Low back pain (LBP) is a common complaint in the elderly Japanese population. Although previous studies showed that height loss was associated with LBP, it remains unclear whether LBP is associated with body composition. The objective of the present study was to investigate whether body composition and physical characteristics, including height loss, were associated with LBP.The present study is retrospectively registered, and the participants were 2212 community-dwelling Japanese people aged over 60 years who participated in the Shimane CoHRE study in 2016. We investigated the presence of LBP, body composition parameters , physical characteristics (body height and height loss), chronic diseases, history of fall, smoking, and drinking habits. We examined the relationships of body composition parameters and physical characteristics with point prevalence of LBP using multivariate logistic regression.The point prevalence of LBP was 43.2% in women and 39.5% in men. Logistic regression models showed that body height and body composition were not significantly associated with LBP; however, height loss was associated significantly with LBP in women and men . Hypertension  and chronic heart disease  in women and history of fall  and cerebrovascular disease  in men were significantly associated with LBP. However, body composition was not associated with LBP in either gender.The present study demonstrated that height loss, but not body composition, was related to LBP in community-dwelling elderly people. To elucidate the cause of LBP, it is important to consider the relationship with height loss.The online version of this article (10.1186/s12891-019-2580-6) contains supplementary material, which is available to authorized users. Low back pain (LBP), a common symptom of the elderly, is associated with a marked decrease in health-related quality of life , 2 and pA previous survey reported that the point prevalence of LBP ranged from 12 to 33%, 1-year prevalence ranged from 22 to 65%, and lifetime prevalence ranged from 11 to 84% . In the Many researchers have studied the physical characteristics of subjects with LBP. For example, LBP has been reported to be associated with overweight/obesity –18 and sTherefore, the aims and objectives of the present study were to examine the relationship between body composition, physical characteristics, and LBP with respect to height loss in general community-dwelling older people.This cross-sectional study is a part of the cohort study conducted by the Center for Community-based Healthcare Research and Education in Shimane University (Shimane CoHRE study). It is an ongoing health examination for the community-dwelling people in Unnan-city, Okinoshima-cho and Ohnan-cho, Shimane Prefecture, Japan. The study protocol was approved by the Ethics Committee of Shimane University School of Medicine (#3149) and Unnan City Hospital (#20180004). Written informed consent was obtained from all participants.In this study, we used the CoHRE study data, which was collected from June to November 2016. A total of 3036 community-dwelling Japanese people participated in the health examinations. The inclusion criteria for this study were as follows: (1) individuals who were over 60 years old; (2) individuals answered the questionnaire regarding LBP and history of fall; (3) individuals whose demographic data, including age, gender, and the tallest recalled height were recorded; (4) individuals whose body compositions were examined; and (5) individuals who were informed of the protocol and purpose of the current study and consented to participate. According to the criteria, a total of 2212 subjects were included in the current study  method with MC-780A multi-frequency segmental body composition analyzer  , 33. BodBone mass was measured using quantitative ultrasound (QUS) . QUS has advantages including absence of exposure to radiation, low cost, and portability. The estimated values were compared to young adult mean (%YAM) of the same gender. A value 100% means same value as healthy young men or women . This meThe present body height was measured using a stadiometer. The tallest body height was obtained from self-reported questionnaire as follows: “What was your tallest height (when you were 20 years old)?” Height loss was calculated by the subtraction of the present height from the tallest height , 35.Other variables were obtained from the self-administered questionnaires. We inquired about age, gender, history of fall within 1 year , smoking , alcohol consumption  and chronic disease . These potential confounders were reported to be associated with musculoskeletal pain, including LBP –42.t-tests for continuous variables and χ2 tests for categorical variables. Although some data were not normally distributed, this analysis method was used because the number of participants was sufficiently large.The characteristics of study participants were compared between participants with LBP and those without using independent Multivariate logistic regression models stratified by gender were used to explore the association between the presence of LBP (dependent variable), body composition parameters, physical characteristics, and covariates (independent variables). According to these models, adjusted odds ratios (ORs) and 95% confidence intervals of the LBP-related parameters were calculated. ORs were adjusted for age, body composition, and additional covariates such as body characteristics and the presence of chronic disease. We used for the following potential confounders: age, body height, muscle mass, fat mass, smoking, alcohol drinking, history of fall, hypertension, dyslipidemia, diabetes, cerebrovascular disease, chronic heart disease, and height loss. Body weight and BMI were not included as dependent variables of multivariate analysis because of their high Pearson’s correlation coefficients with muscle mass and fat mass . All statistical analyses were performed using the IBM SPSS Statistics 22 software package .The level of significance was set at The characteristics of 2212 participants are shown in Table p < 0.01) was negatively associated with the presence of LBP in Model 1 (Table p < 0.01) but not body height was significantly associated with LBP. Furthermore, the presence of hypertension  and chronic heart disease  had a significant association with LBP in women. In men, height loss , history of fall  and cerebrovascular diseases  were significantly associated with LBP Additional file 2:Table S2. A multiple linear regression analysis on height loss with the present body height and body weight. (XLSX 27 kb)


Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on CP/CPPS.We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by grading of recommendations assessment, development, and evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform a NMA to synthesize direct and indirect evidence.The results of this NMA will be submitted to a peer-reviewed journal for publication.PROSPERO CRD42018111408. Epidemiological investigations have shown that 2.2% to 13.8% of adult men are suffering from it, and approximately 30% to 50% of men would suffer from it in particular periods of their lives. Related literature reports that the prevalence of CP/CPPS and the related symptoms of it in China is as high as 46.6%.–5 Its impacts not only deteriorate the patients‘ physical and psychological health, but also the social economy, which, because of the high incidence and the recurrence. Thus, the National Institutes of Health (NIH) has listed CP as one of the chronic diseases that affect the quality of life of residents, which include myocardial infarction, unstable angina, and active Crohn disease.Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a common urinary system disease in the male population, has the symptoms of repeated, long-term pain and discomfortableness around pelvic floor area and lumbosacral portion, besides, varying degrees of lower urinary tract symptoms  would also become visible.–8 At present, there is no specific therapy for this disease in modern medicine and we mainly adopt antibiotics, α-blockers, and so on; however, multicenter clinical studies have shown that the curative effect of single treatment mode is limited or even invalid.–11 In addition, due to the specificity of the anatomical structure of prostate – the deeper intima of the capsule, it is easy to cause local microcirculation disturbance, blockage of blood stasis, drainage blocked. All the factors above make the drug difficult to reach the lesion and cannot fully effective, which make the disease become recurrent and chronic.The pathogenesis of CP/CPPS is complicated which has not yet been completely illuminated. Literature reports that there are kind of connections between prostate hyperplasia and CP/CPPS.–15 Studies also show that acupuncture could accelerate the central nervous system to produce endogenous opioid peptides and activate relevant receptors by stimulating related acupoints, which achieves peripheral analgesia. Besides, it could also achieve the anti-inflammatory effects by promoting the levels of β-Ep in inflammatory tissue and serum.