportion was established based on the target compressive strength of 45 MPa at 28 days, and the materials used in this paper are reported in To evaluate the EMI SE and impact resistance of the reinforced concrete, twelve specimens were prepared, as detailed in The near-field condition method was used for the EMI SE test of concrete specimens, in which customized EMI instrumentation  utilizes a frequency range of 400–1400 MHz based on the transmitting and receiving facility. This method was demonstrated to show similar results to the far-field condition results, based on MIL-STD-285 . The detFor the evaluation of impact resistance, a drop-weight impact test was conducted on all specimens under low-velocity impact loading conditions, employing a user-defined setup. The detailed setup of the drop-weight impact test is shown in HSDC consisting of polyethylene and steel fibers with no specific orientation was developed and investigated. Well-known for their strength-improving qualities, hybrid fibers help to reduce cracking and tensile strain, while simultaneously enhancing electrical conductivity and improving toughness ,14,15.fl = 19.5 mm, and reinforced concrete showing a length of fl = 35 mm, thus leading to the conclusion that the fibers are significantly shorter in HSDC. Fiber length, size, shape, and aspect ratio all played an important role in the SE of the concrete when reinforced with fibers [The results of the EMI SE test for HDSC of differing thicknesses are shown in h fibers .The results for the EMI SE tests of concrete specimens with varying thicknesses of HSDC are shown in a and b are the regression coefficients, and T is the thickness of HSDC.Additionally, it is evident that the increase in spacing of two strengthening layers in HSDC does not directly affect growth in SE for the reinforced specimen, therefore an increase in SE is not simply achieved through the application of increased thickness in HSDC, as shown in 2) of 0.989 and 0.944, respectively. An improvement of 35.4–65.7% in SE properties is observed in specimens strengthened by double-layer HSDC compared to that of single-layer strengthening when referring to the proposed prediction equation. Interestingly, HSDC strengthened members for both single- and double-layer strengthening saw the majority change in frequencies between 1000–1400 MHz.Experimental results showed a strong agreement with that of predicted values in specimens strengthened by single- and double-layer HSDC concrete, showing coefficients of determinations . The fourth and fifth drop blows saw crack widths of 5.00 mm and 5.50 mm in H5D and H10D, respectively. Unsurprisingly, the H20D sample that had the largest HSDC thickness was the most resilient when considering impact loading. Furthermore, the cracking patterns observed on the bottom side of the test specimen demonstrated hairline crack widths as the primary form of cracking, with a width of approximately 0.05 mm after the first impact. Crack widths of 0.70 and 1.10 mm were measured after the fourth and fifth blow, respectively, and were seen to be the maximum crack widths at that time. In comparison to the H5D and H10D samples, the strengthening materials in H20D were more successful in controlling and mitigating crack growth. The sixth impact load resulted in new deformation to the specimens on their underside, showing fibers bridging the pre-existing large diagonal cracks; additionally, wide diagonal cracks presented, originating in the center of the specimen, and ending at its edges. Large diagonal cracks resulting from fracturing are reproduced in Furthermore, the influence of the number of strengthening layers and thickness on the impact capacities of specimens, using total imparted energy, is shown in As found in previous research ,20, the Specimens strengthened with 20 mm of HSDC exhibited the lowest SE decrease ratio compared to those of the other specimens, which exhibited as approximately 7.1 and 24.7%, respectively. This is because specimens strengthened by 5 and 10 mm of HSDC exhibited large amounts of spalling at the center of the bottom surface in the impact region, which significantly decreased the effective thickness. However, specimens strengthened with a single layer exhibited smaller values of SE decrease ratios compared with double-layer-strengthened specimens, at similar damage area ratios. This is presumably because the single-layer strengthening method confirmed slightly improved SE values; thus, comparatively small values were measured before and after the impact test. The specimens strengthened by a double layer exhibited higher SE levels in terms of damage compared to single-layer-strengthened specimens (with and without an impact test). Furthermore, although various areas of damage decreased the effective thickness of test specimens, the SE decrease ratio exhibited similar values at similar damage area ratios in those specimens without different strengthening thickness, according to the uniformly distributed steel fiber.The specimens strengthened with HSDC displayed an increase in SE with increasing strengthening thickness, which was 2.4–35.3, 7.0–31.9, and 6.9–43.8 dB, respectively, comparatively higher than specimens without strengthening. For the single- and double-layer HSDC strengthening, a strengthening area ratio greater than 40% produced an SE that was over 20 dB.The properties of specimens reinforced with a double layer