Background: Impaired gait and balance are associated with severity of leukoaraiosis. Evaluation of balance is based on neurological examination using Romberg's test with bipedal standing, assessment scale, and posturographic parameters. The goal of this study was to determine the relationship between static equilibrium and grades of white matter hyperintensities (WMHs) using static posturography as a quantitative technical method.Method: One hundred and eighteen (118) patients with lacunar infarct were recruited and assessed on MRI with Fazekas's grading scale into four groups. On admission, age, gender, height, weight, Berg Balance Scale (BBS), mini-mental state examination (MMSE), and static posturography parameters were recorded, and their correlations with WMHs were determined.Results: Age was significantly and positively correlated with severity of WMHs . WMH score was negatively correlated with BBS score  and MMSE score . There was a significant positive correlation between track length anteroposterior  and severity of WMHs . Partial correlation analysis and multiple logistic regression analysis indicated that track length AP with eyes closed, was a predictor for the severity of WMHs (p< 0.05).Conclusion: The severity of WHMs is associated with age, cognitive decline, and impairment in balance. Posturography parameter in track length in AP direction with eyes closed in relation to cognition and balance, may be a potential marker for disease progression in WMHs. Changes in cerebral white matter, also called white matter hyperintensities (WMHs), which are seen in one-third of the ischemic stroke population, are risk factors for acute stroke . AlthougA growing body of evidence suggests that postural instability and falls are common and devastating problems in older adults . Some clStatic posturography could be used for accurate and objective measurement and analysis of subtle changes in reflexes in maintaining balance, with specialized techniques . It is an = 28); grade 1 for patients with mild WMHs ; grade 2 for patients with moderate WMHs , and grade 3 for those with severe WMHs .A total of 118 patients admitted and treated in the Department of Geriatric Neurology were prospectively recruited from the Affiliated Brain Hospital to Nanjing Medical University between January 1, 2019 and December 31, 2019. The criteria used were: age above 18 years; patients diagnosed with lacunar stroke according to the TOAST criteria through magnetic resonance imaging (MRI), and patients who were referred with chief complaints about cognitive deficit and imbalance not directly related to the presence lacunar stroke. This study excluded patients in the following categories: (1) patients with contraindications to MRI; (2) patients with WMHs from other identified causes; (3) patients with hemorrhage, severe stroke, Alzheimer's disease, Parkinson's syndrome, paralysis, and aphasia; (4) patients with evidence of a cardiac embolic source or cerebral large vessel disease ; (5) patients with orthopedic diseases, peripheral neuropathy and proprioceptive loss according to physical examination for the nervous system, MRI for spinal cord, and electromyography examination; (6) patients with benign positional vertigo, Meniere's Disease and vestibular neuritis and other peripheral vertigo disease according to positioning test and the video head impulse test . The video impulse test was performed as follows: patients sat on chairs, wearing the head pulse test system, looking at the target 120 cm in front. The clinician performed transient, passive and rapid head pulse motion on the plane of the horizontal semicircular canal (left and right), about 15° in about 100 ms. Sensors of the test system detected eye and head movements. Gain was calculated by comparing the areas under the head movement and eye movement curves , the patClinical data were collected from all patients, with respect to age, gender, height, weight, Berg Balance Scale (BBS), and mini-mental state examination (MMSE). The Berg Balance Scale (BBS) is a 14-item scale which quantitatively assesses balance and risk of falls. The items are scored from 0 to 4 for a total score of 56. High scores in this test indicate excellent balance. Mini-mental state examination (MMSE) is a 10-item screening tool for evaluation of cognitive function. It is 30-point scale for assessing orientation, memory, attention, calculation, and language.2), (3) track length mediolateral (ML) (cm), (4) track length anteroposterior (AP) (cm), (5) track length per unit area (cm/cm2), and (6) average velocity (cm/sec).Postural instability was measured using a digital platform consisting of two-foot plates with four in-built vertical force transducers for determination of instantaneous fluctuations in the center of pressure . With eyp-values were two-sided. Differences were assumed as statistically significant at p < 0.05.All statistical analyses were performed using the SPSS . Categorical variables for gender are expressed as counts (percentage). Numerical variables are presented as mean ± standard deviation. Chi-square statistics for gender and bivariate correlation analysis (Spearman correlation coefficient) for numeric variables were conducted to determine their correlations with different grades of WMHs. The associations between track length AP in eye closed and age, BBS and MMSE were determined using bivariate correlation analysis (Pearson correlation coefficient). To further evaluate the association between static posturography and WHMs grades, partial correlation analysis and logistic regression analyses were carried out. The r = 0.39, p < 0.05). The BBS scores indicated that deficits in balance significantly decreased in different grades . In addition, there was a negative correlation between MMSE score and WMHs grade . There were no significant differences in gender, height, and weight amongst patients in the different grades.The clinical features which were correlated with WMHs grades are summarized in r = 0.70, p < 0.05). As shown in r = 0.27, p < 0.05); BBS , and MMSE . In order to evaluate the potential influences of age, BBS, and MMSE, correlation analysis between track length AP and WMHs grades was repeated using partial correlation analysis, after adjusting for age, BBS, and MMSE. The correlation between track length AP and WMHs grades remained significant  in To investigate correlation between static posturography and severity in WMHs patients, correlation analysis was used . There wp < 0.05).Based on the results of correlation analysis, logistic regression analyses were carried out to identify independent indicators of grades in WMHs. As shown in In this study, the potential clinical use of static posturography in the assessment of severity of WHMs was determined. There was a positive correlation between age and WMHs severity. In different grades of WMHs, there was a significant negative correlation between balance and cognitive function represented by BBS and MMSE, respectively. Posturography parameter in track length in AP with eye closed was related to age, BBS, and MMSE, indicating the importance of evaluating severity of WMHs using partial correlation analysis and logistic regression analyses.r = 0.33), after adjusting for age, BBS and MMSE. In the results logistic regression analyses, track length AP with eyes closed was identified as an independent indicator of grades in WMHs. Those results indicated static posturography could be applied as a new accurate and objective assessment method of balance for WMHs severity.It is known that WMHs are highly prevalent in the elderly, and they increase the risk of acute stroke, Alzheimer's disease, and Parkinson's disease –17. ThesAssessment of locomotion based on the overall coordination of balance involves the vestibular, kinesthetic, visual, and tactile analyzer . TherefoIn this study, it was found that WMHs were associated with age, cognitive decline, and abnormality in balance. Thus, static posturography may be an accurate and objective assessment of the presence of an imbalance in WMHs. Nonetheless, this investigation has some limitations. In the first place, it is a single-hospital study. Therefore, the possibility of case selection bias cannot be ruled out. Thus, a multi-center clinical trial is needed. Secondly, track length AP with eyes closed is a sensitive index but other parameters could be significantly different in WMHs if the number of samples is increased. Besides, there is need for research on the associated pathway in vestibulospinal reflex and cognitive decline. Mild proprioceptive loss and peripheral neuropathy might influence AP track length eyes closed, as study participants included those aged over 80 and with diabetes. In the future, prospective studies should explore combining a number of physiological and anatomical assessments, to include static posturography, functional MRI, and specific tests of vestibular function such as video head impulse test and vestibular evoked myogenic potentials.Static posturography may be an accurate and objective assessment method for balance in aged patients with WMHs. It may offer a new target for practical evaluation and further treatment of patients with balance deficits in WMHs.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Nanjing Brain Hospital. The patients/participants provided their written informed consent to participate in this study.GZ and LJ: Participation in the whole work, drafting of the article, and data analysis. BL and JS: perception and design, operation, and final approval of the version to be published. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


