Hidden blood loss (HBL) after total hip arthroplasty (THA) would lead to many undesirable consequences. Traditional Chinese medicine (TCM) is now increasingly used for hidden blood loss. We performed this systematic review and meta-analysis to summarize the effect and safety of TCM treatment of HBL after THA.  We searched PubMed, Embase, Cochrane Library, CNKI, VIP, WanFang, and CBM for the updated articles published from the inception of each database to May, 2022, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The efficacy and safety of TCM treatment of HBL after THA were synthesized and discussed by the outcomes of total blood loss (TBL), hidden blood loss (HBL), hemoglobin (Hb), and hematocrit (HCT), and the incidence of adverse reactions. Z = 3.89, P < 0.00001), HBL , Hb , and HCT , and had less incidence of adverse reactions .  A total of 12 articles and 881 patients were included. There were 441 cases in the intervention group and 440 cases in the control group. Compared with the control group, the intervention group had more advantages in TBL (MD = −251.68, 95% CI = ;  TCM has advantages in the efficacy and safety of treating hidden blood loss after THA. The strength of the evidence of the research results is limited by the quality of the included literature, and more high-quality RCTs are needed to confirm. Total hip arthroplasty (THA) is the most commonly used and effective treatment for femoral neck fractures, hip arthritis, developmental dysplasia of the hip, and ischemic necrosis of the femoral head . THA is HBL refers to the accumulation of blood in the joint cavity, or extravasation into the interstitial space, and the loss of hemoglobin (Hb) in the body caused by factors such as traumatic stress and other factors that induce hemolysis , of whicWe searched PubMed, Embase, Cochrane Library, CNKI, VIP, WanFang, and CBM for the updated articles published from the inception of each database to May 1st, 2022. When duplicate publications were identified, we chose the most complete and recent trial. Two investigators (Z.Y. and X.W.) independently retrieved the related studies in the database and excluded duplicate publications. The combined text and medical subject heading (MeSH) terms were cross-searched using MeSH and free words as follows: (((Hidden blood loss[Title/Abstract]) AND ((((Hip Prosthesis Implantation[Title/Abstract]) OR ) OR ) OR )) AND ((((Decoction[Title/Abstract]) OR (Tang[Title/Abstract])) OR (Fang[Title/Abstract])) OR  OR ((Chung I Hsueh[Title/Abstract]) OR )))) AND )Inclusion criteria are as follows: (1) Type of Study: the study must be a randomized controlled trial (RCT); (2) Participants: patients receiving THA; (3) Intervention measures: the intervention group must be treated with TCM  or combined with western medicine, and the control group is treated only with western medicine; and (4) Outcomes: TBL, HBL, Hb, hematocrit (HCT), and incidence of adverse reactions.Exclusion criteria are as follows: (1) studies are not RCTs; (2) patients not receiving THA; (3) incomplete or unidentified data; (4) duplicate publications; and (5) abstracts, reviews, case reports, and letters.Two independent researchers (Z.Y. and X.W.) read the title, abstract, and full text, screened the literature according to the inclusion and exclusion criteria, and cross-checked the results. If there is a disagreement, the third researcher (Y.L.X.) will be consulted. Extract data from the included literature, including first author, sample size of the study, gender, mean age or age range, intervention protocol, duration time, and outcomes.The quality of the included studies was assessed by The Cochrane Risk Bias Tool in the Cochrane Handbook for Systematic Reviews of Interventions. The following messages were evaluated: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessments, incomplete outcome data, selective reporting, and other biases.P < 0.1 or I2 > 50%. When high heterogeneity existed, a random-effects model was used for meta-analysis. Sensitivity analysis was also used to analyze the source of heterogeneity. Publication bias was evaluated visually by funnel plots and considered significant when P < 0.05 in either Begg's test or Egger's test when the inclusion was more than 10 articles.RevMan5.4 and Stata15.0 software was used for statistical analysis. The included studies are tested for homogeneity. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to report dichotomous data, and mean differences (MD) with 95% CI were used to report continuous data. Statistical heterogeneity was considered present when Our initial search yielded 85 articles in total, 32 of which were removed for duplication. After screening titles and abstracts, a further 17 items were taken away. 36 articles were reviewed, among which 12 were included in this meta-analysis –26. No f12 studies with a total of 881 subjects were included in the meta-analysis. The outcomes of the studies are shown as follows: TBL, HBL, Hb, HCT, and incidence of adverse reactions. The main characteristics of the 12 articles were summarized in The results of the risk of bias assessment for all included studies are summarized in P < 0.00001, I2 = 98%). The sensitivity analysis was carried out one by one, and it was found that there was no significant change, thus the random effects model was used. The meta-analysis demonstrated there was a significant difference between the two groups   .P < 0.00001, I2 = 99%). The random effects model was used. The HBL in the intervention group was less than that in the control group  (12 studies –26 invol=0.0008) .Subgroup analysis showed that TCM for tonifying qi and blood and TCM for activating blood stasis both have a significant difference in HBL , which wP < 0.00001, I2 = 88%). The sensitivity analysis was carried out one by one, and it was found that there was no significant change, thus the random effects model was used as well. The meta-analysis demonstrated there was a significant difference between the two groups   .P=0.04, I2 = 64%). The sensitivity analysis was carried out one by one, and it was found that there was no significant change, thus the random effects model was used. The HCT in the intervention group was more than that in the control group   .Z = 2.64, P=0.008) (One study  involvinP=0.008) .P=0.001) of the HBL suggested that there was potential publication bias in the included studies.The publication bias of outcomes was evaluated using funnel plots based on the HBL of 12 studies. The funnel plot , which wTHA is recognized as one of the most effective surgical methods for the treatment of end-stage hip joint disease . There aThe “yin collateral impairment” and “hematocheiza” described here are actually the same as the hidden blood loss described today. Blood circulating out of the vessels that cause swelling of the affected limb after the operation is called blood stasis. In this case, TCM thinks the bleeding cannot be stopped blindly but should remove blood stasis and stop it. In “A Treatise on Blood Troubles,” a famous classic TCM book on blood syndrome proposed four methods of treating blood syndrome: hemostasis, removing blood stasis, tranquilizing blood, and invigorating deficiency, which have been used by future generations to this day. Therefore, to treat blood syndrome, it is necessary to distinguish the cause of it. It could be caused by the stagnation of qi that blocks the normal flow of blood in the vessels, the deficiency of qi to promote blood circulation, or blood deficiency that leads to the inability to fill the vessels, so the flow rate slows down. Different etiologies and syndromes have different methods of differentiation and treatment.This study systematically reviewed the clinical efficacy and safety of TCM in the treatment of HBL after THA. A total of 12 articles were included for the meta-analysis. The included studies used Bazhen Decoction, Tanshinone Capsules, Sanqi Zhixue Decoction, Taohong Siwu Decoction, Yiqi Huoxue ointment, Fuyuan Decoction, Yunnan Baiyao, Shiquan Dabu Decoction, and Chuanxi San to treat HBL. The prescriptions used are regulating qi and activating blood stasis to stop bleeding, tonifying qi and blood to stop bleeding, and all treatments were from the cause of blood syndrome. Therefore, the subgroup analysis showed that whether taking TCM for tonifying qi and blood or activating blood stasis, the HBL in the intervention group was smaller than the control group. The results of the meta-analysis showed that TCM has more advantages in TBL, HBL, Hb, HCT, and the incidence of adverse reactions after THA, and the difference is statistically significant.Our review has several limitations. First, the sample size of this meta-analysis was relatively small. As a result, the unknown risk of bias caused by incomplete data could constrain our results. Second, due to the large heterogeneity of the included studies, only a random effect model can be adopted, which will have a certain impact on the results. Third, the intervention protocol varied significantly in the duration of treatment time, ranging from 7 to 30 days, and the type of intervention TCM varied from each other . At the same time, the control group received different interventions as well, which may be the reason for the high heterogeneity.Despite these limitations, this meta-analysis provides information on the association between TCM and HBL after THA.In conclusion, this article shows that TCM is more effective and safer than Western medicine in treating HBL after THA. Therefore, in the clinical treatment of HBL after THA, TCM should be added to the conventional treatment to improve the clinical efficacy. However, due to the small number of included studies and their low quality, our conclusions remain to be confirmed by further high-quality RCTs.