were greater than those of specimens reinforced with a single layer . The specimen’s improved impact resistance characteristics corresponded with the strengthening side numbers and thickness, and similar strength trends were achieved for specimens with 20% strengthening area ratios.Specimens reinforced by 20 mm of HSDC had the lowest SE decrease ratio when compared to other specimens reinforced by 5 and 10 mm of HSDC, which showed around 7.1 and 24.7%, respectively. This is due to large amounts of spalling in the center of the bottom surface in the impact region in specimens strengthened by 5 and 10 mm, which greatly reduced the effective thickness. Although multiple incidents of damage were displayed and lowered the effective thickness of test specimens, the SE reduction ratio demonstrated equal values in similar damage area ratios of specimens that had uniformly dispersed steel fiber.This research was conducted to assess the SE and impact resistance properties of concrete walls strengthened with high-strength high-ductility concrete. A variety of strengthening methods were adopted to evaluate the SE and impact resistance. From this investigation, the following conclusions can be drawn:Therefore, concrete structures that have been strengthened by HSDC could be chosen in applications exhibiting the need for increased SE.


Tuberculous meningitis is difficult to diagnose and is associated with high mortality. Recently, several studies evaluated the intensified regimen containing higher dose rifampin to treat tuberculous meningitis. However, this topic remains to be concluded. Therefore, this systematic review and meta-analysis was conducted to evaluate pharmacokinetics parameters, safety, and survival benefits of high-dose rifampin for tuberculous meningitis.via The Cochrane Risk of Bias Tool. The meta-analysis was performed by Review Manager 5.3 software, the synthesis of the data was shown in mean difference (MD) or relative risk (RR), and 95% confidence intervals (CIs).Data were searched from PubMed, EMBASE, The Cochrane Library, and Web of Science for studies describing an antituberculosis regimen including a higher dose of rifampin for patients with tuberculous meningitis. The quality of eligible studies was evaluated p < 0.00001; MD = 0.74, 95%CI , p < 0.00001], as well as the area under the time concentration curve between 0 and 24 h (AUC0−24) of rifampin  in plasma, but the overall survival did not improve . For adverse events, the results showed a statistically significant lower incidence of hypersensitivity compared with the intervention group . Fortunately, other common adverse drug reactions such as liver injury, neurological events, myelosuppression, and cardiotoxicity had no significant increase .There were six randomized control trails included in this meta-analysis. The results showed that the concentration in plasma and cerebrospinal fluid (CSF) were significantly higher in the intervention group than the standard group [MD = 22.08, 95%CI , This meta-analysis suggested that the intensified treatment regimen including a higher dose of rifampin significantly increased the rifampin concentration both in the plasma and CSF, and it was safe in patients with tuberculous meningitis, but resulted in no improvement in survival rates. Mycobacterium tuberculosis. It typically affects the lungs which is called pulmonary tuberculosis, however, the disease can also affect other areas such as bones, lymph nodes, abdomen, central nervous system, and so on, named as extrapulmonary tuberculosis. According to the 2020 World Health Organization global tuberculosis report, approximately 10.0 million people fell ill with TB in 2019, and 1.4 million people died because of TB infection  and meninges, accounting for approximately 5 to 10% of all extrapulmonary TB (Tuberculosis (TB) is a common disease caused by onary TB . The clionary TB . In patiM. tuberculosis  AND “mening*”) OR “central nervous system tuberculosis”) AND “rifampi*”). The search strategy consisted of entry terms and MeSH terms. Studies were considered eligible based on the following criteria: (1) The original study population were people with a diagnosis of tuberculous meningitis. The diagnosis of tuberculous meningitis could be achieved by clinical diagnosis, microbiological confirmation, molecular tests such as nucleic acid amplification or Xpert MTB/RIF Ultra, brain imaging like computed tomography (CT) and magnetic resonance imaging (MRI), and immunodiagnostic tests such as interferon gamma release assays. (2) The intervention group received an intensified antituberculosis regimen consisting of a weight-based dose of rifampin more than 10 mg/kg/day; the delivery method could be intravenous or oral, and alongside other antituberculous drugs. (3) The control group accepted standard therapy containing rifampin at 10 mg/kg/day, along with other antituberculosis medications. (4) Articles described treatment outcomes including pharmacokinetic parameters for rifampin in serum containing an area under the time concentration curve between 0 and 24 h (AUC0−24), maximum concentration (Cmax) in plasma and CSF, mortality, and adverse events (AEs). A study was excluded if it was a case report, case series, comment, editorial, letter, review , animal experiment, or the full text was unavailable.In this systematic review and meta-analysis, we searched the electronic databases PubMed, Embase, Web