One out three parents belonged to a mutual support association (n = 78), and 26% (n = 69) of the children used alternative therapies. Furthermore, 75.4% (n = 199) of the children received no psychological support. Children whose parents had a higher educational level and occupations status made greater use of parallel healthcare resources.; (4) Conclusions: A significant proportion of children used multiple health resources in addition to the public healthcare system depending on sociodemographic determinants. Studies are needed to determine whether the use of these alternative services achieves better levels of health.Background: Children with complex chronic conditions have a high need for health and social care resources. Many parents explore parallel resources such as alternative therapies, associations, psychological support, private medical consultations, and other out-of-pocket expenses for healthcare. The use of these alternative health resources is sometimes unclear and may lead to health inequalities. To characterize the use made of alternative healthcare resources for children with complex chronic conditions. Additionally, we evaluate the influence of sociodemographic factors on the distribution of this utilization of resources; (2) Methods: Cross-sectional study. Children with complex chronic diseases were treated at a tertiary hospital in Granada, Spain in 2016. We analyzed their use of healthcare resources and socioeconomic variables. This research complies with STROBE guidelines for observational studies; (3) Results: In total, 265 children were analyzed . A total of 105 children (39.6%) attended private consultations with specialists, and 12.1% ( Many children’s lives are threatened or limited by an increased prevalence of chronic diseases, which are characterized by major health-related needs, severe chronic conditions, functional limitations, and the frequent need for healthcare resources . These cIn those countries with a generalized public healthcare system, many parents explore parallel resources outside this setting. Thus, intending to seek the best options for the care and well-being of their children, they resort to optional resources such as alternative therapies ,), associations (non-profit patients and caregivers associations), psychological support (private psychology consultation), private medical consultations and other out-of-pocket expenses for healthcare . HoweverThe use of these alternative health resources is sometimes unclear, and further study may clarify their potential impact on health inequalities and the care program provided. Moreover, a better understanding of the patterns of use of these resources could provide valuable information in developing a child and family-centered approach to healthcare.The main aim of this study is to characterize the use made of alternative healthcare resources for children with complex chronic conditions. Additionally, we evaluate the influence of sociodemographic factors and the presence of life-threatening complex chronic conditions on the distribution of this utilization of resources.This study is cross-sectional and focused on children with complex chronic conditions. The study was designed in accordance with the conceptual framework for health inequalities developed by the Spanish Commission to Reduce Social Inequalities in Health among structural determinants of health inequalities  . MoreoveThe study was conducted at the Virgen de las Nieves University Hospital in Granada (Spain), which is part of the national public healthcare system, and the reference hospital for the population of Granada aged under 18 years . In 2015, the hospital provided 66,382 pediatric consultations and treated 14,336 children, of whom 42 later died . In subsp = 0.05, with a precision of 6% and a 95% confidence level, 262 children were necessary to be recruited  and were treated at the hospital in 2016. The children’s parents were approached during their visit to the hospital, and their consent to participate was requested, after ensuring that there was no life-threatening situation , or any other condition that would limit understanding, verbal communication or the ability to provide consent. Assuming a prevalence of 10%, estimated from a previous pilot study carried out in the hospital, with a ecruited .The participants were recruited from the lists of subjects attended during outpatient consultations, from hospitalized children or those referred by the case management nurse, after identification by their main diagnosis, according to the 9th International Classification of Diseases (ICD-9). Subsequently, children with LT-CCCs were identified according to the criteria proposed by Feudtner et al. , who claA database was made with the children cited and hospitalized with the inclusion criteria, reviewed daily by the principal researcher. Data were integrated into the database by standardized variables and pre-defined verification alerts to ensure uniform coding and to avoid errors during the population of the database.After identifying the sample, the use of parallel health services  in the previous twelve months was ascertained from self-administered questionnaires delivered to the parents, together with the information about the study and request for signed informed consent. This process was conducted at the end of the consultation or during hospitalization, always in the presence of a member of the research team. The answers regarding utilization of health services were dichotomous (YES/NO). Private consultations were assumed for any visit to private medical specialists or any other type of additional private expenditures.The questionnaire items included sociodemographic data such as participants’ age, gender, LT-CCCs. Social class  was measured on individual parents by neo-Weberian indicators of occupational social class (CSO-SEE12) .Descriptive and exploratory analyses were conducted to obtain frequencies, central and dispersion measures. The normality of distributions was evaluated by the Kolmogorov-Smirnov test. Bivariate analysis was performed to measure healthcare utilization by sociodemographic characteristics, LT-CCCs categories, or gender by chi-square test or Fisher’s test when indicated. Statistical significance for probability values was set at <0.05. Post-hoc power analyses were performed to evaluate the main bivariate analyses performed, such as the difference in private insurance by educational and occupational status. SPSS software . Version 24.0 was used for the statistical analysis.The sample was composed of 265 family groups  (see participants flowchart-n = 104) had attained only a primary school level of education, and 36.1% (n = 92) were dedicated to an unskilled occupation. Among the mothers, the profile was similar, except that 29.7% (n = 78) had attained a university level of education vs. 22.1% (n = 57) for the fathers; 59.7% (n = 157) of the mothers were unemployed (The father’s education profile showed how 40.3% (employed .n = 237) were of Spanish nationality, and the rest from other countries. Children were treated mainly for neurological diseases , congenital diseases , oncological diseases  and metabolic diseases . Additionally, the complexity of children’s health status was evidenced by the number of them who needed medical devices at home such as continuous oxygen therapy , mechanical ventilation , enteral feeding , urinary catheter , gastrostomy , or tracheostomy .The final sample of children consisted of 265 participants, ranging from 2 months to 17.3 years, with an average of 7.3 years (SD 4.6); 43.4% were female, 56.6% were male, and 89.4% (n = 32) of the parents had additional private health insurance. Most of these parents had a university degree  or worked in a managerial or supervisory occupation . The post-hoc analyses revealed a power greater then 90% in all analyses.From the sample , 12.1% (n = 104) attended private consultations with specialists or had other types of additional private expenses. This finding was significantly associated with education . A similar pattern was observed among the managerial/supervisory level of fathers  and mothers . The post-hoc analyses revealed a power greater than 80% only in the case of mothers’ educational status, being lower in the rest of comparisons.Moreover, 40.3% (n = 199) of the parents. Psychological resources were accessed via associations , by private consultation , or by public hospital consultations . This support was more commonly received by children whose fathers  and mothers  had higher education and a high-level occupation . The post-hoc analyses revealed a power under 80% in all these comparisons.No psychological support was available for 75.4% ; although was significantly more frequent among the mothers with a university degree . With reference to occupation, those fathers with managerial employment , and mothers in the same situation , had more probability of belong to an organization for mutual support. The post-hoc power analyses yielded figures under 80% in all comparisons.There was no difference among fathers regarding belonging to a mutual support association and having a higher educational level , as were mothers . Fathers with managerial and supervisory positions  and mothers in analogous positions  made a greater use of alternative therapies. None of these analyses obtained a post-hoc power over 80%.Fathers with university studies were most likely to use alternative therapies for their children  was generated by children with neurological diseases (post-hoc power = 79%).Analysis by categories showed that most of the spending on additional private consultations  (post-hoc power = 94.1%).No significant differences were observed in the use of alternative therapies or mutual support associations by PCCC, while 50.8% vs. 6.5% of the spending on psychological support was for children with oncological diseases .Only four of those families that did not have Spanish nationality (14.3%) made use of private consultations   to addreOur study shows that most use of alternative therapies is made by those parents with a higher occupational and educational level. There is a growing acceptance of these therapies among families of children and adolescents with multiple chronic conditions Nevertheless, in many cases, their effectiveness has been questioned , althougOur findings corroborate those of previous research in that the parents’ income and level of education are significant predictors of the recourse to alternative therapies ,38. MoreThis study is subject to certain limitations, such as a lack of statistical power to evaluate some comparisons by subgroups. Additionally, due to the cross-sectional design, no causal inference may be determined in the detected associations. Further research should be conducted to determine whether inequalities in the use of healthcare resources persist over time or whether our findings reflect a conjunctural finding. Furthermore, our study results may be strongly influenced by the characteristics of the Spanish model of public healthcare services; if so, they cannot readily be extrapolated to countries where there is no universal, free system of public healthcare insurance. Further, longitudinal, studies are needed to determine whether the use of these alternative services achieves better levels of health, in the medium and long term, among the population affected.In Spain, unequal use is made of health services for children with complex chronic diseases. In many cases, is associated with the parents’ occupation and level of education. Although in some cases differences arise from the non-availability of certain services, in general, it is the parents with a higher occupational and educational level who are best able to identify and use alternative resources .These findings highlight the multifaceted nature of complexity. Parallel resources are not usually included in the dialogue between nurses and users when making decisions on children’s health care. Monitoring the use of different services and evaluating whether the care systems satisfy their needs considering socioeconomic inequalities, will assist in informing nursing services through identifying and allocating resources to reduce these barriers, and to offer comprehensive and coordinated care.


