Conclusions: Sports university students are not immune to depression and inactive lifestyles. Excessive recreational screen time may have an adverse effect on depression, which is somewhat independent of physical activity.Background: Sports university students are usually expected to lead an active life and have a lower risk of depression. Therefore, there are few studies on depression and its risk factors among this population. This study aimed to investigate depression and its association with sedentary behavior and physical activity in sports university students. Methods: A cross-sectional survey was conducted among undergraduates majoring in physical education in a sports university in Beijing in March 2021. Students were asked about sociodemographic information, domain-specific sedentary behavior, physical activity, and depression . Chi-squared test and logistic regression were carried out to analyze the data. Results: Among a total of 584 participants, the detection rate of depression was 49.1%. The median of total sedentary time was 7.29 h per day. After adjusting for covariates, recreational screen time (OR = 1.540,  University students are in a transitional period of growth, and the change of environment and the expectations of family and society for higher education imposes stress on university students, making some of them suffer from mental health problems. Depression is one of the common mental health problems among university students ,2, whichSB is defined as a person in a sitting or reclining posture requiring an energy expenditure lower than 1.5 metabolic equivalents . A recenPA has been shown to be associated with depression among university students ,12,13,14Sport university students are expected to lead an active lifestyle. High levels of PA and low levels of SB have been believed to be associated with a positive self-concept and reductions in mental health problems, such as depression and anxiety . As a reTo this end, our study investigated depression, SB, and PA of students of a sport university and analyzed the association of depression with total and domain-specific SB and PA so as to provide a profile of depression and SB among this population and a reference for potential interventions in their lifestyle.A cross-sectional survey was conducted on undergraduates majoring in physical education, a typical discipline in Beijing Sport University in March 2021, which included athlete students of physical education courses and non-athlete students of sport science courses. Undergraduates in grades 1 to 3 were asked to complete an online self-administered questionnaire. Senior students were excluded because they had been in internships and had not led a typical school life. Measures for SB, PA, depression and demographic information were included in the online questionnaire.Participants were asked to report their SB (h per day) across several domains: attending class, completing schoolwork, recreational screen time, socializing, performing hobbies, and any other sedentary activities over the last 7 days. PA was investigated by asking the frequency of participation in vigorous physical activity . Participants indicated their participation level by checking one of the following categories: every day, a few times a week, a few times a month, a few times a year, and under no circumstances.Depression was measured using a nine-item Patient Health Questionnaire (PHQ-9). The responses were divided into four levels according to the frequency of symptoms in the past two weeks: never = 0 points, several days = 1 point, more than half of the time = 2 points, and almost every day = 3 points. The total score of the scale was 0 to 27 points. Those scoring 5 and above had depressive symptoms . This sc2). According to the Chinese Guideline for Overweight and Obesity Prevention, BMI ≥ 24 kg/m2 was defined as overweight. Demographic information included gender, grade, profession, place of hometown, whether only child or not, parents’ marital status and monthly family income, body mass index (BMI), smoking and drinking. BMI was calculated based on self-reported weight and height .p < 0.05.The data were analyzed using the Statistical Package of the Social Sciences . The median, inter-quartile range (IQR), mean, and standard deviation (SD) of total and domain-specific sedentary time were presented. Then, they were treated as dichotomous variables based on the median. The mean was used when comparing sedentary time with the other research reported in the Discussion section of this paper. The detection of depression, VPA, and demographic information was also treated categorically and was presented as number (%). The between-group differences were tested by the Chi-squared test (Bonferroni method). The association of depression with total and domain-specific SB and VPA was examined by a stepwise backward logistic regression, after adjusting for demographic information. Odds ratios (ORs) with 95% confidence intervals (CIs) were presented. The significance level was A total of 584 participants completed the questionnaire and were included in the analysis. The response rate was 33.4% among athlete classes and 74.3% among non-athlete classes. The basic characteristics of participants are shown in Most participants were male students (59.8%), 42.3% of the sample were freshmen, 61.8% were athlete students, 54.8% came from urban places, 57.9% were an only child in their family, 11% were overweight (BMI ≥ 24), 14.9% reported a smoking habit, and 61.6% reported a drinking habit . p < 0.001), freshmen and sophomores (p = 0.036), athlete students (p = 0.005), and students with married parents (p = 0.042)  . The time spent in SB is shown in In the following analysis, the total and domain-specific SB were treated as dichotomous variables based on the median, and the frequency of participating in VPA was regrouped into three categories for the balance of distribution in each subgroup. p < 0.001). Students from a high-income family (above 9000 CNY per month) were more likely to have longer sedentary time than students from families with lower incomes . Students participating in VPA a few times a month or less were more likely to report longer sedentary time than students participating in VPA more frequently (p < 0.001).The characteristics of the participants stratified by level of total sedentary time (≥7.29 h and <7.29 h) are presented in p = 0.009) and had less screen time (p = 0.008) and less total sedentary time (p = 0.036). Students participating in VPA a few times per month or fewer presented higher depression rates than those reporting more frequent VPA participation (p < 0.001).Stratified by the detection of depression, the levels of SB and frequency of VPA of the participants are shown in p = 0.035), while those spending more time completing schoolwork were less likely to be detected with depression . Compared with students who participated in VPA a few times a month or less, those who participated in VPA every day  and a few times per week  were less likely to be detected with depression. The total sedentary time and time spent in attending class, socializing, performing hobbies, and other sedentary activities were not significantly associated with the detection of depression  , global Potential explanations for the prevalence of depression in this study are as follows. First, unexpected demands for both academic and athletic achievements may make students overwhelmed. Non-athlete students of sport science were required to master one sport skill in addition to a heavy academic burden. Athlete students have to withstand stress from physical training and competition . Second,Anywise, our research findings suggested that the depression symptoms of students of sports universities should be taken seriously, and measures should be taken according to the results of risk factor analysis.It was found in our study that sports university students spent on average 7.70 h per day in total SB, 2.22 h in attending class, and 2.30 h recreational screen time, which were close to the results in global university students in a recent meta-analysis  . NeverthGender, PA, and obesity were potential correlates frequently examined by studies on university students. Our research found that, compared with female students, male students performed better in total sedentary time, which is consistent with the results of research among Ukrainian university students , freshmeThere are mixed results regarding the interrelationship between SB and PA . Our resOur research found that being overweight was not associated with total sedentary time, which is contrary to most previous research ,43. The A meta-analysis of studies on the general population showed that SB is associated with an increased risk of depression, although the results of the individual studies were mixed . In addiThe results of the multivariate regression showed that recreational screen time was associated with an increased risk of depression among sports university students, while sedentary time spent completing schoolwork was associated with a decreased risk of depression; total sedentary time and other modalities of SB were not significantly associated with depression. Online education and paperless schoolwork have become increasingly popular among university students, especially after the breakout of the COVID-19 pandemic. Sports university students usually complete their schoolwork on computers or mobile phones. Our study indicated that sedentary time spent on educational purposes does not increase the risk of depression; time spent completing schoolwork may have a positive effect on reducing depression and only recreational screen time was associated with the increase in depression rate. Consistent with the view of some researchers ,45, we sMoreover, our study showed that SB is a risk factor independent of VPA for depression among sports university students, which is consistent with most previous research taking depression as a health outcome ,17,18. PThis study has several limitations. First, the response rate in the questionnaire survey for athlete students was low, and the sample was from students in one sports university in Beijing. Therefore, the sample representative of sports university students needs to be considered. Second, the cross-sectional study design of this study could only analyze the association of depression with SB and PA, and could not make a causal inference. Third, the variables in our research were self-reported, which renders them vulnerable to subjectivity. The use of SB questionnaires is a developing field . GeneralIn the future, prospective cohort studies with a large-scale and more representative sample can be carried out on SB, PA, and psychological problems of sports university students to explore the causality between health behaviors and psychological problems and provide more evidence for the design of psychological interventions for this population.By investigating depression, SB, and PA of sports university students, it was shown that depression is commonly found among this population, and their sedentary time is close to the level of global university students. Our results provide evidence of the association of depression with total and domain-specific SB by showing that only recreational screen time was associated with an increased risk of depression; educational sedentary time spent completing schoolwork was associated with a decreased risk of depression, and there was no relationship between depression and other modalities of SB. This study also supported that the effect of SB on depression is somewhat independent of the frequency of VPA. Sports university students are not immune to depression and inactive lifestyles. Their mental health and health behaviors require attention. Future research on the causal relationships between various reasons for SB, levels of PA, and depression are necessary for more targeted interventions among this population.


