Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD.n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways.Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, β-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls.Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD. Major depressive disorder (MDD) and bipolar disorder (BD) are two different psychiatric disorders with commonly overlapping symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), MDD is characterized by the presence of major depressive episodes, whereas patients with BD have depressive episodes preceding or following a mild manic or manic episode [American Psychiatric Association ]. TypicaDelayed diagnosis and misdiagnosis of bipolar disorder may result in the use of antidepressant monotherapy, creating an increased risk of patients moving to a hypomanic or manic episode , 6. ApprMetabolomics is a new addition to the field of histology, focusing on measuring the downstream effects of environmental, genomic, and proteomic variation in individuals by identifying and quantifying small molecules called metabolites . By asseUsing an NMR metabolomics approach, our group has conducted several studies on the search for BD biomarkers in the early stages –17. ThesTherefore, in the present study, we used an NMR metabolomics approach to analyze serum metabolic phenotypes in BD, MDD, and healthy controls to initially explore biomarkers that may help differentiate BD and MDD and to further understand the pathophysiology of both diseases.Ethics approval for this study is held by the medical ethics committee of Shanxi Bethune Hospital . All subjects enrolled in the study gave their written informed consent. A pair of licensed, experienced psychiatrists were in charge of the recruiting procedure.The current study was conducted at the Department of Psychiatry in Shanxi Bethune Hospital from July 2019 to February 2021. Fifty-nine patients with BD who fulfilled the bipolar depression criteria of the DSM-5  were recruited. MDD subjects were recruited from the same site and during the same time period. Fourteen candidates of MDD, who were diagnosed with MDD  using the Structured Clinical Interview, were recruited. Patients with any physical or other mental disorders were excluded, as were patients who had substance abuse issues. To reduce the risk of misdiagnosed BD subjects among the MDD subjects included in this study, a licensed psychiatrist in our department who has specialized in the diagnosis and treatment of BD and MDD for several years systematically applied the validated structured interviews to diagnose each patient.During the same time period, healthy controls (HC) were recruited from the Medical Examination Center in the same hospital. The candidates, who had no history of neurological, systemic medical illness, or DSM-IV Axis I/II illness, were recruited. Finally, 10 HC subjects were included. The demographic and clinical characteristics of the included subjects are shown in The blood samples of all subjects were collected by medical professionals at the Shanxi Bethune Hospital in the morning after a 12-h fast. The blood was mixed inverted after clotting and stored for 30 min at room temperature (about 20°C) before centrifugation at 3,000 rpm for 15 min. Then, the serum was collected and stored in a −80°C refrigerator for future use.The serum samples were thawed in ice water, and 450 μL supernatant was removed and placed into an EP tube, 350 μL D2O was added, and the mixture was centrifuged at 4°C for 20 min (13000 r/min). Then, 600 μL supernatant was transferred to a 5 mm NMR tube and stored at 4°C until the NMR test. NMR was performed using a Bruker 600 MHz AVANCE III NMR spectrometer, with Carr-Purcell Meiboom-Gill pulse sequence, and the following parameter settings: free induction attenuation (64K data points), self-axonal relaxation delay (320 ms), 64 scans.1H NMR spectra were manually phased, and the baseline was set using MestReNova software . All the serum 1H NMR profiles were Fourier transformed and phase baseline adjusted. Chemical shift correction was performed on the profiles based on creatinine . The region of δ 4.70–5.20 ppm was excluded due to residual water. The data were then normalized to the total sum of the spectra.All the acquired 1 to perform pathway analysis using the human pathway library. Pathways were screened according to the p-values of pathway enrichment and impact values of pathway topology analysis.Partial least square discriminant (PLS-DA) analysis was performed, followed by orthogonal partial least square discriminant (OPLS-DA) analysis using SIMCA-P 14.1. To determine the pathways involved in differentially occurring metabolites, they were further introduced to MetaboAnalyst 5.0t-test was used to detect and identify differences in markers between BD and MDD. All clinical scale data were expressed as the mean ± SD. Continuous variables were analyzed using a one-way analysis of variance, while categorical variables were analyzed using the Chi-square test. All statistical analyses were performed using SPSS 20.0 . A p-value of ≤0.05 was considered statistically significant for demographic analysis.The There were no significant differences in age, education, or sex ratio  among the BD, MDD, and HC. There were also no significant differences between the BD and MDD groups concerning the age at onset, duration of illness, and HAMD scores. 2 the chemical shift, peak shape, and coupling constant of each metabolite were confirmed, and the 1H-NMR metabolite maps of the blank, BD, and MDD groups were obtained (According to previous literature and the NMR data website (HMDB),obtained , from whobtained .1H NMR metabolic profiling using supervised PLS-DA, and the results were shown in All serum samples were analyzed by t-test was performed to screen out the metabolites with significant differences .p < 0.05).Similarly, the group of MDD was significantly separated from HC group in the PCA  and PLS-p < 0.05, nine metabolites differentially expressed in the BD group were identified. 3-hydroxybutyric acid, N-acetyl glycoproteins, β-glucose, pantothenate, mannose, glycerol, and lipids levels were significantly higher in the BD group , while lactate and acetoacetate levels were significantly lower . The relative concentrations of the nine identified metabolites are shown in p-values from enrichment analysis and greater impact from pathway topology analysis, respectively. This model is mainly related to: (1) glycolysis/gluconeogenesis; (2) glycerolipid metabolism; (3) synthesis and degradation of ketone bodies; (4) butanoate metabolism; (5) pantothenate and COA; (6) pyruvate metabolism; and (7) galactose metabolism.p < 0.05, eight metabolites differentially expressed in the MDD group were identified. 3-Hydroxybutyric acid, N-acetyl glycoproteins, pyruvate, choline, acetoacetate, and lipids levels were significantly higher in the MDD group , while acetic acid and glyceryl level were significantly lower . The relative concentrations of the eight identified metabolites are shown in In clinical practice, BD cases are often misdiagnosed as MDD , so findThese differential metabolites above may provide initial insights into the metabolic differences between BD and MDD. Despite the differences in metabolites between MDD and BD, the results of the pathway analysis suggest that most of the most important pathways are shared in these diseases, which is consistent with the findings of previous studies. Notably, most of the key metabolites and their associated pathways appear to focus on three common themes, namely (1) mitochondrial/energy metabolism, (2) neuronal integrity, and (3) signaling/neurotransmission, as described below.Our study found that lactate and acetoacetate were significantly lower in the BD group. Imbalance in energy homeostasis in BD has been previously reported , 25. PreIn addition, the present study found that β-glucose and mannose were significantly elevated in the BD group and that glycolysis/gluconeogenesis was a common metabolic pathway in BD and MDD. Previous studies have shown that there was glucose impairment during some severe psychiatric episodes, even before the start of treatment , 28. RecOur study also found that pyruvate and choline were significantly elevated and acetic acid was significantly decreased in the MDD group, while these metabolites were not significantly altered in the BD group. Alterations in choline metabolism are associated with disruptions in intraneural signaling , 34, andIn the present study, 3-hydroxybutyric acid was the metabolite that jointly distinguishes BD and MDD from HC. In a previous study , this biWhat’s more, we found elevated pantothenic acid levels in the BD group compared to the MDD group, which is consistent with the findings of a previous study that found significantly lower vitamin B12 levels in patients with BD, which may lead to elevated pantothenic acid levels. Pantothenic acid itself is a component of coenzyme a and a precursor of NAA, which is abundant in neurons and is considered an indicator of mitochondrial dysfunction and a marker of neuronal integrity and viability , 44. IntMays et al.  found siThis is only a preliminary study of the differential diagnosis of BD and MDD based on metabolomics biomarkers and serum metabolic pathways, and the results suggest that it is feasible to find biomarkers in the field of metabolomics to differentiate BD and MDD, and also that these differential metabolites may be used as future biomarkers for the diagnosis of BD and MDD in clinical practice. However, the study also has some limitations. First, this study used a small sample size study with a small sample size, which may affect the stability and reliability of the results. Second, other factors, such as diet, body weight, and medication, may also affect the metabolic phenotype of BD and MDD, and the effects of these factors need to be further explored in future studies. Third, it is important to note that the metabolomics platform used in this study may have limitations, as different metabolomics platforms have different sensitivity and accuracy for the detection of different metabolites. Therefore, future studies will need to be validated using multiple metabolomics platforms to further determine the specificity and accuracy of these differential metabolites. Another potential limitation is that our study was a cross-sectional study and could not determine the relationship between metabolite levels and disease progression.Overall, the present study provides useful clues for finding biomarkers to differentiate BD from MDD and highlights the importance of metabolomics in this field, but more studies are needed to further confirm the reliability of these findings and the potential for clinical application. In addition, a deeper understanding of the pathophysiological mechanisms of BD and MDD is also needed to help us better understand the differences in metabolic phenotypes and thus better identify and treat both diseases.In summary, this study used an NMR metabolomics platform to explore the metabolic phenotypic differences between BD and MDD, and found that the metabolic phenotypes of BD and MDD were significantly different from those of healthy controls. Glycerolipid metabolism was significantly involved in BD and MDD. Pyruvate metabolism was significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD. The clinical significance of this study is the discovery of different metabolic phenotypes between BD and MDD, as well as of potential biomarkers for distinguishing BD from MDD. Our findings contribute to the future development of an objective laboratory-based diagnostic test to distinguish between BD and MDD patients, which is very meaningful for the precise diagnosis and treatment of clinical psychiatric disorders. Future studies require more rigorous experimental designs, larger sample sizes, and longitudinal studies to validate our results and conclusions.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.The studies involving humans were approved by the Medical Ethics Committee of Shanxi Bethune Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.X-LS, L-NM, and YR contributed to the manuscript preparation. X-LS, L-NM, and Z-ZC performed the data analysis and statistics. JJ and Y-BX oversaw the data/demographic data collection. YW and YR were in charge of design and implementation of the study and contributed to the data interpretation. All authors contributed to the article and approved the submitted version.


