Osteoporosis causes bone fragility, increasing the risk of fractures. Evidence suggests a strong correlation between obesity and fracture risk. Physical training is known to enhance bone resistance and protect from fracture; however, its osteogenic effect in the presence of obesity remains unknown.We sought to evaluate the influence of exercise training on bone health indices in individuals with obesity.This systematic literature search was conducted using common electronic databases from inception - December 2019. The following key terms (and synonyms searched for by the MeSH database) were included and combined using the operators “AND,” “OR,” “NOT”: [(“body mass index” OR obesity OR obese OR overweight OR fat mass) AND  AND ].p = 0.046). Subgroup analyses indicated a significant small increase in the WB BMD  in the endurance training group, a non-significant trivial increase in the WB BMD  in the resistance group, and a non-significant trivial increase in the WB BMD  in the combined training group. In addition, a significant small decrease was found in the weight of trained subjects .After screening, 10 studies  were included in the final analysis . Two studies investigated males, six females, and two, both sexes. The training duration was at least eight weeks with 2–3 sessions/week. Physical training displayed a significant trivial impact on the whole body (WB) BMD (0.13 SMD; 95% CI , Physical training has little to no effect on the WB BMD in subjects with overweight/obesity. Currently, insufficient evidence to advocate for any specific type of exercise for enhancing bone health exists for overweight/obese individuals. Investigations examining the impact of varying types of physical exercise on WB BMD of obese individuals are needed. The worldwide incidence of obesity continues to grow and is largely attributable to an imbalance between energy intake and energy expenditure, which leads to an increase in body fat accumulation, which adversely affects health , included one or both sexes, and specifically evaluated whole-body BMD, before and after the intervention, in individuals with obesity.PICOS  criteria were used as the inclusion criteria for the current review see  Moher e. This sy(1) did not meet the minimum requirements of an experimental study design , (2) did not meet the minimum requirements regarding training design , (3) were not written in English or French, (4) involved individuals were not overweight/obese, (5) did not include the measurement of whole body bone mineral density (WB BMD) or (6) did not include sufficient information that allows the determination of effect size. Additionally, the following exclusion criteria were adopted to reduce confounding factors: duplicate publications or sub-studies of included studies, studies involving pathologies, and studies associating exercise with a nutritional intervention  or pharmacological drugs. Moreover, review articles were not included in the current systematic review.Studies were excluded if they This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Systematic Reviews of Interventions  without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus, and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for the gray literature analysis. The following key terms (and synonyms searched for by the MeSH database) were included and combined using the operators “AND,” “OR,” “NOT”: [(“body mass index” OR obesity OR obese OR overweight OR fat mass) AND  AND ]. Only eligible full texts in English or French were considered for analysis.Three investigators among the authors  independently performed searches in the electronic databases, and disagreements were solved by consensus.via e-mail to provide data not included in the published research. Two researchers (AB and KS) independently performed the data extraction, and disagreements were resolved by consensus.Inclusion or exclusion of articles was decided with the application of the PICOS criteria see  to the thttp://www.pedro.fhs.usyd.edu.au), which has been shown to have good reliability and validity  scale (2) and weight (kg)). Mean group differences in WB BMD and weight between pre-and post-intervention periods were divided by a pooled SD, based on the assumption of a large correlation (r = 0.7) for each group. The standardized mean differences (SMD) were calculated to determine Cohen's d for each study and Hedge's g was used to account for potential bias in small sample sizes.Effect sizes (ES) were computed to discern the standardized effect of acute and long-term training on the outcome variables  were calculated using random-effects models (DerSimonian and Laird approach), that account for true variation in effects between studies, as well as random error within a single study. Values for ES were defined as trivial (<0.2), small (0.2–0.6), moderate (0.6–1.2), large (1.2–2.0), and very large >2 . The I2 (0.0%) parameter indicated the homogeneity of the results, whilst the visual inspection of the funnel plot (nel plot  did not p = 0.048) was detected among these studies, and the I2 (0.0%) parameter indicated homogeneity of the results.The subgroup of endurance training, as shown in the forest plot , includep = 0.203) was detected among these studies. The I2 (0.0%) parameter indicated homogeneity of the results.The subgroup of resistance training  includedp = 0.86) was detected among these studies. The I2 (0.0%) parameter indicates the homogeneity of the results. Concerning the impact of the type of physical training on the WB BMD, the comparison between the subgroups (p = 0.46).The subgroup of combined training  includedubgroups  did not p = 0.011). The I2 (0.0%) parameter indicated homogeneity of the results.Five studies , involving 124 participants, investigated the impact of physical activity on weight . The resTo the best of our knowledge, this is the first meta-analysis to have investigated the influence of the type of physical activity intervention on bone mass in individuals with overweight/obesity. The results show that physical activity is likely to increase the WB BMD in individuals with obesity.The findings of the present study are supportive of two recent meta-analyses (Ashe et al., To further understand the influence of physical exercise on bone, it is important to better comprehend how varying weight statuses may be related to bone health. Accordingly, our results demonstrated a small, but significant, reduction in body weight. Indeed, this outcome extends previous meta-analytic results showing that physical activity promotes weight loss in adolescents with obesity (Stoner et al., Our analysis showed that endurance training slightly increases the bone density in individuals with obesity. The three studies included (El Hage et al., Our analysis demonstrated that resistance training has little to no effect on the WB BMD. The training programs ranged between 12 to 96 weeks and involved free weights, elastic bands, machines, and circuit training as the interventions for both genders. A previous meta-analysis (Kelley et al., In our analysis, seven papers had an average participant age of more than 55 years (Bocalini et al., The greatest increase in WB BMD was reported in the study of (Huang et al., This meta-analysis showed that the combined exercise training had little to no effect on the WB BMD. Two studies were included in the analysis; Choquette et al.  and BolaNotably, the subgroups comparison did not reveal any significant differences among the types of training. The highest effect was observed in the endurance training, in which the age of the samples was lower compared to the other subgroups.Although we have presented a novel addition to the literature, this meta-analysis has some limitations that must be mentioned. The number of studies that investigated the impact of endurance and combined training on bone health in subjects with overweight/obesity was relatively small. Furthermore, the training program's duration was highly variable, ranging from eight (Kim et al., Our systematic review and meta-analysis suggests that physical training have little to no effect on the WB BMD in subjects with overweight obesity. This conclusion, however, is based upon a limited number of available studies. Furthermore, there is also insufficient evidence at this time to advocate a specific type of exercise for enhancing bone health. Additional well-designed randomized controlled trials, investigating the impact of different types of physical exercise on bone health, in both sexes, and among individuals with overweight/obesity, especially during adolescence and adulthood, are needed before any firm recommendations can be made.The original contributions presented in the study are included in the article/supplementary files, further inquiries can be directed to the corresponding author/s.HZ, AJB, and RE contributed to the conception or designof the work. AJB, SK, AJ, and RE independently performed searches in the electronic databases, evaluated articles, and extracted data for the review. All authors confirm responsibility for the following: review conception and design, interpretation reviewed the results, and approved the final version of results, manuscript preparation, writing, editing, the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


The adoption of health information technology (HIT) is an important measure for improving healthcare quality and safety, which is affected by many hospital factors, but it has not yet been estimated in the Mongolian hospital sectors. This study examines how hospitals' organisational and geographical characteristics influence the adoption of HIT in Mongolian tertiary and secondary care hospitals.  А cross-sectional study involving the executive directors and medical equipment engineers was conducted in 39 hospitals. Data acquired from questionnaires are (1) hospitals' organisational and geographical characteristics, including bed-size capacity, ownership type, status, and location of the hospitals, and (2) the adoption rate of HIT, and its categories are based on the Health Information and Management Systems Society's classification (2002). The dependent variable was measured as numbers and the rate of HIT programs adopted clinical, administrative, and strategic information technologies (IT). A regression analysis was used to estimate the factors of impact on the adoption of clinical, administrative, and strategic IT. β = 0.256, P < 0.001; administrative IT: β = 0.3654, P < 0.001; strategic IT: β = 0.0006, P < 0.001), for-profit , teaching , and urban location .  