Background. The etiology of obstructive sleep apnea (OSA) syndrome in children significantly differs from adults. In previous studies, only some of the indices have been investigated using CBCT. This study compares all the measurable indices of airway dimensions and anatomical cephalometric landmarks between children with OSA and healthy ones using cone-beam computed tomography (CBCT).Methods. Dimensions of the airway and cephalometric values were measured on CBCT scans of 50 children aged 8–12  and then compared between the two groups. The results of this study were analyzed with independent t test using SPSS 17 at a significance level of P<0.05.Results. Area, length, volume, anteroposterior length, and size of the upper airway in subjects with OSA were lower than those in healthy children, while the average values of SNA, SNB, and ANB in the OSA group were higher than those in the healthy group . Also, BaSN, PNS/AD1, and PNS/AD2 measurements in subjects with OSA were lower than healthy subjects . In addition, the width and anteroposterior length of the upper airway, SNB, BaSN, PNS/AD1, and PNS/AD2 indices were significantly different between the healthy group and those with OSA (P<0.05).Conclusion. Reduced upper airway dimensions, adenoid tissue enlargement, and cranial base flexion might play an important role in OSA development in children. However, most skeletal variables, such as the anteroposterior relationship of jaws and jaw rotation, were not significantly different between the two groups. In adults, ASO is usually accompanied by obesity, but most children with OSA are not obese. In contrast, adenotonsillar hypertrophy is considered one of the major causes of OSA in children.8 Therefore, different tools have been designed for OSA screening, such as the Berlin questionnaire and STOP and STOP-Bang questionnaires that are completed in a few minutes and are valid.12 The gold standard of OSA diagnosis is in-lab polysomnography which is expensive and time-consuming.13 Studies have revealed that besides narrow upper airway (UA), aging, Berlin questionnaire high scores, and gender  are among the risk factors of OSA.1 Also, soft tissue to craniofacial space ratio, which is the ratio of upper airway soft tissue volume to nasopharyngeal and oropharyngeal craniofacial space, is higher in OSA patients.14 Some studies have used lateral cephalograms to evaluate UA dimensions in children with OSA, revealing decreased pharyngeal diameters at levels of the uvula, adenoids, and tongue,15 with a significant, positive correlation with MRI findings. Therefore, it is a valid method for retropharyngeal and nasopharyngeal measurements.16 Several studies have evaluated airways in OSA children using cone-beam computed tomography (CBCT) as a three-dimensional (3D) and precise imaging method, concluding that the presence and severity of OSA are correlated with lateral obstruction of UA and a narrow nasopharyngeal area.17 There is a relationship between sleep disorders and children’s physical, emotional, and neurocognitive problems; therefore, OSA diagnosis is important in the childhood period. This study aimed to compare superior airway dimensions and cephalometric anatomic landmarks between 8–12-year-old children with OSA and healthy children using CBCT images, which is the first study in this age group to the best of our knowledge. This study also helps determine specific measurements that suggest OSA possibility in children, leading to more precise diagnosis and effective treatment approaches. This descriptive study was carried out on CBCT scans of 50 children aged 8–12 , referring to the Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Tabriz University of Medical Sciences for different reasons. CBCTs of children in this age range were found in the department archives, and Berlin questionnaires were filled for every sample in the study using telephone calls.15 The inclusion criteria consisted of OSA confirmed by the Berlin questionnaire for the OSA group and scans of healthy children matched to those with OSA regarding gender and age from the archives, whose health was confirmed by the Berlin questionnaire as the control group. Exclusion criteria consisted of the presence of any syndromes or clefts, a history of surgery in the palatopharyngeal area, significant medical and growth conditions, a history of the face and neck trauma, upper airway anomalies, asthma, and any upper airway acute or chronic infection. All the CBCT scans were obtained by a NewTom VGi cone-beam CT unit , and image reconstruction was conducted by NNT Viewer software (version 2.21). The images were observed on a 19-inch LCD monitor  with a resolution of 1024*1208 and 32 bits by an OMF radiologist. The images were exported as DICOM (.dcm) files and then imported to Mimics10.10  software for airway analysis. To determine the volumetric region of interest, a mid-sagittal picture was exported, and upper and lower limits of the UA region were defined as below:Upper limit: A line parallel to the FH (Frankfurt Plane) at the level of the most distal point of the hard palateLower limit: A line parallel to the FH at the level of the most anterior-inferior point of the second cervical vertebra (C2). To evaluate the width and anteroposterior dimension of UA, an axial picture of the region with the smallest dimension was selected.2. UA length was measured from PNS to the most anterior-inferior point of C3 and mm2 in the oropharyngeal region. Using Mimic software, the volume and cross-section area of UA were automatically measured in mmt test was used to compare data between the groups. Data analysis was performed using SPSS 17, and P < 0.05 was considered statistically significant. The results of this study were reported by descriptive statistics . Kolmogorov-Smirnov test showed normal distribution of quantitative variables ; therefo The OSA group consisted of 12 female (48%) and 13 male (52%) patients (mean age = 9.25 ± 1.08 years). Twelve females (48%) and 13 males (52%) were included in the control group (mean age = 9 ± 2.56 years).t test.P = 0.547, 0.606, and 0.706, respectively). According to the results, UA area, volume, and length were smaller in the OSA group compared to the control group, but the difference was not statistically significant . The width and the anteroposterior dimension of UA were significantly lower in the OSA group compared to the control group (P = 0.114), SN-MP (P = 0.902), PP-MP (P = 0.801), and PNS-AD1 (P = 0.913). There was no statistically significant difference between groups regarding SNA (P = 0.366), ANB (P = 0.012); on the other hand, BaSN angle and PNS-AD2 values were lower in the OSA group than healthy participants . SNB values were higher in the OSA group , computed tomography (CT), and CBCT can be employed for the 3D evaluation and analysis of organs; therefore, they might help detect areas of obstruction or decreased dimensions of UA as well.20 This study used CBCT to evaluate UA dimensions and other cephalometric measurements, which provide a 3D display of head and neck hard and soft tissues with lower x-ray exposure to the patient compared to CT imaging.21 Upper airway obstruction can occur in one or several areas from nostrils to the larynx, which needs to be precisely identified to increase treatment effectiveness and improve patients’ quality of life. It seems logical that some UA dimensions in OSA patients differ from those in healthy children; in this study, we evaluated the width, area, length, anteroposterior dimension, and volume of UA in OSA and healthy children. The results revealed that UA width and UA anteroposterior dimensions were significantly lower in the OSA group, with no significant difference in UA area, length, and volume between healthy and OSA children. It seems reasonable that lower UA area, volume, and other UA dimensions can lead to resistance to airflow, making the person susceptible to OSA.1 reported that UA width in CBCT measurements was significantly lower in the OSA group than in the healthy group. In a study by Buchanan et al,22 UA width was significantly lower in the OSA group, confirming the findings of the current study. Volume and area were significantly lower in the OSA group, consistent with the current study results. However, these findings were not statistically significant in our study, which might be related to different ethnic groups compared to our study. Also, in Buchanan and colleagues’ study, UA was longer in the OSA group, which contrasts our results. The reason might be the use of different points for defining UA length  compared to our study. However, a study by Neelapu et al23 was consistent with our study regarding longer UA in OSA patients due to lower hyoid position. Enciso et al24 showed that the UA area was significantly lower in children with OSA than in the control group, indicating the same but non-significant difference in our study. These findings can be justified by considering the higher sensitivity of MRI for soft tissue evaluation compared to CBCT. MRI assessment of UA dimensions by Arens et al This study also evaluated some cephalometric measurements:SNA, SNB, ANB as indicators of jaws position and relationship BaSN angle to show the amount of cranial base flexion SN/MP and SN/PP as indicators of vertical growth pattern PNS to AD1 and AD2 distances to represent adenoid tissue projection in the pharyngeal space 25 who claimed that mandibular retrognathism had a positive correlation with OSA severity. However, some other studies failed to find any differences in mandibular position between OSA and control groups.26 Considering the age limit of this study’s samples in whom the mandible is still actively growing, this distinct result is significant, suggesting that mandibular retrognathism might not be a risk factor for OSA in children. Similarly, the results of ANB comparisons between the two groups in this study showed that skeletal anteroposterior relationships might play no significant role in OSA development in children. Although SNA and ANB values showed no statistically significant differences between the two groups, the SNB angle was significantly larger in the OSA group. Therefore, there was no significant difference in maxillary anteroposterior position between the two groups; however, the mandible was significantly more anteriorly positioned in the OSA group according to SNB measures, contrasting some previous studies like Ryu et al, SN/MP and PP/MP angles were higher in healthy samples, with no statistically significant differences. Therefore, it can be concluded that the vertical dimension might not be responsible for OSA in children.27 BaSN angle was significantly lower in the OSA group, consistent with studies that showed a positive correlation between cranial base flexion and anteroposterior airway dimensions that might influence OSA development.29 Similar to previous studies, a significantly smaller distance between PNS and AD2 and a non-significant, smaller distance between PNS and AD2 in the current study demonstrate the possible role of adenoid tissue enlargement in OSA development in children. The results of this study demonstrated that Reduced UA dimensions might play an important role in OSA development in children; however, most of the skeletal variables, such as the anteroposterior relationship of jaws and jaw rotations, were not significantly different between children with OSA and the control group. There was significantly more flexion of the cranial base in the OSA group, resulting in a narrower UA in these children. Adenoid tissues were larger in children with OSA compared to healthy children. We would like to acknowledge the staff of the Department of the Oral and Maxillofacial Radiology, Faculty of Dentistry, Tabriz University of Medical Sciences, who warmly helped us in performing the study. FE and AHS planned the study. AHS, MS, and AN performed the study. PN and AHS performed the literature review. PN drafted the manuscript, and FE carried out the statistical analyses and interpretation of data. AHS critically revised the manuscript for intellectual content. All the authors have read and approved the final manuscript. This study was not supported financially by any organization. This study was approved ethically by the Ethics Committee of Tabriz University of Medical Sciences: IR.TBZMED.REC.1397.150. The authors report no conflict of interest in this study.