The aim of this study was to describe and update current knowledge of manual therapy accuracy in treating cervical and lumbar radiculopathy, to identify the limitations in current studies, and to suggest areas for future research. The study was conducted according to PRISMA guidelines for systematic reviews. A comprehensive literature review was conducted using PubMed and Web of Science databases up to April 2020. The following inclusion criteria were used: (1) presence of radiculopathy; (2) treatment defined as manual therapy ; and (3) publication defined as a Randomized Controlled Trial. The electronic literature search resulted in 473 potentially relevant articles. Finally, 27 articles were accepted: 21 on cervical (CR) and 6 in lumbar radiculopathy (LR). The mean PEDro score for CR was 6.6 (SD 1.3), and for LR 6.7 (SD 1.6). Traction-oriented techniques are the most frequently chosen treatment form for CR and are efficient in reducing pain and improving functional outcomes. In LR, each of the included publications used a different form of manual therapy, which makes it challenging to summarize knowledge in this group. Of included publications, 93% were either of moderate or low quality, which indicates that quality improvement is necessary for this type of research. Radiculopathy is described as nerve root irritation resulting from various pathologies, including herniated intervertebral disc 22% cases), bone spurs, spinal instability, and trauma ,2. Upper2% cases,Cervical radiculopathy (CR) is most prevalent in individuals over 40 years of age, with an annual incidence of 83.2 per 100,000 persons . This maReferred symptoms, including pain, cause more significant disability when compared to local pain alone . AlthougManual therapy forms can be joint-oriented , soft-tissue-oriented (massage forms), neural-tissue-oriented (neurodynamic), or mixed (specific exercises). Most of these treatments are successful in improving radiculopathy symptoms ,20, but The aim of this study was to (a) describe and update knowledge of manual therapy accuracy in treating cervical and lumbar radiculopathy; (b) to identify the limitations of current studies; and (c) to suggest areas for future research.The study design was a systematic review and was conducted following the PRISMA guidelines. The protocol was registered a priori in the PROSPERO database under the following registration number: CRD42020143399.Publications (up to 30 April 2020) were searched in PubMed and Web of Science. Additionally, we conducted a manual search in the references of the included articles. The review included only publications in English. The following inclusion criteria were used: (a) presence of radiculopathy and/or radicular pain, and/or sciatica ; (b) treatment defined as manual therapy ; (c) publication defined as a Randomized Controlled Trial (RCT); and (d) English language. Studies of surgical radiculopathy treatment, or those not performing between-group analyses for the measured outcomes, were excluded from the review. The following keywords were used to search for an appropriate article: (radiculopath* OR hernia*) AND . Radiculopathy localization was not determined before the search; however, it was extracted at the data analysis stage. Grey literature was not searched in this review.A data extraction form was created to extract relevant data . Screening of research records and risk of bias assessment was conducted by two independent reviewers (T.K. and B.C.), with the intervention of a third researcher (A.S.) in case of disagreement. Included studies underwent a methodological quality assessment for risk of bias using the Physiotherapy Evidence Database (PEDro) scale. This scale consists of a checklist of 11 scored yes-or-no questions giving a methodological quality score. Score 9 to 10 is considered excellent, 6 to 8 is good, 4 to 5 is fair, and 3 or below represents poor quality . If the The mean PEDro score of all included RCTs was 6.6  out of 10. For CR, the score was 6.6 , and for LR the score was 6.7 . Based on IVS, out of the 26 analyzed publications, three publications (11%) obtained a score classifying the quality of the publication as ‘high’, 12 (44%) as ‘moderate’, and 12 (44%) as ‘limited’. Analyzing the individual items of the PEDro questionnaire, the analyzed publications most often lost points for a failure to refer to blinding of the therapists (96%), the participants (93%), and the assessors (41%). Further points were lost for a failure to meet the criterium of ‘concealed allocation’ (44%) and ‘intention-to-treat analysis’ (30%). The electronic literature search resulted in 473 potentially relevant articles. After removing duplicate articles, 392 articles qualified for the title and abstract analysis. At this stage, 333 items were rejected, while 59 were accepted for full-text analysis. Finally, after considering the eligibility criteria for the review, 27 articles were accepted: 21 for cervical and 6 for lumbar radiculopathy. The list of excluded studies has been provided as a In seven studies, as an intervention, one of the studied groups received manual therapy alone (four in CR and three in LR). Most often, manual therapy was combined with exercises and physical therapy . In CR, twelve studies used cervical traction. In LR, every study used different manual therapy techniques: one study used mobilization, one traction, one manipulation, one flexion-distraction technique, and one The Mulligan bent leg raise.The first purpose of this study was to describe current knowledge regarding the effectiveness of manual therapy in CR and LR. Functional outcome is considered to be the main criterium in assessing an intervention’s efficacy for CR and LR, which can divide patients’ treatment into surgical or non-surgical. The most specific, with internal consistency and excellent test-retest reliability ,62 assesTreatment with CR, unlike LR, mainly focused on traction techniques in most authors. This situation is due mainly to a much more comfortable grip and control in the cervical spine than in the lumbar spine, which is a more specific technique. While Ayub et al. (2019) combined traction with other treatment forms such as neural mobilization (passive vs. active), none of the treatment methods was found to be superior to the others . Afzal eNeural mobilization is a type of technique aimed at healing neural tissue which is considered to be one of the main problems in radiculopathy after mechanical compression . Nerve rJoint techniques are appropriate in treating joint-oriented dysfunction. This type of impairment can be taken into consideration regarding the biomechanical background of CR and LR. The relation of facet joints may be imbalanced, which can result in joint(s)’ hyper- or hypomobility. These techniques are aimed at treating hypomobile segments, while the hypermobile needs to be stabilized by in-depth muscle training. No author provides details on patients’ manual examination, called “joint play” in manual therapy, which is essential in stating whether this individual needs to be mobilized in this segment in this particular direction. Although Ayub et al. (2019) and Bukhari et al. (2016) applied mobilization in their research, it was only part of a multimodal approach aiming to differentiate traction techniques, with no further details provided on mobilized segment ,48. YounA specific exercise program has been used by several authors ,52,53,54Regarding LR, a limited number of RCTs was found to be eligible in this review. Among the five studies, few methods of treatment for LR were used by authors, and, unlike CR, no trends in choosing treatment form were observed. No unity was found in functional outcome assessment across all included studies. Only two of five studies included neurodynamic tests (SLR) ,57. MousDue to the diversity of treatment methods used, it is challenging to compare their effects. Satpute et al. (2019) applied spinal mobilizations with leg movement plus exercise and electrotherapy, compared to exercise and electrotherapy alone  and founExercise programs are present in two out of five (40%) of our findings ,60. GudaWhen analyzing the efficacy of neural tissue mobilization, two authors applied this type of treatment ,57. DespThe overall quality of the included studies’ is low to moderate. Only one study designed an intervention with blind therapists , and twoThe main recommendations relate to the standardization of clinical examination with objective methods or specific devices and full details on the intervention. The decision-making process would be more fruitful with advanced radiological imaging and functional outcome extended by neurodynamic tests that correlate with symptoms in distal parts of the body. As symptomatic radiculopathy most often impairs the extremities’ function, it should be essential to focus on this field and control the outcome using clinical tests such as ULNTs for CR and SLR and SLUMP for LR. Insufficiently detailed information is most often found for specific techniques. No detailed pre-intervention assessment is normally provided, which complicates the selection of appropriate treatment.First, we considered only papers in English. Second, in this study, the literature review was conducted using two databases, without a grey literature search, which could limit the generalizability of obtained results. Due to the controversial homogeneity of the manual therapy methods used and the specific aim of this paper, we decided not to design our study as a meta-analysis, which could also be seen as a limitation. A small number of LR clinical trials was also a significant barrier in unifying treatment methods for this pathology. Another limitation was the poor quality of most of the available publications.Traction-oriented techniques are the most frequently chosen treatment form for CR and are also efficient in reducing pain and improving functional outcomes. Mobilization techniques often lack information about the patient’s examination before the baseline, which makes it challenging to evaluate its efficacy. Exercise programs itself are efficient and improve patients’ outcomes, but there is no standardization of specific activities to specific pathology algorithm. Due to a radiculopathy background and possible symptoms, the decision-making process, including neurodynamic tests, should be mandatory for all CR and LR individuals. Based on the available literature, the multimodal approach with traction component is the most efficient for CR, and the multimodal approach with traction component, spinal mobilizations, and activation of core muscles for LR. No single-method therapy is recommended for treating both CR and LR.