of Science, and The Cochrane Library for English language articles published up to 1 July, 2021, with the search terms , HIV infection, glucocorticoids used or not, standard rifampin dosage, standard treatment regimen, high-dose rifampin dosage, intensified regimen, and treatment outcomes.The risk of bias of the included studies was assessed using the Cochrane Risk of Bias Tool, which was recommended by the Cochrane handbook version 5.10 . It inclP < 0.05. The studies' heterogeneity was assessed by the Chi-square (α = 0.1) and I-square tests, with P < 0.1 and I2 > 50% indicating heterogeneity. A random effects model was applied regardless of heterogeneity. If heterogeneity was observed among the studies, subgroup analysis was performed to investigate the possible source of heterogeneity.The outcomes were analyzed by RevMan 5.3 software. The dichotomous variables were expressed as ratio and frequency, while the continuous variables were reported as mean and standard derivation (SD). For an included study containing the data of the median as well as the maximum and the minimum, the results were analyzed after the data were transformed through the conversion formula. The effect size of the intervention on dichotomous variables and continuous variables was shown in risk ratio (RR) with 95% confidence intervals (CIs) and mean difference (MD) with 95%CIs, respectively. Results were considered as significant when A total of 1,185 published studies were retrieved from the electronic databases. After removing 485 duplicated articles, a total of 700 records remained. Then these studies were screened by the titles and abstracts, after this step, 648 studies were excluded. A total of 52 studies were selected for careful full-text assessment. Finally, six articles were included into this meta-analysis. The study flow diagram of the included studies is shown in The six included RCTs were published from 2013 to 2021, involving data from 1280 participants. Among these people, 567 patients had HIV infections. Of these included studies, the intervention group had rifampin dosages ranging from 13 mg/kg/day intravenously to 35 mg/kg/day orally. The intervention groups in three trials containing 63 participants who were administered high-dose rifampin intravenously, the remained 1,217 patients took rifampin orally. In two studies the intensified regimen involved quinolones, one of them containing levofloxacin at 20 mg/kg/day , while aThe Cochrane Risk of Bias Tool was applied to assess the risk of bias of the included studies. Two studies could not be blinded because intravenous and oral administration of rifampin was compared , 15, so max of rifampin , p < 0.00001; I2 = 88%. Subgroup analyses were conducted to explore the sources of heterogeneity, containing rifampin application methods, higher dose rifampin treatment duration, rifampin dosage, and whether the intensified regimen used drugs besides HZE , p < 0.00001; 2. Through the subgroup analysis, the rifampin dose and intervention treatment period were the most probable reason for heterogeneity  , 15, 16,p = 0.90; The overall effect by the random effects model demonstrated that hepatotoxicity had no significant difference among the two groups [RR = 0.98, 95%CI , p = 0.01; The occurrence of developing an allergic reaction was found with statistical significance in the high-dose rifampin arm compared with the standard dose arm [RR = 1.72, 95%CI , p = 0.23; Two studies , 15 repop = 0.22; Four articles , 15, 16 p = 0.70; Two studies conducted by Heemskerk  and RuslThe mortality and disability rates of TBM are still high despite sufficient antituberculosis medicated therapy and the use of adjunctive corticosteroids, so it is very necessary to find new ways to improve the treatment outcome of TBM. Due to the long time it takes to explore new drugs for TB, the best way is to make full use of existing drugs. In recent years, a higher dose of rifampin for TBM has been assessed in several articles. Thus, in this systematic review and meta-analysis, we evaluated the pharmacokinetic parameters of rifampin in CSF and plasma, as well as the safety and survival benefit of the antituberculosis therapy regimen including a higher dose of rifampin. We found that increasing the dosage of rifampin could obviously increase the rifampin concentration in CSF and plasma, however, without significantly improving survival rates compared with the standard regimen. For adverse events, no significant difference was found in the safety between the two groups besides the occurrence of hypersensitivity.max along with the dose increase of rifampin. When administering the dose at 35 mg/kg/day for 2 weeks, the average AUC0−24 was approximately 10 times higher than the exposure of rifampin at 10 mg/kg/day, from 26.3 to 235.4 h.mg/L. The same results were observed in a trial enrolling patients diagnosed with pulmonary TB who were given a regimen containing a higher dose of oral rifampin at 15 and 20 mg/kg daily for a longer period of 2 months, which resulted in a more than proportional increase in the level of rifampin exposure in plasma  As Mycobacterium tuberculosis . In accordance with the present results, previous studies have demonstrated that no significant difference in terms of safety between a standard dose rifampin regimen and a higher dose rifampin regimen in pulmonary tuberculosis .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.