–18 TCM believes that acupuncture can regulate the balance of qi and blood in the human body and the function of body could also be improved by stimulating acupoints. Moreover, it becomes increasingly popular because of its unique advantages of simplicity, convenience, efficacy, and inexpensive.Acupuncture, 1 essential part of traditional Chinese medicine (TCM), has been widely used in clinical trials recently. Recent studies have shown that there are remarkable effects in reducing chronic pain and tissue fibrosis around the pelvic floor area. Previous clinical trials have shown that acupuncture could ameliorate pain and improve the quality of lives in patients who suffer from CP/CPPS, and these effects are sustained.,20 However, due to the limitation of the scale and sample size of the clinical centers, the current level of evidence-based medical evidence is still not sufficient. Therefore, we hope to evaluate the efficacy and safety of acupuncture in treating CP/CPPS by using network meta-analysis, which aims to provide sufficient evidence for its clinical application.After preliminary search and analysis of the database, we found that the frequency of randomized controlled trials (RCTs) of acupuncture treatment in CP/CPPS has been showing an increasing trend.2http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111408). The protocol follows the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) statement guidelines. We will describe the changes in our full review if needed.This systematic review protocol has been registered on PROSPERO as CRD4218111408 . The cases which relate to prostatic hyperplasia, prostate cancer, or other prostate-related diseases would be excluded. In addition, there is no limitation in region, citizenship, nationality, and source of cases.2.1.32.1.3.1The intervention will include all piercing acupuncture, including hand-acupuncture, electroacupuncture, fire needle, plum blossom needle, abdominal needle, and so on. Other nonpiercing acupunctures such as acupressure, acupressure, acupressure, moxibustion, and so on will be excluded. Acupoint injections will also be excluded. Pharmaco-acupuncture-true and acupoint injection will be rejected, we consider that their methods and theories are different from TCM. The treatment duration and frequency are not limited.2.1.3.2The control interventions will include a placebo, a virtual acupuncture, a conventional drug such as an alpha-blocker, an antibiotic, a botanical preparation, a nonsoul anti-inflammatory drug, and the like. However, RCT of acupuncture combined with drugs or other Chinese medicine methods will be excluded.2.1.42.1.4.1The National Institutes of Health's Symptom Score Index (NIH-CPSI) score for CP/CPPS will be used as the primary outcome measure. Every dimension  of NIH-CPSI will be evaluated, and the lower the total score, the lighter the clinical symptoms of the patient.2.1.4.2Secondary outcomes include:(1)changes in international prostate symptom scores before and after treatment;(2)changes in international erectile function scores-5 before and after treatment;(3)comparison of effective rates between groups and the incidence of adverse events.2.2Database Search: PubMed, Cochrane Library, AMED, EMbase, World SciNet, Nature, Science online and China National Knowledge Infrastructure, China Biomedical Literature CD-ROM Database, China Resources Database. Search for clinical research literature on acupuncture CP/CPPS published in domestic and foreign biomedical journals from the establishment of the library to December 2018. Based on the standards of the Cochrane Collaboration Workbook of the International Evidence-Based Medicine Center, a manual and computer-based method will be used to conduct related literature searches. The search terms include: chronic prostatitis, chronic pelvic floor pain syndrome, nonbacterial prostatitis, acupuncture, acupuncture therapy, acupuncture, electroacupuncture, fire needle, plum blossom needle, skin needle, and abdominal needle. Manually search for topics, abstracts, and so on related to the research of Chinese Journal of Male Science, Chinese Acupuncture and Acupuncture.2.32.3.1Two investigators used EndnoteX7 software to conduct a preliminary assessment of the title and abstract of each document in the database based on the established criteria for inclusion in the study to select eligible studies. After a preliminary assessment, the full text of the selected literature would be evaluated, and the uncontrolled study, no randomization, inconsistent evaluation criteria, and similar data would be excluded. Any differences in screening that occurred during the screening study would be discussed in order to get consensus, if it still cannot be resolved, then the third author would be intervened. The primary selection process is shown in a PRISMA flow chart Fig. 2.3.2Two investigators independently extracted information from the included literature. The extracted content includes research design, random hiding and blinding, basic information of the included cases, intervention methods, observation indicators, and test results of the treatment group and the control group. The extracted literature data will be filled in a unified data statistics table. For studies that provide baseline and post-treatment data, we will estimate the change values by the method recommended by Cochrane. The complete PubMed search strategy is summarized in Table 2.3.3Two investigators will independently evaluate the methodological quality of the included literature by using the Cochrane Collaboration's ROB tool which includes whether the random method is correct, whether blinding is used, whether it is hidden, whether it is lost or quit, whether it uses intent-to-treat analysis, whether the data results are accurate, and other risks of bias. According to the relevant standards in the Cochrane Intervention System Evaluation Manual, it will be divided into low risk, high risk, and unclear.2.3.4In the event of data loss during the screening and extraction of literature data, first, we will actively investigate the cause of data loss. Then we will contact the experimental research author by telephone, mail, and so on to achieve the purpose of supplementing the missing data. If the lost data cannot be retrieved, we will only extract and analyze the useful data, besides, we will indicate the situation.2.3.52.3.5.1The numerical variable will be expressed as the normalized mean difference (standardized mean difference [SMD]) with a confidence interval (CI) of 95%. The heterogeneity of each pairwise comparison will be tested by chi-square test (test level α = 0.1). If there is no heterogeneity, a fixed effect model will be used. If there is significant heterogeneity between a group of studies, we will explore the reasons for the existence of heterogeneity from various aspects such as the characteristics of the subjects and the degree of variation of the interventions. Sensitivity analysis or meta-regression and subgroup analysis to explore possible sources of heterogeneity when necessary. We will use qualitative analysis of the funnel plot and graph symmetry to assess publication bias. Quantitative methods such as Begg testing and Egger testing will be used to help assess publication bias in the application.2.3.5.2We will use GeMTC 0.14.3 software to analyze the data. STATA 13.0 and WinBUGS 1.4.3 will be used to perform NMA to synthesize direct and indirect evidence. The NMA will mainly use the Bayesian Markov chain-Markov Chain Monte Carlo random effects model and simulate with 5 chains. The convergence of the simulation will be evaluated by using the potential reduction factor and the Gelman-ubin-rooks diagram. The choice of the final model will depend on the biased information standard (DIC) value. In general, models with smaller DIC values are better. The total effective rate is counted, and the odds ratio is used to analyze the statistic. The effect size is expressed in 95% CI, and the numerical variable is expressed as SMD. The treatment level for each result will operate on the cumulative sorting curve (SUCRA) interface. The evidence relationship incorporated into the study will be calculated by STATA. If there is a “closed loop,” the node splitting method will be used to evaluate the inconsistency of each loop.2.3.6If there is significant heterogeneity between a group of studies, we will explore the reasons for the existence of heterogeneity from various aspects such as the characteristics of the subjects and the degree of variation of the interventions. Sensitivity analysis or subgroup analysis is performed as necessary to explain heterogeneity.2.3.7The forest map and funnel plot were drawn and analyzed using Rev Man5.3 software, and the funnel plot was used to analyze potential publication bias.2.3.8The quality of evidence for the main outcomes will also be assessed with the grading of recommendations assessment, development, and evaluation approach. The evaluation included bias risk; heterogeneity; indirectness; imprecision; publication bias. And each level of evidence will be made “very low,” “low,” “moderate,” or “high” judgment.3 Studies have shown that drug intervention can improve the overall NIH-CPSI score and ameliorate most of the symptoms of CP/CPPS patients to a certain extent, but there is no single drug can continue to significantly ameliorate all symptoms of CP/CPPS patients.–23 TCM has a profound theoretical foundation and abundant clinical experience in the treatment of CP/CPPS. Acupuncture, 1 essential part of TCM, has the characteristics of few side effects, simple and easy to use, and has long been used to treat genitourinary diseases. Acupuncture therapy mainly achieves therapeutic effects by stimulating the body's righteousness and regulating the balance of qi and blood. In recent years, acupuncture therapy has been widely used in clinical trials of CP/CPPS. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of lives of patients.At present, there are vast of therapies in treating CP/CPPS; however, the efficacy is still unsatisfactory due to the particularity of the anatomical structure of prostate.Although abundant studies have evaluated the effectiveness of acupuncture in treating CP/CPPS, evaluation and comparison between various treatments are still insufficient. To the best of our knowledge, NMA has not been used in recent years to compare the effectiveness of acupuncture in the treatment of CP/CPPS. The results of NMA can provide a possible ranking for acupuncture treatment of CP/CPPS. We hope that the results will provide clinicians with the best options for treating CP/CPPS and provide them with research directions. Due to the limited number of relevant high-quality studies and the few sample size included, the strength of the arguments of the conclusions is to some degree limited. Therefore, we hope that more large-scale, high-quality randomized controlled trials should be necessary in the future. Besides, improving the quality of the original research and conducting high-quality multicenter RCTs to explore the clinical efficacy of acupuncture treatment of CP/CPPS is also indispensable, through which could make the conclusion more objective and reasonable.BW and HSL are the guarantor. JSW and BHB contributed to the conception of this review. JSW drafted the manuscript of the protocol and BHB revised it. HHD developed the search strategies while XDY and KGZ will implement them. JSW and BHB will also screen the potential studies, extract data and assess quality. In case of disagreement between the 2 data extractors, JSW will advise on the methodology and work as arbitrator. BHB will complete data synthesis. All authors approved the final version for the publication.Data curation: Yi Lei, Xueyun He, Jingshang Wang.Formal analysis: Xiaoyong Gong, Wei Zheng.Project administration: Chaohui Xue.Supervision: Jiajia Ma.Validation: Jiajia Ma.Writing – original draft: Yahui Xue, Yongqiang Li.Writing – review and editing: Yi Lei, Bao Zhang.