P = 0.021). Furthermore, Pearson's correlation analysis revealed that abundance of Haemophilus was positively correlated with negative psychiatric symptoms , while abundance of Coprococcus was negatively correlated with negative psychiatric symptoms . Moreover, abundance of Haemophilus was positively correlated with cognition , excitement , and depression . The study findings suggest that alterations in certain gut microbiota may interfere with psychological symptoms in schizophrenia. Our results provide evidence that may help in the development of therapeutic strategies using microbial-based targets. The data that support the findings of this study have been deposited in the NCBI (https://submit.ncbi.nlm.nih.gov/) with accession number SUB9453991.Increasing evidence indicates an interaction between dysbiosis of the microbiota and the pathogenesis of schizophrenia. However, limited information is available on the specific microbial communities associated with symptoms of schizophrenia. Therefore, this study aimed to investigate gut microbiota dysbiosis and its relationship with psychopathologies in schizophrenia. We recruited 126 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria—acute group (patients with acute schizophrenia), remission group (patients with schizophrenia in remission), and control group . Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Microbiota compositions, diversity and community structure were evaluated using 16S rRNA sequencing. Pearson's correlation analysis was used to evaluate the association between bacterial taxa and psychotic symptoms. The beta-diversity of microbiota composition in the acute group was distinct from that in the remission and control groups (PC1 = 21.11% vs. PC2 = 12.86%,  Schizophrenia is a severe psychiatric disorder that significantly affects patients' quality of life , 2. It ivia secretion of different biochemicals, such as γ-aminobutyric acid, dopamine, norepinephrine and serotonin . All participants provided written consent prior to study participation in accordance with the principles of the Declaration of Helsinki. The trial clinical registration number was chiCTR1800019343.n = 42), remission group , and control group . All patients were hospitalised at the AMHC between January 2018 and September 2020, healthy controls are the healthy people recruited by the hospital physical examination centre , —acute group  6.0.0. According to the trial standards, patients of acute group and remission group diagnosed with schizophrenia met the criteria of the DSM-5. The inclusion criteria for the patients in the acute group were as follows: (1) age = 18–60 years, (2) fulfilment of the DSM-5 criteria for schizophrenia, (3) the first episode of schizophrenia without anti-psychotic treatment, and (4) PANSS total score ≥60 points. The inclusion criteria for the patients in the remission group were as follows: (1) fulfilment of the first and second criteria of the acute group, (2) patients with a total course of disease <10 years, received only second-generation anti-psychotic, such as risperidone, quetiapine, and aripiprazole, (3) the patient's clinical symptoms disappeared after treatment and self-consciousness and social function had recovered for at least 3 months, and (4) PANSS total score <60 points. Healthy controls were recruited from the local community at the same time as other participants through advertising. The exclusion criteria were as follows: (1) a history of craniocerebral trauma, organic cerebral diseases, physical diseases, or other mental disorders; (2) a history of alcohol or other substance use; (3) diabetes, hypertension, dyslipidemia, endocrine disease, or known medical conditions that might affect metabolism; (4) pregnant or lactating women; (5) a history of digestive tract diseases, abdominal surgery, or intestinal infection in the past 3 months; (6) administration of electroconvulsive therapy without convulsions before enrolment;(7) diet change significantly in the past 6 months; (8) treatment with antibiotics or corticosteroids, probiotic preparations, or other immune preparations in the past 3 months.Participants were screened by experienced psychiatrists for inclusion in the study. The initial clinical diagnoses were validated using the MINI 6.0.0. It is a concise diagnostic interview for psychiatric disorders developed jointly by psychiatrists in the United States and Europe. It has been structured to meet the criteria for a brief psychiatric interview that can be conducted in 15 min. All patients underwent the MINI 6.0.0 to confirm the clinical diagnosis of schizophrenia .Table 2. A Mandarin version of a five-factor model of the PANSS has been proven to have good reliability and validity, with a Cronbach's alpha coefficient of 0.928 and an intra-class coefficient of 0.878 .t-test, and discontinuous variables were compared using the χ2 test.The SPSS, version 22.0, statistical package for Windows  was used for data analysis. Demographic data and clinical characteristics were compared among the three groups. Continuous variables were analysed using an independent samples 10 fold change ratios from medians were calculated from the group medians of highly abundant bacteria at the genus level. Pearson's correlation analysis was used to identify the relationship between dysbiosis intestinal flora at the genus level and psychiatric symptoms. For all statistical analyses, P < 0.05 (two tailed) was considered significant.To explore the diversity of the gut microbiota, we performed R (version 3.3.2) and R Studio (version 1.0.136) to calculate a range of estimators. Principal coordinate analysis (PCA) based on the Unweighted UniFrac distance matrix was used to identify differentially abundant operational taxonomic units. A linear discriminant analysis effect size (LEfSe) procedure was used with the Kruskal–Wallis rank-sum test to identify microbiome biomarkers in the faecal samples from the three groups at various taxonomic ranks. Bacteria with a linear discriminant analysis score of 2 were defined as significantly abundant. For the construction of the heat map, logP = 0.007).The baseline demographic and clinical characteristics of the study participants are presented in P = 0.021). The results of beta-diversity analyses demonstrate that the overall composition of the microbiota in acute group has changed obviously compared with remission and healthy groups.To explore the richness and diversity of the bacterial community within the acute, remission, and healthy groups, we calculated the alpha and beta metrics. The alpha-diversity was not different among the three groups . For betFusobacteriales, Actinomyces, Turicibacter, Turicibacterales, and Chthoniobacterales, while the healthy control group was enriched with Lachnospira and Coprococcus. At the order level, two microbiota members Succinivibrionaceae and Lactobacillaceae displayed an enriched trend in the remission group. Five microbiota members, Tissierellaceae, Turicibacteraceae, Chthoniobacteraceae, Actinomycetaceae, and Enterococcaceae were identified in the onset group. At the phylum level, we found that four microbiotas, Desulfovibrio, Mitsuokella, Lactobacillus, and Succinivibrio, were enriched in the remission group. The cladogram  = 11.72, P = 0.001], Desulfovibrio , Succinivibrio , Coprococcus , Lachnospira , Haemophilus , Clostridium , and Lactobacillus . Post-hoc Tukey's multiple comparison test further assessed the differences in these eight markers among the three groups. The results showed a high abundance of Coprococuus and a low abundance of Megasphaera, Succinivibrio, and Clostridium in the healthy group. The Megasphaera and Megamonas numbers was high in the remission group, while those of Haemophilus and Faecalibacterium were low in the acute group.Further analysis will focus on the relationship between dysbiosis markers of microbio and psychotic symptoms among three groups. The genus-level analysis identified 42 genera in the three groups . We obseHaemophilus was positively associated with negative psychiatric symptoms , while abundance of Coprococcus was negatively associated with negative psychiatric symptoms . Moreover, abundance of Haemophilus was positively associated with cognition , excitement , and depression .Previously, correlation analysis has revealed that the structures of the bacterial community are related to disease symptoms. To assess the association between these dysbiosis markers and psychotic symptoms, we performed Pearson's correlation analysis for these dysbiosis markers with five factors of the PANSS . The resMental health is ‘a state of well-being in which the individual realises his or her own abilities, can cope with the normal stresses of life, works productively and fruitfully, and makes a contribution to his or her community’ . The gutWe analysed the gut microbiomes of patients with schizophrenia at the AMHC, Anhui, China. The data compared the gut flora at the genus level among the acute, remission, and healthy groups. First, we observed an overall alteration in the diversity and abundance of bacterial communities in the gut microbiota of individuals at different stages of schizophrenia. The results of alpha estimators did not reveal alterations among the three groups, and these outcomes are consistent with those of previous studies , 37. TheSuccinivibrio, Haemophilus, Lactobacillus, Megasphaera, Desulfovibrio, Coprococcus, Clostridium, and Lachnospira were altered during different stages of schizophrenia. Previously, these bacteria have been shown to be associated with neuropsychiatric disorders  compared to that in healthy subjects. We found that abundance of https://submit.ncbi.nlm.nih.gov/) with bioproject number (PRJAN750612).The data that support the findings of this study have been deposited in the NCBI . All participants provided written consent prior to study participation in accordance with the principles of the Declaration of Helsinki. The trial registration number was chiCTR1800019343. The patients/participants provided their written informed consent to participate in this study.XZ and JC were responsible for study design and manuscript editing. CZ, MZ, and UA were responsible for literature searches, statistical analyses, and manuscript writing. QX, C, JY, and KW were responsible for clinical-scale assessment data collection. ZW, LY, and YC were responsible for clinical blood data collection. All authors have contributed to and have approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Disorder of locomotor function is universal in patients with spinal cord injury (SCI) and has a severe impairment on their quality of life. Metformin, the first-line antidiabetic drug, has been used to improve locomotor function in SCI rats through antioxidative mechanisms recently.  A search strategy was conducted from databases, including PubMed, Web of Science, MEDLINE, and Scopus database until April 2021. The methodological quality of the animal experimental studies was assessed according to the Systematic Review Centre for Laboratory animal Experimentation's Risk of Bias tool. The weighted mean difference was calculated with the random-effects model.  Seven eligible studies on SCI and metformin were reviewed. The meta-analysis indicated that SCI rats receiving metformin therapy showed a significant locomotor function recovery. Limitations and no obvious publication bias were presented in the studies.  