Compared with the DAM group, the preoperative  and postoperative  TWSTRS scores in the DBS group were significantly higher . We found no correlation between prognostic factors and patient age, gender, or disease duration for either surgical procedure. However, prognostic factors were related to the length of the postoperative follow-up period in the DBS surgery group . The mean hospitalization cost in the DBS group was 6.85 times that found in the resection group . The total complication rate was 4.26%. We found both resection surgery and DBS showed good results in the patients with spasmodic torticollis. Compared with DAM, DBS had a greater improvement in TWSTRS score; however, it was more expensive. Prognostic factors were related to the length of the postoperative follow-up period in patients who underwent DBS surgery.The surgical methods for treating spasmodic torticollis include the denervation and myotomy (DAM) of the affected muscles and deep brain stimulation (DBS). This study reports on the long-term efficacy, prognostic factors, safety, and hospitalization costs following these two procedures. We collected data from 94 patients with spasmodic torticollis, of whom 41 and 53 were treated with DAM and DBS, respectively, from June 2008 to December 2020 at the Chinese People’s Liberation Army General Hospital. We used the Tsui scale and the global outcome score of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to evaluate the preoperative and postoperative clinical conditions in all patients. We also determined the costs of hospitalization, prognostic factors, and serious adverse events following the two surgical procedures. The mean follow-up time was 68.83 months (range = 13–116). Both resection surgery and DBS showed good results in terms of Tsui (Z = −5.103,  Spasmodic torticollis (ST) is a chronic neurological disorder in which the head turns or tilts in jerky movements or sustains a prolonged and awkward position due to the involuntary contractions of neck muscles. ST is associated with neck pain, significant restrictions in daily activities, and reduced social participation and thus has a profound effect on quality of life . Oral trWe collected data from 94 patients with ST who underwent DAM or DBS from June 2008 to December 2020. Although DAM was previously the primary surgical therapy used to treat ST, it was surpassed by DBS in 2012. ST is clinically classified according to neck posture, and the types include rotational torticollis, laterocollis, retrocollis, anterocollis, and various combinations of these. There were no patients with pure anterocollis in the present study. Four cases were diagnosed as tardive cervical dystonia. All patients underwent pharmacotherapy, and some patients also underwent psychotherapy and physiotherapy. Cervical botulinum toxin injections were given in 68 patients. In total, we analyzed data from 52 men and 42 women. The mean age was 46.82 years , the mean duration of symptoms was 44.73 months , and the mean follow-up period was 68.83 months long . DAM was performed in 41 patients, and 53 patients underwent DBS .Forty-one patients underwent DAM techniques. The triad procedure ,5 was usFifty-three patients underwent DBS. One or two days prior to surgery, MRI was performed on all patients using a 1.5 or 3.0 T scanner . On the day of surgery, a model F stereotactic head frame  was positioned on the patient and a computed tomography (CT) scan was performed. The CT images were fused with the pre-surgical MRI, and preoperative planning was conducted to determine the optimal entry points for a safe electrode trajectory and avoidance of blood vessels  and ventricles. A Robotic Stereotactic Assistance  device was used to guide the surgical procedure in a minority of patients. Intraoperative microelectrode recording (MER) was routinely performed in most patients. Single-channel MER or multi-channel MER was generally performed using intraoperative microelectrodes  and the Leadpoint Neural Activity Monitoring System (Medtronic Inc.), although an Alpha Omega recording system  was used in a minority of patients. The electrodes were advanced to 8 mm above the target using a clinical microdrive . After MER, the DBS electrodes  were guided into place. General anesthesia was used during the entire surgical procedure. After implantation of the bilateral intracerebral electrodes, an intraoperative MRI scan  was immediately performed. The main purpose of this iMRI was to assess the accuracy of the electrode positioning, which was confirmed using a fused image of the intraoperative 3D T1-weighted sequence and the preoperative plan. The intraoperative MRI was also used to examine the possibility of intraoperative bleeding, infarction, and intracranial gas accumulation (pneumocranium).In most patients, the implantation target was the globus pallidus internus (GPi). The anatomical coordinates of the target posteroventral GPI was 3 mm anterior to the midcommissural point, 18–21 mm lateral to the midplane of the third ventricle, and 4–6 mm below the intercommissural line. In two patients who had ST combined with Parkinson’s disease (limb tremor), electrodes were implanted in bilateral subthalamic nucleus (STN) targets; in one patient with ST combined with intense head tremors, electrodes were implanted in bilateral VIM targets; and in one patient with ST combined with Parkinson’s disease (limb tremors and stiffness), four electrodes with two rechargeable pulse generators were implanted in bilateral STN and GPi targets. For stimulation parameters of GPI, amplitude, pulse width, and frequency were 2.2–4.0 V, 60–120 μsec, and 130–180 Hz, respectively.In one patient (Patient 2), the Activa PC  was replaced by an Activa RC  at postoperative 5 years and one month because of battery energy depletion. Rechargeable pulse generators were implanted in 21 patients. Eight patients chose the Medtronic Inc. device and 24 patients chose the Beijing PINS Medical Co. device  .Patient clinical condition was evaluated using the Tsui scale  and the ® Statistics Version 24.0  for statistical analyses. Measurement data are expressed as (x ± s). Two independent sample t-tests were used for comparisons between groups, and paired t-tests were used for comparisons within groups. The count data are expressed as % and the chi-squared test was used for categorical variables. The Wilcoxon signed rank sum test was also used to analyze the data. p < 0.05 was considered statistically significant.We used SPSSp = 0.404; p = 0.073; p = 0.740)  .p = 0.000). This is because the DAM technique was the primary surgical therapy for ST before 2012, and DBS has since replaced DAM as the primary surgical therapy. The medical expenses were lower in the DAM group (p = 0.000). The mean hospitalization costs were USD 5934.03  in the DAM group and USD 40,636.54  in the DBS group, such that the cost of the treatment in the DBS group was 6.85 times that of the DAM group . The mean preoperative total TWSTRS score was 48.81 (range = 30–68) in the DAM group and 47.71 (range 24–67.25) in the DBS group. The mean postoperative total TWSTRS score was 28.21 (range = 0–64.25) in the DAM group and 18.57 (range = 0–53) in the DBS group. The postoperative scores improved significantly in both groups (p = 0.000). The mean improvement in the postoperative TWSTRS score was larger in the DBS group (61.08%) than in the DAM group (42.2%) (p = 0.002)  .p = 0.011), and the postoperative Tsui scores improved significantly in both groups (p = 0.000). The mean preoperative Tsui score was 8.61 (range = 2–19) in the DAM group and 10.02 (range = 2–17) in the DBS group. The mean postoperative Tsui score was 4.68 (range = 0–14) in the DAM group and 3.62 (range = 0–13) in the DBS group. The mean improvement in the postoperative Tsui score was not significantly different: 45.64% in the DAM group and 63.87% in the DBS group (p = 0.072) (The Tsui score was higher in the DBS group before surgery (= 0.072) .p = 0.000). This indicates that in the DAM group, a shorter disease history was associated with more severe symptoms. In terms of prognosis, we found no significant correlations between gender, age at surgery, disease duration, the length of the follow-up period, or postoperative curative effect  compared with those with a disease duration longer than 24 months , indicating that women had more serious symptoms. Furthermore, the preoperative Tsui scores in patients over 50 years old were higher than in those younger than 50 years. This indicated that older patients in the DBS group had more serious symptoms, such as the degree and prevalence of head tilt and the occurrence of tremor . In terms of prognosis, we found no significant correlations between patient gender and age at surgery, disease duration, or postoperative curative effect. However, the prognosis was related to postoperative follow-up time such that patients with a longer period of postoperative stimulation had significantly greater reductions in symptoms. Specifically, the TWSTRS score  and Tsui score were significantly decreased  in patients for whom the follow-up period was longer than 48 months . Intraoperative bleeding occurred in one patient. Specifically, a fresh blood outflow conduit formed during the DBS procedure. The operation was immediately suspended, and strict blood pressure control was applied along with hemostatic agents. An intraoperative MRI revealed a large amount of hemorrhaging (about 20 mL). To address this, a drainage tube was implanted via stereotactic guidance in the hematoma through another bone hole, and the patient was immediately subjected to intraoperative hematoma aspiration. With the consistent maintenance of the drainage, the patient had only mild hemiplegia, representing a good outcome . In anotp < 0.001). The DAM procedure is performed in only a few neurosurgical departments worldwide, and other authors have reported similar results [Both DAM and DBS had good results in our patients with ST  and 45.64% (range = 0–100), respectively, following the DAM surgery. Thus, the outcome in our patient group was less favorable than that reported in the literature. Wang et al. [p = 0.002). Specifically, the TWSTRS total score was reduced by 61.08%  in the DBS group. However, there were no significant differences  in the mean postoperative Tsui improvement score. This may be because the Tsui score only assesses the degree of head and neck tilt, shoulder lift, duration of head tilt, and head tremor, while the TWSTRS assesses these factors as well as quality of life and degree of pain relief. Improvements in quality of life and pain relief are most closely aligned with the needs of ST patients.GPi-DBS has been found to be an effective and relatively safe treatment for patients with severe generalized or segmental dystonia ,18. KissFew studies have reported on the prognostic factors related to the surgical efficacy of ST treatments, especially those related to resection surgery. In the DAM group, we found that patients with disease durations of less than 24 months had more severe symptoms than those with a longer disease duration. However, in terms of prognosis, there were no significant correlations between patient gender and age at surgery, disease duration, the length of the follow-up period, and the postoperative curative effect.Regarding the prognostic factors related to DBS surgery outcome, Hua’s meta-analysis showed that the effect of DBS on ST was related to the age at surgery, such that patients who had a younger age of onset were more likely to have a good postoperative outcome. Further, there was no correlation between the surgery outcome and gender, medical history, or follow-up time . Howeverp = 0.094). Fiorella et al. compared selective peripheral denervation (20 patients) with pallidal stimulation (15 patients) for the treatment of cervical dystonia and concluded that GPi-DBS was superior because it had a larger benefit, even if it carried a greater risk of severe complications [Which of the two surgical methods (DBS and DAM) is preferable