We found a concerning relationship between the characteristics and adoption of HITs. On average, the number of HIT programs adopted was 18, covering nine clinical IT programs, six administrative IT programs, and three strategic IT programs. The adoption rate of overall HIT was 33.29% in the hospitals. In regression analysis, the organisational and geographical characteristics' impact and HIT adoption of hospitals was positively associated with large bed-size (clinical IT:  Our study found that the HIT adoption rate in Mongolia is poor, and its adoption is mainly positively associated with bed-size capacity, status, and location of the hospitals. Also, we found that the ownership type is partially affected HIT adoption. Health information technology (HIT) is an important tool for improving healthcare quality and patient safety . In HIT The system consists of two tiers: primary and referral level care. Primary level care is delivered by family health centre, soum (a country subdivision) health centre, and inter-soum hospitals. People who seek medical attention first go to primary level care, and in case the sickness could not be diagnosed or treated, they would go to referral level care which provides specialized care. Whereas, secondary and tertiary care facilities provide the referral level care in Mongolia. If secondary care hospital could not provide a healthcare, patients have to seek medical services from tertiary care hospital. Tertiary care hospitals provide high level of multispecialty care in the capital of Mongolia, Ulaanbaatar , 4. HospIn Mongolia, the health insurance law was approved in 2015, and it was principally focused on the gatekeeper role of primary care similar to the UK system. However, the law reformed again for the Taiwan model which was based on performance and patient choice of facilities in 2021 [Mongolian public hospitals are financed from the state budget, the health insurance fund, and client fees. Public hospitals mostly serve poor lower middle-income people, who make up about 60% of the total population, whereas higher income citizens tend to seek care from private hospitals or abroad. Thus, improving public hospital management is beneficial to the poorer and lower middle-income groups. The public healthcare sector accounts for 78% of total hospital beds and 80% of total hospital admissions and absorbs nearly 70% of the national health budged .HITs are reported to enhance patient safety by reducing complications and mortality rates, as well as by minimizing medical errors covering clinical, administrative, and strategic information technologies . HoweverThe aim of our research was to determine the relationships between a hospital's  characteristics and the adoption rate of HIT in Mongolian tertiary and secondary care hospitals.Avedas Donabedian's the “Structure-Process-Outcome” conceptual model on to the dominant theoretical model in health services research. This conceptual model analyses the quality of healthcare from three dimensions: structure, process, and outcome [We applied  outcome . Accordi outcome . Due to   H1 Larger hospitals will adopt HIT more extensively than smaller hospitals.  H2 Teaching hospitals will adopt HIT more extensively than nonteaching hospitals  H3 For-profit hospitals will adopt HIT more extensively than not-for-profit hospitals  H4 Urban hospitals will adopt HIT more extensively than rural hospitalsBased on the results of previous studies , 15, we А cross-sectional study was conducted in 39 hospitals by asking the executive directors and medical equipment engineers. The setting included 34 secondary care hospitals, which are district and provincial hospitals administered by an agency of district or provincial governments, and five tertiary care hospitals are owned by an agency of state that located in capital of Mongolia. Data acquired from questionnaires are (1) hospitals' organisational and geographical characteristics, including bed-size capacity, ownership type, status and location of the hospitals and (2) the adoption rate of HIT, and its categories are based on the Health Information and Management Systems Society's classification (2002). The dependent variable was measured as numbers and the rate of HIT programs that adopted clinical, administrative, and strategic information technologies (IT). A regression analysis was used to estimate the factors of impact on the adoption of clinical, administrative, and strategic IT.Characteristics consist of organisational  and geographical (location).According to the World Health Organization's classification, hospitals can be divided as three groups based on the hospital bed-size capacity that having up to 100 beds are considered as small, more than 100 to less than 300 beds are medium, and more than 300 beds are large hospitals, respectively .All hospitals were placed into 1 of 3 categories based on their response to the American Hospital Association survey: major teaching hospitals, minor teaching hospitals, and nonteaching hospitals . As there are no major teaching hospitals in Mongolia, the concept of teaching hospitals, includes hospitals affiliated to medical university .Two types of ownership are analyzed in this study: for-profit and not-for-profit  hospitalhospitals' location  [Geographical characteristic refers to each n/rural) .Clinical IT consists of systems designed to improve patient care, such as computerized physician order entry systems, electronic medical records, and pharmacy information systems Administrative IT includes applications intended to streamline and improve internal data processing activities, such as patient registration systems, billing systems, and payroll processing systems Strategic IT includes applications intended to improve critical decision-making activities, such as managed care software, nurse staffing systems, and executive information systems The HIT categories were formulated from a list compiled by the Health Information and Management Systems Society (2002) leadership survey and was further refined based on an extensive literature review and consultations with HIT experts . It inclOur dependent variable was measured as a raw count (frequency) and rate (%) of HIT applications checked by respondents and individual counts of applications as well as checked within each application cluster .The clinical IT programs scale ranged from 0  to 25 . Likewise, the administrative IT programs scale ranged from 0 to 18, and the strategic HIT scale programs ranged from 0 to 9. The overall IT adoption index, created by summing up the three component scales programs, ranged from 0 to 52 for each hospital.Statistical analysis was performed using SAS 9.1 software. The negative binomial regression was used to identify the organisational and geographical characteristics that impact the adoption of clinical, administrative, and strategic IT in Mongolian hospitals.Hospitals were divided, based on the number of hospital bed-size capacity, into the three groups: seventeen of the hospitals' bed-size capacity were small (43.5%) and 17 were medium (43.5%), whereas only five hospitals (12.8%) were categorized as large.Nearly two-thirds (64%) of the hospitals were located in rural areas, while 36% were located in urban areas. A majority of the hospitals were nonteaching (76.9%) and not-for-profit (87.2%). See On average, the number of HIT programs that are adopted by hospitals reached 18, of which nine were clinical IT programs, six were administrative IT programs, and three were strategic IT programs. The overall adoption rate ranged between 29.02 and 38.05% with a mean of 33.29%. It indicates that less than half of all Mongolian hospitals adopted the three clusters of technologies at the time of the survey, as shown in For-profit hospitals' adoption rates were 11.6 clinical programs, 6.7 administrative programs, and 4.14 strategic programs, compared to the not-for-profit adoption rates of 8.45 clinical programs, 5.85 administrative programs, and 2.10 strategic programs. Therefore, for-profit hospitals were higher adoption rates of HIT (43.2%) than not-for-profit hospitals (29.87%).Teaching hospital's adoption rates  were higher than nonteaching hospitals  than non-teaching hospitals (24.53%).Finally, urban hospitals had a higher technology adoption rate (30.42%) than rural hospitals (13.42%).Regression analysis for organisational and geographical characteristics showed impact on rate of HIT adoption. In the result, organisational and geographical characteristics were impacted on the adoption of clinical technologies.P < 0.001), location (P < 0.001), and teaching status (P < 0.05) of the hospitals, see We examined the relationship between each element of the healthcare IT cluster and the hospitals' organisational and geographical characteristics. The adoption of clinical technologies in Mongolian secondary and tertiary care hospitals were positively associated with bed-size (P < 0.001), urban location (P < 0.01), and teaching status (P < 0.01) of the hospitals. However, ownership type did not appear to affect the adoption of administrative technologies. And, the adoption of strategic IT was positively associated with bed-size (P < 0.001), urban location (P < 0.001), and ownership type (P < 0.01). Hospital location did not significantly impact the adoption of strategic IT.As can be seen from P < 0.05).The hypothesis H3 was partly rejected, whereas the hypotheses H1, H2, and H4 were accepted  than Mongolian hospitals' adoption rate. A study conducted in the United States of America reported a 50% failure rate for clinical technology implemented in healthcare organisations .From the organisational characteristic perspective, we found that the hospital bed-size capacity was the most important predictor of the adoption of all three HIT. Large bed-size hospitals consistently adopted the largest number of clinical, administrative, and strategic IT programs compared to small and medium bed-size hospitals. These results are similar to the previous findings that Neset et al. also found positive associations between hospital bed-size capacity and adoption of clinical and strategical IT, but not with administrative IT . This imWe also found that the ownership and status of hospital were influencing factors of the adoption of HIT. However, only the ownership of hospital had no effect on clinical IT. Lee et al. reported that the rate of clinical IT adoption differs in degree by hospital characteristics. Large bed-size, teaching, and for-profit hospitals were closely related to clinical IT adoption, while teaching, not-for-profit, and large bed-size hospital had higher clinical IT adoption rate . This imFrom the geographical characteristic perspective, our analysis suggested that urban location was the most important indicator of the adoption of all categories of HIT. This suggestion confirms some of the findings of other studies , but somAdditionally, Ingebrigtsen et al. conducted a systematic review to examine the evidence of associations between clinical leadership and successful information technology (IT) adoption in healthcare organisations. Their results show that clinical leaders who have technical informatics skills and prior experience with IT program management are likely to develop a vision that comprises a long-term commitment to the use of IT. This leads to proactive leadership behavior and partnerships with IT professionals that are associated with successful organisational and clinical outcomes . This stOur study found that the HIT adoption rate is poor compared with developed countries. And, the adoption of all three HIT is mainly positively associated with bed-size capacity, status, and location of the hospitals in Mongolia. Also, we found that the ownership type is partly affected administrative and strategic IT adoption. This study confirmed that organisational and geographical characteristics (structure) impact the adoption of HIT (process), which implies that modifying organsational construction and promoting geographical access (structure) may impact on the adoption of HIT (process). Our suggestion is to enhance hospitals with these structural attributes conducive to more HIT adoption especially for developing countries. The influence of structural attributes on the type of HIT adoption should be generalized with caution.This study has some limitations that are worth mentioning. The current study focused only on organisational and geographical characteristics' impact on the adoption rate of HIT without considering clinical leadership, due to the unavailability of the data and the limitations of paper length.In addition, due to limited information, we were not able account the medication error and patient healthcare outcome impact on adoption of HIT. We only performed the analysis of binary categories because of the limited sample size. In the future, we will address these characteristics' impact on the adoption rate of HIT and their impact on medical quality, as well as conducting a national-level study to fully explore the role of individual characteristics on hospitals' HIT adoption rate and medical quality.