Metformin can promote the recovery of the locomotor function of SCI rats. However, the use of this meta-analysis was influenced due to the not high quality of studies. Consequently, more high-quality studies are necessary for preclinical studies of SCI in the future. Spinal cord injury (SCI) is a serious traumatic disease, usually caused by external mechanical injury, leading to paralysis and other serious consequences , 2. The Therefore, drug therapy and cell transplantation are widely concerned and studied –9. HowevκB signaling pathway [Metformin is a widely used drug to treat diabetes since the 1960s . But acc pathway –16. ConsWe aimed to verify the hypothesis: metformin has a better curative effect than placebo on locomotor function recovery in the rat SCI model. Therefore, meta-analysis was performed to evaluate the recovery of locomotor function in SCI rats according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.A search strategy was conducted from databases, including PubMed, Web of Science, MEDLINE, and Scopus database until April 2021. Relevant studies were searched using the terms “dimethylbiguanidine”, “dimethylguanylguanidine”, “glucophage”, “metformin hydrochloride”, “hydrochloride, metformin”, “metformin HCl”, “HCl, metformin”, “spinal cord trauma”, “spinal cord traumas”, “spinal cord injury”, “spinal cord injuries”, “spinal cord contusion”, “spinal cord laceration”, “post-traumatic myelopathy”, “traumatic myelopathy”, “spinal cord transection”, “rat”, and “rats”. In addition, the reference list of the relevant papers was searched for additional relevant studies. The identified studies were verified following the selected criteria by two experienced investigators individually .Articles were evaluated, respectively, for preliminary screening by two reviewers in agreement with the title, abstract, and full text. Arguments discussed by a third person were resolved. The language was restricted to English research.Researches were included according to the following criteria: (1) SCI rat models were involved with traumatic SCI, including compression and contusion injury. (2) The motor function was evaluated deliberately. (3) Intervention of metformin was compared with placebo control in SCI rats. The dose and the administration method of metformin, duration of treatment, and follow-up time were unrestricted. (4) Physiological saline, vehicle, or no treatment were included in the control groups.Researches were excluded according to the following criteria: (1) Nontraumatic injury, penetrating injury, and complete transverse spinal cord injury of the SCI rat models were excluded. (2) The study of clinical case reports, genetically modified rats, and metformin combined with other intervention treatments was excluded. (3) Review, duplicated, and not related articles were excluded.The Basso, Beattie, and Bresnahan (BBB) scale was identified as the most important outcome indicator . Since tData were independently extracted from included literature by three authors . The following terms were extracted: the first author, publication year, country, rat strain, weight and gender, the model and level of the SCI, the number of rats per group, the type and timing of intervention, the duration of follow-up, and the records of BBBs . The numThe methodological quality of the animal experimental studies was assessed according to the Systematic Review Centre for Laboratory animal Experimentation's Risk of Bias tool (SYRCLE's RoB tool) . The terP < 0.05 was regarded as statistically significant. The heterogeneity of included papers was evaluated by I2. The analysis of sensitivity and subgroup was used to find the source of heterogeneity. The publication bias was estimated by Egger's test and funnel plot.Statistics/Data Analysis 14.0  was used to analyze the data extracted from the studies for meta-analysis. The weighted mean difference (WMD) was used to describe the data of the same unit, and the standardized mean difference (SMD) was used to describe the data of the different units. The 95% confidence interval (CI) was used for two types of results. A total of 65 studies were retrieved in the database. Thirty-nine duplicate studies were removed. Subsequently, 18 studies were excluded due to the abstract and title. Then, the full text of 8 studies was evaluated, and 1 study was excluded due to the lack of motor function evaluation . FinallyCharacteristics of the studies included in this meta-analysis are presented in The SYRCLE's RoB tool was used to evaluate the bias risk in all 7 independent studies . In geneI2 = 91.5%; p < 0.0001; The meta-analysis indicated that SCI rats receiving metformin therapy showed a significant locomotor function recovery in all studies. After the intervention of metformin, the BBBs score increased , and more than 50 mg/kg  bring about a similar effect on motor function recovery , BBBs of the SCI model of compression was significantly promoted in rats. In the rest of the studies , BBBs of the SCI model of contusion was also significantly promoted in rats  of metformin conducted in Iran on BBBs was significantly higher in rats. The rest of the studies  of metformin conducted in China on BBBs was also significantly promoted in rats (There are different countries of metformin on recovery of the BBBs score in rats with SCI. Subgroup analysis was carried out according to different countries. One study (WMD = 4.37; 95% CI, 2.12-6.63;  in rats .The Egger test and funnel plot of publication bias have been evaluated for BBBs . The pubAs far as we are aware, this is the first meta-analysis to evaluate the motor function recovery of metformin in SCI rats. Seven studies on the laboratory intervention of metformin in SCI rat models were summarized to show the preclinical effect. The meta-analysis found that the treatment of metformin of SCI rats contributed to motor function recovery. Compared with the SCI control group, a valuable promotion of the BBBs score was indicated in rats after SCI in the metformin groups. Subgroup analysis of different doses of metformin, SCI models, and countries was all performed to show the beneficial promotion of the motor function recovery after the administration of metformin. In general, the overall quality of the studies was not high, and the allocation concealment, blinding, random outcome assessment, complete outcome data, and free of inappropriate influence of funders were not reported in all studies.This is the first meta-analysis on metformin administration in rats after SCI. Subgroup analysis of different doses, countries, and SCI models was performed to detect the effect of metformin on SCI rats. The result of animal studies is of great significance to human beings and may be used as an effective drug to restore motor function in clinical trials. All the included studies were published within 5 years.However, some limitations exist in this meta-analysis. There is a shortage of original articles which is common in the other meta-analyses. Despite the more influential English database being searched, the relevant articles may still be omitted. The quality of the meta-analysis was not very high according to the SYRCLE's RoB tool. Publication bias, which means that the positive result and large sample are always easier to be published, erodes the authority of our study. None of the studies described allocation concealment, blinding, random outcome assessment, complete outcome data, and free of the inappropriate influence of funders. In general, the real effect is inclined to be different from our evaluated effect due to the not high quality of the involved article in this meta-analysis.SCI causes secondary pathological changes, including neuronal inflammation and apoptosis, resulting in temporary or permanent spinal cord dysfunction , 25. In In general, metformin administration could contribute to the recovery of locomotor function in SCI rats according to this meta-analysis. Different doses of metformin, SCI models, and countries have similar effects. Despite the not high methodological quality, metformin would be a promising reagent of SCI treatment. A further study of metformin should be conducted in preclinical trials.


An increased HbAA concentration was noted with reduced high triglyceride and low high-density lipoprotein cholesterol levels in the adjusted model (p < 0.05). High fasting plasma glucose level significantly correlated with HbGA concentration in the adjusted model. In conclusion, AA exposure alters metabolic syndrome markers in adults. Additional clinical and animal studies will clarify the role of AA exposure at different stages in the progression of metabolic syndrome-related diseases.Metabolic syndrome encompasses multiple conditions that increase the risk of cardiovascular disease, and exposure to environmental chemicals can cause metabolic syndrome. This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey (2003–2006) on 4318 adult participants to assess the association between acrylamide (AA) exposure and metabolic syndrome. Concentrations of hemoglobin-adducted AA (HbAA) and hemoglobin-adducted glycidamide (HbGA) were evaluated. Metabolic syndrome markers related to HbAA and HbGA and the effect of exposure to AA and GA on the prevalence of metabolic syndrome were studied by ANOVA and multivariate logistic regression analyses, respectively. HbAA concentration inversely correlated with the number of metabolic syndrome markers ( Acrylamide (AA) is used to synthesize the well-known polymer polyacrylamide and to treat effluents from water treatment plants and industrial processes. AA exposure was first linked to neurotoxicity in 1997 in Sweden due to a serious event of environmental pollution by the leakage of a sealant during a tunneling project ,3. The SMetabolic syndrome encompasses several metabolic abnormalities that include central obesity, insulin resistance, hypertension, dyslipidemia, high triglycerides (TG), and low high-density lipoprotein (HDL) cholesterol and is strongly associated with an increased risk of diabetes, stroke, and cardiovascular disease (CVD) . MetabolExposure to hazardous materials can cause various physiological disturbances, resulting in damage to various organ systems, including those involved in metabolism . AA expoThe US National Health and Nutrition Examination Survey (NHANES) is a nationally representative, complex sampling survey that combines interviews and results of physical examinations. All data were acquired from the NHANES website. Use of the NHANES data was approved by the NCHS Research Ethics Review Board, and all participants had provided written informed consent. We included participants aged ≥18 years old in the NHANES dataset from 2003–2006 and excluded persons with missing data. Ultimately, 4813 participants were included. Participants were divided into two groups based on the presence or absence of metabolic syndrome. The clinical definition of metabolic syndrome was provided by the National Cholesterol Education Program’s Adult Treatment Panel III (ATP III)  Table 1Table 1.Blood samples were obtained by the laboratory at NHANES, National Center for Health Statistics, Centers for Disease Control and Prevention. The blood specimens were collecting in the of whole blood and separated to different vessels for examination. Specimens for acrylamide- and glycidamide hemoglobin adducts analysis may be fresh or frozen erythrocytes or EDTA-whole blood. The sample solutions used for HbAA and HbGA measurements were subjected to the modified Edman reaction, and the Edman products were isolated and analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS). This method is linear for HbAA and HbGA in the range 1.25–80 nmol/L. The bench quality control (QC) pools used in this method comprised three concentration levels , and the results were checked in triplicate after each run .Ethnicity was categorized as “Mexican American,” “Other Hispanic,” “non-Hispanic white”, “non-Hispanic black” or “Other Race”. Plasma aspartate aminotransferase (AST), creatinine (Cr), cholesterol, and glucose levels constituted the routine biochemistry