BCP-ALL patients with 85% accuracy; and the phase shift of the first derivative in the spectral range 1050–1042 cm−1 correlating with white blood cell (WBC) and blast cell count in BCP-ALL patients contrary to the samples obtained from healthy controls. Although verification in larger groups of patients will be necessary, these promising results suggest that FTIR spectroscopy may have future potential for the early screening of BCP-ALL.Early detection of the most common pediatric neoplasm, B-cell precursor lymphoblastic leukemia (BCP-ALL), is challenging and requires invasive bone marrow biopsies. The purpose of this study was to establish new biomarkers for early screening to detect pediatric leukemia. In this small cohort study, Fourier transform infrared (FTIR) spectra were obtained from blood sera of 10 patients with BCP-ALL and were compared with the control samples from 10 children with some conditions other than neoplasm. Using various analytical approaches, including a new physical model, some significant differences were observable. The most important include: the different peak area ratio 2965/1645 cm Acute lymphoblastic leukemia (ALL) is the most frequent cancer diagnosed in children and represents approximately 25% of all cancers diagnosed up to 15 years old .The diagnosis of ALL is usually established by examining bone marrow aspirates. This invasive procedure is often performed under general anesthesia in children and the indications for bone marrow biopsy should be considered carefully, particularly in younger children. Unfortunately, there are many transient conditions, such as infections, that can imitate acute leukemia in their clinical and laboratory presentation. Therefore, the implementation of an effective, rapid tool for the early detection of leukemia from serum could limit the number of unnecessary bone marrow aspirations under general anesthesia.−1), with characteristic absorbance peaks corresponding to nucleic acids, proteins, carbohydrates, and lipids. Contrary to standard diagnostic tools, FTIR is a rapid, cost-effective, and reproducible tool. Significantly, it requires minimal sample pre-processing. In recent years, many studies have demonstrated the application of FTIR spectroscopy to the early detection of cancer-specific chemical changes in tissues, cells, and biofluids, thus raising the potential that it could be used for screening and early diagnosis of neoplasms : 1641/1537, 2926/1641, 2926/1537, 1070/1239, 3277/1537, 3277/1641, and 1641/1239 for the BCP-ALL group; as well as corresponding to the peak area ratios in the control group: 1645/1538, 2924/1645, 2924/1538, 1071/1241, 3278/1538, 3278/1645, and 1645/1241. As might be expected, the majority of the peak area ratios tested were not significantly different between both groups. However, the peak area ratio 2965/1645 cm−1 was significantly different, with median values for BCP-ALL vs. control of 0.54 (range 0.066–1.505) and 1.595 (range 0.585–2.527), respectively (p = 0.002). The peak at 2965 cm−1 corresponds to asymmetric stretching vibrations of CH3 group in lipids, while band 1645 cm−1 corresponds to C=O stretching of α-helix proteins. Any other differences visible in the graphs of average spectra in both BCP-ALL and controls  were not statistically significant and are irrelevant for classification.There was no significant difference in the maximal absorbance values of representative peaks corresponding to fundamental compounds . Sheng et al.  have dem2A/dν2 normalized spectrum for the region from the 1600 cm−1 to the 1700 cm−1, and the Gaussian deconvolution of the amide I band for the control and BCP-ALL samples. The positions of the second derivatives minima correspond to the positions of the individual spectral lines. These lines overlap, forming the amide I band, but each of them can be assigned to a specific protein conformation , reveals graphical patterns which can be used to classify patients or persons from the control group, according to the absorption dynamics. Strictly speaking, the graphs (RefSpec(k), PatSpec(k)) and (RefSpec(k), ConSpec(k)) on Cartesian space for the region Presentation of the data on the Cartesian space In these narrow regions of wavenumbers, two opposite dynamics can be noticed for the patients, namely covariant and contravariant compared to the reference IR spectra. These dynamics can be labelled by phase shift between the first derivative of reference IR spectra (RefSpec) and the first derivative of IR spectra for patients, PatSpec or ConSpec. In the covariant case, the phase shift is equal to 0, and in the contravariant case, it is equal to π  ratios were lower in leukemia patients’ serum. Unfortunately, the examined sera were obtained from patients with different types of leukemia .Sheng et al.  showed t−1 (corresponding to carbohydrates), 1270 cm−1 (amid III), and 1592 cm−1 (amino acids) were significantly reduced in spectra obtained from plasma of healthy persons compared to patients with chronic lymphocytic leukemia. Furthermore, cluster analysis of the obtained spectra at those specific regions provided an excellent classification of the healthy and the patient samples, which correlate completely with clinical data.In another study , the auPrevious publications have reported the application of FTIR to the diagnosis and monitoring of acute lymphoblastic leukemia. These studies have focused, however, on the examination of bone marrow or isolated lymphocytes examination ,30,31,32−1 is correlated with WBC as well as blast cell count in BCP-ALL patients, contrary to the samples obtained from healthy controls, wherein no relationship with WBC was confirmed. We have shown that this connection is not random. It can be explained by different composition of leukemic sera resulting in the rapid proliferation of leukemic cells in blood and bone marrow. Compared with controls, patients with acute leukemia show serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline, and fatty acid metabolisms [−1 and 1645 cm−1 (2965/1645) and the position of the peak for the amide I band maximum in the average leukemic and normal FTIR spectrum.In our initial data analysis, we found that the first derivative of the spectral data allowed for greater discrimination between the patient groups. From this, we developed a new original approach for spectral data analysis based on Lissajous figures and on the dynamics of the absorbance in spectra. The first derivative of the spectra was used to plot Lissajous figures. Their phase shift in the spectral range 1050–1042 cmabolisms ,34. The abolisms , who stuWe are conscious that the number of analyzed samples is too small to draw definitive and strong conclusions about the clinical importance and practical application of the obtained results. We believe though that these results are promising and that they justify further studies in larger groups of patients. After positive verification, this tool could be applied for early ALL screening.In conclusion, there are some interesting differences between the FTIR spectral profile of leukemic and normal serum. These differences may offer a potential route to the early identification of children with ALL using FTIR spectroscopy and in so doing could limit the number of invasive procedures and accelerate the diagnosis of individuals. These results must be verified in prospective studies in larger groups of patients and healthy individuals.Ten patients with newly diagnosed BCP-ALL were included in this study. They all were hospitalized in the Department of Pediatric Hemato-oncology, Clinical Regional Hospital in Rzeszow, Poland. The median age of our study group was 8 years (range: 2–17 years.), and the male/female ratio was 3:2. All serum samples were obtained at diagnosis for routine medical tests. The diagnosis was confirmed by bone marrow biopsy with the expression of the antigens corresponding to precursor B lymphocytes.Four healthy pediatric donors and six children with conditions other than neoplasm and benign conditions were included in the control group. All blood samples were taken because of other medical indications. The median age in this group was 8 years. (range: 0.5–15.5 years), and the male/female ratio was 1:1.The study was conducted under Institutional Review Board Protocol No. 1/01/2020 from 30/01/2020 at the University of Rzeszow. The experimental protocols used in this study were approved by the institutional ethics committees (IECs) of the University of Rzeszow and were carried out following the approved guidelines. Informed consent was obtained from all subjects or their guardians before blood sample collection.Following standard procedures, whole blood samples were collected into clot activator tubes and were left to clot at room temperature for a minimum of 30 min and a maximum of 2 h. Blood serum was obtained by two-step centrifugation; first at 3000 rcf for 5 min, and then the supernatant from this was recentrifuged (5000 rpm for 5 min) to prevent blood cells contaminating the FTIR spectrum. All serum samples were frozen (−80 °C) until analysis.2) slides and left to dry for approximately one hour to eliminate water interference in FTIR spectra.Shortly before analysis, serum samples were thawed at room temperature and 10 µL of blood serum was pipetted onto the calcium fluoride  equipped with attenuated total reflection (ATR) plate, single-reflection snap ATR crystal as a source of mid-infrared radiation, and MCT (Mercury–Cadmium–Telluride) IR (infrared) detector.All sera spectra were acquired in the mid-infrared (MIR) range of 400–4000 cmThe plate was cleaned with ethanol (95%) before each spectrum was recorded and the air was measured as a background. For each serum sample spectra were recorded in duplicate or triplicate. A total of 63 spectra were collected during this study.−1). In the first step, the analysis of the second derivative for a given region of individual spectra was calculated using the Savitzky–Golay differentiation . The obtained information was used for the curve-fitting procedure. Gaussian functions were then fitted to the observed bands. The analyzed band consists of 8 spectral lines. The sum of the value of all maxima absorbance corresponding to α-helix and β-sheet were considered.To investigate the secondary structure of proteins contained in the tested serum samples, the second derivative analysis and the curve-fitting procedure in the amide I spectral region was applied. The lines forming this band are highly sensitive to molecular geometry and hydrogen bonding, which allows for the analysis of the protein secondary structure ,21,35. Thttps://opus-application.software.informer.com/7.0/) and KnowItAll Academic Edition . Moreover, in each FTIR spectrum, vibrations corresponding to nucleic acid, phospholipids, proteins, and lipids were analyzed. The number of obtained data was from FTIR; therefore, to determine a similarity between analyzed groups, a PCA analysis was done. PCA reduces the dimensionality, the number of variables of the data, by maintaining as much variance as possible. This analysis was done using Past software . Moreover, to determine the similarity between samples within the groups, a hierarchical cluster analysis (HCA), using Past software, was done. Further data analysis including clustering and dimensionality reduction was performed using Python 3.6  and Scikit Learn 0.19.1 .For all obtained spectra, vector normalization and baseline correction were applied. These operations were performed using OPUS 7.0  by implementing the Youden index.p < 0.05. The calculations were performed using Dell Inc.’s Dell Statistica , version 13 (2016).The level of significance was