Significant improvements in the PST group for symptoms of distress, quality of life and self-efficacy were also observed. There was no significant difference in mobility. The treatment effect was consistent at all follow-ups. Attrition rate was low (13%). Conclusions: PST was associated with a significant and sustained improvement in a range of outcomes in people with recent vision loss. Further large scale RCT is now required.Background: Problem-Solving Treatment (PST) has been used to treat and prevent depression in a variety of settings. However, the impact of PST on improving psychological well-being in those with recent vision loss remains unknown. The aim of this study was to evaluate whether PST may lead to better psychological well-being in people with recent vision loss through a pilot parallel-group randomised controlled trial. Methods: Participants who were diagnosed with visual impairment during the previous 3 months were randomly allocated to either an 8-week PST or treatment as usual (N = 61). Outcome measures were administered at baseline, 3, 6, and 9-months. Results: A linear mixed model demonstrated that PST significantly improved psychological well-being  (treatment effect = 2.44; 95% CI = 0.40–4.47;  Epidemiological data in the UK indicates incidence of depression amongst older adults with visual impairment to be 13.5%, compared to 4.6% among older adults with normal vision ,3. InsteProblem-solving treatment (PST) is an established, brief, structured psychological intervention that specifically addresses individuals’ confidence, motivation and psychological well-being by teaching a rational and systematic approach to problem solving and addressing negative perceptions that may interfere with finding solutions . It is aA single-blind, multicentre, parallel-group pilot RCT of PST plus usual care (PST group) versus Treatment As Usual (TAU group) for people newly diagnosed with visual impairment. This included an assessment of adherence, recruitment and retention.Participants were eligible for inclusion if they were:adults (≥18 years of age);community-dwelling ;diagnosed with severe, irreversible sight loss, or registered as sight impaired  or severely sight impaired (blind) within the previous 3 months.Participants were excluded if they (i) participated in psychiatric or psychological assessment or intervention within the previous 3 months; (ii) had severe cognitive impairment  across London, South East and Central England. For the community recruitment, information about the study were sent via the appropriate Sensory Needs Service team approximately a week after the participants received their Certificate of Visual Impairment (CVI), along with a reply slip and pre-paid envelope. For the NHS recruitment, participants were provided the same information pack by an NHS-based Vision Support Officer (VSO), an ophthalmologist, or a research nurse. If they chose to participate, participants were screened for suitability by the telephone, and if deemed suitable, then a home visit was arranged for the Study Coordinator to obtain informed consent and the full assessment was conducted. This research adhered to the tenets of the Declaration of Helsinki.All assessments were administered by the Study Coordinator at week 1 (baseline), 3, 6 and 9 months. However, assessments at 3 and 6 months were limited to outcomes of well-being, symptoms of distress, mobility, and quality of life to reduce participant burden. The exceptions to this were in those instances where the 9 months follow-up were not possible, in which case the full assessments were conducted at 6 months instead. Baseline assessments were conducted at participants’ homes, while subsequent assessments were conducted over the telephone where possible.The primary outcome was measured by the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) . This asSecondary outcomes were as follows:(i)psychological distress, as measured by the Hospital Anxiety and Depression Scale ;(ii)functional mobility, measured by the Self-assessed Instrument for Perceived Visual Ability for Independent Mobility  and Life(iii)quality of life, measured by the Impact of Vision Impairment Questionnaire  and the (iv)problem-solving ability, measured by the Social Problem Solving Inventory—Revised: Short ;(v)self-efficacy, measured by the Generalized Self-efficacy Scale .The reliability and validity of the above scales are reported in their respective publications. Self-reported information on health resource use over the previous 4 weeks were also gathered by a health resource use questionnaire developed for a previous study .Total scores were computed using the recommended algorithm for each scale, with mean imputation used as appropriate for each scale scores, but not the total scores.Our sample size of 120 patients was chosen to detect an improvement on the Warwick-Edinburgh Mental Well-being Scale of 5 points  with a Participants were randomly allocated with a 1:1 allocation to either PST or TAU, using stratified randomisation to balance severely sight impaired (blind) vs. sight impaired  across the groups. An independent web-based randomisation service was used which was administered by the study therapist, and the outcome assessor and study team was masked to group allocation. Blocking was used within strata with random block sizes of 2, 4 and 6. After randomisation the study therapist informed the participants of the group allocation. Participants could not be masked to group allocation because the intervention was psychosocial. However, they were reminded not to disclose which arm of the study they were assigned to at the beginning of each assessment, in an attempt to minimise detection bias.In the PST group the participants took part in six PST sessions of 45–60 min over an eight week period. Sessions were delivered by a study therapist trained in PST by Dr. Mynors-Wallis, the developer of PST. The first 4 sessions took place weekly, and the last 2 sessions every two weeks. All PST sessions took place at the participant’s home. PST consisted of seven stages, with core elements of the structure present in all sessions. These stages represent discrete steps in either the treatment process  or in the problem-solving process itself  . TypicalAll analyses were carried out using all available data with participants in the groups to which they were originally randomised, and no imputation was performed for missing data. Baseline participant characteristics were described using means (SDs) or medians (interquartile range) for continuous measures, and proportions for categorical measures.For the primary analysis, a linear mixed model was used to evaluate the effect of treatment on the primary outcome measure, the Rasch-transformed WEMWBS score at 3,6, and 9 months with fixed effects for treatment, time, severity of vision loss (stratification factor), and baseline Rasch-transformed WEMWBS score, and a random effect for patient. As a sensitivity analysis, the primary analysis was repeated using the raw WEMWBS scores as the outcome. Additionally, the primary analysis was repeated after including covariates for age, gender, and cause of visual impairment as fixed effects in the model, to adjust for observed imbalances in the baseline characteristics.As a secondary analysis, we explored whether the effect of treatment changes over time by including an interaction between treatment and time as a fixed effect in the primary analysis model. We also explored whether the effect of treatment differed for the severity of vision loss groups in a similar manner. These secondary analyses should be only considered as exploratory as the study was not powered for them.Linear mixed models were also used to evaluate the effect of treatment on the different secondary outcomes, with fixed effects for treatment, time, severity of vision loss, and baseline score, and a random effect for patient. All analyses were carried out using Stata 13.1.Ethical approval was obtained through the NHS Research Ethics Committee (reference number 13/LO/0416). The trial registration number was ISRCTN87854656, and the UK Clinical Research Network Portfolio number was 14289.The estimated mean difference in Rasch-transformed WEMWBS score between the two groups  was 2.61 (95% CI: 0.27 to 4.95), 1.78 (−0.60 to 4.16), and 3.11 (0.53 to 5.69) at 3, 6, and 9 months, respectively, after adjustment for baseline score and severity of visual impairment .p = 0.019) points higher than that of treatment as usual group, after adjustment for baseline score and severity of visual impairment. Adding age, gender and cause of visual impairment to the analysis model resulted in the same conclusion  as did use of the raw WEMWBS score as the outcome .Overall, the PST group had an average Rasch-transformed WEMWBS score that was 2.44  (There was no evidence to suggest that the effect of treatment changed over time ( = 0.50) .p = 0.012) for HADS Total. Additionally, there was evidence that IVIQ scores were higher for people receiving PST with an estimated effect of 0.23 units (raw score rather than Rasch score) . People receiving PST also had higher Self Efficacy scores with an estimated effect of 0.27 points . There was little evidence of a difference for the remaining secondary outcomes  of the health resources questions for each group suggest that participants in the PST group reported fewer visits to the GP at Surgery (0.5 (0.6) vs. 0.8 (0.8)) and Nurse at Surgery (0.1 (0.3) vs. 0.4 (0.9)) at 6 months, as well as reporting fewer days in which they were unable to follow usual activities at 9-months (4.4 (8.9) vs. 13.7 (13.1)) .This trial demonstrated that PST is feasible for people newly diagnosed with visual impairment and that PST is potentially efficacious with regard to psychological well-being. Adjusting for baseline score and severity of visual impairment, the PST group had significantly better psychological well-being (our primary outcome), than the treatment as usual group. The PST group also demonstrated significantly better quality of life scores and depression and anxiety scores compared to the treatment as usual group. Therefore, the present research suggests that PST is an intervention that shows promise in improving wellbeing and quality of life, and reducing depression and anxiety, in people diagnosed as blind or partially sighted. Improvements in wellbeing, depression, and quality of life are maintained at the 9-month follow-up point, suggesting potential long-term effects of the intervention. Furthermore our secondary analyses suggested that PST is effective in both people who are partially sighted and those with severe visual impairment. There was no measurable impact of PST on mobility measured by two separate scales. This suggests that the effects of PST are mainly psychological as expected, and confidence in dealing with various problems do not readily translate to their levels of mobility. One explanation for this is that participants could explore any problems in their lives through PST, and so confidence in a particular aspect of their lives  may not easily translate to more confidence in their mobility levels.In terms of acceptability and feasibility, although recruitment was slower than expected, the recruitment was better via NHS compared to community methods. Additional means of improving recruitment needs to be considered in any future trials . In addiThere were several limitations to this study. First, there was a difference in some of the baseline measures between the two groups. However, the sensitivity analyses demonstrate that this imbalance was not problematic. In our study we had no attention control group, and it is possible that the effects we saw were due to the extra attention from up to six home visits by the therapist, rather than the PST itself.The sample size of our study, which although was sufficient to detect a significant difference in the two groups on several key variables, was still not large enough to allow a clear interpretation of the secondary analyses as well as the subgroup analyses. Thus it is not known whether self-efficacy is a mediator of change for the primary outcome , although self-efficacy was significantly better in the PST group than the treatment as usual group.Our study expands on the study by Rovner  by demonThis study was powered to detect a meaningful change in the primary outcome, that is, it was a fully powered pilot study. However, we did not recruit as many participants as intended, and therefore the results may need to be interpreted with some caution. A larger RCT is now required to enable us to better explore the secondary outcomes, subgroups and mediators. It would also provide better precision when it comes to estimating treatment effects. In our study the control group only received usual care. In future studies, active control groups should also be included. The data from this trial suggest that direct engagement with participants should be used to increase recruitment.


