P < 0.05). However, the vetsin group had significantly reduced levels of albumin, globulin, total protein, liver glutathione (GSH), superoxide dismutase enzyme (SOD), catalase, and glutathione S-transferase (GST) enzyme activities (P < 0.05) by comparison to control. Meanwhile, modifications in liver functions, oxidative stress, DNA damage, liver injury, and PCNA expression were alleviated when vetsin was administered alongside MLE. The authors conclude that vetsin may have many side effects and that MLE can ameliorate biochemical changes, oxidative stress, hepatic injury, PCNA, and P53 alterations induced by vetsin administration.It is common for food to be made more palatable through the use of the flavour enhancer monosodium glutamate, also known as vetsin powder. The purpose of the study described in this paper was to explore how vetsin-induced hepatic toxicity, DNA fragmentation, damage, and oxidative stress modifications could be mitigated with moringa leaf extract (MLE). To that end, 40 male rats were separated into four groups: normal control, positive control or MLE, vetsin, and vetsin combined with MLE. Results indicated that, compared to the control group, the levels of serum alanine aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), liver malondialdehyde (MDA), DNA damage, injury, PCNA, and P53 expressions were significantly enhanced by the administration of vetsin ( Vetsin (monosodium glutamate) is derived from amino acids, or glutamate, and is a popular flavour enhancer used to generate a savoury or umami taste in a variety of foods worldwide. Vetsin is commonly found in Asian cuisine and thus often associated with Chinese restaurants, but it is now frequently found in the Western diet, too .From a structural perspective, there is no difference between the glutamate molecules disseminated from the gastrointestinal tract to the circulation, irrespective of the type of food from which they derive . The disMoringa oleifera can be found in the Asian and African tropical and subtropical regions and is valuable not only nutritionally but also pharmacologically [The edible tree ogically –7. Tradiogically . Moringaogically , 9–12. TMoringa oleifera leaves were purchased between May and June from farmers in Riyadh. The leaves were air-dried in a laboratory for five days and ground into fine particles using a simple hammer mill. The MLE was prepared by mixing one gram dried and powdered leaves with 10 ml boiling water for five minutes, according to Berkovich et al. [One kilogram of monosodium glutamate (vetsin) powder was obtained from Qingdao Huifenghe MSG Co. Ltd., China. For the MLE, fresh h et al. .Forty male albino rats were sourced from the animal house of the College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia, each with a weight of between 110 and 130 g and aged 9-10 weeks. The rats were kept in cages in suitable environmental conditions  and were put on a diet of commercial pellet, without water restrictions. All of the experiments were conducted in compliance with the guiding principles for the care and use of laboratory animals of King Saud University in Riyadh, Saudi Arabia. The experiments were initiated 14 days after the animals were procured to allow them to become accustomed to the laboratory setting.The male rats were separated into four groups with ten rats in each, and over the four weeks of the experiments, all rats were given the same amount of food. The first group was the control group, which did not undergo any treatment. The second group was subjected to intragastrical administration of 200 mg/kg body weight of MLE over the course of four weeks. The third group was subjected to intragastrical administration of 5 mg/kg body weight vetsin powder over the course of four weeks. The fourth group was subjected to intragastrical administration of 5 mg/kg body weight vetsin powder combined with 200 mg/kg body weight MLE over the course of four weeks.When the experimental work was completed, the rats were subjected to overnight fasting. For the purposes of clinical chemistry, the rats were euthanized at the end of the fourteenth week, to permit the sampling of blood via retro-orbital puncture with the use of blood capillary tubes without heparin, in keeping with specifications. Following 10-minute incubation at room temperature, the blood samples were allowed to coagulate before being subjected to 15-minute centrifugation at 3000 rpm. After collection, the serum was isolated and stored in clean stopper plastic vials at −80°C in preparation for the examination of the serum parameters.All experimental procedures were performed in accordance with King Saud University's ethical standards for experiments involving animals.The approach proposed by Schumann and Klauke  was adopAt the end of the experimental period, rats from each group were euthanized and subjected to a complete necropsy after 10–12 hr of fasting. Liver tissues were weighed, cut, and homogenized (10% w/v) separately in ice-cold 1.15% KCl 0.01 mol/l sodium potassium phosphate buffer (pH 7.4) in a Potter-Elvehjem type homogenizer. The homogenate was centrifuged at 10,000 g for 20 min at 4°C and the resultant supernatant was used for different enzyme assays.The approach proposed by Mesbah et al.  was adopDNA damage analysis and quantification were conducted with the comet assay (single cell gel electrophoresis) method. 100 mg samples of liver were obtained from every experimental group and subjected to mincing in a chilled homogenising buffer consisting of 0.075 M NaCl and 0.024 M Na2EDTA, before undergoing gentle homogenisation with the use of a homogenizer  in ice. A suspension of cells was subjected to a 10-minute 700× g centrifugation at 4°C, followed by resuspension in cold buffer. An epifluorescence microscope permitted visualisation of the slides. The DNA migration length (comet tail length) caused by genotoxicity was established by scanning digital images in an image analyser in the case of the control and MSG groups. Observation of at least 505 arbitrarily chosen cells per sample allowed the determination of tail length (TL), representing the distance between the comet head and the final signal in the tail that could be seen, the DNA tail intensity (TI), representing the DNA fraction in the tail divided by the DNA quantity in the nucleus multiplied by 100, and the DNA tail moment (TM), representing the product of the DNA quantity in the tail and TL. Every assay was carried out three times and contrasted with control.Liver tissue samples were fixed with 10% formalin solution for 48 hours and then processed for paraffin sectioning. Sections were stained with Ehrlich's haematoxylin and counterstaining with eosin was applied for histopathological examination according to Bancroft and Stevens .μm deparaffinised sections, with rat antibodies PCNA monoclonal antibody .As proposed by Tousson et al. , an AvidP53 proteins in the liver tissues were detected using the Avidin–Biotin Complex (ABC) method according to Tousson et al.  and the P < 0.05. The SPSS software  was used to conduct every statistical analysis.To determine whether the experimental groups had any differences of significance, one-way ANOVA was employed for statistical analysis, with expression of data in the form of mean values ± SE. In the case of biochemical data, statistical significance was established, to be indicated by Rats that were treated with the dose of MLE appeared healthy and did not show any clinical signs of disease and no mortality was recorded during the experiment duration. Neither was any mortality recorded during the experiment duration in treated rats with vetsin or with vetsin plus MLE; however, yellowish body hair and faintness were observed.P < 0.05) (P < 0.05)   but sign < 0.05) . In cont < 0.05)  and 2.P < 0.05) (P < 0.05)   but sign Figures  and 4. I Figures  and 4.P < 0.05). As can be seen in DNA damage in hepatic tissues was analysed via a comet assay. The control and MLE groups did not differ significantly in terms of DNA damage (tail length) in hepatic tissues. In contrast, the vetsin group differed from the MLE group in that it exhibited increased tail length, tail DNA%, and tail moment, which reflected that DNA damage was significant . The results of the experiments conducted revealed that, unlike the control group, rats given vetsin exhibited, on