They also had prolonged sleep latency (p < 0.001) with reduced sleep efficiency (p < 0.001). Patients in exacerbation of IBD had higher scores in PSQI (p = 0.008), ESS (p = 0.009), but not in AIS, compared to those in remission. Participants with comorbid chronic diseases had higher scores in PSQI and AIS, but not in ESS, compared to others. Multiple regression revealed that the sleep questionnaire results were significantly affected by mood level (BDI), but not by the aforementioned pain scales. Sleep impairment in IBD patients is a common problem that deserves attention in everyday clinical practice and mood level seems to be the main factor affecting the quality of sleep in IBD patients.The causes of disordered sleep, frequently reported by patients with inflammatory bowel diseases (IBD), are poorly understood. The study aimed to evaluate sleep quality in IBD patients and to identify factors affecting their sleep. IBD patients (n = 133) and healthy controls  were included in the study and completed sleep questionnaires , Athens insomnia scale (AIS), and Epworth sleepiness scale (ESS)), Beck Depression Inventory (BDI), and pain scales . IBD patients attained higher scores in all sleep questionnaires compared to HC: PSQI, AIS, and ESS (all  Inflammatory bowel diseases (IBD) represent the group of chronic gastrointestinal tract diseases, including Crohn’s disease (CD) and ulcerative colitis (UC) ,2,3. ImpSleep is a physiological state in which people spend over one-third of their life, but so far it is poorly understood ,7. The aNumerous studies on sleep quality among IBD patients have been published ,15,16. TTherefore, the aims of the study were assessment of sleep quality and the search for factors affecting sleep among IBD patients.There were 190 study participants recruited for the study in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland, which included 133 IBD patients (68 with CD and 65 with UC) and 57 apparently healthy subjects serving as control (HC).The severity of the disease was assessed by clinical scales: Harvey–Bradshaw Index (HBI) for CD and Partial Mayo Score (PMS) for UC. Disease remission was defined as a score below 5 points according to HBI and 2 points according to PMS ,20.Information on the course of the disease, previous gastrointestinal operations, the presence of fistulas , perianal fissures, abscesses, the disease onset, extraintestinal complications , information about the current treatment, smoking and other chronic diseases  were collected.The inclusion criteria comprised of the signing of informed consent to participate in the study, age over 18 and under 65, and diagnosis of IBD based on clinical, radiological, endoscopic, and histopathological criteria. Exclusion criteria were previous abdominal and thoracic surgery in the last six months, active malignant disease except for skin basal cell carcinoma, addiction to alcohol or other psychoactive substances, diagnosed and treated psychiatric disorders.Healthy volunteers were recruited for the study according to the snowball sampling method . The addThe study protocol was accepted by the Ethical Committee of the Medical University of Lodz, Poland (number: RNN/433/18/KE). All respondents received information for the patient and were asked to sign informed consent to participate in the study.Respondents completed questionnaires of sleep quality, mood level, and pain intensity. The study was conducted in a ward and outpatient clinic, which are part of the Department of Digestive Tract Diseases. The researchers provided participants with instructions regarding the questionnaires. All patients who consented to participate in the study, completed all questionnaires. Sleep quality was measured by PSQI , Athens p < 0.05). Thus, they were presented as median with interquartile range (IQR: first–third quartile) and non-parametric tests were used: Mann–Whitney U test for two independent samples, and Spearman’s rank correlation for two continuous variables. Fisher’s exact test (nmin < 5), χ2 with Yates’ correction (5 ≤ nmin < 15), and χ2 (nmin ≥ 15) were used for testing dependencies between nominal data. Moreover, we decided to conduct a multiple regression analysis (a forward stepwise model) to determine the impact of dependent data, including BDI and pain parameters , on selected sleep questionnaires . A p-value less than 0.05 was considered as statistically significant; only for multiple testing between dependent subgroups the Bonferroni correction was used .Statistical analysis was performed using Statistica 13.1PL . Obtained data had non-normal distribution  suffered from active IBD, while 50 participants (37.6%) were in remission. The characteristics of the study participants are presented in p = 0.025). Similarly, higher percentage of IBD patients scored more than 5 points in AIS, namely 49.6% (n = 66) vs. 26.3% of HC . Further, at least 11 points in ESS was attained by 21.1% of IBD patients (n = 28) while only by 5.3% of HC .IBD patients attained higher scores in all sleep questionnaires compared to HC. They also had prolonged sleep latency, more often complained of nocturnal defecation, and their sleep efficiency was reduced compared to HC . Six or p = 0.740), AIS , and ESS , respectively.Results of sleep questionnaires were similar in CD and UC patients: PSQI , but not with AIS , nor ESS . There were also positive correlations between PMS (estimated for UC patients) and PSQI , AIS , as well as ESS . The age of IBD patients did not correlate with the PSQI , AIS , and ESS  scores.HBI values (estimated for CD patients) were positively correlated with PSQI  and the severity of depression according to BDI as well as pain according to VAS and LPS, The problem of disordered sleep in immune diseases has been recently widely studied ,16,27,28In our study, patients with CD and UC had similar sleep quality measured with PSQI and AIS, and daytime sleepiness according to ESS. Sobolewska et al. also did not notice differences in the quality of sleep between CD and UC on a small group of patients measured by PSQI . InteresWe showed, that IBD patients had greater sleep-related problems measured by PSQI compared to HC. The severity of the disease had an impact on the results of PSQI and patients in exacerbation had worse sleep quality compared to those in remission and HC. In another study, the decreased quality of sleep measured by PSQI in CD patients compared to healthy controls was also noted and the correlation between the severity of the disease and the PSQI score was observed . We did Additionally, we noticed more frequent sleep interruption by getting up to the toilet in IBD patients compared to HC, as well as among patients in IBD exacerbation than in remission. Therefore, unsurprisingly, diarrhea may be one of the main causes of disordered sleep.Although many guides for patients highlights the problem of insomnia in IBD, the studies using scales dedicated to its evaluation are few. In the Canadian Community Health Survey, the likelihood of bowel disorders increased with the frequency of insomnia problems; however, the severity of insomnia was measured using questions elaborated by the authors . RecentlPatients in our study attained higher median results of ESS reflecting daytime sleepiness than HC. However, only 21% of IBD patients scored 11 or more points (which characterizes at least mild sleepiness). Iskandar et al. did not notice the difference in ESS between CD and HC, but patients with active disease had higher scores than in the remission. There were also no differences in the results of actigraphy and urine melatonin levels between CD and controls . In anotSleep is affected by many factors, such as mood, stress, and medications. One of them is the use of glucocorticosteroids, their negative effects on sleep have been reported . NeverthDisordered sleep may also be affected by the concurrent depression, which in the patients with IBD is more often diagnosed than in the general population ,46,47. NPain also represents an important factor affecting sleep quality in the general population . We haveThe limitation of this study was the use of subjective methods to assess the quality of sleep. On the other hand, the questionnaires used were validated and are still widely used. The use of three questionnaires assessing sleep in its various aspects increased the value of information obtained. However, future research should also include polysomnography and actigraphy to better understand the nature of sleep disturbances in IBD patients. The division of patients by clinical condition based on subjective scales (HBI and PMS) was also a limitation to this study. However, these scales are based on the complaints reported by patients that have an important impact on their perception of the quality of life.Sleep impairment in IBD patients is a common problem that deserves attention in everyday clinical practice. Adequate sleep counseling can not only improve the quality of life of these patients, but also can have a positive effect on the course of the disease. Mood level, but not pain, is the main factor affecting the quality of sleep in IBD patients. Future research should focus on the search for causes of reduced quality of sleep and their impact on the risk of morbidity or exacerbation of the disease.


