In recent years, the use of the ketogenic diet as a proper nutritional treatment for lipedema has been hypothesized in the literature. This is the first clinical study evaluating the ketogenic diet and carboxytherapy in lipedema patients. In the present study, it was decided to use a modified Mediterranean ketogenic diet (MMKD) in combination with carboxytherapy. Since lipedema is characterized by microangiopathy, local hypoxia, and increased subcutaneous adipose tissue (SAT) deposition, carboxytherapy could improve painful symptoms and skin tone. A total of 22 subjects were included in the data analysis, divided into three groups; 8 patients underwent MMKD combined with carboxytherapy sessions (KDCB group), 8 underwent MMKD nutritional treatment alone (KD group), and 6 patients underwent only carboxytherapy sessions (CB group), for a total of 10 weeks of treatment for all three groups. It was observed that the ketogenic diet effectively induced weight and fat mass loss, including in the limbs, areas considered unresponsive to diet therapy in lipedema patients. However, the best results were obtained from the combination of the ketogenic diet and carboxytherapy, which showed improvements in both body composition and skin texture and a reduction in pain, along with an improvement in sleep quality. It would be helpful to conduct a clinical trial on a larger scale and over a more extended period to observe the results in the long term as well. Lipedema is an autosomal dominant inheritance, progressive, multifactorial, and disabling disease, characterized by an accumulation of pathological subcutaneous adipose tissue (SAT) in the superfascial area, microangiopathy, chronic tissue inflammation, and pain. Symptoms usually occur at puberty, pregnancy, or menopause, assuming the role of estrogens in the pathophysiological process. The diagnosis is clinical, the adipose tissue develops descending symmetrically and bilaterally, and the lower limbs are the most affected sites. It is classified into five types based on the distribution of the lipo-edematous adipose tissue and into four stages based on the severity of the disease . The firAlso, we wanted to evaluate the efficacy of carboxytherapy for a reduction in subcutaneous fat and a reduction in painful symptoms. Its use for therapeutic purposes dates back to the 1930s, when it was used as thermal therapy (baths in carbonated water) for treating patients with obliterating peripheral arterial disease . The goaBetween May 2022 and May 2023, a pilot study was conducted at the Section of Clinical Nutrition and Nutrigenomics, University of Rome Tor Vergata, and 34 patients diagnosed with lipedema were enrolled. Inclusion criteria were diagnosis of lipedema, female sex, and consent to the protocol. Exclusion criteria were age <18 or >65 years; diagnosis of lymphedema; stage 4 lipedema; drug or alcohol abuse; psychotic disorders; acute or chronic renal failure; liver failure; neoplastic disease under treatment; pregnancy and lactation; menopause for more than 2 years; hepatitis B and C; HIV/AIDS; and COVID-19. Four patients declined to participate. Therefore, 30 patients were randomly divided into three groups; 11 patients underwent MMKD combined with carboxytherapy sessions (KDCB group), 12 underwent MMKD nutritional treatment alone (KD group), and 7 patients underwent only carboxytherapy sessions (CB group), for a total of 10 weeks of treatment for all three groups. From the KDCB group, 3 patients withdrew; from the KD group, 4 patients withdrew; from the CD group, 1 patient withdrew . In the end, 22 patients completed the study, 8 in the KDCB group, 8 in the KD group, and 6 in the CB group .A complete medical and nutritional evaluation was performed at baseline (T0) and after ten weeks (T1). All patients were interviewed via telephone every two weeks with a nutritional recall of the previous 24 h to monitor compliance with the dietary treatment and were questioned about any complications or side effects. Carboxytherapy sessions were performed once a week for the ten weeks of treatment by the same operator (S.S.).ClinicalTrial.gov NCT01890070. Approval was obtained from the Ethics Committee of the Calabria Region Central Area Section (register protocol no. 146 17/05/2018).All enrolled patients signed an informed consent form according to the principles of the Declaration of Helsinki. This trial is registered with At T0 and T1, a trained nutritionist assessed the subjects’ eating habits through a thorough food history. A 24 h recall and a food frequency questionnaire were conducted to identify the amount of intake and weekly frequency of different foods .® dietary analysis software .All subjects received the MMKD with a 20% calorie restriction of daily energy requirements. Daily protein intake was calculated as 2 g/kg of total lean mass (LM), according to Colica et al. . The dieThe main characteristics of the MMKD are as follows: seasonal vegetables; foods rich in mono- and polyunsaturated fats, such as olive oil, nuts, avocado, oily fish, and fresh cheeses with reduced saturated fat content; lean meat of organic origin; and use of herbs and spices to reduce the amount of added salt. Processed and preserved foods such as frozen ready meals, cured meats, canned products and sausages, simple carbohydrates and sugars, sugary alcoholic and soft drinks, and fresh fruits (except for red fruits) were excluded.The Mediterranean adequacy index (MAI) was calculated using the ratio of caloric intake  from typical Mediterranean carbohydrates and foods  to nontypical foods . MAI values are considered acceptable when the value is >5 and 100% adequate if >15 .The method consists of the supply of CO2 through highly sophisticated electronic machinery , which allows supplying of pure gas, free from contaminants, with specific preset parameters of dose, flow, speed, and temperature. The CO2 passes through a disposable sterile tube at the end of which a 30-gauge 13 mm needle or 4 mm microlance is inserted. The dose and speed depend on the treatment site and the clinical indication. The injection can be superficial, intradermal, or subcutaneous. The rate that CO2 takes to cross the tissue varies according to the characteristics of the tissue of the subject being treated . In our CO2 determines increased local blood flow rate; increased arteriolar and metarteriolar sphygmicity (short-term effect); stimulation of true and false neoangiogenesis, with an increase in microcirculation (long-term effect); extero-receptor activation, linked to hyper-distension of subcutaneous tissues, with the production of bradykinin, increase in cyclic adenosine monophosphate (cAMP), and activation of intra-adipocyte lipase; and Bohr effect amplification, with the more significant release of oxygen (O2) at the tissue level . Possibl2) and classified according to the World Health Organization (WHO) [After a 12 h overnight fast, an anthropometric assessment was performed for each patient. Body weight and height were measured with a scale and stadiometer  while the subject was standing wearing underwear. Data were collected to the nearest 0.1 kg and 0.1 cm, respectively. Body mass index (BMI) was calculated as body weight (kg)/height (mon (WHO) . Hip andBody composition was assessed according to the standard method . PatientBased on % FM, subjects are classified as normal weight (NW) for % FM < 30, and obese for % FM ≥ 30. Android and gynoid distribution were confirmed when gynoid and android total fat tissue (%) were >30 ,24.The appendicular skeletal muscle mass index (ASMMI) was calculated as follows:2). The intermuscular adipose tissue (IMAT) was calculated according to Colica et al. [2) for women.(LM legs + LM arms)/height  was calculated using the De Lorenzo formula :BMR = [, who have worked on the European Quality of Life project since 1990. It is a standardized instrument that can be used for different purposes; in this case, it was used to assess the possible changes in health status at other times (T0 and T1) and to contribute to the standardized assessment of the verification of the effectiveness of the dietary treatment used in patients with lipedema.The second section of the EQ-5D includes an assessment using visual analog scale (VAS) graphically represented by a graded scale ranging from 0  to 100  on which the respondent indicates the level of perceived health status. In this case, the EQ-5D evaluates the comparison of the change in the numbers obtained between the first part and the second part at T0 and T1, particularly in assessing any improvements regarding not only general health status but also pain, discomfort, and the psychological aspect related to depression and anxiety .The EQ-5D is reported in Examinations of patients with lipedema showed that the areas of increased pain and soreness overlapped with those of fibromyalgia, even though this condition does not characterize lipedema. Therefore, to assess the effect of diet and carboxytherapy on pain and asthenia, it was decided that the FAS would be used. This simple self-administered test assesses asthenia, pain, and sleep disturbances based on the 16 non-joint sites listed on the self-assessment pain scale (SAPS) in a single measure (range: 0 to 10) .The FAS is reported in This is an instrument used to assess symptoms and signs related to pain in fibromyalgia pathology. It consists of the diffuse pain index, which refers to the distribution of the pain symptom in the last week at the time of observation; generalized pain index, which details the body regions affected by pain; and symptom severity index, which considers symptoms such as asthenia, nonrestorative sleep, and cognitive problems, reported in the last week, and symptoms such as migraine, abdominal pain or cramps, and depression, reported in the last six months .The FSS is reported in The FIQR is an updated version of the fibromyalgia impact questionnaire (FIQ). It consists of twenty-one numerical rating scales from 0 to 10 (where 10 is “worst”) that explore the three main domains of function, widespread impact, and symptoms. The revised version expanded the original scale by adding new questions about sensitivity, balance, memory, and environmental sensitivity. All questions refer to the previous seven days. The final score  is calculated as follows: the algebraic sum of the 9-item function domain (range 0–90) is divided by three; the algebraic sum of the 2-item general impact domain (range 0–20) remains unchanged; and the algebraic sum of the 10-item symptom domain (range 0–100) is divided by two. These three partial scores are then added together .The FIQR is reported in The DERS is a self-reported measure that aims to assess emotion dysregulation. It is widely