the one hand, higher levels of ALT, AST, ALP, and GGT, which might suggest cellular leakage and functional impairment of hepatic cell membranes , 27, andThere is also agreement between the present study and those by Farombi and Onyema  and OnyeIn a similar way, Ortiz et al.  found thThe alterations observed in the hepatic enzymes ALT, AST, ALP, GGT, albumin, globulin, and total protein can be reversed with MLE, which has a protective effect on membrane permeability because it targets oxidants and can function as a free radical scavenger , 35, 36,P < 0.05) and significantly lower levels of GSH, SOD, GST, and catalase (P < 0.05). Thus, it could be deduced that high levels of lipid peroxidation are damaging to hepatic tissue and impair the ability of antioxidants to eliminate excess ROS production [Various pathologies are associated with involvement of free radicals, which are targeted by antioxidants, and thus help in disease prevention. Lipid peroxidation may be the reason for the cellular toxicity of vetsin. This study reported that, by comparison to control, the vetsin group had significantly higher liver MDA levels  and nonenzymatic antioxidants , whilst decreasing the activity of MDA in hepatic tissues. The results obtained in this study are consistent with those of Uma et al. , who foun et al. , who useMoringa oleifera extract. The quantitative assessment of genotoxicity caused by vetsin was based on its strong ability to cause DNA damage; the study results revealed that, by comparison to the vetsin group, the vetsin + MLE group reduced DNA damage in hepatocytes. Similarly, Farombi and Onyema [This study conducted experiments on rats to investigate the extent to which vetsin-triggered oxidative stress and genotoxicity could be counteracted by d Onyema  reportedThe vetsin experimental group in this study exhibited hepatocyte deterioration, significant necrosis, and scattered growth of Kupffer cells among certain hepatocytes and around the portal area, significant blockage of blood sinusoids, and elevated hepatic expression of PCNA and P53. Such observations corroborated the findings by Eweka and Om'Iniabohs , who fouOur observations indicate that monosodium glutamate induces necrosis in rat hepatic tissues, corroborating earlier studies by Oscar et al.  and OrtiThis study noted that vetsin elevated the expression of PCNA and P53 in the liver, which was suggestive of intensified proliferation and apoptosis. However, Egbuonu et al.  found inSuch effects, and its antioxidant property, mean that MLE plays an important role in the treatment of iatrogenic and toxic liver disorders . Treatme


No significant difference in failure rate was found among the types of prosthesis employed (p = 0.27). The mean peri-implant bone level change at the end of the follow-up in each study ranged from 0.3 to 1.7 mm. Conclusion: Immediate loading of implants appears to have long-term predictability and success rate under well-defined circumstances.Background: The aim of this systematic review was to evaluate the survival rates of immediately loaded implants after at least five years. Besides implant failure, the amount of marginal bone loss around implants and the complication type were assessed. Methods: The electronic search was undertaken on Medline, Scopus, and Cochrane Central Register of Controlled Trials using key terms such as: “immediate loading”, “immediate function”, “immediate restoration”, “immediate temporization”, “dental implants”, “fully edentulous patients”, “partially edentulous patients”. The search terms were combined using the Boolean operators AND, OR. The last electronic search was performed on 15 February 2018. Two authors independently screened the studies, extracted the data, and assessed the risk-of bias. The main outcomes recorded for each study were: implant and prosthesis success and survival, marginal bone level change, incidence and type of complications. Kaplan–Meier analysis was used to estimate cumulative survival rates. Results: Thirty-four prospective studies with at least five-year follow-up, published between 2007 and 2017 were included. A total of 5349 immediately loaded implants in 1738 patients were analyzed. The mean follow-up was 72.4 months : 64.53, 80.25 months, range 60 to 147 months). The mean weighted implant survival was 97.4% . Cumulative survival rate of implants placed in the mandible was significantly higher than for the maxilla ( The original Brånemark protocol for placing dental implants required a two-stage surgery with a submerged healing period of at least three months in the mandible and six months in the maxilla, allowing the implant to osseointegrate without exposure to external trauma . Under dTwo types of immediate loading have been described in the literature. One is the immediate functional loading (IFL), or immediate occlusal loading, which refers to the use of a temporary or definitive prosthesis seated the same day as the surgery in occlusal contact with the opposing arch . An alteThe purpose of the present systematic review is to investigate the prognosis of immediately loaded implants, through assessment of implant and prosthesis survival and success rates after at least five years of functional loading. Furthermore, the amount of marginal bone loss around implants, the type and incidence of complications, and the occurrence of implant failures were assessed to determine if immediate loading of implants can be the treatment of choice under well-defined circumstances.The present review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines .A PICO question was devised to identify the objectives and the inclusion criteria where, P is, population or patient, I, intervention, C, comparisons, O, outcomes, and S stands for study design. When the aim of a systematic review is to determine the efficacy of an intervention, only randomized controlled trials must be searched. The present review aimed at evaluating the prognosis of immediate loading, independent of comparison with conventional delayed loading, which has a well-established prognosis. In other words, it was not mandatory to select only comparative clinical trials, randomized or not. The PICO question was: “In partially and fully edentulous patients, what are the implant and prosthesis survival rates, the incidence of complications and the marginal bone level changes after a minimum of five years in patients treated with immediately loaded implants, reported by prospective clinical trials?”.A comprehensive electronic search was undertaken on Medline, Scopus, and Cochrane Register of controlled trials, to identify prospective clinical studies reporting the main outcomes  of immediately loaded implant-supported restorations. The search was conducted using the following search string, composed of key terms combined with the Boolean operators AND, OR: ((immediate loading OR immediate function OR immediate restoration OR immediate temporization) AND dental implants AND  AND edentulous) AND (patients OR arch OR site OR jaw OR mandible OR maxilla)). The references of the selected articles and previous reviews were also examined for identifying further eligible studies. The last electronic search was performed on 15 February 2018.Human studies.Publication in English language.Prospective studies , controlled clinical trials (CCT) or prospective case series (PCS)).Functional fixed prosthesis delivered within 72 h after postimplant placement.At least five years follow-up after prosthesis delivery.At least 10 patients treated with immediately loaded implants.Patients older than 18 years.Data regarding success and/or survival of immediately loaded implants, as well as complications, had to be reported.No restriction was placed regarding the publication year.Case reports, retrospective studies, and reviews of the literature, as well as animal and in vitro studies, were excluded.When papers from the same group of authors were identified, with very similar databases of patients, materials, methods, and outcomes, the authors were contacted to clarify whether the pool of patients was indeed the same. In the case of multiple publications relative to different aspects or phases of the same study, only the one reporting results with the longest follow-up was considered.The studies to be included in this systematic review had to meet the following