The cardiovascular effects of training have been widely investigated; however, few studies have addressed sex differences in arteriolar adaptation. In the current study, we examined the adaptation of the gracilis arterioles of male and female rats in response to intensive training.Wistar rats were divided into four groups: male exercise (ME) and female exercise (FE) animals that underwent a 12-week intensive swim-training program ; and male control (MC) and female control (FC) animals that were placed in water for 5 min daily. Exercise-induced cardiac hypertrophy was confirmed by echocardiography. Following the training, the gracilis muscle arterioles were prepared, and their biomechanical properties and functional reactivity were tested, using pressure arteriography. Collagen and smooth muscle remodeling were observed in the histological sections.Left ventricular mass was elevated in both sexes in response to chronic training. In the gracilis arterioles, the inner radius and wall tension increased in female animals, and the wall thickness and elastic modulus were reduced in males. Myogenic tone was reduced in the ME group, whereas norepinephrine-induced vasoconstriction was elevated in the FE group. More pronounced collagen staining was observed in the ME group than in the MC group. Relative hypertrophy and tangential stress of the gracilis arterioles were higher in females than in males. The direct vasoconstriction induced by testosterone was lower in females and was reduced as an effect of exercise in males.The gracilis muscle arteriole was remodeled as a result of swim training, and this adaptation was sex dependent. The human body adapts to regular sports activities, such as adaptation processes, which appear in almost all parts of the body and at different levels of organization . During Power training  is characterized by muscle tone elevation, increased total peripheral vascular resistance, and slightly increased cardiac output. In contrast, in endurance training , cardiac output, heart rate, and blood flow velocity increase significantly, vessels in the skeletal muscles dilate, and total peripheral vascular resistance decreases .Training affects vessels in different tissues in a different manner. In vessels of skeletal muscles (involved in training), flow is transiently increased; this is in contrast to visceral vessels, where flow decreases during exercise. During physical activity, the arterial pressure can be elevated, causing a cyclic increase in vessel wall tension, leading to morphological, biomechanical, and functional adaptation of the vessel. Elevation of endothelial nitrogen-oxide synthase (eNOS) is a characteristic feature in response to increased cyclic wall tension and repetitive shear stress, and results in an increase in NO-dependent vasodilation .In the case of peripheral musculocutaneous artery branches, the diameter of the vessel increases during a single exercise bout, and the vessel wall becomes thinner. However, the dilated vessel caliber is not always observable at rest , 2017. Tin vitro pressure myograph, we found that physical training in females led to an increase in contractility, while, in males, endothelium-related dilatation capacity was increased  and EU Directive 2010/63/EU. The program was approved by the Animal Care Committee of Semmelweis University and Hungarian authorities (permission number: PEI/001/2374-4/2015).Forty young adult male and female Wistar rats (12 weeks old) were housed at a constant temperature (22 ± 2°C) with a 12-h light-dark cycle. The rats were supplied with standard laboratory rat chow and tap water in vitro studies was as follows (in mmol/l): 119-mM NaCl, 4.7-mM KCl, 1.2-mM NaH2PO4, 1.17-MgSO4, 24-mM NaHCO3, 2.5-mM CaCl2, 5.5-mM glucose, and 0.0345 EDTA (ethylenediaminetetraacetic acid). The calcium-free Krebs–Ringer solution contained 92 NaCl, 4.7 KCl, 1.18 NaH2PO4, 20 MgCl2, 1.17 MgSO4, 24 NaHCO3, 5.5 glucose, 2 EGTA (ethylene glycol tetraacetic acid), and 0.025 EDTA. Salts were purchased from Reanal . Noradrenalin (NE) and testosterone (T) were obtained from Sigma-Aldrich . The frozen aliquots were diluted daily.Pentobarbital (Euthasol) from CEVA Santé Animale  was used for anesthesia. The composition of the normal Krebs–Ringer solution (nKR) used for n = 9), male exercise , female control , and female exercise .Following 7 days of acclimatization, the animals were randomly divided into four experimental groups: male control  were subjected to a long-term (12-week-long) swim training program, which led to physiological left ventricular (LV) hypertrophy, as previously described . The aniEchocardiographic assessments were performed as described previously  to confi•Stroke volume (SV) = LVEDV – LVESV•SV index = SV/body weightin vitro vascular measurements, while the distal part of the same vessel was fixed and used for histology. The distal part of the isolated gracilis arteriole can be a bit narrower than the proximal, as it may give side branches . There can be minor variations in the orientation of arteriole segments in the paraffin blocks due to their very small size and possible side branches. The excised arteriole was immersed in warm (37°C) oxygenized nKR solution in a glass-bottomed tissue bath  and was cannulated at both ends with plastic microcannulas (approx. 100-μm diameter). For gas bubbling, a gas mixture of 20% O2, 5% CO2, and 75% N2 was used, maintained at a pH of 7.4. The volume of the bath was 12 ml, and the solution was changed at 2.8 ml/min, using a roller pump. Drugs were added to the bath to yield the required final concentration (superfusion was suspended for this period). The microcannulas were also filled with warmed, oxygenated nKR, and were connected to servo-controlled pumps  to set the intraluminal pressure. The gracilis arterioles were extended to their normal in situ length and pressurized under no-flow conditions. The organ chamber was positioned on the stage of an inverted microscope (Leica), with a light path to enable visualization of the changes in the outer and inner diameters of the arteries. Magnified pictures of the pressurized segments were acquired, using a DCM 130 E camera. Analysis of the arterioles was performed offline, using a specific image-analysis software . Length calibration was performed, using a micrometer etalon .At the end of the swimming training program, the rats were anesthetized with pentobarbital . The right common carotid artery was cannulated, blood pressure was measured, the chest was opened, and a slit was cut on the right atrium. Then, the whole body of the animal was perfused with 150-ml nKR solution. The hearts were removed, and their weights were measured. Among the adductor muscles, the gracilis muscle was identified, and its arterioles were carefully prepared under a preparation microscope (Wild M3Z) and removed. We started the preparation of the arteriole by separating the vascular bed of its from the accompanying vein and connective tissues. The proximal part of the vessel was used for the –8, 10–7, and 10–6 M; each concentration lasted 10 min), and the diameters were measured. Thereafter, without washing out the NE, the pressure diameter curves were recorded repeatedly. The drug was washed out, and the diameter of the segments was measured again after 10 min of incubation at 50 mmHg. The effects of testosterone were tested at concentrations of 10–8 and 10–6 mol/L (5–5 min for equilibration). Finally, the solution was changed to a calcium-free KR solution, and, after 30 min of incubation at 50-mmHg pressure, diameter plots in the passive state of the smooth muscle were recorded from 0 mmHg in 10 mmHg steps up to 100 mmHg.The following protocol was used to study the biomechanical and contractile parameters of the arterioles. Arterioles were taken from rats and incubated in oxygenated Krebs–Ringer solution at 50 mmHg of intraluminal pressure for 30 min. Arterioles develop spontaneous contractions under such circumstances . FollowiThe biomechanical parameters were calculated as follows:•o – ri;Wall thickness, h = r•i;Wall/lumen ratio, Q = h/d•∗ri/h, according to the Laplace–Frank equation;Wall stress, σ = P•An incremental tangential elastic modulus of the cylindrical segments;•inc = [2rori2*ΔP)/((ro2 – ri2)∗Δro];E•inc = ΔV/VΔP.Incremental distensibility was Do and ri are the actual values of the outer and inner radii in μm, di is the inner diameter in μm, P is the transmural  pressure, Δro is the alteration of the outer radius during a pressure rise of ΔP according to where h is the wall thickness in μm, rThe following parameters were calculated from the pressure-diameter data:•iCa2+free – rinKR)/riCa2+free∗100Myogenic tone (%) = (r•iCa2+free – riNE)/riCa2+free∗100Constrictions to NE (%) = (r•inKR – riT)/rinKR∗100Testosterone contraction (%) = , resulting in black (nuclei and elastic fibers), yellow (collagen and reticular fibers), red (muscle and fibrin), and blue (ground substance and mucin) areas. Sections were photographed with a Nikon Eclipse Ni-U microscope with a DS-Ri2 camera  at 10× magnification. To evaluate the results, pentachrome staining was separated into individual color channels on the images, using ImageJ software. After converting the separated images to black and white, the degree of staining was determined, using the non-calibrated optical density (OD).post hoc test was performed. In the case of non-normal distribution, the Kruskal–Wallis test, with Dunn’s post hoc test, was performed. P-values < 0.05 were considered to indicate statistically significant differences.GraphPad Prism 5 software  was used for statistical analysis. Values are expressed as means, with the standard error of the mean included. Normal distribution was tested, using the Shapiro–Wilk method. In the case of normal distribution, two-way analysis of variance (ANOVA) with Tukey’s Body mass significantly increased during the 12-week observation period, but body mass elevation was significantly lower in the trained male group than in the sedentary male group. No difference was detected regarding body mass of the FC and FE groups . The heaMales of similar ages had higher body weights than females in both the sedentary and trained groups. Some differences in the advantage of males remained in the trained group despite less extensive weight gain during exercise in these animals. The heart weight/body weight ratio measured postmortem was significantly higher in female animals (FC and FE) than in males (MC and ME) .The echocardiographic data are shown in No significant difference was found in LV wall thickness between the control male and female sedentary groups, with the exception of LVPWTs, which were lower in females. The stroke volume was lower in female rats than in male rats in both the control and exercised groups. In contrast to SV, the SV index was significantly higher in females in both the control and exercise groups. The LVAWTs, LVPWTd, and LVPWTs were significantly smaller in female-exercised rats than in exercised-male rats.Despite the fact that all harvested arteriolar segments were anatomically and morphologically identical at preparation, there was a significant difference in the inner radius of the vessels between the groups in the relaxed state. The inner radius was significantly higher in the female-exercised animals than in the control females . The walImportantly, the inner radius elevation could only be observed in the exercised females. While there was no significant