profile. Analyses were performed with a Beckman Synchron LX20. Smoking status was determined by participants’ answers to the question “Do you currently smoke cigarettes?” The physical condition interview data provided the health status and medical history as reported by the individual and the agent, including emphysema and angina/angina pectoris.p < 0.05 indicates a statistically significant difference.All data analyses were performed using SPSS . We applied the Kolmogorov-Smirnov test for normal distribution. The Chi-square test was used to analyze categorical data, the t-test was used to analyze continuous data. The Mann-Whitney U test was used to analyze HbAA and HbGA concentrations. ANOVA was used to analyze the markers for metabolic syndrome related to HbAA and HbGA concentrations. The extended model was used to adjust for covariates. Values of HbAA and HbGA were log-transformed. Multivariate logistic regression models were used to analyze the effect of exposure to AA and GA on the markers for metabolic syndrome. Multi-variant linear regression analysis was used for HbAA and HbGA concentrations and continuous variables for each marker . Model 1 was unadjusted, whereas Model 2 was adjusted for age, gender, ethnicity, serum AST, serum creatinine, emphysema, angina/angina pectoris, and smoking status. Quartile-based analysis was performed to evaluate the trends in HbAA and HbGA concentrations and the association of prevalence of metabolic syndrome. N = 20470) and accounting for those not attending baseline data collection sessions, 4813 participants were finally available for analysis in this study. The participants were divided into the metabolic syndrome group (N = 1064) and the non-metabolic syndrome group (N = 3749) (After screening for eligible participants ( = 3749) . The meap = 0.275 and 4–5: β coefficient = −0.127; 95% CI = −0.229, −0.025; p = 0.015). Most results for correlation with log-transformed HbGA were not significant in the adjusted model, except for high glucose level . Increased concentrations of HbAA were noted with high triglycerides and low HDL cholesterol in the adjusted model (p < 0.05) (p < 0.05). The association between concentrations of HbGA and metabolic syndrome was not significant. < 0.05) . High blThis is the first study to demonstrate the correlation between metabolic syndrome and HbAA and HbGA levels, which indicate exposure to harmful substances caused by smoking, dietary habits, and occupation. The results revealed a significant negative correlation between metabolic syndrome and HbAA and HbGA concentration. There were no apparent correlations in adjusted model. However, among the metabolic syndrome markers, negative associations with HbAA were observed for high TG and low HDL cholesterol, and negative association with HbGA was observed for high glucose.The toxicological health hazards of AA exposure are well-known. The main sources of AA in the human body are diet, especially Western-style foods, and occupation. AA has been identified as a carcinogen and is shown to exhibit neurotoxicity, genotoxicity, and deleterious reproductive effects. One of its metabolites, GA, is considered to exhibit even stronger cytotoxicity ,8. HowevInsulin resistance is central to the development of metabolic syndrome. Increased intracellular fatty acid metabolites contribute to insulin resistance by impairing insulin-signaling pathways. Smoking is a major source of AA exposure, and chronic smoking is associated with high age- and body mass index (BMI)-adjusted plasma insulin levels that are independent of other factors known to influence insulin sensitivity . In a stInsulin resistance can alter systemic lipid metabolism, which then leads to the development of dyslipidemia and includes high levels of plasma TG and LDL and low levels of HDL cholesterol . LowerinStudies on rodents have shown that maternal AA exposure during pregnancy is related to the weight loss of offspring . In subpThe mean AA exposure in Europe is estimated to be in the range of 0.31–1.1 µg/kg body weight/day for adults (>18 years old), and the major contributors to the exposure in adults are fried potatoes, coffee, and soft bread, whereas in adolescents and children, the major sources of exposure are fried potatoes, soft bread, potato crisps, and biscuits . The resAA hemoglobin biomarkers are inversely associated with CVD, including congestive heart failure, coronary heart disease, angina pectoris, heart attacks, and strokes, in people exposed to environmental tobacco smoke and in active smokers. However, there is no significant correlation between hypertension and AA exposure in the risk of CVD . In the A pro-inflammatory state is considered a marker for metabolic syndrome. As mentioned earlier, AA exposure results in oxidative stress featured by increasing ROS and MDA levels and GSH consumption. Moreover, AA activates the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) pathways that are regulated by MAPKs . In the First, this was a cross-sectional study based on observational and retrospective analyses of existing data from a single period rather than on long-term repeated observations with limited causal inference. Second, the information comes directly from participants’ self-reports, and other data confirming the diagnosis or following dietary habits are limited because AA consumption is one of the main sources of AA exposure. Third, metabolic syndrome is multifactorial, and the incidence of insulin resistance in men and women increases with age and hormone changes, and these variants cannot be adjusted for due to restricted data access. The mean age difference was found in two groups of our study participants. Similar age cohorts studies are required for further evaluation. Fourth, exposure to acrylamide may also be an indicator of exposure to multiple chemicals, including other endocrine-disrupting chemicals, which is hard for covariates adjustment in this study. Fifth, liver genes and enzymes affect the differences in the metabolism of AA exposure in human. Among the components of metabolic syndrome, liver enzymes are also closely related to lipid metabolism and sugar metabolism. In this study, we could not assess the impact of genetic differences between ethnic groups.The findings of this study indicate that Hb-adducted AA, the biomarker of exposure to AA is negatively associated with high triglycerides, low HDL cholesterol, markers of metabolic syndrome. Hb-adducted GA, the metabolite of AA in human, is negatively associated with high glucose. As exposure to AA from smoke and food has become a worldwide concern, the findings of this study provide an epidemiological data of AA exposure. The toxic effects of AA include neurotoxicity, reproductive toxicity, genotoxicity, and carcinogenicity. The results of the study indicate that AA could play a role in different stages of progression of metabolic syndrome-related diseases. In the future, the association between long-term exposure and disease progression in different ethnic groups (including dietary habits and smoking status) needs further research to clarify the effects of AA on human health.


Computational aid for diagnosis based on convolutional neural network (CNN) is promising to improve clinical diagnostic performance. Therefore, we applied pretrained CNN models in multiparametric magnetic resonance (MR) images to classify glioma mimicking encephalitis and encephalitis.A data set containing 3064 MRI brain images from 164 patients with a final diagnosis of glioma (n = 56) and encephalitis (n = 108) patients and divided into training and testing sets. We applied three MRI modalities  as the input data to build three pretrained deep CNN models , and then compared their classification performance with radiologists’ diagnostic performance. These models were evaluated by using the area under the receiver operator characteristic curve (AUC) of a five-fold cross-validation and the accuracy, sensitivity, specificity were analyzed.p<0.05). For Inception-v3 and ResNet-50 models, T2WI offered the highest accuracy, followed by CE-T1WI and FLAIR. The performance of Inception-v3 and ResNet-50 had a significant difference with radiologists (p<0.05), but there was no significant difference between the results of the Alexnet and those of a more experienced radiologist (p >0.05).The three pretrained CNN models all had AUC values over 0.9 with excellent performance. The highest classification accuracy of 97.57% was achieved by the Inception-v3 model based on the T2WI data. In addition, Inception-v3 performed statistically significantly better than the Alexnet architecture (The pretrained CNN models can automatically and accurately classify these two diseases and further help to improving clinical diagnostic performance. For an intracranial lesion, the first question faced by the neuroradiologist is whether it is a neoplastic or non-neoplastic lesion. Glioma and encephalitis are two common diseases of the central nervous system that sometimes overlap in their clinical symptoms and radiographic presentations . HoweverMRI is most commonly used to assess brain diseases due to its superior contrast compared with other imaging modalities. In current conventional MR imaging methods, it is not difficult to classify encephalitis from a single enhancing glioma with perifocal edema, mass effect, and necrosis. However, some gliomas  show focal area enhancement or no enhancement lesions without mass effect or necrosis, which may be misdiagnosed as encephalitis, resulting in delayed treatment , 2. On tSome advanced MR modalities such as diffusion-weighted imaging (DWI), MR spectroscopy (MRS) and perfusion-weighted imaging (PWI) play important roles in differentiating glioma and encephalitis to some extent. However, generally advanced imaging techniques require additional expense and time to perform and may not be routinely performed for every patient in clinical practice. By contrast, FLAIR, CE-T1WI, and T2WI are almost always available. However, conventional MRI modalities do not fully perform deep mining of the intrinsic features of images given the limitations of the subjective vision of the human eye. To improve the diagnostic accuracy and efficiency, advanced and automated methodologies are needed.Recently, computational aid in diagnosis became a fast-developing research area, combining radiology imaging and computers in a noninvasive fashion to extract a large number of high-dimensional features to help improve clinical diagnostic performance , 5. SeveThus, in this study, we aimed to train CNN models to automatically classify glioma mimicking encephalitis and encephalitis by analyzing conventional multiparametric MRI images. We made three comparisons of the classification performance to find the most suitable classifier model for the classification problem: (a) a comparison of three existing pretrained CNN architectures  with different parameters and layers, (b) a comparison of the effects of different MR modalities  on a model based on the same network, and (c) a comparison of quantified deep learning models with radiologists’ diagnostic performance.For this retrospective analysis, ethical approval was obtained by our institutional review board , and the informed consent requirement was waived. The study population consisted of 164  patients enrolled at the institution consecutively between January 2012 and January 2020. The glioma mimicking encephalitis inclusion criteria were as follows: (1) histopathologically confirmed cerebral gliomas, and (2) patients with atypical MR imaging such as patchy or large patchy abnormal signals and insignificant enhancement without mass effect or necrosis, which are difficult to differentiate from encephalitis. Encephalitis inclusion criteria: encephalitis had the lesion on MRI, and was confirmed by cerebrospinal fluid analysis, antibody testing, virus examination, surgery or pathological biopsy, or confirmation of the diagnosis because the lesion completely or largely disappeared or turned into encephalomalacia during the follow-up period. In addition, before a routine MRI examination, no patients had a previous brain biopsy or treatment, and three MRI modalities  were used. The exclusion criteria were followed as: (1) the lesion was too small and its diameter was less than 10 mm, (2) MRI images had motion and other artifacts with poor quality that affected the analysis. The number of raw images in the glioma mimicking encephalitis and encephalitis group was 1570 and 1494 images, respectively.All MR images were obtained on a GE 3.0 T scanner  equipped with an eight-channel head coil. All images were stored in the picture archiving and communication systems . The acquisition parameters of were as follows: conventional axial T1WI , axial T2WI  and FLAIR sequence . Axial contrast-enhanced T1WI  was obtained after intravenous rejection of 0.1 ml/kg gadobutrol . The scan range included the region from the calvarial vertex down to the foramen magnum.To compare the diagnostic performance of the pretrained CNN models with a visual assessment, MRI images of all 164 cases were independently reviewed by the same two neuroradiologists . They were blinded to clinical information but were aware that the patients were either encephalitis or glioma without knowing the exact number of patients diagnosed with each entity. The two readers assessed only conventional MR images  and recorded a final diagnosis using a 4-point scale . Cohen’s kappa coefficients were used to assess the interdiagnosis agreement by the two radiologists, which was interpreted as follows: <0.20 = slight, 0.21–0.40 = fair, 0.41–0.60 = moderate, 0.61–0.80 = good, and 0.81–1.00 = excellent.All MRI images  were exported in.jpg format without annotation from the original digital imaging communication in medicine (DICOM) format on PACS. Then we use the Opencv image-processing library to cut out the redundancy around the images, such as the skull and eyes, and only retain the brain parenchyma of the original image matrix. The flowchart was added to the supplementary materials. After that, images containing lesion areas were selected by the two experienced neuroradiologists. This screening can ensure that all features contributing to the classification are retained, and remove the nonfocus sections that interfere with the classification.Data augmentation plays a vital role in the utilization of deep learning in medical images, especially in our task, which lacks data. The training data were augmented four times by randomly choosing four methods from a list of six methods: contrast transformation, brightness conversion (increased and decreased), sharpening and flipping . The test data set was kept as origin. Last, in order to implement our experiment more efficiently, as the CNN’s network architecture we chose the bilinear interpolation to resize all the images to 224 × 224.One of the most important reasons for the tremendous success of deep learning is that it can handle massive amounts of data. With the development of the Internet, thousands of different data can be obtained in a very short time. Nevertheless, in the field of medical imaging, there is usually a lack of data sets. Moreover, the annotation of medical images is not only tedious, laborious, and time-consuming but also demanding of costly, specialty-oriented skills that require experienced radiologists. Transfer learning is an effective method to solve this problem . TransfeBased on the idea of transfer learning, we selected current popular CNN networks  to classify encephalitis and glioma mimicking encephalitis of intracranial diseases with similar manifestations on MRI. We trained them using the ImageNet data set. After that, we utilized our own training data set to fine-tune these models and evaluate them in order to choose the model with the best performance. The transfer learning process for the classification of these two brain diseases is shown in After Alexnet was proposed and had tremendous success in image classification tasks during the ImageNet Large-Scale Visual Recognition Challenge (ILSVRC) in 2012, more and more deep convolutional neural networks with superior performance were proposed and applied in scientific research and practical applications, such as computer vision and natural language processing. All basic structures are the same, including the convolutional layer, pooling layer, and fully connected layer.In 2012, the Alexnet was the first architecture to use a deep convolutional neural network, which showed the best results and achieved significant improvement over traditional non-deep methods for the ILSVRC task  curve that is drawn by the false positive rate and true positive rate as our principle evaluation measure. The ROC and the area under the curve (AUC) were used to evaluate the discrimination performance of these models using DeLong tests, and The preprocessing and classification methods were coded in python using Keras and Opencv. Evaluation methods were implemented using scikit-learn. All experiments were performed using Ubuntu OS on a machine with an Intel Xeon E5 2687W V3, NVIDIA GeForce 1080ti GPU, and 16 × 8GB of RAM.The CNN networks we chose  were all fine-tuned from ImageNet pretrained models. In these experiments, we fixed the hyperparameters to be the same so that we could choose the best model with excellent performance. For fine-tuning, the number of training epochs was 50, and the minibatch size was 32 image instances. We used Adam as our optimization method, and the hyperparameters had momentum: 0.9, weight decay: 0.0005 and base-learning rate: 0.001.p<0.05). The classification accuracy on FLAIR, CE-T1WI and T2WI of ResNet-50 was 88.95%, 93.33% and 95.75%, respectively. The Alexnet performance was statistically significantly lower than that of the ResNet-50 architecture when based on FLAIR modality (p<0.05). There was no statistically significant difference between ResNet-50 and Inception-v3 for any of the modalities.In this paper, we focused on three pretrained CNN models in classifying glioma mimicking encephalitis and encephalitis. p>0.05, DeLong test).To further examine the effect of different MRI modalities on model performance, FLAIR, CE-T1WI, and T2WI single modality networks were constructed, and the classification accuracies are shown in p<0.05, DeLong test) for any MRI modality. However, there was no significant difference between the AUC of the Alexnet model and those of the experienced neuroradiologist of reader 2 . These findings indicate the Inception-v3 and ResNet-50 models have a higher level of performance than radiologists' diagnostic performance. The performance of the Alexnet model is better than that of a resident neuroradiologist and equivalent to that of an experienced neuroradiologist.The diagnostic performance of visual assessment for these two diseases was evaluated by two neuroradiologists. The AUC were 0.891, 0.770 and the accuracy were 80.61% and 76.97% for readers 1 and 2, respectively. Interagreement between the two neuroradiologists was rated as moderate . Based on the results in In this study, three pretrained CNN models were fine-tuned using a transfer learning approach that was successfully implemented for the automated classification of glioma mimicking encephalitis and encephalitis on conventional MR images. Classification models with AUC values of 1.00–0.90 and 0.90–0.80 were regarded as excellent and good, respectively. In this study, no matter what MRI modality as the input data, three pretrained CNN network all had AUC values over 0.9 with excellent performance. Inception-v3 based on the T2WI modality achieved the highest classification accuracy. And then we demonstrated the utility of deep learning to classify neoplastic and non-neoplastic situations of the brain, yielding excellent diagnostic values over the visual analysis of neuroradiologists, which is consistent the results of other studies –8, 23.In terms of the structure of the three pretrained CNN models, namely Alexnet, ResNet-50, and Inception-v3 models for our classification problem. The Inception module of the Inception-v3 was able to extract features under different receptive fields, and combine these features to obtain deep features with stronger robustness, so as to achieve the best classification accuracy in this study. The structure of ResNet-50 model mainly improved the perspective of model optimization, but the size of receptive field was unchanged, resulting in its performance lower than Inception-v3. Notably, there was no significant difference between Inception-v3 and ResNet-50 models. As for Alexnet model, the number of convolution layers was too small to obtain advanced convolution features, resulting in the worst classification performance, which was significantly lower than that of inception-v3 and slightly lower than that of ResNet-50. Therefore, the deeper-layered Inception-v3 and ResNet-50 models provided features that are more suitable for distinguishing these two diseases than the thin-layered Alexnet model. Previous studies also confirmed it. Yang et al.  used AleSelecting which images to use is usually the basis for a machine learning study. In fact, the different MR imaging modalities used in machine learning studies of glioma in the current literatures with various conclusions. Some researchers reported that radiomics features extracted from the CE-T1WI with a better performance than other single MR sequences when grading the gliomas , 27 and There are some limitations in the present study. First, the sample size was relatively small for deep learning analysis and single-center study. Therefore, multicenter data sets and a larger patient cohort are needed to verify the current findings. Second, we did not include clinical data and imaging features to train a clinical model to compare with CNN models, and we will continue to study in the future. Third, we did not evaluate the diagnostic performance of deep learning based on T1WI sequence as it is difficult to automatically identify lesions, besides, the diagnostic performance of deep learning was not compared with combined sequences since the single sequence has achieved well results.In this study, we applied the transfer learning approach of three pretrained CNN models  to automatically classify glioma mimicking encephalitis and encephalitis on conventional MRI images. The results demonstrated that the three pretrained CNN models had excellent classification performances that were superior to those of the neuroradiologists. The Inception-v3 and ResNet-50 were significantly superior to Alexnet. And no matter what network was applied, the single MRI modality as the input data can obtain high and similar performance, among them Inception-v3 related to T2WI input achieved the highest classification accuracy. Thus, the pretrained CNN models can aid in the accurate and noninvasive classification of glioma mimicking encephalitis and encephalitis by automatically extracting deep features from multiparametric MRI images.The original contributions presented in the study are included in the article/The study involving human participants was reviewed and approved by The First Affiliated Hospital of Chongqing Medical University. For this retrospective analysis, the informed consent requirement was waived.Conception and design: SX and WW. Provision of study material or patients: WW, WZ, and QW. Collection and/or assembly of data: WW, WZ, and QW. Data analysis and interpretation: WW, JL, and JY. Manuscript writing: WW, JL, and WZ. Manuscript review: SX and JY. Final approval of manuscript: WW, JL, JY, QW, WZ, and SX. All authors contributed to the article and approved the submitted version.This research was supported by Chongqing Research Program of Basic Research and Frontier Technology [no. cstc2018jcyjAX0633] and the Fundamental Research Funds for the Central Universities [no. 2018CDXYGD0017]. We appreciate the funding to support the research.