P=0.001). ROC curve analyses showed the sensitivity and specificity at 33% and 98%, respectively. Among patients with PD, those with pareidolias demonstrated higher State-Trait Anxiety Inventory-state (P=0.044) and State-Trait Anxiety Inventory-trait (P=0.044) than those without pareidolias. Pareidolias can be found in patients with PD without visual hallucinations, and the pareidolia test may be a highly specific test for differentiating PD from MSA. Thus, anxiety may be associated with pareidolias in patients with PD.Pareidolia is a visual illusion of meaningful objects that arise from ambiguous forms embedded in visual scenes. Previous studies showed that pareidolias are frequently observed in patients with Parkinson's disease (PD) as well as dementia with Lewy bodies. However, whether pareidolias are useful for differentiating PD from other neurodegenerative parkinsonism disorders including multiple system atrophy (MSA) is unclear. The noise pareidolia test (NPT) was performed in 40 and 48 patients with PD and MSA, respectively. A receiver operating characteristic (ROC) curve analysis was used to evaluate sensitivity and specificity. Results of neuropsychological tests were also compared between patients with PD with and without pareidolias. Visual hallucinations were present in none of the subjects. Pareidolic response in the NPT was observed in 47.5% and 18.8% of patients with PD and MSA, respectively. The number of pareidolic responses in patients with PD was significantly larger compared with patients with MSA ( Visual symptoms are common in Parkinson's disease (PD), which include double vision, blurry vision, watery eyes, illusions, feelings of presence and passage, and visual hallucinations , 2. MorePareidolias are visual illusions of meaningful objects that arise from ambiguous forms embedded in visual scenes and have phenomenological similarities with visual hallucinations . The parThe present study aimed to evaluate the usefulness of pareidolias evoked by the pareidolia test for differentiating patients with PD from MSA. Additionally, the clinical background and results of neuropsychological tests between patients with PD with and without pareidolias were compared to explore the underlying neural mechanism of pareidolias in patients with PD.This retrospective study was approved by the institutional review board of Chiba University Hospital. Moreover, informed consent was waived.N-methyl-D-aspartate receptor antagonist. Based on these criteria, 40 and 48 patients with PD and MSA were included in the present study, respectively. MSA diagnosis was classified according to whether the clinical syndrome was dominated by parkinsonism (MSA-P) or cerebellar ataxia (MSA-C). Among the 48 patients with MSA, 19 and 29 were classified as having MSA-P and MSA-C, respectively. The diagnoses for all subjects remained stable during a median 10.5 months (range: 1–37 months) of clinical follow-up after the pareidolia test.Patients with PD and MSA who underwent the pareidolia test between May 2018 and October 2020 at the institution of the current study were identified from the database. The pareidolia test was ordered by the treating physician for patients with different disease stages for initial evaluation or for indicating device-aided therapy in about one-fifth of the patients with PD. On the contrary, almost all patients with MSA underwent the test, except for those who could not due to visual loss or other reasons. The inclusion criteria for PD and MSA were patients who qualified the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria  and the The medical records of both patients with PD and MSA were reviewed for age and disease duration at the pareidolia test, Frontal Assessment Battery (FAB), and Addenbrooke's Cognitive Examination (ACE-III) . For pat2) with a spatial frequency of 1/f3 were used in this test. The face is included in eight. They were instructed to state whether they observed a face or not on the presentation of each image. The participants were requested to point the face when a face was observed. For each NPT image, responses were classified as [To understand the mechanism of the pareidolias occurring in patients with PD and MSA, pareidolias were assessed using the noise pareidolia test (NPT) , which iχ2 test for sex; the Mann–Whitney U test for age at pareidolia test, disease duration, ACE-III , and FAB; and Student's t-test for ACE-III (fluency). To evaluate the differences in the pareidolia test (pareidolia and missed) between the patients with PD and those with MSA, one-way analysis of covariance was performed, with age and disease duration as covariates.All statistical analyses, except for receiver operating characteristic (ROC) curve analyses, were performed using SPSS software . ROC curve analyses were performed using JMP Pro 14.2.0 . Demographic data of patients with PD and MSA were compared using the χ2 test for sex and the number of patients taking a dopamine agonist. The Mann–Whitney U test was performed to analyze for age during the pareidolia test, disease duration, ACE-III , pareidolia test (pareidolia and missed), HAMD-17, RBDSQ-J, dopamine agonist dose, catechol-O-methyltransferase inhibitor (COMTI), monoamine oxidase type B inhibitor (MAOBI), trihexyphenidyl, zonisamide, istradefylline, and amantadine, and Hoehn and Yahr. Student's t-test was used for ACE-III (fluency), STAI (state anxiety and trait anxiety), freezing of gait, levodopa dose, and levodopa equivalent units . Finally, Welch's test was used for FAB, whereas Fisher's exact test was performed to analyze the number of patients taking levodopa, COMTI, MAOBI, trihexyphenidyl, zonisamide, istradefylline, and amantadine and the number of deep brain stimulations postoperatively. P < 0.05 was considered statistically significant.ROC curve analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate PD from MSA. Moreover, the optimal cutoff score was determined using the Youden method . The demP=0.020). Disease duration was significantly longer for patients with PD than for patients with MSA (P < 0.001). Except for age at the pareidolia test and disease duration, no other significant differences in the demographic characteristics among the subject groups were noted. Moreover, none of the patients met the Movement Disorder Society Task Force Level 1 criteria for PD with dementia based on the results of neuropsychological tests [al tests .P=0.004). One or more pareidolic responses were observed in 3 of 19 MSA-P patients and 6 of MSA-C patients (P=0.488). The number of pareidolic responses in patients with PD was significantly larger than that in patients with MSA  showed one or more pareidolic responses: the rate was higher than patients with MSA . STAI-trait (trait anxiety) score was also significantly higher for patients with PD than for those without pareidolias (P=0.044). Except for the STAI score, no significant differences in the demographic characteristics and other clinical data among the two groups were noted.Patients with PD with pareidolias were defined as those showing one or more pareidolic responses in the pareidolia test. A comparison of patients with PD with and without pareidolias is shown in Pareidolic responses in patients with PD and MSA without hallucinations were investigated using the NPT. Pareidolic responses were more frequently found in patients with PD than in those with MSA. Although a ROC curve analysis demonstrated that the pareidolia test with the optimal cutoff score did not show high accuracy for differentiating PD from MSA, having two or more pareidolic responses in the pareidolia test was highly specific for PD. Moreover, patients with PD with the pareidolic response had higher STAI score than those without the pareidolic response, and anxiety may be associated with pareidolias in patients with PD.Pareidolias can be found not only in patients with PD with visual hallucinations but also in those without visual hallucinations. The prevalence of pareidolias in the NPT for patients with PD without visual hallucinations was 47.5% in the current study. In a previous report including patients with PD both with and without visual hallucinations, the prevalence of pareidolias in the scene pareidolia test was 62.2%, and a subset of patients with PD without visual hallucinations exhibited pareidolias . SimilarThe pareidolia test may be a highly specific test for differentiating PD from MSA. Lewy body disease and MSA share clinical features, such as parkinsonism, autonomic failure, and cognitive impairment, and are often difficult to distinguish. Previous autopsy series including patients with antemortem MSA diagnosis showed that diagnostic accuracy was 62%–86%, and the most frequent alternative pathological diagnosis was the Lewy body disease –24. PrevAnxiety may be associated with pareidolias through developing abnormal perceptual priors/biases in Lewy body disease. The STAI has been applied in previous studies for the quantification of anxiety symptoms in patients with PD , 29, andThis study has several limitations. First is the selection bias inherent in a retrospective study from a single tertiary center. Another potential source of selection bias in this study is that only about one-fifth of patients with PD presented to our department during the study period were included. However, as a result, this study included patients with PD with a wide range of disease duration (0.6–26.3 years) and did not include patients with overt dementia. Second, pathologic confirmation was not done, and the possibility of misdiagnosis in some cases cannot be excluded. Finally, of the two versions of the pareidolia test, the noise and scene pareidolia tests, only the NPT was used. The scene pareidolia test has been reported to be superior than the NPT in differentiating DLB from Alzheimer's disease . Using tIn conclusion, pareidolias can be found in patients with PD without visual hallucinations. Moreover, the pareidolia test may be a highly specific test for differentiating PD from MSA.