used in treatment and research settings for adults with emotional disorders , so it is useful for investigating the possible presence of psychological disorders in patients with lipedema.The model on which DERS is based proposes six emotion regulation factors, translated into six subscales: (a) lack of awareness and understanding of emotions ; (b) lack of acceptance of emotions (“I have difficulty making sense of my feelings”); (c) difficulty controlling impulses ; (d) difficulty engaging in goal-oriented cognitions and behaviors when distressed ; (e) unwillingness to accept specific emotional responses ; and (f) lack of access to strategies for feeling better when distressed . Developed initially as a 36-question measure, a short 18-question form was created that retains the original six subscales. The measure is scored so that higher scores reflect more significant impairment or dysregulation ,30,31.The DERS is reported in Lipedema patients may present with eating disorders. Therefore, a validated diagnostic tool for food addiction (FA), the YFAS, was used to identify individuals with addictive eating behaviors. The original YFAS (25 questions) was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV for substance dependence, including the consumption of highly palatable foods . Later, the scale was replaced with the YFAS 2.0 (35 questions) in response to the revised criteria for substance-related disorders and addictions in the DSM-5. YFAS 2.0 introduced the following diagnostic criteria: use despite interpersonal or social consequences and, in physically dangerous situations, craving. A severity classification was also introduced.The YFAS version 2.0 is a thirty-five-question questionnaire with an eight-point response scale. It measures the eleven criteria of substance-related disorders and addictions to food and eating. For the potential “diagnosis” of food addiction, at least two of the eleven addiction and substance use disorder criteria must be met, and significant impairment must be present. The YFAS also measures eating behavior impairment.Both versions have two scoring options: a symptom count , a diagnostic score that predicts the achievement of a symptom threshold , and the presence of clinically significant impairment or distress (self-perceived). With respect to the first version, the YFAS 2.0 differentiates the severity level of FA based on symptom count , paralleling the DSM-5 severity ,33.The YFAS 2.0 is reported in p-value < 0.05. Statistical analysis was performed using IBM SPSS Statistics V25.0 .The data collected before statistical evaluations were analyzed for the presence of outliers, and the Shapiro–Wilk test was performed to evaluate variable distribution. The data presented are expressed as mean and standard deviation, to evaluate differences between the times. Related sample t-tests or Wilcoxon signed rank tests were used to assess the differences in the variables examined at the follow-up. Results were significant for p = 0.001), reduced sugars (%) (p = 0.001), decreased fiber (g) (p = 0.011), and increased animal proteins (%) (p = 0.001). In addition, statistically significant results were obtained for increased MUFA and PUFA content (p = 0.001). Statistically significant increases in vitamin D (μcg) (p = 0.001) and vitamin E (mg) (p = 0.001) content were also observed, while vitamin C (mg) was significantly reduced (p = 0.07). A significant increase in the MAI when comparing the dietary patterns followed at T0 and T1 (p = 0.001) was observed.At T0 and T1, the results of dietary component analysis  were calculated using food frequency. The average dietary components of the patients’ eating habits at T0 and the average dietary components of KD at T1 were compared . SignifiAfter screening through the inclusion criteria, 30 subjects, all female, were included in the data analysis .p = 0.63 and p = 0.83).According to BMI and % FM, 13.8% of patients were found to be normal weight, 20.7% normal weight obese, and 65.5% obese. According to the distribution of FM, 44.8% had a gynoid distribution, 55.2% had a mixed-type distribution, and none had an android distribution. An ANOVA test was performed to analyze the BMI and % FM differences between the three groups at T0. No differences were highlighted , 12 with the ketogenic diet only (KD group), and 7 with carboxytherapy only (CB group).p = 0.009, p = 0.008) and the KD groups . These parameters were not significantly different in the CB group. In relation to circumferences, only the hip was significantly different in both the KDCB and KD groups , while waist circumference was significantly reduced only in the KD group (p = 0.03). No difference in the CB group was detected.After 10 weeks of treatment, a significant decrease in most of the parameters analyzed was shown . Weight p = 0.005, p = 0.012), as was leg FM, in grams and percentage . The same results were obtained in the KD group for total FM g and % (p = 0.019 and p = 0.044), while FM in legs was significantly reduced only in g (p = 0.015). Differently, in the CB group, no significant results related to these parameters were found. In addition, significant decreases in the percentage of android and gynoid FM and IMAT were shown in both the KDCB group  and the KD group . In contrast, in the CB group, none of these parameters changed significantly  was significantly reduced , and of the FIQR, which explores the three main domains of symptoms, function, and general impact (p = 0.032), indicating significant improvements in sleep quality and quality of life and a reduction in pain after 10 weeks of treatment.Different tests on quality of life and pain were administered to the three groups at baseline and follow-up. A statistically significant improvement was found in the KDCB group at the level of the FAS, which investigates asthenia, pain, and sleep disturbance . Moreover, our results showed an improvement in the MAI between the diet followed by the patients before our dietary intervention and the diet followed according to our MMKD pattern, although it did not reach the level of Mediterranean adequacy , as expected given the low amount of carbohydrates. This goes to underscore how the MMKD used was rich in antioxidant and health-beneficial foods [The nutritional treatment, in this case, is a diet inspired by the Mediterranean diet in terms of food choice but ketogenic given that it is low in carbohydrate intake, low in salt and simple sugars, includes no processed foods, and is high in antioxidant foods, such as foods with high concentrations of PUFA and MUFA . These nutrients play an essential role in the inflammatory process by promoting an anti-inflammatory effect . In factal foods ,39. HoweIn fact, it has already been seen that a low-calorie diet based on foods rich in anti-inflammatory and antioxidant nutrients could contribute to the well-being of patients with lipedema . In our In recent years, the use of the ketogenic diet as a valid nutritional treatment for lipedema has been hypothesized in the literature . In factIn the present study, it was decided to use an MMKD, for the reasons discussed above, in combination with carboxytherapy. Indeed, lipedema is characterized by microangiopathy and local hypoxia, so we hypothesized that carboxytherapy, through the restoration of microcirculation, could improve painful symptoms and skin tone. Brandi et al. studied the effect of CO2 therapy on skin laxity in the knee and thigh region, observing an improvement in skin texture, as also expected for lipedema . In addiHowever, data on carboxytherapy are quite divergent in the literature, and many authors do not mention the parameters used regarding volume, infusion rate, and application technique, thus making it difficult to suggest a more effective procedure.In any case, to the best of our knowledge, this is the first clinical study evaluating the effect of carboxytherapy on women with lipedema. What was found in our study was a significant improvement in skin texture, as shown a–c.p = 0.001, p = 0.015 and p = 0.003, p = 0.03, respectively). These results confirm and strengthen the evidence on diet therapy from our previous study [In contrast to the previous literature ,35,42,43p = 0.585, p = 0.384, p = 0.538).Furthermore, contrary to what was observed for very low-calorie ketogenic diets (VLCKD) , LM was p = 0.049, p = 0.032). These data could reflect a reduction in inflammatory phenomena induced by adipose tissue as a consequence of a customized MMKD rich in antioxidant nutrients [The same results for FM were not found in the group that performed only carboxytherapy. In fact, the primary goal of carboxytherapy is to restore and improve skin microcirculation, not to reduce fat mass; any lipolysis is only a secondary effect ,45. Otheutrients , in combMoreover, a relationship between vitamin D levels and the development of anxiety and depression was previously observed . The incThe main limitations of this study are the small number of participants and the short intervention period. It will be necessary to further investigate the efficacy of the proposed treatments on a larger sample and for longer periods of time. In addition, this study lacks a comparison with a sample of non-lipedema patients to compare the results obtained. Moreover, it might be useful to assess patients’ oxidative and inflammatory status to check the antioxidative and anti-inflammatory power of nutrients administered through the diet.To our knowledge, this is the first clinical study evaluating the ketogenic diet and carboxytherapy in lipedema patients.It was observed that the ketogenic diet effectively induced weight and fat mass loss, including in the limbs, areas considered unresponsive to diet therapy in lipedema patients. The best results were obtained from the combination of the ketogenic diet and carboxytherapy, which showed both an improvement in body composition and a reduction in pain, along with an improvement in sleep quality.This study confirms the need, according to the consensus of the various international guidelines, to maintain a multidisciplinary and integrated approach to lipedema, demonstrating that no isolated treatment, at present, can be completely effective.Nutrition should have a primary role in the management of lipedema, as it could be, in the long term, an effective tool to reduce the low-grade inflammation that is almost always present in this condition. In parallel, it is necessary to continue studying this disease and its pathophysiology to have targeted therapeutic strategies.Given the promising results of this pilot study, it would be useful to conduct a clinical trial over a more extended period and on a larger scale to observe the results in the long term as well.