Limited research has focused on the clinical features of sudden sensorineural hearing loss (SSNHL) in pediatric patients. This study is aimed to investigate the relationship between clinical features and the baseline hearing severity and outcomes of SSNHL in the pediatric population.We conducted a bi-center retrospective observational study in 145 SSNHL patients aged no more than 18 years who were recruited between November 2013 and October 2022. Data extracted from medical records, audiograms, complete blood count (CBC) and coagulation tests have been assessed for the relationship with the severity  and outcomes .P = 0.004) and a higher platelet-to-lymphocyte ratio (PLR) (P = 0.041) were found in the patient group with profound initial hearing than in the less severe group. Vertigo  and lymphocyte count  showed significant associations with the threshold of the initial hearing. In the multivariate logistic model, the probability of recovery was higher for patients with ascending and flat audiograms compared to those with descending audiograms . Patients with tinnitus had a 3.2-fold increase in the probability of recovery , while the baseline hearing threshold  and duration to the onset of therapy  were negatively associated with the odds of recovery.A lower lymphocyte count (The present study showed that accompanying tinnitus, the severity of initial hearing loss, the time elapse and the audiogram configuration might be related to the prognosis of pediatric SSNHL. Meanwhile, the presence of vertigo, lower lymphocytes and higher PLR were associated with worse severity. Sudden sensorineural hearing loss (SSNHL) is an urgent otologic condition that should be managed promptly. The frequency of SSNHL in adults is expected to range from 5 to 27 cases per 100,000 per year . NeverthTo date, there have been a limited number of studies focusing on pediatric patients with SSNHL. It is probably due to the low prevalence. It is common knowledge that children are not “small” adults. Thus, accurately describing the symptoms and relevant medical history is not easy for them. Hearing loss, especially unilateral hearing loss, is sometimes a less perceptible symptom. Thus, it can be difficult to clarify whether a child's hearing loss occurs “suddenly” or in the long run. Another unanswered question is whether SSNHL in children is the same as that observed in adults. Previous study found differences with respect to the recovery rate and audiogram configuration between adult and pediatric patients with SSNHL , 7. HoweAmong the existing studies on pediatric SSNHL, there were some inadequacies. First, the small sample size reduced the power of the statistical analysis. Second, most of the previous studies were conducted in a single center, which made them more susceptible to bias; and third, the statistical methods used were commonly limited to univariate analysis, which was not able to exclude confounding factors to identify adequately independent correlations.In the present study, we analyzed the clinical parameters associated with the severity and prognosis of SSNHL in children and developed interpretable prognostic prediction models to improve counseling.We conducted a retrospective analysis of pediatric patients with SSNHL aged ≤ 18 years who consecutively visited two Chinese tertiary centers  between November 2013 and October 2022. All the patients underwent a comprehensive clinical assessment, including a neurotological physical examination, audiometry, and imaging. The follow-up visit was conducted in person at the hospital, and 145 patients  were included in the study . We utilThe participants enrolled were assessed using pure-tone audiometry. Pure-tone air and bone conduction thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz were examined based on the standard audiometric methodology. The average baseline hearing threshold was calculated at the affected frequencies of air conduction (frequencies with hearing loss >20 dB HL). The severity of initial hearing loss was classified as follows: mild hearing loss: 20–40 dB HL; moderate hearing loss: 41–60 dB HL; severe hearing loss: 61–80 dB HL; and profound hearing loss: >80 dB HL. We categorized the configurations of the audiogram into four types as described in our earlier study : ascendiU-test, Fischer's exact test, and the Student's t-test, between the two subgroups. The Kruskal–Wallis test was applied to the ordinal variables for the group comparison. In addition, post-hoc pair-wise comparisons were used where there were more than two subgroups. The “glm” package was used to fit multivariate models to explore the factors that affected either the initial hearing or the hearing outcomes. The multivariate linear regression included the baseline hearing threshold as the response variable. Based on the variables having significance in the comparison between groups, the presence of vertigo, the lymphocyte count, and the monocyte count should be incorporated into the model. However, the analysis (Pearson correlation coefficient) revealed a significant linear correlation between the lymphocyte count, the monocyte count, and PLR. Furthermore, when these variables were included in the model, high variance inflation factor (VIF) values were observed. Therefore, we only chose the lymphocyte count to avoid potential collinearity. To analyze factors affecting hearing outcomes, a binomial categorical variable (recovery vs. non-recovery) and a continuous variable  were utilized as dependent variables. Significant variables from the univariate analysis for hearing recovery were included in the multivariate linear and logistic regression models, adjusted for age, sex, and time to the onset of therapy. To include nominal variables in the linear regression, a dummy variable was developed with a value of 1 if the case matched the description and 0 otherwise. Regression coefficients, standard regression coefficients, 95% confidence intervals, and odds ratios were calculated using regression models. All analyses were conducted using RStudio  and R (http://www.R-project.org). A two-sided p-value of < 0.05 was deemed statistically significant.We analyzed the initial severity of hearing loss and hearing outcomes based on Siegel's criterion. The patients with an average baseline hearing threshold graded as profound (>80 dB HL) were allocated to the profound group, whereas those with less severe baseline hearing were assigned to the not profound group. According to Siegel's criterion, patients whose hearing outcomes were classified as CR or PR were allocated to the recovery group, and the remaining patients were assigned to the non-recovery group. The Shapiro–Wilk test was used to determine if a continuous variable was normally distributed. Continuous data with a normal distribution were given as the mean and standard deviation, whereas non-normal data were presented as the median and interquartile range. The frequency and proportion were used to characterize nominal variables. Subgrouping comparisons were performed using appropriate statistical tests, such as the Mann–Whitney ‘P = 0.021). Regarding the configurations of the initial audiogram, the flat configuration was the most common , and a significant difference in the initial hearing was detected among groups (P = 0.001). Eighty-one patients had complete blood count (CBC) test results, and 83 patients had coagulation factor test findings. The study found that patients with profound initial hearing loss had a significantly lower absolute lymphocyte count compared to those without . The patients in the profound group had a higher level of PLR and a lower level of monocytes than their counterparts with less severe hearing loss.P = 0.044) . The configurations of the audiograms were significantly different across the groups (P = < 0.001). Patients with cophosis figures had significantly different recovery than those with descending (P = 0.020), ascending (P < 0.001), and flat figures (P < 0.001). Patients with descending figures had significantly different recovery than those with ascending (P = 0.011) and flat figures (P = 0.038) after post-hoc comparison. The thresholds for the initial and final hearing comparison, sorted by the initial configuration, are shown in P = < 0.001; descending: P = < 0.001; flat: P = < 0.001). A worse final hearing was found in patients with descending figures than with ascending (P = < 0.001) and flat (P = 0.016) figures, respectively. The threshold for a final hearing with ascending figures was similarly lower than for that with the flat figure (P = 0.019). No statistical difference was found in complete blood cell and coagulation test biomarkers across the recovery group and the non-recovery group.= 0.044) . There wP = 0.007), lymphocyte count  (P = 0.001), baseline hearing , and configurations . The odds of recovery were 3.2 times higher for patients with tinnitus than for those without tinnitus . The threshold for baseline hearing  and the onset of therapy  were negatively associated with the odds of recovery. To predict the hearing outcomes of pediatric patients with SSNHL, a nomogram was established by incorporating the following parameters: tinnitus, the onset of therapy, baseline hearing, and configuration  , and indurations . In the urations , the patguration .The present bi-center study found some predictive factors of hearing outcomes in pediatric patients with SSNHL, including tinnitus, the time elapsed from the onset of the symptoms to the commencement of the treatment, initial audiogram configuration, and hearing levels. We observed a higher proportion of accompanying vertigo, a greater degree of inflammatory biomarkers (lower the concentration of lymphocytes. and a higher level of PLR), and worse hearing outcomes  in patients with more severe initial hearing loss. Meanwhile, according to the multivariate linear regression model, we developed a nomograph as a simple predictive tool for the final hearing threshold.The coexisting symptoms of vertigo 29–56%) and tinnitus (41–90%) were frequently observed in adult patients with SSNHL , 20. The% and tinIn terms of audiograms, we observed that patients with ascending and flat configurations had lower thresholds for the final hearing and greater recovery odds than patients with descending figures; these findings were consistent with the conclusions drawn by Qian et al.  and ChenThis study's results found that the lymphocyte count correlated with the initial hearing thresholds, with a marginally higher value in patients who recovered. Although a low lymphocyte count was identified as a risk factor and a poor prognostic factor in adults , 14, recIn the current study, we observed that among the ears studied, 36.7% had profound initial hearing, and among these ears, 45.3% showed no improvement. The findings were similar to the conclusion drawn by a recent meta-analysis , with 36To