Metabolic syndrome (MS) is not a single disease but a cluster of metabolic disorders associated with increased risk for development of diabetes mellitus and its complications. Currently, the definition of MS published in 2009 is widely used, but there are more versions of the diagnostic criteria, making it difficult to conduct scientific discourse in this area. Increased arterial stiffness (AS) can predict the development of cardiovascular disease both in the general population and in patients with MS. Pulse wave velocity (PWV), as a standard method to assess AS, may point out subclinical organ damage in patients with hypertension. The decrease in PWV level during antihypertensive therapy can identify a group of patients with better outcomes independently of their reduction in blood pressure. The adverse effect of metabolic disturbances on arterial function can be offset by an adequate program of exercises, which includes mainly aerobic physical training. Non-insulin-based insulin resistance index can predict AS due to a strong positive correlation with PWV. The purpose of this paper is to present the results of the review of the literature concerning the relationship between MS and its components, and AS assessed by PWV, including clinical usefulness of PWV measurement in patients with MS and its components. Metabolic syndrome (MS) is not a single disease but a cluster of metabolic disorders such as abdominal obesity, atherogenic dyslipidemia, elevated blood pressure (BP), insulin resistance (IR), and higher glucose levels . For decMS is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and its complications. Cardiovascular diseases (CVDs) are one of the most important causes of morbidity and mortality in the population of patients living with T2DM ,13,14. MMS was shown to be associated with increased oxidative stress. Obesity and IR are the MS component that contributes the most to this relationship . On the Therefore, it is important to identify subclinical vascular damage in patients with MS and its components who should be taken into careful consideration for appropriate treatment. Increased arterial stiffness (AS) can be considered to be a good predictor of the development of subclinical cardiovascular dysfunction, so the assessment of AS can be useful in the identification of patients with increased cardiovascular risk ,21.According to the American Heart Association as well as European experts’ consensus, the measurement of pulse wave velocity (PWV) remains a standard method to assess AS ,23. TherHowever, there are some limitations to the measurement of PWV. Specialized equipment and experienced personnel are required to perform the measurement. In addition, care should be taken to ensure that the measurement is carried out in appropriate conditions, such as, among others: a quiet, dry room, ensuring thermal comfort; moreover, the measurement should be carried out after a ten-minute rest in a lying position. The BP value and heart rate (HR) should also be taken into account during the interpretation of the PWV value, as these parameters can influence the PWV measurement result .The purpose of this paper is to present the results of the review of the literature concerning the relationship between MS, its components, and AS, with the greatest emphasis on AS assessed by PWV, including the clinical usefulness of PWV measurement in patients with MS and its components.Increased systolic blood pressure (SBP) or diastolic blood pressure (DBP) are both MS components. In patients with high cardiovascular risk such as patients with MS, it is crucial to assess subclinical dysfunction of the cardiovascular system in order to initiate preventive measures, adequate life changes, and treatment early ,26. TherIncreasing AS defines the loss of the arterial wall’s resistance to expansion by an increment in volume; as a result, it is linked to increased BP ,32. AS ip = 0.003) [In a cohort study in which 54,849 middle-aged patients participated, it has been shown that both SBP and DBP depend on AS. Compared to patients with normal PWV values, moderate, moderate–high, and high PWV values were responsible for a 3.03-, 5.44-, and 7.87-times higher incidence of hypertension, respectively . Hyperte= 0.003) .p < 0.001) and HR (p = 0.07) levels between visits during the period [However, in a four-week observational study performed by Kubalski et al., it was found that the PWV value changes with BP and HR. PWV was related to BP , an analysis of 8450 patients demonstrated a 42% lower risk of death associated with a decrease in the PWV value observed after one year of antihypertensive therapy compared to patients in whom the PWV value remained not reduced. Furthermore, the results of the SPRINT study were independent of BP reduction and Framingham risk score [In the management of arterial hypertension, it is crucial to pay attention to a low sodium diet, as well as exercise training. High sodium intake is related to water retention, an increase in systemic peripheral resistance, and changes in the structure and function of large elastic arteries . The impWhen considering abdominal obesity, it has been shown that in obese patients the PWV is significantly higher compared to normal healthy individuals, proving that abdominal obesity is a significant factor in the development of AS ,49,50. BIn a prospective study performed by Kae-Woei Liang, it has been proved that after a three-month weight reduction program, brachial–ankle PWV in patients with obesity and MS, compared to the healthy control group, decreased slightly. However, in those in whom weight regaining was observed in a sixty-month follow-up period, compared to the healthy control group that also experienced weight regaining, the brachial–ankle PWV increased by a significantly higher amount. Interestingly, brachial–ankle PWV at the 60th month after weight regaining in obese patients with MS was even worse than the baseline values, was associated only with SBP or DBP increments, and when compared to healthy individuals proves to be beyond the aging process. In addition, brachial–ankle PWV values after weight regaining were independent of body weight, high-sensitivity C-reactive protein (hs-CRP), or insulin resistance changes . HoweverThe weight loss program in obese patients is based on diet changes and regular exercise ,60,61. IDyslipidemia is a metabolic disturbance associated with an impaired concentration of basic lipid parameters, such as blood level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and/or the presence of dysfunctional lipoproteins in the blood .The whole spectrum of possible underlying pathophysiological mechanisms of the influence of lipid profile on atherosclerosis has not yet been well established. Lipid disorder may lead to cardiovascular disease in different ways . Elevatep = 0.024). Moreover, the results of this study were independent of other MS components, age, gender, smoking status, LDL-C, and statin treatment [In a prospective study involving 1934 patients, the correlation between elevated TG and AS was analyzed. The authors of this study define AS by cardio–ankle vascular index (CAVI) as independent of BP compared to brachial–ankle PWV. The elevated level of TG was shown to be associated with higher CAVI values , BMI , TC level , LDL-C level , TG level , non-HDL level , and TG/HDL-C ratio  was shown to have a significant impact on PWV values [In the retrospective study conducted by Alparslan Kilic, in which data from 1584 patients were analyzed, age  is defined as a logarithm from the TG/HDL-C ratio . In a reAS increases in patients with MS and IR ,79. Predp < 0.001). In addition, they proved METS-IR to have the strongest correlation with AS over other non-insulin indexes, including TG/HDL-C ratio. When including METS-IR in the Framingham Hypertension Risk Prediction Model, a more precise hypertension incident predicament was observed [In a prospective study published in 2019, researchers proved the correlation between METS-IR and PWV, SBP, and DBP independently of age, sex, smoking status, and hypertensive therapy. METS-IR in 34% predicts PWV changes  calculated from waist circumference, BMI, and body height has been confirmed to identify people with MS and increased AS . Nedogodp < 0.001) and to have higher PWV  than those without MS [p < 0.05 for all variables) [p = 0.005) or increased all-cause mortality (p = 0.002) [Patients diagnosed with arterial hypertension have a high prevalence of metabolic syndrome regardless of controlled or resistant hypertension . Hypertethout MS . Predictriables) . Chen et= 0.002) .The conclusions from selected studies on vascular stiffness in patients with MS are presented in As shown in our analysis, there is no single pattern for elevated risk of CVD in patients with MS. MS, as a group of metabolic disorders, is strongly associated with subclinical vascular damage, marked by increased PWV value ,100. As Abdominal obesity is an important component of MS. The ambulatory AS index of the obese subjects is significantly higher than in the healthy controls ,105,106.It is important to measure PWV under stabilized BP and HR values, particularly in patients with newly diagnosed hypertension in whom detection of organ damage mediated by asymptomatic hypertension has an impact on risk stratification ,112. PWVThe risk of increased AS depends on hyperlipidemia at young ages . DyslipiAs shown in a study performed by Gong et al., AS became significant with increasing numbers of the metabolic components . HoweverDue to the strong correlation between PWV and METS-IR that extends beyond sex, age, smoking status, and hypertensive treatment, as shown in the analyzed studies, METS-IR could be treated as a subrogating of AS in routine primary care . FurtherMS and its components are a significant problem for healthcare systems worldwide. CVD is the leading cause of morbidity and mortality, and, on the other hand, MS predisposes the development of CVD. The identification of patients with features of subclinical dysfunction of the cardiovascular system in the population of patients with MS and its components is also very important in clinical practice, and PWV measurement is a valuable tool for this purpose.AS defined by PWV is positively correlated with both SBP and DBP. It may indicate subclinical organ damage in patients with hypertension. In addition, the decrease in PWV level during hypertensive therapy can identify a group of patients with better outcomes independently from BP reduction.Obese patients with MS who have lost and regained weight are predisposed to have a significant increase in PWV, above their baseline levels. The adverse effect of metabolic disturbances on arterial function can be offset by an adequate program of exercises, which includes mainly aerobic physical training.The TG/HDL-C ratio demonstrates the ratio between the atherogenic and preventive lipoproteins. The increased TG/HDL-C levels ratio is positively correlated with increased PWV levels and is an independent risk factor for cardiometabolic disease, with a consecutive correlation that was not proved separately for TG and HDL-C levels.IR affects AS and accelerates arterial aging. Non-insulin-based IR index, such as METS-IR, can predict arterial stiffens due to a strong positive correlation with PWV.We have presented a heterogeneous group of studies focused on PWV in patients with MS and its components. It should be highlighted that it is important to take into account the level of cardiovascular risk in the population with MS. In addition, several modalities are available in the assessment of AS including recording the pulse waves by a tonometer transducer, standard BP cuff, doppler ultrasound, and magnetic resonance imaging (MRI). Most of the studies presented have used the tonometry transducer method. However, different points of measurement were taken into consideration, such as carotid, femoral, brachial, and ankle. In addition, the distance between the two surface sites and the time delay between the waveform is used to determine PWV, and it may be impacted by the obesity in measurements.Although this subject is of great interest and the knowledge of the association between AS and MS and its components has increased significantly, further research is necessary, which perhaps will allow the use of the measurement of PWV rroutinely in the treatment of patients with MS. A novel approach and applications of existing drugs to specifically target pathways involved in modulating AS may provide further support to its broader assessment and treatment to improve cardiovascular outcomes.