Background: Periprosthetic fractures (PPF) of the femur close to the hip joint have serious consequences for most geriatric affected patients. In principle, apart from the highly uncommon conservative therapy, there are two therapeutic options. On the one hand, the prosthesis-preserving treatment by means of osteosynthesis using plates and/or cerclages in general is available. On the other hand, a  change of the prosthesis with optionally additive osteosynthesis or a proximal femoral replacement can be performed because of prosthesis loosening or non-reconstructable comminuted fractures as well as most cemented stem variations.The aim of this retrospective study is the analysis of periprosthetic proximal femoral fractures in the presence of a total hip arthroplasty (THA). The outcome of the operated patients is to be investigated depending on the type of care (osteosynthesis with prosthesis preservation vs. prosthesis change).Material and methods: In a retrospective case analysis, 80 patients with THA and PPF were included. They were divided into two groups. Group I represents the osteosynthetic treatment to preserve the implanted THA (n=42). Group II (n=38) includes those patients who were treated by a change of their endoprosthesis with or without additional osteosynthesis. Specifics of all patients, like gender, age at fracture, interval between fracture and implantation, length of in-patient stay, body mass index, osteoporosis, corticomedullary index and complications such as infections, re-fracture, loosening, material failure or other complications, were recorded and compared. Furthermore, the patients were re-examined by a questionnaire and the score according to Merle d’Aubigné and Postel.Results: In group I the mean follow-up time was 48.5±23 months (4 years) whereas group II amounted 32.5±24.5 months (2.7 years) (p=0.029). Besides, there were significant differences in age  and length of in-patient stay . According to the score of Merle d’Aubigné and Postel, there were significantly better values for the pain in group II with comparable values for mobility and walking ability.Conclusion: The treatment of periprosthetic proximal fractures of the femur is dependent on the classification (Vancouver and Johannsen) and in particular on the prosthetic anchoring as well as the extent of the comminution zone. Older patients and patients with osteoporosis are more frequently treated with an endoprosthesis revision. Patients, who have been treated with an osteosynthesis for preserving their endoprosthesis, showed a shorter length of in-patient stay and fewer complications than people with replacement surgery. In contrast to that, patients with prosthesis revision had better outcomes concerning the score of Merle d’Aubigné and Postel. The increasing number of primary total hip endoprosthesis (THA) with longer implant lifetimes as well as associated age- and implant-related changes due to osteoporosis and wear reactions is leading to an accumulation of revisions based on complications , 2], , . A natioThe aim of this retrospective study is to analyze periprosthetic proximal femoral fractures of patients with THA treated in our clinic. Finally, the outcome of the operated patients is to be investigated depending on the type of care (osteosynthesis with prosthesis preservation vs. prosthesis change).Before conducting this study, the vote of our university ethics committee was obtained (044/14032016).A retrospective case analysis of our patient archiving system  identified all patients which were treated due to a femur fracture in our hospital (university maximum care provider) from January 1, 2010 to December 31, 2016 . Subsequently, all patients with a periprosthetic femoral fracture were determined (178 patients). After exclusion of patients with PPF besides total knee arthroplasty, 93 patients with PPF and an existing THA were included. Due to a conservative therapy, 13 patients were excluded, too. The remaining 80 patients were divided into two groups. Group I represents the osteosynthetic treatment to preserve the implanted THA. These were 42 patients who had been treated with plate osteosynthesis with or without additional cerclages or isolated with cerclages. Group II with 38 patients includes those people who were treated by a change of their endoprosthesis with or without additional osteosynthesis.The selection decision of the surgical procedure will be determined on the basis of the fracture classification (Vancouver and Johannsen) and in particular on the stability as well as the anchoring type of the endoprosthesis, the comminution zone and the fracture localization , 16]. F. F16]. FAngular-stable non-contact bridging (NCB) plates from Zimmer Biomet Holdings  and angle-stable less invasive stabilization system (LISS) plates from DepuySynthes  were used for osteosynthesis. As cerclages 1.5 mm wire cerclages from the company DepuySynthes  were utilized. The treatment during endoprosthesis change varied and was adapted to the individual circumstances. In doing so, implants from the following companies were applied: Zimmer Biomet Holdings, Warsaw, IN, USA: 12; Peter Brehm Chirurgie-Mechanik e.K., Weisendorf, Germany: 8; Orthodynamics GmbH, Lübeck, Germany: 7; AQ Implants GmbH, Ahrensburg, Germany (Eska Implants GmbH & Co. included): 4; Mathys AG, Bettlach, Switzerland: 3; DepuySynthes, West Chester, PA, USA: 3; AlloPlus GmbH, Saarbrücken, Germany: 1. Moreover, all patients got the same standard treatment as well as a follow-up according to uniform guidelines.In all patients, specific characteristics were recorded and compared. They included gender, age at fracture, interval between fracture and implantation, length of in-patient stay, body mass index and osteoporosis (absolute (percentage)). In order to objectify the bone quality, the ratio of medullary canal to cortical thickness was determined on the basis of the corticomedullary index introduced by Barnett and Nordin (BNI) in 1960 on the preoperative x-ray of the pelvis and the anterior-posterior image of the femur, respectively. Additionally, the electronic files and x-rays of all patients were retrospectively evaluated and complications such as infections, re-fracture, loosening, material failure or other complications  and the time to complication recorded. Furthermore, all patients were re-examined in July 2017 by means of a questionnaire. Thus, complications (see above) were gathered once again and the function of the THA was inquired by means of the score according to Merle d’Aubigné and Postel . This scThe statistical analysis of the data was done using Microsoft Excel  and IBM SPSS software . The Kolmogorov-Smirnov test and the Shapiro-Wilk test were used to determine the normal distribution of the data. In addition, the Mann-Whitney nonparametric test and the Chi-square test were applied. P values of 0.05 or less were considered as statistically significant.In group I the mean follow-up time was 48.5±23 months (4 years) whereas group II amounted 32.5±24.5 months (2.7 years) (p=0.029). The patient’s specifics are shown in Table 1 The classification of fractures showed a significant difference between the groups. Using the Johannsen classification, a balanced distribution between the three given types was found in group I, whereas in group II an imbalance in favor of Johannsen type II with 71% was given  and in particular on the prosthetic anchoring as well as the extent of the comminution zone. Older patients and patients with osteoporosis are more frequently treated with an endoprosthesis revision. Patients, who have been treated with an osteosynthesis for preserving their endoprosthesis, showed a shorter length of in-patient stay and fewer complications than people with a replacement surgery. In contrast to that, patients with prosthesis revision had better outcomes concerning the score of Merle d’Aubigné and Postel.The inhomogeneous treatment by various prosthesis and osteosynthesis systems represents a limitation of this study that is based on the inhomogeneity of the fractures, typical for these types of patients. Further limitations are the retrospective study design, the varying lengths of the follow-up period and the small collective size.BNI: Barnett-Nordin indexLISS: less invasive stabilization systemNCB: non-contact bridgingNIS: nationwide inpatient samplePPF: periprosthetic fracturesTHA: total hip arthroplastyDZ und CP contributed equally to this work.JF initiated the work and is the head of the expert team. CP has carried out the data collection and presentation. She also has contributed significantly to the preparation of the manuscript. DZ was part of the expert team and a major contributor in writing the manuscript. ME as well as RM gave statistical support, endorsed the drafting of the article and revised it critically. CP helped with data collection. TP, AR and JF were mainly responsible for the treatment of the patients as well as members of the expert group. All authors read and approved the final manuscript.The authors declare that they have no competing interests.We acknowledge the support of the German Research Foundation (DFG) and the University Hospital Leipzig within the program of Open Access Publishing. This study was funded by the German Research Foundation (DFG) and the University Hospital Leipzig within the program of Open Access Publishing. The funding body had no impact on the design of the study, collection, analysis and interpretation of data as well as writing the manuscript.The datasets used and/or analyzed during the study are available from the corresponding author on reasonable request.The ethics committee of the University Hospital Leipzig, Germany, granted ethical approval (ref. no. 044/ 14032016). The committee is listed in the Institutional Review Board (IRB) of the Office for Human Research Protections (OHRP) IORG0001320, IRB00001750. All patients of our study gave their written consent for participation and publication of their anonymized data.