for patients with ST? Francesco et al. compared GPi-DBS with resection surgery in patients with ST and seemed to favor the former. In their study, the DBS procedure had a better outcome in terms of long-term efficacy and was rated as more satisfactory by patients in terms of pain relief . Furtherications . GPi-DBSications . Taken tications ,13,14,16ications ,25,26,27Why can DBS better improve the clinical symptoms of patients with ST? We infer the following factors: (1) DBS regulates the brain network, the cortex-striatum-thalamus-cortex loop, so all the peripheral nerves in the neck are regulated, while ST only involves multiple muscles of the neck; DMA can only remove the limited muscles and nerves of the neck, and the deviation of the neck involves more muscles, not a few muscles; (2) DBS is a long-term neuromodulation, the parameters can be adjusted, the clinical effect will be better, and the brain function can be reconstructed. However, for DMA surgery, cervical nerve reinnervation in 1–2 years may lead to the recurrence of symptoms; (3) the etiology of ST is brain dysfunction. DBS directly acts on the cortical basal ganglia circuit, which is the etiological treatment, while DMA is the symptomatic treatment, and the removed muscles and nerves are normal.In terms of sex ratio, there is an anomaly in our results. There were 52 males and 42 females, more male patients than female patients, which is different from the overall prevalence of isolated cervical dystonia, which typically has much higher proportions of females. That is because we only counted patients who have undergone surgery, not the incidence rate of isolated cervical dystonia. Whether patients can receive surgical treatment is related to economic conditions and traditional concepts in China. This is why the article analyzes the hospitalization expenses of patients. In developing countries, economic factors have an important impact on whether patients can take reasonable treatment.To the best of our knowledge, no previous reports have examined the cost of selective peripheral denervation in ST patients. In this study, we found that the mean medical costs were USD 5934.03 in the DAM group. The patient with the highest costs  underwent a subdural selective C3–5 sensory nerve root rhizotomy and then developed a postoperative epidural hematoma, which required a second operation, the rehabilitation of limb function, and a prolonged hospital stay.In terms of the cost of DBS, Lad et al.  utilizedp < 0.001). Although no previous studies have compared hospitalization costs between DBS and DAM in ST patients, we expect that the hospitalization costs of DBS are routinely higher because of the cost of the procedure and implanted device. These implanted devices are not covered by medical insurance in most parts of China, and so the surgical treatment of ST via DBS undoubtedly carries an increased financial burden for people in developing countries. Thus, when choosing a surgical method to treat ST, patients and physicians must consider efficacy, safety, and also the patient’s financial situation.The present study is the first to report on the cost of DBS in China. We found that the mean cost of DBS was USD 40,636.54 . Forty-two (79.25%) patients received rechargeable pulse generators, which were more expensive. A patient with four electrodes and two rechargeable pulse generators had a high cost , as did a patient who had intraoperative bleeding during the DBS procedure  and had to pay extra for drainage tube implantation, the treatment of hypostatic pneumonia, the rehabilitation of limb function, and a prolonged hospital stay. Compared with previous literature, the mean total cost of hospitalization was lower in our patient group. However, compared with the DAM group, the costs associated with DBS were almost 6.85 times higher (In recent years, most authors seem to favor DBS for treating ST. However, DBS-related complications, such as surgery-related bleeding or infarction, hardware-related infection, lead fracture, lead migration, stimulation-related symptoms, are not uncommon. Although there were no fatalities in our patient group, one patient experienced a hemorrhage, resulting in permanent moderate hemiplegia, and another patient developed ischemia in the left frontal lobe, with no long-term complications. There were no hardware-related complications or stimulation-related symptoms, potentially because of the small number of cases. There were no serious complications associated with DAM, likely because it does not interfere with the central nervous system; one patient who underwent the subdural procedure had temporary quadriplegia because of epidural hematoma, but there was no permanent hemiplegia.Both DAM and DBS showed good results in our group of patients with ST. Compared with DAM, DBS had a more improvement in TWSTRS score, although the hospitalization cost was substantially higher. The choice of the surgical method for ST in developing countries should be individualized and should consider both efficacy and affordability. The outcome of DBS was not significantly correlated with age at surgery, gender, disease duration, or postoperative curative effect but was related to the postoperative follow-up duration.


Dual-tasking (DT) while walking is common in daily life and can affect both gait and cognitive performance depending on age, attention prioritization, task complexity and medical condition. The aim of the present study was to investigate the effects of DT on cognitive DT cost (DTC) (i) in a dataset including participants of different age groups, with different neurological disorders and chronic low-back pain (cLBP) (ii) at different levels of cognitive task complexity, and (iii) in the context of a setting relevant to daily life, such as combined straight walking and turning.Ninety-one participants including healthy younger and older participants and patients with Parkinson's disease, Multiple Sclerosis, Stroke and cLBP performed a simple reaction time (SRT) task and three numerical Stroop tasks under the conditions congruent (StC), neutral (StN) and incongruent (StI). The tasks were performed both standing  and walking (DT), and DTC was calculated. Mixed ANOVAs were used to determine the effect of group and task complexity on cognitive DTC.A longer response time in DT than in ST was observed during SRT. However, the response time was shorter in DT during StI. DTC decreased with increasing complexity of the cognitive task. There was no significant effect of age and group on cognitive DTC.Our results suggest that regardless of age and disease group, simple cognitive tasks show the largest and most stable cognitive effects during DT. This may be relevant to the design of future observational studies, clinical trials and for clinical routine. In daily life, it is very common to encounter situations that require performing two tasks simultaneously, such as walking and talking on the phone. In research conditions, this is referred to as dual-task (DT), as opposed to single-task (ST). In particular, a large body of research has focused on the interaction between cognitive tasks  and motor tasks , showing that DT can affect the performance of one or even both of the tasks involved compared to ST . The effWalking is one of the most common motor activities performed daily, and a large number of situations involving DT occur during walking. In addition, factors that negatively affect the ability to walk, such as neurological disorders, orthopedic impairments, and balance disorders, have a profound impact on people's independence and quality of life . SeveralAnother factor involved in the interaction between gait and cognitive tasks is task complexity, but only a few studies have investigated its influence on cognitive DTC, with variable results. Some studies have reported higher cognitive DTC as cognitive task complexity increases –36. The Requiring demanding attentional skills and the integrity of executive functions , DT has Recently, cLBP has been shown to be associated with impaired attention and working memory  and alteTherefore, the aim of the present study was to investigate the effects of DT on cognitive DTC (i) in a dataset including participants of different age groups, with different neurological conditions and cLBP, (ii) at different levels of cognitive task complexity, and (iii) in the context of a setting relevant to daily life, such as combined straight walking and turning. The idea for the experimental paradigm was based on the fact that short walking episodes combined with turns better reflect everyday situations than the straight walking paradigms used in previous studies  and thatIn the present study we analyzed a dataset from a cross-sectional study designed to develop and validate mobility algorithms. This included participants with different age groups, with different neurological disorders and cLBP. Detail of the dataset protocol can be found in .Participants were longitudinally recruited through flyers placed in public facilities  and in neurology departments and outpatient clinics at University Hospital Schleswig-Holstein (UKSH), Kiel Campus, Germany . Inclusion criteria were (i) age 18 years or older and (ii) ability to walk independently without walking aids. Exclusion criteria were (i) Montreal Cognitive Assessment score <15 and (ii) other movement disorders affecting mobility performance, as judged by the assessor. Participants were divided into 6 groups according to age and diagnosis. Healthy participants were divided into “younger” (age 18–45 years) and “older” (age ≥ 60 years). Participants with neurological disorders included patients with PD [according to the UK Brain Bank criteria ], MS [acThe study was approved by the ethical committee of the Medical Faculty of Kiel University (D438/18) and was conducted in accordance with the principles of the Declaration of Helsinki. All participants provided written informed consent before the start of measurements. The study is registered in the German Clinical Trials Register (DRKS00022998).Demographic data including age, sex, weight, and height were collected. Overall cognitive function was assessed with the Montreal Cognitive Assessment . MobilitParticipants performed two smartphone-based cognitive tasks of different complexity. The first task consisted of a simple reaction time test (SRT) in which participants had to tap the screen as fast as possible after the appearance of a black square. Six time intervals ranging from 1,000 to 2,000 ms (in 200 ms increments) were used for the appearance of the black square. Each condition appeared 4 times for a total of 24 trials, administered in random order. The response time in ms was recorded for each trial, and the average of all trials was calculated for each participant. The second task consisted of a numerical Stroop test in which participants had to choose the higher number from two options . The Strfindchangepts.Participants were measured with a 3D optical motion capture system . Reflective markers were placed on the head, sternum, pelvis, and feet. The exact placement of the markers is described elsewhere . Data weTurning phases were extracted by the method described above, the total time spent during turning was computed and used to calculate the turning ratio according to the following formula:To assess the impact of DT on cognitive performance, DTC was calculated using the following formula , 64:Post-hoc t-tests with Bonferroni's correction for multiple tests were performed in case of significant ANOVA main effects. If necessary, Greenhouse-Geisser's correction for non-sphericity were applied. Partial eta squared , R v4.0.3 and RStudio v2022.02.2+433 for Windows . Descriptive statistics were calculated for the examined variables. To assess the difference in DTC across the 6 groups and different cognitive tasks, a mixed ANOVA test was used, with the factors “task” and “group.” To assess the difference in response times across the 6 groups between ST and DT, separate mixed ANOVA tests were used, one for each cognitive task, with the factors “condition” and “group.” A total of 91 participants were enrolled in the study.  = 48.630; p < 0.001; post-hoc analysis showed significantly higher cognitive DTC in SRT than in all Stroop conditions , with no significant differences among these in the overall group and in all subgroups except in patients with cLBP  = 71.999; p < 0.001;  = 9.411; p = 0.003; Post-hoc analysis showed that response time was significantly higher in DT than in ST in all groups in SRT. On the other hand, in StI, response time was significantly lower in DT than in ST only in the younger participants, while no significant difference was found in the other groups  = 8.000; p < 0.001;  = 3.022; p = 0.015;  = 10.626; p < 0.001;  = 10.663; p < 0.001;  = 15.337; p < 0.001; Post-hoc pairwise comparisons for factor “group” and details of response time in ST and DT are shown in detail in A significant effect of factor “group” was found [Foop test . Post-hoThis analysis on a cross-sectional dataset aimed to evaluate the effect of motor-cognitive DT at different cognitive task complexities on cognitive DTC during turning and walking in healthy participants, patients with different neurological conditions, and patients with cLBP. We found a significant effect of cognitive task complexity on cognitive DTC while age and disease did not have a significant effect on cognitive DTC in the population studied here. These results are discussed in detail in the following.Cognitive DTC depended on cognitive task complexity, both in the overall group and at the subgroup level, with DTC decreasing as task complexity increased. This is in contrast to what we expected. A significant difference in response time between ST and DT was found during SRT and StI, but not during StC and StN. During SRT, a higher response time was observed in DT, compared with ST  and thisAttention and task prioritization have been shown to have an important effect on motor-cognitive DT involving walking , 67, 76.SRT and Stroop tasks require different cognitive functions. The SRT is a measure of processing speed , while tAs SRT is a simple task, it is also possible that the learning curve was so fast that DT effects were well-presented with this paradigm, but that the learning curve was substantially lower for the Stroop tasks which may have led to better results during the DT sessions .Differently from what we expected, we found no significant differences across groups in cognitive DTC . This reFinally, we found no interaction between the factor “complexity” and “group” on cognitive DTC. Previous studies have reported an influence of age on the effect of task complexity on DTC, with younger participants showing a significant DTC on cognitive performance only in the most challenging cognitive tasks, whereas older participants were reported to be more prone to DT effect at a lower level of cognitive task complexity . The domWe acknowledge that this study has limitations. First, the sample size of some groups, in particular the cLBP group, is low. This is explained by the basic design of the cross-sectional study, which provided the dataset used in the present article. However, we believe it is still useful to show data on the entire spectrum of diseases studied to open the possibility of generating new hypotheses for future studies. Second, participants had, on average, relatively high levels of physical and cognitive abilities. This may limit the generalizability of our results, and further studies including participants with lower functional scores may be needed. Third, in DT, participants were not instructed to prioritize any of the tasks. This could have led to different attentional strategies. However, we argue that this problem is difficult to avoid. For example, we cannot exclude that the instruction “Please do not prioritize any of the tasks” does not lead to the activation of another (cognitive) task during the experiment. Fourth, standing while performing a cognitive task might be considered an  resource-consuming task. Indeed, this paradigm has been used in previous studies as a DT postural paradigm –89. In fDT while walking has a different effect on cognition depending on the complexity of the cognitive task. Cognitive tasks that are more complex and involve executive functions showed lower cognitive DTC and even better cognitive performance in DT than in ST. The underlying mechanisms could involve task prioritization, cross-talk interaction, or a combination of learning processes and interference between the two tasks. Age and disease group did not have a relevant effect on cognitive DTC in our cohort. These findings could help movement disorder specialists, neurologists, general practitioners, allied health therapists and patients to interpret the interaction between cognitive abilities and walking in a context that more closely reflects everyday walking conditions, and could be useful to industry and academic principal investigators to design effective assessment batteries that focus on DTC.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 Ethical Committee of the Medical Faculty of Kiel University (D438/18). The patients/participants provided their written informed consent to participate in this study.EW, CH, and WM designed the study. EW collected data. EW and EB performed data analyses. EB and WM wrote the first draft of the manuscript. EW, RR, CH, and FP reviewed manuscript draft. All authors contributed to the article and approved the submitted version.This study was funded by the Open Access Publication fund of the Christian-Albrechts-University of Kiel for scientists of the CAU by Schleswig-Holstein state government. We acknowledge the financial support by DFG within the funding programme Open Access-Publikationskosten.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.


With more than 120 million rural-to-urban migrants, urbanization of the rural population requires deeply exploration in China.This study focused on settled citizens who obtained urban Hukou (household registration) during urbanization and investigated their perceptions of health services in China.A cross-sectional comparison study with an original, closed questionnaire was conducted in two major cities of Hubei, central China, covering health status and both the satisfaction with and utilization of health services. In total, 863 residents with urban Hukou participated in this study; migrants formed the study group and original city residents formed the control group. Propensity score matching (PSM) was used to reduce choice bias in the analysis steps. Besides basic description of the data, ordinary least squares regression (OLS regression) was used to discover the relationship between basic demographic indicators and health expenditure.PSM yielded 290 effective pairs for analysis. The results indicated an improvement in health status for migrant residents (study group) with a higher average score of self-reported health status and lower prevalence of chronic diseases than the control group. These scores were also better than the standard urban level in central China. The study group showed a higher clinic visit utility (69.63%), lower hospitalization utility (8.28%), less convenience of health service utility, and lower health expenditure than the control group. For the study group, the biggest difference was observed in satisfaction with health service costs, which was the least improved aspect after they obtained urban Hukou. The regression results demonstrated that age, family size, living expenditures, and marital status impacted health costs in the overall model and the influences of these factors differed between the study and control groups.Obtaining urban Hukou helps migrant residents to meet their health service needs and receive equal access to health services. However, after obtaining urban Hukou, migrants also face great pressure in terms of health consumption. This study therefore offers guidance on the next steps for progressing China's urbanization. Urbanization is a natural historical process following the development of industrialization, which includes the urban concentration of non-agricultural industries and the migration of rural populations to urban areas , 2. ChinRapid urbanization creates significant changes and influences social development and lifestyles , 8. It pThe urbanization of the rural population, or becoming an urban resident (referred to as new city citizens in this research) in China is an issue requiring exploration . The disIn the face of contradictions and challenges during urbanization and new requirements for improving the overall quality of urbanization, the Central Committee of the Communist Party of China and the State Council have issued a series of relevant policy documents, focusing on solving the existing rural-to-urban migration problems . A threeTherefore, this study aimed to prove the effectiveness of China's new urbanization reform, and provide evidence for the trend of urbanization by examining health equity in the process of urbanization. It also attempted to understand the social situation of rural-to-urban migrants and the changes they face after obtaining urban Hukou.Face-to-face survey with closed questionnaires were conducted to investigate the equity of health service delivery in the process of urbanization and to identify the disparities and influencing factors of health service demands. The aim was to gain insights that could facilitate effective and precise policy development.via random sampling (see Section Participants and Procedure) from January to June 2018 in Wuhan and Xiangyang, two cities in Hubei, which were the top 10 cities for urbanization and economic development in central China . Personal identifying information was removed and participants remained anonymous during the entire study process. The research team kept all paper documents and electronic data secure.A unified definition of the new city citizen group is lacking, as they emerged less than a decade ago. To clarify the research objective, this study defined new city citizens as people who have moved from rural areas to work and settle in cities. To understand how the new city citizen group changed throughout the urbanization process, a quasi-experimental research strategy was adopted in this study. Specifically, a study group and control group were created as part of the cross-sectional survey. A specific section in the questionnaire for the study group was designed to determine the health service satisfaction before and after settle-down.For the study and control groups, we selected migrant residents and original residents, respectively; both groups had urban Hukou, to avoid any confounding effect of the policy acting as an extraneous variable.study group vs. control group) from communities in the sample area were selected through random sampling  college students with a school collective Hukou, and (2) those with no change in Hukou status after settling down (termed floating people). Based on previous research experience and a literature review, questionnaires with over 20% missing data were excluded , 17.The identity of migrant citizens shifts from farmer, to floating people, to new city citizen. As the study focused on settled citizens who had obtained urban Hukou during the urbanization process, we asked the study group about their experience regarding the use of health services before and after they had obtained urban Hukou, to identify changes in health services.The questionnaire was distributed utilizing the convenience sampling method in the sample communities by professional investigators. All investigators received relevant training prior to the investigation. Both written and oral informed consent was obtained from all participants before conducting the survey. After obtaining permission, the respondents were asked to complete a paper-based questionnaire in a face-to-face setting.This study used an original questionnaire with four sections as shown in P <0.01) demonstrated good structural validity among the dimensions and the overall score. The different dimensions are elaborated below:The content validity index (CVI) for the questionnaire was 0.704, whereas item CVI ranged from 0.67 to 0.73. The results of the validity test of the questionnaire's reliability  indicated good internal consistency. The correlation coefficient test  were obtained.Self-reported health status, chronic disease history, and self-reported illnesses over the previous two weeks were used to evaluate health status.The central authority of China launched the new round reform of health service system in 2009, aimed to establish a safe, effective, convenient and affordable health service system. Referring to the goal of the new round reform of health service system, this study gave a four questions satisfaction evaluation with health services, including technology level, expenditure, convenience, service attitude. And the study group was asked to answer a separated part, “changes of satisfaction with health services before and after settling down”. The two-part section used a 6-point Likert scale .Affordability, access, health needs, and behaviors were evaluated. Affordability included health insurance coverage and health expenditure. Access included convenience in terms of distance and time taken to reach the nearest health institution. Healthcare service usage included use of clinical and in-hospital services.Data were obtained from questionnaires and official statistical reports. EpiData 3.0  was used for data entry, and SPSS26.0  was used for statistical analysis with coefficients equality estimation replenished by SPSSAU . Propensity score matching (PSM) was used to reduce the choice bias in the analysis steps. With one-to-one matches without replacement, more balanced groups were matched with a set of baseline characteristics, including investigated city, sex, age, marital status, education background, family income, occupational status, and family size see .th and 75th percentiles). Categorical variables were reported as counts and percentages. The normally distributed continuous data were tested using t-test, non-normally distributed using the Kolmogorov-Smirnov test, and categorical data using the chi-square test. After the correlation analysis, related basic demographic indicators and health service indicators were incorporated into the regression model  for the multiple analysis of health service utility . Then, the non-normality test, the related continuous data was transformed for the regression model improvement. Furthermore, this study attempted to determine whether the independent variables had the same influence on the dependent variable in different citizen groups. Regression analysis was used for both the study group and control group. The equality of regression coefficient for the two groups was tested (t-test and Chow test) to compare the difference of influence between the two groups. Statistical significance was set at P < 0.05 for a two-sided test.Univariate and bivariate statistical models were adopted to evaluate the data. Continuous variables were described using mean and standard deviation (SD), while non-normally distributed data were described using median and quartile range  participants in the study group and 290 participants in the control group. After the PSM analysis, 290 effective pairs and 580 cases were obtained for research analysis at the ratio level of 1:1.n = 312) were women, 75.34% were married, and 88.28% were employed. The median family size was three people, and families comprising three or four was common (84.3%). Among the study group, the sex ratio was 1:1.25 (men to women), the average age was 39.99 years (±11.22), and 72.41% were married . Of all the participants, 53.79% ( married .p <0.01), occupation rate (p = 0.04), and annual family expenditure [60,000 vs. 50, 000 Chinese yuan ; No statistically significant differences were found between the study and control groups in terms of gender, age, and marital status; however, the control group had a higher education level  were satisfied with the health services, with no statistically significant differences between the two groups . MeanwhiIn terms of different dimensions, the biggest difference was observed in satisfaction with health service costs, which was also an aspect that new city citizens reported as improving the least after they obtained urban Hukou .In terms of access convenience, there were no statistically significant differences between the groups for distance to the nearest health institution, with 65.0% of the participants living within one km of a basic healthcare institution. However, it appeared that the study group might spend more time traveling to these institutions .p <0.05; In terms of affordability, 98.23% of new city citizens were covered by China's basic health insurance. Although the basic structure was similar, compared with cityward migrants, employment basic medical insurance (EBMI) coverage and commercial insurance ownership were higher among original residents . Health pclinic−visti = 0.01, phospitalization = 0.03, The study group had a higher clinic visit utility rate and lower hospitalization utility rate than the control group  and 15 min (67.76%) of the nearest health institution, which was slightly more inconvenient than the national average during the same period  and the China Medical Board-Opening Competition program 2015 (No. CMB15-223). The sponsors played no role in the design and implementation of the study, collection, management, analysis, and interpretation of the data, preparation, review, and approval of the manuscript, and decision to submit the manuscript for publication. This research received considerable assistance from A/Prof. Xingjie Hao, and Lec. Peng Wang with the statistics and data analysis, and help from Mrs. Li Zhang, Mrs. Zhihong Ding, Mr. Min Zhang for the field survey.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: The long-term success of nonsurgical weight reduction programs is variable; thus, predictors of outcome are of major interest. We hypothesized that the intestinal microbiota known to be linked with diet and obesity contain such predictive elements. Methods: Metagenome analysis by shotgun sequencing of stool DNA was performed in a cohort of 15 adults with obesity (mean body mass index 43.1 kg/m2) who underwent a one-year multidisciplinary weight loss program and another year of follow-up. Eight individuals were persistently successful (mean relative weight loss 18.2%), and seven individuals were not successful (0.2%). The relationship between relative abundancies of bacterial genera/species and changes in relative weight loss or body mass index was studied using three different statistical modeling methods. Results: When combining the predictor variables selected by the applied statistical modeling, we identified seven bacterial genera and eight bacterial species as candidates for predicting success of weight loss. By classification of relative weight-loss predictions for each patient using 2–5 term models, 13 or 14 out of 15 individuals were predicted correctly. Conclusions: Our data strongly suggest that gut microbiota patterns allow individual prediction of long-term weight loss success. Prediction accuracy seems to be high but needs confirmation by larger prospective trials. Obesity has become a worldwide problem that requires substantial improvement of both prevention and therapy in children and adults . While bAkkermansia abundance, which remained stable for two years. The Firmicutes/Bacteroidetes ratio was higher in subjects with obesity with metabolic syndrome than in the so-called “healthy obese”. Most interestingly, participants who succeeded in losing their weight consistently over the two years had a different microbiota pattern at baseline compared to patients who were less successful in weight reduction [In a previous trial , we studeduction . Therefoeduction . Here, w2 and age of 40 ± 8 years , approved by the ethics committee of the University Hospital of Tübingen, Germany. The study was conducted at the Optifast®52 center at the Metabolic Unit of the University of Hohenheim , including adults who lived in the Stuttgart area. Advertisement for the Optifast®52 program in Stuttgart was displayed in local newspapers, on billboards, and on social media. All individuals included volunteered to participate in the present study after they received detailed written information about the study and its purpose, as well as personal informative meetings with the Optifast®52 team if desired. The primary endpoint of the study was weight-loss maintenance. The secondary endpoints comprised quality of life, as well as anthropometric and biological assessments, as described in detail in the study registration on ClinicalTrials.gov. The study was conducted according to the declaration of Helsinki. Written informed consent was obtained from every subject. Study details and methodology have been described elsewhere [2) and mid-age (30–50 years) at baseline, and a subject’s affiliation to the same enterotype  to minimize interindividual variability. Among those who fulfilled these criteria, we selected 8 individuals who were highly successful regarding weight-loss maintenance after two years , and 8 matched pairs who were not successful . One had to be excluded from analysis because microbiota analysis failed. A threshold of 10% weight loss and maintenance of it for at least one year has been proposed as the definition for successful weight-loss maintenance [For the present study, we selected 15 subjects according to defined criteria (see below) out of a larger cohort of adults with obesity with a mean body mass index (BMI) of 42.4 ± 6 kg/m 8 years  from a mlsewhere . Brieflyntenance . In factntenance .®52, Nestlé Health Science Germany GmbH, Frankfurt, Germany) described before [After inclusion into the study, all participants underwent a defined and highly effective multidisciplinary weight loss program . Quality check comprised per base sequence quality, per-sequence quality scores, per-base sequence content, per-sequence GC content, per-base N content, sequence length distribution, sequence duplication levels, kmer content, and over-represented sequences. All samples showed satisfactory values for each parameter tested. Next, the sequences were processed using PRINSEQ for removing low-quality reads, trimming of poly-Ns, and A/T tails [http://ab.inf.uni-tuebingen.de/software/malt/; accessed on 4 November 2021) with a maximum allowed e-value of 1.0. The BLASTX files were imported into MEGAN5 . MEGAN5 carries out binning of the reads into taxonomic and functional categories based on the BLASTX hits. The minimum bit score used for the analysis was 50 and a minimum support of 50 reads for each taxonomic category was used for the LCA algorithm. Ultimately, reads were assigned to a taxonomic and functional category. On average, about 50% of the reads in each sample were assigned to some category, 79% thereof were down to the level of genera and about 61% to the level of species. The samples were normalized with respect to each other. The functional annotation of the reads was performed based on the KEGG library . Microbiome data handling was in line with recent recommendations [For whole metagenome analysis, we used shotgun sequencing of stool DNA to assess taxonomic and functional features at baseline, as described earlier in detail . DNA was/T tails . Each sandations . MetagenCorrelation coefficients between each predictor variable from the set of genera/species on one hand and delta BMI/RWL on the other hand were calculated and ranked to obtain a first overview of potentially promising candidate variables .Caldicellulosiruptor, Thermaerobacter, and Thermobacillus) were eliminated prior to reduction, as they do not normally occur in the gut microbiome, and hence, are likely misclassifications. Third, the respective proportions of genera and species were calculated and represented the values