Psoriasis is a common, recurrent, immune skin disease, which seriously affects patients’ quality of life. In clinical practice, modified Runji ointment can effectively treat mild-to-moderate psoriasis with blood dryness syndrome, but there is a lack of high-quality evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of nano-modified Runji ointment in the treatment of mild-to-moderate psoriasis with blood dryness syndrome.This study will be a randomized double-blind placebo-controlled trial. A total of 80 patients will be recruited and randomly divided into an intervention group (nano-modified Runji ointment group) and a placebo group at a ratio of 1:1. All included patients will receive 8 weeks of nano-modified Runji ointment or placebo ointment respectively, twice a day. The primary outcome will be the change in psoriasis area and disease severity index score at week 8 compared to baseline. The secondary outcomes will be rash area score, pruritus score, Dermatology Life Quality Index score, traditional Chinese medicine symptom score and adverse events.This study may provide high-quality evidence for the efficacy of nano-modified Runji ointment in the treatment of mild to moderate psoriasis with blood dryness syndrome. The results of this study will be published in peer-reviewed journals.https://www.chictr.org.cn/edit.aspx?pid=55884&htm=4ChiCTR, ChiCTR2000034292. Registered July 1, 2020,  Runji ointment is a common medicine used to treat psoriasis with blood dryness syndrome by ancient TCM doc. Our pre-experiment showed that modified Runji ointment can alleviate the symptoms of dry skin rash and itching in patients with psoriasis of blood dryness syndrome, and promote the regression of the rash.2http://www.chictr.org.cn/edit.aspx?pid=55884&htm=4). This study was conducted in accordance with the principles of the Declaration of Helsinki (2014 edition). The protocol was reviewed and approved by the Medical Ethics Committee of Shunyi Hospital of Beijing Traditional Chinese Medicine Hospital .Before the first patient was enrolled in this study, it was registered with the Chinese Clinical Trial Registry, registration no. ChiCTR2000034292 ; and signed the informed consent form. The informed consent process was in accordance with the provisions of good clinical practice.5Any of the following cases will be excluded: patients treated with vitamin D 3, retinoic acid, or corticosteroids within 1 month; those who are allergic to the study drug; complicated with cardiovascular, cerebrovascular, liver, kidney, hematopoietic system, and other serious primary diseases and mental patients; pregnant or lactating women with family planning within 3 months; and patients who are participating in clinical trials with other drugs.6The random sequence will be generated by the professionals of the data management center using SAS 9.2 software . According to the ratio of 1:1, patients will be assigned to the intervention group (nano-modified Runji ointment group) and placebo group. The random allocation table and random code will be kept strictly confidential, and the allocation hiding will continue throughout the experiment.7The treatment plan will blind the enrolled patients, and the investigator and clinical pharmacist will also be blinded. Only the Key Unit of Methodology in Clinical Research of Shunyi Hospital of Traditional Chinese Medicine has access to the random allocation table. Those who participated in the study and those related to the trial will also be blinded. After the study is completed, the research team can view the blind assignment. In the event of a medical emergency, it is necessary to understand the patient's previous treatment and the current treatment plan, and the researcher will unblind. The researcher will try to contact the project leader first, then contact the relevant statistician, and use a separately arranged emergency code to unblind.8Radix Angelicae sinensis, Caulis Spatholobi, Rhizoma Dioscoreae, Radix Rehmanniae recens, Rhizoma Smilacis Glabrae, Nidus Vespae, and Radix Clematidis. The drug dosage form was granules, twice a day for 8 weeks, and it is provided by Guangdong Yifang Pharmaceutical Co., Ltd.All enrolled patients underwent the TCM decoction Yangxue Huoxue Decoction, a prescription for the treatment of psoriasis with blood dryness syndrome. It is composed of A sinensis, Fructus Cannabis, Caulis Spatholobi, Caulis Polygoni Multiflori, Fructus Aurantii, Radix Angelicae dahuricae, Radix Clematidis, and Radix Lithospermi. Preparation process: these medicines were soaked in sesame oil for 48 hours, and then fried at an oil temperature of 100°C to 120°C until they were browned, the oil was filtered, and then the medicines were nanometerized using nanotechnology to make nano ointment. The placebo ointment used by the placebo group is mainly composed of petrolatum and pigment, which makes its