Some researchers reported that pleiotrophin (PTN) is associated with the development and metastasis of various tumors and it is a poor prognostic factor for the tumor patients. However, the results of other researches are inconsistent with them. It is obliged to do a meta-analysis to reach a definite conclusion.The published studies relevant to PTN were searched in the databases including PubMed, Embase and Web of Science until March 20, 2018. A meta-analysis was conducted to evaluate the role of PTN in clinicopathological characteristics and overall survival (OS) of cancer patients.Our meta-analysis indicated that the high expression of PTN was remarkably associated with advanced TNM stage  and poor OS  in tumor patients. The expression of PTN was not associated with tumor size , lymph node metastasis (LNM) , distant metastasis (DM)  and histological grade .The high expression of PTN is significantly relevant to the advanced TNM stage and poor OS in tumor patients. PTN can serve as a promising biomarker to predict unfavorable survival outcomes, and it may be a potential target for tumor treatment. Tumour has become a leading cause of death in recent decades, and about 8.2 million people died from cancers and 14.1 million cancer cases were latest diagnosed all over the world in 2012,9, whileIn order to obtain the potential qualified reportes, a systematic network reference search was conducted focusing on multiple website databases, including Embase, PubMed, and Web of Science until March 20, 2018 and the search keywords were as follows: “pleiotrophin”, “PTN”, “cancer”, “tumor”, “clinicopathology”, “prognosis” and “survival”. The relevant reviews and references cited in the searched articles were also filted to avoid leaving out any potentially usable references. Besides, other related articles were also available by examining the reference lists by hand.The selected criteria were as follows: 1) the expression level of PTN in primary cancerous tissues was measured; 2) dichotomous model was appraised by immunohistochemistry (IHC); 3) related clinicopathologic parameters were reported; 4) hazard ratio (HR) and 95% confidence interval (CI) between PTN expression and overall survival could be picked up directly or calculated indirectly in the study. The removed criteria were as follows: 1) the letters, experiments, or articles that researched on animal models; 2) repeated research publications; 3) the expression of PTN was detected in serum or at PTN mRNA level.Two investigators (Zhou J and Yang Y) independently extracted the information and data from all eligible studies through cross-check. The data and information were got together from every study using a purpose-designed form: the author, the year of publication, the country, the type of cancer, the overall number of patients, number of patients in the high PTN expression group and the low PTN expression one, number of patients with big tumor size, TNM (Ⅲ/Ⅳ), LNM, DM and survival data in each group, and the standard for high PTN expression. The survival results of both original and adjusted data were overall survival. The disagreements between the two investigators were settled by discussion until a agreement was reached with the third investigator (Zhang Y). Quality evaluation was based on the Newcastle-Ottawa quality assessment scale (NOS). The NOS scores varied from 0 to 9. Six points or more were deemed as high quality.2 metric and Q statistic. The P value<0.05 for the Q-test and the I2-value>50% were took into account to be indexes of serious heterogeneity. The random-effects model was selected for the researches with a remarkable heterogeneity . Or else, the fixed-effects model was applied . Sensitivity analysis was performed to ensure the steadiness of the combined results. Publication bias was appraised by Egger’s test and a funnel plot, and P<0.05 demonstrated remarkable bias. The P value <0.05 was deemed statistically significant.The current meta-analysis was carried out using the RevMan5.3 software and Stata SE13.0 software. The prognostic effect of high PTN expression was assessed by both adjusted and unadjusted hazard ratios (HRs) and their 95% confidence intervals of overall survival from the primary studies. According to the standard of each study, the expression of PTN was divided into high and low level groups. Reported HR and 95% CI were directly collected from the researches. If HR and 95% CI were not shown in these studies, the means of Tierney et al. and ParmAfter the initial search algorithm, a total of 745 articles were retrieved. Unrelated articles were excluded from headlines and abstracts, and 149 articles were further evaluated in the full text. Those articles, which were Review or Case and did not provided survival data to extract, dichotomous variables and valuable data, were excluded. Finally, this meta-analysis contained 10 articles including a total number of 851 patients . The aveThe association between PTN expression and OS was reported in seven studies–7,9,13. 2 = 60%, P = 0.03), thus the random-effects model was employed. The analysis displayed a pooled OR = 1.12 , as shown in The number of patients with tumor size was reported in six studies in view of different PTN expression levels, totally including 532 patients. There existed notable heterogeneity in the studies . The meta-analysis indicated a pooled OR = 1.95 , as shown in 2 = 0%) when the study from Wang 2015 was removed. The pooled OR estimates were significantly changed to 3.18 . Thus, the LNM was significantly related to the high PTN expression. This analysis confirmed the instability of our results which needed to be treated with caution.Three studies discussed the number of patients with LNM in according to different PTN expression levels, which included 201 patients. The random-effects model was applied because of significant heterogeneity among the studies . The pooled odds ratio (OR) of the high PTN expression group compared with low PTN expression group was 2.78 , as shown in It was reported that the number of patients with DM on account of different PTN expression levels in four articls, which consisted of 288 patients. In virtue of remarkable heterogeneity in the studies,the random-effects model was put to use . The analysis showed a pooled OR = 1.95 , as shown in 2 = 0%). The analysis of these left studies indicated a statistically obvious association between the high histological grade and the high PTN expression. The combined OR estimates were 2.71 . This analysis confirmed the instability of our results which needed to be treated with caution.On the basis of different levels of PTN expression, five studies covered the number of patients with histological grade, including 452 patients. The random-effects model was applied because of significant heterogeneity in the studies . The meta-analysis demonstrated a combined OR = 2.79 , as shown in The number of patients with TNM stage on the basis of different levels of PTN expression was reported in seven studies, including 539 patients. The fixed-effects model was employed because of restricted heterogeneity among the studies . The analysis indicated a pooled HR = 1.77, as shown in Seven studies reported 643 patients with OS in the light of different levels of PTN expression. The fixed-effects model was carried out for small heterogeneity in the studies , LNM (P = 0.544), DM (P = 0.385), HG (P = 0.084) and OS (P = 0.873) , Fig 8B PTN, previously designated heparin binding growth-associated molecule, is a multifunctional growth factor that regulates various cellular functions, including cell proliferation, migration, and angiogenesis in endothelial cells, and is a highly conserved member of the human gene families. Human PPTN has been confirmed to be upregulated in some types of cancers–9,13,14 On the mechanism of PTN expression regulation, there are a large number of upstream and downstream molecules. PTN expression is up-regulated by many growth factors and cytokines implicated in cancer growth, such as tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), platelet-derived growth factor B, ciliary neurotrophic factor and fibroblast growth factors (FGF) 2 and 10. InterfeThis study indicated that the expression of PTN was remarkably associated with TNM stage and OS. Meta-analysis revealed that the expression of PTN was not associated with tumor size, LNM, DM and histological grade. These three included studies appeared significantly statistical heterogeneity for LNM and the five studies for histological grade. This heterogeneity might have been a result of several design discrepancies among the studies for LNM, including the criterion of high PTN expression, which was obviously different in Wang et al’s study in 2015. When the outlier study was eliminated from the meta-analysis, there existed no proof of heterogeneity in the remaining studies (P = 0.39), and a meta-analysis demonstrated the LNM was significantly related to the high PTN expression. In the same way, this heterogeneity for histological grade might have been from different tumor types in the Yao et al’s study in 2009. There was no evidence that heterogeneity existed in the left studies when excluding outliers from meta analysis (P = 0.97). Meta-analysis showed that high histological grade was significantly correlated with the high PTN expression. These results showed that the overexpression of PTN was closely relevant to invasive behavior of tumor cells and PTN was a prospective biomarker to forecast the prognosis of tumour patients.In addition, PTN plays important roles via different pathway in different tumors. Over-expression of PTN in three breast cancer cell models has resulted in increased and rapid cancer growth characterized by extensive remodeling of the microenvironment, including increased angiogenesis and striking increases in mouse protocollagens Ialpha2, IValpha5, and XIalpha1, as well as elastin and matrix metalloproteinase-9. The PTNThe result of this meta analysis should be explained under several important constraints. In evaluating the association between PTN expression and LNM/ histological grade, the heterogeneity detection indicated significant heterogeneity. The heterogeneity might be caused by different tumors and different cut-points of high PTN expression. Moreover, some studies of small sample might also contribute to the formation of heterogeneity. Aslo, there might be different proportion of advanced tumors in different research centers, which could be a cause of heterogeneity.Secondly, P value in Egger’s test showed significant difference in the TNM stage group. This meant that there was publication bias in the TNM stage group. Bias was mainly due to the inclination of positive publication and the ignore of negative results. Publication bias could only increase the unreliability. In addition, the summary in meetings was excluded, which might lead to publishing bias.Thirdly, although most data were directly available in research, some studies only offered survival curves, which leaded to possible deviations between estimated and actual statistical data. In order to reduce the deviation as much as possible, detailed steps had been taken.At last, population primarily came from East Asia and did not well represent the population all over the world.Generally speaking, this meta-analysis suggests that the high expression of PTN is significantly relevant to advanced TNM stage and poor OS and can serve as a promising biomarker to predict unfavorable survival outcomes. PTN may be a potential target for tumor treatments. Meanwhile, the high expression of PTN is not associated with tumor size, LNM, DM and histological grade. So, larger scale, multicentre and higher quality studies will be needed to verify our results.S1 File(DOC)Click here for additional data file.