the best of our knowledge, our study on SSNHL in children is one of the largest of its kind, with a sample size of 145 patients. Furthermore, we conducted a bi-center investigation, which increases the representativeness of the target population and reduces individual bias compared to single-center studies. Nonetheless, there are several drawbacks. First, because of the respective research design, it was impossible to confirm causal relationships between the investigated factors and the severity or outcomes. Second, the investigation was exploratory without a scientistic hypothesis or pivot statistical estimate—no sample size calculation to ensure a significant statistical power. Meanwhile, due to the low prevalence of SSNHL in children, only a portion of the patients had complete blood counts and coagulation tests available. Third, only the total lymphocyte count was determined; no subtype analysis was performed. Therefore, further research is warranted to focus on the potential biomarkers in children to demonstrate whether these biomarkers differ from those in adults.In conclusion, it was an exploratory study on pediatric patients with SSNHL. Some factors, including accompanying tinnitus, the severity of the initial hearing loss, the onset of therapy, and the configuration of audiograms, might be related to the prognosis of pediatric patients with SSNHL. Meanwhile, the incidence of vertigo, lower lymphocytes, and higher PLR were associated with poor hearing severity. Further research is needed to establish a more accurate understanding of the relationship between pediatric SSNHL and its underlying mechanisms, given the diversity of clinical trials involving adults and children.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China and Ethics Committee, The First People's Hospital of Foshan, Foshan, PR China. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.DB contributed to the study design, data analysis, and manuscript writing. YL and XZ contributed to the study design, data collection and analysis, and manuscript writing. ZD and DD contributed to the data analysis, collection, and holding. All authors contributed to the article and approved the submitted version.


In all, 51 dogs  were seropositive to at least 1 pathogen, i.e., 4 in Italy  and 47 in Greece . Dirofilaria immitis antigens were found in 39 dogs , while antibodies against Ehrlichia, Anaplasma and Leishmania were detected in 25 , 8  and 5  dogs, respectively. None of the dogs tested seropositive for B. burgdorferi s.l. Statistical analyses were performed to evaluate associations between exposure to CVBDs and possible risk factors. The present results indicate that dogs living in enzootic areas may be seropositive for one or more CVBDs in absence of clinical signs. Rapid kits are among first line tools for the detection of CVBDs in clinical settings, as they are cost-effective, straightforward and quick to use. Also, in-clinic tests used herein allowed detection of co-exposure to CVBDs investigated.Canine Vector-Borne Diseases (CVBDs) are widespread in Europe and enzootic in many other countries. Though severe illnesses may occur, dogs living in enzootic areas often show vague or no clinical signs of CVBDs. Undiagnosed infections/co-infections in subclinically infected animals favor the spread of CVBDs and increase the risk of transmission to other animals and, in some cases, humans. This study has evaluated the exposure of dogs living in key enzootic countries, i.e., Italy and Greece, to major CVBDs via the use of in-clinic diagnostic kits. Overall, 300 privately owned dogs without/with single mild clinical signs living in different regions of Italy (n. 150) and Greece (n. 150) were included in the study. As part of a clinical examination, a blood sample was collected from each dog and subjected to two serological rapid tests, i.e., the SNAP Ehrlichia canis, Anaplasma platys, Anaplasma phagocytophilum, Borrelia spp. and Rickettsia spp., the nematode Dirofilaria immitis and the protozoans Leishmania infantum and Babesia spp., transmitted by mosquitoes, sandflies and ticks, respectively [In enzootic areas, dogs are exposed to the bite of arthropods able to transmit several pathogens, representing a primary threat to animal and human health ,3,4,5,6.ectively ,11,12,13ectively ,19,20,21Infected dogs may display signs of varying severity, from none or mild to severe and life-threatening clinical manifestations and abnormalities ,11,12. HVarious diagnostic techniques are used to assess the serological status of canine populations living in regions enzootic for CVBDs. While assays that quantitatively evaluate the seropositivity and the antibody titers in exposed/infected animals  are typically applied on large-scale surveys, individual diagnosis in the clinic often requires the use of rapid, cost-effective and straightforward qualitative or semi-quantitative tests. Also, some specific-peptides-based rapid kits allow the detection of co-exposure to different pathogens, compared to other serological methods that in many cases are based on the use of whole cells. In addition to the usefulness for preliminary screening and the aid in diagnosis for individual animals, the same rapid tests may be used also in epizootiological studies.In this survey, two in-clinic rapid kits were used to evaluate apparently healthy dogs living in enzootic regions of major CVBDs, to provide further surveillance on the exposure to CVBDs in key enzootic countries and data for continued refinement of control programs, aiming to protect animal and human health.A total of 300 privately owned dogs living in different regions of Italy and Greece were included in the study. In Italy, 50 dogs were selected in Northern (Site A), Central (Site B) and Southern regions (Sites C and D) each. In Northeastern Greece, 25 dogs from each of the six selected sites (Sites E–J) were included in the study . The samThe survey was conducted in the framework of routine medical checks coordinated by local veterinarians and dogs were selected based on the following criteria: (i) willingness of the owners to monitor the health status of their dogs; (ii) dogs living in areas enzootic for CVBDs; (iii) dog age that permitted at least one vector season experienced; (iv) absence of clinical diseases compatible with any of the major CVBDs under study.Prior to enrollment, each dog was subjected to a physical examination to evaluate the presence of clinical signs possibly related to CVBDs. For every single clinical sign, a score ranging from 0 to 3 was assigned, as follows: 0 , 1 (mild), 2 (moderate) and 3 (severe). A clinical score was calculated for each dog based on the sum of the scores of each clinical sign and each dog was categorized as follows: clinically healthy dog (score 0–5), mild disease (score 5–30), moderate disease (score 31–55), severe disease (score 55–75). Only clinically healthy dogs were included in the study.Signalment and anamnesis, including data on age, sex and breed, were recorded for each dog. A consent form was signed by the owner before blood collection, which was performed via venipuncture of jugular, cephalic or saphenous veins. The blood was transferred into a tube without anticoagulant and centrifuged after clot formation to separate serum and then tested immediately.Overall, 124 (41.3%) dogs included were male and 176 (58.7%) were female. A total of 36 dogs (24%) enrolled in Italy were ≤2 years old and 114 (76%) were >2 years old. In Greece, 42 (28%) and 108 (72%) were ≤2 years old and > 2 years old, respectively. Among the enrolled dogs, 174 (58%) were crossbred and 126 (42%) were purebred dogs.-® 4Dx® Plus Test  for the detection of Dirofilaria immitis circulating antigen  and of antibodies against specific peptides of Anaplasma phagocytophilum , Anaplasma platys , Ehrlichia canis , Ehrlichia ewingii  and the C6-peptide of Borrelia burgdorferi s.l.  [SNAPy 98.8%) ;-® Leishmania Test   for the detection of antibodies against L. infantum [SNAPinfantum .Each serum sample was subjected to two different serological examinations performed by the veterinarians according to the manufacturer’s instructions:p < 0.05) between possible risk factors and exposure to CVBDs. Possible risk factors  were evaluated with a binomial logistic regression with a strength measured using the Odds Ratio (OR) and a 95% Confidence Interval.The GraphPad Prism 9 Software was used for the statistical analysis, based on Fisher’s exact test to evaluate the presence of significant associations  dogs included in the study were seropositive to at least one CVBD pathogen .L. infantum. Also, one dog sampled in Southern Italy in TF2 was seropositive for the D. immitis antigen , followed by Ehrlichia spp. . Accordingly, D. immitis and Ehrlichia spp. were the most-recorded pathogens in dogs with a single seropositive result .Three dogs  sampled in Italy—one and two from central and Southern Italy (Sites B and D), respectively—in TF2 were seropositive for  antigen . Overall antigen . Of thesEhrlichia spp. + D. immitis  and Ehrlichia spp. + A. platys/phagocytophilum + D. immitis   .Among the dogs included in the study, 45  displayed at least one clinical sign  and 5  of them were seropositive for at least one CVBD.p = 0.0062; OR = 0.3265), crossbred dogs  and sampling during timeframe 2 . Being a crossbred dog was a risk factor for seropositivity to CVBDs from the results of the binomial logistic regression . No other statistically significant associations were detected.The Fisher’s exact test revealed three statistically significant factors associated with the seropositivity to at least one CVBD pathogen: age more than 2 years  [Ehrlichia spp. herein detected represented exposure to E. canis, as this is the only species occurring in dogs in Europe, and due to the vast distribution of its main vector, Rhipicephalus sanguineus. Northern Greece historically displays the highest seroprevalence of D. immitis compared to the rest of the country [ellents) ,41. With country . Despite country , a combi country ,44.Such a marked difference in the seropositivity rate of CVBD pathogens in dogs from Italy and Greece was not detected in recent studies; by contrast, a similar occurrence of CVBDs was reported ,30. The L. infantum, E. canis) and/or that were repeatedly exposed to one or more CVBDs may be clinically healthy for a certain period of time and then develop overt disease, e.g., kidney disease, only in a later stage of the infection [L. infantum within canine and human populations, as they are more rarely examined and screened compared to dogs displaying clinical signs compatible with leishmaniosis [L. infantum among vectors and animal hosts.It should be kept in mind that dogs that tested seropositive for vector-borne pathogens  in sites of Greece, especially during TF2.D. immitis infection (in combination with appropriate microfilariae-based