properties and appearance look similar to the ointment in the intervention group. The ointments for the intervention and placebo groups were obtained from the Institute of Chemistry, Chinese Academy of Sciences.The medicine used by the intervention group is nano-modified Runji ointment. Its ingredients are Radix The frequency of use of the nano-modified Runji ointment and placebo ointment was twice a day for 8 weeks. The dosage of each drug was determined according to the size of the skin lesions. Approximately 2 palm areas (approximately 2% of the body surface area) can use 1 fingertip unit ointment.99.1The primary outcome was the change in the psoriasis area and disease severity index score (PASI) from baseline to week 8. PASI is the gold standard for the diagnosis and evaluation of psoriasis, a simple and effective scale proposed in 1978.[E, erythema; I, infiltration; D, scales; A, area; H, head; U, upper limbs; T, trunk; L, lower limbs. The scoring range of skin lesion area: 1, <10%; 2, 10% to 30%; 3, 30% to 50%; 4, 50% to 70%; 5, 70% to 90%; 6, 90% to 100%. The scores for I and D ranged from 0 to 4: 0, no symptom; 1, mild; 2, moderate; 3, severe; 4, very severe. E's scoring method: 0, no erythema; 1, mild erythema; 2, moderate erythema; 3, significant erythema; 4, severe erythema. The total PASI ranged from 0 to 72 points. The higher the score, the more serious the condition.9.29.2.1The area of skin lesions was evaluated using the palm area method.9.2.2The visual analog scale method was used to evaluate the degree of itching of the subjects in the past week, which is represented by a 100 mm long line. 0: no itching, 100 mm: most itching, and the degree of itching is unbearable.9.2.3The Dermatology Life Quality Index is a questionnaire commonly used in the daily diagnosis and treatment of the Dermatology Department.9.2.4The TCM symptom score was used to measure changes in the symptoms of blood dryness syndrome. The syndrome score scale was divided into 3 dimensions: scaly, itching, and dry mouth. The score of each dimension was 0 to 7 points, and the total score was 0 to 21 points. The higher the score, the more severe the symptoms.All patients will be followed up by experienced investigators . The above outcome indicators will be evaluated at 0, 2, 4, 6, 8, 12, and 24 weeks. All the observed indicators are shown in Table 9.2.5All adverse events (AEs) will be recorded and any serious AEs will be reported to the Research Ethics Committee within 24 hours. When AEs occur, the study investigators will request that the patient terminate the treatment and then determine whether this event was related to the nano-modified Runji ointment. The principal investigator may implement urgent safety measures to protect patients from immediate harm. If the AE is related to the nano-modified Runji ointment, it is termed as a side effect. If the side effect is mild and the patient agrees to commence, the treatment will continue after the symptoms abate or disappear. Patients will withdraw from the study if serious AEs are observed.9.3We expect that after the end of the treatment period, the PASI of patients in the intervention group will drop by 2 more than in the placebo group, with a standard deviation of 3. It is now inferred that the probability of type I error is 5% on both sides, and the probability of type II error is 20%. Therefore, 36 patients were included in the study. Considering the 10% loss to follow-up rate, each group needs to recruit 40 patients.9.4Data collection and management are required before the start, during, after treatment, and during the follow-up period. Research data was recorded on the case report form form and then entered into the electronic system (double data entry). All personal private information about the patients was hidden.9.5P values <.05 (two-tailed) will be considered statistical significance.A statistician blinded to the patient allocation for each group performed all analyses using SPSS 21.0 software . Statistical analysis will be performed on an intention-to-treat basis. The intention-to-treat analysis included all randomized patients. We will describe the data using frequency counts and proportions for qualitative variables and means ± standard deviation will be used for normally distributed quantitative variables, and median (interquartile) will be used for non-normally distributed quantitative variables. We will apply the chi-square test to examine the differences between the intervention and placebo groups for qualitative variables, the t-test to examine the differences between 2 groups for normally distributed quantitative variables, and the Wilcoxon rank-sum test for non-normally distributed quantitative variables. A generalized linear model was applied to quantitative variables with repeated measures. In this study, 10The WHO regards psoriasis as a serious global problem.TCM has a long history of treating psoriasis, which divides psoriasis into 3 types of syndromes: blood heat syndrome, blood stasis syndrome, and blood dryness syndrome.