Moringa oleifera and Azadirachta indica trees, then dried and powdered. Characterizations of gum polysaccharides were performed using TLC, GC-MS, NMR, etc., and sugar molecules such as glucose and xylose were found to be present. Effects of the gums on Abelmoschus esculentus growth were observed through root growth, shoot growth, and biomass content. The exposure of the seeds to the plant gums led to bio stimulation in the growth of the plants. Poor quality soil was exposed to the gum polysaccharide, where the polysaccharide was found to improve soil quality, which was observed through soil analysis and SEM analysis of soil porosity and structure. Furthermore, the plant gums were also found to have bio-pesticidal activity against mealybugs, which showed certain interstitial damage evident through histopathological analysis.Plant gums are bio-organic substances that are derived from the barks of trees. They are biodegradable and non-adverse complex polysaccharides that have been gaining usage in recent years due to a number of advantages they contribute to various applications. In this study, gum was collected from  The use of chemicals and synthetic fertilizers has been growing consistently over the recent decades, causing adverse effects to the non-target environment, and posing a threat to the ecosystem . HoweverAzadirachta indica (AI), commonly known as neem is a tropical evergreen tree native to the Indian sub-continent. Various parts of the trees have been exploited in a number of applications for the past 4000 years due to their unique properties [Azadirachta indica tree, is a complex hetero-polysaccharide that is clear and brown in color [Moringa oleifera (MO), also known as the “Miracle Tree”, is a highly valued plant that is predominantly cultivated in the tropics and subtropics. Leaves, flowers, and immature pods of Moringa oleifera are suitable for consumption due to their high content of amino acids, vitamins, minerals, proteins, fiber, and lipids [Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium and Enterobacter aerogenes [Moringa oleifera, a member of the Moringaceae family, turns to a brownish color on exposure to the sun and the environment [operties . The leaoperties ,13. Neemin color . It beloin color , anticanin color  and antiin color . Among iin color . It was in color . It can in color . Moringad lipids  and as ferogenes . Anti-aserogenes . White gironment . It is pironment  and is aironment .Phenacoccus solenopsis  in greenhouses can be observed all year and are most commonly visible on shoot tips and the undersides of leaves, covering them in vast amounts of white waxy material [Phenacoccus solenopsis has the potential to harm or destroy native plant species. Pesticides can be used to get rid of them; however, the presence of the white waxy coating makes eradication difficult. Limited studies are available on the applications of these two gums as plant growth promoters and bio-pesticides. Their polysaccharides are similar to the polysaccharides generated by soil microbes. They are superabsorbent and aid in the modification of water retention capacity and the improvement of soil structure and physical qualities. These gums have been used in the past to remove oils and heavy metals from soil [Acacia senegal and its nitrogenous derivatives, such as arabic acid, ammonium arabate, arabamide, fraction of high protein, and fraction of low protein, were utilized to promote growth in Winka seeds. The number of leaves, height, and dry weight of plants treated with the gum and its compounds differed significantly [Infestations by material . These amaterial . Due to rom soil ,30,31 anrom soil ,33,34. Pficantly . TherefoOpuntia cochenillifera (L.) has been reported to possess alkaloids and terpenes/steroids by the Dragendorff, Mayer, and Wagner tests [Acacia tortilis gum contains flavonoids, saponins, steroid, quinone, and tannin as confirmed by thin layer chromatography [Moringa oleifera gum displayed peaks around 200–240 nm and 279 nm , of the Central Rift Valley of Ethiopia, has been reported to possess 15% moisture and 3.56% ash content [Acacia Senegal was found to contain 12.02 ± 0.02% moisture and 2.45 ± 0.01% ash content, while xanthan gum contains 10.64 ± 0.55% moisture and 7.60 ± 0.05% ash content [TLC was performed for MO and AI gum using the solvent systems ethanol:water (2:1) and ethanol:chloroform (2:1), respectively. Rfera gum  where Rfdica gum . Rao anddica gum , also. A content . In anot−1, corresponding to O-H stretching of alcohol groups in the gum polysaccharide  was purified, and the absorbance maxima were detected in the range between 200 to 280 nm and at 410 nm for MO and AI gum polysaccharide, respectively . FT-IR accharide . The pred xylose . Glucosed xylose . Similar1H NMR spectrum of MO gum polysaccharide revealed signals corresponding to the presence of galactose and xylose. The peak at 4.820 ppm revealed the presence of H-1 of β-glucose. The peak at the ppm of 5.27 and 3.782 shows the presence of the H-1 and H-2 of α-galactose. The peak at 3.361 ppm depicts the presence of β-xylose  was showing reduced growth  and 258 nm (AI) in UV-Vis spectroscopy may indicate the presence of glucose and the absorbance peaks around 210 nm confirm the presence of xylose [Azadirachta indica gum polysaccharide and suggested the presence of glucose and xylose with absorbance peaks at around 265 nm and at 210 nm, respectively. According to Udo et al. [Acacia senegal and Anacardium occidentale trees were 210 and 200 nm, respectively. The basic polysaccharide structure was revealed by the intense peak in the range 1010 to 1030 cm−1 in FTIR spectra, indicating the stretching vibrations of the glycoside bridge (C–O–C) and confirming the presence of polysaccharides [Araucaria heterophylla gum reported by Gayathri and Sundara, [Acetobacter xylinum. Kumar et al. [Vina mungo. Kharbade and Joshi, [Xanthomonas campestris using TLC.In this study, two plant gum polysaccharides—from f xylose , as prevf xylose  performeo et al. , the abscharides ,63. ThinSundara,  reinforcr et al.  also repd Joshi,  revealedd Joshi,  also revAcacia senegal gum and its nitrogenous derivatives was found to significantly improve the growth, which was comparable with the results observed in this study [Eucomis autumnalis proved to be a promising and ecologically friendly approach to boost plant growth that can be suggested for long-term ornamental plant production.Biostimulants are a type of chemical that is now used to aid in the growth and development of horticultural plants. The addition of polysaccharides in the form of biopolymers is known to improve seed germination and seedling growth . Plant gis study . It is sis study ,72. Whenis study . Polysacis study . In a stis study , a biostA stable and continuous pore system is required to form a well-defined soil structure that is essential for favorable plant growth. It is also one of the most useful parameters to determine whether the soil system can be characterized as a plant medium for plant growth . A well-Phenacoccus solenopsis) are covered with vast amounts of white waxy material and can be found on shoot tips and the undersides of leaves. They are usually oval in shape and clump together to form a bunch. They also deform the stems, dry up the leaves and infest all parts of the host plants except the roots. Different parts of MO and AI trees have been reported to have pesticidal activities [Mealybugs  and Azadirachta indica (AI) were scraped off from the barks of trees found in our garden in Chennai, Tamil Nadu. The obtained gums were subjected to complete drying and later powdered and stored in an airtight container. The powdered gums were used for further study and characterization (All methods were performed in accordance with the relevant guidelines and regulations. Leaves of rization .245) for the MO and AI gums using the solvent systems ethanol:water (2:1) and ethanol:chloroform (2:1), respectively. Bands were visualized by exposing the samples to an iodine-saturated chamber and also by spraying DPPH (on the plates which were not exposed to iodine). The MO and AI gum polysaccharides were subjected to phenol sulfuric acid assay to identify the presence of monosaccharides [Qualitative phytochemical analyses for the presence of alkaloids, flavonoids, saponins, reducing sugars, amino acids, phytosterols, tannins, and glycosides were performed for the crude gums (MO and AI) ,84,85,86charides . Ash andcharides  and Gundcharides .Gum polysaccharide (MO and AI) was purified by following the method of Samrot et al.  and was 1H and 13C nuclear magnetic resonance (NMR) spectra were also recorded using 400 MHz NMR .The purified polysaccharide was dissolved in distilled water and characterized using UV-Vis analysis  and FTIR analysis . TGA was conducted on the polysaccharides to determine their thermal degradative properties (SDT Q600 V20.9 Build 20). Abelmoschus esculentus seeds were obtained from a local vendor and utilized for this study, as they are easy to grow, and the seed size meets the primary requirement for any seed handling system [g system . The seeg system .An in-vitro study of the effect of gum polysaccharides on plant growth was carried out for a period of 9 days. One milliliter of a 10% plant gum polysaccharide (MO and AI) solution was applied to the seeds, which were placed in a cotton bed in clean, air-dried petri dishes. The setup was maintained in a humid chamber at room temperature, and the seeds were sprayed with distilled water at every 24 h to maintain moisture content. The seed germination and growth with the study concentrations were observed on every 3rd consecutive day .GerminaThe root and shoot growth along with biomass were observed on every 3rd day for the period of 9 days. The total weight of each plant was weighed to calculate the biomass. The observations for the study were performed in triplicates.The effect of plant gum on improvement of soil quality was studied in-vivo for a period of 30 days. Poor-quality soil was collected from a construction site in Tambaram, Chennai, Tamil Nadu. A 10% plant gum solution was mixed thoroughly with a pot containing poor-quality soil for uniform dispersion. The mixture was left undisturbed for 24 h in a closed container, after which the seeds were sown in the soil. Seed germination and growth were observed on every 10th consecutive day. Poor-quality soil without plant gum was used as negative control, and garden soil enriched with cow dung manure was used as positive control.The root and shoot growth along with biomass were measured on every 10th day for a period of 30 days. The total weight of the plant was weighed to calculate the biomass. The