Background: The purpose of this study was to explore the role of everyday executive functions in relation to intelligence and adaptive behaviour in children and adolescents with mild intellectual disability. Method: A group of children and adolescents, previously diagnosed with mild intellectual disability were assessed according to intelligence, everyday executive functions and adaptive behaviour. The association between everyday executive functions and intelligence was examined, and it was explored whether intelligence or everyday executive functions would best predict adaptive behaviour. Results: Adaptive behaviour was significantly predicted by executive functions, but not by intelligence. Nor was intelligence significantly related to everyday executive functions in this group. Conclusions: Although fundamental in diagnosing intellectual disability, intelligence cannot predict adaptive behaviour. Assessing everyday executive functions and adaptive behaviour, as well as acknowledging the strong association between them, provides valuable information in the process of optimizing developmental support for children and adolescents with mild intellectual disability. Since the 1950s, more emphasis has gradually been placed on adaptive behaviour in the diagnosis and understanding of intellectual disability . A modelAdaptive behaviour has over the years become an increasingly well-defined construct, encompassing social, communication and practical skills that can be empirically assessed using validated inventories . One exaExecutive function is a term describing a range of related higher order thinking skills that underpin the regulation of thoughts, emotions and behaviour – functions of great significance for goal achievement and everyday functioning . SeveralThere has been some interest in how executive functions relate to intelligence. In general populations, executive functions and intelligence are found to be related, but separate constructs , and theThe relation between executive functions and intelligence has been studied in some such populations, for example, those on the autism spectrum who have lower IQ. Although results have often indicated a degree of executive difficulty in these populations, executive functions have not correlated highly with intelligence . For insThere is less knowledge about everyday executive functions, and how they relate to intelligence, in clinical groups of children and adolescents with mild intellectual disability and mixed aetiology, without concurrent autism spectrum condition. In one relevant study using behavioural measures, It is not clear how everyday executive functions relate to adaptive behaviour in children and adolescents with mild intellectual disability. The executive function “inhibitory control”, measured behaviourally, has been found to be a significant developmental and modulation factor for the specific adaptive behaviours “conceptual and practical skills” in children and adolescents with mild intellectual disability . The milUsing a parent/caregiver-report, like the BRIEF to assess everyday executive functions in this group of children and adolescents can give information regarding strengths and difficulties, which can enable more targeted interventions that are specifically tailored according to the individuals´ needs and abilities. Gaining more knowledge regarding how everyday executive functions relate to intelligence and adaptive behaviour in children and adolescents with mild intellectual disability can be useful for clinicians wanting to provide the family and teachers with much needed information of what to expect, and where to place support in the life of children and adolescents with mild intellectual disability.The primary aim of the present study was to explore the relationship between everyday executive functions and intelligence in a group of children and adolescents with mild intellectual disability. A secondary aim was to explore whether intelligence or executive functions best would predict adaptive behaviour in this group. Previous research did not allow us to make specific hypotheses regarding the aims.Initially, a total of 75 children and adolescents, previously diagnosed with mild intellectual disability from habilitation hospital outpatient clinics in the Central Norway Region, were invited to participate in the study, see The final sample consisted of 40 children and adolescents  in the age range of 10-17  with a diagnosis of mild intellectual disability, and mixed aetiology who participated in the study from September 2018 to July 2020. See Adaptive behaviour: To measure the youth´s adaptive behaviour, parents/caregivers were interviewed with the Vineland Adaptive Behavior Scales Interview, Second Edition,   . The VinI, n=36) .Everyday executive function: To assess the children and adolescents´ everyday executive functions, parents or caregivers filled in the Behavior Rating Inventory of Executive Function   . The BRIF, n=36) . A studyF, n=36) . For theIntelligence: For participants where intelligence tests results were more than two years old, new tests were administrated (n=38), using the Wechsler Intelligence Scale for Children, Fourth Edition , or the Wechsler Adult Intelligence Scale, Fourth Edition  (r= 0.97), and also for correlations between subtests and indexes  . For the indexes . For the indexes .Mild intellectual disability was already diagnosed based on the ICD-10 criteria , Wechsler Full-Scale Intelligence Quotient (FSIQ), and Vineland-II Adaptive Behavior Composite (ABC) differed based on gender or age groups. The association between Wechsler Full-Scale Intelligence Quotient (FSIQ) and BRIEF Global Executive Composite (GEC) was analysed with the Pearson correlation coefficient. The correlated correlation coefficients were compared using the method based on the Fisher z-transformation, as recommended by t(35)=-0.48, p=0.63, males: M=67.65, SD=12.63, females: M=69.79, SD=13.58), nor age-group (t(35)=0.30, p= 0.77, 10-13 years: M=69.50, SD=13.09, 14-17 years: M=68.07, SD=12.00). There were no significant differences in Vineland-II (ABC) based on gender (t(34)=-0.15, p=0.88, males: M=64.00, SD=9.96, females: M=64.60, SD=13.42) nor age-group (t(34)=-0.37, p=0.71, 10-13 years: M=63.100, SD=10.85, 14-17 years: 64.69, SD=11.71).t(34)=2.008, p=0.053 based on gender, where the males  scored higher than the females . Results indicated no significant differences in Wechsler (FSIQ) based on age-groups (t(34)=0.83, p=0.41), where the youngest group scored  and the oldest group .With respect to Wechsler (FSIQ), independent sample t-tests indicated a result that approached a significant difference r=-0.12, p=0.51) between the BRIEF (GEC) and the Wechsler (FSIQ). There was also a weak and non-significant correlation  between the Wechsler (FSIQ) and the Vineland-II (ABC), although this was of slightly higher magnitude. The correlation between the BRIEF (GEC) and the Vineland-II (ABC) was moderately strong and significant . These two correlation coefficients (Wechsler (FSIQ) - Vineland-II (ABC) versus BRIEF (GEC) - Vineland-II (ABC)) were significantly different (p=0.007).There was a weak and non-significant correlation (p=0.23), whereas the BRIEF (GEC) was a significant predictor . As seen in Results of linear regression analyses are shown in This study explored the role of everyday executive functions in relation to intelligence and adaptive behaviour in a group of children and adolescents with mild intellectual disability. Results indicated that intelligence and everyday executive functions were not significantly related, and that a global measure of everyday executive function was a significant predictor of adaptive behaviour in children and adolescents with mild intellectual disability. By contrast, full-scale IQ was not a significant predictor of adaptive behaviour in this group.The finding that adaptive behaviour can be significantly predicted by everyday executive functions, but not by full-scale IQ, is important, because it confirms the structure of the existing diagnostic criteria in that we cannot predict how a child functions in everyday life based solely on an IQ measure . FurtherThe significance of adaptive behaviour should be acknowledged, and the strong relationship between everyday executive functions and adaptive behaviour should be recognized. Assessment of everyday executive abilities and adaptive behaviour can provide valuable information about individual strengths and difficulties in everyday settings, which again can create a basis for educational planning and developmental support. Shifting the focus, from levels of intelligence to strengths and difficulties across cognitive, executive and adaptive abilities, can lead to a more realistic picture of functioning in children and adolescents with mild intellectual disability. More focus on adaptive behaviours can contribute to the discovery of the individual´s resources.Research in the population without intellectual disability has suggested that intelligence and executive functions are related, but separate constructs . We wantThe current study shows that we cannot derive information about either executive function or adaptive ability from measures of intelligence, as these measures were not significantly related to each other. The implication is that we need to look at the broader aspects of functioning in obtaining a fuller understanding of children and adolescents with mild intellectual disability. Additionally, the prevalence of mental health problems has been found to be many times higher in groups of children and adolescents with intellectual disability, compared to children and adolescents without intellectual disability, and commonly reported conditions have been depressive disorders, conduct disorders and anxiety disorders . It is pIt could be argued that the correlation found between the global measure of executive function and adaptive behaviour comes from a possible overlap in what the two tools assess, or because they both are parent ratings, unlike the full-scale IQ measure from the Wechsler intelligence test, which is directly assessed. It could also be that the concepts themselves overlap. In the field of assessment of executive functions, intelligence and adaptive behaviour, there is the inevitable challenge associated with the purity of the definition of concepts associated with both the genotype and phenotype. Also relevant in this context, is the task-impurity problem , that poIn spite of these uncertainties, this study adds weight to the notion that because of great variation in cognitive profiles for people with intellectual disability, it is important to assess individual strengths and weaknesses in executive, and other specific cognitive functions in order to reach a better understanding of aspects concerning abilities of daily life , and to A possible limitation of the study was that the age distribution was somewhat skewed, with more children in the older age-groups, which could possibly impact on the results. Also, there were more males than females in the group. Analyses showed that there were no significant differences in intelligence, adaptive behaviour, or everyday executive functions based on gender or age-group. Knowing that mild intellectual disability was the main inclusion criterion, the skewness of age in the selection could reflect that mild intellectual disability is often diagnosed later in adolescence, rather than earlier in childhood. Another limitation is that new testing gave a wider range of IQ scores than expected on the basis of the diagnostic criteria of IQ scores in the 50-69 range . As statThe results from the present study show that adaptive behaviour cannot be derived from knowing the IQ of children or adolescents with mild intellectual disability, as these constructs were not significantly related to each other. Further, there was no significant correlation between everyday executive function and intelligence. This offers support to findings in the population without intellectual disability, that intelligence and everyday executive functions are separate constructs. The key finding, that adaptive behaviour was predicted by everyday executive function, underpins the importance of collecting knowledge about function across settings, to obtain a richer and more nuanced understanding of functioning in children and adolescents with mild intellectual disability. Through assessing everyday executive abilities in the real-world setting, by use of a parent/caregiver-rated inventory such as the BRIEF, clinicians and families can acquire important information which again can provide a basis for optimizing support for children and adolescents with mild intellectual disability. Acknowledging the strong association between everyday executive functions and adaptive behaviour can lead to more targeted support for children and adolescents with mild intellectual disability.