[Golden Mirror of Medicine, is a topically applied ointment used by ancient TCM doctor to treat psoriasis. It consists of Radix A sinensis and Radix Lithospermi. According to the clinical manifestations of patients with blood dryness syndrome, our research group added Fruits Cannabis, Caulis Spatholobi, Caulis Polygoni Multiflori, Fructus Aurantii, Radix A dahuricae, and Radix Clematidis, and made them into modified Runji ointment. Previous studies have shown that the modified Runji ointment can effectively alleviate the symptoms of psoriasis with blood dryness syndrome.Runji ointment, from However, this study also has some limitations: first, this study only included patients with mild-to-moderate blood dryness psoriasis. It is not clear whether the modified psoriasis is effective in patients with severe psoriasis and other syndromes. Second, the ointment is taken home by the patient for self-use. Although the patient was required to record the medication events and conditions, the true medication compliance could not be confirmed.Conceptualization: Guanru Li, Liyun Sun.Data curation: Guanru Li.Funding acquisition: Guanru Li.Investigation: Yue Qiu, Libo Du, JiaLi Qian, JiuLi Liu, TengFei Ma.Methodology: Guanru Li, YaQuan Hou, Liyun Sun.Project administration: Guanru Li.Resources: Libo Du, Kaixuan Zhao.Writing - original draft: Guanru Li.Writing - review & editing: Guanru Li, Liyun Sun.


M = 22.00; SD = 3.83), were administered a set of questionnaires pertaining to IA, problematic social media use, emotional (dys)regulation, and personality traits. Pearson’s correlations showed significant associations between IA and the investigated variables, and the tested mediation model highlighted the crucial role played by emotional (dys)regulation in the fear of missing out and problematic use of social networks. Overall, the findings provide support for a new integrated model for understanding the features, predictors, and risk factors of IA.Internet addiction (IA) has mostly been investigated with the fear of missing out and difficulties in emotional regulation. The present study examined the link between IA and variables related to problematic social media use , together with emotional (dys)regulation and personality traits, providing new insights and an integrated assessment of IA. In total, 397 participants, aged 18–35 years ( Internet addiction (IA), also known as problematic internet use, has been defined as problematic and compulsive use of the internet, resulting in significant impairments to daily life functioning. IA is closely linked to computer addiction, which may otherwise be referred to as online addiction and technological addiction. More in detail, IA is an addictive disorder characterized by intensive and obsessive use of the internet, including social networking, video, and online gaming sites ,2.In particular, social network overuse can be considered as one form of IA, where individuals exhibit a compulsion to use social media ,4 leadinAs such, it encapsulates a wide range of psychopathological behaviors , whose common matrix seems to be impulse dysregulation ,10,11 anDysregulated emotional responses may foster addictive behavior as a means of coping with high levels of stress. In this vein, individuals with a propensity towards emotional distress have been found to be more likely to engage in substance use. Specifically, studies of opioid ,17, cocaDespite this empirical evidence of the role of emotional dysregulation in addictive behavior, many questions still remain. In particular, it is not yet known whether emotional dysregulation is a cause, correlation, or consequence of addictive behavior.IA is not currently listed as a formal disorder by the main diagnostic classifications, such as the Diagnostic and Statistical Manual of Mental Disorders—fifth edition (DSM-5)  and the The internet enables users to connect with others, discover new worlds, acquire new knowledge, and create positive emotions . Therefore, IA might reflect an individual’s attempt to cope with and escape from negative emotions in everyday life and promote more positive affect. However, the positive emotional reinforcement that may arise from use of the internet can easily produce an imbalance, leading to abuse or overuse . Indeed,Furthermore, deficiencies in the ability to effectively identify and describe emotions  has been shown to significantly predict IA. For instance, in a sample of adolescents, IA was strongly correlated with a reduced ability to understand emotional reactions, control impulsive behavior in response to negative emotional experiences, and use effective emotional regulation strategies . The useFear of missing out  has been defined as an individual’s