Giardia duodenalis infection is distributed worldwide and can achieve prevalence around 60%, especially in developing countries. This protozoan is divided into eight assemblages, in which A and B have high zoonotic potential, whereas C to H are host-specific. This scenario is changing as molecular studies progress, highlighting that knowledge on host-specificity still has a long way to go. Understanding the players involved in transmission routes enables rational designs of control strategies. Considering the high prevalence of giardiasis, this review aims to gather together the data on available studies on the distribution of G. duodenalis assemblages in Brazil until September 2020. Giardia is an intestinal protozoan found in a wide spectrum of animal hosts . In mammals the infection occurs by G. duodenalis, synonymous with G. lamblia and G. intestinalis. Although there is no consensus on the most appropriate name, in this review we will use G. duodenalis.G. duodenalis present worldwide distribution, showing prevalence of 2-7% in developed countries and can reach over 30% in low and middle-income countries.G. duodenalis transmission in outbreaks, in endemic areas direct transmission has great epidemiological relevance.G. duodenalis species meant that its subspecies were initially organised into groups, which are currently called assemblages or genotypes. The first divisions in G. duodenalis assemblages were carried out according to specificity by the host from which the isolate originated.,,G. duodenalis.,The great genomic diversity found in the G. duodenalis species is phylogenetically divided into eight assemblages, classified from A to H.,,,,Nowadays, the ,,,,,,,When symptomatic, the most frequent symptoms of giardiasis are consequence of acute or chronic diarrhoea, such as abdominal colic, flatulence, dehydration, nausea, vomiting and fatigue.G. duodenalis assemblages, especially in regions with high frequencies of infection.The different molecular characterisation tools have played an important role not only to better understand the characteristics of the assemblages, but also to understand the zoonotic cycles of transmission. Further genotyping studies are needed in order to elucidate the complexity involved in the transmission dynamics of G. duodenalis frequency in children can be higher than 60%.,,,,G. duodenalis assemblages could contribute to reducing giardiasis. In this context, this review aimed to describe the distribution of G. duodenalis assemblages in Brazil between 2007-2020.Brazilian studies about the epidemiology of giardiasis indicates that the Giardia duodenalis assemblages circulating in Brazil”. The electronic database, Medical Literature Analysis and Retrieval System on-line (Medline), was used.A review was carried out based on an exploratory and descriptive bibliographic survey in September, 2020, with the main theme: “Giardia lamblia) OR  OR  AND assemblage] AND Brazil; (3) [(Giardia) AND (genotype)] AND Brazil; (4) [ OR (Giardia lamblia) OR  AND (genotype)] AND Brazil  terms were used to define the search for: (1) etiological agent: “Giardia”; (2) characteristic of the etiological agent: “assemblage” or “genotype”; (3) geographical area: “Brazil”. To search with the aforementioned descriptors, the Boolean operator “and” was used. Thus, we obtained the following research strategy: (1) [(Giardia) AND assemblage] AND Brazil; (2) [(D Brazil .Giardia isolates (n = 5); studies that performed analysis in silico or from data available from databases (n = 2); studies that were not performed with isolates from Brazil (n = 2); in vitro and experimental model studies that did not perform genotyping of original isolates (n = 4); studies that used DNA from single cysts of G. duodenalis separated using a micromanipulation technique (n = 1); studies on archaeological material (n = 2); studies that did not use original G. duodenalis genotyping results and that had already been addressed in previous papers (n = 2); studies review (n = 1).The following inclusion criteria were used for the selection of manuscripts: articles retrieved in full, published in English until the year 2020. The following were excluded: studies that did not perform genotyping of the Frequency and distribution of genotyping studies in BrazilG. duodenalis in the country makes it difficult to implement strategic control actions that are targeted to potential sources of transmission. The scarcity of studies associated with the absence of a national infection survey makes it hard to understand the evolution of parameters related to the frequency of giardiasis in the population. Currently, it is not possible to say whether the G. duodenalis distribution in Brazil is changing upwards or downwards.Knowledge of the geographic distribution of parasitosis, such as giardiasis, is essential to target specific control measures. In Brazil, giardiasis is a public health problem with an unknown prevalence. Most of the studies in this field results from research by individual groups, and are usually sectional and aimed at local scope parasitological surveys. The lack of information about the transmission dynamics of G. duodenalis infection (over 40%), all genotyping studies are relatively recent, with the first one dating back to 2007.Although there are many areas with high frequencies of G. duodenalis genotyping, while two others (North and Northeast) share only two studies, each carried out from human samples. Most of the studies were developed in the Southeast region (30/41). This region is responsible for the main share of the country’s gross domestic product (GDP), and despite its small geographic dimension, it concentrates a large number of research institutes and postgraduate courses (48.45%).Brazil is a country of large continental proportions , composed of 27 states and a federal district divided into five regions . Of the Brazilian regions, one of them (Midwest) does not present any studies of Giardia and its genotypes in wild animal studies. All studies were carried out using samples of wild animals that had some proximity to humans  which would facilitate transmission.,,G. duodenalis assemblages in these animals in a natural environment.Brazil has the greatest biodiversity on the planet. It is estimated that about 11,000 known vertebrate animal species and 210 species of mammals have already been observed.G. duodenalis genotyping are carried out with samples of humans, domestic animals or farm animals  of  animals . Up to nGiardia in humans, and the largest diversity of animals in the world, the Brazilian contribution to the understanding of G. duodenalis diversity is scarce. In relation to developed countries, such as Portugal, Spain, Italy and China, Brazil has few studies of G. duodenalis genotyping, and most of them are concentrated in a single region. Further studies on the topic should be promoted, both in humans and in domestic, farm and wild animals, in order to assist in understanding the dynamics of transmission of G. duodenalis.Despite the high prevalence of G. duodenalis in BrazilGenotyping strategies of Giardia and/or discriminate G. duodenalis assemblages.G. duodenalis typing, the genes most widely used are those that encode the proteins Triose Phosphate Isomerase (tpi),gdh)G. duodenalis genotyping studies carried out from 2007-2019 (29/35) used the sequencing of regions of classically-used genes. βg, gdh and/or tpi were used in all studies, with the exception of one research study that used only the target SSU-rRNA.bg, gdh or tpi  is suggested for genotyping;gdh and tpi markers, but orfC4 and SSu-rRNA were also observed.,,,,,,gdh, tpi, orfC4; PCR-RFLP: βg, gdh).tpi target, when compared to gene sequencing.In Brazil, assemblage-specific PCR was used in four studies, mainly with the ,,,,,,,,,gdh, and sometimes appeared combined with the target βg.,,,,,,,βg target for genotyping in PCR-RFLP.PCR-RFLP was used for genotyping in ten studies, most of which were accompanied mainly by gene sequencing (8/10).G. duodenalis isolates is undeniable; however, all other sequencing brings an extremely relevant contribution to the scientific literature. The choice of the genotyping tool must be determined according to the investigation focus. PCR-RFLP proved to be a good strategy for an initial survey of circulating assemblages. Assemblage-specific PCR can be of great value in places where infectious assemblages are already known. Due to the divergences between the gene targets used in the sequencing, the use of more than one marker is recommended, as data from multi-locus sequencing brings more robustness to understanding the assemblage transmission dynamics. However, new gene markers and new financially viable tools are urgently needed to stimulate the expansion of genotyping studies and, consequently, enable a better understanding of the real zoonotic potential of G. duodenalis assemblages.The relevance of the whole genetic sequence for a better understanding of G. duodenalis assemblages in environmental samples from BrazilCirculation of Giardia, for more than 5,300 years.,G. duodenalis isolates circulating at that time.The presence of intestinal parasites dates from antiquity. In Brazil, the findings in coprolites and mummies point to the existence of these infections for more than 7,000 years and the existence of Giardia in water and food is associated with contamination by faeces from humans and/or animals, so different species and assemblages can be found. The main form of G. duodenalis infection, reported mainly in cases of outbreaks, is via waterborne transmission.The occurrence of G. duodenalis in water are basically concentrated in the State of São Paulo,,,,,,,G. duodenalis assemblages A, B, C, D and E suggests the contamination of water sources by faeces from different groups of hosts.In Brazil, genotyping studies of G. duodenalis isolates from sewage samples identified the presence of assemblages A, B and C  Is it possible that the circulation of these assemblages has always occurred and the scarcity of studies has hindered their previous identification? (2) Is it possible that the high frequency of interspecific contact could increase the pressure of infection and consequently select individuals capable of infecting this new host?Although the division of ,,,,,,,,,,,,,,,,,,,,,,,,In Brazil, assemblages A, B, C and E have already been identified in isolates from human faeces samples distributed in 21 studies carried out in the nine states.G. duodenalis zoonotic transmission, mainly anthropozoonotic. The two genotyping studies of G. duodenalis in cats carried out in São Paulo,Domestic animals have great relevance in ,,,,,,tpi and gdh). This could explain the identification of many different assemblages in these dog samples,In dogs, infection by host-specific assemblages (C and D) was observed in Minas Gerais, São Paulo, Santa Catarina and Paraná  Fig. 3)Fig. 3).,,,,In Rio de Janeiro, only assemblage A was identified in dogs.G. duodenalis isolates from these domestic animals still remains an unknown field.In Brazil, all assemblages  were identified in domestic animals, demonstrating the epidemiological importance of pets in maintaining cysts in the environment. The identification of assemblages A or B circulating in pets suggests that hosts other than dogs and cats may be involved in the transmission cycles. However, the genotyping of G. duodenalis in infecting wild animals, assemblages with high anthropozoonotic potential (A and B) were already identified in these animals .,,,Even considering the scarce knowledge of ,,,,,In farm animals , the assemblages A, B and E