test), for starting an in-depth diagnostic approach in the case of L. infantum infection or for steering the diagnosis towards tick-borne diseases in presence of compatible clinical signs. Testing for CVBDs should become routine in clinical settings, as this would allow the detection of subclinical infections that may subsequently exacerbate , and when dogs are adopted or do not receive regular veterinary preventive care. While rapid kits are useful and easy to use routinely in veterinary practices, other laboratory serological tests  are often necessary for the confirmation of infection and/or the quantitative assessment of seropositivity. It is important to avoid unnecessary treatments and to set up a proper diagnostic and therapeutic strategy after a careful clinical evaluation by the veterinarian and on a case-by-case basis. Although clinically healthy dogs generally do not need therapy , knowledge of their parasitological/serological status is necessary to set a proper follow-up and to apply prophylactic measures to limit the spread of the pathogen.In conclusion, rapid kits are among the first-line tools for the diagnosis of CVBDs in clinical settings, due to their limited cost and speed of execution and due to the high specificity ensured by the specific peptide targets for antibody detection. In-clinic kits are useful for the diagnosis of Rickettsia spp., Hepatozoon spp.) and the presence of the latter pathogens can be investigated only using laboratory serological tests  and/or molecular analyses (PCR). New rapid diagnostic tools would be highly appreciated by veterinarians in clinical settings, as a laboratory diagnosis using IFAT/ELISA or PCR is usually more expensive, possibly reducing the compliance of the owners to perform the investigation, and is more prone to cross-reactions in some cases [No rapid kit is currently available for the serodiagnosis of other important CVBDs (e.g., me cases . Therefome cases .


This study aims to evaluate the clinical efficacy and safety of rimegepant for the treatment of migraine in adult patients using a meta-analysis.The PubMed, EMBASE, and Cochrane Library were searched up to March 2022. Only randomized controlled trials (RCTs) that evaluated migraine and other comparator treatments in adult patients were included. The clinical response at the post-treatment evaluation, including acute pain free and relief effect, whereas the secondary outcomes were the risk of adverse events (AEs).P < 0.00001; relief at 2 h: OR = 1.80, 95% CI , P < 0.00001]. And there was no significant difference between the occurrence of adverse events in the experimental and control groups .A total of 4 RCTs involving 4,230 patients with episodic migraine were included. Outcome indicators for the number of pain free and relief patients at 2 h, 2–24 h, 2–48 h post-dose showed that rimegepant had better effects relative to the placebo [free at 2 h: OR = 1.84, 95% CI , Rimegepant has better therapeutic effects compared to placebo and no significant difference in adverse events. Migraine is one of the most common causes of severe headaches in the world . People There are several monoclonal migraine drugs targeting the CGRP receptor that have been marketed worldwide . In 2018Recently, the FDA expanded the indication for rimegepant to be used for the prophylactic treatment of migraine in adults and approved it as the first CGRP receptor antagonist to be approved as an efficacious orally disintegrating tablet for the acute treatment of migraine in adults with or without aura. The drug is currently the only migraine medication that both treats acute migraine attacks and helps prevent future attacks. But some scholars believe that rimegepant is the new garment of the emperor because of the lack of study patients .Thus, we will increase the number of studies based on the existing studies and conduct a meta-analysis of the efficacy of rimegepant to obtain a more realistic clinical efficacy of rimegepant, while meanwhile assessing the effect of the treatment dose on migraine control and adverse effects. Our study summarizes efficacy and safety studies from multiple randomized controlled trails, offsetting the lag caused by the number of patients included.in vitro studies; (b) pharmacokinetic-pharmacodynamic assessment; (c) review and abstract; and (d) phase I trials. Two reviewers (Qinghui Wang and Fei Lin) searched and examined publications independently to avoid bias. A third reviewer (Yi Zhu) resolved and decided on any disagreements. The following data were extracted from all the included studies: authorship, year of publication, study design, study duration, study site, study population, participants and comparators, clinical outcomes, and risk of adverse events (AEs). The modified intent-to-treat (MITT) population included all ITT patients with a confirmed diagnosis and conditions that met the study protocol criteria. The clinically evaluable (CE) population included patients from the MITT population who had a qualifying symptom as per the criteria for trial entry, received a trial drug, did not receive any medication not assigned within the trial that could confound interpretation of the results, and had an assessment of outcome during the protocol-defined window. Our institute did not require ethical approval for systematic reviews and meta-analyses.We followed the PRISMA guidelines throughout the formation process of our study. We searched PubMed, Embase, and the Cochrane Library. The following search terms were used: “Rimegepant” (Supplementary Concept) OR BMS-927711 Studies were included if they met the following criteria: (a) the RCT; (b) patients had a history of migraine for at least 1 year before the age of 50, 2–8 moderate or severe migraine attacks per month, and <15 days per month for the previous 3 months; (c) the intervention of rimegepant and comparison with other medications to treat migraines; and (d) the outcome of efficacy, including pain relief 2 h after administration and AEs. All languages of publication could be included. However, studies were excluded if they met the following criteria: (a) We observed several indicators of pain free and pain relief to better describe the efficacy. Including migraine pain free at 2 h, without the use of rescue medication; the second set of endpoints included migraine relief at 2 h without the use of rescue medication. Then we, respectively, assessed sustained pain free and relief at 2–24 h and sustained pain free and relief from the most bothersome symptom (MBS) at 2–48 h. We screened the articles and assessed the results as per the guidelines . TreatmeI2 measure. Heterogeneity was considered significant when P < 0.10 or I2 > 50%. The random-effect model was used when the data were significantly heterogeneous, and the fixed-effect model was used when the data were homogeneous. First, analyze the causes of heterogeneity. Subgroup analysis, sensitive analysis, Breslow-Day, and regression approximation can be used for factors that may produce clinical and statistical heterogeneity. If the heterogeneity cannot be eliminated after excluding interference factors, a random effect model (REM) can be selected for pooled data analysis. Combined odds ratios (OR) and 95% confidence intervals (CIs) were calculated for outcome analyses.The Review Manager 5.2 software was used to create the risk of bias plot in individual studies. And the Cochrane risk-of-bias tool was used to assess the quality of the included RCTs and their associated risk of bias. Statistical analyses were performed with the fixed-effects model. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for outcome analyses. The degree of heterogeneity was evaluated with the Chi-squared test. The proportion of statistical heterogeneity was assessed using the n = 3), single group study (n = 2), and inconsistent outcome measures (n = 2). Finally, four RCTs containing 4,230 patients were included in our meta-analysis. The specific process and included study characteristics are shown in A total of 688 research articles and abstracts from Pubmed, Embase, and the Cochrane Library were identified. One hundred and eight studies were removed due to duplicates. After removing duplicates and uncorrelated titles, eleven of these articles were directly related to the topic of interest. There are seven full-text articles excluded, with reasons as follows: same study  but no significant difference in dizziness or urinary tract infection. As side effects, reported adverse events include vomiting, diarrhea, paresthesia, dysgeusia, chest discomfort, myalgia, etc. ,  = 0.06] . Then weia, etc. .In this study, we included a total of 4 RCT studies, including 4,230 patients. In February 2020, rimegepant received its first global approval in the USA for the acute treatment of migraine (aura) in adults . So we aOur results indicate that in terms of efficacy, both for 2 h, 2–24 h, 2–48 h post-dose symptom-free and relief, the efficacy of the rimegepant is significantly different from that of the placebo. One study  has showIn terms of adverse reactions, the most common adverse effects of rimegepant were vomiting, dizziness, and urinary tract infections. We find no significant difference between the occurrence of adverse reactions in the rimegepant group and the control groups. For several adverse events commonly reported, nausea was significantly different from the control group; dizziness and urinary tract infection were not different compared with the control group, and previous research did not show any effect on liver function.Our advantage is that we simultaneously evaluated the efficacy of pain free and pain relief after rimegepant 2 h, 2–24 h, and 2–48 h post-dose, reducing the possible errors of assessing pain free after 2 h alone. Meanwhile, we evaluated the role of long-term time-based quantitative use for migraine prophylactics, and several studies showed that long-term timed use of rimegepant contributed to the number of fewer migraine attacks per month.Of course, there are also some limitations in this paper. Our study was not the first meta-analysis, and we didn't register, but the number of patients and studies has increased significantly in comparison to previous research. This study did not contain other anti-CGRP drugs or compare the efficacy of rimegepant with other drugs. Studies have shown that anti-CGRP monoclonal antibodies are also effective, safe, and well-tolerated drugs . When deMigraine is highly associated with disability . It is cIn summary, our study confirms that rimegepant has better therapeutic effects compared to placebo and no significant difference in adverse events.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.QW and FL conceived and designed the study. QW, SW, YZ, and FL analyzed the data and wrote the manuscript. All authors reviewed and approved the final version of the manuscript.