The aim of the presented study was to examine the in vitro antimicrobial activity of rutin hydrate (RH) alone and in combination with amikacin against 12 reference strains of Gram-positive and Gram-negative bacteria. The antibacterial activity assay was evaluated in the concentration range of 2–2048 µg/mL. A serial microdilution method was used to determine the minimal inhibitory concentration (MIC) of the examined compound against reference strains. RH showed varying potential against the tested strains with MICs ranging from 128 to 1024 µg/mL. In order to examine the combinatory profile of RH and amikacin, the fractional inhibitory concentrations (FICs) were determined. The RH–amikacin combination was more active against Gram-negative bacteria where four synergism and two additive interactions were noted. For four out of six Gram-positive isolates, an indifferent effect of RH and amikacin was demonstrated, and for two strains, the tested combination had an additive effect. The results of this study showed that RH possesses antimicrobial potential in vitro towards the tested reference isolates. Moreover, it shows a promising combined effect with amikacin against Gram-negative bacteria. Antimicrobial Resistance (AMR) is a significant global problem with serious public health risks. The treatment options and ability to control infections are gradually being exhausted, and the duration of infection and hospitalization has increased, all of which have led to an increase in mortality . Due to Ruta graveolens L.), from which the name of the organic chemical compound is derived. Some examples of the sources of rutin are Japanese pagoda tree flowers (Styphnolobium japonicum), buckwheat herb (Fagopyrum esculentum), and eucalyptus leaves , among many others. Rutin is also commonly found in vegetables and fruits, mainly citrus fruits, and plant-based drinks [Many previous studies have shown that compounds of natural origin have antibacterial activity alone and in combination with selected antibiotics ,5,6,7,8.d drinks . Pure rud drinks .The structure of rutin determines its biological activity, which, in turn, influences its pharmacological properties. The main advantage of rutin is its antioxidant properties. Due to the presence of free hydroxyl groups, rutin has the ability to neutralize reactive oxygen species. By reducing free oxygen radicals, rutin protects the cells of the human body because it limits the formation of damage-causing mutations in the genetic material. In addition, quercetin-3-O-rutoside as an antioxidant prevents the peroxidation of phospholipids that form the cell membrane and consequently reduces the damage caused by free radicals. In this way, rutinoside directly contributes to the protection of cells against apoptosis caused by DNA damage or cell lysis as a result of cell membrane instability ,12.In addition, it has been proven that rutin exerts an antiatherogenic effect because it inhibits the oxidation of low-density lipoproteins and consequently reduces the formation of atherosclerotic plaques, which, in turn, have a protective effect on the cardiovascular system. Moreover, rutin slows down the oxidation of vitamin C, which means that ascorbic acid in the presence of rutin has a prolonged antioxidant effect. This property has been used in medical preparations and dietary supplements. Vitamin C, in addition to its important role as a free radical scavenger, is also a cofactor in proline and lysyl hydroxylases, which catalyze the hydroxylation of proline and lysine, respectively. Hydroxyproline and hydroxylysine are the main amino acids of collagen, which is an important structural element of blood vessels because it gives them durability and elasticity. In addition, rutin inhibits the activity of hyaluronidase, which is responsible for the digestion of collagen, and also reduces the activity of metalloproteinases responsible for the degradation of the extracellular matrix. All these properties contribute to the improvement of blood vessel conditions due to an increase in their elasticity and at the same time a reduction in their fragility and permeability .The antibacterial properties of rutin have also been proven, which may find practical applications in the era of antibiotic resistance. Previous scientific research has demonstrated the antimicrobial activity of rutin against both Gram-positive and Gram-negative bacterial strains ,15,16,17Staphylococcus aureus (MRSA) [The antibiotic tested in this study was amikacin, which is used in the treatment of many nosocomial infections caused by Gram-negative bacteria, e.g., urinary tract infections or infections associated with the vascular line. In addition, it acts against some Gram-positive bacteria, e.g., methicillin-resistant s (MRSA) . Figure Staphylococcus epidermidis ATCC 12228 and Staphylococcus aureus ATCC 25923, the growths of which were inhibited at concentrations of 0.5 and 1 μg/mL, respectively. In turn, a concentration of 2 μg/mL inhibited the growth of the following strains: Bacillus subtilis PMC 2021 and Enterobacter clocae ATCC 13047, and a concentration of 4 μg/mL was active against the isolates of Enterococcus faecalis ATCC 29212 and Staphylococcus epidermidis ATCC 35984. An MIC value of 8 μg/mL proved to work against Escherichia coli ATCC 25922 and Proteus mirabilis ATCC 7002. An amikacin concentration of 16 μg/mL was found to be active against Pseudomonas aeruginosa ATCC 27853. The highest concentration inhibiting the growth of microorganisms (64 μg/mL) was recorded for the following strains: Staphylococcus aureus ATCC 43300, Klebsiella pneumoniae ATCC 27736, and Acinetobacter baumannii ATCC 19606 (p = 0.105) between Gram-positive and Gram-negative bacteria (Amikacin turned out to be the most active against the strains CC 19606 . In summbacteria .p = 0.676) between Gram-positive and Gram-negative bacteria  was observed for two strains: Pseudomonas aeruginosa ATCC 27853 and Acinetobacter baumannii ATCC 19606. An MIC of 256 μg/mL was noted for four strains: Klebsiella pneumoniae ATCC 27736, Proteus mirabilis ATCC 7002, Bacillus subtilis PCM 2021, and Enterococcus faecalis ATCC 29212. The MIC was 512 μg/mL for the remaining four isolates: Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300, Staphylococcus epidermidis ATCC 12228, and Escherichia coli ATCC 25922 . However, to more precisely investigate differences in the action of the “rutin hydrate—amikacin” combination on Gram-positive vs. Gram-negative bacteria, a larger study group should be used. The descriptive and non-parametric statistics for the MICs of amikacin alone and with rutin hydrate for Gram-negative and Gram-positive strains are presented in The final stage of the research was the determination of the FIC index values. The results of the checkerboard assay for the reference strains are presented in Staphylococcus aureus ATCC 43300, Klebsiella pneumoniae ATCC 27736, and Acinetobacter baumannii ATCC 19606. Due to the resistance of amikacin to most aminoglycoside-modifying enzymes, it is used in the treatment of infections of strains resistant to other aminoglycosides. This antibiotic is the one most frequently applied to semi-synthetic aminoglycoside. However, strains resistant to amikacin have developed over the years. The first acetyltransferases that inactivated amikacin were reported for P. aeruginosa. Adenyltransferase, in turn, was found in K. pneumoniae, E. coli, Serratia marcescens, and Proteus vulgaris, and phosphotransferases were isolated from E. coli. Amikacin is no exception among other antibiotics, and bacteria develop resistance to it as well [The need to launch a new antibacterial drug in the era of antibiotic resistance has prompted scientists around the world to return to natural medicine methods and analyze the potential antibacterial mechanisms of action of plant-derived compounds. The antimicrobial potential of polyphenols, especially rutin, has been confirmed in in vitro studies on bacterial cultures ,25,26,27 as well . The intB. subtilis in the presence of rutin at a concentration of 256 μg/mL was inhibited at a rate of about 75%. The growth inhibition of P. aeruginosa at a concentration of 1024 μg/mL was approximately 90%. In turn, in cultures of E. coli and S. aureus, a rutin concentration of 512 μg/mL inhibited bacterial growth by approximately 70%. Research conducted by Jhanji et al. showed that the rutin solutions used by them in the concentrations defined in this study as the MIC values inhibited the growth of the indicated bacterial strains in the range of 70–90% [B. subtilis (FIC index = 0.25), “rutin-berberine-ciprofloxacin” against P. aeruginosa (FIC index = 0.25), and “rutin-berberine-amoxicillin” against S. aureus (FIC index = 0.125).Jhanji et al. in 2021 examined the antimicrobial potential of rutin on four selected reference strains in comparison with commonly used antibiotics, which were streptomycin, ciprofloxacin, and amoxicillin. They observed that the growth of f 70–90% . Additioefflux pumps and interfere with biofilm formation. Both mechanisms have been confirmed in in silico and in vitro studies on bacterial cultures. Interestingly, in our study, RH turned out to be more active against the reference strain S. epidermidis ATCC 35984 (128 μg/mL), which has the ability to form a biofilm, than against the biofilm (-) strain S. epidermidis ATCC 12228 (512 μg/mL). Our next studies will focus on assessing the ability to form biofilm under the influence of rutin hydrate.In addition, Jhanji et al., in research conducted in 2020, considered a mechanism of antimicrobial activity in rutin . ResearcK. pneumoniae ATCC 700603 and E. coli ATCC 25922 reference strains. The MIC value of rutin against the E. coli strain was 512 μg/mL, which was the same as in this study. In turn, the MIC value for K. pneumoniae was 1024 μg/mL, which was four times higher than the concentration of 256 μg/mL obtained in our study against K. pneumoniae ATCC 27736. The difference in the obtained MIC values is probably due to the fact that K. pneumoniae ATCC 700603, unlike K. pneumoniae ATCC 27736, produces extended-spectrum beta-lactamases [Wang et al., in their study, focused on the analysis of the antimicrobial potential of rutin against the ctamases .K. pneumoniae strains under the influence of rutin. Their research showed that rutin had a strong ability to inhibit biofilm formation in weak, moderate, and strong biofilm-producing strains. The ability to inhibit biofilm formation was confirmed by analyzing the expression profile of 15 genes involved in biofilm formation. A significant reduction in the expression of several genes from this group was observed, which correlated with a reduction in the accumulation of K. pneumoniae biomass. A significant inhibition of biofilm formation was observed at rutin concentrations of 512 and 256 μg/mL [In addition, Wang et al., like Jhanji et al., studied the inhibition of biofilm formation in 56 μg/mL .S. aureus ATCC 43300 reference strain. It was found that the tested compounds in combination with antibiotics enhanced the