This is a retrospective study to investigate the effects of Carboxyhemoglobin (COHb) and Methemoglobin (MetHb) levels in the diagnosis and prognosis of Pulmonary Thromboembolism (PTE).Cases that were confirmed with PTE diagnosis using CT Pulmonary Angiography (CTPA) or Ventilation/Perfusion Scintigraphy were accepted as pulmonary embolism. And patients which were excluded using the same methods were accepted as the control group. Patients with carbon monoxide poisoning, Chronic Obstructive Pulmonary Disease (COPD), sepsis, pneumonia, asthma, idiopathic pulmonary fibrosis, bronchiectasis, decompensated cardiac failure or those who used drugs that cause methemoglobinemia  were not included in the study.2 levels in the group excluded for PTE diagnosis were statistically significantly higher (p=0.028). In our study, six of our patients (8.1%) died in the early stages because of PTE.In our study, 462 patients were examined with an initial PTE diagnosis. Among these patients, 107 patients who met the inclusion criteria were included in the study. The mean age of all patients was 56.44 ±17.3 years (21–86) and the mean age of patients with PTE diagnosis was 55.3 years and the mean age of excluded patients was 59 years (p:0.27). When the blood gas parameters of both groups were compared, COHb levels in the groups with PTE diagnosis were statistically significantly higher (p=0.001), and the POIn our study, COHb level was found to be statistically significant in the group with PTE. However, this value was not higher than the normal COHb level in the blood. We found that MetHb and COHb levels were not statistically significant in the prognosis of PTE. Pulmonary Thromboembolism (PTE) can be defined as blocking of the pulmonary artery or one of its branches with materials  from another part of the body –3. PTE iCarbon monoxide (CO) can bind to the place in the hemoglobin (Hb) molecule that oxygen binds and thus remove oxygen from hemoglobin . IncreasIn order for hemoglobin to bind reversibly with oxygen and carry oxygen to tissues, iron should be kept in ferric (Fe 2+) form. Hemoglobin in Ferric (Fe 3+) form which has oxidized iron atom and is unable to bind oxygen is called MetHb –17. In sOur objective was to investigate whether COHb and MetHb levels were contributed to PTE diagnosis and prognosis in patients who were examined for PTE in our center.This is a retrospective study to investigate the effects of COHb and MetHb levels in the diagnosis and prognosis of pulmonary thromboembolism. Patients suspected of PTE who presented to the Chest Diseases Outpatient Clinic and Emergency Department of the School of Medicine of Akdeniz University between 01.11.2015 and 31.08.2016 were included in the study.Patients admitted to Chest Diseases Outpatient Clinic and Emergency Department with complaints of chest pain, shortness of breath, palpitation or having PTE pre-diagnosis by clinical and laboratory signs were recorded in our hospital automation system. Afterwards diagnosis was confirmed with related diagnostic procedures or excluded. The name and protocol numbers of the patients with diagnosis code I26 (Pulmonary embolism), I26.0 , I26.9  from the hospital automation system were recorded. Demographic characteristics and clinical information of patients were collected twice in our hospital. We examined both forms of medical records (handwritten and electronic). In the event of unrecorded data or if any discrepancy appeared in either one of the sources, the respective case was rejected.The patients were divided into two groups. Cases that were confirmed with PTE diagnosis using CT Pulmonary Angiography (CTPA) or Ventilation/Perfusion Scintigraphy were accepted as pulmonary embolism. And the patients which were excluded using the same methods were accepted as the control group. CTPA and V/P scintigraphy reports were given by expert radiologists.Patients with CO poisoning, Chronic Obstructive Pulmonary Disease (COPD), sepsis, pneumonia, asthma, idiopathic pulmonary fibrosis, bronchiectasis, decompensated cardiac failure which could cause carboxyhemoglobinemia or those who used drugs that caused methemoglobinemia , positive smoking status at the time of admission and absence of blood gas analysis on arrival were not included in the study. The diagnosis of COPD was ruled out by pulmonary function test.Well’s score and Pulmonary Embolism Severity Index (PESI) at the time of arrival was calculated based on the appropriate baseline clinical, demographic, and serologic characteristics of each patient using the values retrieved from the computerized medical records system.2, PO2, MetHb and COHb values in blood gas were recorded.Demographic and clinical characteristics including age, heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure of all patients were recorded. D-dimer, troponin, Brain Natriuretic Peptide (BNP), creatinine levels, and full blood counts were entered in data form. D-dimer level > 0.55 mg/dl, BNP level 100 mg/dl and troponin level >0.01 mg/dl was accepted as significant. Arterial blood gas measurements taken at ambient temperature at the early stage following the complaints of patients monitored in the Emergency Department (before oxygen therapy), outpatient clinic and/or Chest diseases Department were entered in the data form. pH, PCOPatients diagnosed as having acute PTE were classified, based on early mortality risk, in groups of high (massive PTE), intermediate (sub-massive PTE), and low risk (non-massive). Patients with hemodynamic instability  were considered affected by high-risk PE and therefore as candidates for thrombolytic therapy. A PESI score greater that 85 points was considered as indicative of intermediate risk in hemodynamically stable patients. Patients characterized by intermediate-risk status and at the same time imaging and biochemical findings compatible with Right Ventricular (RV) dysfunction and/or myocardial necrosis were classified as intermediate risk patients. Finally, hemodynamically stable patients with acute PTE and a PESI score less than 85, with no RV dysfunction or myocardial necrosis were considered as low risk.W-test. Since Shapiro–Wilk’s test results showed the fitting of the observed data against a normal distribution, and statistical analysis of clinical data between two groups consisted of unpaired t-tests, whereas the Chi-square/Fisher’s exact tests were used for categorical variables. Analyses were performed with IBM SPSS Statistics for Windows, Version 20.0  software and two-tailed P value less than 0.05 was considered statistically significant.Results were reported as the mean ± SD and categorical variables were given as percentages. The normality of distribution was confirmed by the Shapiro-Wilk’s The study was approved by the Ethics Board of School of Medicine of Akdeniz University.In our study, totally 462 patients were evaluated for PTE pre-diagnosis. In 302 patients PTE diagnosis was verified, whereas in 160 patients PTE was excluded. In PTE group 228 patients and in other group 127 patients were excluded from the study because of various causes . Finally total 107 patients having inclusion criteria were included in the study .Basic clinical and laboratory characteristics of the patients enrolled in the study are shown in 2 levels in the group excluded for PTE diagnosis were statistically significantly higher (P=0.028)  were significantly higher in the group diagnosed with PTE, no significant difference in other parameters was found between these two groups. When the blood gas parameters of both groups were compared, COHb levels in the groups with PTE diagnosis were statistically significantly higher (P=0.001), and the POP=0.028) .When sub-group analysis of patients diagnosed with PTE was made, troponin (P=0.0001), BNP (P=0.002), D-dimer (P=0.001) levels, Pulmonary Artery Pressure (mPAP) (P=0.023) and Wells (P=0.016) and PESI (P=0.001) scores in patients diagnosed with massive and sub-massive PTE were significantly higher compared to patients diagnosed with non-massive PTE. There was no significant difference between the two groups for all other parameters .No statistically significant correlation was found in regard to PESI, Wells score, troponin and D-dimer levels of both COHb and MetHb in the Spearman correlation test.In our study, six of our patients (8.1%) died in the early stages because of PTE. Four (66.6%) of the patients were male and 2 (33.3%) were female. When deceased and survived patients were compared, mean Wells and PES score, D-dimer and troponin levels were significantly higher in deceased patients. No significant difference was found in any of the investigated parameters .Pulmonary embolism is a disease, which is commonly seen in the chest diseases practice and has a mortality rate of 10–15% within the first three months period after the diagnosis ,20. It iThere is no single laboratory marker for definite diagnosis of PTE. Therefore, studies are mostly focused on an ideal marker that provides a diagnosis. Ideal prognostic and diagnostic markers should be easily evaluated and tested. MetHb and COHb are values that can easily be measured in the blood gas.Various biochemical markers are used for PTE diagnosis. The most known and widely used of these is D-dimer test. The level of D-dimer, which is a specific fibrin split product, can increase in Deep Vein Thrombosis (DVT), PTE patients, atherosclerotic cardiac diseases, renal diseases, mesenteric diseases, and cerebrovascular stroke ,2,22–24.2 levels were significantly lower in the group with PTE diagnosis, however, no statistically significant difference was found for pH and PCO2 levels. In the study conducted by Masotti et al.  and the mean age was 55.3 years in patients diagnosed with PTE. In the study of Kakavas et al. when compared with parameters that show the severity and risk of the disease such as troponin, BNP and Apache II, MetHb and COHb values were found to be significant . HoweverIn our study, COHb values were significantly higher in patients diagnosed with pulmonary embolism versus patients who were excluded for pulmonary embolism. The mean COHb value in the normal healthy population is between 0.3–2.6%. Although this value was in the normal range, it was significantly higher when compared with the control group. In the analysis of pulmonary embolism subgroup, when patients with non-massive PTE diagnosis were compared with patients with massive and sub-massive PTE diagnosis, no significant difference was found between COHb levels. In the study by Kakavas et al., COHb values in patients diagnosed with high risk (massive PTE + sub-massive PTE) PTE were low, however, our study does not support this. COHb levels were low in mortality patients in Kakavas et al’s study . TherefoNo significant difference in MetHb values was found between the group with PTE diagnosis and the group excluded for PTE diagnosis. When we look at the subgroup analysis of the group diagnosed with PTE, the low risk group and medium and high risk groups were compared and no significant difference was found for MetHb levels. Kakavas et al. reported that MetHb levels could rise in the high risk group with PTE diagnosis . HoweverOne of the three clinical conditions; massive, sub-massive and non-massive is found in PTE. Massive PE is seen in 4.2% of all PE cases and has a mortality rate of 58% , medium risk (sub-massive) or low risk (non-massive) patients for early mortality will determine treatment options (anticoagulants/thrombolytic) and prognosis. Several clinical scoring methods are used for prognostic evaluation. The most commonly used is PESI . Using 1RV dysfunction is an important prognostic indicator of PTE. Although echocardiogram (ECHO) is not routinely used in PTE diagnosis, it can be used for unstable patients who present with hypotensive shock, since it can show thrombus in right cardiac cavity and right cardiac failure ,22, 23. In literature Schuerholz et al.  found thOur study had its own limitations. The main limitation of this study is its retrospective observational design. Consequently, the data of a few patients could not be retrieved. However, it was possible to verify the data included in our study from different sources , and therefore, we consider them to be adequately precise. An additional limitation was the small number of patients in each subgroup that made statistical analysis difficult. Thus, our results should be interpreted with caution.Consequently PTE is a frequent disease that could result in mortality. In our study, COHb level was found to be statistically significant in the group with PTE. However, this value was not higher than the normal COHb level in the blood. Different from the only study in the literature, we found that MetHb and COHb levels were not statistically significant in the prognosis of PTE. We think that this difference is caused by the characteristics of the patient population. We believe that, this should be supported with prospective studies.