were reported, as expected -II Fig..40,In Brazil, assemblages G and H were not yet identified, probably due to the scarcity of studies in rodents and marine mammals. From marine waters, only isolates found in oysters were phylogenetically classified as assemblage A.Final considerationsG. duodenalis assemblages circulating in the country, and most of the regions still need to be explored. G. duodenalis genotyping is an important strategy to learn about the genetic variability of the species, mainly, to help understand potential transmission cycles. Despite the high frequency of this protozoa, especially in Brazilian children, little has been explored about the epidemiology of assemblages in humans and animals. In wild animals, we do not know whether G. duodenalis infection occurs in the natural environment and which circulating assemblages would be involved in this case. By sequencing or PCR strategies, and its variations, the circulation of assemblages A, B, C, D, E and F are being reported. Assemblage A in particular, and also assemblage B, have a high anthropozoonotic potential, so their occurrence is expected in different host species. The others assemblages (C-H) are considered host-specific, but can cause the infection of different, atypical hosts, as observed in human infection by assemblage C (host-specific for dogs) and E , in canine infection by assemblage E and in toucan infection by assemblage A. Despite these data, given that few areas of the country were studied and also that few hosts were investigated, knowledge about the real epidemiology of G. duodenalis assemblages in Brazil is still a long way to go.Brazil is a country with extensive territorial proportions, which means that it presents geographical, climatical biomes with cultural and GDP differences. However, there is a lack of knowledge about the


Objectives: The status of children with comorbid congenital anomalies (CAs) and their effects on related hospital resource utilization have been minimally investigated. We aimed to describe the congenital anomalies comorbidity status and their effects on hospital resource utilization  by pediatric patients.Setting: This study was conducted in five tertiary care children's hospitals in Shanghai, China.Participants: Data were obtained from the inpatients' electronic health records; diagnoses were recorded using International Classification of Disease, Ninth Revision codes. In total, 7,890 children were diagnosed with congenital anomalies (13.13%), which were either primary or secondary.Primary and secondary outcome measures: The dependent variables were length of stay and cost. The independent variables were demographic and clinical characteristics and CA status.Results: In total, 50.98% of the hospitalized patients had comorbid CA conditions. Medical+CA patients were associated with a longer LOS , and CA+medical patients were associated with higher costs . Cardiovascular, musculoskeletal, and genitourinary diseases were the top three comorbid diseases. The average LOS for the top three comorbid diseases was longest in the medical+CA group, followed by CA+medical group. Cardiovascular disease was the most frequent comorbidity , and the cost of cardiovascular disease was highest in all groups.Conclusions: A high prevalence of comorbid CA conditions was observed among pediatric inpatients in the sampled tertiary hospitals in China. Strategic planning should be improved to guide resource utilization for complex comorbid CA care. Due to the tremendous progress in prenatal diagnosis and improvements in health care services brought about by increased focus on primary health care, there has been a significant reduction in infant and childhood mortality rates in most countries over the past two decades –4. HowevCAs may contribute to long-term disability in children, and hospitalization expenses impose a sizable burden on their families, health systems, and societies –10. In rAlthough the abovementioned studies found that patients with a single CA had markedly improved hospital resource utilization, including hospitalization, LOS and cost , 15, theWe conducted a retrospective, cross-sectional study of hospitalized children with CAs from 2013 to 2016 using the child inpatient electronic health record (EHR) database from five tertiary hospitals in Shanghai, China. Among the five hospitals, one is a tertiary pediatric hospital, and the other four are all general tertiary hospitals that have pediatric departments or units of standard size. The EHR data of inpatients with CA disorders in all public health institutions were extracted from the Information Center of Health and Family Planning Commission of Pudong New Area of Shanghai. The Pudong New Area was selected because it represented the average health and economic status of Shanghai , 6–11 years (school age), and 12–17 years (adolescence). We did not include infants because they were more likely to have single diseases, much longer LOSs and higher hospitalization costs, and the differences between infants and the older children were large, which would lead to large variations. The discharge database for children included the following information: demographic characteristics, billing information, and diagnoses classified by the International Classification of Disease, Ninth Revision (ICD 9), Clinical Modification.Hospital resource utilization included variables of the LOS and the cost of each hospitalization within the CA comorbidity group and the CA-only group. These variables were all continuous. Considering that the variables were not normally distributed, we examined both the mean and median.A comorbidity was considered present with either a primary or secondary diagnosis of a disease . First, In the multivariate analysis, the independent variables consisted of demographic and clinical characteristics. The demographic characteristics were sex, age, insurance type, and residence status. Inpatients were classified into one of three age groups: 3–5, 6–11, and 12–17 years. Insurance was classified into three types: governmental (basic insurance for residents), out-of-pocket, and commercial. Among the three types of insurance, the commercial type has the highest reimbursement ratio, followed by the governmental type. We included complex chronic conditions (CCCs) and kinds of surgical operations as clinical characteristics. CCCs were defined according to version 2 of Feudtner's CCCs classification system to reflect whether the inpatient had other chronic diseases and the number of chronic diseases. In this study, the participants were classified into three groups according to the number of chronic diseases: 0, 1, and ≥2 .All analyses were performed with SAS, version 9.3 . To assess the distribution of patients with various demographic and clinical characteristics according to the prevalence of CA comorbidity, we used the chi-square test (Cochran–Mantel–Haenszel test). Analysis of variance (ANOVA) was used to explore discrepancies in LOS and cost. By using multivariate linear regression, we estimated multivariate models of the association between the prevalence of the three types of CA status  and hospital resource utilization (LOS and cost). In addition, the comorbid diseases of CA patients and the associated hospital resource utilization within the three CA diagnostic groups were further analyzed.This study was approved by the ethics committees of Tongji University (ref: LL-2016-ZRKX-017). The research presented minimal risk of harm to its subjects, and the data were obtained from hospitalization discharge records that were collected anonymously.A total of 7,890 hospitalized children with either a primary or secondary CA diagnosis (13.13%) were included. Of these patients, 542 (6.87%) were categorized into the medical+CA group, 3,480 (44.11%) were in the CA+medical group, and 3,868 (49.02%) were in the CA-only group; 50.98% of the hospitalized patients presented with a comorbid CA condition.P < 0.001), while those in the CA+medical group had a shorter LOS . Regarding cost, the CA+medical comorbidity group was highly associated with higher cost , and the medical+CA group was also associated with a higher cost than the CA-only group .P < 0.001) and higher cost . Compared with the 3–5-year-old group, the 6–11-year-old group had a significantly longer LOS  but a lower cost , and the 12–17-year-old group also had a lower cost than the 3–5-year-old group . Regarding insurance type, commercial insurance exhibited a considerably stronger negative association with cost  than government insurance. Regarding residence status, residents had a shorter LOS  and lower cost  than the nonregistered residents. Notably, the CCC status of the hospitalized patients was positively associated with both LOS and cost (P < 0.001); the greater the number of CCCs was, the greater the resource utilization in terms of LOS and cost would be (P < 0.001). Additionally, the statistical analysis showed that hospitalized patients who underwent more than one kind of surgical operation had a longer LOS , and the costs were significantly higher in the groups with one surgical operation  and the group with more than one surgical operation .In addition, the inpatients' demographics and clinical status revealed specific effects on hospital resource utilization. Girls tended to have a longer LOS . The research presented minimal risk of harm to its subjects, and the data were obtained from hospitalization discharge records that were collected anonymously.Conceived and designed the study: JS, WY, RL, and ZW. Analyzed the data: HJ, ZY, and LL. Contributed reagents, materials and analysis tools: LG, RY, NC, and QL. Wrote the paper: JS, WF, and ZW. Revised the paper: JS and NC. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The differences were partly associated to variations in the gliadins:glutenins ratio. It depended on the genotype whether the grain and semolina protein percentage and gluten strength compensated one another in terms of alveographic indices to give the dough a strength similar to that of the modern cultivars in the range of moderately high temperatures, which resulted from delayed sowing. Further studies aimed at exploring the genetic variability of quality traits in the large genetic pool represented by the several Italian old and intermediate durum wheat cultivars still available are therefore advisable.The growing interest in old durum wheat cultivars, due to enhanced consumer attention on healthy, traditional products and low-input agricultural systems, partly relies on their different quality characteristics compared to modern cultivars. Nine Italian durum wheat cultivars from different breeding periods were compared in two late-sown (January) field trials in order to subject their grain filling period to high temperatures similar to those expected in the future. Late sowing moved anthesis forward by about 10 days and increased the mean temperature during grain filling by 1.3 °C compared to that obtained when using the common sowing period of November–December. In these conditions, old cultivars were on average less productive than modern ones (2.36 vs. 3.54 tons ha Triticum turgidum subsp. durum Desf.) in 2016 amounted to about 40 million tons. The European Union is the world leader in the production of durum wheat, with 9.4 million tons (t) produced each year. Italy is the main European producer, generating about 4 million tons, i.e., 10% of world and 41% of European Union production . Pasta is the main product, although about 24% of global durum wheat production, reaching 70–90% in some Middle East countries, is used for bread-making [The global production of durum wheat . The environment is typically Mediterranean, with a long-term mean annual rainfall of 553 mm, mainly concentrated between October and April. The soil is sandy-clay-loam with a depth of about 0.6 m due to underlying layers of limestone (typic Xerochrepts).mediterraneum’ type [The treatments consisted of nine Italian durum wheat landraces/cultivars from different breeding eras. Their names, geographic or genetic origins, and years of release are shown in um’ type . Saragolum’ type .syriacum’ types. The three earliest constitutions, Creso, Svevo, and Claudio, are Rht1 semi-dwarf cultivars (‘modern’ group). Creso was one of the first semi-dwarf cultivars released in Italy. It was widely grown for at least 30 years despite its lateness. The distinguishing trait of cultivar Svevo is its reputation for producing good quality pasta [Its importance lead to its extensive use in the subsequent crosses, and in 1987 about 80% of the Italian durum wheat cultivars had Senatore Cappelli in their pedigree  includedty pasta .High Molecular Weight Glutenin Subunits (HMW-GS) were separated by SDS-PAGE (Sodium Dodecyl Sulphate-PolyAcrylamide Gel Electrophoresis), and protein extraction was done from 20 mg of durum semolina . The ideCultivars were compared in a randomized complete block design with three replications.