difference in the inner radius between the sedentary males and females, the exercised females had wider gracilis arterioles than the males . MoreoveThe myogenic tone of the gracilis muscle arterioles in the male exercise group was significantly lower than that in the vessels harvested from MC rats . In termA training-induced reduction in myogenic tone was only observed in the male animals. Sex differences in myogenic tone did not reach statistical significance in either the control or trained groups . TraininThe medial smooth muscle content was not significantly altered by the training . The denThere was a significant difference between the male-control and female-exercised animals; the FE rats demonstrated more intense muscle staining in their tunica media than the MC rats . MoreoveIn the current study, we examined the effects of exercise training on gracilis muscle arterioles in the male and female rats. To the best of our knowledge, this is the first study to investigate sex differences in a swim-training model of skeletal muscle arteriole biomechanics and pharmacology. The major findings of our investigation can be summarized as follows: (1) The massive exercise load of our protocol is demonstrated by the development of an “athlete-type” heart in our animals. (2) Vascular adaptation in the trained muscle showed sex differences in that the females showed an increase in the supplying arteriolar diameter (dilatation), while the males demonstrated thinning of the arterial wall . (3) Wall tension increased in the exercised females as a result of vascular dilatation, while, in males, the elasticity of the vessels was increased. (4) As a result of swimming, the adaptation range (the range between maximum contraction and maximum relaxation—it determines the ability for vasomotion) of the gracilis arteriole widened during both contraction and dilatation, but this proved to be dependent on sex; myogenic tone decreased in the males, while the maximum contraction capacity increased in the females. (5) Our histological findings also showed sex differences in response to physical exercise. In the females, the smooth muscle content of arterioles increased, while in the males, there was more collagen in the media. These results confirm our theory that sex plays an essential role in the sport adaptation of skeletal muscle arterioles. Further studies may provide a basis for the implementation of individual/sex-optimized training programs.Echocardiographic examinations were performed to test the training status of the animals. In accordance with our previous results and published data in the literature, 12 weeks of the swim training leads to substantial myocardial hypertrophy in both males and females .Although training adaptation of peripheral vessels has been examined in several earlier studies, part of these observations is focused on larger (conduit) arteries . AlteratIt is known that the walls of the peripheral arteries thicken and their diameter increases as a result of physical exercise , 2017. Ein vitro pressure myograph to track the morphological parameters of vessels in their passive state, from which the biomechanical parameters were derived. Elastic parameters are connected to geometry and will be discussed in the later subchapter.The effect of training the wall stress increased in the females, while no change was observed in the males; this may be caused by the enhanced vascular diameter, and the fact that the wall tension is directly proportional to the lumen radius of the vessel and inversely proportional to wall thickness. In the literature, both increases and decreases in vascular wall tension have been reported as effects of training in different vessels . These cThe functional adaptation caused by training was not uniform along the vascular system. The vessel segments have different functions, depending on their size, location in networks, and lying in different vascular beds. Small vessels and arterioles contract spontaneously if common physiological conditions are present; a spontaneous or myogenic tone can be observed. There are contradictory findings in the literature concerning the effect of chronic exercise on myogenic tone, with studies showing increased, decreased, and unchanged basal arterial tone . In oldeIn our studies, the vasoconstriction-lowering effect of training could be observed in young male rats. There is an observation according to vascular adaptation in trained elderly animals can be different in metabolically different types of muscle. High oxidative portions of gastrocnemius (red gastrocnemius) are low perfused, while low-oxidative portions of gastrocnemius (white gastrocnemius) are relatively highly perfused when compared with young animals . EnduranThe length and extent of training can explain the difference between these observations. We found that 12 weeks of strenuous work is sufficient for geometrical and histological wall remodeling. Moreover, even the sympathetic innervation of these vessels could have changed when sufficient time was provided.Testosterone has an acute vasoactive effect; the strength of which varies according to species and vessel types . In our The absolute cardiac parameters measured by echocardiography were significantly lower in the females but were higher when adjusted to the lower weight of the female animals. Based on the literature, the Akt-protein may play a role in the enhanced relative cardiac hypertrophy of females. In our previous study, phosphorylation of Akt increased in both sexes as a result of exercise but was more pronounced in the females . In an eSignificant sex differences were observed in the control group with respect to the wall thickness. In exercised female animals, we found an increase in the inner vascular diameter, while the wall thickness remained unchanged. This increase was more pronounced than in the case of the exercised males. The male controls had thicker vascular walls, the trained males had narrower vascular diameters, and the wall thickness/lumen ratio was higher in the males than in the females in both the control and trained groups. The effect of sex differences on the vascular wall thickness/lumen ratio in gracilis and other arterioles was studied in previous studies on hypertension . SimilarThe observed higher wall thickness/lumen ratio in our male animals resulted in lower vascular wall tension of the gracilis vessels in both the control and trained groups.The distensibility and elastic modulus are parameters that describe the elasticity of the vessels. Higher distensibility and lower elastic modulus result in greater vascular elasticity. The elasticity of the gracilis vessels increased as a result of training, but it showed sex-related differences. In the males, the elastic modulus decreased, whereas, in the females, the distensibility increased at low pressures. Similar to our findings, a decrease in elastic modulus and an increase in distensibility of resistance coronary arteries were observed in the rats trained on a treadmill . The incSimilar results have been found in a previous study on coronary arterioles of swimming rats, in which the myogenic tone of trained male rats was significantly lower than that of females . In contIn aortic rings of rats after 10 weeks of training, there was a reduced norepinephrine sensitivity. It could be observed only after 4–10 weeks of training. Removal of endothelium diminished that reduced sensitivity, proving its endothelial origin .Based on this and on our observations, it may be considered that, as a result of training, the vascular reactivity increases in both sexes; in trained males, relaxation is more pronounced, while, in trained females, higher contraction is observed. The regulatory effects of estrogen and testosterone may play a role in these effects, and further investigations are needed to explain the observed sex differences.Substantial sex differences could be demonstrated in the acute vasoactive effect of testosterone; the most intensive contraction was found in the male control animals, which decreased to the level of the females as a result of exercise. One explanation for this phenomenon is that exercise increases the metabolism of testosterone to estrogen, which compensates for the vasoconstrictor effect of testosterone . In addiOur histological observations also showed sex differences in the training-induced histological remodeling of skeletal muscle arterioles. While females improve their smooth muscle ratio, male rats enhance the amount of collagen in the tunica media. The differences in the histological composition may be related to the observed differences in wall elasticity and contractility.One limitation of our experiments is that they have been performed on relatively young animals, which makes it difficult to adapt to mammals with a slower life cycle, or to humans, where circulatory problems arise mostly in advanced age. Further observations are needed to reveal the degree to which different sex hormones are responsible for the observed sex differences.As a result of a strenuous swimming exercise program, a peripherally located skeletal muscle arteriole, the gracilis arteriole adapts to physical activity; this adaptation shows sex differences: In the females, the wall thickness remained unchanged, and the diameter increased, while, in the males, the diameter remained the same, and thinning was observed in the vessel wall. In the males, the elastic modulus decreased due to exercise, while, in the females, increased distensibility was observed. Sport adaptation also appears in the altered contractility of the vessels, and we succeeded to identify substantial sex differences in the sport-induced alterations of basal and induced tones. In the males, the myogenic tone decreased, whereas the maximum contraction was enhanced in the females. The biomechanical and functional changes following chronic physical activity may be considered as physiological regulation. The observed processes ensure increased flow during physical activity, defense against increased wall stress during work dilation, and represent a convenient way to reduce blood flow during inactivity.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The animal study was reviewed and approved by the Animal Care Committee of Semmelweis University and Hungarian authorities (Permission Number: PEI/001/2374-4/2015). Throughout the experiments, the regulations of the “Guide for the Care and Use of Laboratory Animals” by the National Institutes of Health  and the EU Directive 2010/63/EU were followed.PM: formal analysis, investigation, data curation, and writing—original draft, review, and editing. MB and AM-K: investigation, data curation, and writing—review and editing. BB, EH, RB, JB, and AO: investigation, formal analysis, data curation, and writing—review and editing. TR, BM, and SV: conceptualization, methodology, validation, writing—review and editing, and funding acquisition. NÁ: conceptualization, methodology, validation, and writing—review, and editing. GN: formal analysis, data curation, investigation, conceptualization, methodology, validation, writing—review and editing, and funding acquisition. MT: formal analysis, investigation, resources, data curation, writing—original draft, review, and editing, visualization, validation, and project administration. All authors contributed to the manuscript, and read and approved the final version of 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.