antibacterial effect against the examined staphylococcal strains. The relationship between flavonoids and antibiotics was additive in most cases, but synergism was also observed in a few cases. Moreover, Amin et al. examined potassium release to determine the effect of antibiotic–flavonoid combinations on the cytoplasmic membrane for the tested staphylococci. They proved that flavonoids alone or in combination damage the bacterial cell membrane [The confirmation of the antimicrobial potential of rutin opens many research paths that will be aimed at analyzing the change in the antibacterial properties of rutin in the presence of other polyphenols with a similar effect, as well as antibiotics and various forms of rutin preparation, e.g., in the form of nanoparticles, biomaterials coated with rutin, etc. The validity of searching for compounds against which rutin exhibits synergy and/or potentiates antibacterial activity has been confirmed by research conducted in 2015 by Amin et al. These scientists decided to determine the effect of rutin, morin, and quercetin (in various combinations) with 12 selected antibiotics on 100 clinical MRSA strains and the membrane . The useThe results obtained and presented in this paper confirm the logic and effectiveness of using rutin hydrate as an agent combating antibiotic-resistant bacterial strains. This potential is conditioned by specific mechanisms of action, the study of which is the second step in confirming the usefulness of rutin in bacterial infections. Numerous studies have indicated that rutin, as a polyphenol, modifies the permeability of bacterial cell membranes and changes the stiffness of the cell wall, which leads to the loss of its integrity . In addiThe research results discussed above, as well as the results presented in this paper, indicate the antimicrobial potential of rutin. In addition, they prove that this compound increases the antibacterial potential of antibiotics. Due to the anti-biofilm activity of rutin indicated by several researchers, it seems important to further study this compound in this respect. Moreover, it is necessary to examine the combination “rutin hydrate-amikacin” on clinical strains of Gram-negative bacteria with different resistance mechanisms.Bacillus subtilis PCM 2021, which was obtained from the Polish Collection of Microorganisms . The tests were carried out on twelve selected strains of Gram-positive and Gram-negative bacteria: Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300, Staphylococcus epidermidis ATCC 12228, Staphylococcus epidermidis ATCC 35984, Enterococcus faecalis ATCC 29212, Bacillus subtilis PCM 2021, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 27736, Proteus mirabilis ATCC 7002, Enterobacter cloacae ATCC 13047, Pseudomonas aeruginosa ATCC 27853, and Acinetobacter baumannii ATCC 19606. Rutin hydrate was obtained from Sigma Chemical Co. .All reference strains of bacteria came from the ATCC culture bank , except the strain In order to determine the lowest bacterial-growth-inhibiting concentrations for rutin hydrate and amikacin, the serial microdilution method was used with sterile, 96-well titer plates  with a final volume of 200 µL ,30.5 CFU/mL) in TSB was added to each well (rows B–G). Row H wells were used to control the sterility of the medium. In addition, in row A of each plate, a suspension of TSB medium and the tested compound at various concentrations was prepared, which allowed the subsequent measurement of background extinction. Each examined strain was measured in triplicate. The next stage of the study was the incubation of the titer plates at 37 °C for 24 h. After incubation, the optical density of the culture was measured at 595 nm. Absorbance results for individual strains were read using a Multiskan EX reader  [An amount of 100 µL of TSB medium (BTL) was aliquoted into all wells of the titer plates. The next step was to prepare serial dilutions of the tested compounds (from 1024 to 1 µg/mL). Tested compounds were not introduced into the 12th column of the titration plate, which was a growth control. Next, one hundred microliters of mid-logarithmic-phase bacterial cultures (5 × 10Finland) ,32. MICsFinland) . The MICThe sensitivity of the tested reference isolates to the combination of amikacin with RH was assessed by determining the fractionated inhibitory concentration (FIC) value for each strain. The checkerboard microdilution method with modifications ,35 was uThe plates prepared in this way were incubated in an aerobic incubator at 37 °C for 24 h. The absorbances at 595 nm were then read. Next, the percentage increase in individual wells relative to the growth control was calculated. Only wells that represented less than 50% bacterial growth compared with the growth control were considered for FIC index determination.MICA + B—MIC of the antibiotic in the presence of a polyphenolic compound;MICB + A—MIC of a polyphenolic compound in the presence of an antibiotic;MICA—MIC of the antibiotic itself;MICB—MIC of the polyphenolic compound itself.The MICs for rutin hydrate and amikacin for each strain were then recalculated. At the end, the FICs  were calculated, i.e., the fractional inhibitory concentration for RH and amikacin and their sum for each well. The following formula was used:Next, on the growth inhibition border, the FIC index was established for each strain. The FIC index was the point where synergistic/additive or indifferent effects were the most visible.FIC ≤ 0.5—synergism;0.5 < FIC ≤ 1—additive action;1 < FIC ≤ 4—indifference;FIC > 4—antagonism .Based on the FIC index value for each strain, the relationship between rutin hydrate and amikacin was assessed according to the following scale:p < 0.05.In order to check whether there were differences in the obtained MICs of RH or amikacin values between Gram-positive and Gram-negative bacteria, the Mann–Whitney U test was used for two independent samples. The same test determined whether there were statistically significant differences in the amikacin MICs, and the MICs decreased after the addition of RH between Gram-positive and Gram-negative bacterial strains. Statistical calculations were made in the Statistica 13.0 program. The level of statistical significance was The results of the presented study demonstrate that rutin hydrate possesses antibacterial properties against the tested reference strains, and this effect is similar for both Gram-positive and Gram-negative bacteria. The combination of “amikacin–RH” was effective against Gram-negative bacteria, where in four cases, a synergistic effect was found, and in two, it was additive. On the other hand, two additive interactions and four indifferent effects were noted for Gram-positive bacteria. The in vitro synergistic interaction of RH and amikacin suggests that this effect could also be observed in vivo. Future studies should focus on the mechanism of action of RH on bacterial cells.


Accurate assessment of body composition (BC) is important to investigate the development of childhood obesity. A bioelectrical impedance analysis (BIA) device is portable and inexpensive compared with air displacement plethysmography (ADP) for the assessment of BC and is widely used in children. However, studies of the effectiveness of BIA are few and present different results, especially in pediatric populations. The aim of this study was to evaluate the agreement between BIA and ADP for estimating BC.The BC of 981 Chinese children (3–5 years) was measured using the BIA device  and ADP (BOD POD).P < 0.05), but the opposite trend was shown in children with obesity (P < 0.05). The agreement between FM and FFM measured by the two methods was strong (CCC > 0.80). The linear regression equation of 5-year-old children was constructed.Our results showed that BIA underestimated fat mass (FM) and overestimated fat-free mass (FFM) in normal weight children , especially in 5-year-old children or children with obesity. Further research is needed to standardize the assessment of BC in children. Obesity and overweight are defined as an abnormally high or excessive accumulation of fat according to the World Health Organization. Childhood obesity is a growing public health concern worldwide , and theBody mass index (BMI), defined as the body mass in kilograms divided by the height in meters squared, is a widely used measure of overweight and obesity. It is considered easy to apply; however, BMI is limited by not distinguishing between different compartments of body composition. In other words, BMI provides no information about fat mass (FM) and fat-free mass (FFM), which confer different health outcomes. Studies have indicated that the distribution and location of adiposity are associated with an increased risk of metabolic diseases , 7. EstiAt present, several techniques are utilized for body composition analysis (BCA), such as anthropometric estimates, dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), computed tomography (CT), air displacement plethysmography (ADP), and bioelectrical impedance analysis (BIA) . Among t® is a commercially available ADP instrument for assessing body composition that is used in clinical, commercial, and research settings  MFBIA and (b) ADP (BOD POD). The ADP was used as a standard against which the MF BIA was compared. In China, children generally enter kindergarten at ~3 years old and stay there for 3 years  before elementary school, so most kindergarten children are between 3 and 6 years old. We recruited 1,011 Chinese children from three kindergartens in the Jinghai District in Tianjin between September 2020 and December 2020. Under the care of their parents and the guidance of professional researchers, 1,011 children underwent body composition measurements using ADP, but 30 of them were excluded due to missing BIA measurements. We obtained written informed consent from all children's guardians. The studies involving human participants were reviewed and approved by the IRB of Tianjin Women's and Children's Health Center (BGI-IRB 17116-201711). This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for cross-sectional studies.To address potential sources of bias, all assessments were conducted by trained data collectors, most of whom were nurses, and school doctors. A set of strategies was implemented for data quality control. First, quality control of examinations was performed by the same professional researchers, who strictly followed a standardized protocol. Second, all participants fasted after 20:00 the day before the physical examination, fasted on the day of the examination, and then underwent BIA and ADP (BOD POD) to measure FM and FFM on the same morning. The height of the children was measured by trained staff using wall-mounted stadiometers, and the weight was measured by ADP, both accurate to 0.1 cm. Then, BMI was calculated. The z scores for weight-for-height and BMI-for-age were calculated using ADP measurements, and according to the WHO standard, overweight or obesity in children was defined by weight-for-height or BMI-for-age of 2 and 3 for children under 5 years