−2. Each 10 m2 plot consisted of eight 8.3 m rows, separated from one another by 0.15 m. Nitrogenous (80 kg N ha−1) and phosphoric fertilizer (92 kg P2O5 ha−1) were applied before sowing in the form of urea and ammonium bi-phosphate, and the plots were sprinkler-irrigated to prevent the development of any moisture stress. Weeds, pests, and diseases were chemically controlled. During the course of the experiment, weather conditions  were recorded at a meteorological station located in an adjacent field.The sowing bed was prepared by ploughing to a depth of 0.25 m, followed by surface cultivation. In both seasons, the materials were sown (on 13 January in the season 2005/06 and on 5 January in the season 2006/07) with an 8-row planter at a density of 200 viable seeds m2 (4.0 m × 0.15 m inter-row) from an inner row within the plot. The total biomass was obtained by weighing these air-dried samples. Spikes were then separated, counted and threshed, and the Harvest Index was calculated by determining the ratio between the grain and the total biomass weight. The number of spikes per m2 was obtained by dividing the number of spikes by the harvested area. Grain yield was calculated on a per plot basis.Anthesis date was recorded as the time at which 50% of the spikes in a plot had visible anthers. Physiological maturity was set as stage 90 in the Zadoks’ Scale . Plant hw/v dry semolina/flour. Mixing times differed from those usually used for bread wheat. Wet and dry gluten contents and the GI were determined using the AACC Method 38–12 [Thousand-grain weight, protein percentage at 13% moisture content, test weight (hectolitre weight), and percentage of yellow berry were determined on mature grains. Samples of 50 kg per cultivar were milled with a traditional stone mill, following standard procedures for durum wheat. Semolina and flour quality were assessed by measuring nitrogen and protein percentage, gluten index (GI), alveographic indices, and gliadin-to-glutenin ratio (gli:glu). Nitrogen content was determined with the Kjeldahl method using a conversion factor of 5.7 to calculate the protein percentage . The Chood 38–12 . Gluten od 38–12 . Dry gluod 38–12 . The repp < 0.05). Overall differences in yield and quality traits of cultivar groups were investigated by principal component analysis (PCA) executed on the correlation matrix of the cultivar traits, followed by a rotation of components . Component loadings were calculated as simple correlations (using Pearson’s r) between the components  and the original variables [The significance of the differences between the years, the three groups of cultivars, and their interaction were analyzed using the cultivar means as replications. Least squared means were presented to correct for the unequal number of cultivars in the three groups. Where the F test suggested a significant treatment effect, means were separated by the Student’s t-test . These differences were mirrored in an almost similar duration of grain filling in the three groups.In both seasons, old cultivars were later than intermediate and modern cultivars both in anthesis and maturity, such that a negative relationship was calculated between these pheno-stages and the year of release .These larger grains probably contributed to a lower protein percentage via a dilution effect, whereas grain quality was better in this year in terms of both test weight and yellow-berry incidence. The very low mean grain weight recorded in 2007 (below 40 mg) was indicative of shrunken grains, as pointed out by the very low absolute weight . The cultivar rank in protein percentage was very consistent between years, despite the difference in environmental conditions, as shown by a correlation coefficient of 0.75* between the protein percentages of the nine cultivars in 2006 and in 2007.The positive effect of breeding on grain yield via the increased harvest index at similar levels of above-ground biomass was demonstrated by the corresponding correlations with the year of release. The increase in grain yield with the year of release was in turn accompanied by a significant increase in grain number mRaw material was ground by a stone mill and sifted into a main product, semolina, and a by-product, referred to as ‘flour’, since it appears as white and fine as bread wheat flour . SemolinThe lack of interaction for the quality traits shown in By contrast, gluten strength, as measured by GI, was higher in 2006 than in 2007; this was probably a consequence of the higher glutenin percentage obtained in 2006 which decreased, although not significantly, the gli:glu ratio. No other quality trait was affected by the season. r = 0.91**, n = 9).Protein quantity and quality were affected by breeding in opposite directions, as the decrease in semolina protein percentage going from the old to the modern cultivars was counterbalanced by a corresponding increase in gluten strength, either expressed as GI or W. No differences between groups of cultivars were detected in the percentage of the different protein fractions and in the other alveographic indices, despite the strong positive relationship between W and P, the alveographic index associated to dough tenacity  to the EU Quality index for durum wheat , followed by gluten strength (30%). In some countries, grain protein content influences the amount of money paid to wheat farmers due to the importance of this trait for the quality of both pasta and bread. Grain protein percentage can vary as a consequence of genotype, environment, or genotype × environment and, as pointed out in most of the papers estimating the contribution of these parameters to protein percentage variation in sets of modern cultivars, the environment is the main component % to the . On the o et al. , at leasInterestingly, while the genotypic differences in protein percentage were attributable to the sole storage proteins, i.e., the gluten fraction, the higher protein percentage observed in 2007 compared to the preceding season was due to a higher fraction of metabolic proteins, i.e., globulins and albumins, with an unchanging level of gluten percentage but a decrease in the glutenin fraction. As structural/metabolic protein fractions accumulate mainly during the early phase of grain growth, i.e., from anthesis to approximately 20 days after anthesis when most endosperm cells are still dividing, whereas storage-protein fractions accumulate later, from about 6 days after anthesis to the end of grain filling ,46, we cGlu B1 locus, and the differences in the environmental conditions to which their grain filling was exposed as a consequence of their different phenology.In the present study, gluten strength, which is the second most important trait in defining wheat quality, was evaluated using both the GI method  and the Glu B1 locus, Creso, the oldest among modern cultivars, carrying the HMW-GS 6 + 8 genotype, and the other two modern cultivars possessing the HMW-GS 7 + 8 genotype. The 6 + 8 genotype has been identified as the best one for bread making by Ammar et al. [In Italy, the improvement in the pasta-making quality of durum wheat through breeding has already been documented ,9,13 andr et al. ; by contr et al.  and Boggr et al.  found thr et al. , who shoGlu B1 locus distinguishing the intermediate cultivars. This observation highlights that no single allele is absolutely necessary for adequate gluten strength, which is the consequence of specific combinations of alleles [For this reason, in our experiment, genotypic variation in GI was large, and mainly associated to the year of release of the cultivars and to the different kinds of glutenin molecules encoded by the different genes, in agreement with previous findings, ,13,51. A alleles , and thaGlu B1 locus, but also to a higher gli:glu ratio deriving from a greater expression of the B-type LMW-GS in terms of percentage of total storage proteins. On the other hand, the PCA analysis highlighted that the lateness of old cultivars exposed their grain filling to higher temperatures compared to the modern constitutions, and that this situation negatively affected GI by altering the gli:glu ratio via a decrease in glutenin percentage. Ultimately, therefore, our results agree with De Santis et al. [Our data did not show any difference between the cultivar groups in the proportion of the different protein fractions, although De Santis et al.  attributs et al. . In the s et al.  did not The observed environmental variation in GI, contradicting Sekuralak et al.  who did Initially proposed for determining bread wheat dough quality, the alveograph has also become widely accepted internationally as an indicator of the gluten strength of durum wheat, in part because of the weak discrimination power of GI for moderate to low strengths of gluten . Alveogr−4) were similar to those reported by De Vita et al. [Glu B1 locus for modern and intermediate cultivars did not result in a different gluten strength.The values of W recorded in this experiment (56–117 J 10a et al.  and Motza et al. , but lowa et al. ,47,57. Aa et al. , the oldThe alveographic index W did not vary between seasons, contradicting Guzman et al.  and FoisOn the other hand, when the old cultivars grown in this experiment were compared as a group with the group of modern cultivars, dough strength as expressed by W was significantly higher in the modern cultivars in spite of their lower protein percentage. Given the large and outstanding genetic variability recognized by Royo et al.  in the IIn the range of moderately high temperatures explored, achieved through the use of delayed sowing with the aim of mimicking future increases in temperature, the technological quality of old Italian cultivars was higher compared with the modern cultivars in terms of grain and semolina protein percentage, but lower in terms of gluten strength. Whether the two components of wheat quality compensated one another in terms of alveographic indices to give dough of strength similar to that of the modern cultivars depended on the genotype. The intermediate group of cultivars, characterized by a grain quality and gluten strength comparable to modern cultivars, deserves further studies aimed at exploring their genetic variability for quality traits.