observations for the study were performed in triplicates.To test the effect of gum polysaccharide on soil, the following parameters were observed: soil porosity , water hMoringa oleifera and Azadirachta indica were also investigated for their pesticidal activity. The study was conducted for 48 h under room temperature. Mealybugs collected from Hibiscus sp. infested plants were utilized for this study. The mealybugs were exposed to different concentrations of both plant gum polysaccharides—MO and AI . Four clean, air-dried petri dishes were used for each plant gum polysaccharide, which was applied onto the surfaces of the dishes. Ten mealy bugs per plate were released onto the surface of the plant gum polysaccharide-treated petri dishes, and host leaves were also added as feed for the organisms. The open surface of the petri dish was covered with moist filter paper (Whatman filter paper) and holes were punched into the papers for aeration [The plant gum polysaccharides obtained from aeration . The morAll experiments were carried out in triplicates and represented as mean ± standard deviation. Test results were compared with control after performing one-way ANOVA with Tukey HSD.Moringa oleifera and Azadirachta indica—were scraped off from the barks of the trees, dried, powdered and used for further processing. Characterization of the gum polysaccharides revealed the presence of various monosaccharides including glucose, galactose, xylose etc., which are believed to enhance the plant growth. Seeds exposed to gums were found to increase the root and shoot development and also improved the soil porosity and quality. Furthermore, histology studies revealed that the plant gum could cause severe impact in gut of mealybug, thus can be used as biopesticides.In this study, two plant gum polysaccharides—from


Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients.n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID.Adult CeD patients (p = 0.010) and had more joint symptoms , whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health  in PGWB, more overall gastrointestinal symptoms , and constipation  in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up.Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support. Celiac disease (CeD) is an immune-mediated condition driven by ingested gluten in genetically susceptible individuals. The disease may manifest at almost any age with heterogenous gastrointestinal and extraintestinal symptoms . AlthougNevertheless, this approach remains debatable, particularly in the absence of data on the long-term prognosis of undetected CeD in AID patients. Acceptance of the treatment—strict and life-long gluten-free diet (GFD)—in these often asymptomatic individuals may also be suboptimal . TherefoThere is a long tradition of active case finding and risk group screening of CeD in Finland –16, and via media advertisements and with the help of the Finnish Celiac Society , and other medical history. The clinical presentation of CeD was further divided into either “gastrointestinal”  or “extra-intestinal”   or anti-reticulin antibodies and tissue transglutaminase antibodies (TGA) were also recorded when available and classified as positive or negative.Self-reported adherence to the GFD was evaluated as a part of the interview. Adherence was further categorized to strict diet (no reported lapses), occasional lapses (lapses less than once a month) and no diet (lapses more frequent than once a month) . The useAll participants underwent measurement of CeD serology at the time of the interviews. Serum IgA class EmA were measured by indirect immunofluorescence with human umbilical cord as a substrate . Titers The validated Gastrointestinal Symptom Rating Scale (GSRS) was used to evaluate current gastrointestinal symptoms. The survey consists of 15 questions further divided into five subgroups representing indigestion, diarrhea, constipation, abdominal pain, and reflux. The questions are rated on a Likert scale from 1 to 7 and the final points are given within the same range as an average of the scores on each subgroup. Values for each sub-dimension score are calculated as a mean of the relevant items. The total GSRS score is calculated as a mean value of all 15 items and thus also has a range between 1 and 7. Higher scores indicate more severe gastrointestinal symptoms , 28.Health-related wellbeing was estimated using the Psychological General Well-Being (PGWB) questionnaire, which has 22 questions rated on a Likert scale from 1 to 6, higher scores denoting better wellbeing. The questions are further classified into six groups representing anxiety, depression, wellbeing, self-control, general health, and vitality. The results are given as a sum of each individual question and may range as follows: anxiety 5–30 points, depressed mood 3–18 points, positive wellbeing 4–24 points, self-control 3–18 points, general health 3–18 points, and vitality 4–24 points , 30.U-test for continuous variables. P-value < 0.05 was considered significant. Binary logistic regression was used to ascertain if CeD diagnosis in childhood was significantly associated with the frequency of concomitant AIDs in the evaluation while on GFD. The possible effect of current age on self-perceived PGWB general health  years and 74.9% were females. Concomitant AID was present in 185 (23.0%) subjects and 621 (77.0%) had only CeD. There were 21 different AIDs in total, the most common of these being thyroid disease, type 1 diabetes (T1D), rheumatoid arthritis, Sjögren's syndrome and psoriasis . Median p = 0.040). The CeD + AID and CeD only groups were comparable in sex, presence of CeD in first-degree relatives, positivity for CeD autoantibodies, degree of histological damage at diagnosis, and presence of symptoms in childhood (p < 0.001).CeD + AID patients had received CeD diagnosis at an older age and less often in childhood than those with CeD only. However, the statistical significance of the latter disappeared after adjusting for current age , and thehildhood . MoreoveAfter a follow-up of median 9.7 (quartiles 5.7 and 16.1) years, CeD + AID and CeD only patients did not differ in dietary compliance, use of gluten-free oat products, current or previous smoking status, frequency of CeD seropositivity and presence of regular follow-up for CeD . In bothWhen evaluated by GSRS, patients in the CeD + AID group suffered more overall gastrointestinal symptoms and constipation than those with CeD only on GFD . CurrentIn additional separate analysis of the two most prevalent coexisting AIDs, PGWB general health median score was 12  in subjects with thyroid disease and 13  in those with T1D, compared to 12  in all patients with AID. The corresponding figures for GSRS total score were 2.0  in thyroid disease, 2.0  in T1D and 2.1  in all AID patients.We found coexisting AID in 23% of the CeD patients, which is close to the figure of 21.8% observed in a previous Finnish study . For comCeD + AID patients were older at CeD diagnosis than those with CeD only, which may be attributed to several factors. Although the screening of CeD in AID patients should increase diagnostic yield, the long time needed for many AIDs to develop during the life course  may actuIn addition to the similar proportion of screen-detected patients, CeD + AID and CeD only groups were comparable at diagnosis as regards main clinical presentation and frequency of distinct symptoms except arthralgia, as well as seropositivity for CeD and severity of histological damage. According to these results, a co-existing AID does not seem to be directly associated with the presentation of untreated CeD, but instead more indirectly, depending on whether the patients are found at early disease stage in AID-based risk group screening , 47. Howvia the CeD society are likely more aware of the importance of a strict GFD. In fact, we recently also observed lower adherence in a special group of adult T1D patients diagnosed with CeD in childhood (Contrary to the recommendations but in line with our previous experience –52, mosthildhood . Taken tDespite the equal adherence, CeD + AID patients reported more gastrointestinal symptoms and poorer general health than those with CeD only. It remains unclear if the symptoms were due to the active CeD or AID or to both, but it is important to realize that delayed diagnosis of CeD may predispose to suboptimal clinical response . EarlierThe main strengths of our study were the large and well-defined cohort of CeD and AID patients and the use of validated and widely used follow-up questionnaires to elicit gastrointestinal symptoms and physiological wellbeing. Retrospective collection of medical data at diagnosis and lack of knowledge of the exact timing of the AID diagnoses were limitations. Furthermore, the CeD patients were not screened systematically for AIDs, e.g., with specific laboratory tests, and underdiagnosis of the often clinically heterogenous AIDs may have affected to the results. Additionally, a small proportion of the study surveys were incompletely filled, and dietary adherence was not evaluated by validated questionnaires. The follow-up time on GFD was also relatively short in some of the patients and we were not able to assess the effect of the healthcare site of follow-up on the long-term outcomes. Finally, there is a risk for selection bias in the study recruitment, as for instance symptomatic patients and with more severe AID might have been more eager to participate.To conclude, co-existing AIDs were common in patients with CeD but were not significantly associated with either the disease presentation at diagnosis or most of the long-term treatment and health outcomes. Nevertheless, the increased prevalence of persistent gastrointestinal symptoms and poorer self-perceived health on GFD indicates a need for more personalized follow-up strategies.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of Pirkanmaa Hospital District, Tampere University Hospital, Tampere, Finland. The patients/participants provided their written informed consent to participate in this study.RT, KKu, AE, LK, and HH designed the study, contributed to data analysis and interpretation, and drafting of the manuscript. Additionally NV, SK, and KKa critically reviewed the results and made a substantial additional contribution to the manuscript. All authors reviewed and approved the final version.The work was funded by the Academy of Finland, the Sigrid Juselius Foundation, the Foundation for Pediatric Research, the Päivikki and Sakari Sohlberg Foundation, the University Consortium of Seinäjoki, and the Competitive State Research Financing of the Expert Area of Tampere University Hospital. The funders had no role in the design or conduct of the study.