Background: Drug-induced thrombocytopenia (DITP) is a severe adverse reaction and a significantly under-recognized clinical problem in children. However, for post-marketing pharmacovigilance purposes, detection of DITP signals is crucial. This study aimed to develop a signal detection model for DITP using the pediatric electronic medical records (EMR) data.Methods: This study used the electronic medical records collected at Beijing Children’s Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DITP. In the first stage, we calculated the crude incidence by mining cases of thrombocytopenia to select the potential suspected drugs. In the second stage, we constructed propensity score–matched retrospective cohorts of specific screened drugs from the first stage and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The novelty of the signal was assessed by current evidence.Results: In the study, from a total of 839 drugs, 21 drugs were initially screened as potentially inducing thrombocytopenia. In total, we identified 18 positive DITP associations. Of these, potential DITP risk of nystatin  and latamoxef sodium  were two new DITP signals in both children and adults. Six associations between thrombocytopenia and drugs including imipenem , teicoplanin , fusidic acid , ceftizoxime sodium , ceftazidime , and cefepime  were considered as new signals in children.Conclusion: This study developed a two-stage algorithm to detect safety signals of DITP and found eighteen positive signals of DITP, including six new signals in a pediatric population. This method is a promising tool for pharmacovigilance based on EMR data. The platelet count is usually less than 100×10en death . DITP deen death . The woren death . It has en death , neuroloen death , and anten death , could len death .A spontaneous reporting system (SRS) remains the cornerstone of post-marketing drug safety surveillance at present in China, despite its limitations, such as lack of denominator data to calculate incidence, underreporting, and delayed reporting of adverse drug reactions (ADRs). Considering the limitation of the passive surveillance system, active surveillance using routinely collected health data, such as electronic medical records (EMRs), has become an essential complementary method for drug safety in the clinical practice . CompareSeveral studies have been conducted to develop methods for detecting DITP signals using electronic health records  using laThis study aimed to develop a two-stage procedure to detect signals of DITP in the child population using EMR data, and provide candidate drugs for further precise drug monitoring and causality validation studies.We conducted this retrospective cohort study using Beijing Children’s Hospital (BCH) longitudinal inpatient database, which has been described previously . If a peThe study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board (IRB) of Beijing Children’s Hospital, Capital Medical University , with a waiver of informed consent. All the data we used have been de-identified to protect patients’privacy and confidentiality. This study was reported according to the RECORD-PE statement.9/L after study entry were excluded  was < 100×10excluded .9/L after administration of a particular medicine within the appropriate therapeutic dose range.The laboratories of BCH are certified and accredited under the appropriate International Organization for Standardization standards. According to the Guidelines for Medical Nomenclature Use of Adverse Drug Reactions, issued by the National Center for ADR Monitoring of the China Food and Drug Administration (CFDA) in 2016 and the method of IHI Global ADR Trigger Tool , the tri1) Considering the confounding by indication, we excluded the records of patients containing a diagnosis of diseases that affects PLT shown in . The rem1), and the time for discharge of each hospitalization of every involved patient was labeled as Timestamp 2 (T2). We calculated the number of drug users (b) during the period of T1–T2.2) The time when a patient in Group 1 obtained an initial normal platelet count results after admission was signed as Timestamp 1 .3) The hospitalization records of patients in Group 1, which were potential DITP events during T1–T3.4) We calculated the number of users for each medicine in Group 2 who were identified by DITP trigger (a) during the period of T5) The ratio a/b for each drug was calculated. The suspected drug met the following criteria were selected for further association analysis: 1) the ratio a/b > 0.120, considering the a/b values of solvents for intravenous infusions, such as normal saline and glucose injection, ranged from 0.092 to 0.118, which can be regarded as the value of background since it is well known that normal saline and glucose injection have no effect on DITP; 2) number of total users (b) > 1,000, ensuring sufficient sample size and adequate power.To identify suspected drugs potentially associated with DITP for further association analysis, we developed a fifth-step workflow see in . Only noAccording to the above screening procedure of suspected drugs, we conducted a series of retrospective propensity score-matched cohort studies to detect the association between suspected drugs and DITP by comparing differences in DITP event rates between the exposed and unexposed groups.9/L before index time. To accurately assess the drug–DITP associations, patients who were diagnosed with medulla-suppressed diseases  and its 95% confidence interval (CI) were estimated to assess the association between specific suspected drugs and the incidence of DITP events. The signal of DITP was positive if the lower limit of the 95% CI of OR was greater than 1.0; otherwise, it was regarded as a negative signal.Not all statistically significant associations could be regarded as potential new signals. Thus, further validation was needed to evaluate these signals. Since there was no recognized gold standard for evaluating the relevance of the DITP association, we performed a manual review of the summary of product characteristics (SPCs) included in the Micromedex, DXY Drugs Information, and electronic literature databases, including PubMed, Embase, and China National Knowledge Infrastructure and Wanfang Database. In addition, according to the published literature about adults and children, George JN et al. established DITP-related drug database, which had been updated till 2018 . AccordiWe compared the baseline characteristics of each screened suspected drug group and the unexposed group. For each patient, we calculated person-time of follow-up as the amount of time from the index time to the end of follow-up. DITP incidence rates were calculated for each cohort. We calculated propensity scores for the initial prescription of a specific suspected drug using the logistic regressions. The variables included in the model included age, gender, admission time, and major diagnosis (based on the classification in ICD-10). For a particular suspected drug, the records from the exposed group were matched 1:4 to those of the unexposed group using the caliper matching method . Then we compared the OR of DITP in each specific suspected drug cohort with the corresponding unexposed group cohorts using conditional logistic regression models. Patients with missing values for age, gender, and admission date were excluded from the analysis. We also performed sensitivity analyses to assess the robustness of our findings. We used the propensity score regression method other than matching in the primary analysis.p values were two-sided, and p < 0 0.05 was considered significant for all tests. MySQL software version 14.14  was used as the database management system to extract the required data from BCH’s EMR database. Data were processed and summarized using the pandas v1.2.2 model in Python 3.7. R 3.5.2 software  was used for statistical analysis, and SAS 9.4 TS Level M5  was used for forest plot demonstrating the results of association analysis.All After combining drugs with the same ingredients and ATC but different dosages and forms, 388 drugs remained. Among these drugs, 210 satisfied the screening criteria that the total number of drug users was >1,000, and the rate of a/b was beyond 0.12. After excluding the chemotherapy drugs and drugs that affected PLT count, 186 suspected drugs were identified as suspected drugs and were selected for further analysis for DITP signals. Among them, 21 drugs met the inclusion criteria . These were amphotericin B, chlorpheniramine, vancomycin, imipenem, fluconazole, sulfamethoxazole, loratadine, meropenem, promethazine hydrochloride, teicoplanin, nystatin, fusidic acid, ceftizoxime sodium, ceftazidime, cefpiramide, cefepime, linezolid, cefoperazone sodium and sulbactam sodium, milrinone, heparin, and latamoxef sodium. These twenty-one drugs were considered as suspected drugs and chosen for DITP signals detection in stage 2 .The results of data extraction for the suspected drugs for each step are presented in p < 0.001, see details in p < 0.001), one antifungal , one cardiotonic , and one anticoagulant . The remaining three drugs  were found not associated with DITP. The detailed results of all the 21 drug–DITP associations are shown in Of the 21 suspected drugs, 18 showed positive signals including 14 anti-infective drugs , except for amphotericin B. The OR of amphotericin B and DITP was 2.24 , which was different from that in the primary analysis using the PS matching method .The novelty of 18 positive DITP signals observed in stage 2 was further evaluated through SPCs and current literature . Two druUsing the two-stage data-driven algorithm, our study found that nystatin and latamoxef sodium were associated with DITP in both adults and children. In addition, imipenem, teicoplanin, fusidic acid, ceftizoxime sodium, ceftazidime, and cefepime were associated with DITP in children. These drugs may be the suspected drugs for post-marketing surveillance and regulation.George JN et al. systematically reviewed the published case reports about DITP from 1966 to 1997  and estaDrug-induced thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient, especially for critically ill patients . Often tS. nunsei and structurally similar to amphotericin B, is a kind of polyene macrolide antibiotic that mainly inhibits the cholesterol in the cell membranes of fungi and mycoplasma. Although we did not find any reports