inclusion criteria:Firstly, titles and abstracts of articles identified through electronic search were screened independently by two reviewers  to exclude irrelevant papers and non-prospective studies, and to select articles fulfilling the inclusion criteria. When a decision could not be made based on the title and abstract, the full text was obtained and assessed, and a third reviewer was involved (MDF). For all eligible studies, the full text was obtained and analyzed in order to confirm that the studies met the inclusion criteria and determine the list of articles included in the review. For all studies excluded at this stage, reasons for exclusion were provided.Data from included studies were independently extracted by two reviewers (F.G. and V.K.). Cases of disagreement were subject to joint evaluation by the reviewers until an agreement was reached. A third reviewer (MDF) was consulted if needed.The following information was extracted from each included study and recorded using a specially designed data sheet: year of publication; study design; study setting ; sample size calculation (yes/no); blinding of evaluators (yes/no); type of fixation (cemented or screwed); number of patients, number of implants, number of implants per patient, number of male or female patients, mean age and range, number of smokers, number of postextraction immediately loaded implants, location , jaw, time of loading , type of loading , type of prosthesis , type of definitive prosthesis retention (screw retained or cemented), implant brand and type, surface type, torque levels, flap or flapless approach, patients demographics , mean follow-up duration, number of dropouts, reason and time of failures, marginal bone level changes after one year and after five years of follow up, soft tissue changes, aesthetic evaluation, and type and number of complications.The quality of the included studies was assessed by means of the Newcastle–Ottawa Scale (NOS) for nonrandomized clinical studies (case-control and cohort studies). The scale is a star system based on three domains: 1. Selection of study groups ; 2. Comparability of the groups ; 3. Ascertainment of either the exposure or outcome of interest for case-control or cohort studies, respectively . Stars are awarded so that the highest quality studies are assigned up to nine stars.p = 0.05.Data were tabulated and analyzed using the software Microsoft Excel 2016  and the software GraphPad Prism 5.0 . For the data synthesis, weighted mean values, median, 95% confidence intervals and ranges were used. Distribution of implant failures was assessed using a time-to-event analysis. Studies that did not provide information regarding the timing of implant loss were excluded from the analysis. Life table analysis and Kaplan–Meier analysis were used to estimate cumulative implant survival rate. The cumulative survival rates of implants in the maxilla and mandible were compared using log-rank (Mantel–Cox) test. The significance threshold was set at The search results and the flow of study selection is shown in A total of 135 implant failures was reported. Most failures occurred early after loading or during the first year. In particular, 60.9% of failures occurred within the first six months and 75.0% in the first year, as seen in The overall mean weighted implant survival was 97.41% . Cumulative implant survival up to five and ten years follow-up was 97.66% and 96.94%, respectively, as seen in p = 0.0008 and p = 0.0027, respectively), i.e., immediately loaded implants placed in the maxilla tended to fail more than those placed in the mandible.In the mandible, cumulative implant survival at five and ten years follow-up was 98.42% and 97.26%, respectively, while in the maxilla, it was 97.01% and 96.81%, respectively, as seen in p = 0.27). For three studies in which multiple prosthesis types were used, it was not possible to split implant survival data based on prosthesis type [Mean weighted implant survival for single tooth, partial fixed prosthesis and full-arch fixed prosthesis was, respectively, 96.19% , 98.51%  and 96.71% . No significant difference in failure rate was found regarding prosthesis type  that were easily resolved chairside. Biological complications, consisting of peri-implantitis and peri-implant mucositis, were less frequently reported, but were often associated with late implant loss.The results of the methodological quality assessment are reported in Among the innovative procedures marking significant steps forward in implant dentistry, immediate loading stands out for its importance in routine clinical practice . Under dAccording to the recommendations of ITI Consensus Statement in 2014 , the defAchievement of adequate stability depends on controlling micromovements in the interface between the implant and bone , as eachA trending question in the field of implantology regards marginal bone loss that occurs around implants. Recent reviews and consensus papers state that, besides peri-implant infection, there may be various other reasons for the loss of marginal bone . These iThe ultimate goal of immediate loading protocol is to reduce the number of surgical interventions and to shorten the time frame between surgery and prosthesis delivery, all without compromising the success rate of the procedure. Immediate temporization of implants has been introduced to meet many needs, including the high survival rates of implants and prosthetic restorations, the preservation of marginal bone levels, and the satisfaction of patients. This leads to the primary objectives of this paper: (a) assessing the survival rates of immediately loaded implants after a minimum of five years of function, (b) assessing the survival rates of the prosthetic restorations, and (c) assessing the levels of marginal bone loss around these implants after one year and five years.These protocols will ultimately lessen patients’ reservations, resulting in increased acceptance of implant therapy . VariousBone preservation is a key factor for aesthetic outcome  as supraFunctional, biological, and aesthetic considerations need to be made for achieving predictable long-term tissue stability . Peri-imEvidence-based medicine aims to provide patients with the best possible treatment by integrating the clinician’s skill with the best available scientific evidence from the literature, and by taking patients’ preferences and needs into consideration. Today, patients are no longer considered inert subjects who passively undergo the doctor’s decisions. Rather, they actively and knowledgeably participate in the decision-making process regarding their treatment.As a result of this shift in patient–clinician relations, it has become evident that treatment outcomes need to be assessed through patient-based parameters, with the patient becoming central in the overall analysis. Involvement of the patient in treatment outcome assessment is becoming more and more common. It is no longer sufficient to claim the treatment a success merely based on clinical and technical aspects. Conversely, it is necessary that the patient is satisfied with as many aspects as possible, which provides not only complete restoration of function and aesthetics, but also psychological well-being. Immediate loading not only demonstrates a high long-term predictability, but appears to be able to meet all of the above aspects addressing the patient’s needs. In modern implant dentistry, immediate loading should become routine treatment. Nevertheless, it is just as important not to forget that such a treatment can bring to excellent levels of satisfaction, but must only be applied when the fundamental clinical requirements are satisfied. In fact, any abuse or misuse of immediate loading might increase the risk of failure, with biological and psychological consequences for the patients. The distribution of the included articles over the years shows that there is a growing interest in immediate loading, allowing more insight into the most adequate clinical protocols, favoring the integration of immediate implant loading into everyday practice.In conclusion, the results of this review confirm that immediate implant loading is a predictable protocol that can be the therapy of choice under appropriate circumstances, leading to excellent, long-lasting favorable outcomes and high patient satisfaction.