DiaryMood and utilized ecological momentary assessment (EMA), as it measured subjects’ mood, self-esteem and craving three times per day and the time spent using the dating apps per day during one week. A convenience sample of 22 online dating app users participated in the present study. Findings from a three-level multilevel analysis indicated that increased time spent on dating apps predicted craving among dating app users and that notifications led to an improved mood and higher self-esteem. The results are discussed in relation to previous online dating studies. In sum, the present study sets a precedent for the use of EMA within the scope of online dating research, which may promote further studies adopting this methodology.Smartphones are part of individuals’ daily lifestyles, as are smartphone applications such as dating apps. Previous evidence suggests that high engagement in dating applications can be detrimental to some users’ wellbeing. However, much of the published research has relied on cross-sectional studies and self-report measures. Therefore, the present study aims to overcome the limitations of subjective measures in cross-sectional designs by investigating for the first time the relationship between dating app users’ wellbeing  and objective measures of their use during a one-week period. To do this, the present study employed a newly developed application,  Approximately 84% of the world’s population  owns a smartphone . ConsequRelatedly, loneliness and/or relatedness needs have been raised in previous studies as predictors of higher dating app engagement and problematic use ,11. In a“pervasive apprehension that others might be having rewarding experiences from which one is absent” [Nevertheless, the number of notifications received can have an effect on users’ wellbeing, irrespective of the notification source , because high numbers of notifications can lead users to feel overloaded and experience decreased wellbeing , causing absent”   model  posits tMost of the past research examining online addictions, and more specifically, problematic use of online dating, has relied upon self-report methodologies. For instance, in a review of the published studies in social psychology in the year 2018, it was reported that 68% of the published studies relied exclusively on self-report measures . This coH1) and lower self-esteem (H2), as well as a higher craving to be on an online dating app (H3). It was also hypothesized that notifications would lead to higher cravings to be on an online dating app (H4), increased mood (H5), and increased self-esteem (H6). Finally, it was hypothesized that the number of launches  would lead to decreased mood (H7), decreased self-esteem (H8), and a higher craving to be on an online dating app (H9).Previous findings regarding media addictions and dating app research have highlighted relationships between the number of notifications and users’ wellbeing , frequent checking of smartphones with the development of habitual usage and increased feelings of craving, and high-frequency dating app use with lower mental health and general wellbeing. The present study investigated the relationship between wellbeing measures, including self-esteem, mood, and craving, and objective measures of dating app use . To do this, a newly developed smartphone application was employed to collect real-time data from participants . It was hypothesized that higher usage time on dating apps would lead to lower mood (DiaryMood) in which participants responded to questions regarding the following areas three times a day: (i) mood, (ii) self-esteem, and (iii) craving . In addition, participants included their daily use of dating applications, the number of launches , and the number of notifications they received from dating applications. Participants were advised to set alarms on their smartphones to complete questions during each measurement timepoint. Additionally, calendar reminders were also scheduled via the email addresses that participants used to express their interest in taking part in the study to ensure completion of the measures. In order to participate, participants were required to be at least 18 years old and current users of at least one online dating application. The study required participants to record each of the measures for seven consecutive days , and it required a few seconds to respond to each measure across the three timepoints (~20 s). Although participants needed to be contacted via email to participate in the study, the data from participants were anonymized so that their emails were not associated with their data. To do this, once participants stated their interest in participating, they were given a unique code and password for their access to the app. Once they launched the application , they were asked to create a unique code that only they knew in case a participant wanted to remove their data from the study and to keep complete anonymity . In order to increase participation, the study offered a compensation of a £20 Amazon voucher, approved by the research team’s university ethics committee. Participants received an information form and a consent form after stating their interest in participating. Once they had signed the consent form, they were sent the link to download DiaryMood onto their smartphones. Once the study finished, participants were given a debriefing form and the link to their voucher.The study consisted of real-time self-reported repeated measures collected using a newly developed smartphone app . Participants were recruited through social media networks , where the study was posted. Further participants were recruited through the university’s research credit participation system. Participation was voluntary, and participants contacted the first author to express their interest in taking part in the study. In order to be eligible for the study, participants needed to (i) be at least 18 years old, (ii) be current users of dating apps, and (iii) be Android users. Further details on the participants’ socio-demographics can be found in A total of 22 participants took part in the study (DiaryMood) was developed to include the measures for the present study. DiaryMood included sociodemographic items . Regarding the measures, DiaryMood included three items concerning mood, self-esteem, and craving. Each of the items was presented on a single screen, where participants needed to tap on one of the options and press ‘continue’ afterwards. For mood, participants responded to the following item: “Rate your mood” on a Likert scale ranging from 1 (extremely unhappy) to 5 (extremely happy) [Log your stats of use”. When clicking on the tab, participants were presented with three boxes that included their daily use of dating applications, total use time (in minutes), number of notifications, and number of launches. To access the objective measures, participants were asked to collect data from the wellbeing section on their Android smartphones. For a visual example of DiaryMood, see To collect the data, an Android-based application (y happy) . For sely happy) . For cray happy) . For theAnalysis was carried out in RStudio . First, descriptive statistics were analyzed with regard to sample demographics, means, and standard deviations of the study variables . SubsequMmood = 3.39, SDmood = 0.95; Mself-esteem = 3.39, SDself-esteem = 1.12) with a small divergence during the weekend when mood was slightly higher than self-esteem (see Mcraving-Wednesday = 2.59). Usage was highest at the start of the week, while differences were not statistically significant. Tuesday’s average use was 41.68 min (the highest during the week). The second highest day of use was Thursday with an average of 35.59 min, followed by Saturday with 33.18 min (see ICCs) suggested that 55% of the variance in launch averages was explained by between-participant variation. Therefore, 45% corresponds to within-participant variation, indicating that the difference was higher between participants’ numbers of launches than the differences in launches within participants. In the case of craving, 18% of the variance was attributed to between-participant variance and 82% to within-participant variance, indicating that each participant’s level of craving differed across the week more than the difference found between each other’s levels of craving  than self-esteem and usage , and mood and launches . In addition, objective measures  showed strong correlations with each other: notifications and launches , notifications and usage , and usage and launches .Associations between variables are shown in p = 0.014). In the case of self-esteem, for every one-unit increase in notifications, self-esteem increased by 0.23 . For craving, it was found that for every on-unit increase in usage, craving increased by 0.19 . Further results from the three models are presented in Three models, one for each outcome variable  were tested. Each of the models was compared against alternative models in terms of their fit indexes . The resulting models and their fit indexes are presented in DiaryMood) was developed. The study collected the data in participants’ natural settings and registered 12 daily responses per participant in real time, based on the principles of EMA [The present study investigated the relationships between objective measures of dating app use  and users’ wellbeing  during a one-week period. To do this, a smartphone-based application for Android phones  in relation to higher use of online dating apps [According to the MLM results, no significant effect was found for the time spent on dating applications  on mood or self-esteem. Therefore, neither ing apps ,40,41 aning apps . Neverthing apps  reporteding apps . H3 was supported. More specifically, higher dating app use time predicted higher levels of craving. Related to this finding, Hormes et al. (2014) [In relation to craving and use of time, a significant association was found. Therefore, . (2014)  reported. (2014) , in whic. (2014) . Further. (2014) . Conside. (2014)  for dati. (2014) . H4 was not supported by the MLM. Previous literature has suggested that notifications can act as reminders of activity and increase feelings of FOMO [H5 and 6,H which indicate that notifications would be associated with better mood and self-esteem, as supported by the findings in the MLM analysis. According to these findings, dating app users experienced a positive outcome when they received dating app notifications, which is in line with previous findings where participants reported using dating applications to fulfil their short-term needs [In the case of notifications and craving, no significant relationship was found in the MLM analysis. Therefore,  of FOMO . Receivi of FOMO . Moreove of FOMO ,14, whicrm needs ,41,49. FH7), self-esteem (H8), or craving (H9). Oulasvirta et al. (2012) [Regarding the number of launches, there were no significant findings in the MLM analysis for mood (. (2012)  reported. (2012) ,51. NeveN = 22) may have reduced the statistical power to find significant effects. Second, the sample was collected via convenience sampling; therefore, the findings cannot be generalized to the general population of online dating users [The present study is not without limitations. First, the small sample size  will promote further research employing objective methods, (ii) will provide evidence that apps such as DiaryMood are advantageous tools to carry out empirical studies on online addictions, and (iii) will provide further evidence in the study and conceptualization of problematic use of online dating.The present study assessed the relationships between objective measures of dating app use  and users’ wellbeing. Participants responded to daily questions for seven days utilizing the