of the predictor variables for each data set.Determination of the gut microbiome of the patients led to two native data sets comprising the bacterial genera and the bacterial species data. Both these data sets contained the patient ID, the success rate (PS or NS), RWL and delta BMI, and relative abundances at baseline for the respective genera and species, i.e., the relative abundances of 1020 different bacterial genera (first data set) and 2529 different bacterial species (second data set). Next, the data sets were reduced to contain only the first 102  and 106  columns, corresponding to the most abundant genera or species, which cover ~99% , and ~96%  of the gut microbiome, respectively. The rationale of this approach is due to many genera or species only occurring in a low number of individuals, and at very low frequencies; thus, increasing the potential of a considerable effect of measurement errors. In case of the genera data set, three genera . In our case, the number of predictor variables (p = 102 and p = 106 for the two data sets) is quite large compared to the number of patients (n = 15). Therefore, three avenues were pursued to locate the most important predictor variables contained in T: (I) the determination of the correlation between each predictor variable and delta BMI/RWL, (II) an elastic net regularization approach, and (III) multiple linear regression models in a Monte Carlo approach to complement the set of the most important predictor variables .Prior to the downstream analyses, microbial raw count data were converted into different forms: relative abundance, Z score of relative abundance, and centered log-ratio transformed (Clr) data. Clr data were used in principal component analyses (PCA) and in computing the Euclidean distance for permutational multivariate analysis of variance (PERMANOVA) tests using the Adonis function in the vegan package  , always for the optimal λ cross-validated in the same repeat. As responses that quantify the success of the intervention, both delta BMI and RWL were used independently. Applying this method, we identified four bacterial genera and three bacterial species as candidates for predicting success of the weight-loss intervention: the genera were Akkermansia (class Verrucomicrobia), Alistipes (class Bacteroidia), Symbiobacterium, and Pseudoflavonifractor (both class Clostridia), while the species were Alistipes finegoldii, Akkermansia muciniphila, and Ethanoligenens harbinense  are shown. Variables have been sorted by highest values for genera and species. In both cases, ∝ = 1 and 5 folds were used. Genera and species that were eventually selected are in boldface. The same information for other values of ∝, and 3, 8, or 15 folds, is shown for both genera and species in After the elastic net regularization model suggested an initial set of predictor variables, this set was complemented using an MC approach that tested a large number of multiple linear regression models. The predictor variables selected by elastic net regularization and the MC approach were combined to a set of terms that represent the most-promising candidates to predict weight loss according to the present data set. jβ were calculated) for both genera and species, and for delta BMI and RWL. The best models for each number of terms and their predictions for each patient, when applied to the data sets with an added weight-loss column, are listed in Using predictor variables from df = 6) had the lowest AICc in terms of the delta BMI response (74.9), while the best models for 3 and 4 terms had nearly equal AICc values (100.3 vs. 101.2) for the RWL response. The terms used in these models were Marvinbryantia, Megasphaera, and Symbiobacterium in the case of the model with just three terms and the RWL response, and Marvinbryantia, Megasphaera, Symbiobacterium, and Blautia in the other cases. For both responses, relative standard errors for the coefficients varied between 12% and 50%, while adjusted R2 value varied between 82% and 86%. Estimating an R2 value for an independent test data set by performing a cross-validation on the data set with 3, 5, 8, and 15 folds, and calculating the R2 value from the averaged predictions, we obtained values between 67% and 69%, again for both responses.In case of the genera, a model with 4 terms (df = 6) had the lowest AICc in all cases, and the terms used in the models were Alistipes finegoldii, Bacteroides caccae, Bacteroides stercoris, and Roseburia intestinalis in all cases. The relative standard errors for the coefficients varied between 10% and 31%, the adjusted R2 value ranged between 91% (delta BMI) and 93% (RWL), and the cross-validated R2 value from the averaged predictions were ~80% for the delta BMI response and 83–85% for the RWL response, depending on the number of folds used . In detail, patients who were successful in the program had a higher abundancy of Akkermansia, Alistipes, Pseudoflavonifractor, and Symbiobacterium genera  and six species  as candidate indicators for persistent success in weight loss. Preliminary confirmation studies revealed that a single genera or a single species of bacteria are obviously insufficient to make a prediction (own unpublished results); however, it is likely that the identified patterns of bacterial genera or species do allow a prediction of weight loss success. The present study constitutes an important first step to assess possible associations between gut microbial composition and success of a multidisciplinary weight loss program. Based on the findings shown here, future studies can be designed to establish specific recommendations and guidelines for clinical practice, e.g., thresholds for each of the predictive bacteria.Our present analysis revealed a set of seven bacterial genera and eight species from the commensal intestinal microbiota that are potential candidates to predict the likelihood of long-term weight loss success. In our previous studies, the genera PS group . At the NS group . In the Alistipes in the gut. Alistipes was more abundant at baseline in PS participants. This is in line with Lapthorne et al. [Alistipes. In a recent study, the abundance of Alistipes was positively correlated with body weight, fat mass, serum cholesterol and triglycerides, leptin, IL-6 and lipopolysaccharide contents, as well as PPARγ gene expression in mice [Our findings on weight-loss prediction by microbial patterns based on statistical analyses are confirmed by biological considerations regarding the known functionality of the bacterial candidates we identified . For exae et al. , who sho in mice .Akkermansia is another potential indicator for persistent weight loss success. Individuals with higher abundance of A. muciniphila at baseline have been shown to display a greater improvement in insulin sensitivity markers and body composition after dietary intervention [A. muciniphila abundance and being overweight, obesity, untreated type 2 diabetes mellitus, or hypertension [A. muciniphila at the end of the weight-loss intervention program than at baseline. In another study, it was shown that relative abundances of several species including those of Alistipes spp. and A. muciniphila increased after Roux-en-Y gastric bypass surgery in parallel with weight loss and metabolic improvements [According to our data, rvention . In humartension ,22,23,24ovements .Symbiobacterium and Pseudoflavonifractor, which were more abundant in the PS group of patients, both in our previous [Symbiobacterium comprises four species, of which S. thermophilum, a syntrophic bacterium that lives in strict symbiosis with Bacilli, has been studied most extensively [Symbiobacterium species had been related to obesity or metabolic disease. The genus Pseudoflavonifractor only consists of two species, which have also never been associated with obesity or metabolic disease. Thus, these groups of bacteria warrant more attention, especially in the context of obesity-related diseases.Of interest are also the genera of previous  and presensively . HoweverMegasphaera was found elevated at baseline in the PS group and thus can be considered to be a possible predictor for weight loss success. A major bacterial population found that present or elevated in postsurgery subjects with obesity is related to the species M. elsdenii [Megasphaera [Megasphaera abundance is associated with blood glucose and insulin levels [Blautia, implicating a role for these two genera in host glucose metabolism [Marvinbryantia and Blautia that we newly identified as possible predictors for weight loss have been positively correlated with body weight [In addition, the genus elsdenii . It has asphaera . Megasphn levels , as welltabolism . The geny weight .Ruminococcacaeae were found [Oscillibacter belonging to this family was significantly under-represented in patients with nonalcoholic fatty liver disease (NAFLD) [Oscillibacter with obesity [Oscillibacter was a determinant of weight loss success, although less prominent than the genera discussed before.Among the bacteria associated with lower risk of weight gain, several operational taxonomic units (OTUs) assigned to the family of re found ,33,34. I (NAFLD) . Other s obesity ,36,37. IA. finegoldii, A. spHGB5, and A. muciniphila, several butyrate-producing species were identified by our statistical approach, such as Roseburia intestinalis, which was selected as a predictor variable for weight loss success from the MC approach using multiple linear regression models. Consistent with our findings, results from animal studies have shown that an increased abundance of R. intestinalis was associated with weight loss and reduced glucose intolerance [R. intestinalis was shown to be present at lower concentrations in individuals with type 2 diabetes compared to healthy subjects [Bacteroides stercoris  have been identified as butyrate producers [On the species level, eight bacterial species were identified which might have a major impact on weight-loss prediction. Apart from olerance . In humasubjects ,40,41,42roducers .Megamonas and Prevotella were identified as strong markers in the NS group. In the present analysis, Megamonas hypermegale was also identified as a predictor variable for weight loss success from the MC approach. To our knowledge, these are the first data in humans hinting at a link of Megamonas with body weight. Consistent with our results, Megamonas abundance was found to be negatively correlated with weight-loss rate in dogs [Prevotella dentalis was also found as a predictor variable using the elastic net regularization, though it was not among the top predictors. In contrast, Ethanoligenens harbinense, on our list of predictors, has not been studied, to our knowledge, in the context of obesity so far.In our previous study , the bac in dogs . PrevoteOur study has both strengths and limitations that deserve consideration. The rather small sample size of 15 individuals may limit the explanatory power of our analyses. However, the accuracy of our prediction model is high; therefore, the power should be, in fact, sufficient, despite the small number of participants. The strengths of our study comprise the high quality of microbiome sequencing by shotgun sequencing, and the up-to-date multivariate statistical approach. Nevertheless, our findings need confirmation by larger prospective trials.We identified seven genera and eight species within the fecal commensals which might predict persistent weight loss success in obese individuals undergoing nonsurgical therapy. Assessment of these commensals by next generation sequencing or routine qPCR techniques could allow personalized recommendations regarding whether an individual should follow the nonsurgical weight-loss approach or not, increasing the success rate in obesity therapy. Despite a relatively small sample size, the detailed and complex statistical analysis enabled an astonishingly accurate prediction of success and failure with regards to long-term weight loss. These findings warrant further analyses in future confirmatory studies.