To evaluate the feasibility of brainstem auditory evoked potential (BAEP) for rehabilitation prognosis prediction in patients with ischemic stroke, 181 patients were tested using the Korean version of the modified Barthel index (K-MBI) at admission  and discharge (follow-up K-MBI). The BAEP measurements were performed within two weeks of admission on average. The criterion between favorable and unfavorable outcomes was defined as a K-MBI score of 75 at discharge, which was the boundary between moderate and mild dependence in daily living activities. The changes in the K-MBI scores (discharge-admission) were analyzed by nonlinear regression models, including the artificial neural network (ANN) and support vector machine (SVM), with the basal K-MBI score, age, and interpeak latencies (IPLs) of the BAEP . When including the BAEP features, the correlations of the ANN and SVM regression models increased to 0.70 and 0.64, respectively. In the outcome prediction, the ANN model with the basal K-MBI score, age, and BAEP IPLs exhibited a sensitivity of 92% and specificity of 90%. Our results suggest that the BAEP IPLs used with the basal K-MBI score and age can play an adjunctive role in the prediction of patient rehabilitation prognoses. In terms of rehabilitation in patients with stroke, the decision making relating to “how to” and “how long” is quite challenging because accurate prognosis of the outcome remains difficult . The cliEvoked potentials (EPs) have been widely applied in assessing sensory and motor organs, as well as afferent neural pathways, not only for clinical diagnosis but also for intraoperative neurophysiology monitoring . MoreoveHowever, human studies using the EP for predicting the rehabilitation outcome in patients with stroke are scant. Rollnik evaluated the median somatosensory EP (SEP), brainstem auditory EP (BAEP), and visual EP (VEP) to predict good and poor outcomes, which were divided by a Barthel index (BI) of 50 at discharge . The BI Machine learning algorithms have been actively applied to predict the recurrence and survival of various diseases ,17. The This study followed the Declaration of Helsinki in medical research and was approved by the Institutional Review Board of Chungnam National University Hospital, Republic of Korea . As this study was a retrospective medical record study, informed consent was waived by the Ethics Committee, which approved the study. A total of 181 subjects with ischemic stroke were screened among patients who were treated in a regional rehabilitation center from May 2018 to April 2019. Included subjects were older than 18 years at the onset of stroke and had suffered an ischemic stroke with corresponding lesions and/or evidence of acute arterial occlusion on MRI. Patients who had a hemorrhagic stroke or other neurological diseases, such as brain tumor, Parkinsonism, or Guillain–Barre syndrome confirmed by MR images and clinical symptoms, were excluded to increase the homogeneity of the target population. Patients with hemorrhagic transformation or recurrence of stroke in admission were excluded, and no other complications that could affect BAEPS were found. Information on number of lesions, extent, and clinical manifestations was not collected. Although the degrees of hearing loss were not confirmed by the pure tone test, patients with severe hearing impairment after stroke were not included in the present study. All subjects were able to communicate with clinicians and clinical pathologists during the rehabilitation process, without auditory assistance. Details of the subject characteristics are presented in The BAEP is the electrical potential generated by the auditory nerve and brainstem within the first 10 ms following an acoustic stimulus. A typical BAEP consists of a series of 5 to 7 vertex-positive waves labeled by Roman numerals (waves I–VII). It is considered that waves I through III are produced by the auditory branch of the cranial nerve VIII and lower, whereas waves IV and V originate from the upper brainstem . The BAEThe MBI is used extensively in Europe and Asia for performance measurement in ADL . The MBIFirst, to determine the effects of stroke onset (first ever vs. recurrent), lesion location (brainstem vs. other locations), duration from onset to study, and duration from onset to discharge on the BAEP IPLs, we performed partial correlation analysis between each factor and BAEP IPLs while controlling the effect of other factors.p-values. Moreover, we assigned a weight to each input parameter and trained the weight vector using a gradient ascent method of the k-nearest neighbors algorithm. The parameter weights were compared to estimate the relative importance in the regression of delta K-MBI. We also performed stepwise regression and observed the change of adjusted r-squares to confirm the significance of BAEP IPLs as input variables.Second, we also performed regression analysis on the change in the K-MBI score (delta K-MBI) using the basal K-MBI score, age, and three IPLs  of the BAEP. Two nonlinear regression models using an artificial neural network (ANN) and the support vector machine (SVM) were applied. ANN and SVM regression were employed because these have exhibited high performance without overfitting in many clinical applications ,29. In tThereafter, we applied ANN and SVM with the basal K-MBI score, age, and three IPLs to predict the rehabilitation prognosis, which was divided into favorable and unfavorable outcomes. The ANN and SVM have also been widely used for classification tasks ,31,32. Ir = 0.16, p = 0.03). No significant relationship was found between BAEP IPLs and other factors.r = 0.90, p < 0.001), but the relationship between the delta and basal K-MBI scores had a relatively weak correlation , as illustrated in r = 0.09, p = 0.19; measurement to discharge: r = −0.10, p = 0.16; onset to discharge: r = 0.21, p = 0.07).The classification result based on the K-MBI score of 74, which was the boundary between mild and moderate dependence, is presented in r = 0.55, p < 0.001; SVM: r = 0.59, p < 0.001).r = 0.70, p < 0.001; SVM: r = 0.64, p < 0.001). The weights of all parameters obtained from the k-nearest neighbors algorithm are listed in p < 0.05). The adjusted r-squares with different input variables are listed in r-squares was confirmed when incorporating the BAEP IPLs  as input variables, which is consistent with the results of ANN and SVM regressionsThe test results of the models with the basal K-MBI score and age, as well as the models with the basal K-MBI score, age, and BAEP, are listed in In the ANN model with two input features, the sensitivity and specificity were 84% and 86%, respectively. In the SVM model with the same two inputs, the sensitivity and specificity were 84% and 90%, respectively. When adding the three BAEP IPLs as input features, the sensitivity and specificity in the ANN model increased to 92% and 90%, respectively, whereas those in the SVM model were 88% and 86%, respectively. The AUC values of the ANN and SVM models when using the basal K-MBI score and age were 0.90 and 0.87, respectively. When adding the three BAEP IPLs, the AUC values of the models increased to 0.93 and 0.90, respectively .The main findings of this study are twofold. First, the BAEP IPLs with a basal K-MBI score and age significantly improved the regression predictive ability on the changes in the K-MBI scores between admission and discharge. Second, the BAEP IPLs also contributed to the prognostic performance of nonlinear machine learning models when predicting the favorable and unfavorable groups with the K-MBI score at discharge.In the regression analysis of the change in the K-MBI score between admission and discharge, we found that the BAEP IPLs could contribute considerably to the outcome prediction. It has been controversial, but some studies reported that BAEP could be a predictor of the prognosis of patients with supratentorial or infratentorial stroke . A previA strong association was observed between the basal and follow-up K-MBI scores, whereas the change in the K-MBI score exhibited a lower dependence on the initial status. Moreover, when analyzing the favorable and unfavorable groups, 30% of patients (35 out of 117) with an unfavorable outcome at admission improved to the favorable group following the rehabilitation process. The ANN model exploiting the BAEP IPLs together with the basal K-MBI score and age could increase the sensitivity and specificity of predicting the unfavorable outcome up to 92% and 90%, respectively. This improvement in the prediction was also clearly confirmed by the ROC curves. It is likely that the neural network model is well suited to estimate the nonlinear relationship of rehabilitation outcomes. This is in line with a previous study, which found that the optimal outcome prediction performance for acute stroke was achieved with the deep neural network. Although different input features such as clinical variables or medication history  were applied in the previous study, the deep neural network outperformed other machine learning models such as random forest or logistics regression .The present study exhibits several limitations. The size of the test dataset was relatively small, and the test was performed only in a retrospective nature. The degrees of hearing loss were not confirmed by the pure tone test. The confirmation of the hearing ability can provide more accurate information to differentiate the effect of hearing loss vs. stroke and then to evidence the contribution of BAEP in the prognosis prediction of patients with stroke. Subjects were also limited to patients with ischemic stroke on the supratentorial or infratentorial regions, or both. There was a lack of data on the pathogenesis of ischemic stroke and lesion size. Furthermore, there was a lack of data with large delta K-MBI scores over 50. Additional features from auditory middle-latency and late responses that measure cortical-subcortical functions and multiple measurements could provide more information for the prognosis of patients with stroke. Several studies reported an association between the functional prognosis or poor outcome of stroke patients and multimodal evoked potentials (MEP and SEP), and greater predictability was found when combined as multimodal evoked potentials ,41. Simi