fear that other people are having fun without them . WegmannSeveral studies have linked FoMO to the overuse of SNs ,59,60,61Excessive use of SNs may also lead to social media addiction—an uncontrollable and compulsive behavior ,67,68 thAlthough FoMO has been identified as potentially responsible for problematic use of social networks, it should come as no surprise that compulsive users of social networks may experience FoMO as a result. Individuals engaging in higher levels of social network use seem to be more likely to experience online vulnerability and exhibit higher levels of FoMO . One posThe continuous need to stay in touch offered by social media may, therefore, exacerbate the FoMO in accordance with the reinforcement spiral model , which eResearch has demonstrated a strong relationship between personality and IA, as well as behavioral addictions, more generally ,76,77,78The present study aimed at investigating the relationships between IA and variables identified in the literature as related to this construct . Specifically, the hypotheses were as follows: Hypothesis 1 (H1).The following correlations identified in the literature would be verified:a. Positive correlation between IA and variables related to problematic social media use;b. Positive correlation between IA and emotional (dys)regulation; andc. Correlation between IA and personality traits; in particular, a positive correlation with neuroticism and a negative correlation with conscientiousness.Hypothesis 2 (H2).There would be a direct positive effect of emotional (dys)regulation (the independent variable) on IA (the dependent variable).Hypothesis 3 (H3).There would be an effect of the independent variable on the proposed mediator , and an effect of the proposed mediator on the dependent variable; and an effective mediation model could be established including neuroticism and conscientiousness as covariates .SD = 3.83). With respect to education, 1.8% had a primary or middle school diploma, 73.6% had a high school diploma, 16.6% had a bachelor’s degree, 7.1% had a master’s degree, and 1.0% had a postgraduate degree. Regarding occupation, a vast majority of participants were students (80.9%), 0.3% worked in law enforcement, 2.3% were conceptual employees, 1.3% were executive employees, 1.0% were managers, 0.8% were teachers, 1.5% were workers, 2.5% were practitioners, 1.8% were healthcare professionals, and 7.8% were “other”.The sample was comprised of 397 Italian young adults . Ages ranged from 18 to 35 years, with an average age of 22.00 years (The Internet Addiction Test (IAT)  is a widThe Bergen Social Media Addiction Scale (BSMAS)  is a selThe Fear of Missing Out Scale (FoMOs)  is a 10-The Difficulties in Emotion Regulation Scale (DERS)  is a 36-The Big Five Inventory-10 (BFI-10)  is a selParticipants were recruited online, and they voluntarily and anonymously responded to the survey, which they accessed through a designated link . Participants indicated their informed consent prior to beginning the survey, and they were free to interrupt or quit the survey at any point, without providing an explanation for doing so. Expedited ethics approval was obtained from the Institutional Board of the Department of Psychology, Faculty of Medicine and Psychology, “Sapienza” University of Rome (IRB 2193/2020), in accordance with the principles embodied in the Declaration of Helsinki.r) were calculated to study the associations between scores on the IAT, BSMAS, FoMOs, DERS, and BFI-10 Neuroticism and Conscientiousness (sub)scales. The mediation model was run using PROCESS version 3.5, as developed by Preacher and Hayes for SPSS, version 26 . PROCESS estimates indirect effects  and conditional indirect effects  using bootstrap confidence intervals. In the present study, the bias-corrected 95% confidence interval (CI) was calculated using 5000 bootstrapping resamples. Effects were considered significant when the resulting confidence interval did not contain 0. A serial mediation model (Model 6) was tested using PROCESS Model Templates, in order to explore whether the association between difficulties in emotional regulation  and IA  were mediated by social media addiction  and FoMO , using BFI-10 Neuroticism and Conscientiousness subscale scores as covariates.Pearson’s correlation coefficients , except for the BFI-10 Conscientiousness score, which showed a weak negative correlation with all the aforementioned variables.B = 0.230 [SE(HC0) = 0.04] p < 0.001 ) was significant. Furthermore, as shown in B = 0.161), and the bootstrapped 95% CI did not include 0 .Subsequently, we tested the prediction concerning the link between difficulties in emotional regulation , IA , media addiction , and FoMO . The total effect of the DERS score on the IAT score (B = 0.807) and negatively (B = −0.496) associated with the IAT score, respectively  were significantly