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Antimicrobial resistance (AMR) is an increasing global threat that affects human, animal and, often less acknowledged, environmental health. This complex issue requires a multisectoral One Health approach to address the interconnectedness of humans, animals and the natural environment. The prevalence of AMR in these reservoirs varies widely among countries and thus often requires a country-specific approach. In New Zealand (NZ), AMR and antimicrobial usage in humans are relatively well-monitored and -understood, with high human use of antimicrobials and the frequency of resistant pathogens increasing in hospitals and the community. In contrast, on average, NZ is a low user of antimicrobials in animal husbandry systems with low rates of AMR in food-producing animals. AMR in New Zealand’s environment is little understood, and the role of the natural environment in AMR transmission is unclear. Here, we aimed to provide a summary of the current knowledge on AMR in NZ, addressing all three components of the One Health triad with a particular focus on environmental AMR. We aimed to identify knowledge gaps to help develop research strategies, especially towards mitigating AMR in the environment, the often-neglected part of the One Health triad. Antimicrobial resistance (AMR) is a growing, serious global threat to human, animal and environmental health associated with antimicrobial use in humans and animals and waste discharges, including pharmaceutical wastewater ,2,3. AMRThere is international recognition that to comprehensively address the risk from AMR, a “One Health” approach across human health, animal health and the natural environment is necessary ,9. In 20Human, animal and environmental reservoirs contribute to the epidemiology of AMR, and transmission pathways are plentiful, both within and across the human, animal and environmental spaces  15]. AM. AM15]. The global AMR crisis has led to a considerable increase in the number of studies investigating AMR in all three One Health-related areas; however, efforts have focused on human health and animal health and largely neglected environmental health ,24,25,26In NZ, human antimicrobial consumption is relatively high compared to similar countries, possibly due, in part, to antimicrobials being commonly prescribed for seasonal viral respiratory conditions in which antimicrobial treatments have no benefit ,28. FromWhilst there appears to be an effort to reduce human antimicrobial use in NZ over the past 5–10 years, there is still a need for further reduction. The recent research by Duffy et al.  suggestsNZ is one of the countries with the lowest use of antimicrobials to treat animals in the Organisation for Economic Co-operation and Development (OECD) ,35. In 2However, some sectors use intensive farming systems or are moving towards intensification, which may be contributing to an increase in antimicrobial use. Between 2004 and 2015, the total sales of antimicrobials for agricultural use in NZ increased by about 2.5% per year, and by another 3% from 2016 to 2017 ,41. The While sales data can be used to estimate antimicrobial use, they may be misleading as farmers can receive bulk prescriptions, and some veterinary antimicrobials are not species-specific. In 2015, the NZ Veterinary Association (NZVA) launched the profession’s aspirational goal that “by 2030 NZ Inc. will not need antimicrobials for the maintenance of animal health and wellness” . The NZVAntimicrobial use for companion and nonproduction animals was at 3.0% of the total NZ antimicrobial sales in 2019 . AntimicIn contrast to the human consumption of antimicrobials, veterinary use has been low, and concerted efforts have been made to control the use of antimicrobials in NZ compared to other OECD countries. It will be important to maintain this controlled approach in agriculture and aquaculture in the future.Antimicrobials are used in community and hospital settings, veterinary clinics and on farms and for agriculture purposes, and thus these compounds are continuously released into the environment. Pathways for antimicrobial residues into the environment include discharges from WWTPs, including hospital sewage, antimicrobial manufacturing plants and agricultural wastes such as manure.Antimicrobials are only partly metabolised by humans and animals, and thus a certain proportion is excreted as the active parent chemical in faeces and urine, contaminating wastewater and manure . Some anAntimicrobials may be discharged in the environment via medicine manufacturing sites. In NZ, there are five medicine manufacturing sites that are licensed for production of antimicrobials and preparations of antimicrobials . If and Antimicrobials in the natural environment are of concern as they not only deteriorate environmental or water quality, but also impact the natural communities present. Their presence and persistence can affect all trophic levels, from soil microbes to plants, and thus food production. Even low, subinhibitory concentrations of antimicrobials have been shown to affect several physiological reactions in microorganisms: changes in transcription levels ; initiatThere are concerns that antimicrobials in the environment exert selection pressure and add to the evolution and dissemination of AMR ,79. Howe−1), roxithromycin , sulfamethazine  and trimethoprim . According to Bengtsson-Palme and Larsson [There are few published studies investigating the presence and concentration of antimicrobials in NZ environmental or wastewater samples. To the best of our knowledge, only one preliminary study investigating pharmaceuticals, including ten antimicrobials, in the NZ environment (marine sediments at 13 locations around Auckland) has been conducted . Four an Larsson , the mea Larsson .To understand the long-term impacts on the environment, especially those related to effluent and wastewater disposal, more data are required. Consideration needs to be taken of both the immediate and cumulative effects across all trophic levels and the potential impacts on human health through the food chain and other transmission pathways. https://surv.esr.cri.nz/antimicrobial/antimicrobial_resistance.php (accessed on 20 April 2022). Antibiograms from most NZ diagnostic laboratories, who almost all use EUCAST interpretation standards, are available online: https://www.nzmn.org.nz/antibiograms/ (accessed on 20 April 2022).Resistance to many common antimicrobials is endemic in NZ, in both community and healthcare settings . While NHafnia, Morganella, Proteus, Providencia, Serratia and Yersinia) are now included in other families in the order Enterobacterales; we, therefore, now use the order name Enterobacterales to cover the genera previously included in the family Enterobacteriaceae) with production of carbapenemases conferring resistance to carbapenems  or production of extended-spectrum beta-lactamases (ESBLs) leading to resistance against third-generation cephalosporins  is concerning both in NZ and worldwide [There are several key groups of AMR bacteria of significance to human health in NZ. The increased appearance of Enterobacterales ).Carbapenemase-producing organisms isolated from humans are continually monitored in NZ with hospital and community laboratories requested to refer all isolates to the national Antibiotic Reference Laboratory at ESR for confirmation and further characterisation. The majority of reported infections with carbapenemase-producing Enterobacterales (CPE) in NZ are associated with a history of international travel. However, there is increasing transmission reported within NZ and CPE in patients with no overseas travel history. In 2019, travel history was reported for 87 of the 104 CPE patients, with 79% reporting overseas travel as the likely place of infection. In 2020, travel history was recorded for 66 of the 80 CPE patients, with 80% reporting overseas travel as the likely place of infection. Over the last 10 years, the number of patients diagnosed with CPE has been increasing steadily  , with tyhttps://surv.esr.cri.nz/antimicrobial/esbl.php/ (accessed on 20 April 2022)).Numbers of ESBL-producing isolates from clinical infections have reached a level where continuous surveillance is no longer undertaken at the national level. Since surveillance of ESBL-producing isolates started in NZ in 1996, the encountered types of ESBLs have shifted from TEM- or SHV-type ESBLs to CTX-M-type ESBLs in the 2000s and 2010s [Pseudomonas aeruginosa and Acinetobacter baumannii are also included in the WHO’s priority pathogens list with priority 1 “Critical” [P. aeruginosa and, since late 2021, all carbapenem-resistant A. baumannii to ESR for confirmation and further characterisation. Carbapenemase-producing P. aeruginosa were first found in NZ in 2009. The numbers of carbapenemase-producing P. aeruginosa remain much lower than the numbers of CPE, with under 40 isolates obtained between 2009 and 2020 inclusive (unpublished data). In contrast to other countries, the threat of a carbapenem-resistant P. aeruginosa health care-associated infection is currently very low in NZ [Carbapenem-resistant ritical” . In NZ, ow in NZ ,96. Staphylococcus aureus (MRSA) is included in the WHO’s priority pathogens list with priority 2 “High” [S. aureus infections in NZ [S. aureus isolates (from 17% in 1999 to 29% in 2013) [S. aureus [Methicillin-resistant 2 “High” . The nat2 “High” . In 2017ns in NZ . The ratin 2013) . Similar. aureus ,98.Enterococcus faecium and E. faecalis—are associated with serious multidrug-resistant infections, and E. faecium is also included in the WHO’s priority pathogens list with priority 2 “High” [vanA and vanB [vanA E. faecium has been increasing since 2015, which is concerning because vanA VRE are resistant to both vancomycin and teicoplanin while vanB VRE are generally susceptible to teicoplanin. While the primary transmission of VRE is thought to occur in hospitals [Vancomycin-resistant enterococci (VRE)—primarily 2 “High” . In NZ, 2 “High” . The mosand vanB . In NZ, ospitals —through ospitals . Careful consideration needs to be taken when prescribing antimicrobials as there is strong evidence that overprescribing and reliance on one antimicrobial drives resistance over time. Antimicrobial resistance in the clinical setting is well-monitored in NZ; however, there are still knowledge gaps regarding the prevalence of resistance in the community as well as transmission routes, particularly environmental and zoonotic transmission pathways.Campylobacter, E. coli, Enterococcus, Salmonella, Staphylococcus, Streptococcus and coagulase-negative staphylococci (CNS) isolates in