The importance of menstrual cycle physiology in appetite and obesity is poorly understood. We investigated the effects of body mass index (BMI), menstrual cycle phase and sweet and salty taste on monetary valuation of snack foods.We recruited 72 women and after the application of in- and exclusion criteria 31 participants with healthy weight and 25 with obesity remained. The participants completed a willingness to pay (WTP) task to measure subjective value of 30 snack food items in the pre-ovulatory and mid-luteal cycle phases.p = 0.002). Hence, WTP was inversely related to BMI, but the strength of the relation depended on cycle phase and taste. The WTP of participants with healthy weight for salty taste changed across cycle phase but the WTP for sweet taste was not affected by cycle phase. Moreover, the cycle effect for the salty snacks ceased in participants with obesity.Generalized linear mixed model (GLMM) analysis revealed that BMI, cycle phase and snack taste interacted to influence WTP (−0.15 , The inverse effect of BMI on WTP valuation of snack foods contrasts with the positive effect of BMI on pleasantness ratings for milkshakes by the same women that we previously reported. This indicates that the two measures reflect different aspects of food-related valuative processing in obesity. Furthermore, the WTP data suggest that the selection of salty snacks may differ from that of sweet snacks in the pre-ovulatory phase of the menstrual cycle for individuals of healthy weight. The cycle phase does not seem to affect food valuation of participants with obesity. These findings are relevant to understanding and treating obesity in women. This mechanism is part of a two-roads-to-food-reward model, where food reward is substantially influenced by the flavor-nutrient learning process happening in the gut  and results not only from conscious reward signals based on food perception, taste and oral somatosensation (the high-road). Furthermore, a number of differences in taste perception have been linked to obesity and reproductive hormone status  for completing the study.2) or with grade 1 or 2 obesity (BMI 30–39.9 kg/m2) and who reported that they were weight stable and not dieting were invited to participate. Eligible women were provided with the Three-Factor Eating Questionnaire (TFEQ) and the Eating Disorder Examination-Questionnaire (EDE-Q) to complete at home before the first test visit and to return by mail.The participants were recruited and screened for eligibility at the department of Reproductive Endocrinology . In the pre-screening phase, general, endocrinologic and mental health were assessed through a Clinical Assessment Questionnaire designed for the present study. Only individuals fulfilling our previously described  in- and We recruited 72 physically and psychiatrically healthy women who were cycling normally and not using hormonal contraception. Four women withdrew from the study prior to completion, one was excluded due to insufficient German language skills, and two were excluded because of technical difficulties with the tasks. The participants were invited to attend two test visits, one in the pre-ovulatory phase and one in the mid-luteal phase of the menstrual cycle, with order randomized. Tests were timed in relation to menstrual cycle phases, calculated based on cycle information obtained from the participants  and confirmed against progesterone levels. For this paper, the pre-ovulatory phase targeted measurements from 16 ± 2 days prior to menstruation, i.e., shortly before ovulation, with low progesterone levels (3.0 ± 7.9 nmol/l). The mid-luteal phase targeted 7 ± 3 days prior to menstruation with high progesterone levels (21.4 ± 18.5 nmol/l). Six participants were excluded because their blood hormone levels were not in agreement with calculated cycle phases in either cycle phase. Another six participants for which only one cycle phase could be confirmed were retained, with their missing data accounted for in the statistical analyses. Three participants were excluded because their mean cycle length was not within the normal range (25–35 days).ad libitum meal. The meal consisted of ham sandwiches and tap water, and the consumed amount was determined by comparing the weight of sandwiches before and after the meal. Weights were transformed to kcal and analyzed as ad libitum consumption level. Participants had 30 min to finish the meal and then returned to the scanner and repeated the three valuation tasks. Hence, the participant performed the tasks in two satiety states  and two menstrual cycle phases , resulting in four sessions in total.Participants were advised not to drink or eat anything after 10pm on the evening prior to both test visits. The study compensation fee served as credit for the WTP task. In this task, participants bid money on a scale from 0 to 2.5 CHF in accordance with their desire to obtain different food items, which were pictures of 15 sweet and 15 salty common snack foods displaying a serving size of the product in front of its package on a black background. The snacks predominantly comprised chocolate bars, nut bars, cookies, gummy bears, crackers, olives, crisps, and salted nuts. To account for potential successive contrast influences among food items, this procedure was done twice for each food item in different order, resulting in 60 WTP bids. The participants bid on a continuous scale using a trackball, which they moved to the desired bid amount and then pressed to confirm their choice. The compensation method for the task was determined by an incentive-compatible auction mechanism . At the At different time points throughout the experiment, participants rated a number of subjective states. These included hunger, satiety, desire to eat, nausea, tiredness, feeling well, anxiety, discomfort, agitation, and dizziness. The participants provided these ratings using a generalized visual analog scale ranging from “not at all” to “as strong as possible” . The par2). For the Spearman correlation analyses and the generalized linear mixed model (GLMM) analysis, BMI was treated as a continuous variable, whereas for group comparisons, we used the categorical variable weight status, i.e., healthy weight or obese.Statistical analyses were performed using Microsoft Excel 2013 and R version 4.0.2 . Particis) for WTP bids, BMI, ad libitum consumption levels, TFEQ scores, and the subjective state ratings from the time points around the WTP task, excluding missing values. A correlation matrix  were considered invalid, i.e., entered the analysis as missing values. In addition, we excluded items with WTP bids of zero in all four experimental sessions due to an apparent dislike of these items. Visual inspection of the histograms and the quantile-quantile plots indicated that the WTP bids and several other dependent variables were not normally distributed. Therefore, non-parametric statistical analyses were done for all analysis except the GLMM, which was based on a beta distribution. We computed Spearman correlation coefficients  to between 0 and 1, as previously suggested (conv = ([WTPNorm(n−1) + 0.5]/n) where n is the number of samples , we used a beta regression model and a logit function as link . The datuggested , and tra samples . We used samples . We inclBMI and ad libitum consumption level (AdlibConsum) were z-scored at a group level and day of test visit , Satiety (Fasted or Fed), cycle phase , and Taste  were used as binary variables. Two- and three-way interactions were included. We calculated the p-values using the Wald statistic. To correct for the multiple tests using WTP bids as dependent variable , we applied the Bonferroni procedure, resulting in a nominal threshold of 0.01 (= 0.05/5), and only effects for which p-value < 0.01 were considered significant. To display significant interaction effects we used the R functions ggpredict and ggplot . The TFEQ scores cognitive eating restraint and hunger susceptibility did not differ between participants with healthy weight and with obesity (p = 0.414 and p = 0.058) but disinhibition of eating was higher in the obese than in the healthy weight group .We report the results for 56 women who fulfilled our selection criteria. rs ≤ 0.1, p ≤ 0.011) and negatively with satiety rating  and BMI . Analysis of the TFEQ scores revealed a weak but significant correlation of BMI with cognitive eating restraint and hunger susceptibility  and a moderate correlation of BMI with disinhibition of eating . We also found very weak correlations of WTP with cognitive restraint and with disinhibition of eating , whereas those of women with obesity did not change significantly across cycle phases  whereas the mid-luteal WTP bids were lower in participants with obesity than those with healthy weight . Thus, obesity eliminated the effect of the menstrual cycle on WTP for snack foods that was evident in women with healthy weight (The WTP bids (in CHF) of participants with healthy weight were significantly reduced in the pre-ovulatory compared to the mid-luteal phase . This difference arose in both cycle phases  and weight groups . Hence, WTP differed depending on the taste of the snack foods presented, i.e., sweet or salty.On average, the WTP bids for sweet snacks were higher than the ones for salty snacks . Specifically, average WTPconv was higher in fasted compared to fed satiety state . The predictor snack type (“taste”) showed a trend-level effect but did not survive Bonferroni correction. There were two significant interactions predicting WTPconv bids (pcorrected < 0.01). The first interaction was between snack type and cycle phase , the second one between snack type, cycle phase and BMI . As shown in conv was inversely related to BMI but the strength of the relation depended on cycle phase and snack type. That is, for both snack types in the mid-luteal phase and for sweet snacks in the pre-ovulatory phase, mean WTPconv decreased similarly from ∼0.50 in participants with the lowest BMI to ∼0.35 in participants with the highest BMI. In contrast, WTPconv for salty snacks in the pre-ovulatory phase was less, ∼0.41, in participants with the lowest BMI, and decreased less steeply, to ∼0.37 for participants with the highest BMI. Furthermore, WTP bids for salty foods were generally higher in women with lower BMI than with high BMI, especially during the mid-luteal phase. In contrast, for sweet snacks, WTP bids were also generally higher in women with lower BMI, but were not affected by menstrual cycle phase.The GLMM outcomes are summarized in In this study we used a WTP method to measure the subjective value of snack foods in women with healthy weight or obesity. We report an inverse relationship between WTP and BMI, which depends on snack taste and cycle phase. The decreasing WTP with increasing BMI is opposite to what we found in a milkshake tasting task, where