Introduction: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive and extensive motor deficits. Patients may also have cognitive impairments or alteration of emotional processing. Very few studies, however, have looked at deficits in how they experience their own feelings .Methods: We assessed alexithymia in 28 patients with ALS using the 20-item Toronto Alexithymia Scale (TAS-20), comparing them with a control group matched for sex, age, and education level. We took into account both the total score of the TAS-20 and its three subscores corresponding to the three dimensions of alexithymia: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Patients also underwent a neuropsychological assessment and anatomical magnetic resonance imaging (MRI) in order to correlate cognitive performances and gray matter volume and level of alexithymia.Results: On average, ALS subjects had a significantly higher total score and DIF sub-score of the TAS-20 than controls indicating an increased alexithymia in patients. Total and DIF Scores correlated significantly and negatively to gray matter volume of the prefrontal cortex, right superior temporal pole and parahippocampal gyri. No correlations were found between scores on executive functions and those on the TAS-20.Conclusion: The first stage of one's own emotional processing seems to be affected in ALS independently of executive dysfunction. This trouble seems to be underpinned by cerebral regions that are well known to be both implicated in alexithymia in healthy subjects and altered in ALS. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of upper and lower motor neurons, with relentless progressive muscular paralysis causing severe functional disability and leading to death. Median survival is 3 years after onset of the disease and 2 years after diagnosis .Approximately half of all patients with ALS have some degree of cognitive impairment, mainly affecting executive functions such as mental flexibility, attention, and verbal fluency . ComorbiAlexithymia is a concept that was introduced by Nemiah and Sifneos to characterize the psychological profile of patients with psychosomatic disorders. The term literally means lack of words for emotions, and has been defined as “a diminution or absence of the basic human ability to experience feeling” , and no patient had a severe cognitive deficit (MDRS ≥ 127) .All patients were examined by an experienced neurologist (F.V. or L.C.). They met the new El Escorial criteria for probable or definite ALS . None ofFor each patient, we noted disease duration, clinical onset topography (limb vs. bulbar), the severity of ALS at the time of the study according to the ALS Functional Rating Scale revised form (ALSFRS-R), the Norris ALS Scale, which assesses the impact of bulbar involvement, and the Medical Research Council Muscle Strength Scale . Patients were able to speak and/or write intelligibly, had a forced vital capacity above 50% of the predicted value, and no clinical evidence of nocturnal hypoventilation. None of the patients had any additional severe or chronic illness, MRI contraindications, or communication difficulties severe enough to compromise the administration of cognitive tests. They gave their written informed consent, and the study was approved by the regional independent ethics committee.strongly disagree) to 5 (strongly agree). The TAS-20 assesses three dimensions of alexithymia, by means of three specific subscales: Difficulty Identifying Feelings (DIF) is measured by summing responses to Items 1-3-6-11-9-13-14, Difficulty Describing Feelings (DDF) by summing responses to Items 2-4-7-12-17 and Externally Oriented Thinking (EOT) by summing responses to Items 5-8-10-15-16-18-19-20  , a reliaZ-scores for each patient using means and standard deviations of the control group with pathological threshold defined at Z = ±2.Global cognitive functioning was gauged with the widely used MDRS, which provides a sensitive measure of the degree of frontal-subcortical impairment . Both paTo assess behavioral changes induced by the disease, we have proposed the French version of the Neuro-Psychiatric-Inventory Questionnaire (NPI-Q) to relatives. This questionnaire is composed of 12 items corresponding to 12 symptoms: apathy, delirium, hallucination, etc. Caregivers had to note if each symptom is present or absent and if present they have to evaluate its severity (from 1 to 3) and its impact on themselves (from 1 to 5) . We thus2, in-plane resolution = 1 × 1 mm2). The MRI examination was carried out within 24 h of the clinical testing.For each patient, a high-resolution T1-weighted anatomical image was acquired on an Achieva 3T scanner  using a three-dimensional fast field echo sequence , modulated to correct for nonlinear warping effects, and smoothed with a 10-mm full width at half maximum Gaussian kernel using the VBM5 toolbox implemented in SPM5 software (www.fil.ion.ucl.ac.uk). Images were masked to exclude non-gray matter (GM) voxels from the analyses.The MRI data were segmented, spatially normalized to Montreal Neurological Institute (MNI) space . The threshold of significance was set at a et al.  and loweAs some variables were not normally distributed, non-parametric tests were used. U Mann-Whitney test was employed to compare the patients and healthy controls on age, years of education, TAS-20 scores, MDRS score, TMT B-A reaction time difference, verbal fluency score and index, HSCT score and LN sequencing score. A chi-square test allowed us to compare sex ratio and proportion of non-alexithymic versus alexithymic participants across the two groups. In the patient group, correlations between TAS-20 scores and cognitive performances were calculated with Spearman's correlation coefficient.p = 0.005 (uncorrected for multiple tests) for the voxels and a cut-off of k (corresponding to the number of voxels in a particular cluster) >100. Anatomical localization was based on Talairach's atlas and the Anatomical Automatic Labeling atlas . We usep = 0.99, age, = 0.09, but not for education level, p = 0.02. Regarding global cognitive and executive functioning, patients scored lower than controls on the MDRS, p < 0.001, HSCT, p < 0.001, TMT B-A, p = 0.01, LN sequencing task, p < 0.01, letter verbal fluency scores, p < 0.001, and index, p < 0.001). All patients were impaired in at least one cognitive test but only 57 % of them were defined as “cognitively impaired,” meaning that they were deficient in at least two tests. Scores obtained at the NPI-Q are reported in Table The demographic, clinical, and neuropsychological characteristics of the two groups are shown in Table χ 2 = 0, p p = 0.02.Regarding alexithymia level, and as indicated in Table r = 0.41, p = 0.03), but not with education level, clinical data , MDRS score, behavioral status (scores of the NPI-Q) or executive function performances .In the patient group, TAS-20 scores correlated with age  and to underestimate its emotional component, represented by emotionalizing and fantasizing . HoweverThe clinical importance of a high level of alexithymia in ALS remains to be specified. Type I alexithymia could induce psychosomatic manifestations, which could in turn skew the ALS patients' physical condition and make their medical management more difficult if psychological care is not proposed. High levels of alexithymia have been found to be correlated to less capacity of empathy . As shoAlexithymia has been found to impair quality of life (QoL) in the general population , and in Our group of patients is in line with the generally accepted finding that in ALS about half of the subjects have “normal cognition” and half have some sort of “cognitive impairment” . Even ifspecific, and partly independent of executive dysfunction in ALS.We found no correlations between our patients' set-shifting abilities, working memory and ability to inhibit responses, and their alexithymia level. A high level of alexithymia has been found to be associated with impairment of executive functions as assessed using the TMT and verbal fluency tasks –42. But Patients with ALS are widely acknowledged to have deficits in recognition of other people's emotions, and in both cognitive and affective ToM , 44. In This is the first study to have assessed the correlation between GM volume and alexithymia level in ALS. We found significant negative relationships between the TAS-20 total score and DIF subscore and the GM volume of the prefrontal cortex  and ACC. In other words, patients with a high level of alexithymia had reduced GM volume in these areas. These results are consistent with observations in healthy individuals, as several neuroimaging studies have reported decreased GM volume in the ACC and medial prefrontal cortex, in healthy individuals with a high level of alexithymia –51.Reductions in GM density in ALS have been observed in the frontal lobe and, more specifically, in the inferior , 53, middiscrete body features) corresponds to the perception of changes in the activity of discrete parts of the body . This bodily perception is mediated by the somatosensory cortex. In Stage 2 (whole body patterns), discrete Stage 1 representations are integrated in order to detect/represent coherent whole-body patterns. The anterior and middle insula and dorsal ACC may play a crucial role in this stage (emotion concept) involves mentalizing the integrative whole-body perception and giving meaning to what is perceived and felt. Likely candidates for Stage 3 emotion processing are the rostral ACC and adjacent regions of the medial prefrontal cortex (MPFC). Different stages in this emotion processing presumably correspond to different alexithymia dimensions, with DIF corresponding to Stage 1 or 2 of Prinz's model insofar as this dimension reflects a perceptual process of relatively low cognitive level, and DDF and EOT to Stage 3. Our results support the idea that the ACC has an integrative function for perceived sensations, while the inferior and middle frontal gyri are involved in mentalizing emotions.In our study, the total scores of the TAS-20 were correlated with three clusters , whereas for the DIF subscore, only the ACC (the biggest cluster) and the inferior and middle frontal gyri were found to be correlated. There have been a few studies of the neural correlates of the various dimensions of alexithymia. Demers et al.  found a is stage . Stage 3Cortical damage in ALS may involve both temporal and limbic areas , 53. In p < 0.005 (uncorrected for multiple tests). This threshold is not very robust but our results are consistent with the few relevant data in the literature, which gives credit to our study. The fact that the TAS-20 scale only captures three of the five previously described dimensions of alexithymia may be a methodological limit of the present study. Finally, we focused on executive functions because these are the most impaired in ALS patients and thus implications of other cognitive domains in alexithymia were not studied. Further studies are needed, first to validate our findings and then to better assess the clinical implications of alexithymia in ALS, in terms of QoL of both patients and caregivers for example. It would also be interesting to stratify the alexithymia data along clinical and genetic subtypes of the disease.Our study has some limitations. The first one is that as the patients are only mildly physically affected and may thus not be representative of an ALS standard population, generalization of the results must be done with caution. Another limitation is that our threshold of significance for neural correlates has been set at To our knowledge, this is the first study assessing alexithymia in patients with ALS compared with a matched control group, specifically focusing on the various dimensions of alexithymia. Our results add to the accumulating evidence that a number of central nervous functions are impaired in ALS besides motor control, including the processing of emotions in the self. These emotional disabilities could explain patients' paradoxical psychological reactions. In ALS, emotional self-perception involves brain regions that are known to contribute to emotion processing in healthy individuals. Even if the nature of emotional neurological circuits has been well established, the precise role of specific neurological structures remains to be delineated. ALS could be a good model for improving current understanding of the emotional brain.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.All subjects gave their written informed consent, and the study was approved by the regional independent ethics committee.SB was actively involved in this study from design to drafting. She conduced all the statistical analyses and played a central role in interpreting the results and writing the article. FD and M-SB greatly contributed to the neuroimaging part of the study. AM and LC participated in the acquisition of clinical and cognitive data, especially in the careful screening of our cohort. FD, LC, and FE provided their critical revision of the manuscript. BD and FV supervised and coordinated the teamwork from start to finish. Their Knowledge and expertise in neuropsychology and ALS pathology were crucial for the design, analyses and interpretation of the result of the project. They were also particularly involved in the revising of the manuscript. All authors read and improved 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.