The ICD-11 has adopted a classification of Personality Disorders (PD) that abolishes the established categorical PD types in favor of global severity classification with specification of individual trait domains. To facilitate and guide this profound transition, an overview of current research on empirical associations between established PD types and ICD-11 trait domains seems warranted. We identified a total of 9 relevant studies from 2018 to 2022, which were based on both clinical and community samples from U.S., China, Brazil, Denmark, Spain, Korea, and Canada. The patterns of associations with ICD-11 trait domains were systematically synthesized and portrayed for each PD type. Findings overall showed expected and conceptually meaningful associations between categorical PD types and ICD-11 trait domains, with only few deviations. Based on these findings, we propose a cross-walk for translating categorical PD types into ICD-11 trait domains. More research is needed in order to further guide continuity and translation between ICD-10 and ICD-11 PD classification in mental healthcare, including facet-level ICD-11 trait information. Moreover, the nine reviewed studies only relied on self-reported ICD-11 trait domains, which should be expanded with clinician-rated trait domains in future research. Finally, future research should also take ICD-11’s essential PD severity classification into account. The accumulating body of research on the AMPD trait domains is therefore helpful and informative when it comes to the preparation of the now official ICD-11 specification of trait domains , 5. NeveA considerable number of publications have already addressed the trait-based conceptualization of PDs in general, primarily from the perspective of the AMPD criterion B traits , 7 and tThere are currently eight psychometrically sound approaches to the measurement of ICD-11 trait domains, which include the empirically based algorithm for the Personality Inventory for DSM-5 (PI-D) , 14, the1.1.In this short article, we aim to provide an overview of current research on the relationship between traditional PD types  and ICD-11 trait domain specifiers  by presenting and synthesizing findings from studies that explicitly operationalize all five ICD-11 trait domains. Subsequently, we discuss the identified pattern of associations for each PD type. Eventually, we propose how the synthesized findings may inform a “cross-walk” to be used by clinical practitioners in the transition from the traditional types to the new trait domain specifiers.We used PubMed, PsycINFO, Web of Science, and a broad snowballing method to identify a total of nine relevant studies investigating associations between traditional PD types and ICD-11 trait domain scores , 24–30. 2.Sampling, population, and measurement characteristics for each study are presented in 2.1.Paranoid PD was primarily associated with the trait domains of Negative affectivity and Dissociality, in that order. The primary role of Negative affectivity seems conceptually meaningful because mistrustfulness is a core feature of Paranoid PD as well as an explicit feature of ICD-11’s definition of Negative Affectivity. The secondary role of Dissociality is consistent with previous research and empirical frameworks of psychopathology suggesting that features of Paranoid PD belong to the spectrum of externalizing disorders , 36. Mor2.2.Schizoid PD was consistently associated with the trait domain of Detachment, which is explicitly defined by features of social detachment including limited capacity for enjoyment and lack of social interactions and intimate relationships along with emotional detachment including aloofness with limited emotional experience and expression . This de2.3.Dissocial PD was consistently associated with the trait domain of Dissociality and Disinhibition, in that order. This is consistent with meta-analytic evidence indicating that Dissocial PD is characterized by both antagonistic features of callousness and lack of remorse as well as disinhibited features of recklessness, risk taking, and impulsivity , 7. In o2.4.Borderline PD was almost consistently and primarily associated with high scores on Negative affectivity and Disinhibition, which aligns with the fact that this PD type is essentially characterized by emotion dysregulation  and self-destructive impulsivity . As evident from 2.5.Histrionic PD showed a mixed pattern of small to moderate associations with Dissociality, Disinhibition, and Negative Affectivity, which aligns with the fact that this PD type is essentially characterized by self-centeredness and longing for attention , excitement and attention seeking , and excessive and labile emotionality . Two studies also indicated negative associations with Detachment , 28, whi2.6.Anankastic PD was consistently associated with the trait domain of Anankastia and secondarily with Negative Affectivity, which aligns with the fact that this PD type is characterized by aspects of both perfectionism  and behavioral constraint  as well as some feelings of excessive doubt and caution . Interestingly, based on a clinical interview-rated sample, Bach et al.  also fou2.7.Anxious PD was consistently associated with the trait domains of Negative affectivity and Detachment, which aligns with the fact that this PD type is essentially characterized by anxiousness and low self-esteem exhibited as avoidance of situations and activities  along with interpersonal and social withdrawal . Moreover, the majority of the studies also showed substantial associations with Anankastia, which may indicate the emotional constraint and overconcern about avoiding potential negative consequences of any activity characterizing individuals with Avoidant PD , 51.2.8.Dependent PD was consistently associated with Negative Affectivity, which aligns with the fact that this PD type is essentially characterized by low self-confidence exhibited as dependency and frequent reliance on others for advice, direction, and other kinds of help. Moreover, and perhaps surprisingly, the majority of studies also showed substantial associations with Disinhibition. This secondary pattern may be attributed to ICD-11’s inclusion of irresponsibility (or lack of desire to take responsibility) for defining Disinhibition, which is also consistent with previous PID-5 research on Dependent PD . Moreove2.9.Narcissistic PD was almost consistently associated with the trait domain of Dissociality, and secondarily with both Anankastia and Disinhibition. The primary association with Dissociality aligns with the self-centeredness, entitlement, expectation of others’ admiration, and lack of empathy defining this domain. The association with Anankastia may indicate “narcissistic perfectionism,” which serves to enhance competitiveness, self-esteem, and grandiose self-presentation . The ass3.The field is gradually leaving the categorical PD types behind in favor of a new empirically informed approach that is now officially introduced by WHO in the ICD-11 , 61. The3.1.The identified pattern of associations was overall found to be conceptually meaningful and consistent with previous research and theoretical propositions  , 62. Thu3.2.In contrast to DSM-5’s AMPD framework, the ICD-11 classification includes a separate domain of Anankastia corresponding to Compulsivity and partially to reversed Disinhibition. In the present overview, we found that the trait domain of Anankastia accounts for essential features of Anankastic (obsessive–compulsive) PD, as expected, while it somewhat also accounts for features of Narcissistic PD  and Avoidant PD . Negative associations with Disinhibition  did not seem to account for these features, which supports WHO’s decision of including a separate domain of Anankastia. For example, Narcissistic PD was characterized by both Disinhibition  and Anankastia , which would not be possible to portray and code simultaneously on a single bipolar domain of Disinhibition . This is overall consistent with empirical findings and clinical arguments supporting the utility of a separate domain of Anankastia , 63–66, 3.3.Two of the most indistinct and heterogeneous PD types across the nine studies were Borderline PD and Narcissistic PD, which both seem to allow for different expressions and trait constellations.Borderline PD was captured by a broad pattern of trait domains ranging from internalizing features  to externalizing features . This composition seems consistent with research suggesting that Borderline is not a distinct PD type but rather an index of global personality pathology and severity, which aligns with the original metaphorical use of the term “borderline” or “borderland” , 68. TheNarcissistic PD is another PD type that is not straight forward to characterize using trait domains, which also seems related to the many possible faces of narcissism. It makes a substantial difference whether narcissistic PD is characterized by vulnerable features , perfectionistic-controlling features  or features of impatience and self-stimulating impulses due to a sense of entitlement . More broadly, the role of Disinhibition may also indicate aspects of procrastination  as often seen in vulnerable narcissism. Overall, the complex constellation of trait domains for narcissistic features is consistent with the traditional conceptualization that Narcissistic PD involves moderate–severe impairments in personality functioning , 71.3.4.