the same participants’ pleasantness ratings increased with BMI . This inOur findings reveal that valuation appears to be higher for sweet than for salty snack foods, especially for participants with obesity and in the pre-ovulatory cycle phase. In contrast, mid-luteal WTP bids of participants with healthy weight did not differ by taste. Hence, while the WTP for salty snacks increased from the pre-ovulatory to mid-luteal cycle phase, the WTP for sweet snacks did not depend on cycle phase. This absence of cycle effect for sweet food parallels the findings on pleasantness of milkshakes . The midPrevious neuroimaging studies demonstrated correlations between WTP and activity of different brain regions . Some of2 receptor expression was lower in individuals with severe obesity compared to humans with healthy weight  as a predictor for WTPn hunger  and thatn hunger . In appae to eat .We used BMI as a metric to discriminate between people with and without obesity rather than other methods like dual energy x-ray absorptiometry (DXA) because it remains a simple and accurate measure for obesity on a population level . HoweverThis study aimed to measure food valuation and to investigate whether it changes with BMI, cycle phase, and taste. Our major findings were that WTP changes across the menstrual cycle for participants with healthy weight and for salty food items. This indicates that obesity research should focus more on the influences of, first, types of foods and eating occasions and, second, reproductive hormones on reward processing, in particular dopamine signaling and anticipatory food valuation. Furthermore, the reduction in the effect of menstrual cycle changes on food valuation in women with obesity is a novel finding which, if reproduced by future studies, may be critical for future obesity research.brigitte.leeners@usz.ch.The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Requests to access the datasets should be directed to BL, The studies involving human participants were reviewed and approved by Ethics Commission of the Canton of Zurich. The patients/participants provided their written informed consent to participate in this study.LH planned and performed the data analysis and wrote the first draft of the manuscript. SG collected and curated the data, planned and supported the data analysis. SW programmed the task and collected data. GG, MR, and BL realized recruitment and selected the participants. BL, LA, NG, PT, MR, and SW designed the study. All authors contributed to the manuscript and approved the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children  were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54–4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64–4.77) m/s) ( Cardiovascular disease (CVD) is the leading cause of mortality globally, accounting for 18 million deaths annually ,3. The bThe assessment of arterial stiffness by pulse wave velocity (PWV) has become an established surrogate biomarker to estimate cardiovascular risk in the large arteries ,15. In an = 1255) of the first primary school class from Basel City (26 schools) were invited to take part in the study. The children were 6–8 years old at baseline and have been followed up with a medical- and fitness screening in 2018. Written informed consent for study participation was obtained from the children and their parents at both time points. The medical and physical fitness assessments took place on separate days on-site regular school settings. The measurement of arterial stiffness was implemented in 2018. The parents of the children were requested to fill out a questionnaire about their SES, lifestyle behavior, and childhood health. Detailed information about the cross-sectional assessment is provided in the publication of baseline data [http://www.clinicaltrials.gov: NCT03085498, accessed date 2 August 2021).The Sportcheck Follow-up Study is a longitudinal cohort study of 223 school children based in Basel City, Switzerland and set up in 2014 . The stuine data . The stuCentral PWV was assessed by using a non-invasive and valid oscillometric Mobil-O-Graph device ,27,28,29Anthropometric measurements, including height and weight, were assessed by a wall-mounted stadiometer  and bioelectrical impedance analyzer . BMI categories were applied according to the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) reference values . The cutThe parental questionnaire included items of SES, migration background, and parental lifestyle, which were previously developed in a school-based intervention study in Switzerland . HousehoIn addition, we assessed PA behavior of the mother and father, as well as the PA behavior together with their child. Parents, who have reported to be never or rarely physically active were categorized as having a low PA level. Being physically active once a week was determined as a medium PA level, and all above  was determined as a high PA level. The same categorization was set for being physically active as a family. p = 0.005. A sample size calculation was conducted a priori based on the previously reported association between BP and retinal vessel diameters [Univariate analysis of covariate (ANCOVA) was performed to analyze the association of household income, education level, migration background, and parental PA behavior with PWVin children. The first model was adjusted for the covariates of age and sex at baseline. The additional model was extended by the covariates of household income, education level, or migration background. Furthermore, the Bonferoni post hoc method was applied to reveal the direction of the results. The results are presented by the means and its 95% confidence intervals with a two-sided level of significance of iameters . A sampliameters . All ana2), BP , and cardiorespiratory fitness performance (1.9 ± 1.8 stages) after 4 years follow-up, which corresponds to an age-related normal development. The prevalence of overweight increased by 2% along with no changes in obesity from baseline to follow-up. Only one child was classified as severe underweight, and two children were classified as moderate underweight at baseline. Furthermore, a decreasing trend in elevated and high systolic (−7%) as well as diastolic BP (−5%) was observed from baseline to follow-up. The 10–12-year-old children had a mean PWV of 4.7 m/s (±0.3) on average. Regarding the development of household income over four years, 12.3% of the families had a higher income at follow-up and respectively, 4.9% of the families had a lower household income at follow-up.The flow diagram of the recruitment and enrollment process is shown in n = 40), medium , or high  household income (p = 0.573) were detected. A slightly lower mean PWV was observed in children with parents of a high education level  compared to a low  or medium  education level. However, this association was not statistically significant (p = 0.554). Furthermore, we found little evidence for an association between migration background and childhood PWV between the groups of parents with  or without  European nationality (p = 0.445).The association between baseline household income, education level, and migration background of the parents with arterial stiffness in children is shown in n = 82) compared to children of mothers with a low PA behavior  (p = 0.049). No significant association between child PWV and the three categories of low , medium , and high  PA behavior of the father was found (p = 0.483). Regarding the relationship of being physically active as a family, a trend toward a lower childhood PWV in the most active families  was detected compared to the families with a medium  or low  PA behavior, however, without statistical significance (p = 0.108). Our study results demonstrate that maternal PA behavior influences arterial stiffness in children over four years. Children of mothers with a high PA level had significantly lower PWV at follow-up compared to children of mothers with a low PA level. Furthermore, we found little evidence for a relationship between parental SES and migration background with the development of childhood arterial stiffness. Our data indicate no significant prospective association of parental education level, household income, or migration background with PWV in children. In another prepubertal child cohort, we have previously shown that household income and parental educational level are cross-sectionally associated with PWV in children . HoweverParental SES can hardly be adjusted, but parental lifestyle behavior is adaptable. Therefore, we assessed parental PA behavior and time spent physically active as a family in relation to the development of childhood arterial stiffness. Our study results indicate that children of mothers with a high PA level have a significantly lower arterial stiffness compared to children of mothers with medium or low PA behavior. It has become evident that children of active mothers are twice as likely to be active as children of inactive mothers,  which isOur findings have several practical implications. In young children with short lifetime exposure to socioeconomic and environmental risk factors, the vascular health of large arteries was not altered. It appears that longer-term exposure is necessary to establish the association of these risk factors with vascular alterations in adolescence and young adulthood ,41. HoweOur findings need to be interpreted in light of some limitations. The lost-to follow-up rate was 27% due to illness at the day of examination, relocation, or personal reasons. However, differences in the baseline characteristics between the follow-up and non-follow-up participants were small and thus, the present cohort can be considered as representative of the original population . AnotherA higher maternal PA level was related to a favorable development of arterial stiffness in children over four years. Little evidence for a prospective association of SES and parental migration background with arterial stiffness in children was found. Parental lifestyle, in particular maternal PA, seems to be a key part of the exposure that affects the development of childhood arterial stiffness. However, more longitudinal studies with follow-up into adulthood and potential manifest CVD are warranted to determine the clinical relevance of social disparities and parental lifestyle behavior on arterial stiffness progression in childhood. Nevertheless, our results indicate the importance of an active parental lifestyle to achieve good vascular health in childhood as a preventive measure to reduce CVD development later in life.