food-producing and farm animals  and in milk, as well as among E. coli, other Enterobacterales, Staphylococcus spp. and CNS in companion animals  were resistant to streptomycin, sulfamethoxazole or tetracycline. None of the E. coli isolates was resistant to the tested third-generation cephalosporins (cefotaxime and ceftiofur), the fluoroquinolone ciprofloxacin or gentamicin and none of the isolates produced ESBLs. Some Enterococcus faecalis isolates were resistant to streptomycin (36%) and tetracycline (55%). Similar findings have been reported for cattle, with 53% of E. coli resistant to streptomycin and 47% resistant to tetracycline [Enterococcus spp. were resistant to streptomycin and tetracycline, respectively. Rushton-Green et al. [E. faecium lineages did not show a correlation between human and animal isolates, whereas one E. faecalis lineage (ST108) was highly prevalent in both human and animal isolates for several years after avoparcin use was discontinued and is indicated to have persisted and resurfaced again as late as in 2017 [A 2009/2010 NZ survey of AMR bacteria present in food and food animals  reportedacycline . Likewisn et al.  investig in 2017 . E. coli [A recent review on AMR bacteria in dairy cows concluded that there is no evidence that the use of antimicrobials in NZ has resulted in the emergence of multidrug-resistant pathogens . HoweverE. coli ,109. AmpE. coli . WorldwiE. coli ,124,125.Campylobacter spp. isolates from an NZ beef survey [Campylobacter spp. found that all the isolates were susceptible to the antimicrobials tested  with the exception of five isolates derived from pig offal which were resistant to erythromycin [C. jejuni lineage (ST6964) was identified in NZ poultry that was resistant to both fluoroquinolones and tetracycline [Testing of f survey  revealedhromycin . Howeveracycline . This liacycline . Streptococcus uberis resistant to beta-lactams [S. aureus, S. uberis and CNS isolates from milk but a high prevalence of resistance against oxacillin in S. aureus isolates (35%). Internationally, there is a high incidence of MRSA in livestock, particularly in pigs and poultry. Transmission events have been inferred between livestock and humans, predominantly associated with pig farms ,128. In -lactams . McDouga-lactams  found a E. coli [Enterobacteriaceae [E. coli, Staphylococcus pseudintermedius and CNS isolates while Nisa et al. [Staphylococcus pseudintermedius isolates. The proximity of companion animals to humans is both a concern and a possible explanation for a higher prevalence of AMR bacteria in pets compared to livestock.NZ studies suggest the prevalence of resistant bacteria in companion animals is higher compared with livestock. In one study, approximately 4% and 7% of the cats and dogs, respectively, carried ESBL- or AmpC-producing E. coli , while ieriaceae . In NZ deriaceae  found moa et al.  found meThe low usage of antimicrobials in veterinary and agricultural practice in NZ has resulted in low rates of antimicrobial resistance. The NZVA’s aspirational goal to reduce unnecessary antimicrobial use positions NZ well to keep resistance rates low in animal husbandry and enables further reductions. A potential zoonotic transmission from animals (including pets) to humans needs further investigation.Studies suggest the main source for environmental dissemination of antimicrobials, AMR bacteria and genes is surface water predominantly impacted by human and/or animal waste and, to a lesser extent, waste application to land . Whilst Human sewage and effluents from WWTPs have been proposed among the main sources of environmental contamination with antimicrobial residues, ARB and AMR genes (ARG), contributing to the spread of AMR ,59,133. Culture-dependent and culture-independent detection methods have been used to detect ARB and ARGs conferring resistance to all classes of antimicrobials at WWTPs worldwide and in their effluents, showing that treatment efficacy is quite variable and mostly insufficient ,138,139.Effluents from both households and hospitals contribute to the quantity and diversity of ARB and ARGs in sewage systems, but it is likely that hospital effluents only contribute a minor proportion as the total volume of residential and industrial wastewater is significantly greater ,141,142.In NZ, so far, only a few small studies have investigated the presence of ARB and ARGs in WWTP effluents or environmental waters . StudiesWhichever treatment is used, the process is not targeted at emerging compounds , bacteria or their genes but aims to remove organic components, nutrients  and suspended solids. Differences in treatment plant design and operation influence the fate of ARB and ARGs in wastewater; conventional activated sludge treatment combined with advanced treatment methods—such as UV or ozonation—show improved removal of ARB and ARGs compared to activated sludge alone ,140,148.In NZ, after treatment, wastewater is discharged either to waterways (rivers or the ocean) or to land . A surveIn addition to municipal wastewater systems, there are about 270,000 domestic on-site wastewater management systems (OWMSs) in NZ, serving approximately 20% of the population. OWMSs discharge wastewater into the land through disposal fields, potentially transporting antimicrobials, ARB and ARGs into the environment . AMR determinants may also settle out into the OWMS sludge, which is pumped out intermittently and taken to WWTPs. The potential risk to OWMSs from AMR is twofold. The first is from antimicrobials themselves which can enter the septic tank system unchanged or in the form of active metabolites and may harm the beneficial bacteria present within the system. The second risk is co-selection for AMR due to the ongoing presence of antimicrobials leading to ARB discharge into the environment.OWMSs mirror conventional wastewater treatment systems in removing organic compounds, nutrients  and suspended solids; however, their removal capacity for AMR is limited. There is also potentially a higher risk from septic tank systems as more concentrated inputs could occur from households using prescribed antimicrobials. Within OWMSs and the surrounding disposal fields, the function of anaerobic bacteria can be reduced, leading to increased sludge accumulation in the OWMSs and higher biological oxygen demand in the environment. The aerobic bacterial population pre-treatment and the soil environment can also be negatively impacted. With OWMSs, there is an additional risk to groundwater, which in rural communities is often used for drinking, in many cases with little to no pre-treatment. This poses a risk to human health, and the use of antimicrobials could increase the risk by reducing the efficacy of OWMSs. Salmonella spp. and enterotoxigenic E. coli can persist in environmental water for long times [Wastewater contributes to the transmission of AMR by serving as a major environmental reservoir for AMR and by providing an ideal environment for AMR microorganisms and genes . High leng times ,153. DueApplication of human and/or animal wastes to land—solids, manure, greywater or wastewater—is common practice worldwide. In NZ, application of animal wastes is widely accepted and practiced while application of treated human waste is often met with concerns. Treated wastewater in NZ is mostly discharged to waterways, but 33% is applied to land, with land disposal systems varying widely . When waAntimicrobial use in farm environments and consequently the emergence and distribution of ARB and ARGs in farm wastes is of concern for both human and animal health. Worldwide, pathogens of human concern resistant to antimicrobials have been detected in animal manure, dairy farm environments and food products ,157,158.Antimicrobials or their residues can persist in the soil environment and potentially accumulate in the environment by adsorption to soil particles ,160 and There is a lack of research into the extent of antimicrobials (or their residues), ARB and ARGs entering the NZ environment from animal wastes. A report compiled by the NZ Ministries of Health and Primary Industries pointed to a lack of consistent surveillance and research on the risk to the environment from animals .Conventional activated sludge processing at WWTPs is inefficient at removing antimicrobials which end up in sludges and biosolids that may be applied to land. Some antimicrobials, such as sulphonamides, fluoroquinolones, erythromycin and tetracycline are preferentially removed into the sludge, either by physical adsorption or enhanced adsorption through addition of flocculants ,169,170.As mentioned in the previous section, there is a paucity of knowledge on the risk of OWMS wastewater application to land from antimicrobials or ARGs. This is also the case for biosolids application to land.With the growing pressure on water supplies globally, there has been an increase in reclamation of water, including in waste streams. The use of greywater (domestic wastewater excluding wastewater from toilets) for irrigation of crops, golf courses and landscapes is becoming more common, but there is increasing concern that this could provide another AMR pathway to land ,172,173.E. coli were isolated from all water sources with concentrations of multidrug-resistant E. coli isolates increasing in the following order: surface water (2.2 × 102 cfuL−1), WWTP effluents (4.0 × 104 cfuL−1), WWTP influents (1.8 × 107 cfuL−1) and health-care wastewater (4.1 × 107 cfuL−1). A Canadian study [E. coli were isolated downstream of the effluent outflow, but not downstream of the land used for dairy farming. AMR bacteria are present in surface water all over the world, and wastewater significantly contributes to this. A Dutch study investigated 30 water bodies and wastewater samples from five health care institutions, seven municipal WWTPs, and one airport WWTP . Multidran study  found than study  also indE. coli from these urban waterways were genetically similar to human clinical (derived from urinary tract infections) and dog faecal isolates [E. coli between 2004 and 2012 [vanB, which confers resistance to vancomycin. In a spatiotemporal follow-up study of 20 sites, three of the ten AMR genes were detected in 1.3% of the biofilm samples, with more genes detected close to intensive farming areas, suggesting a moderate correlation [E. coli and the presence of six different genes associated with virulence and one group of AMR genes. In the September (spring) sampling, water and sediments of two rivers were positive for the blaCTX-M genes which confer resistance against beta-lactams, including penicillins and third-generation cephalosporins [E. coli in surface water across NZ and in mussels deployed in an urban harbour and confirmed the presence of microorganisms resistant to some of the tested clinically relevant antimicrobials, including ESBL-producing E. coli in the water samples [In NZ, a limited number of studies have investigated AMR in surface water (summarised in isolates ,178. In and 2012 . Anotherand 2012 . Three Arelation . Fish & osporins . Further samples ,184,185.Whilst studies are underway and our knowledge is improving on the fate and impact of AMR in the natural environment, there are still more data needed to provide evidence of the impact on human health.Antimicrobial resistance and antimicrobial usage in humans are relatively well-monitored and -understood in NZ, with ready access to antimicrobial dispensing data and ongoing monitoring of the key groups of clinical AMR pathogens. Human use of antimicrobials is high in NZ, and pathogens with resistance to antimicrobials are found in hospitals and the community and are increasing. However, compared to other countries, the public health burden of AMR in NZ is fairly low . Some pa