During the same period, the number of participants using public transportation  has doubled ), and the proportion of inactive transportation  more than tripled. Concurrently, the transportation time almost doubled with an increase of 25.9 min over the 10 years (p < 0.001). The prevalence of active transportation increased with age. Participants with higher family income and education reported a lower prevalence of active transportation. Females were more likely to use active transportation (OR (95% CI): 4.41 (4.14–4.70) and 2.50 (2.44–2.57), respectively, for 2002 and 2010–2012, where males were the reference). Before the prevalence of active transportation and physical activity gets lower, there is a need for the public health sector and the transport and land use sector to work together to develop related policies and initiatives with the aim of promoting active transportation and public transportation to increase the levels of physical activity and to decrease the risks of chronic diseases.Giving the rising trends in obesity and chronic diseases in China, strategies to increase physical activity are important. Transport-related activity is a substantial source of physical activity and can be easily incorporated into the daily lives. It is a key social factor of health, which can help improve people’s mental and physical health and decrease environmental pollution. However, little is known about recent trends in transportation modes and time in China. Between 2002 and 2010–2012, information about transportation behaviors of Chinese population aged 15 years or older were collected within two Chinese Nutrition and Health Surveys. A stratified multistage cluster sampling method was conducted to select participants. Sociodemographic information, transportation modes, and time were collected during face-to-face interviews. The study included 82,377 (mean age 41.2 years) and 143,075 (mean age 48.7 years) participants in the 2002 and 2010–2012 surveys respectively. The weighted prevalence of active transportation  decreased from 83.8% in 2002 to 54.3% in 2010–2012 ( China is facing an obesity and chronic diseases epidemic due to the population aging, urbanization, and unhealthy lifestyles . ChronicInsisting on walking, cycling, and other active modes of transportation is one of the main means to increase the total daily physical activity of the population to prevent the occurrence of chronic diseases and to improve well-being. In view of mounting evidence on the health benefits of walking and cycling, some countries encouraged residents to increase transportation-related physical activity  to improve individual health and to reduce air pollution, carbon emissions, traffic dangers, and other harmful impacts of car use. In Canada, suitable point-of-choice prompts were designed for university students to promote active transportation . In the An increase in physical activity among the Chinese population is crucial because only 13.8% of them engage in physical activity and 42.0% of adults are overweight or obese ,25. CompData used in this study were from Chinese Nutrition and Health Survey (2002) and Chinese Nutrition and Health Surveillance (2010–2012). The two surveys were nationally representative cross-sectional studies covering all 31 provinces, autonomous regions, and municipalities directly under the central government of China . A stratified multistage cluster sampling method was conducted in the two surveys to recruit participants. Both survey research protocols were approved by the Ethics Committee of National Institute for Nutrition and Health (2013–018). Written informed consent was obtained from each participant. Basic information registration questionnaire contents included general demographic information  for both surveys.In the 2002 survey, the whole country was divided into six strata: metropolises, small and medium-sized cities, and categories one to four villages based on their socioeconomic status, geographic characteristics, and social development information. A stratified multistage cluster sampling method was conducted to recruit participants from 132 surveillance sites of six strata areas. The personal health questionnaire was used to collect transportation mode- and time-related information. In the 2010–2012 survey, the whole country was divided into four strata: metropolises, small and medium-sized cities, normal villages, and poor villages based on their socioeconomic status, geographic characteristics, and social development information. The physical activity questionnaire was used to collect transportation mode- and time-related information.Both surveys used face-to-face interviews, and the interviews were conducted at the homes of the participants by a well-trained investigator. To ensure data reliability, quality control measures, and evaluation indexes were made at the national, provincial, and district levels, quality control was carried out in the earlier and later stages of and during the field surveys.The present study combined two datasets: 2002 and 2010–2012 for participants aged 15 years or older. For the purposes of this article, data from 225,452 respondents was analyzed, out of whom 82,377 were from the 2002 survey and 143,075 were from the 2010–2012 survey. Age was grouped as a categorical variable: 15–29.9 years, 30–44.9 years, 45–55.9 years, and 60 years or older. Residence was assigned for all participants as two strata areas: urban areas and rural areas. Educational level was categorized into three levels: primary school or below, junior or senior high school, and college or above. The socioeconomic status was grouped as follows: low, middle, high, and no response.The participants were asked the following: what is the main transportation mode when you traveled in the past three months? How many minutes did you spend on travel per day? Four response options for transportation modes were available: walking; cycling; bus, subway, or shuttle bus; and car, electric bicycle, motorcycle, or taxi. The participants could select only one type of transportation mode. According to the contribution to the health and physical activity, the transportation modes were classified as active transportation, public transportation, and inactive transportation. Active transportation included walking and cycling; public transportation included taking a bus, subway, or shuttle bus; and inactive transportation included driving or taking a car, motorcycle, taxi, or electric bicycle.p-value < 0.05 was regarded as statistically significant.Due to the differences in age, gender, and regional distribution of the Chinese population between 2002 and 2010–2012, the prevalence of transportation modes and mean level of transportation time were standardized by age, gender, and region based on the 2010 national population census data, thus providing nationally representatively estimates. A complex sampling weight was assigned to each participant according to the study design. All statistics were calculated using SAS9.3 . The Proc Surveyfreq and Proc Surveymean procedures in SAS were used to analyze the proportion, mean, and 95% confident interval (95% CI). The transportation modes were presented as percentages, and transportation time was expressed as mean. The Chi-square test was performed for comparing the proportion of transportation modes between the two surveys and in different subgroups. Survey multinomial logistic regression was used to evaluate association between the sociodemographic characteristic factors and the transportation modes. The Kolmogorov–Smirnov test was used to determine the normality. Due to the abnormal distribution, the Mann–Whitney U-test was used to examine the differences between genders, region types, and the two surveys of transportation time. The Kruskal–Wallis Rank sum test was used to examine the differences in age groups, education levels, and annual average income per capita. A two-tailed The sociodemographic characteristics among the participants are shown in p < 0.001). The trends in the prevalence of transportation modes over the 2002–2012 surveys were generally similar for participants of almost all subgroups. The greatest decline occurred during the 30–44.9 age group compared to the other age groups, with a decrease by 44.4%. The proportion of participants living in rural areas who use active transportation declined more than that of those living in urban areas. The prevalence of active transportation among males declined more than among females. The declines in active transportation decreased with the increasing annual average income per capita. The lowest decrease in prevalence of active transportation was observed among the participants reported attending only primary school or below education compared to their counterparts.The prevalence of public transportation increased from 7.5% in 2002 to 15.7% in 2010–2012, and it increased in all subgroups. More increases were among those who were female, were older, lived in rural areas, had lower education levels, and had lower annual average income per capita . From 2002 to 2012, the number of participants using inactive transportation increased from 8.7% to 29.9% and a similar trend was found in each subgroup. The participants who were female and lived in rural areas reported higher increases than their counterparts. The participants who were in the ≥60 age group, with only primary school or below education level, and with low annual average income per capita had the highest increases compared with their counterparts.The specific proportion of participants who walked; cycled; used public transportation; or rode in a car, on an electric bike, on a motorbike, or in a taxi for the whole sample are shown in p < 0.001). In both surveys, females were significantly more likely to use active transportation (OR (95% CI): 4.41 (4.14–4.70) and 2.50 (2.44–2.57), respectively, for 2002 and 2010–2012, where males were the reference) and public transportation (OR (95% CI): 3.68 (3.36–4.03) and 2.20 (2.12–2.28), respectively, for 2002 and 2010–2012, where males were the reference). Whereas participants with high annual average income per capita were less likely to use active transportation and public transportation. The prevalence of active transportation and public transportation increased with age. The higher the education level, the higher the prevalence of public transportation. Using active transportation was significantly more common in participants living in rural areas than those living in urban areas in 2002. Public transportation use was more pronounced in urban areas than rural areas for both surveys; however, the gap was sharply reduced in 2010–2012.We entered the sociodemographic characteristic factors into multinomial logistic regression model to evaluate the association with transportation modes. There was a significant increase of transportation time between 2002 and 2010–2012 . The parThis study investigated trends in transportation modes and time based on large, nationally representative surveys among the Chinese population. The analysis indicated that, although active transportation was still very prominent, a significant downtrend in the prevalence of active transportation was observed between 2002 and 2010–2012. Somewhat more worrisome, the population using inactive transportation increased dramatically, more than tripling. The reported levels of active transportation were still high when compared to the USA and UK ,27, but China’s urbanization has accelerated since 1996, and the rapid urbanization stage was 2002–2012. In 2012, the urbanization rate was 52.57% ,31. The This study also showed that the transportation time almost doubled with an increase of 25.9 min over the past 10 years. The increase in transportation time was also influenced by the rapid urbanization and home–work separation. Long transportation time was associated with reductions in health-related activities, including sleeping, physical activity, food preparation, and time eating with family . WorkersFrom 2002 to 2010–2012, the proportion of public transportation increased from 7.5% to 15.7%; nevertheless, the increase was much lower than in the inactive transportation. Compared with the people who used private cars, public transportation users had an easier time achieving 10,000 steps due to the walking associated with public transportation . A studyThe major strengths of this study were that the sample was large and was nationally representative, and therefore, the results can be generalized to the Chinese people and can contribute to scientific evidence for the national policy on transportation mode and time. The main lack of this study was that the result was self-reported, where recall may lead to bias.Active transportation to travel among the Chinese decreased significantly from 2002 to 2012, while inactive transportation increased sharply. In rural areas, higher education level and annual average income per capita were negatively associated with active transportation in 2010–2012. These trends may represent a critical loss of physical activity for the Chinese and may explain part of the increase in obesity and chronic diseases in China. Therefore, there is a need for the public health sector and the transport and land use sector to work together to develop related policies and initiatives with the aim of promoting active transportation among the Chinese by reducing structural and environmental barriers, thus contributing to increasing the levels of physical activity and decreasing the risks of chronic diseases.