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background and objective: Nephrolithiasis (NL) is a public health problem in the population of Southeast Mexico because of its high prevalence and recurrence. The evolution of this pathology can result in renal damage and may even cause chronic kidney disease (CKD), leading to a reduced glomerular filtration rate (GFR), decreased kidney function, and kidney loss in advanced stages. However, few studies support this evidence in the population. The present study aimed to determine risk factors associated with CKD in adult patients in an endemic population of Mexico. Materials and methods: A case-control study was carried out with patients diagnosed with NL. Additionally, the clinical information of patients , characteristics of the stones , and biochemical parameters were collected. Results: The recurrence of NL was associated with CKD . In addition, male sex (p = 0.016), surgical history (p = 0.011), bilateral kidney stones (p < 0.001), and urinary tract infections (p = 0.004) were other factors associated with CKD. Interestingly, thirty-two patients younger than 50 years old with >2 surgical events presented a significant decrease in GFR (p < 0.001). Conclusions: The recurrence of NL and the number of surgical events were risk factors associated with CKD in patients with NL treated in our population. Nephrolithiasis (NL) is a disease characterized by a saturation of crystals in the nephrons that can generate kidney stones and damage renal tissue and function . GeneticThe worldwide prevalence of NL ranges from 1% to 20%, varying according to age, sex, race, geographic location, and environmental factors. For example, a higher incidence has been reported in men 40–60 years old compared with women .Patients with NL have a 51–68% chance of developing chronic kidney disease (CKD) ,8.The Centers for Disease Control and Prevention estimated that 15% of the adult population (37 million people) in the USA presented CKD in 2019, being more common in people aged 65 and older (38%) and less prevalent in people 54–65 (13%) and 18–44 (7%) .On the other hand, there is an increased prevalence of non-communicable diseases (NCDs) in the Mexican population. According to the National Health and Nutrition Survey, 2018(ENSANUT), type-2 diabetes mellitus (T2DM) is present in 15.3%, hypertension represents 12.9%, and obesity is prevalent in 35.3% of the population over 20 years old. In the same survey, Southeast Mexico had a prevalence of 15.4% for T2DM, 32.7% for hypertension, and 36.1% for obesity . In thisDue to the lack of evidence of risk factors associated with CKD in patients with NL in the Mexican population and the high prevalence and recurrence of this pathology, we conducted the present study to identify the risk factors associated with CKD in an endemic population Mexico.The study design was case-control and cross-sectional. Patients over 18 years old with NL diagnoses verified by computed tomography scan and treated at the Urology Department of the Regional High Specialty Hospital of the Yucatan Peninsula (HRAEPY in the Spanish acronym) between January 2018 and June 2020 were included. Patients with acute kidney injury (AKI) and prostatic hypertrophy diagnoses were excluded. 2). The case group comprised patients with NL and CKD (GFR < 60 mL/min/1.73 m2). In both groups, GFR was calculated using the CKD-EPI formula. The sample size was calculated using OpenEpi software  for an unmatched case-control study . Subjects were divided into two groups according to their GFR values. The control group consisted of patients with NL without CKD , recurrence of NL, presence of CKD, history of recurrent urinary infection, and general urine test and urine culture results. Additionally, the nutritional status of the patients was assessed using the body mass index (BMI).According to the surgical procedures, all patients who underwent kidney stone extraction at the host hospital underwent endourological procedures. Thus, the main surgical procedures performed were percutaneous nephrolithotomy and laparoscopic nephrectomy in patients with irreversible kidney damage. Nephrostomy and abscess drainage were carried out to improve kidney function. The hospital also received patients from other hospitals with a diagnosis of NL and a history of previous surgeries. The urology department evaluated these patients, and the previous diagnosis was confirmed. They were scheduled for surgical intervention when required. From all cases, surgical history was obtained  for NL and the number and type of surgical procedures.Radiological characteristics of the stones, such as the number, size (length and width), location , radiodensity (expressed in Hounsfield units), and the presence of staghorn stones, were documented. In addition, biochemical parameters  were also recorded.t-test or Mann–Whitney U-test were performed to compare the mean or median. Data were expressed as the mean ± standard deviation or median and quartiles. Frequencies were expressed in percentages. Differences between proportions were analysed using the Mantel–Haenszel chi-square test. Correlations between two variables were evaluated using the Pearson test. Multivariable logistic regression tests were used to explore NL risk factors. The variables were calculated using Jamovi software, computer software version 1.6, . Values of p < 0.05 were considered statistically significant.Continuous variables were evaluated using the Kolmogorov–Smirnov test to analyse the type of distribution. Student’s In this study, a total of 204 patients with NL were included: 79 patients with CKD  and 125 patients without CKD . p = 0.001) and systolic blood pressure (p = 0.004) when patients with and without CKD were compared. As expected, haemoglobin, uric acid, urea, serum creatinine, and GFR showed statistically significant differences when patients with and without CKD were compared (p < 0.001)  . Only onp = 0.742), the number of stones , presence of staghorn stones , and Hounsfield units (HU)  between patients with and without CKD . Additionally, T2DM was statistically significant in the adjusted analysis.p = 0.078) and left kidney  did not show significant differences between patients with and without CKD. Only having stones in both kidneys  was statistically significant in patients with CKD compared with patients without CKD .Regarding the location of the kidney stones, the right kidney  to control the impact of age on GFR and by the number of surgical events . These results are expressed in p = 0.954) and frequency of CKD (p = 0.783).Patients 50 years old or younger had more surgical events than older patients, which resulted in a decrease in GFR values and more cases of CKD . In patip = 0.037) and urinary tract infections . However, when hypertension and urinary tract infections were considered in conjunction, the significance was lost .A multivariable logistic regression of CKD patients was performed to determine whether the recurrence of NL is a risk factor for CKD, independent of hypertension and urinary tract infections. The results showed that recurrence of NL remained statistically significant independent of hypertension , thus promoting renal impairment.Although women were the majority in this study, the male sex was a risk factor in patients with CKD, also representing the older population. In contrast, a study by Shoag et al., found that a history of kidney stones was associated with a statistically significant increased risk of CKD among women. Nonetheless, no significant association was evident in men. Shoag et al., proposed a characteristic pathophysiology process in each gender . While iUnadjusted results indicated that hypertension is a risk factor associated with CKD, but the significance was lost when the results were adjusted, although it should be noted that there was still a trend, which could be due to the number of participants. In this context, many studies have confirmed the role of hypertension in the development of CKD thus, we do not rule out the impact of hypertension, and this effect was attributed to the sample size .The increase in prevalence of CKD in our population may be due to the coexistence of several clinical associations that accelerate renal function damage. Although T2DM was a statistically significant factor in the adjusted analysis by BMI, sex, and age, it was more frequent in patients without CKD, suggesting that T2DM is not an exclusive risk factor for CKD. Moreover, it is important to mention that factors such as the disease course and age of diagnosis were not considered. In this regard, studies suggest that T2DM and factors such as NL, urinary infections, and obesity can increase the risk of irreversible kidney damage, but further studies with an increased sample size that include data on disease course and age of diagnosis are needed ,20. Previous studies have shown an association between staghorn stones and CKD . Interesp = 0.032). Infectious processes are usually frequent in patients with NL hence, these infections could be due to an obstructive process that can damage the kidney parenchyma, leading to increased morbidity and a high risk of mortality [Urinary tract infections were risk factors for CKD in female patients  . In addip = 0.001), and age was a risk factor. Likewise, the percentage of patients with an invasive surgical history also significantly differed between those with and without CKD , suggesting a relationship between both parameters. Glassock et al., in their reports, suggested that GFR decreases with age, even in healthy older patients [p < 0.001)  . In suppOn the other hand, no statistically significant differences were observed when comparing patients older than 50 years with more than two surgical events versus patients younger than 50 years old. Therefore, the high risk conferred by number of surgical events was independent of age. It is important to mention that significance remained when analysing whether recurrence of NL was a risk factor for CKD independent of hypertension and urinary tract infections.The study showed some biases (Berkson bias): (a) all patients were selected from the High Specialty Hospital, who were referred from other medical units; (b) most of them had comorbidities ; (c) as the present study was cross-sectional, it was not possible to know the GFR of patients prior to each surgical event. In addition, some of them lived in a rural area without enough resources to cover the cost of traveling and attending all medical appointments, leading to an incorrect medical control of the disease progression.Regarding urine supersaturation, this was not evaluated because the excretion of urinary components are modified once the GFR is impaired. Hence, we considered that it was not appropriate to include this comparison with patients with CKD.The recurrence of NL and the number of surgical events were risk factors associated with CKD in patients with NL in our population. Additionally, male sex, bilateral kidney stones, and urinary tract infections were also risk factors for CKD in patients with NL. These findings indicated that independent of the type of surgical procedure, recurrence of NL increases the risk of irreversible kidney damage, and many patients may lose a kidney and require substitutive therapy, which increases mortality in the population.