Background: Substance-related addictive disorders are known to be overrepresented in non-heterosexual individuals, but it is largely unknown whether this is also the case for behavioral addictions such as problem gaming and gambling. This study aimed, in a pilot web survey design, to assess whether problematic gambling, gaming and internet use may be more common in individuals with a non-heterosexual orientation.Methods: An online survey was distributed through media and social media, and answered by 605 individuals . Problem gambling, problem gaming and problematic internet use were measured through structured screening instruments .Results: Problem gaming and problematic internet use were significantly more prevalent in non-heterosexual subjects. Instead, problem gambling did not differ between heterosexual and non-heterosexual respondents. Psychological distress and social media use for more than 3 h daily were significantly more common in non-heterosexual respondents. In the overall sample, gaming and gambling were associated statistically.Conclusion: Based on the present pilot online survey, problematic gaming and internet use, but not problem gambling, may be more common in non-heterosexual populations. This area merits more and larger studies, and potentially preventive efforts aimed for non-heterosexual individuals in the population. Possible explanations and study limitations are discussed in the paper. Gambling disorder, listed as one of the addictive disorders in the DSM-5 manual , is beliIn sexual minorities, i.e., individuals with a sexual orientation other than heterosexual, research related to gambling and gaming is scarce. In contrast, an overrepresentation of alcohol and illicit drug use disorders is well documented . EspeciaIn addition to the overrepresentation of non-heterosexual individuals in other addictive disorders, specific factors call for the study of gambling- and gaming-related problems in people identifying as non-heterosexual. Online games may offer opportunities for gender swapping, ‘avatar’ naming, and experimentation with sexual identification, to an increasing extent compared to the ‘real world’ setting . On the Based on this research gap, the aim of this pilot study was to investigate whether the prevalence of problem gambling, problem gaming and problematic internet behavior may differ depending on sexual orientation or gender identity.Data collection was performed with a web-based questionnaire, designed as a self-selective test distributed online between April and June 2017, where the participants clicked a web-link to access the survey. The survey was spread online and presented as a self-test for problem gaming and problem gambling, aiming to address individuals above 15 years of age. The survey was promoted through online advertising in social media and in Swedish news media , and two universities assisted in spreading the survey online among students and staff. In order not to bias the inclusion of individuals with respect to sexual orientation or other socio-demographic or other variables, the test did not specifically address any of these sub-groups.heterosexual, bisexual, homosexual, and other. In the analysis, sexual orientation was divided into two categories; heterosexual represented one group, while homosexual, bisexual and other represented one group together, categorized as sexual minority group in this study. Given the low number of transgender respondents, no specific analysis was carried out for transgender identification as a potential risk factor.Participants were asked to define sexual orientation, and could choose between The researchers collaborated with a marketing survey company, which set up the questionnaire electronically and handled the incoming data. IP addresses were blocked when collecting data, such that the survey was completely anonymous. It was mandatory to answer all of the questions to be able to continue to the next page in the survey. One question had the response alternative “do not want to answer” and those answers were handled as missing data and excluded in the analysis. The survey was carried out in Swedish, however, with an option to choose from a range of minority languages (very few respondents chose another language than Swedish). Given the pilot and descriptive nature of the study, no power calculation was carried out, and the study included subjects until the pace of study inclusion slowed down.Informed consent online was necessary for the survey to open. The study was approved by the regional ethics committee, Lund, Sweden (file number 2017/16).All measures in this investigation Table  were sel1.The NODS-CLiP , validated for the screening of problem gambling, indicated by one or more affirmative answers .2.The Gaming Addiction Scale (GAS), validated in a Dutch population , for the3.The Problematic and Risky Internet Use Screening Scale 3 (PRIUSS) , consistAt the end of the survey, a recommendation was provided to the respondents; risk behavior  was communicated, along with a recommendation to seek help, and with a stronger emphasis for participants reaching the higher problem level. Cut-offs for this risk assessment were the scoring of one (three) CLiP items, at least ‘sometimes’ on four  GAS items, or six (nine) or more on the PRIUSS.U-test was used calculating continuous data and Chi-Square test for categorical data.All statistical analyses were performed in SPSS version 24. Statistical associations were calculated between problematic gambling, problematic gaming, internet behavior, sexual orientation, number of hours communicating with others online, experience of social contacts outside the internet and experienced need for seeking health care because of psychological distress. Mann Whitney n = 356), 34% (n = 203) were studying, 4% (n = 27) were retired and 2% (n = 11) were job seeking. Heterosexual was the most common sexual orientation  and 10% (n = 62) defined as homosexual, bisexual or other. There were 45% (n = 272) defining as men, 52% (n = 312) defining themselves as women and 1% (n = 6) defining as transgender [gender was missing in two percent (n = 15)].Answers from 943 participants were collected in the online inquiry, 605 of which were fulfilled and further analyzed. The median age was in the range 30–39 years. Most participants were employed . In contrast, the median GAS value was significantly higher in the non-heterosexual group (13.0 [IQR 8-17.25]), than in the heterosexual group (9.0 [IQR 7-14]) and the difference between the groups reached statistical significance (p < 0.001). Reaching the GAS threshold for problem gaming was more common in non-heterosexual  than in heterosexual individuals . The median value in PRIUSS 3 was 3.0 (IQR 1-5) in the heterosexual group and 4.0 (IQR 2-7) in the non-heterosexual group (p = 0.02). Also, social media use for more than 3 h daily was more common in non-heterosexual  than in heterosexual respondents . The experienced need for seeking health care because of psychological distress was 61% (n = 38) in the non-heterosexual group, significantly higher than in the heterosexual group where the corresponding percentage was 41% , whereas social isolation, measured as a too low number of social contacts outside the internet, was not more common in non-heterosexual respondents  than in heterosexual individuals . GAS was significantly higher in problems gamblers (p < 0.001), whereas the PRIUSS score was not associated with problem gambling (p = 0.91).Problem gambling was not more common in non-heterosexual respondents than in heterosexual . There are still few studies in the area, and it has been described that risk factors of these two constructs are only partially overlapping . While spost hoc analysis was run for the variable most commonly missing . This small group of subjects did not differ significantly from individuals with gender data available; neither with respect to problem gambling (p = 0.39), problem gaming (p = 0.92), PRIUSS value (p = 0.80) or the need to seek treatment for psychological distress (p = 0.45). Thus, at least from the present data, no systematic differences could be seen with respect to non-substance-related addictive behaviors or psychological distress for the few subjects who did not report gender data.The present pilot study has limitations. This study had a self-selective study design, which may attract mainly participants with a certain interest in gambling, gaming and internet use, and participants in our study were mainly younger adults. Also, the absolute number of non-heterosexual individuals was low, which limits the transferability of the result to sexual minority group. In addition, due to a technical problem, some study items were possible to skip although this was not intended by the authors, such that there were some missing data for a total of 21 respondents, although only for some items. Despite a low number of missing data, a Also, previous literature has suggested that study questionnaires may demonstrate some invariance in psychometric properties depending on individuals’ sexual orientation. While it is beyond the scope of the present study to further analyze this, it should be borne in mind that our knowledge is limited concerning how instruments addressing gambling, gaming and internet behavior are perceived by individuals from different sexual groups. Likewise, due to a low number of respondents identifying as transgender, the present study does not allow for analyses of other gender identifications; thus, future studies need to include sufficiently large number of respondents for a sub-analysis of transgender individuals to be possible.In conclusion, this pilot web survey studied potentially addictive behaviors, which have been very sparsely addressed in previous literature, with respect to sexual minority status, and demonstrated that problem gaming and problematic internet use may be more common in non-heterosexual groups. In behavioral addictions, emerging as problematic in recent years, sexual orientation may need to be addressed in prevention and assessment, and more research in the area is warranted.The study, including its design, information, and consent procedures, was approved by the Regional Ethics Committee Lund, Sweden (file number 2017/16). All participants provided informed consent .AH was the main responsible of the study. NB was responsible of the practical planning of the study, under AH’s supervision and also wrote the main part of the manuscript. Both authors were carried out the statistical analyses and read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AH receives an overall research funding from Svenska spel AB, the government-owned Swedish gambling monopoly. This funding is non-project-specific  and does not affect the research idea, study design or interpretations of results of the study.


Objectives: Studies on survival of people with clinical diagnosis of dementia can provide estimates of care outcomes of a health system and offer real-life insights on how to provide better support for the target population. This study aims to estimate survival from the point of recorded diagnosis of dementia, compared with people without dementia. Methods: This case-control study used data from Clinical Data Analysis and Reporting System (CDARS), a population-wide databased managed by Hong Kong Hospital Authority. All patients aged 60 years or over with a first-ever code for dementia from 2001 and 2010  were matched with patients without dementia by sex and index date at a 1: 2 ratio. We adopted Cox proportional hazard model to estimate hazard ratios, with and without adjustment for age, sex, and comorbidities . Results: A total of 5,847 patients have a diagnosis of Alzheimer’s disease (AD), and 7,729 have vascular dementia (VaD). The median survival time, calculated based on the Kaplan-Meier estimator, for patients with dementia of any kind, AD, and VaD were 1163, 2448, and 1268 days, respectively. Compared with the control group, the raw and adjusted hazard ratios for dementia were 2.78  and 1.14 (1.13-1.17), respectively. Conclusions: Median survival times were much lower than figures reported by other regions and in screened populations. The high risk of death may be an indicator of late diagnosis and hence call for promoting early diagnosis to ensure timely intervention.