Applied research using the phase angle (PhA) in children and adolescents has increased notably. Using multilevel modeling in a fully Bayesian framework, we examined the relationships between PhA, age, sex, biological maturity status, and body size in 10–16-year-old adolescents.n = 241; men, n = 278) from Campinas, São Paulo, Brazil. Biological maturity status was assessed with self-examination of pubertal development for sexual maturity and maturity offset protocol to estimate age at peak height velocity (PHV) for somatic maturity status. Stature and body mass were measured by anthropometry. Phase angle was calculated based on raw resistance and reactance values (50 kHz frequency) obtained by bioelectrical impedance with the foot-to-hand technology.The sample comprised 519 adolescents  than girls . When including body mass in the multilevel models, corresponding changes in the overall body mass mediate most of the influence of the maturity status and age group on the phase angle.The multilevel regression analysis revealed that boys had significantly higher values of phase angle than girls, adjusting for age group and sexual maturity status. Overall, older and more mature adolescents had higher values of phase angle. When considering aligning variation in the phase angle by distance to estimated PHV (maturity offset), there was a higher association between the phase angle and time before and after predicted age at PHV for boys (The present study demonstrated that the variability in phase angle is related to inter-individual variation in sex, age, and maturity status, as well as differences in body size. Research with adolescents considering phase angle should use multilevel modeling with standardized parameters as default to adjust for the concurrent influence of sex, age, maturity status, and body size. R) and reactance (Xc) of a current as it passes through tissues of the body measured  has been an attractive method to assess body composition . The BIAmeasured , 7. R re tissues . Xc reprembranes , 6. BodyR and Xc  results from the two vectors representing R and Xc, PhA is the angle between Z and R , which often requires coping with an imbalance in sample size and heterogeneity among individuals. Therefore, multilevel models should be used as default, as they allow and explicitly model the data structure by allowing for residual components at each level in the hierarchy or cluster , 30. NevIn the present study, using Bayesian multilevel modeling, we examined the age-, sex-and maturity-associated variation in PhA adjusting for the influence of body size in adolescents aged 10 to 16.n = 241; boys, n = 278) from Campinas, São Paulo, Brazil. Participants in this study were adolescents enrolled adequately at the local school, detaining a regular frequency of physical education. In addition, the study did not consider children with physical disabilities (permanent or temporary), children impeding participation in any of the procedures, or those using prescribed medicine. For each participant, all the measurements were obtained in the morning, after an overnight regular fast (8 h), refraining from vigorous exercise for at least 15 h, avoiding caffeine and alcohol during the preceding 24 h, and consuming a normal evening meal the night before.This study used a cross-sectional design on 519 adolescents  approved the research. All procedures followed Resolution No.466 of 2012 of the National Health Council of the Ministry of Health of Brazil and were conducted following the Declaration of Helsinki. Participants and their parents or legal guardians provided informed written consent.Chronologic age was calculated and recorded to the nearest 0.1 years by subtracting the birth date from testing. The participants were categorized by age group as follows: 10–11 years old (10 to 11.9 years); 12–13 years old (12 to 13.9 years); and 14–15 years old (14.to 15.9 years). Stature was measured with a vertical portable stadiometer  to the nearest 0.1 cm. Body mass was measured with a calibrated portable balance  to the nearest 0.05 kg. Technical errors of measurement were 0.29 cm for stature and 0.51 kg for body mass, based on replicated measurements of 20 participants.We estimated the maturity status using two approaches: (i) sexual maturation, using self-examination of pubertal development, and (ii) somatic maturation, using estimations with the maturity offset and age at PHV using sex-specific equations .Before the self-physical examination, the participants were provided with a standardized series of realistic color images with an explanatory text to individually assess their pubertal development , followiWe used the simplified versions of the gender-specific maturity offset protocol  to deterPhA was assessed using a single frequency (50 kHz) BIA device, model Quantum II . All adolescents were instructed to remove all objects containing metal before taking the BIA measurement. Next, participants were laid barefoot, in a supine position, with the legs abducted at a 45° angle, arms far from the trunk, and hands pronated on a table isolated from electrical conductors. After 5 min of resting, the participants' skin was cleaned with alcohol, and two electrodes were placed on the surface of the right hand and two others on the surface of the right foot, according to the recommended protocol . The evaR and Xc in ohms (Ω), and, from these variables, PhA was calculated using the following published equation  all the outcomes for interpretative convenience and computational efficiency. Given the limitations in the agreement between maturity indicators, we explored the influence of maturity status by considering the sexual maturity status as a discrete variable with five levels  and the somatic maturity status using the maturity offset as a continuous variable.i, we used indexes a, s, and m for age group, sex, and sexual maturity status, respectively. The group-level effect terms  and the data-level terms  were drawn from normal distributions with variances to be estimated from the data:To model the influence of age group, sex, and sexual maturity status on PhA, we used varying-intercept models where each participant's outcome (intercept) was estimated as a function of his/her age group, sex, and estimated sexual maturity status (model 1). Hence, for individual We replicated the model 1 structure, adding body mass as a populations level effect (model 2):Considering the somatic maturity status, we used a varying-intercept and a varying-slope model to model PhA as a function of his/her estimated maturity offset, age group, and sex (model 3). We allowed for individuals' maturity offset to vary by sex (varying slope):Again, we added body mass as a population-level effect to the model, but in this case, a varying-intercept model was used (model 4):i), we used the “brms” default prior, Student-t   for the intercept  and a normal prior  for group-level parameters. For the data-level residuals  . Conside 0, 2.5) . We fitt 0, 2.5)  using th 0, 2.5) , which c 0, 2.5) .The distribution of stages of pubic hair within age groups by sex is given in Estimated maturity offset in the sample of adolescents by sex and age group is summarized in The characteristics of the sample by sex are summarized in The multilevel regression models examining variation in PhA associated with gender, age group, and sexual maturity stage are summarized in model 1 of Back transformed posterior estimates of PhA adjusted for body mass, sex, age, and maturation are given in r = 0.31, 90% CI: 0.23 to 0.39) than girls . When adjusting for body mass in the model, the association of PhA with the estimated maturity offset became small  and similar for girls and boys  and adjusting for body mass (model 4) are summarized in and boys . The assand boys .PhA has been considered an important tool for the diagnosis of malnutrition and clinical prognosis, which can be associated with changes in cell membrane integrity, changes in fluid balance, and information on cell health and integrity  , 40. TheThe growth characteristics of this sample of Brazilian adolescents were consistent with other reports of healthy young populations –43. In aper se on PhA when individual variability is aligned to biological maturity indicators; in the present study, on self-examination of pubertal development and time before or after PHV, it has been noted that PhA values were higher, albeit with small magnitude, in early maturing adolescent football players than in late maturing players, considering the skeletal maturity status using the Tanner-Whithouse-3 method . Furthermore, although we took advantage of Bayesian inference in our models, the sample was from the same region within a cross-sectional design, limiting generalizations. Therefore, future studies should adjust PhA considering biological, contextual, and fitness characteristics based on longitudinal observations.In summary, our study demonstrated significant interindividual variation in PhA among female and male adolescents. Furthermore, the variability in PhA is related to interindividual variation in sex, age, maturity status, and body size differences. Overall, the present study results highlight the need to account for the transient influence of pubertal growth on body size, shape, and composition and its effect on the interpretation. PhA has been proposed to assess body composition using whole-body BIA that can represent the intracellular/extracellular water ratio , providihttps://osf.io/j2yzez/.Publicly available datasets were analyzed in this study. This data can be found at: The studies involving human participants were reviewed and approved by the Ethics Committee of the Pontifical Catholic University of Campinas (CAAE: 79625817.6.0000.5481) approved the research. All procedures followed Resolution No.466 of 2012 of the National Health Council of the Ministry of Health of Brazil. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AM, HC, and GG-J: conceptualization. RQ, AL, and HC: data curation. AM and HC: formal analysis and writing-original draft. GG-J: project administration. AM and GF: investigation. AM, RQ, AL, GF, HC, and GG-J: writing-review and editing. All authors contributed to the article and approved the submitted version.RQ was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES (finance code 001). The study was partially supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation).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.