about nystatin-induced thrombocytopenia, the other polyene macrolide antifungal drug amphotericin B also acted on sterols of fungal cell membranes, which was documented to induce thrombocytopenia in some cases. One in vitro study found that amphotericin B’s effect on platelet membrane GP (GP1b) was concentration-dependent and could be influenced by duration of platelet storage   . FurtherThe association between latamoxef sodium and thrombocytopenia was considered another new signal. Latamoxef sodium is a beta-lactam antibiotic used to treat various infections caused by sensitive bacteria. The mechanism of some other kinds of beta-lactam antibiotic–induced thrombocytopenia were that they could induce the production of antibodies, which would bind to platelet membrane protein only in the presence of drug or interact with platelet antigen . DespiteStaphylococcus aureus infection. The hematological side effects such as thrombocytopenia have been rarely reported in European and Asian adult populations  were identified as potentially new signals in children. All these drugs are anti-infectives for systematic use (their ATC codes are classified in J). Imipenem is a new class of carbapenem antibiotics, and it has the broadest antibacterial activity of all antibiotics available for systemic use in humans . Some adulations . Ceftizoulations . Similarulations . BecauseCompared with the proposed tool with those based on the spontaneous reporting system, our study integrated multisource data from the hospital information systems, biochemical laboratory, and drug prescription records. The active surveillance based on the routinely collected data integration is an effective approach for pharmacovigilance, which can detect a previously unrecognized adverse drug signal in the real practice immediately as well as provide more detailed information about symptoms, signs, diagnosis, timing sequence, and medication to analyze the potential association for drug–ADR pairs. Recently, some novel studies about ADR signal detection have been developed. Lee S et al. developed a comprehensive controlled vocabulary-based ADR signal dictionary and integrated this tool with an electronic health record for real-time large-scale pharmacovigilance studies . When deGiven that this study was a hospital-based observational design, several limitations on this research should be noted. First, although testing for antibiotic-induced antiplatelet antibodies remains the gold standard in the diagnosis of DITP, we had no access to the laboratory confirmation of DITP at the time of initial presentation because tests for drug-dependent antiplatelet antibodies are not available in most clinical laboratories. Given the feasibility, we chose PLT counts as the trigger of DITP to detect signals. Second, dose-related effects and possible residual confounders, such as concomitant drugs and the time-varying confounding by underlying diseases, were not controlled, leading to potential bias. Third, since our study is only based on EMR data from a single center, the sample size of some exposure to specific drugs, such as amphotericin B, was small and limited, which could lead to poor representation of results. Regulatory agencies have spared no effort for facilitating ADE signal detection through multiple heterogeneous data sources at present .Notable progress has been made in China in establishing the project named “China ADR Sentinel Surveillance Alliance” (CASSA) . At presIn this study, we developed a pharmacovigilance method to explore potential DITP signals using routine EMR data. The two-stage designed algorithm was performed to first select suspected drugs and then determine the associations between DITP and drugs. Eighteen positive signals of DITP, including six new signals in children, were detected. Our study promotes the application of EMR datasets in pharmacovigilance and offers candidate drugs for further causality assessment studies.


Background: The main theme of this systematic review and meta-analysis is to synthesize the evidence of randomized controlled trial of evidence of Pilates intervention, in comparison to control groups and other forms of exercise, for falls prevention in healthy older adults.Methods: The following electronic databases were searched up to October 2020; EMBASE, Scopus, Google Scholar, MEDLINE (Ovid), Science Direct, Cochrane, and CINAHL. The recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses were followed. A PICOS approach was adopted as a framework to formulate the research question and set the inclusion and exclusion criteria. Participants were healthy older adults, defined as older adults who have maintained functional ability, including participants of both genders, those with a falls history, non-fallers, and individuals who were considered to be sedentary or active. Randomized controlled trials studies, written in the English language, from the decade, were included if they focused on specific outcome measures to decrease falls risk; functional mobility, mobility, fear of falling, gait, and postural stability. The PEDro scale was used to assess risk of bias.Results: There were included 12 studies. In total, 702 healthy older adults' participants were included. Pilates showed an effect in mediolateral directions in comparison to control groups , mobility  and fear of falling . In relation to other exercises group, Pilates showed positive effects in functional mobility , mobility . No evidence of an improvement was found between the groups for dynamic gait index , anteroposterior directions of balance  and functional mobility when compared to control groups (no exercise) .Discussion: Pilates may be effective in decreasing the risk of falls in older adults. Pilates intervention was found to improve functional mobility, mobility, gait, fear of falling and postural stability and therefore there is some evidence to suggest that Pilates reduces certain risk factors for falls in healthy older adults. However, there is an absence of high-quality evidence in regards to the impact of Pilates on reducing falls and further robust RCTs are needed.Systematic Review Registration: [PROSPERO], identifier [CRD42021206134]. A fall is “an unexpected event in which the participant comes to rest on the ground, floor, or lower level” [, p. 1618The aging process is associated with decreased walking ability and walking speed. In individuals between the ages of 25 and 75 years, it is known that muscle power declines by 49% and muscle strength declines by 33% in this period . In oldeThe Pilates method was developed in the 1920's by Joseph Hubertus Pilates and based on “Contrology” which aimed to coordinate the balance of the body, mind and spirit. The Pilates method also focused on concentration, strength and mobility . PilatesSeveral previous systematic reviews –18 have A recent meta-analysis of Pilates found improvement in postural stability in older adults , 20. TheThe systematic reviews and meta-analyses are important because they summarize the empirical evidence and analyse the results of Pilates intervention studies. They summarize information with regard to the effectiveness of Pilates RCTs for health care professionals which, might help to inform them and their clinical practice of the benefits of Pilates interventions for older adults. However, previous meta-analyses on the effectiveness of Pilates in falls prevention have shown that studies are still lacking and there is no definitive evidence on Pilates interventions in reducing/ preventing falls. Furthermore, it is still unclear whether postural balance and gait can be improved with Pilates intervention. Regarding gait, there is a distinct lack of data concerning the potential impact of Pilates intervention on the spatiotemporal parameters of gait in healthy participants, and there is a dearth of evidence from RCTs and systematic reviews. Relating to balance, a previous meta-analysis did not separate the measures of postural balance for fall risk, such as mediolateral and anteroposterior parameters and fear of falling, in healthy participants. It is important to address and clarify these fall factors to reduce any knowledge gaps for future researchers.Further improvements in the clinical practice of Pilates for specific age groups and guidelines are needed in the context of Pilates, since broader falls prevention guidelines are available. Therefore, it is necessary to include the following in meta-analyses: randomized clinical trials (RCTs) in evidence-based Pilates practice; falls protocol for longer follow-up; and recording falls during the intervention . The research question asked whether Pilates training reduces the risk of falls in healthy older adults, defined as older adults who have maintained functional ability, including participants of both genders, those with and without a fall history and those considered sedentary or active.The main theme of this systematic review and meta-analysis is to synthesize the evidence of RCTs of Pilates intervention in comparison to control group (no exercise) and to other exercises focuses on reducing the risk of falls by improving falls risk factors for the following outcome measures; mobility, functional mobility, fear of falling, gait, postural stability and falls recorded during the Pilates intervention.This systematic review and meta-analysis followed the general guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The protocol for this systematic review registered in the International Prospective Register of Systematic Reviews (PROSPERO) number CRD42021206134.The studies selected met the following inclusion criteria using PICOS:Population (P): Healthy older adults 60 years of age and older .Intervention (I): All Pilates interventions, including mats, accessories and equipment.Comparators (C): A comparison of Pilates training with parallel groups, including a control group with no intervention and a control group with other exercises.Outcomes (O): Pre- and post-tests with regard to fear of falling, mobility, functional mobility, gait and postural stability by platform.Study design (S): RCTs and peer-reviewed publications written in the English language and dated between 2010 and 2020.Not all studies included were necessarily aimed at evaluating the effects of Pilates in preventing falls in older adults. This was due to a lack of studies that investigate the effect of Pilates on falls