old and BMI-for-age of 1 and 2 for children above 5 years old , which measured impedance at varying frequencies  across the legs, arms, and trunk. Children were required to be fasting and have an empty bladder. When in the measurement, children in light clothing stood on the platform without shoes and held both hands at a 45-degree angle away from the body; four tactile electrodes were in contact with the palm and thumb of both hands, and the other four were in contact with the anterior and posterior aspects of the sole of both feet. The measurements were collected, and then, the FM and FFM were calculated by an undisclosed proprietary algorithm.FM and FFM were assessed by ADP using the pediatric option of the BOD POD Gold Standard Body Composition Tracking System . Body mass was measured using an electronic scale, and body volume was assessed in a closed chamber utilizing the relationship between pressure and volume. Children entered the ADP system without shoes in a tightfitting swimsuit and a swimming cap, and their total body volume was measured. Volume measurements were always performed in triplicate and strictly according to the manufacturer's instructions. Body volume was corrected for surface area artifacts and thoracic gas volume. Surface area artifacts and thoracic gas volume were estimated based on the equations that were developed and built into the machine.t-test was used to compare the differences in the anthropometric measures of the participants between boys and girls, and a paired t-test was used to compare the differences between FM and FFM measured by BIA and ADP. The root mean square error (RMSE) is derived from the linear regression results of FM or FFM measured using the BIA device or ADP and used to represent the absolute value of the difference between the measurements of the two methods. Lin's concordance correlation coefficient (CCC) and Bland–Altman analysis were used to evaluate the agreement between the two methods. To eliminate proportion bias, the data were logarithmically transformed, and then, the Bland–Altman analysis was performed . The independent erformed . Controlt-test analysis of the enrolled and excluded children showed that there was no significant difference in sex, age, BMI, and FFM level by ADP between these two groups, but there was a significant difference in FM measurement (P = 0.047). The descriptive characteristics of the study sample reported in After excluding 30 children due to missing BIA measurements, 981 children with both ADP and BIA measurements were enrolled in our study . An independent P < 0.001), and the RMSE was 1.178 and 1.068 kg, respectively. Stratified by age, the mean FM measured by BIA of the 3- and 4-year-old groups was also lower than that measured by ADP (P < 0.05), and the RMSE of all groups was within 1.6 kg. Stratified by BMI, compared with ADP measurements, both boys and girls with normal weight had lower FM and higher FFM measured by BIA (P < 0.05). In contrast, both boys and girls with obesity had higher FM and lower FFM (P < 0.05), and the RMSE was 1.341 and 1.235 kg, respectively. Stratified by age, the mean FFM measured by BIA of the 3- and 4-year-old groups was also higher than that measured by ADP (P < 0.05), and the RMSE of all groups was within 1.7 kg. Stratified by BMI, the mean FFM measured by BIA was higher than that measured by ADP in both boys and girls of normal weight (P < 0.05).The Bland–Altman analysis plots of agreement between FM and FFM measured by BIA and ADP are shown in P < 0.001). Due to the limitation of sample size, overweight and obesity were combined into the “non-normal weight group,” and the agreement of FM classification in all groups was poor . However, in girls, the agreement of FFM classification in all weight groups was good . In boys, the agreement of FFM classification was good  in the normal weight group but poor in the non-normal weight group .R2 of the linear regression association increased with age. This suggests that the linear regression association between ADP and BIA measurements was stronger in the 5-year-old children. Thus, the linear regression equation of 5-year-old children was conducted as follows:ADP = 0.660*FMBIA - 0.211*sex - 1.403*age + 0.173*BMI, R2 = 0.855;FM: FMADP = 0.890*FFMBIA + 0.216*sex + 2.010*age + 0.267*BMI, R2 = 0.850.FFM: FFMP < 0.05), but the opposite trend was shown in children with obesity (P < 0.05). The agreement between FM and FFM measured by the two methods was strong (CCC > 0.80), and with increasing body size (including age or BMI), the correlation was gradually enhanced. Thus, the linear regression equation of 5-year-old children was constructed.There are various techniques available for body composition assessment. The researcher should make an informed decision and choose the most appropriate method for BCA regarding accuracy, availability, validity, safety, and cost. In the present study, we compared the validity, differences, and precision between BIA and ADP in Chinese children from 3 to 5 years of age. Compared with ADP as a standard, our results showed that BIA underestimated FM and overestimated FFM in normal weight children  in Chinese children aged 3–5 years. A variety of indicators were used to evaluate the results of the two methods, and linear regression equations of the BIA and ADP measurements in 5-year-old children were also developed. In an environment of increasing concern for children's health and obesity development, our results provide strong evidence for the feasibility of BIA as a substitute for ADP. As a relatively inexpensive, convenient, and reliable method of body composition measurement, BIA is expected to be widely used in large-scale pediatric population screening or clinical investigation in the future.KB    can accoIn this study, the consistency and the rate of correct classification of FM were lower than those of FFM. The reason might be that ADP evaluates FM and FFM based on body densitometry at the same time, while BIA evaluates FFM first and then uses the total weight to subtract FFM to calculate FM. This results in a higher measurement error for FM than for FFM.When comparing the differences, it was found that the difference between FM and FFM was statistically significant only in children of normal weight. In addition, the CCC values for evaluating consistency increased with age or BMI, and the LoA range in combined Bland–Altman analysis also showed a decreasing trend with increasing age or BMI. This might be because the BIA calculation formula is mostly based on adult data, and body water content was negatively correlated with age and BMI. As the body composition of children becomes more similar to that of adults as their age or BMI increases, the difference between the two methods decreases.P < 0.05), but the opposite trend was shown in children with obesity (P < 0.05). The effects of obesity status on the measurement of body composition by BIA can cause an increase in relative extracellular water in children and affect the hydration status, resulting in the overestimation of FM measured by BIA , the consistency between BIA and ADP was gradually enhanced. MFBIA  could provide a portable alternative to ADP in clinical and research settings for the assessment of body composition in older or higher BMI children. Further research is needed to standardize the assessment of body composition in children.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the IRB of Tianjin Women's and Children's Health Center (BGI-IRB 17116-201711). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.FC conceptualized and designed the study, carried out the analyses, and reviewed and revised the manuscript. GL conceptualized the study, supervised data analyses, and reviewed the manuscript. LW and YC analyzed the data and wrote the initial draft of the manuscript. JW, JL, GH, DH, and ZL were involved in data acquisition and data processing. XX and TZ conceptualized and supervised data analyses. All authors critically reviewed the manuscript for interpretation and intellectual content and approved the final manuscript as submitted.


To describe the incidence and to analyze risk factors associated with cholestasis in neonates with gastroschisis.This is a retrospective cohort study in a tertiary single center analyzing 181 newborns with gastroschisis between 2009 and 2020. The following risk factors associated with cholestasis were analyzed: gestational age, birth weight, type of gastroschisis, silo closure or immediate closure, days of parenteral nutrition, type of lipid emulsion, days of fasting, days to reach a full diet, days with central venous catheter, presence of infections, and outcomes.Among the 176 patients evaluated, 41 (23.3%) evolved with cholestasis. In the univariate analysis, low birth weight (p=0.023), prematurity (p<0.001), lipid emulsion with medium-chain triglycerides and long-chain triglycerides (p=0.001) and death (p<0.001) were associated with cholestasis. In the multivariate analysis, patients who received lipid emulsion with fish oil instead of medium chain triglycerides/long chain triglycerides (MCT/LCT) emulsion had a lower risk of cholestasis.Our study shows that lipid emulsion with fish oil is associated with a lower risk of cholestasis in neonates with gastroschisis. However, this is a retrospective study and a prospective study should be performed to confirm the results. The incidence of gastroschisis has been increasing worldwide since 1995 and it is about 4.42 cases for every 10.000 live births).Gastroschisis is a birth defect of the abdominal wall. In most cases the defect is on the right side of the umbilical cord insertion, being rarely on the left. Complex gastroschisis, prematurity, and low birth weight are associated with worse clinical outcomes, with higher mortality (<5% in large centers), a higher incidence of sepsis and catheter-related infections, cholestasis, short bowel syndrome, longer time to achieve full enteral nutrition, longer parenteral nutrition (PN) time and longer hospital stays.Gastroschisis can be classified as simple, when the defect is isolated, and complex, when the defect is associated with other intestinal anomalies such as intestinal atresia, intestinal perforation, necrotic segments or volvulus. Prolonged use of PN is associated with significant complications, high morbidity, and potential mortality. Intestinal failure-associated liver disease (IFALD) is the most prevalent complication affecting children who receive long-term PN. Since it is multifactorial, there are several proposals to explain IFALD: prematurity, time to reach full enteral nutrition, type of lipid emulsion, the presence of multiple infections, and intestinal dysbiosis.After surgical correction of gastroschisis, a period of intestinal hypomotility usually occurs and the etiology of the intestinal dysfunction has yet to be clarified. Lipid emulsions based purely on vegetable oils also contain higher concentrations of phytosterols compared with other lipid sources . There is evidence that phytosterols may contribute to the