Breast cancer (BC) is the most common type of cancer worldwide. Globally, BC is rapidly becoming a major common health problem among women. This study aimed to evaluate the association between nutrient intake patterns and BC risk among Jordanian women.A total of 400 Jordanian women 20-65 years of age were recruited in this case-control study. Two hundred women recently diagnosed with BC were matched in age, income, and marital status to 200 BC-free women. A food frequency questionnaire was used to assess nutrient intake patterns.trend=0.001). In the high calcium, phosphorus, and vitamin D nutrient pattern, a significant inverse trend was detected for the risk of BC. The high-fat nutrient pattern showed a significant direct association with BC risk in the third  and fourth  quartiles (ptrend=0.001).In this study, 3 nutrient intake patterns were identified: a high vitamin C and β-carotene nutrient intake pattern; a high calcium, phosphorus, and vitamin D nutrient intake pattern; and a high-fat nutrient intake pattern. A significant increase in BC risk was associated with the high vitamin C and β-carotene nutrient pattern (the highest for the fourth quartile; odds ratio [OR], 5.42; 95% confidence interval [CI], 2.11 to 13.91; pA significant increase in BC risk was detected for the high vitamin C and β-carotene nutrient intake pattern and the high-fat nutrient intake pattern. However, for the high calcium, phosphorus, and vitamin D nutrient intake pattern, a significant inverse trend was observed. Cancer is a leading cause of death in both more and less economically developed countries. The burden of all types of cancer is expected to grow worldwide due to population growth and aging . ApproxiAlthough a number of risk factors have been identified for BC, some are difficult to modify . While dThe study was conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975 and subsequent amendments. The proposal was approved by the Institutional Review Board of the 2 participating hospitals: King Hussein Cancer Center (KHCC) and Al-Basheer .A case-control design was used to evaluate the nutrient intake patterns a risk factor associated with BC among Jordanian women.Two hundred patients who had recently been diagnosed (up to 3 months from diagnosis) with BC were enrolled in the study through convenience sampling. All BC patients were taken from KHCC and Al-Basheer Hospitals, the main 2 hospitals in Jordan that offer cancer therapy. Data was collected between October 2016 and September 2017. The control group was included from the community  who underwent either a mammogram or clinical examination to verify that they were free of BC. The ratio of cases to controls was 1:1. Matching between the patients and control subjects was performed for the following variables: age, income category, and marital status. The inclusion criteria for the patients were: a recent diagnosis of BC (up to 3 months from diagnosis), Jordanian nationality, age between 20 years and 65 years, and the ability to communicate verbally. The exclusion criteria included critical or terminal illness, hospitalization, an inability to communicate verbally, and suffering from other types of cancer or other diseases that required a specific diet. Data from patients who decided to terminate the interview, gave unrealistic answers during the interview, or were diagnosed at an age older than 65 years were excluded (16 cases and 24 controls). The sample size was calculated as: number (women diagnosed with BC in 2014)=1,174; confidence interval (CI), 95%; margin of error, 5%; and response distribution, 85%. The calculated sample size was 170. In general, approximately 20% of the population of patients diagnosed with BC in 2014 in Jordan was enrolled.For the cases, the hospital setting was utilized for data collection. Hospitals with specialized oncology units were included . The outpatient department in each hospital was the setting for data collection. Permission from each hospital to use a private room in a suitable physical condition to carry out the interviews was obtained. For the controls, KHCC and Al-Basheer Hospitals were the setting for data collection.A 3-part package was used to collect data for the purposes of the study. The package consisted of 3 structured questionnaires: a personal information sheet, a food frequency questionnaire (FFQ) , and 7-dThis sheet was composed of questions related to age, marital status, education, employment, monthly family income, residency area and house condition, smoking status, medication, and previous and current health problems.Information on diet was collected using the validated Arabiclanguage FFQ . The FFQThe physical activity levels (PARs) questionnaire, developed by Sallis et al.  for the Measurements of weight were taken to the nearest 0.1 kg, with minimal clothing and without shoes, using a calibrated portable scale. Height was measured to the nearest 0.5 cm with participants in the full standing position without shoes using a calibrated portable measuring rod. BMI was calculated as the ratio of weight in kilograms to the square of height in meters. Height and weight were measured according to Lee & Nieman .Representatives from each hospital called each participant to invite them to participate in the research. During the first meeting with the participants, the investigator explained the purpose of the study and allowed participants to read the consent form before signing it. Each participant understood that she could withdraw from the study at any time she wanted and that doing so would not harm her in any way. The potential risks and potential benefits were also explained in detail, and it was communicated that the present study posed no risk. A signed consent was obtained before data collection. The information obtained from patients was treated confidentially. Only oncologist knew the patients’ names, and she was the only one who gave them their ID number. All used tools and instruments (questionnaires) were labeled with patient ID.trend values. Age (continuous), BMI (continuous), PA level (continuous), total energy intake (continuous), occupation, education level, marital status, and family history for the BC participants were evaluated as potential confounders [Descriptive analyses were conducted to examine the frequency of different variables. The chi-square test was used to detect significant differences among categorical variables. The t-test was used to assess differences between continuous variables from the cases and controls, which are presented as mean±standard deviation (SD). Logistic regression was used to calculate odds ratios (ORs) and 95% CIs, while linear regression was used to calculate pfounders . The sigPrincipal component analysis of the entire population was conducted using a selected set of 28 major nutrients, macronutrients, and micronutrients to derive dietary patterns . FactorsThe results of this case-control study highlighted the associations of some dietary and lifestyle risk factors with the risk of developing BC. trend=0.001). For the high calcium, phosphorus, and vitamin D nutrient pattern, a significant inverse  trend was detected against BC. The high-fat nutrient pattern showed a significant association with BC risk in the third  and fourth  quartiles, with a ptrend of 0.001.The ORs and corresponding 95% CIs of the BC cases and controls by quartiles of factor scores and continuous factor scores for the 3 nutrient intake patterns are shown in The results of this study add to the evidence for an association between BC risk and diet and lifestyle behaviors. In our study, a significant difference between cases and controls in BMI was detected; furthermore, the risk of BC increased as the BMI increased from normal body weight to overweight or obesity. BMI has been found to be associated with the risk of BC incidence, and this association has been reported in many studies ,15-17. ARegarding diet, 3 nutrient intake patterns were identified in this study: a high vitamin C and β-carotene nutrient pattern, which was associated with an increased risk of BC; a high calcium, phosphorus, and vitamin D nutrient pattern, which showed a protective effect against BC; and a high-fat nutrient pattern, which was also associated with a higher risk of BC.Although several studies demonstrated that vitamin C and β-carotene may favorably influence BC risk because of their antioxidant properties -25, our The second nutrient pattern in our findings was characterized by high calcium, phosphorus, and vitamin D intake, which may reflect high levels of dairy product consumption. According to our results, this nutrient pattern was significantly protective against BC. This finding is in agreement with the previous findings of Knekt et al. , who demtrans form is likely to have been responsible for this relationship. The association between BC risk and trans fatty acids in general and MUFAs in the trans form was precisely studied by Chajès et al. [cis forms of MUFAs was unrelated to BC risk, while a high serum level of trans MUFAs, presumably reflecting a high intake of fried foods, likely contributed to an increased risk of invasive BC in women [trans fat intake in cases was higher than in controls and the percentage of total trans fats among total nutrients intake showed a significant trend (p<0.05) for BC risk. Furthermore, Wirfält et al. [In the third nutrient pattern, which was characterized by high fat intake, a higher intake of MUFAs and PUFAs was found to significantly increase the risk of BC. In particular, among MUFAs, the s et al. . Those ain women . A findit et al.  concludet et al. . Similart et al.  documentt et al.  found tht et al.  reportedt et al. , who sugt et al.  were notIn a study of this type, we rely greatly on the ability and memory recall of participants to accurately and carefully provide information from a period when it was not necessarily important to remember the details of meals that were consumed, or PAs that were undertaken. It is understandable that some individuals may have a better recall than others, and that biases may exist in the minds of those being interviewed, and indeed, in the interviewer. We also did not take into account the possible effects of cooking on the bioavailability of the various nutrients, although we attempted to control for a range of potential confounders. Alcohol consumption was not measured because its consumption is culturally discouraged in Jordan. Only 2 women reported alcohol consumption. Although the sample size was small, it was representative, as confirmed by statistical calculations. The enrollment of the participants utilized convenience sampling, and was based on their agreement to participate in the study, which imparts some degree of bias in terms of sample selection. Jordan is a small country with an estimated population in 2012 of approximately 9.5 million people, and a cancer diagnosis rate for BC of 32.1 per 100,000. In 2014, a total of 1,187 newly diagnosed BC cases in both genders were reported by the Jordanian Cancer Registry. We had difficulties in recruiting more participants to increase our sample size.A major strength of our study is the use of a validated and detailed FFQ to collect dietary data from our study population. Even though dietary data were collected only once, the FFQ has been reported to be an adequate instrument for measuring macronutrient and micronutrient intake. However, confirmative studies should verify and extend the presented data on Jordanian dietary habits in order to establish recommendations for people in Jordan to reduce BC incidence.In conclusion, 3 nutrient intake patterns were identified in this study: a high vitamin C and β-carotene nutrient intake pattern, which was associated higher BC risk; a high calcium, phosphorus, and vitamin D nutrient intake pattern, which showed a protective effect against BC; and a high-fat nutrient intake pattern, which was also associated with a higher risk of BC.


Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess . Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes  of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP ( Acute pancreatitis (AP) is one of the most frequent gastrointestinal causes of hospitalization with significant morbidity and mortality in the US  AND .” We restricted our search to original human studies published in English without time period limitations. A manual search of the reference lists of relevant full-text articles was conducted to identify further potentially eligible articles. The search was conducted separately by two authors , who also assessed study eligibility and extracted data from the selected studies independently. Disagreements were resolved by consensus with the help of a third party (PH).The titles and abstracts of the publications from the literature search were screened and the full text of potentially eligible articles was obtained. We included studies in which blood pH or a related parameter  and severity scores or LOS or mortality ratios were reported for the same group(s) of patients with AP. From all included articles we extracted the sample size, the reported mean pH or its related parameter for the studied patient groups with the corresponding standard error (SEM) or deviation, as well as the severity score, LOS, and mortality ratio within the group. To analyze the influence of the change in acid-base status on the severity and the outcome of AP, in each study we assigned the patient groups as a lower pH group and as a higher pH group, irrespective from the original basis for grouping used by the authors of the study.We used mortality ratio of the AP patients groups as the primary outcome. Regarding secondary outcomes, we used two commonly applied severity indices  and the LOS.We assessed the quality of each study included in the meta-analysis by using the Newcastle-Ottawa Scale  for LOS and severity scores as the effect size data. The secondary outcomes were compared between the lower and higher pH groups (see above) within each study, and then the estimated pooled mean values were calculated. The relevant studies were compared with standard meta-analysis tools  in case of each outcome.2 statistical test, where I2 is the proportion of total variation attributable to between-study variability . The selection of patients, study design, and the used methods showed variability among the studies included in our analyses, which also resulted in statistical heterogeneity. Since the lack of statistical significant results on these heterogeneity tests could be also due to the lack of power because of the small number of studies eligible for the analyses, we used the random effect model in case of each forest plot, similarly to our earlier meta-analysis  and Stata  software.The experiments were performed in 40 female FVB/N mice . This commercially available, multipurpose mouse strain is characterized by excellent reproductive performance and it was repeatedly used by our group to study the mechanisms of AP . All experiments were conducted in compliance with the European Union Directive (2010/63/EU) and the Hungarian government decree .4Cl) administration with drinking water (8.2 ± 0.5 ml/day/mouse) as reported in earlier studies  on days 1 and 6; (iii) administration of NH4Cl with drinking water (as in group 1) and i.p. injections (as in group 2); and (iv) controls, receiving NH4Cl-free tap water and 2 i.p. injections of saline on days 1 and 6.To develop a mouse model of chronic MA, the mice were randomly divided into the following 4 groups for a 12-day treatment: (i) ammonium chloride (NHTwo different types of AP were used in this study. Mild acute pancreatitis (MAP) was induced by alcohol and fatty acid as described earlier . Blood samples were collected by cardiac puncture. Serum amylase activity was measured by using a colorimetric kinetic method . Serum concentrations of creatinine and glucose as well as urea concentration in urine were measured with commercially available laboratory kits . Arterial blood samples were collected in sealed plastic capillaries (170 μl), which were previously treated with lithium and heparin. Analysis of the arterial blood samples was performed by a blood gas analyzer  within 1 min after blood collection at room temperature (22°C).Histological evaluations were performed as described earlier  and Microsoft Excel  software was used for statistical analysis. The effects were considered significant when P < 0.05. In the experimental part of the study, data are reported in the Mean ± SEM format.Data were compared by one-way ANOVA followed by Holm-Sidak test, two-way ANOVA followed by Fischer Least Significant Difference test, or two-tailed Student's The flow chart of the study selection is presented in Figure P < 0.001).First, we investigated the association between systemic (blood) pH status and our strongest endpoint, viz., the mortality. Our meta-analysis revealed a logit event rate of −0.09 , corresponding to an average mortality rate of 51.0%  in the more acidotic patient groups, while in the patient groups with higher pH or bicarbonate level the logit event rate was −3.68 , which corresponds to an average mortality rate of 3.0%      Figure . The pot4Cl, which decreased blood pH to 6.80 ± 0.04, but it did not cause any pancreatic damage  in the combination  treatment group as compared to controls (16.5 ± 0.9 vs. 26.4 ± 0.8 mmol/l) , suggesting that SAP further deteriorates MA  . Importantly, MA significantly lowered urine urea levels in mice with MAP compared to mice with MAP without pre-existing MA   of acidifying treatments in mice. We found that MA can be induced in mice by the combined administration of oral and i.p. NHP < 0.05), increased necrosis , and elevated leukocyte infiltration  compared to MAP in mice with normal blood pH , necrosis , leukocyte infiltration , and serum amylase activity   mice Figure , which iH Figure . PancreaIn the present study, we revealed a strong association between blood pH and the outcome of AP with meta-analysis of human studies. Our analyses showed that lower blood pH predicts higher mortality rate, longer LOS, and worsens the severity of AP. A significant negative correlation between blood pH and mortality rate in severe forms of AP was found with meta-regression analysis of the human studies. To better clarify how MA can interact with AP, we developed a mouse model of chronic MA and showed that SAP worsens the MA in the mice. In the same model we also demonstrated that pre-existing MA further deteriorates the tissue damage in both mild and severe forms of AP.Although previous human studies indicated a link between MA and AP  effect of acid-base disturbances on AP. Until such or similar trials are conducted, we are restricted to use different (not so direct) approaches such as meta-analyses and animal experiments.To discover whether a pre-existing MA worsens the outcome of AP or MA is rather the result of the progression of AP, we moved from the “bedside to the bench.” Gorelick's workgroup has discovered that low extracellular pH induces pathophysiological changes in acinar cells , however its use to increase pH in diseases associated with acidosis not due to bicarbonate loss is questionable because of its adverse effects, for example, intracellular acidosis, hypokalemia, and decreased serum ionized calcium concentration -1, 6, 8, and tumor necrosis factor (TNF)-α, were shown to play a role in AP in experimental animals (Norman et al., per se promotes the activation of neutrophils (Martinez et al., The production of pro- and anti-inflammatory cytokines was repeatedly shown to depend from the extracellular pH (for reviews, see Kellum et al., In summary, by the meta-analysis of literature data available from human studies we found a significant correlation between low systemic pH and the outcome of AP, indicating that lower pH level is associated with higher mortality rates, longer LOS, and more severe AP. With regards to the mechanism, in experimental animals we showed the existence of a bidirectional interaction between MA and AP, in which pre-existing MA deteriorates AP and, vice versa, AP further increases the severity of MA. Our findings suggest that systemic pH level should be closely monitored in patients with AP and that interventions to normalize the low pH of patients with AP should be considered in clinical settings. Well-designed, targeted clinical trials are warranted to evaluate the effects of the therapeutic interventions of acidosis in patients with AP.ZRu and AG conducted the literature search of meta-analysis and the quality assessment of included studies, and extracted data from the articles. ET, JM, ZB, and PH performed the experiments. PH and AG conceived and supervised the meta-analysis and the experimental procedures and obtained funding. ZRu, ET, LP, JM, AG, and PH analyzed and interpreted the data. ZRu, ET, LP, PH, and AG wrote the paper. LP, EO, AV, GV, LC, KM, AM, ZRa, ZB, JK, IF, and JM reviewed and contributed to the manuscript. All authors 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.