A current challenge for endometriosis surgery is to correctly identify the localizations of disease, especially when small or hidden (occult endometriosis), and to exactly define their real extension. The use of near-infrared radiation imaging (NIR) after injection of indocyanine green (ICG) represents one of the most encouraging method. The aim of this study is to assess the diagnostic value of NIR-ICG imaging in the surgical treatment of endometriosis compared with the standard of treatment.The Gre-Endo trial is a prospective, single-arm study (NCT03332004). After exploring the operatory field using the white light (WL) mode, patients were injected with ICG and then observed in NIR mode. All suspected areas were classified and chronicled according to lesions visualized only in WL, NIR-ICG, or in the combination of both. Lesion not visualized in WL was considered as suspect occult lesion (s-OcL). In addition, a random control biopsy from an apparent negative peritoneum visualized in WL and NIR-ICG imaging was taken for all patients (control cases). All lesions removed were considered “suspect endometriosis” until pathology.p = 0.001 and p = 0.835, according to McNemar’s and Cohen’s kappa tests, respectively).Fifty-one patients were enrolled between January 2016 and October 2019. A total of 240 suspected lesions have been identified with both methods (WL + NIR-ICG). Two hundred and seven (86.2%) lesions out of the overall 240 were visualized with WL imaging, and 200 were confirmed to be pathologic (true positive for WL). The remaining 33/240 (13.75%)  lesions were identified only with NIR-ICG imaging and collected as s-OcL. All 33 s-OcLs removed were confirmed to be pathologic (c-OcL = 100%). NIR-ICG vision showed PPV of 98.5%, NPV of 87.1%, Se of 87%, and Sp of 98.5%, confirming that this kind of imaging is an excellent diagnostic and screening test (The use of NIR-ICG vision alone and combined with WL showed good results in intraoperative detection rate and fluorescence-guided surgery of endometriosis. Furthermore, NIR-ICG allowed surgeons to remove occult lesions that otherwise would remain, leading to possible greater postoperative pain and a higher risk of persistence and relapse. Endometriosis is considered a public health problem compromising the social, employment, financial, and reproductive quality of life of the patients . When phEarly technical difficulties have been overcome by surgeon experience and the refinement of techniques; a frequent current challenge involves identifying endometriosis localizations, especially when small or hidden (occult endometriosis) –9, to noIndeed, there is evidence that postoperative recurrence of endometriosis may be due to incomplete resection during the primary surgery .Furthermore, eradicating surgery for endometriosis presents the risk of “overtreatment” as well, since the surgeon usually may remove lesions suspected of being endometriosis that are not pathologically confirmed to be endometriosis from 16% to 53% of cases . The excIndocyanine green (ICG) is nowadays increasingly used in gynecological surgery, both in oncological and benign fields –16. It iGiven the typical neovascularization of endometriosis, related to chronic inflammation, the visualization of abnormal areas of peritoneal vascularization could be useful to better identify and define the endometriosis lesions in their real extension and to visualize the lesions even when not obvious, as in puckered peritoneal lesions –11, 20. The use of cameras with near-infrared radiation imaging (NIR) after injection of ICG represents one of the most encouraging methods in this experimental scenario, demonstrating a good profile of safety and accuracy as an intraoperative diagnostic method –11, 24.The aim of this study is to assess the diagnostic value of NIR-ICG imaging in the surgical treatment of endometriosis compared with the standard of treatment, that is laparoscopy in white light (WL), and the standard diagnostic method, that is pathologic finding.The Gre-Endo trial is a prospective, single-arm study  carried on at the Fondazione Policlinico Universitario “A. Gemelli”—IRCCS, Rome, Italy, and Gemelli-Molise, Campobasso, Italy. The local ethics committee approved the experimentation (Prot.sf. A.287/C.E./2013).The NIR-ICG camera system adopted for the study was the Olympus ICG Imaging System Prototype based on the VISERA Pro System , the merchandized camera head CH-S200-XZ-EB connected to VISERA ELITE II system with NIR filter , and the IMAGE1 S™ Rubina imaging technology from KARL STORZ.The ICG adopted for intravenous injection during the procedures was Pulsion  and VerDye .Inclusion criteria were suspected endometriosis with surgical indication for treatment needing laparoscopic and pathologic confirmation. Patients were triaged to surgery according with the common indications for endometriosis . ExclusiPatients with ovarian endometriosis and/or endometriosis of the fallopian tubes were excluded from the study because of the intraoperative lack of fluorescence of the ovaries and the diffuse fluorescence of the tubes because of physiological vascular web density at preliminary pilot surgeries.After obtaining informed consent, patients were included in the study and they could withdraw from the study at any time without impacting treatment. Patient demographic features and preoperative pain were scored using the visual analog scale (VAS) , and theAll the procedures were performed by a team of three well-trained surgeons with >10 years of experience in minimally invasive techniques for endometriosis.torus uteri and the ovarian fossa and freeing the bowel from eventual retrocervical nodule attachment. All suspected areas were classified as either peritoneal superficial endometriosis (PE) or deep infiltrating endometriosis (DIE). All suspected PE was classified as white, black, and red lesions and documented with their anatomic location in the surgical record under WL condition. Similarly, all suspected DIE lesions were also recorded with their anatomic location in the surgical record    under WLs, etc.) Figure 1in toto and analyzed them at multiple levels. A surgical specimen was considered as “pathologic” when containing endometriosis foci (stroma and/or gland and/or hemosiderin) and/or acute or chronic sclerosing inflammatory infiltrate .Normally, WL is the intraoperative gold standard imaging technique for detecting endometriosis, while pathology the definitive confirmation test.We tested the null hypothesis that the possibility of correctly identifying endometriosis could improve from 85% with WL visualization to 100% when assessed together with NIR-ICG. The sample size was calculated according to the Simon two-stage design  using anBecause the control biopsy was achieved from a negative peritoneum using WL and NIR-ICG imaging for all women, the true-negative lesions were defined as the negative lesions for endometriosis that were correctly identified as negative by WL or NIR-ICG imaging; the false-negative lesions were defined as not correctly identified by WL or NIR-ICG imaging. The true-positive lesions were the positive lesions for endometriosis that were correctly identified by WL or NIR-ICG imaging; the false-positive lesions were the lesions identified as positive for endometriosis by WL or NIR-ICG imaging that were not pathologically identified as endometriosis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated for each visualization. Sensitivity (Se) was defined as the number of positive lesions for endometriosis that were correctly identified (true positives) divided by the total number of positive lesions for endometriosis . Specificity (Sp) was defined as the number of negative lesions for endometriosis that were correctly identified (true negatives) divided by the total number of negative lesions . PPV was calculated as the number of true positives divided by the total number of positive results , and NPV was defined as the number of true negatives divided by the total number of negative results . Accuracy was calculated as the number of true positives plus true negatives  divided by the total number of patients studied. Sensitivity, specificity, and accuracy were compared using McNemar’s and Cohen’s kappa tests. The diagnostic performances of WL and NIR-ICG imaging were calculated per patient as well as per lesion. Statistical calculations were performed using the Statistical Package for Social Sciences .p-values <0.05.The receiver operating characteristic (ROC) curve was designed to assess the diagnostic performance of WL and NIR-ICG for identifying pathologic lesions compared to pathology. The statistical significance was set at A total of 135 patients with symptomatic endometriosis were screened and 51 were enrolled between January 2016 and October 2019 Figure 