prevention specifically.The exclusion criteria were: participants with neurological impairment or orthopedic conditions such as lower back pain; the use of dynamic balance to evaluate balance and with no platform used for postural stability and non-RCT studies, such as semi- or quasi-experimental studies.Electronic databases EMBASE, Scopus, Google Scholar, MEDLINE (Ovid), Science Direct, Cochrane and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), were searched until 30th of October 2020.The following search terms were used: Pilates AND healthy older adults, OR elderly OR aged, fall prevention OR risk of fall, fear of falling, postural balance OR balance, functional mobility, gait OR spatiotemporal parameters of gait AND randomized controlled trial.www.covidence.org).The Covidence systematic review component of Cochrane 1.0 extraction was used for importing citations, managing screening and data extraction by the reviewers (The citations were imported into the Covidence systematic review software where any duplicate papers were excluded. Titles and abstracts were screened by two independent reviewers (LD and CM). Any disagreements between the reviewers were mutually resolved to reach a consensus. Potentially eligible articles were then reviewed in full text by two authors (LD and CM) and any disagreements were mutually resolved to reach a consensus.Data were extracted independently by two reviewers (LD and CM) in Covidence. Consensus was reached at a later meeting between the two authors. Data extracted included participant demographics (age and sample size), study details , study design, setting or recruitment, aim, intervention groups and inclusion criteria. Pilates intervention description , participants analyzed, findings and recommendations.The primary and secondary outcomes selected are associated with a decreased fall risk in older adults. Functional mobility: The TUG test is a sensitive and specific tool to identify community-dwelling adults who are at risk of falling, including older adults who have balance impairments and who live independently within a community. Older adults who scored ≥ 13.5 s to perform the TUG were classified as fallers with an overall accurate prediction rate of 90% .The parameters of postural stability: The anteroposterior parameter was associated with a history of falls for the conditions of eyes opened and eyes closed on a firm surface . ImpaireTasks related to gait changes have been identified as fall predictors  among olPrimary outcomes included functional mobility (the Timed-Up-and-Go-TUG task), mobility as the functional reach test (FRT), fear of falling  and postural stability by force platform using COP displacement to evaluate the parameters in mediolateral (ML) and anteroposterior (AP) directions under both eyes open and closed conditions.Secondary outcomes included falls in the past year (within 12 months), the number of falls recorded during the study, gait  and the Dynamic Gait Index (DGI). In case of incomplete or missing data for spatiotemporal parameters of gait for RCTs in healthy subjects.The risk of bias in assessing the quality of the included studies was evaluated by two independent reviewers (LD and CM). Consensus was reached at a later meeting between the two authors.http://www.pedro.org.au/english/downloads/pedro-scale) for RCTs, which contained 10 questions to assess the study quality. A study score of 6–10 is considered moderate to high quality and a score <5 is considered lower quality according to their guidelines (http://www.pedro.org.au/english/downloads/pedro-statistics/). Consensus was reached by the two independent graders and there was no requirement for a third reviewer to resolve disagreements.The inclusion criteria were evaluated using the Database of Physiotherapy Evidence (PEDro) scale . A value of α = 0.05 was considered statistically significant.Data were entered in the software as mean and standard deviation (SD) and the total number of participants in each study allocated into groups. The author considered whether the studies reported on whether or not intention- to- treat analysis was used.https://training.cochrane.org/handbook/current/chapter-06#section-6-5-2. If the extracted data were incomplete, the author was contacted by email for more details.Data reported as standard errors or confidence intervals (CIs) were converted to SD using I2 ≤ 50% and a random-effects model with I2 ≥ 50% were used. Forest plots presented the comparison between the Pilates intervention group and the control group with no exercise. The variables TUG and FRT were also analyzed for Pilates vs. other exercise groups. Dichotomous data for the number of falls in participants during the previous year and the number of falls during the intervention were reported as exploratory due to the lower reporting of data during the intervention programme.Continuous data outcomes were reported as the mean difference (MD) were reported with 95% CIs. Postural stability included two subgroups to evaluate the estimating effects for the variables for mediolateral directions  and for anteroposterior directions . Assuming pooled effects, a fixed-effects model with heterogeneity A total of 1,720 records were screened and 1,657 were excluded. A total of 63 studies were assessed for full-text eligibility and 51 were excluded. Twelve RCT studies were identified after the selection process for systematic review and meta-analysis; one study was excluded as the authors included path length variable as opposed to ML and AP variables of balance  see Fig. The stuIn total, 702 participants were included, with 308 allocated to Pilates group (PG), 316 to Control group, (CG) and 78 to the three-arm exercise group.Nine studies included both men and women , 30–37, Participants were healthy older adults, defined as older adults who have maintained functional ability (WHO). Six studies included healthy participants , 34, 36.n = 338 participants), shared between the Pilates group (n = 168) and control group (n = 170).At baseline, six studies –35, 37 rn = 283 participants) in the previous year at baseline before being allocated to the intervention programme. In the Pilates group (n = 141 participants), the number of fallers was 49 and in the control group (n = 142 participants), the number of fallers was 43. One study reported no events  in the control group .This study focused on the PICO method. The intervention included all types of Pilates methods, but the variables “intensity,” “dose,” and “type of Pilates method” could not be considered in the meta-analysis The strength of this study design is in its synthesisation of the results from the RCTs and the outcomes of fall risk factors.  compared Pilates vs. the traditional group (other exercise group), allocating n = 10 fallers to the Pilates group and n = 8 fallers to other exercise group.Only Josephs et al.  (n = 31 n (%) = 7.5% .Barker et al.  was the Roller et al.  reportedp = 0.703; no statistical significance was found.Josephs et al.  reportedn = 13) and control group (n = 11) during the 24-week follow-up intervention programme. This study was the only one to report the rate of falls per 1,000 person-days across groups, which was calculated as the difference incidence rate ratio = 1.17 . They also stated that n = 2 falls (10%) occurred during the Pilates classes.Barker et al.  reportedn = 77) and the control group with no intervention (n = 74). Badiei et al. .The results show a decreased fear of falling score and statistically significant between groups in favor of the Pilates group:  and two subgroups for anteroposterior directions  (n = 408) in the meta-analysis. All participants (n = 924) were allocated to the Pilates (n = 450) and control  subgroups. The three-arm study (Pilates vs. other interventions) by Mesquita et al.  for 30 s in all the included studies. The studies included balance bipedal performance , quiet sp = 0.001, heterogeneity: I2 = 3%)—the postural stability of the subjects increased  and the control group with no intervention (n = 141). MLEO showed improvement in controlling postural stability with a decrease in the score and significant differences were found between the groups in favor of Pilates intervention: .MLEO: Four studies , 34, 38 n = 116) vs. the control group with no intervention (n = 123). MLEC showed improvement in controlling postural stability with a decrease in the score and significant differences were found between the groups in favor of Pilates intervention:.MLEC: Three studies , 31, 34 Of the 418 participants included in this study, 198 were assigned to the Pilates group and 210 to the control group.p = 0.15, heterogeneity: I2 = 51%) —the postural stability of the subjects increased  vs. the control group with no intervention (n = 114). No difference was found between the groups: .APEO: Three studies , 34, 38 n = 89) vs. the control group with no intervention (n = 96). No difference was found between the groups: .APEC: Two studies , 34 inclp < 0.01) the individual could walk in 6 min (6 MWT)   and the Two studies were included in this meta-analysis , 33, witp = 0.06, heterogeneity: I2 = 86%).Participants showed an increase in their balance and gait scores with Pilates intervention; however, no significant difference was found between groups: .The results show no significant difference between the groups. There was a decrease in the time score (seconds) after Pilates intervention in favor of Pilates: .The results show a statistically significant difference between the groups and improvements in functional mobility in favor of the Pilates group by a decrease in the time score (seconds) after Pilates intervention: .There was a statistically significant difference between the groups and an increase in scores after Pilates intervention: . There was no evidence of heterogeneity.There was a statistically significant difference between the groups and an improvement in the Pilates group, as evident from an increase in the score after Pilates intervention (fixed-effects estimation):  for gait. Moreover, it was not possible to analyse gait due to the lower number of studies included.This systematic review and meta-analysis included only RCTs, meaning the quality and rigor of the methodology were increased. Further outcomes and more evidence from RCTs must be provided. Future studies should consider the number of falls and of faller participants among their primary