development of IFALD, though the role of phytosterols in the development of IFALD remains controversial. Lipid emulsions containing fish oil offer several advantages compared with those containing only soybean oil, including high concentrations of the ω-3 PUFA (docosahexaenoic acid and eicosapentaenoic acid), and the antioxidant α-tocopherol, reduced ω-6 PUFA content, and a reduced phytosterol load.The lipid emulsions medium-chain triglycerides/long-chain triglycerides (MCT/LCT) contain high concentrations of ω-6 polyunsaturated fatty acids (PUFA) such as linoleic acid, and relatively low concentrations of α-tocopherol that it exhibits strong antioxidant effects compared with the lipid emulsions containing fish oil.Knowing that gastroschisis is a congenital malformation that can occur with prolonged fasting, use of PN and infection, it becomes important to assess the incidence of cholestasis and the factors that may be related.The objectives of the study included reporting the overall incidence of cholestasis in this specific population as well as the risk factors for it. Among these factors, we relate some inherent to gastroschisis such as the use of a silo, the need for reoperation and others common to cholestasis such as fasting and use of PN. We also emphasize the concern to report the role of lipid alone in the incidence. A multivariate analysis was performed evaluating the role of lipids in PN in the incidence of IFALD.This is an observational, retrospective, cohort study conducted in newborns with gastroschisis treated at the Neonatal Intensive Care Center of the Child and Adolescent Institute, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brazil, between January 2009 and December 2020. The study was approved by the Ethics Committee of the Department of Pediatrics and the Ethics Committee for Analysis of Research Projects of the institution, protocol no. 2,476,188.The inclusion criteria was the diagnosis of gastroschisis, and the exclusion criteria was the development of short bowel syndrome. In order to carry out the Cox model, newborns who received the lipid emulsion twice a week were excluded.Regarding nutrition, in our unit, PN is started on the first day of life for hemodynamically stable newborns in infants with gastroschisis. Since May 2016, the lipid emulsion of choice has been a mixture with fish oil. Before 2016, lipid emulsion with MCT/LCT was used twice a week (from January 2009 to March 2012) and then daily (from April 2012 to April 2016). The lipid emulsion SMOF 20% has the following components and proportions: soybean oil (6%), MCT (6%), olive oil (5%), fish oil (3%) and soy-based emulsion containing 50/50% MCT/LCT. In PN, we usually use a dose of 3 g/kg/day of lipid as well as amino acids and glucose infusion rate according to blood glucose. Standardized in PN, we use trace elements, selenium and multivitamins.All data was collected from medical records. The following epidemiological and clinical variables were analyzed by dividing groups according to the presence of cholestasis: gestational age (weeks); birth weight (grams); type of gastroschisis (simple or complex); silo closure or immediate closure; reoperation, fasting time (days); type of lipid emulsion (MCT/LCT 20% or mixed lipid based emulsion with fish oil); total time of PN (days); time to achieve full enteral nutrition (days) ; length of hospitalization (days); infection and outcomes (discharge or death). at any time of hospitalization.The laboratory variables analyzed were central and peripheral blood culture, catheter culture, urine culture and direct bilirubin (DB) in (mg/dL). Cholestasis was defined as presence of direct bilirubin (DB) greater than 2 mg/dLResults are presented in proportions, means with standard deviation or medians with interquartile range. Continuous variables were tested for normality using Kolmogorov-Smirnov test. Comparisons between groups were performed using Mann-Whitney U test for continuous variables and chi-square for categorical variables.Cholestasis was analyzed using Cox’s proportional regression. The results are expressed in terms of hazard ratio  and adjusted for potential confounders for cholestasis . Potential confounders and models were identified using a theoretical framework through direct acyclic graphs (DAG).All analyses were performed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Macintosh, version 25.0. A p-value lower than 0.05 was considered significant.A total of 181 patients with gastroschisis between 2009 and 2020 were enrolled. Among these, five evolved with short bowel syndrome and were excluded from the study, and 49 received the lipid emulsion twice a week.Of the 176 newborns, 53.4% were male and there was a predominance of preterm infants (56.8%). Complex gastroschisis was present in 15.3% of patients (27 cases), with a reoperation rate of 25.6%. During the first surgical approach it was necessary to use the silo in 15.9% of the cases, most of them being reoperated within seven days. Bloodstream infections occurred in 36.9% of newborns and the survival rate was greater than 90% .Median birth weight was 2320 grams, median fasting was 22 days and median time of PN was 27 days. The median time to reach a full enteral diet was 27 days, ranging from 21 to 40. Regarding the length of hospital stay, the median was 35 days.The incidence of cholestasis was 23.3%, considering direct bilirubin (DB) >2 mg/dL in any measure during hospitalization; similar to that found by Fallon et al.: 27.6%. but lower than those found in other Brazilian regions. A study conducted in Belo Horizonte (MG) showed a mortality rate of 14.9%.It is known that neonatal cholestasis can be multifactorial, as in the case of newborns with gastroschisis. The need for the time of delivery with a gestational age closer to 37 weeks, low birth weight, the need for prolonged fasting and PN due to the dysmotility of the pathology, the use of a central venous catheter, the possibility of surgical re-approach and the presence of complex gastroschisis make this condition an interesting model to analyze cholestasis. Our model suggests that soy-based intralipids are associated with higher cholestasis risk compared to lipid emulsions containing fish oil, even after adjusting for potential confounders . Of the 181 newborns studied, five evolved to short bowel and were excluded from the analysis. Ninety-four newborns were male, 56.8% were premature and 25.6% required surgical re-approach. Compared to Raymond and other studies, prematurity had a similar rate (56.3%). Mortality was 9.7%, a little higher than that found by Raymond et al.,Low birth weight (p<0.023) and prematurity (p<0.001) were associated with cholestasis. The increased incidence of cholestasis in the most premature infants is likely to owe in part to the functional immaturity of the hepatobiliary system. Compared with full-term infants, preterm neonates are inefficient in processing bile acids.Cairo et al. found an incidence of cholestasis of almost 80% in newborns with gastroschisis, but using direct bilirubin greater than 1 mg/dL and also showed that all patients improved cholestasis with initiation of enteral feeds. In this study, we demonstrated that cholestasis was associated with almost all studied parameters: birth weight, gestational age, complex gastroschisis, reoperation, fasting duration, total PN duration, time to achieve full enteral nutrition, central venous access duration, positive blood culture, Neonatal Intensive Care Unit duration, death, and daily intralipid. While Fallon et al. found increased duration of PN and increased incidence of cholestasis with silo placement compared to the primary closure of the abdominal wall defect, we did not observe this in our patients.The presence of prolonged fasting, PN, the lipid emulsion used and infections, as well as other factors, play a role in the etiology of IFALD. PN in the setting of intestinal dysmotility and metabolic and infectious complications remains a major cause of morbidity and mortality in the gastroschisis population.Lipid emulsions have evolved over the decades with the aim of reducing the risk and/or evolution of IFALD. IFALD was the primary cause of death of children with intestinal failure. While the pathophysiology of IFALD is multifactorial, much attention has been devoted recently to the critical role that ω-6 PUFA containing intravenous lipid emulsions (ILEs) play in the development of IFALD.11 regarding lipid emulsion in PN for neonatal and pediatric use is to avoid the use of pure soy due to the high level of phytosterols and the use of a mixed emulsion with or without fish oil is recommended. In this study, we tried to find the risk factors for cholestasis and the role of the lipid emulsion as a unique factor. In the Cox regression, the use of lipid emulsion without fish was involved in the incidence of cholestasis.The most current recommendation of the European Society for Paediatric Gastroenterology Hepatology and Nutrition — ESPGHAN 2018A recent randomized, controlled pilot study showed that the use of lipid emulsion with fish oil reduces the risk of progressive IFALD in children with intestinal failure. Despite the small number of participants, the study is relevant for being a pilot in children. It is not possible to be sure that the benefit of lipid emulsion with fish oil is due to the presence of ω-3 or a lesser amount of ω-6.In this study, it was possible to state that the lipid emulsion with fish oil, when compared to the emulsion without ω-3, is associated with a lower IFALD (p=0.06). Despite being a retrospective study, the sample chosen is of a single, rare pathology and carried out in a single center, ensuring greater uniformity. Our study shows that lipid emulsion with fish oil is associated with lower risk of cholestasis in neonates with gastroschisis, compared to soy-based lipid emulsion. In gastroschisis, despite the presence of confounding factors for IFALD such as low birth weight, gestational age, the presence of complex gastroschisis, among others, the lipid in NP plays an important role in its pathogenesis with a higher weight for emulsion without ω-3.Several important questions remain to be answered about the use of lipid in children with PN-dependent intestinal failure.We know that the type of lipid emulsion was not randomized, and there is a limitation in that the neonates receiving MCT/LCT 20% are a historic group, thus the comparison is between a group treated before April 2016 with the group treated afterwards. Another limitation regards the fact that this is a unicentric study, but with a large number of subjects.Studies in infants and children receiving long-term PN have shown that multicomponent lipid emulsions containing fish oil reduce the risk of cholestasis and improve biochemical measures of liver function.Future randomized controlled trials with a long-term follow-up are necessary to explore the strength of the evidence, especially in the neonatal period, where other factors also appear as confounders — such as low birth weight and prematurity.