ρ rather than Pearson’s r. Nevertheless, the pattern of their findings was largely consistent with findings in the other studies, while particular deviations may also be attributed to differing operationalizations. Fourth, future research should integrate clinician-ratings of ICD-11 trait domains to account for issues such as mono-method bias (The findings presented in this review should be considered in the light of several potential limitations. First, due to the scarcity of identified studies, we could not perform a meta-analysis in order to produce a quantitative analytical synthesis of the data but pursued to conduct a scoping review instead with less restrictive criteria . Third, hod bias , 20. Fifhod bias , 73–75, hod bias .BB conceptualized the idea, supervised during the writing process, and provided critical revisions. BL and JS conducted the systematic search and prepared the first draft of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width , right arm length , waist circumference , leptin , adiponectin , and interleukin 6  were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440–0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients. Cardiovascular disease, in particular coronary artery disease (CAD), is one of the main causes of morbidity and mortality in the world . ObesityVisceral adipose tissue is an important endocrine organ, responsible for secreting hormones involved in a range of processes, e.g., control of sensitivity to insulin and inflammatory process mediators, and vascular hemostasis ,11. BiomA noninvasive three-dimensional (3D) scanning technology has been developed to obtain anthropometric measurements with many advantages over traditional methods, such as computed tomography scanners, X-rays, and bioelectrical impedance . The aimFrom March 2016 to December 2017, a total of 98 patients found to have CAD as confirmed by cardiac catheterization exam at Chang Gung Memorial Hospital, Keelung, were recruited into our study CAD group. The same number of 98 sex- and age-matched patients presenting to our Department of Health Promotion and Examination were enrolled into the control group. Informed consent was obtained from all participants. This study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board of Chang Gung Medical Foundation (201405148B0).x- and y-axis was approximately 1 mm (1.2%), and in the z-axis it was less than 0.1 mm (0.2%) ) between the body measurement combinations and CAD. In order to find associations with CAD in individual patients, biochemical and body shape variables that significantly differed between the non-CAD and CAD groups were further analyzed. This was done by calculating optimal cutoff values for continuous variables using a receiver operating characteristic (ROC) analysis. The statistical software used for the analyses in this study was SPSS 25.0 .Two independent sample p = 0.001). Among lifestyle variables, the CAD group had more smokers ), more patients that did not consume coffee , and more that did not exercise . As regards to risk factors, more patients in the CAD group had hypertension  and diabetes , and fewer patients in the CAD group had hyperlipidemia .A total of 98 patients were recruited into each of the CAD group and control group over a period between March 2016 and December 2017. Baseline characteristics for the study participants are shown in Various biomarkers showed some differences between the CAD and control groups.  Levels oThe 3D body surface scanning measurement results are shown in p = 0.0399), RAL , WC , leptin , adiponectin , and IL6 .The biomarker score, body measurement score, biomarker and body measurement score ware calculated based on the estimated values generated by the Our study results show that lower educational level, no coffee consumption, physical inactivity, low adiponectin, high leptin, and high IL6 levels were associated with CAD. In terms of 3D body measurements, compared to the traditional BMI assessment, smaller CW and RAL with higher WC were also associated with CAD. In addition, the combination of biomarker scores and body measurement scores had the highest predictive value for CAD as shown with ROC analysis. These findings have given us a novel method for assessing the risk of those who may have CAD.Inflammation contributes to CAD, among which IL6 plays an important role in atherogenesis and atherosclerotic plaque destabilization. IL6 is associated with vascular endothelial injury and tissue fibrosis, promotes angiogenesis, and increases vascular permeability . Once ILAdipose tissue is associated with CAD, abdominal adiposity causes development of adipose cells that are enlarged and dysfunctional . These dBy using a more accurate 3D body scanning method, we found that higher WC, lower CW and lower RAL were also associated with CAD. WC, which reflects abdominal obesity, has been suggested to be superior to BMI for CAD risk prediction , and thiFaced with CAD being such an important cause of death worldwide, we sought to explore its associations with the more accurate method of 3D-derived body measurements and biomarkers in an attempt to gain more mechanistic insight.As our study design was of a cross-sectional study, we are unable to infer causality from the results. The 3D body measurements were performed only at one point in time with no repeated estimations or data on changes over time. Our study population was of Chinese adults in a hospital setting so the results might not be applied to other ethnicities, age groups, or populations in the community. Therefore, it may be necessary to clarify these conclusions in further longitudinal studies and in a wider population.In our study, 3D anthropometrics provide incremental information regarding associations of body surface measurements with CAD. It has been shown that shorter RAL and CW, and longer WC measurements combined with lower adiponectin and higher leptin and IL6 levels were associated with CAD. Although the precise mechanisms are far from clear, by combining non-invasive 3D body surface measurements together with biomarkers, we may in future be able to explore a different mechanistic approach to CAD, and non-invasively identify those with this condition in clinical practice, in addition to providing more information in epidemiological studies and preventative medicine.


Background Down syndrome is the most commonly genetic cause of developmental delay and intellectual disability, affecting 1:700 live births. It is associated with heart disease and recurrent infections, among other complications that greatly impair the patient's quality of life.Objective To evaluate the major factors associated with quality of life in a cohort of patients with Down syndrome.Methods We assessed 1,187 patients with Down syndrome, older than 4 years old, with an adaptation of the Personal Outcomes Scale validated for Portuguese language, interviewing patients, parents, and caregivers.Results A bad quality of life was reported in 56.4% of the sample. The main factors associated with better quality of life were female sex, first medical visit before 4 months old, higher parental education, a professionally active mother, and prenatal care. The main factors associated with worse quality of life were family history of alcohol abuse and psychiatric disorders and comorbidity with autism and epilepsy.Conclusion Clinical comorbidities such as autism and epilepsy carry a heavy burden among patients with Down syndrome, while factors related to family support, such as employment status and educational background of the parents, enhance quality of life. The factors associated with quality of life among patients with Down syndrome should be adequately evaluated in medical consultation and targeted in public health policies. Down syndrome (DS) is the most commonly identified genetic cause of developmental delay and intellectual disability. It is characterized by trisomy of the chromosome 21 in 95% of the cases, with the remaining 5% being attributable to translocations and/or mosaicisms.The World Health Organization (WHO) defines quality of life as an individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns”. It is a wide concept that includes physical and psychological health, level of independence, and social relationships.This work is a cross-sectional study that was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies.This study was carried out in a public tertiary care center for patients with DS in Curitiba, state of Paraná, Brazil. Patients above 4 years old with DS, as well as their parents and/or caretakers, on regular follow-up at our service were invited to take part in this study. Attended patients were consecutively invited during the consultations. Patients younger than 4 years old, and patients/parents from whom informed consent could not be obtained were not included.To evaluate quality of life in our sample, we used a version of the Personal Outcomes Scale (POS) adapted for Portuguese language.We established a good quality of life when patients presented good overall development, autonomy for activities of daily living , and practical life activities (such as waiting to be picked up in front of the school or making a payment at a cash machine), as well as an adequate insertion in society, school, and/or their work environment. We defined a bad quality of life as the presence of significant developmental delay, high levels of family dependency, and no opportunities for inclusion or insufficient social skills. In addition, we sought information directly, or from the patient's files, concerning sex, age, age of first medical consult, breastfeeding history, neonatal screening, parental sociodemographic profile, enrollment in a special school, associated clinical comorbidities, physical activity, psychomotor development, family medical history, and results of an ancillary investigation, such as brainstem-evoked response audiometry (BERA).t-test, Mann-Whitney test, Fisher exact test, and Pearson chi-square test, using the Statistica  software. Missing data were handled by listwise deletion. The level of statistical significance was fixed atp < 0.005.Numerical variables are expressed by means and standard deviations, while categorical variables are expressed in terms of proportions and percentages. Comparison between groups was established through StudentThis study was reviewed and approved by the Research Ethics Committee of Universidade Federal do Paraná. All patients and/or their tutors provided written informed consent to take part in this study.We gathered a sample of 1,187 patients, with a predominance of males (55.3% of the sample).The most common karyotype representation was simple or regular trisomy in 1,120 (94.4%) cases, followed by translocation in 31 (2.6%), and mosaicism in 28 (2.4%) patients. Simple trisomy was associated with another genetic abnormality in 7 (0.6%) patients, with Klinefelter syndrome being the most common overlapping chromosomal syndrome.p = 0.01), higher parental educational level (p < 0.001), mosaicism (p = 0.001), adequate prenatal care (p < 0.004), first medical consult in an earlier age (p < 0.001), and mother employed (p < 0.001). The paternal employment status did not present any statistically significant difference among the groups (p = 0.6) (p < 0.001) and psychiatric conditions (p = 0.02), and clinical comorbidities such as autism (p < 0.001) and epilepsy (p = 0.001)  and3.  