Oral health is closely related to both physical and psychological well-being, as it enables individuals to eat, speak, and socialize. The number of teeth is the most used indicator of oral health. Several reports document a relationship of dental status with a variety of indicators of general health but longitudinal studies employing standardized physical performance tests are infrequent in the scientific literature.The Italian elderly participating in the Pro.V.A. longitudinal Study  underwent detailed interview and extensive clinical and instrumental examination that included validated physical performance measures. Participants were classified into 4 groups according to the number of remaining teeth: 0, 1–7, 8–19, and 20+. To explore the association of the number of remaining teeth with physical function and disability, we performed logistic regression analyses with models progressively adjusted for a wide number of covariates, namely anthropometric , comorbidity , muscle strength (assessed for upper and lower limbs), lifestyle  and socioeconomical status .Dental status correlated with most comorbidities, lifestyle, and socio-economic variables at the univariate analysis at baseline and at follow-ups. A good dental status was significantly associated with better physical functioning and lower disability. The presence of 20+ teeth resulted significantly protective (reference group: 0 teeth) versus mobility-related disability (OR = 0.67), disability (OR = 0.54) and inability to perform heavy duties (OR = 0.62), at follow up 1 and low physical performance score (OR = 0.59) at follow up 2. Conversely, the detrimental effect of edentulism, explored in subjects with or without dentures, was present but not as straightforward. Conclusion. The assessment of a geriatric patient should include an oral evaluation as a good dental status is a crucial component of successful aging. Consequently, they proposed a multidimensional approach of the nonpathological elder that included physical and cognitive functions evaluation thus allowing a more appropriate distinction of aging in “usual”, i.e. non pathologic but high risk, and” successful”, i.e. low risk and high function . The con. On the , but lonThe Pro.V.A. Study is an observational cohort study of an Italian population aged ≥65 living in Northeastern Italy, designed to focus on the effects of cardiovascular and osteoarticular disease on disability. The design and the sampling frame of the study have been previously described in detail elsewhere . BrieflyOf the 3099 older adults initially enrolled in the study, 3083 had data concerning their oral, comorbidity and disability status, and leisure time activities. Complete baseline physical performance information was available for 2083 participants. The subjects lost to FU1 included 739 people who died, 312 who missed one or more physical functioning data, and 148 dropouts. The latter were comparable with the subjects who remained in the study, while the other participants lost to FU1 had lower number of teeth, worse physical performance, and a higher prevalence of disability, comorbidities and sedentarism. The proportion of women was highest in the group with missing FU measures (72.8%) and the lowest among the deceased (48.9%). Attrition data between FU2 and FU1 overlapped with those between baseline and FU1. Specifically, 708 had died and there were 301 between the dropouts and the subjects without complete information: all were older, had fewer teeth and more disabilities. Women were more frequent among the participants with missing data.During the physical work-up at the Study centers, trained clinicians State-board qualified to practice dentistry performed an oral examination to assess each patient’s general oral status and number of teeth. All teeth regardless of their condition  were counted when the total number of teeth was being calculated. The presence of an upper and/or lower removable prosthesis was also recorded. Information on self-reported difficulty in chewing and in swallowing was obtained during the home interview by means of two specific questions. The subjects were divided into one of 4 classes depending on their dentition at baseline: edentulous, 1–7 teeth, 8–19 teeth, and 20+ teeth .Information on the subject’s history of falls, difficulty in activities of daily living (ADL), and physical activity habits was collected during an in-person or proxy interview. Physical performance measures were carried out during the home interview, muscle strength tests were carried out at the Study centers. Disability in ADL was defined as the need for help or the inability to perform one or more of the following activities: walking across a room (ADL1), bathing (ADL2), dressing (ADL3), eating (ADL4), transferring from bed to chair (ADL5) or using the toilet (ADL6).rd quartile of the studied population at all time points of the study.The subjects’ physical activity level was figured on the basis of their response to three questions regarding frequency of walking 500 m, riding a bike > 1 km, and gardening. Those who reported never doing these three activities were classified as “sedentary”, those who reported engaging in at least two of these activities every day or more than once a day as “active”, and those with an activity level somewhere in between as “intermediate” . Lower eOverall physical performance was classified in accordance with Guralnik’s model ,17 usingSummarizing, the physical and disability outcome variables at baseline, FU1 and FU2 were dichotomized as follows: i) limited lower extremity function, assessed by mean of the short physical performance battery (SPPB): score ≥9; ii) mobility-related disability: three categories at baseline  was dichotomized at FUs as no subjects were in category 0; iii) physical activity level (sedentarism): none vs moderate/intense; iv) disability in activities of daily living (ADL): 0–1 vs >1; v) (in)ability to perform heavy duties only assessed at baseline FU1.Body mass index (BMI), a general nutrition index, and serum albumin, a biomarker specific for protein energy malnutrition, were used to describe nutritional status. The former is a widely applied index in geriatric clinical practice, mainly used to identify subjects at risk for under-nutrition. The latter is considered an index of long-term malnutrition as its half-life is the longest among all circulating proteins . Serum aDepression was evaluated using the 30-item depression geriatric scale (GDS) ; a scoreThe information regarding socio-economic status (SES) and lifestyle factors, which was self-reported, was gathered during the baseline interview. The following surrogate variables were used for the subject’s socio-economic condition: monthly income , living alone (yes/no), widowhood (yes/no), educational level , number of rooms in the house (dichotomized at 5). The final SES variable was dichotomized, assigning 0 for 0–1 adverse conditions. Smoking status was assessed during the home interview using seven specific questions concerning current or past smoking patterns, type of smoking, the mean number of cigarettes or other per day, age of the participant at beginning, age at quitting (when appropriate). Smoking status was categorized here as dichotomous: yes (current smokers) or no (either never or former smokers). Alcohol consumption was defined as one bottle/can of beer, one glass of wine, one cocktail, one shot of liquor. Drinking was considered a dichotomous variable and a non-drinker someone who did not consume alcohol over the last 30 days. Information on SES and lifestyle factors was obtained from 99% of the participants.t test was used to compare mean values among groups for normally distributed variables and non parametric Mann-Whitney test for non normal variables. The Chi square test was used to compare categorical distributions.The normality of the continuous variables was verified using the Shapiro-Walk test. Quantitative variables were summarized as mean ± standard deviation or median with minimum and maximum; qualitative ones as frequency distributions. Analysis of variance or p level lower than 0.05 was considered significant. All statistical analyses were performed using the R Statistical Software [At FU1 and FU2, mortality was computed according to teeth class. Separate logistic regression models were performed to estimate the independent contribution (adjusted ORs and the respective 95% CI) of the baseline dental status to the different outcome  progressively adjusting (from Model 1 to model 7) for conditions at baseline. In the models, dental status was entered as categorized in four classes , reference group was 0 teeth. All the other variables were entered as dichotomous, except for age that was categorical  and BMI that was continuous. In the progressively adjusted models, besides the baseline tooth class, the following covariates were entered: Model 1: sex, age, and BMI; Model 2: Model 1 + comorbidity  + osteoarthritis, osteoporosis, femoral fracture, history of falling, visual impairment, hearing impairment; Model 3: Model 2 + cognitive impairment, depression, smoking status, alcohol intake, and social variables; Model 4: Model 3 + serum albumin level, serum vitamin D level, neurological impairment (including Parkinson disease), hand strength, leg strength; Model 5: Model 4 + basal physical activity; Model 6: Model 5 + difficulty at chewing and at swallowing; Model 7: Model 6 + value of the model outcome at baseline (for FU1) or at FU1 (for FU2). For the study of the impact of edentulism without dentures, the variable was dichotomized . Degree of collinearity among covariates was estimated using the variance inflation factor . Only the data on subjects with complete dentition records were included in our analyses. A Software .Data about oral conditions were obtained from 3083 subjects  at baseline, from 2196 survivors  at the first FU examination, and from 1640  at the second one.The main features of the study population at the three time points of the study, according to tooth classes at baseline, are shown in Tooth retention, use of removable prosthesis, and the prevalence of self-reported difficulty at chewing or swallowing in the two genders at baseline and FUs is outlined in detail in In the present study we explored the association of dental status with physical performance in an elderly population evaluated at baseline and two FUs. Our analyses showed that subjects retaining 20 or more teeth were significantly protected against poor physical performance even after controlling for a number of confounders, including chronic diseases, muscle strength, smoking status, alcohol habits, socioeconomic status, leisure time activity, and difficulty at chewing and at swallowing. These findings are consistent with and support the results of other studies demonstrating an increased risk of disability, institutionalization, and mortality in subjects with a poor dental status –25. WhilIn the early nineties, the 8020 campaign was promoted in Japan to encourage individuals to strive to retain at least 20 natural teeth by the time they reached 80 yrs of age so they could continue to enjoy eating and socializing ,33. The To our knowledge, this is the first study in which a battery of validated tests was employed to investigate the association between dental status and physical activity in a large population of community-dwelling white elderly of both sexes also characterized for a great number of clinical, laboratory, instrumental, and lifestyle parameters that allow for a wide-ranging adjustment of the relationships. Moreover, the longitudinal design provides insights concerning the persistence of the associations and the predictive role of dental status.The present work has, however, some limitations. The Pro.V.A. Study’s primary endpoint was the prevalence of osteoarticular and cardiovascular disease in the elderly; dentition and in particular periodontitis were not specifically considered. The study nevertheless engaged clinicians State-board qualified to practice dentistry to collect reliable health-related data of a geriatric population including dental health measures such as the number of remaining teeth and the use of dentures. Interestingly, Desvarieux et al  demonstrAmong the mechanisms linking tooth loss to disability, nutrition has been demonstrated to play a crucial role, for its influence on muscle strength and central nervous system and -more in general- to health and susceptibility to diseases. The aim of the present work was not to contribute to this important field. However, we addressed the possible role of nutrition introducing in the regression models both nutritional indexes  and the difficulty at chewing and at swallowing. Nutrition is central in the decline of physical functioning, yet we demonstrated that dentition has an independent role in this transition.Oral status could be surely considered a marker of fragility as well as fitness in the elderly. Checking dentition during a regular geriatric assessment is not a timeconsuming endeavor and provides extremely useful information about the patient’s general health. It can be considered a cost effective measure given the socioeconomical burden of a rapidly increasing, potentially frail old population worldwide and the importance of health-related preventative care . SimilarLast but not least, we should consider that the aesthetic perfection of the body is widely and energetically pursued in our age and time. Attractive, good-looking teeth are part of a wider search for physical beauty and harmony that can improve not only an individual’s quality of life but also his/her self-esteem . Beyond