We present a case of herpes simplex virus-1 encephalitis (HSVE) and discuss the difficulty of early diagnosis and the possibility of a wrong or delayed diagnosis and treatment of this encephalitis. We show the importance of considering HSVE to pursue every case of suspicious medical liability. Herpes simplex virus-1 (HSV-1) encephalitis (HSVE) is a rare viral infection of the human central nervous system (CNS) entailing neurological dysfunction. However, it is the commonest infectious cause of sporadic encephalitis. The annual incidence of HSVE worldwide is estimated to be 1–4 cases/1,000,000 .HSVE has a bimodal age distribution, with peak incidences in children less than 3 years old and those aged 50 years or more. Most cases occur in subjects older than 50 years of both sexes. HSVE is difficult to diagnose and has a poor prognosis. Morbidity and mortality are greater if treatment is delayed or inadequate. In these cases, there could be medicolegal consequences, particularly legal liability for medical malpractice and nervous system injury assessment. We report the case of a 60-year-old man with HSVE.A 60-year-old diabetic patient with chronic kidney disease, and treatment with corticosteroids for nephrotic syndrome, came into our emergency room. He presented with fever, dyspnea, and disorientation and was in a fugue state with naming difficulties and aphasia. A complete blood count showed a white blood cell count of 14,630/ml and his C-reactive protein was 1.2 mg/dl . A computed tomographic scan was negative for brain injury. Cerebrospinal fluid (CSF) tests were positive: the fluid was turbid, glycorrhachia was 141 mg/dl , proteinorrachia was normal, and the CSF white cell count was 135/UI  with a left shift (90% neutrophils and 10% lymphocytes). The patient was given broad-spectrum antibiotic therapy while awaiting the CSF culture results. Two days later, the patient was comatose, with right hemiplegia. He did not obey simple commands and opened his eyes only after painful stimulation. The CSF culture was negative for bacteria, but viral DNA corresponding to HSV-1 was detected in the fluid. Magnetic resonance imaging detected diffuse signal changes in the cortical and subcortical matter, especially in the frontal-temporal region and the parietal region in both cerebral hemispheres, but particularly in the left hemisphere. Doctors diagnosed herpetic encephalitis. They prescribed acyclovir treatment at a dose of 750 mg/250 ml in 3 h three times a day for 21 days because the patient's glomerular filtration rate ranged from 10 ml/min to 50 ml/min. The patient was moved to a rehabilitation facility after 21 days. At discharge from the rehabilitation facility, the patient had a percutaneous endoscopic gastrostomy (PEG) and experienced hyperactivity of the muscle stretch reflex with extension of the knee on the right side. He was able to move his right foot, extend his right knee, and walk unassisted, but he had some problems with his dynamic balance.Six months later, the patient underwent brain MRI, which showed a large unenhanced signal alteration. This alteration was consistent with a malacic area of gliosis in the left temporal lobe and to a lesser extent in the left frontal lobe, in the corona radiata, and in the centrum semiovale. There was also ex vacuo dilatation of the right-left ventricle. On the right side, the signal was iperintense in the temporal, frontal, and parietal periventricular white matter.Ten months after the onset of encephalitis, the patient was treated with PEG for recurrent dysphagia. He had a mask-like face and double incontinence. He was able to obey simple commands but was unable to speak. He had joint limitations in the shoulders, elbows, and hands, with extrapyramidal side effects and pyramidal hypertonia of the upper limbs. The patient had lost all motor function and was totally dependent.There are two main types of HSVE, primary and recurrent. In more than 70% of cases, HSVE is caused by the reactivation of a latent virus in individuals who have previously been infected. Once reactivation has occurred, viral particles are transported via the anterograde axonal transport via the olfactory and trigeminal pathways to the CNS . In 30% d-aspartate) receptor encephalitis.In many cases, the presentation of encephalitis is monolateral in the beginning, but the lesions gradually become widespread and bilateral, and they affect the contralateral temporal lobe asymmetrically. HSVE sometimes affects the occipital cortex. The lesions are uneven and asymmetrical. Herpetic encephalitis is marked by necrotic-hemorrhagic lesions, with perivascular lymphocytic infiltration in the necrotic tissues and the meninges . These rIn most patients, encephalitis develops monophasically. In some cases, the patients return to their doctors after treatment, with an apparent clinical relapse. These patients can be of any age, with a large variety of neurological manifestations, including behavioral or personality changes, memory loss, and seizures. Negative prognostic factors are advanced age, coma or a depressed level of consciousness at onset, and a delayed specific antiviral treatment. Normal electroencephalography predicts survival independently of possible confounders . An earl


Sunscreens were prepared with 2.5% w/w caffeine or in the absence of this compound. In order to evaluate the safety of these formulations, stratum corneum hydration, skin barrier and colorimetry were assessed in vivo in healthy subjects before and after skin treatment with the samples. The efficacy of the sunscreens was assessed in vitro, using PMMA plates and a spectrophotometer equipped with an integrating sphere; and in vivo by the determination of the sun protection factor (SPF). None of the formulations caused erythema or impaired the skin barrier function. The in vitro functional characterization showed higher SPF values for the caffeine formulation. The in vivo studies also confirmed the higher SPF value of the formulation combining caffeine with the filters, compared to the caffeine-free sample. This improvement contributed to an increase of, approximately, 25% in the in vivo anti-UVB protection. In conclusion, caffeine was well tolerated by the skin and increased the photoprotective activity, being a new alternative adjuvant in sunscreens formulation.The excessive exposure to ultraviolet (UV) radiation is the main cause of skin cancer, the most commonly diagnosed cancer in the world. In this context, the development of innovative and more effective sunscreens, with bioactive compounds like caffeine, displaying antioxidant and anticancer potential, is required. This research work assessed  The excessive exposure to ultraviolet (UV) radiation has led to an increase in skin cancer, the most common type of cancer diagnosed in the world , thus inInnovative sunscreens aim to fully protect the cutaneous tissue from the deleterious effects of UV radiation, which is considered an important risk factor associated with skin cancer . This di2/h , avobenzone (3.0%) and titanium dioxide (5.0%). Oil-in-water emulsions were prepared in the absence of caffeine or containing this bioactive compound at 2.5% w/w, as shown in ®, Epitest) containing either 2.5% w/w caffeine sunscreen formulation, caffeine-free sunscreen formulation, or filter paper disk soaked in distilled water (negative control), were applied at each site for 24 h.Twelve healthy male and female volunteers participated in the study, after oral information and written consent. This procedure was performed in accordance with the Helsinki Declaration and with the ethical standards of the local responsible committee on human experimentation. Three sites were marked in the volar forearm of the volunteers. Epicutaneous patches (Finn ChambersStratum corneum (SC) hydration was evaluated with a Corneometer® CM825 (CK Electronics GmbH), and skin barrier function was probed through the transepidermal water loss (TEWL) measured by a Tewameter® TM 300 (CK Electronics GmbH), according to the guidelines of ® Chroma Meter CR-300 (Minolta Camera). The parameter a∗ provided by the device reflects the red chromaticity and can be used to quantify an increase in erythema . The formulations were weighed (0.75 mg/cm2) and uniformly applied over polymethylmethacrylate (PMMA) plates, mimicking the rough skin surface. Samples were arranged in a suitable container covered with quartz plate, to avoid ambient interference, and thus exposed to the sunlight. The exposure of the formulations to solar radiation was conducted between late April and early June of 2014, for 2 h (11 a.m. to 1 p.m.), in São Paulo city, SP, Brazil, with an estimated irradiation intensity of 151.75 mW/m2 (0) and one after the solar stress (tf), being measured after 120 min  solar UV simulator was used. Studies were conducted by IPclin  (The t Method . The tes Brazil) . SPF val Brazil) :® (Version 7) software was used, with a significance level of 5.0% (α = 0.05).Statistical analysis of the data was performed using one-way ANOVA test followed by the Tukey test for multiple comparisons. The GraphPad PrismResults were analyzed as the ratio between the values obtained in each site after patch application and its respective basal values, thus decreasing the impact of inter-individual variability. Although a slight increase in SC hydration was observed, probably attributable to occlusion or to the emollients in the O/W emulsion, no differences were established among the sites treated with the formulations and the negative control . No sign0 and tf)  and at 2.5% w/w caffeine, in different solar irradiation times (t and tf) . AccordiThe value measured in the 2.5% caffeine formulation, with SPF of 19.34, was statistically significantly higher when compared to the caffeine-free sample, with SPF 15.43 .in vitro and in vivo tests when compared to the caffeine-free sample. This improvement contributed to an increase of, approximately, 25% in the in vivo anti-UVB protection. In addition, the in vivo skin compatibility assays showed that the formulation with caffeine did not cause a negative impact in SC hydration or in skin barrier function, nor did they cause any erythema, even when applied under occlusion for 24 h.The sunscreen formulation containing caffeine at 2.5% w/w presented a higher SPF value on both 7. Other studies have shown the anticancer effects of caffeine. It was demonstrated that the topical application of caffeine possibly caused apoptosis in preneoplastic cells , Nevertheless, when in association with the sunscreen system, containing two chemical UV filters - ethylhexyl methoxycinnamate and avobenzone - and the physical filter titanium dioxide, it acted as a SPF enhancer. This improvement can probably be attributed to an antioxidant or an anti-inflammatory activity, attenuating the erythema caused by the UV radiation or even, delaying the erythema formation. Additionally, caffeine contributed as a photostabilizer for the chemical filters, which are known, when associated, to undergo an irreversible photochemical reaction leading to loss of UV protection . Other s2mol-1, possibly not being enough to develop on its own a substantial SPF  occurred slower under oxidative conditions in the presence of UV/TiO2. Noteworthy, in other systems studied, the authors have achieved very similar results in the identification of species formed by caffeine degradation. Therefore, degradation of caffeine is likely to generate persistent organic intermediates that are not so efficiently oxidized as compared to caffeine and this could be the explanation to increased photoprotection.Caffeine has been reported  to scave species . The prond NH2Me . Accordiin vivo and to beneficial actions (One other hypothesis is that caffeine (1) could be metabolized when topically applied on the human cutaneous tissue, and these metabolites might be related to the enhanced photoprotection obtained  actions . Caffein actions . Paraxan actions . Another actions . Theophy actions .In conclusion, caffeine and some of its metabolites could be acting beneficially in the photoprotection and antioxidant activities, besides a relevant photostabilization profile. In this research work, the interest of combining caffeine with UV filters in a sunscreen formulation was established, and its cutaneous biocompatibility was also confirmed. However, a phototoxicity assay would be indispensable to fully assess the safety of this type of ingredient. Higher SPF was obtained when caffeine was combined with the UV filters ethylhexyl methoxycinnamate, avobenzone and titanium dioxide. Caffeine seemed to be, thus, an interesting bioactive compound for use in sunscreens, acting in synergy as a photoprotector and a photostabilizer.This study was carried out in accordance with the recommendations of international standards and International Sun Protection Factor Test Method, . The proAB and CR conceived and designed the experiments. VT, CR, FS, and CdO performed the experiments. CdO, CR, RS, RP-F, and AB analyzed the data. CR, TdA, EM, CdO, RS, RP-F, MV, and AB wrote the manuscript.FS was employed by IPclin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of the present study is to examine how moderate-to-severe ulcerative colitis (UC) is currently managed in real-world clinical practice across the United States (US) and European Union Five .Data from the 2017 Adelphi Inflammatory Bowel-Disease Specific Programme (IBD-DSP) were used. The IBD-DSP is a database of patient chart information abstracted by selected gastroenterologists across the US and EU5. Eligible gastroenterologists who agreed to participate were asked to complete patient record forms for the next seven consecutive eligible adult patients with UC. Only charts from patients with moderate-to-severe UC were included in the analysis (defined as those with documented administration of either an immunosuppressant [IM] or a biologic). Treatment patterns were reported descriptively.i.e., biologic therapy with a concomitant IM) in first line generally varied between 10–20% , 10.8%; infliximab (IFX), 18.2%; EU5: ADA, 12.5%; IFX, 19.9%), though increased in later lines in the EU5. Among patients currently using a biologic therapy, between 10–40% of patients used a higher than indicated dose or greater than indicated dosing frequency during maintenance . In both the US and EU5, the primary reason for switching therapy was efficacy-related.411 and 1191 patient charts were included in the US and EU5 , respectively. For those with complete treatment history, 40.7% and 52.9% used either an IM or biologic as their first treatment (with or without steroids). Usage of these therapies increased in subsequent lines. The percentage of patients treated with combination therapy (In this analysis, many patients with moderate-to-severe UC use an IM or biologic as their first therapy after diagnosis. Combination therapy and dose escalation are also common, and underscore the challenges with managing this patient population. Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the colon that is characterized by intermittent periods of disease flaring and remission , 2. UC ae.g., from the American College of Gastroenterology , corticosteroids, immunosuppressants [IMs]), biologic therapies  and/or small molecule JAK inhibitor (i.e. tofactinib [Pfizer Inc]) to achieve clinical goals depending on severity of disease.The primary therapeutic goal in UC is to induce and maintain long-term disease remission ; howeverterology , the Eurterology , and theterology ) have beHowever, it remains unclear how moderate-to-severe UC is currently managed in real-world clinical practice. A few studies have examined the treatment patterns of UC, though they have often relied upon administrative claims databases and were conducted prior to the approval of several of the available treatments. For example, an article by Loftus and colleagues (2014) examined treatment patterns among patients who initiated IM therapy but, by definition, did not include patients who were treated by biologic therapy . ConversThe goal of the present study was to use medical record data and examine how patients with moderate-to-severe UC are currently treated across clinical practices in the US and Europe. Specifically, the objectives of this study were to assess the treatments used by sequential line of therapy, the frequency of IMs being used in combination with biologic therapy, the frequency of dose escalation with biologic therapies, and the major reasons for treatment switching.Data from the 2017 US and European Union Five  Inflammatory Bowel Disease (IBD)-Disease Specific Programme (DSP) were used. The DSP data consists of medical chart information abstracted by each patient’s physician. The methods of the DSP have been previously published , though i.e., gastroenterologists had to be board-certified, have been a qualified physician for between four and 40 years, make treatment decisions for more than eight patients with Crohn’s disease and seven patients with UC per month, and be active in the treatment management of their patients). Eligible gastroenterologists who agreed to participate in the IBD-DSP were then asked to complete patient record forms for the next seven consecutive eligible patients with UC. Patients were considered eligible if they were adults with UC and had a history of moderate-to-severe disease. More specifically, patients were eligible to be included in the IBD-DSP if they were 18 years or older, had a diagnosis of UC, had received either a steroid, IM, or biologic for their UC, had been considered moderate or severe at some point based on the physician’s perception, or had a full Mayo score of >4 at some point. The patient record form was completed using an electronic data collection platform and included questions on the patient’s demographics, clinical state, current treatment, and general patient management.To acquire these data for the IBD-DSP, gastroenterologists in the US and EU5 were recruited by phone to participate in the study. Potential physician respondents were identified from publically available lists of healthcare professionals. Field-based interviews were then conducted to ensure eligibility , employment status, height and weight , smoking status, and disease duration were all abstracted from the medical charts.i.e., prior treatments along with the reason(s) for switching) was also reported.The current treatments prescribed, their method of administration, dose and frequency, and duration of treatment to date were all abstracted. Complete treatment history  and were largely descriptive, reporting counts and frequencies for categorical variables and means and standard deviations for continuous variables.A total of 411 patient charts from the US were included in the analyses; 53.0% of the patients were female and the mean age was 44.2 years (standard deviation [SD] = 14.2). The mean duration since diagnosis was 4.5 years (SD = 5.0) . Across i.e., the documentation of all treatments used since diagnosis) were included in the overall treatment patterns analysis . Treatments used by line of therapy are reported in To assess the full chronology of the treatments used, only patient charts with a complete treatment history  began treatment with 5-ASAs and/or steroids, as their first-line treatment . Howevere.g., 35.7% in the second line and 45.5% in the third line).The pattern was similar in the EU5 . Forty-se.g., first line: ADA = 10.8%; IFX = 18.2%; VEDO = 42.9%) (IMs were often administered concomitantly with biologic therapy in the US (= 42.9%) .The frequency of combination therapy did not appreciably differ across lines of therapy, though small samples limited the extent to which this could be examined. In the EU5, combination therapy was also common .A total of 19.9% of patients using IFX also used an IM in the first line; 12.5%, 11.1%, and 7.1% of patients using ADA, VEDO, and GOL, respectively, were also using an IM. Combination therapy was more common in the second (26.1%) and later lines  compared with the first line (16.0%) across any of ADA, IFX, VEDO, and GOL.In the US, duration of treatment was longest in the second and first lines of treatment , followed by the fourth and third lines . The duration of treatment was similar across the first three lines of treatment in the EU5 group, and slightly higher in the fourth line: 55.6 weeks (first line), 56.3 weeks (second line), 56.7 weeks (third line), and 60.1 weeks (fourth line).i.e., a higher-than-indicated dose or greater-than-indicated dosing frequency). These results are reported in Among patients currently using a biologic for maintenance therapy (and who had been in maintenance for >3 months), physicians indicated the current dose and frequency prescribed. This was compared against the approved label for each treatment and used to calculate the proportion of patients using an escalated dose .For patients who used more than one therapy, the reasons for switching from their previous therapy to their current therapy were recorded. As switching decisions are often complex, physicians could identify multiple reasons for each switch. The data were organized into higher-level categories for analysis and are presented by line of therapy as shown in Tables e.g., “initial non-response”, “remission not maintained”, “lack of alleviation of pain”)  was due to an efficacy-related reason (f pain”) . Howevere.g., “lack of tolerability”, “side effects”) were the next most common reasons for switching followed closely by mode of administration/convenience.Similar results were observed in the EU5 . EfficacIt is important to assess the real-world clinical practice of therapies for UC. This study provides an updated perspective on the treatment selections, use of combination therapy, dosages used, and reasons for switching among patients with moderate-to-severe UC. Contrary to past studies that have relied upon administrative claims data –13, our Our results suggest immunosuppressants and biologics are initiated early on in the disease course for many patients. Patients who become moderate to severe  used either an IM (approximately 18%) or biologic (approximately 23%) (with or without steroids) as their very first treatment. This finding underscores the difficulty in managing these patients as many present with such severe disease that conventional therapies alone are not considered an adequate initial therapy. Further, it may also illustrate the unmet need, as with so few treatment options available, physicians may opt to be aggressive to maximize the time prior to colectomy.As expected, the use of biologic therapy increases dramatically in subsequent lines. Specifically, the use of ADA and IFX were highest, followed by VEDO (which was used disproportionately in later lines). The use of GOL was modest in both the US and EU5, as was the use of unapproved biologics.This study also explored the frequency of combination therapy. The use of an IM along with a biologic is frequently used to inhibit the development of anti-drug antibodies and maximize the efficacy of the biologic treatment . For exaAnother important aspect to the management of patients using biologic therapy is that of dose escalation or the practice of using a higher-than-labeled dose or more-frequent-than-labeled administration. As noted by therapeutic drug-monitoring guidelines , the usePhysicians also provided direct insight into their reasons for switching therapies. Reasons for switching is multifactorial but almost universally included some aspect of efficacy. Interestingly, in the US, mode of administration/convenience concerns featured prominently as reasons for switching, even more so than safety-related reasons. This suggests the importance of administrative burden and ease of dosing regimen when evaluating therapeutic options. The same was not necessarily true for patients in the EU5. Although mode of administration/convenience factors were still prominent, safety-related reasons were more frequently cited. Drug costs and other financial considerations did not frequently factor in to switching decisions for either region.Although it may be tempting to draw comparisons between regions, it should be noted that the patient populations are different. For example, patients in the EU5 were younger, diagnosed for longer, and more likely to be male than patients in the US. As there is a lack of epidemiological evidence to suggest fundamental differences in the UC patient profile across these regions, these differences are likely attributed to sampling error . Any comparisons across regions must consider the demographic differences as well, which may explain variability in treatment patterns.Several limitations should be noted. These data were abstracted from the medical chart without any auditing; any data entry errors or subjective interpretation of clinical data could have introduced additional measurement error.Overall, the number of patients in the US group was relatively low, and the number of charts with complete treatment history was also modest across both groups. This influenced the degree to which comparisons can be made between groups, across treatment lines, and across treatments themselves. Additionally, the results were purely descriptive without any statistical adjustment for confounding variables.A further limitation was the low numbers of patients reporting surgical intervention, and the lack of detail collected on the extent of the surgery. Further study would be needed to look at treatment patterns in relation to surgical interventions.The very high rates of IM and/or biologic use as first line may represent the inclusion of patients with more severe disease at presentation. Additionally, there may be selection bias for the inclusion of gastroenterologists at academic centers who may be more inclined to treat aggressively at initial diagnosis. Furthermore, it is also possible that the physicians who were willing to participate may not represent the practice patterns at large. This, coupled with the low numbers of patients in the US group, means that it is not clear the extent to which the sample of patients represents the broader UC population. More research would be necessary.In this study of real-world management of patients with moderate-to-severe UC in the US and EU5, many patients received an IM or biologic treatment as their first therapy after diagnosis. Combination therapy with both IM and biologic therapy was also commonly reported. For those patients who used biologic therapy, between 10–40% received a higher-than-indicated dose and/or frequency. The most commonly cited reasons for treatment switching were efficacy-, convenience-, and safety-related. Collectively, these findings provide an updated perspective on the real-world clinical practice of therapies for UC and reinforce the challenges that still exist in managing patients with UC in both the US and Europe.