Notably, MCH level was significant different among three groups (p = 0.009). Thus, all data were separated into two groups according to MCH level, and significant increases in the length of hospital stay were observed between two groups (p = 0.030). A positive correlation between length of hospital stay and MCH was observed . Multiple linear regression analysis showed that MCH was independent correlated with the length of hospital stay, no matter whether severity classification of AP was included . Our results demonstrated that the length of hospital stay was correlated with MCH level in patients with AP, and MCH level at admission may predict the length of hospital stay independent of severity classification in AP. These results may provide a potential evaluation basis for the management of patients with AP.Mean corpuscular hemoglobin (MCH) is a common blood routine test index. To explore the relationship between MCH and length of hospital stay in patients with acute pancreatitis (AP), we included 273 patients with AP without coronary heart disease, diabetes, hypertension and anemia in this study. All data were separated into three groups according to the length of hospital stay. Gender ( AP is oSeverity classification is correlated with the length of hospital stay in patients with AP. Previous data showed that both Revised Atlanta Criteria and Determinant Based Criteria, which stratify AP by severity, strongly predict the length of hospital stay , but theBlood routine test is the most common clinical test at the beginning of hospitalization. Mean corpuscular hemoglobin (MCH) is the average amount of hemoglobin (HGB) per red blood cell and is calculated by dividing HGB by red blood cell (RBC) count. Mean corpuscular volume (MCV) is the average size of a red blood cell, and the mean corpuscular hemoglobin concentration (MCHC) is the average concentration of HGB per unit volume of red blood cells. The disease status of AP has a significant impact on blood routine test, and often abnormal hematological parameters predict adverse clinical events in patients with AP. For example, red cell distribution width (RDW) predicts the severity of patients with AP in pregnancy . It has 22.1Patients with AP from Zhongda Hospital, School of Medicine, Southeast University, were included in the retrospective study, and the diagnosis of all patients with AP was defined in accordance with the criteria of IAP/APA evidence-based guidelines . Blood r2.2p-value of <0.05 was considered to be statistically significant.SPSS software version 23.0 was used to analyze all data. Continuous variables were shown as the mean ± standard deviation, and categorical variables were presented as percentages. The comparisons among three groups of continuous variables were performed by one-way analysis of variance. The comparisons of ordinal categorical variables were performed by rank sum test, and chi-square test was used to compare unordered categorical variables among three groups. Pearson or Spearman’s correlation analyses were employed to examine the correlations between the length of hospital stay and MCH appropriately. The multiple linear regression analysis was performed to analyze the independent effects of length of hospital stay in all subjects. A 33.1p = 0.017) and severity classification (p < 0.001) was found. We observed significant difference of MCH among three groups . We also noticed significant difference of RBC among three groups . There were no significant differences for other variables, including age, smoke, alcohol, cholecystectomy, WBC, HGB, RDW, MCV and MCHC.p = 0.030). We also noticed significant differences in gender (p = 0.029), RBC (p < 0.001), RDW (p < 0.001), MCV (p < 0.001) and MCHC (p < 0.001) between two groups. There were no significant differences for other variables, including age, smoke, alcohol, cholecystectomy, WBC, HGB and severity classification.Due to the above interesting results between length of hospital stay and MCH, we separated all data into two groups according to the median number of MCH . We obse3.2r = 0.172, p = 0.004). To further explore the correlation between length of hospital stay and other laboratory data, we did the correlation between the length of hospital stay and other laboratory data in whole population , severity classification , WBC  and RBC . Length of hospital stay had no correlation with age, smoke, alcohol, cholecystectomy, HGB, RDW, MCV and MCHC.As shown in pulation . Length 3.3p < 0.001; beta = 0.212, p < 0.001). Length of hospital stay was independently correlated with severity classification and gender , as shown in The correlation analyses were carried out in all subjects. The basic demographic characteristics, such as gender, age and AP severity, may influence the length of hospital stay . The lab4We found that length of hospital stay had a relationship with MCH level in patients with AP, and the multiple linear regression analysis showed that MCH level positively correlated with the length of hospital stay independent of severity classification of AP. It has been reported that a few of biomarkers are associated with the length of hospital stay in patients with AP. Serum lactate dehydrogenase (LDH) and its isozyme hydroxybutyrate dehydrogenase (HBDH) were early predictive markers of the severity of AP ,14. LDH The mechanisms of MCH as a predictor of length of hospital stay in AP are not fully clear. However, some hypotheses can be proposed. One potential explanation is that our study did not exclude patients with liver and kidney dysfunction, which caused a decrease in erythropoietin levels . The bodp < 0.001), but there is no significant difference for RDW among three groups divided by the length of hospital stay in p < 0.001, Indeed, the severity classification of AP was a strong risk factor of length of hospital stay in patients with AP, and the more serious the patient was, the longer they stayed in hospital . The lenTo exclude the effects of anemia on the correlation between MCH and length of hospital stay in patients with AP, patients with AP with anemia were excluded in this study. Interesting, after excluding patients with AP with anemia, the statistically correlation between length of hospital stay and MCH still was observed in patients with AP, and HGB was not the risk factor of length of hospital stay according to the multiple linear regression analysis .The present results had some limitations. First, serum samples of patients could not be obtained, so that we could not measure serum concentration of inflammation markers, such as IL-6 and TNF-α. Second, considering different medical treatment of different hospitals, there were differences among the treatment of AP. Although most patients will be treated according to clinical guidelines in different medical institutions, it is still possible to affect the relationship between MCH and length of hospital stay in our study. Third, the patients’ economic position and treatment willingness may be a potential confounding factor that affects our final outcomes in patients with AP.In conclusion, the evaluation of length of hospital stay is conducive to the management of patients by hospital. We demonstrate that length of hospital stay is correlated with the MCH level independent of severity classification in patients with AP, and the MCH level at admission may have an effect on predicting the length of hospital stay in patients with AP.


The aim of this study was to analyze the influence of age and sex on kinematic gait parameters in preschool children, and derive reference values for this population. A total of 383 preschool children  participated in this study. We used the OptoGait system to assess the kinematics of gait at a comfortable and self-determined speed. No significant differences between the sexes were found for the main gait parameters. Among the participants, there was a significant increase in double support, reductions in absolute cadence and the coefficient of variation (CV) of cadence, an increase in absolute step length (SL), and an increase in the walk ratio (WR) from 3 to 5 years of age. However, the normalized SL and normalized WR displayed a significant reduction in both sexes. Partial correlation indicated a significant association of age with SL and normalized SL, and WR. Additionally, WR showed a significant correlation with the CV of cadence. To summarize, no relevant differences in gait performance were found according to sex; however, age was found to influence gait maturation. The normative values established for Spanish preschool children can be used to monitor healthy gait development. The preschool age is characterized by important changes in the acquisition of locomotor skills and nervous system maturation . Among tSeveral previous studies have attempted to characterize gait in children ,4,5,6 baOverall, stride length and cadence are the main kinematic parameters used to analyze gait maturity. Stride and cadence are functions of anthropometric characteristics and sex . At freeThe mean values of kinematic parameters reflect the functional characteristics of gait ; howeverChanges in gait patterns occur as a child matures, but they may also reflect pathological changes in neurological or musculoskeletal systems . PreviouIn the first years, any attempt to categorize gait development should include a standardized baseline of kinematic parameter values with narrow age intervals in order to provide precise normative data . TherefoBecause gait deviations commonly occur in children, in this regard, examination and identification of gait abnormalities allow appropriate clinical decisions to be made. Therefore, developmental centile charts of gait measures offer a solution to assess an individual child’s evolution. Because collections of normative gait data in healthy children significantly diverge from one country to another , we deci2; 207 girls and 176 boys). The sample was selected from a large region of Andalusia (Spain) containing both urban and rural populations. The inclusion criteria for participant selection were: the absence of any neurodevelopmental or neuromotor disability, such as autism or Down syndrome; the presence of any pathological disorder associated with the visual or vestibular systems; and orthopedic or developmental difficulties. Parents signed an informed consent form permitting their children to take part in this research. The study was completed per the norms of the Declaration of Helsinki (2013 version) and was accepted by the Ethics Committee at the University of Jaen (Spain) (DIC.18/3.TES).We conducted a cross-sectional study. A prior sample size calculation was performed using G*Power software . The res2 (in meters).Body mass (kilograms) was measured using a weighing scale , and body height (centimeters) was assessed with a stadiometer . The body mass index (BMI) was estimated by dividing weight (kilograms) by body heightGait speed (GS) was analyzed with photocells  that were placed at the beginning and end of a 5 m corridor a. We useThe assessment was carried out on a flat, straight, noncarpeted surface, and both ends of the walkway were designated by two cones. The subjects were asked to walk at a comfortable and self-determined speed along a 5 m hallway. All subjects wore their own shoes and were asked to walk as naturally as possible. Additional meters at the start and turns were added to avoid recording acceleration or deceleration during walking. Partially recorded footfalls were omitted from the analyses. Children performed three walks for familiarization at a self-selected speed. Ten consecutive walking trials were recorded with an average step count of 56.12 ± 7.49 steps to provide an accurate representation.https://www.R-project.org/, accessed on 1 September 2021)—with the GAMLSS package and MedCalc Software . The significance level was set to α < 0.05. The data are shown in descriptive statistics for means, standard deviations, and centiles. Tests for the normal distribution and homogeneity of variances  were conducted on all data before the analysis. Differences between sex and age groups were analyzed using a two-way ANOVA corrected by the Bonferroni test. A partial correlation analysis was performed between gait parameters (adjusted by age and sex); the magnitude of the correlation among measurement variables was set according to Hopkins et al. [Data were analyzed using SPSS, v.19.0 for Windows  and the statistical software package R—a free software environment for statistical computing and graphics that compiles and runs on a wide variety of UNIX platforms, Windows and MacOS , reductions in the absolute cadence (p < 0.05) and the CV of cadence (p < 0.05), and increases in absolute SL (p < 0.001) and the WR (p < 0.001) from 3 to 5 years. However, normalized SL and WR displayed a significant reduction  in both sexes.The kinematic parameters of gait are shown in p < 0.001 and r = −0.400, p < 0.001, respectively) and with WR . In addition, WR showed a significant association with the CV of cadence . The centiles of cadence, CV of cadence, SL, and CV of SL by age and sex are shown in The partial correlation indicated a significant association of age with SL and normalized SL (r = 0.323, The main objectives of the current study were to examine the influence of age and sex on kinematic gait parameters in preschool children, to determine the profile of change in gait variability with age, and to derive reference values in Spanish preschool children. The main finding of this study was that non-significant differences were found between sexes in the main gait parameters analyzed; however, age showed a significant influence on cadence, SL and its variability, and WR. Taking into account that preschool age is a period of rapid developmental changes, in disagreement with , we can Consistent with previous studies ,7,22, weOverall, WR, as a measure of gait maturation assessment, has often been overlooked in preschool children. WR is commonly a constant value in normal healthy populations, independent of age, height, sex, and gait speed ,20,36. AThis study has several limitations. First, and according to Guffey et al. , childreFrom a practical point of view and considering the lack of reference values for assessing the gait parameters of Spanish preschoolers, the extreme percentiles can be used as a ‘warning sign’, indicating that it may be necessary to conduct supplementary tests to identify potential motor delays in this population in relation to healthy gait development.To summarize, no relevant differences in gait characteristics were found according to sex; however, age was shown to have an influence on gait maturation. The reference values established for Spanish preschool children in the current study could be used to monitor healthy gait development.