Various studies revealed that adolescent girls have limited knowledge pertaining to sexual and reproductive health (SRH). The current study assessed the effectiveness of SRH education among adolescent girls in urban areas of Odisha, India.. For the selection of study participants, adolescent girls who were studying in the ninth and tenth standards were recruited from each school. Eight schools were randomized through restrictive randomization at a 1:1 ratio, with four schools each in the intervention and control arm. Baseline and end-line assessments were done using a pre-tested, semi-structured questionnaire. Following baseline assessment, an intervention was given with the help of handbooks developed by the study authors to the schools in the intervention arm. Outcomes included change in knowledge, attitude and practices pertaining to SRH.The study design was a cluster randomized trial, where the clusters composed of eight Odia  medium government girls’ high schools in Bhubaneswar, the capital city of the state of Odisha, IndiaIn our study at baseline, there were a total of 790 students, where 469 (59.4%) students were in the intervention arm, and 321 (40.6%) students were in the control arm. At baseline, only 282 (60.1%) in the intervention arm and 171 (53.3%) in the control arm were aware that physical bodily changes due to puberty were normal. After the intervention, there was a statistically significant increase in knowledge in intervention group 367 (94.8%) . Most students used sanitary pads as absorbent, 97.2% in the intervention group and 98.4% in the control group. However, after the intervention, the use of other absorbents reduced to zero in the intervention group with a statistically significant difference (p < 0.05). The number of students having awareness on different methods of contraception increased from 51 (10.9%) to 337 (87.1%) in the intervention arm (p < 0.001), and of those having awareness on STIs/RTIs increased from 177 (38.2%) to 371 (96.1%) in the intervention group (p < 0.001).From our study, there is a significant proportional change in knowledge, attitude, and practices pertaining to SRH. Our study recommends policymakers and program managers for the implementation of comprehensive SRH in the regular school curriculum.Trial registration CTRI/2021/01/030490, registered on January 15, 2021. Prospectively registered at https://ctri.nic.in/Clinicaltrials/login.php Adolescent girls lack adequate knowledge pertaining to sexual and reproductive health, for which they face various issues such as teenage pregnancy, unsafe abortions and sexually transmitted infections. Hence the authors conducted this study to assess the effectiveness of school-based sexual and reproductive health education among adolescent girls in Odisha state of India in terms of improving knowledge, attitude and practices pertaining to reproductive health. A total of eight vernacular (Odia language) medium schools were selected for the conduct of the study, and the schools were randomly assigned where four schools received SRH education, and the other four received no intervention. A baseline assessment pertaining to SRH was done among adolescent girls studying in ninth and tenth classes of all eight schools, and then education was given to the four schools in the intervention arm. Students were educated on topics such as puberty, menstrual health, pregnancy, contraception and STIs/RTIs with the help of handbooks prepared by the authors. After 3 months of providing education, an endline assessment was done for the adolescent girls in all eight schools. There was an increase in knowledge, attitude and practices pertaining to SRH among the students who received education when compared to those who didn’t. Hence our study recommends policymakers and program managers include SRH education in the regular school curriculum. As per United Nations Children’s Fund (UNICEF), there are approximately 1.3 billion adolescents worldwide, with 90% of them living in developing countries. Among these, there are around 880 million adolescent girls . The UniIndia, with a population of 253 million, has the world’s largest adolescent population . In 2014Schools act as a platform for providing educational interventions, given the concentration of the adolescent population at schools and the ease of access to health promotion in poor communities without effective health systems . The autThe current study was conducted in Bhubaneswar, the capital city of Odisha state in India. Schools in India are broadly categorized into four types based on the enrollment of students: Lower primary school (classes 1 to 5), Upper primary school (classes 6th and 7th), High school , and Higher secondary school (class 11th and 12th). Each state in the country runs its own Department of Education. Schools in each state are of three kinds: government schools, privately owned schools, and schools that are provided grant-in-aid by the government . After rThe study design was a cluster randomized trial conducted from May 2020 to April 2022. During this period, there was an ongoing COVID-19 pandemic. The schools remained closed as per guidelines from the Government of Odisha (GOO). The schools conducted online classes using various virtual platforms such as Zoom meetings, Google Meet, and YouTube. Permission was taken to assess the students through online and offline modes when required and to give education to school students through both online and offline modes depending upon the school closure. Written informed consent was taken from parents of adolescent girls, and assent was sought from adolescent girls.For sample size calculation, as per a study conducted in Gujarat in the year 2017, the proportion of participants having awareness about STIs varied between 23 and 29% . ConsideThe sampling frame included all eight government girls’ high schools (GHS) in Bhubaneswar, Odisha. Schools were considered as clusters, and restrictive randomization was done to randomize eight schools at a ratio of 1:1, with four schools in each intervention and control arm. For the selection of study participants as per protocol, systematic random sampling was to be done among adolescent girls studying in ninth and tenth classes. However, due to the COVID-19 pandemic, all those who responded to the baseline questionnaire were included, and an amendment in protocol was done regarding the same and was approved by Institute Ethics Committee (IEC), AIIMS Bhubaneswar. Outcome variables included changes in KAP pertaining to domains such as puberty, menstrual health, pregnancy and contraception, STIs/RTIs, and HIV/AIDS.A pre-tested semi-structured questionnaire was developed, which was adopted from the Illustrative questionnaire for interview surveys with young people, World Health Organization . The queHandbook Part 1—Adolescent health statistics, Female reproductive system, Puberty, and Menstrual HealthHandbook Part 2—Pregnancy, Contraception, STIs/RTIs, and HIV/AIDSA literature search was done for the preparation of an intervention package on SRH education. The intervention package consisted of handbooks covering the following topics.The principal investigator has done a literature search through various websites of WHO and UNICEF, which focused on adolescent health. The relevant documents were then downloaded. The content required as per need has been retrieved from the documents and has been included in handbooks. Also, various Indian documents and modules pertaining to adolescent health, textbooks of school, and Obstetrics and Gynaecology, were referred for handbook preparation. The handbooks were developed in the English language. Since the vernacular language is Odia, the handbooks were translated into Odia by a professional Odia translator. The translated handbooks were given to two medico-social workers (MSWs) separately to verify comprehension of the language. The intervention was given in the months of November and December 2021 for the schools in the intervention arm. Owing to the COVID-19 pandemic, schools were running only half—a day, and accordingly, intervention timing was fixed. The author (AG) visited all the four schools in the intervention arm to provide SRH education to school-going adolescent girls. In each school, the intervention included three sessions. Three sessions were done on 3 consecutive days in each school. Each session lasted for about 2 h. The intervention was given to adolescent girls studying in ninth and tenth classes separately. In the first session, education was given on topics such as the female reproductive system, puberty, and menstrual health with the help of the first part of the handbook. The second session included the topics of part 2 of the handbook, i.e., pregnancy, contraception, STIs/RTIs, and HIV/AIDS. The intervention included a PowerPoint presentation with the help of a projector, brainstorming sessions, and a discussion of case scenarios. The third session was an interactive session between the students and teachers, and various doubts were cleared.Following the intervention, an endline assessment was conducted 3 months later among all eight schools using online Google forms. The assessment of each school was done on 8 different days between the months of February and March 2022. Once the endline assessment was completed, the same intervention was provided to students in the control arm. The flow of the study design is depicted in Fig. The recorded responses were exported to Microsoft (MS) Excel except in one school where data was collected through offline forms and entered manually into MS Excel. The data entry was done simultaneously on the same day of the collection of data by the principal investigator. Statistical analysis was done using International Business Machines (IBM)—Statistical Package for social sciences (SPSS) version 26. Descriptive data on socio-demographic details of students are presented in percentage or proportion. Quantitative variables such as the age of the students are expressed as mean and standard deviation. To assess the effectiveness of the intervention, the proportion of students in KAP of all domains was considered. The proportional change was measured among the intervention and control groups before and after the intervention by using the Chi-square test. With the cells having a count less than five, Fischer exact test was used. A p-value of < 0.05 was considered significant.The baseline sample included a total of 790 students from eight government vernacular (Odia medium) girls’ high schools. Among 790 students, 469 (59%) were in the intervention arm, and 321 (41%) were in the control arm. The mean age of students in the intervention arm was 14.4 ± 0.92 years, whereas in the control arm was 14.4 years ± 0. 8 years. The majority of students’ parents, both mother and father, studied till high school (37% and 34.3% respectively), and occupations included mothers being homemakers (91%) and fathers either clerk/shopkeeper/worker (39.7%). There was no statistically significant difference in baseline characteristics between intervention and control groups  medium schools. From various study findings, it was observed that adolescent boys had more knowledge of SRH when compared to girls; the former could not be assessed in our study. Our follow-up period was 3 months; hence there is a need for long-term follow-up in further studies. The effectiveness of intervention can be compared between urban and rural areas and in all types of schools, such as private and English medium schools. Our study did not assess the contraceptive practices among adolescent girls; where only the knowledge component was assessed. The gap between the awareness and utilization of contraceptive methods needs to be assessed. Also, the study did not assess sexual activity following intervention which recommends further studies to assess contraceptive usage, sexual activity, and incidence of teenage pregnancies. There are no randomized trials conducted which assessed these domains in an Indian setting owing to cultural taboos. Hence, there is a need for further evidence to strengthen the interventions pertaining to adolescent SRH.Scale-up assessment: considering the seven key categories for scaling up in the sense of global health, an assessment of the current strategy was done . The NatThe intervention was delivered through schools, which are already established educational institutions. Training teachers and frontline workers to deliver SRH education could potentially be integrated into existing educational programs. Thus, the model can be implemented with existing educational institutional mechanisms, infrastructure, and human resources, including field functionaries of the health department, NGOs and other private stakeholders engaged in implementing health programs at the micro level, indicating a great fit between intervention and any adopting organization. The intervention provided is a collaborative approach with permission obtained from school mass education. National health programs, namely Ayushmann Bharat , envisagAdolescent girls face various issues pertaining to sexual and reproductive health in day-to-day life. Our study assessed the effectiveness of school-based SRH education among school-going adolescent girls in urban areas of Odisha, India. The study showed a significant increase in knowledge, attitude, and practices pertaining to SRH among students in the intervention arm compared to the control arm. The study has generated evidence that schools can act as a platform for providing SRH education to adolescents, which is an immediate need of the hour in shaping healthy young people for the future. Based on the evidence, policymakers and the Department of School Mass Education should include comprehensive SRH education in the regular school curriculum for adolescents’ health and well-being.