Over the last decade, several studies investigated the outcomes in children born very preterm. Only recently there has been an increasing interest in the late preterm infants (born between 34 + 0 and 36 + 6 weeks). This population is at high risk of morbidity and mortality in the first years of life. Other studies reported that they are also at risk of long-term developmental problem. Therefore, the aim of this study is to describe the neurodevelopmental and emotional-behavioral outcome in a sample of late preterm patients.The study included late preterm children and adolescents who had neuropsychiatric and/or neurological symptoms. They underwent a general, neurocognitive and an emotional-behavioral assessment. Exclusion criteria included: patients affected by Central Nervous System congenital abnormalities, neurodegenerative diseases, genetic disorders, epilepsy, or in pharmacological treatment, or adopted children. A descriptive statistics analysis was performed to describe the sociodemographic and clinical characteristics of patients. Risk factors related to late preterm birth, prevalence of neurodevelopmental disorders, and cognitive functioning were recorded and analyzed.The sample included 68 LPI  aged from 2 to 16.3 years , who were affected by one or more neurodevelopmental disorder, including Language Disorder, Attention Deficit Hyperactivity Disorder, Specific Learning Disorder, Developmental Coordination Disorder, Intellectual Disability and Autism Spectrum Disorder. Moreover, in 30.8% of patients, internalizing problems  were detected.Our results support the importance of a long-term surveillance of late preterm and the great need for more longitudinal large population studies in order to collect data on the neurodevelopmental outcomes of this population. Over the last decade, rising rates of the preterm births have been reported; the estimated prevalence is 11.1% of all livebirths worldwide per year . PretermHowever, several studies unveiled that LPI are physiologically and metabolically immature and at risk of a major number of hospitalizations in the first years of life. –10. MoreTherefore, to support the importance of a short- and long-term surveillance of this population of infants, the aim of this study is to describe the neurodevelopmental and emotional-behavioral outcomes of a LPI population.We studied 68 patients late preterm, who were admitted to the Child and Adolescent Neuropsychiatric Unit – University of Bari “Aldo Moro”, between January 2014 and March 2016, for psychopathological or neurological symptoms. We excluded: patients affected by Central Nervous System congenital abnormalities, neurodegenerative diseases, genetic disorders; patients with epilepsy or in psychopharmacological treatment because those factors might have influenced the neurodevelopment and the neurocognitive/emotional-behavioral assessment; adopted children, in case of incomplete or absent data about pre- and perinatal history.This study was approved by the Local Ethic Committee of Azienda Ospedaliero-Universitaria Policlinico di Bari; all children were recruited after obtaining a written informed consent by their parents; in addition, informed consent was also obtained from the patients who could understand the content and aim of the study.We collected information related to: parents’ socio-demographic characteristics, family history of neuropsychiatric disorders, obstetric history  mode of delivery  and pre-term delivery causes , demographic features of the newborn  perinatal complications , psychomotor development. All patients underwent physical and neurological examination, laboratory tests .All patients were assessed by highly-trained clinicians, experts in child and adolescent neuropsychiatry. Neuropsychiatric assessment included a neurocognitive and a social-emotional and behavioral evaluation. Cognitive assessment was performed using age-related scales including: Leiter International Performance Scale - Revised (Leiter-R)  , WechsleThe academic achievement was assessed using standardized protocols including: MT Group Reading Tests for Primary School; MT Group Reading Tests for Middle School; MT Group Advanced Reading and Mathematics Tests for the first biennium of Secondary School; Battery for the Evaluation of Developmental Dyslexia and Dysorthography for Primary and Middle school; Evaluation Tests of Calculation Ability for Primary School and Evaluation Tests of Calculation Ability and Problem Solving for Middle School –23. SociDescriptive statistics were used to describe the sociodemographic and clinicals characteristics of patients. Risk factors related to late preterm birth, prevalence of neurodevelopmental disorders, and cognitive functioning were recorded and analysed. All statistical analysis was conducted using the SPSS software package (version 20.0).Socio-demographic features of LPI are described in Table Late preterm risk factors are summarized in Table Neurodevelopment disorder diagnoses are specified in Table The important increase of late preterm births has been partially related to the greater use of reproductive technologies, and as a result, to a major frequency of maternal-fetal complications during pregnancy , 26, 27.In our sample, all patients received a neurodevelopmental disorder diagnosis. A Language Disorder was diagnosed in 32.4% of our sample. Previous studies have already found that preterm delivery is considered as a major risk factor for early language impairments , 29–31. In our sample, we diagnosed a Specific Learning Disorder occurred in 22.1% of patients, with an impairment in all academic domains, writing/mathematics and reading. Previous studies already described learning difficulties in LPI. Two reviews found an increased risk for school-related activities in LPI with poor performances in writing/composition, mathematics, speaking/listening and reading , 37. A cA Developmental Coordination Disorder was found in 19.1% of patients. In literature, is reported that late and moderate preterm children have a higher risk to develop neuro-motor impairment than in term born infants , 33.An Intellectual Disability diagnosis was made in 17.6% of patients. The mean IQ of these patients was 62.3.A recent systematic review investigated long-term cognitive outcomes of late preterm births at ages 2, 4 and 14, did not find significant differences of their intelligent quotient scores with the full-term ones. However, the authors underline that the quality of evidence of the studies examined is poor due to high risk of bias .In 13.2% of patients we found an Autism Spectrum Disorder (ASD) diagnosis. Preterm birth has been already identified as a risk factor for ASD , 40. A lIn our sample, 30.8% of patients were in clinical range for internalizing problems  at the CBCL questionnaire. There are only few previous studies reporting emotional-behavior problems in LPI , 43, 44;Therefore, our findings confirmed the evidence that the last half of gestation is a crucial period in the brain development. In fact, at 34 weeks of gestation, brain volume reaches only the 65% of the term brain volume; moreover, the cortical volume in LPI is only 53% of the term volume. In addition, myelination processes show a five-fold increase between 35 and 41 weeks; nevertheless, the gyral and sulcal development goes on until the 40 weeks of gestation. Therefore, LPI brain not only is far from being mature and fully functional, but it is also very vulnerable and susceptible to deprivation of normal environmental influences and to adverse environmental factors , 46. BecThe rates of neurodevelopmental disorders in our sample are higher than the global prevalence rates in the general population. However, our study has some limitations that need to be considered. First, the size of the sample is quite small. Moreover, we were unable to make comparison with a control group, because of the difficulty in recruiting healthy children and adolescents born full-term. Another limitation is the highly selected group of late preterm children, all of whom were admitted for neuropsychiatric symptoms. In fact, the absence of healthy late preterm children control group prevented the calculation of the prevalence of neurodevelopmental outcomes among children who were born late preterm. Nevertheless, this preliminary study highlights not only the importance of monitoring programs LPI from the first years of life, but also the growing need for more large-population-based and longitudinal studies to identify at an early stage both potential risk factors and first signs of neurodevelopment disorders.