outcomes during the intervention programme. In addition, studies should include a diary of falls for everyone or an electronic app to monitor the daily falls of each participant. Future studies should investigate any benefits in saving cost of groups and classes with a supplementary home-based Pilates intervention or an individual home-based exercise. May the risk of bias increasing; however, it is difficult to blind the participants and the instructor. Studies with a longer follow-up period are warranted.There is some evidence to suggest that Pilates reduces certain risk factors for falls in healthy older adults. Pilates intervention, when compared to control groups, was shown to improve functional mobility, general mobility, postural balance, gait, and fear of falling of healthy older adults, which may decrease their risk of falls. Pilates intervention, when compared to control groups, showed no improvement in functional mobility than other exercises. Pilates did, however, show greater improvement in mobility than other exercises. It is evident that 4–6 weeks of Pilates intervention without equipment had positive results on general mobility. Pilates was found to improve fear of falling and postural stability in the mid-lateral directions with eyes open and closed, thereby potentially decreasing the risk of falls. Other evidence has shown conflicting results with regard to balance and postural stability including different measures. Further robust studies are needed to evaluate the number of falls and to incorporate falling participants into a Pilates intervention programme with longer follow-up. The intervention programme, including different methods, has implications for future research with regard to the use of mat Pilates, equipment and the number of weeks required for the Pilates intervention.The original contributions presented in the study are included in the article/supplementary files, further inquiries can be directed to the corresponding author/s.LD: study design, database management and search strategies, screened studies for inclusion, extracted data, quality of data extraction, and data extraction for meta-analysis, analysis, acquisition, or interpretation of data, and drafting of the manuscript, wrote and reviewed the manuscript, critical revision of the manuscript for important intellectual content. CM: designed the review, screened studies for inclusion, extracted data, checked quality of data extraction, contributed to writing and editing the review, advised on the review, and approved final review prior to publication, critical revision of the manuscript for important intellectual content. AS: study design and reviewed the manuscript. All authors contributed to the article and approved the submitted.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.


Background: Even though traumatic brain injury (TBI) is a major cause of morbidity and mortality in children around the globe, population-based and nation-wide data to assess the burden of TBI is scarce.Methods:Based on diagnosis related groups from nation-wide hospital data, we extracted data on all TBI-related hospitalizations in children <18 years in Germany between 2014 and 2018. We calculated crude, age-specific and standardized incidence rates for hospitalizations, imaging, intracranial injury, neurosurgery, and mortality.Results:Out of 10.2 million hospitalizations, we identified 458,844 cases with TBI as primary or secondary diagnosis, resulting in a crude incidence rate of 687/100,000 child years (CY). Age-specific rates of computed tomography were below 30/100,000 CY until the age of 10 years and increased to 162/100,000 CY until 17 years of age. Intracranial injury was diagnosed in 2.7%, neurosurgery was performed in 0.7% of patients, and 0.7% were mechanically ventilated. Mortality was 0.67/100,000 CY (0.1%).Conclusions:Despite substantial hospitalization rates for pediatric TBI in Germany, the rates of imaging, the need for mechanical ventilation, neurosurgery and mortality were overall very low. Reasons for hospitalization and measures to reduce unnecessary admissions warrant further investigation. Traumatic brain injury frequently occurs in children and represents a relevant cause of pediatric morbidity and mortality worldwide , 2. TypiIn European countries, annual standardized hospitalization rates after TBI vary between 81 and 643/100,000 persons (children and adults). With 584/100,000, Germany has the second highest annual hospitalization rate in Europe but with a rather low mortality of 8.3/100,000 . For chiThe aim of this study was to calculate nation-wide population-based rates of pediatric hospitalizations for TBI, imaging, treatment, and mortality in Germany. We analyzed a comprehensive data set provided by the Federal Bureau of Statistics that contains information on all hospitalizations of patients <18 years in German hospitals between 2014 and 2018.Since 2004, imbursement for German hospitals is based on diagnosis related groups (DRG). By law (§21 KHEntgG), German hospitals must transmit data on all hospitalizations to the Hospital Remuneration System (InEK). After plausibility control, data are anonymized and forwarded to the Federal Bureau of Statistics. As the submission of hospitalization data is mandatory for reimbursement, hospitals have a strong incentive to supply a comprehensive data set.https://www.forschungsdatenzentrum.de/en/health/drg.For this study we analyzed 10,244,649 hospitalizations of patients <18 years between 2014 and 2018 from all hospitals in Germany. Information on the structure of the DRG data set is supplied by the Federal Bureau of Statistics and has been described in detail elsewhere (We extracted cases with primary or secondary diagnosis of traumatic brain injury (TBI) according to the International Classification of Diseases, 10th Edition, German Modification (ICD-10-GM) (ICD-Code: S06). To assess the clinical course, we extracted information on secondary diagnoses and procedures based on ICD codes and codes for surgeries and procedures  . New varhttps://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Bevoelkerung/Bevoelkerungsstand/_inhalt.html) and calculated mid-year populations for 2014 to 2018. WHO World Standard Population 2000–2025 , intracranial injuries, neurosurgery, visceral surgery, and complications in patients with TBI.There were no missing data on age and primary diagnoses. Missing data on secondary diagnoses and procedures were impossible to detect as we could not distinguish whether the diagnosis was not present or whether the diagnosis was just not coded. We assumed that all diagnoses and procedures that are well-reimbursed were comprehensively coded and focussed on these codes for data extraction.All calculations were carried out using SAS release 9.4 and SAS Enterprise Guide 7.1 .Out of 10,244,649 million hospitalizations <18 years of age, we identified 458,844 cases with TBI as primary or secondary diagnosis. TBI was the primary diagnosis in 418,603 cases  . Male pan = 1,062, overall rate 0.2%)  . Age-staIn this population-based nation-wide study on pediatric TBI, Germany has high hospitalization rates compared to international data , 4. Our Mortality, intracranial injuries, neurosurgery, and complications occurred in only a small fraction of patients. While the incidence rates of hospitalizations for TBI in adolescents align with the rates reported for the entire German population, mortality in the pediatric subset was very low compared to the previously published population-wide mortality . HoweverSeveral studies tried to account for this dilemma by establishing clinical rules to guide imaging practice. Among three of the most relevant rules , PECARN performed best at ruling out clinically important TBI –18. In aHowever, an approach like the PECARN rule will be difficult to implement in Germany, because the current German DRG system drives hospitals to admit their patients for at least one or two nights to avoid cuts in reimbursement. An additional source leading to hospitalizations may be the lack of a valid German guideline on pediatric TBI and vague criteria for hospitalization after head injury in the expired guideline . In the Our study has several limitations owed to the lack of clinical information provided in the DRG data set. Due to the lack of exact information on the causes for admission and death, we likely overestimated these rates. The duration of hospital stay due to TBI may have been shorter than estimated in this study. However, the strength of this study is its comprehensiveness. We analyzed population-based data on TBI-related hospitalizations of children during the 5-year-study period, thereby completely ruling out selection bias and providing nation-wide representative data for Germany.This study addresses one of the key clinical research needs in the field of pediatric TBI by providing nation-wide comprehensive data on hospitalizations and TBI-related morbidity in Germany. It further provides evidence that hospitalization rates for TBI in Germany were higher in children compared to other countries inside and outside of Europe, with very low rates of mechanical ventilation, intracranial injury, neurosurgery, and mortality. Our data highlight the need to clarify whether TBI-related hospitalizations are determined by actual need for treatment or by reimbursement-related reasons. It should be further explored if there is the potential for quality improvement in the German health care system to reduce a higher than needed hospitalization rate.https://www.forschungsdatenzentrum.de/de.The data analyzed in this study is subject to the following licenses/restrictions: the original dataset can be accessed after inquiry to the Federal Bureau of Statistics of Germany. Requests to access these datasets should be directed to Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.AS, CD-S, and NB: study design. AS, CD-S, NB, and PT: statistical calculations and verification. NB: drafting of the manuscript. AS, CD-S, NB, PT, and UF-M: critical review and editing of the manuscript. All authors contributed to the article and approved the submitted version.NB received an internal research grant from the Medical Faculty of the University of Duisburg-Essen (IFORES) and a grant from the Stiftung Universitätsmedizin Essen that enabled the conduction of this work.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.