2All patients underwent laparoscopic surgery, and no laparotomy conversions were recorded. The most performed surgery was uterosacral ligament (USL) nodule removal in 80% of the patients, while retrocervical nodule resection was performed in 78% of the cases. Overall, segmental colorectal resection represented 28% of the cases.early complications were registered: among grade I, one case of urinary retention and one case of fever; among grade II, one case of postoperative bleeding of colorectal anastomosis in postoperative day 2 was noted and controlled by hospitalization and the administration of 500 mg tranexamic acid orally every 8 h for 3 days, three cases of fever needing for antibiotic infusion, and one case of anemia needing red cell-concentrated unit transfusion; among grade III, one case of colorectal anastomosis dehiscence then subjected to resuturing and loop ileostomy creation and one case of vaginal fornix dehiscence after a posterior wall nodule resection needing to be resutured.No hemorrhages, allergic reactions, and/or any type of intraoperative complications were reported. Postoperative complications affected nine (17.6%) patients and were not directly associated to the ICG infusion or to the experimental plan. In particular, only Fifty patients administered with ICG presented tissue fluorescence, except one woman that was completely negative even after a second repeated dose.A total of 240 suspected lesions have been identified with both methods (WL + NIR-ICG). Two hundred and seven (86.2%) lesions out of the overall 240 ones were visualized with WL imaging, and 200 were confirmed to be pathologic (true positive for WL). The remaining 33 out of 240 (13.75%)  lesions were identified only with NIR-ICG imaging and collected as s-OcL Figure 3p = 0.001 and p = 0.835, according to McNemar’s and Cohen’s kappa tests, respectively).Regarding WL vision, the overall PPV and NPV were 96.6% and 86.3%, while Se and Sp were 85.8% and 96.7% Table 5.vs. 46.7%); conversely, it was superior in recognizing black lesion (60% vs. 50%).As far as PE is concerned, NIR-ICG demonstrated higher values of PPV and specificity than WL, while NPV and sensitivity were lower. The accuracy of the NIR-ICG was lower than WL regarding white lesion (40% p = 0.002 and 0.768 and Cohen’s kappa test: p = 0.01 and 0.876). Conversely, WL demonstrated superiority than NIR-ICG in the recognition of prevesical/vesical lesions .As far as DIE is concerned, the two visualization approaches demonstrated superimposable values of Sp, while Se and accuracy resulted higher for NIR-ICG for the visualization of periureteral/ovarian fossas and colorectal nodules (McNemar’s test: p = 0.001) and Cohen’s kappa tests (p = 0.83), revealing that both methods, regardless of the operator, should always be integrated to ensure complete eradication of endometriotic lesions .The role of surgery in endometriosis is to remove the affected tissues to obtain pain relief, to improve fertility, and to abate not only the persistence of disease but also the risk of recurrence that occurs from 20% up to 50% of women at 2 and 5 years after treatment , 32, 33.On the other hand, endometriosis is not cancer, so the excessive search for surgical radicality can imply an increase in perioperative morbidity and can cause serious functional damage, especially if the resection of tissues affected by endometriosis is associated with the removal of healthy tissues surrounding the diseased or mimicking them , 34–43.Furthermore, the sensory perception of the surgeon, albeit an expert one, in identifying intraoperatively suspect lesions for endometriosis based on location, color, size, and depth has obtained well-known limits. Indeed, Stegmann et al. found that the PPV of using only the impression of an experienced surgeon to identify histologically positive lesions was 64.0%, and the NPV was 88%, while the Se and Sp of using this method were 98% and 21%, respectively .Furthermore, the possibility of not recognizing outbreaks of endometriosis that is not visible because it is microscopic or hidden (occult endometriosis) in 6%–13% of the cases may further worsen the effectiveness of surgical clearance , 44.For these reasons, different approaches to increase the potential for intraoperative recognition of endometriosis (enhanced vision) have been investigated using different dyes or technologies such as 3D robotic vision, with different efficacy and safety profiles , 45–47. Moreover, in association with the intraoperative diagnostic role of NIR-ICG, a challenging additional advantage seems to be the capability of distinguishing the diseased tissue from the surrounding healthy ones and to evaluate the residual vascularization of noble organs subjected to dissection and/or eradicating surgery such as the rectum and ureter , 48, 49.In this study, we confirmed what was already found in recent literature about the identification of lesion and the definition of the extent and limitation of lesions from healthy tissues , 48, 49.vs. 85.8% and 98.5% vs. 96.7%, respectively). Moreover, the overall values registered at McNemar’s (p = 0.001) and Cohen’s kappa (p = 0.83) tests showed that NIR-ICG is an excellent screening and diagnostic confirmation test compared with WL. Cohen’s kappa is higher than 0.4 for all types of lesion observed: it means that the evaluation of the two tests is good and independent from the observer.In this cohort, NIR-ICG showed higher values of Se and Sp compared with the standard WL  in patients with previous surgery and ii) after surgical dissection and tissue cruentation (data not shown). However, considering the few cases analyzed, further prospective studies are needed to confirm the excellent result for this subset of patients.Finally, it is necessary to underline, thanks to NIR-ICG, that 33 lesions (c-OcL), which otherwise would not have been removed with standard approaches, had been resected, with a gain of 16.5% in the count of lesions removed only by WL and a gain of 14.16% in the overall count of lesions resected by the combination of the methods.Interestingly, no iatrogenic opening of the bowel during conservative eradication procedures nor intraoperative ureteral lesions or postoperative fistulas occurred; moreover, the postoperative urinary retention observed was only 2%, lower than the rate reported in the literature . These iTo our knowledge, this is the first prospective trial with the most consistent population subjected to the same homogeneous procedure  .Recently, Siegenthaler et al.  found thThe strengths of this study are the single-center prospective design, the considerable population enrolled subjected to the same experimental procedure and the standardized surgery by a limited team of high-volume surgeons, and a dedicated pathologist .The limitations of the present study include the exclusion by the investigation of the adnexal endometriosis and the higher percentage (~89%) of advanced endometriosis stage (stages III and IV for rAFS) that could represent a bias of selection.However, this type of population enrolment could be explained by the fact that our hospital is a third referral center to triage treatment of women with endometriosis who may be suffering from an advanced stage that cannot be treated elsewhere. Moreover, according to recent literature, the enrolment of higher stage of disease may have worsened the detection rate results of the present study . These lThis type of approach has recently been associated with a promising improvement in the quality of life , but furThe use of NIR-ICG alone and above all combined with WL during laparoscopy for endometriosis showed good results in intraoperative detection rate and fluorescence-guided surgery. Furthermore, NIR-ICG allowed surgeons to remove occult lesions that otherwise would remain, leading to possible greater postoperative pain and a higher risk of persistence and relapse.Further prospective studies that overcome the possible biases of this study are warranted to validate and confirm these results and permit a diffusion of fluorescence-guided endometriosis surgery as a useful aid for a more effective and safe surgery.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Fondazione Policlinico Universitario “A. Gemelli”—IRCCS, Rome, Italy (Prot.sf. A.287/C.E./2013). The patients/participants provided their written informed consent to participate in this study.Study concepts: LT, VV, GV, and FC. Study design: LT, GV, and GF. Data acquisition: VV, LT, and MN. Quality control of data and algorithms: GS, FC, and SG. Data analysis and interpretation: GV, LT, GF, and LP. Statistical analysis: GV, LP, and GF. Manuscript preparation: LCT, GV, and SG. Manuscript editing: LT, VV, GS, and GV. Manuscript review: all authors. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.