positively , as well as the connections between IA and emotional (dys)regulation. Despite the considerable literature on this topic, the research aimed at contributing a deeper analysis of the role of emotional (dys)regulation and the interaction between variables related to internet use in the development of IA.The results were largely consistent with the predictions. Specifically, the first hypothesis (H1) was confirmed: IA was found to correlate with all the investigated variables, demonstrating a strong and positive relation to social media addiction, FoMO, emotional (dys)regulation, and neuroticism; and a weak and negative relation to conscientiousness. Moreover, all variables were found to significantly relate to each other, supporting the frame of a vicious circle whereby underlying emotional (dys)regulation exacerbates problematic social media use and the pervasive apprehension that others are engaged in exclusive positive activities, resulting in severe IA. These findings seem to align with the pathways hypothesis pertaining to a specific group of behavioral dependents . This hypothesis was first proposed by Blaszczynski and Nower , and subFurthermore, impulsivity, together with emotional and personality variables, were found to be associated with addictive behaviors in a sample of adolescents, resulting as vulnerable factors for the development of psychopathological diseases in adults . The preLastly, conscientiousness emerged as a protective factor against behavioral addictions defined as “unproductive” , while neuroticism emerged as a general risk factor for the development of psychopathology, as underlined in the literature ,101,102.The second hypothesis (H2) was also confirmed: the mediation model showed a direct effect of emotional (dys)regulation on IA, suggesting that emotional regulation may play an important role in the development of IA. Indeed, studies have shown that individuals with IA—especially adolescents—have greater difficulties with emotional regulation, resulting from excessive suppression and poor cognitive reappraisal ,103,104.Finally, the third hypothesis (H3) was also confirmed: the final mediation model showed the influence of emotional (dys)regulation on FoMO and problematic use of social networks, with a consequent effect on IA. While several studies have investigated the relationship between FoMO and problematic smartphone use ,106 and The results of the present study contribute new insights to the literature on the role of emotional (dys)regulation in the development of pathological Internet behaviors. Plausible mediation pathways were tested, based on theoretical models and research suggesting that emotional (dys)regulation could mediate the development of addictive behaviors. Overall, the results suggest that emotional (dys)regulation could be conceptualized as an independent factor and direct predictor of both IA and variables related to problematic social media use. Further investigations should aim at identifying the specific personality traits and interventions that are effective at decreasing the maladaptive aspects of IA while increasing or enhancing its adaptive aspects.In summary, mediation was revealed between emotional (dys)regulation, IA, and variables related to problematic internet use. Further research should test models that will further our understanding of the relationship between emotional regulation and its adaptive and maladaptive effects. The results of such investigations may facilitate the development of more suitable approaches to assess and treat IA and evaluate outcomes associated with emotional regulation. Research should also seek to replicate the current findings and further investigate which aspects may influence or be influenced by emotional (dys)regulation , in a variety of populations . Finally, the causal conjectures of the present study design should be examined and verified via longitudinal or experimental research.Nevertheless, some limitations of the present study must be considered. First, we were unable to draw causal conclusions or establish the direction of effects, due to the cross-sectional research design. For this reason, it cannot be ruled out that, in some cases, emotional (dys)regulation and the presence of IA may have exerted a mutual influence, or emotional dysregulation may have evolved after the onset of IA. Furthermore, the present study used only self-report measures to assess IA and variables related to problematic social media use; these measures were unable to provide diagnoses, thereby limiting the clinical implications of the results. Furthermore, the study sample may have been affected by selection bias, since the questionnaires were more accessible to certain groups of individuals. Finally, participants’ psychiatric history was not collected, though this data might have influenced the interpretation of the results.