Background: Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limiting inflammatory disease with low incidence and high misdiagnosis rate in children. Furthermore, cases where the clinical presentation resembles acute appendicitis are very rare.Case Presentation: A 14-year-old boy was misdiagnosed as acute appendicitis and received operative treatment at his early visit. He suffered from abdominal pain, vomiting, diarrhea, fever, and lymphadenitis at the ileocecal junction, which were found by B-ultrasonography examination and surgery. Lymphadenectomy, as well as appendectomy, was performed, and KFD was identified by pathological examination. The patient was transferred to our hospital for further therapy because of recurrent fever and abdominal pain after the appendectomy. His temperature became normal after methylprednisolone was administered, and no recurrence was observed till now during follow-up.Conclusions: Necrotizing lymphadenitis involving mesenteric lymph nodes may cause acute-appendicitis-like symptom; KFD should be a diagnostic consideration for mesenteric lymphadenitis. Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease (KFD), is a self-limiting inflammatory disease with nonneoplastic lymphadenectasis. It occurs more frequently in older children, with major clinical manifestations of cervical lymphadenopathy and long-term fever –4. The lA 14-year-old boy presented to the Children's Hospital, Zhejiang University School of Medicine, with main complaints of recurrent abdominal pain accompanied by fever for 14 days. He had middle and upper abdominal pain on day 1 of presentation, accompanied by vomiting and diarrhea. He was diagnosed with acute gastroenteritis at a local clinic, and the symptoms relieved after being administered with intravenous cefuroxime and anisodamine. On day 2 of presentation, his abdominal pain worsened and localized at the right lower abdomen. He also had a low-grade fever, with a temperature of 38.0 °C. Thus, he went to Shaoxing People's Hospital, and physical examination showed obvious pressing pain at McBurney's point at the right lower abdomen. B-ultrasound examination revealed appendicitis (diameter 6 mm) and several lymph node echoes in the right lower abdomen, the largest size of which was 21 × 10 mm. The surgeon considered it was acute appendicitis, and an emergency laparoscopic operation was performed. During the operation, about 10 ml of light yellow transparent liquid was sucked from the ileocecal junction. The normal appendix and swollen lymph nodes in dark red were found in the operative field . LymphadAfter discharge, the boy had low-grade fever accompanied by mild abdominal pain occasionally. Since day 10 of presentation, his body temperature rose to as high as 39.4 °C. Intravenous ceftriaxone for 4 days was prescribed in a local clinic, and his symptoms did not improve at all.As a result, the boy was moved to the Children's Hospital, Zhejiang University School of Medicine. During the course of his illness, he had poor appetite and sleep. He had no past medical history, and his parents denied familial inherited disease. Physical examination on admission finding includes the following: temperature of 38.6°C, heart rate at 100 number/minute (n/min), respiration at 24 n/min, blood pressure at 117/90 mmHg, weight of 53 kg, and height at 170 cm. Enlarged lymph nodes without tenderness were found in the cervical, axillary, and inguinal area. The size of the largest one was 15 × 10 mm. Heart and lung exams were normal. No abdominal tenderness was evoked during abdominal examination. The liver and spleen were not palpable. The diagnoses were KFD and postoperative appendectomy. After admission, the results of the PPD test, mycoplasma antibodies detection, tuberculosis T-SPOT test, and autoantibody test were all negative. The level of procalcitonin in serum was normal. On the fourth day after admission (on day 17 of presentation), the patient agreed to receive intravenous methylprednisolone, and his body temperature dropped to normal at the same day. After being treated with methylprednisolone for 5 days , twice a day; oral for 3 days, 0.5 mg/(kg/d), twice a day), he was discharged without any symptoms. He completed therapy with methylprednisolone according to the doctor's advice, including oral methylprednisolone 6 mg twice a day for 3 days, 6 mg once a day for 3 days, and 2 mg once a day for 7 days. He was followed up for 2 years after discharge, and no similar symptoms or abnormal laboratory findings recurred. The laboratory findings of the patient during the course of illness are shown in KFD is a disease with unclear etiology and pathogenesis , 10. It It is challenging to distinguish KFD from other diseases at the early stage because of nonspecific clinical manifestation. As a result, the rate of misdiagnosis in patients with KFD was high at their first visit , 7. LympBasically, KFD is a self-limiting disease that mainly depends on symptomatic treatment. The use of steroids could shorten the clinical course, especially recommended for those recurrent patients or those with severe clinical symptoms –21. HydrIn summary, KFD is a rare benign self-limiting disease, and cervical lymphadenopathy and fever are the most common onset. It lacks specific clinical characteristics and is easy to be misdiagnosed as lymphoma, lymph node tuberculosis, and other diseases. In this patient, the necrotic lymph nodes were in the ileocecal junction in the abdominal cavity and caused acute-abdomen-like manifestation, indicating that when analyzing lymphadenopathy, KFD should be considered regardless of the parts where lymphadenopathy occurred. If necessary, lymph node biopsy is advised to avoid misdiagnosis and inappropriate treatment.shuqiang@zju.edu.cn. A data access agreement will be required.Within 6 months of this publication, anonymised individual participant data will be available (from the corresponding author) for research proposals approved by an independent review committee. Proposals should be submitted to The studies involving human participants were reviewed and approved by the Institutional Ethics Board of the Children's Hospital, Zhejiang University School of Medicine (2020-IRB-137). Written informed consent to participate in this study was provided by the participants' legal guardian. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian, for the publication of any potentially identifiable images or data included in this article.CZH treated the patient during his hospitalization, conceptualized and designed the report, drafted the initial manuscript, and reviewed and revised the manuscript. YKC collected the clinical and laboratory data, drafted the initial manuscript, and reviewed the manuscript. SZC operated lymphadenectomy and appendectomy, collected the clinical data, carried out the initial analyses, and reviewed the manuscript. WZG diagnosed the patient pathologically, checked the data, and reviewed and revised the manuscript. QS conceptualized and designed the report, coordinated data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.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.