0.001) .thminute, results in ancillary investigation (BERA and audiometry), karyotype (except mosaicism), cardiopathy, and attention deficit hyperactivity disorder did not present statistically significant differences among the groups (The variables weight at birth, neonatal intercurrences, APGAR in the 5 groups .The current study gathered data on quality of life among Brazilian patients with DS comprehending a significant sample, reuniting self-reported information, views and perceptions from parents and caregivers, and data from their medical files. Most prior studies on the subject emphasized only the data reported by the parents.Contrary to general belief, children with working parents did not perform academically and cognitively worse. The reduced availability of time is often compensated by an improvement in the quality of time spent.Patients with DS greatly benefit from such educational strategies. One example is the language domain, in which a wide range of interventions can foster the acquisition of communication skills in children with DS, based on the diversity of free-time activities, regularly-scheduled activities, use of books and magazines, combined with adequate supervision of formal academic activities and a daily routine with defined schedules, emphasizing the importance of clear verbal communication.In analyzing the factors that led to poor quality of life, the presence of clinical comorbidities, namely epilepsy and autism, was noteworthy. This finding was similar to the observed in the study by Haddad et al., but, in their cohort, quality of life was more impacted by bowel conditions and psychiatric disorders.This study has certain limitations that are important to highlight. One major limitation of our report is the lack of standardization among the various research instruments used to assess quality of life, and the scarcity of studies in the context of DS further exacerbates this issue. Despite utilizing a validated quantitative tool such as the POS, the absence of clear cutoff points for quality of life in patients with DS poses a challenge. To address this, we employed a qualitative-quantitative approach and adapted the scale with specific parameters indicating good or poor quality of life. However, as expected in studies involving qualitative aspects, we heavily relied on patient and parental reports, which introduces the possibility of reporting bias. Although we gathered a significant sample, our data was derived from patients being followed up at a single center, thereby limiting the external validity of our study. Moreover, the high level of cultural heterogeneity in Brazil may influence the perception of quality of life and its associated factors.In conclusion, clinical comorbidities such as autism and epilepsy carry a heavy burden among patients with DS, while factors related to family support, such as employment status and educational background of the parents, enhance quality of life. These factors should be considered when devising healthcare policies to improve cognitive, emotional, and social outcomes for patients with DS. More studies are necessary to capture the regional differences among Brazilian patients with DS.


This study aims to verify the new-onset diabetes after kidney transplant (NODAT) incidence in recipients within 1 year after kidney transplantation from a single center in Southern Brazil and to assess the associated conditions.A retrospective study of 258 post-renal transplant patients was performed. Demographic  and clinical  at transplant time and 6 and 12 months after, causes of renal failure, and comorbidities) data were analyzed. All patients were on tacrolimus, mycophenolate mofetil, and prednisone treatment. Patients with and without NODAT were compared.A NODAT incidence of 31.2% was noted 1 year post transplantation. In the univariate analysis, patients with NODAT were older (p = 0.001), mostly had African–American ethnic background (p = 0.02), and had renal failure secondary to high blood pressure (HBP) (p = 0.001). The group of patients with NODAT also had more incidence of post-transplant HBP (p = 0.01), heart failure (p = 0.02), and dyslipidemia (p = 0.001). Logistic regression showed that African–American ethnic background, post-transplant HBP, and dyslipidemia were independently associated with NODAT.This study shows a NODAT incidence that is greater in patients with African–American ethnic background and that is associated with HBP and dyslipidemia. New-onset diabetes after transplant, or NODAT, is one of the major complications after solid organ transplantation ,2. ThereThe pathophysiology of NODAT closely mimics type 2 DM: insulin resistance and insulin hyposecretion develop in both situations. Nevertheless, in NODAT, insulin hyposecretion seems to be a crucial determining factor in glucose tolerance deterioration .Several risk factors were known to be associated with NODAT, such as ethnic background, family history of diabetes, sedentary lifestyle, high body mass index (BMI), and cytomegalovirus and hepatitis C virus (HCV) infection. A high dose of glucocorticoids and the use of immunosuppressive regimen with calcineurin inhibitors may also be associated with this condition -8. NumakGenetic background may influence the prevalence of NODAT in different populations . The incThis retrospective study was approved by the local Committee of Ethics in Research (56934016.4.0000.0103). Charts of kidney transplant patients from a single center, a university evangelical hospital, located in the city of Curitiba, Paraná, Brazil, registered from July to December 2015, were reviewed for epidemiological, clinical, and treatment profile.Patients under 18 years of age, those with DM prior to transplantation, those who had first-degree relatives with DM, and those who had used immunobiological drugs or had graft rejection were excluded.The study sample included 258 patients . All patients were on standard treatment, with prednisone, mycophenolate mofetil, and tacrolimus, which is determined by the Brazilian Health Ministry, Ordinance 1.168, in 2004.The following data of all patients were reviewed retrospectively for 12 months: BMI prior to transplantation and six and twelve months post transplantation, causes of renal failure prior to transplantation, graft origin (either from deceased or living donor), and occurrence of hepatitis C and CMV infections. The diagnosis of DM was made according to the American Diabetes Association, through the analysis of three altered values of blood glucose, which was done by the transplant doctor and was registered in the patient medical record 12 months after transplantation .The obtained data was collected in frequency and contingency tables. The epidemiological and clinical profiles between patients with and without NODAT were compared using the Fisher exact test and chi-square tests for nominal data and unpaired t-test and Mann–Whitney test for numeric data. To assess variables independently, logistic regression was used. The significance level adopted was 5%.The description of clinical, epidemiological, and treatment data of kidney transplant patients being studied are shown in Only three patients had HCV infection. In this sample, the NODAT incidence was 31.2%.When all variables with p < 0.1 were studied through logistic regression, it was found that African–American ethnic background , dyslipidemia , and hypertension  were independently associated with NODAT.In the present study, which included 258 renal post transplanted recipients, all in the same therapeutic regimen, there was a NODAT incidence of 31.2% in the first year after the transplant procedure. It is noteworthy that individuals with DM in the first-degree relatives in the sample were excluded, so the possible occurrence of a common type 2 DM was minimized. In addition, it was observed that NODAT was independently associated with factors such as African–American background, arterial hypertension, and dyslipidemia.2 which is close to the accepted normal range. Therefore, obesity, which is widely linked to DM, was underrepresented in the sample. This may explain the diversity of the results found. Additionally, CMV infection could not be associated with NODAT in this study, considering the very low incidence of infection in patients. The same occurs with HCV infection. However, literature concerning HCV infection and NODAT is ambiguous, with some authors supporting higher prevalence of these findings  and hepatitis C infection . BMI alofindings  and othefindings ,21. In tNODAT's association with African–American background was also described by other authors . This asTacrolimus is considered one of the main NODAT causes,  and all The mechanism involved in tacrolimus-induced NODAT includes diminished insulin secretion, as calcineurin is expressed in pancreas β cells. This medication disrupts mitochondrial permeability, causes inhibition of NFAT transcription factor, and targets cAMP-responsive element-binding protein transcriptional coactivator . In addiNODAT is associated with lower survival of transplanted recipients, and it is an independent risk factor linked to graft failure . FurtherThis is a retrospective study, which is also considered one of the limitations. It is also possible that the occurrence of NODAT would be higher in longer periods of observation.In conclusion, this study shows a higher NODAT incidence in kidney transplant recipients with African–American ethnic background. Moreover, NODAT is associated with higher blood pressure levels and dyslipidemia in all transplant recipients, regardless of the ethnic background. Prospective and multicentric studies may be useful to better understand and prevent NODAT.