Internet addiction (IA) symptoms are common among adolescents and negatively impact their academic performance and development. These symptoms are also associated with lower quality of life (QOL) and increased suicidality. This study aimed to examine the prevalence and the sociodemographic and clinical correlates of IA symptoms in adolescents with major depressive disorder (MDD) and their association with QOL.This cross-sectional study was conducted in three general and four psychiatric hospitals in Anhui Province, China, from January to July 2021. Sociodemographic and clinical data were collected. The Internet Addiction Test (IAT), Center for Epidemiologic Studies of Depression Symptom Scale (CES-D), and World Health Organization Quality of Life Brief version (WHOQOL-BREF) were utilized to examine IA, depressive symptoms, and QOL, respectively.In a multicenter sample of 278 adolescents with MDD, the prevalence of IA symptoms in adolescents with MDD was 46.8% (95% CI: 40.9–52.7%). Logistic regression analysis showed that patients with more severe depressive symptoms , those living in a rural area , and those with poor academic performance  were more likely to have IA symptoms. After controlling for confounding factors, patients with IA symptoms had significantly poorer QOL in the physical, psychological, and environmental domains than those without IA symptoms.IA symptoms are common in adolescents with MDD and appear to be associated with clinical symptoms. We could not infer a causal relationship between IA and depression because this was a cross-sectional study. Considering the positive association between IA symptoms and lower QOL, screening for IA symptoms should be conducted, and effective measures should be implemented for adolescents with MDD. Internet addiction (IA) generally refers to the behaviors of uncontrolled and persistent use of the internet, which can lead to individuals’ distress and social avoidance . IA sympPrevious studies suggested a possible link between depression and addictive behaviors. People with higher levels of depression are more likely to have problem gambling  and compInternet addiction symptoms negatively impact the academic performance and development of adolescents and may even lead to violence and crime , 19. TheA study in Turkey found that the prevalence of IA symptoms in adolescents with MDD during the first assessment in the outpatient clinic was 30%, and the symptoms were associated with hopelessness . AnotherThis cross-sectional study was conducted in three general hospitals  and four psychiatric hospitals  in Anhui Province, China, from January to July 2021. Participants were consecutively recruited from psychiatric outpatients and inpatients in these hospitals if they met the following criteria: (1) aged between 12 and 18 years; (2) had a diagnosis of MDD assessed by two psychiatrists using a structured clinical interview for DSM-V. Patients who met the DSM-V criteria for a diagnosis of other psychiatric or neurological disorders and/or intellectual disability were excluded.All eligible participants and their guardians provided written consent forms after being informed of the method and purpose of the study. The Medical Ethics Committee of Chaohu Hospital of Anhui Medical University approved the study protocol (202009-kyxm-04) before the study.Under the guidance of trained investigators, all adolescents participated in an interview that involved their guardians’ participation. A predesigned questionnaire was used to collect sociodemographic characteristics of the participants, including age (years), gender , living area  , geograpt-tests for continuous variables with a normal distribution, Mann–Whitney U tests for continuous variables with a non-normal distribution, and chi-square tests for categorical variables. Analysis of covariance (ANCOVA) was used to compare QOL scores between groups with and without IA symptoms after controlling for the demographic and clinical variables that significantly differed between the two groups. Binary logistic regression analysis with the “Enter” method was used to examine the independent correlates of IA symptoms by treating the variables with significant group differences as independent variables and the presence of IA symptoms as the dependent variable. We calculated the sample size using PASS version 11.0  with the relevant parameters: the estimated prevalence of IA symptoms (30%), confidence level/1-α (0.95), and acceptable error (0.06). A minimum sample size of 239 was needed. Statistical significance was evaluated by a threshold of P < 0.05 (two-tailed).SPSS software version 23.0  was used for statistical analyses. Demographic and clinical data are presented as means, standard deviations (SDs), and frequency distributions (%). We compared sociodemographic and clinical variables between participants with and without IA symptoms using independent-samples The sociodemographic and clinical data of adolescents with MDD are presented in P = 0.210). The adolescents with IA symptoms had more severe depressive symptoms, worse academic performance, and a higher proportion of living in a rural area than those without IA symptoms . In addition, the adolescents with IA symptoms had lower scores in all domains of QOL than those without IA symptoms. ANCOVA showed that differences in physical , psychological , and environmental QOL scores  between the two groups remained significant after controlling for CES-D total score, living area, and academic performance. However, the group difference in the social domain was not statistically reliable .The prevalence of IA symptoms was 46.8% (95% CI: 40.9–52.7%) in the total sample. There was no significant difference in the prevalence between males and females , living in a rural area (relative to an urban area) , and poor academic performance (compared to good academic performance)  were independently associated with IA symptoms in the adolescents with MDD.The results of multiple logistic regression analysis with the independent correlates associated with IA symptoms are presented in In this study, we examined the prevalence and clinical correlates of IA symptoms and explored their associations with QOL in Chinese adolescents with MDD. We found that the prevalence of IA symptoms in the patient sample was 46.8% 95% CI: 40.9–52.7%), which is much higher than that in Chinese adolescents in extant studies. For example, a survey of 10,158 adolescents from Anhui Province showed that the prevalence of IA symptoms was 10.4% . A more .9–52.7%,Specifically, the prevalence rate of IA symptoms in our study was approximately 1.5 times the rates reported in adolescents with MDD during an initial assessment in a Turkish outpatient clinic (30%)  and in cIn addition, we found that IA symptoms were associated with poor academic performance in adolescents with MDD, which replicated previous findings in general adolescents , 37 and Moreover, we found that adolescents living in rural areas were more likely to report IA symptoms than those living in urban areas. This difference might be closely linked to their differing living conditions and habits. For adolescents living in rural areas, the dominant way to spend time is through online socializing, gaming, and shopping due to the lack of diverse recreational activities. Previous studies have shown that without parental supervision, adolescents left alone in rural areas have unrestricted access to the internet, which could further enhance IA symptoms , 51. In In this study, adolescents with IA symptoms had lower levels of QOL in all domains than those without IA symptoms, which is consistent with the findings in a large-sample study with 12,285 adolescents in Spain  and a muSeveral limitations in this study should be noted. First, because the current design was cross-sectional, the direction of causality between IA symptoms and clinical factors or QOL in adolescents with MDD might not be adequately established. Second, although the prevalence of IA symptoms among adolescents has been widely reported, there was no age- and gender-matched healthy control group in this study. As such, we were unable to make direct comparisons of IA symptom prevalence and QOL between MDD adolescents and those in school or community samples. Third, depressive symptoms were assessed by the CES-D, a self-report tool, rather than an objective measure for depressive symptoms, such as the Hamilton Depression Rating Scale (HAMD). Finally, relevant factors associated with IA symptoms, such as parental internet use, economic conditions, and social support, were not examined. These limitations could be addressed by future studies.In summary, IA symptoms are common in adolescents with MDD, particularly in those with more severe depressive symptoms, living in a rural area, and with poor academic performance. Given the negative impact of IA symptoms on QOL in adolescents with MDD, effective and proactive interventions, including regular screening, improving depressive symptoms, enriching recreational activities, and strengthening parental supervision, should be undertaken in this population.The data used for this study are available from the corresponding author on reasonable request.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Chaohu Hospital of Anhui Medical University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.HL: study design. SW, LX, JW, XY, YS, XW, XL, and YH: collection, analyses, and interpretation of data. SW, LX, and JW: drafting of the manuscript. FG and HL: critical revision of the manuscript. All authors approval of the final version for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.