Although approximate number system (ANS) has been found to predict mathematics ability, it remains unclear if both aspects of ANS (symbolic and non-symbolic estimation) contribute equally well to mathematics performance and if their contribution varies as a function of the mathematics outcome and grade level. Thus, in this study, we examined the effects of both aspects of ANS on different mathematics skills across three grade levels. Three hundred eleven children  from two kindergartens and three elementary schools in Shanghai, China, were assessed on measures of ANS (dot estimation and number line estimation), general cognitive ability , and mathematics abilities . Results of hierarchical regression analyses showed that, in kindergarten, non-symbolic estimation predicted all mathematics skills even after controlling for age, gender, and general cognitive ability. In Grades 2 and 4, symbolic estimation accounted for unique variance in mathematical problem solving, but not in calculation fluency. Symbolic estimation also predicted numerical operations in Grade 4. Taken together, these findings suggest that in the early phases of mathematics development different aspects of ANS contribute to different mathematics skills. The approximate number system (ANS) is a mental system responsible for representing and processing numerical magnitude information . It has Approximate number system consists of two aspects: non-symbolic estimation and symbolic estimation. Non-symbolic estimation refers to the processing of quantities and numerosities without using numerals . It emer1 become efficient in executing simple calculations as early as in Grade 1 . Besides, it is also possible that the effects of grade level interact with the type of mathematics skill assessed in different studies. Mathematics skills include a wide range of skills such as early mathematics skills , numerical operations , calculation fluency (the ability to retrieve arithmetic facts from memory quickly), and mathematical problem solving . Some researchers  have arg 1 e.g., .Only a few studies have also contrasted the effects of both symbolic and non-symbolic estimation in the same study e.g., . Most ofInterestingly, most of the previous studies examining the role of ANS in mathematics did not control for the effects of key cognitive predictors of mathematics such as nonverbal intelligence or executive functioning. Executive functioning, the cognitive skills engaged in goal-directed activities, includes inhibition and working memory e.g., , both of(ten-one)” for eleven), which may facilitate Chinese children learning symbolic numbers . The place-value system in Chinese is relatively transparent  on different mathematics skills  in different grade levels in China. Based on the findings of previous studies , we hypo1)The effects of symbolic and non-symbolic estimation will vary as a function of grade level. Non-symbolic estimation will uniquely predict mathematics skills only in kindergarten, while symbolic estimation will uniquely predict mathematics skills at all grade levels.2)Non-symbolic and symbolic estimation will predict different mathematics skills. Non-symbolic estimation will predict early mathematics skills, that is counting, symbolic number knowledge and arithmetic, and symbolic estimation will predict all mathematics skills except from calculation fluency.SD = 3.31), 107 children from Grade 2 , and 104 children from Grade 4 . The children were recruited on a voluntary basis from two kindergartens and three elementary schools in Shanghai, China. The schools that participated in our study serve primarily middle-class families and the demographics are representative of the general population in Shanghai . In the third page, children were presented with 40 color characters each printed in a color different from the color character . They were asked to read aloud the color of the ink in which the characters were printed as quickly as possible. An 8-item practice trial was used to make sure children understood the instructions prior to testing. A ratio score was calculated by dividing the number of correct responses by the time to finish naming all 40 items. Criterion validity has been reported to range from 0.69 to 0.73  and big animals , and were asked to say aloud whether each animal was small or big as fast as they could. In the first page, animal drawings were printed in a uniform size, and in the second page, big animals were printed in big size and small animals in a small size. In the third page, big animals were printed in a small size and small animals in a big size, and children were asked to name the animal drawing based on their actual size and not based on the size they were printed. The score was the number of correct responses in the third page divided by the time to finish naming the items. Criterion validity has been reported to range from 0.51 to 0.67 . The CroDigit Span Forward from CAS-2  was usedr’s range from 0.54 to 0.91; Test of early mathematics ability TEMA-3;  was usedr’s range from 0.71 to 0.81; Numerical operations, adopted from WIAT-III , TEMA-3 (only in Kindergarten)]. Session B included the cognitive tests  and the ANS tasks (dot estimation and number line estimation). Half of the children in each grade level did first Session A and then Session B. The other half did the sessions in the reverse order.Table 1 shows the descriptive statistics  for all the measures in our study. The distributions of numerical operations and dot estimation were positively skewed and thus log transformation was applied. After the log transformation, their distributions were normalized and the transformed scores were used in further analyses.Tables 2, 3. In kindergarten, both the number line estimation and dot estimation correlated significantly with all mathematics skills (r’s ranged from -0.43 to -0.55). In Grade 2, number line estimation correlated significantly with math problem solving (r = -0.52) and math fluency (r = -0.21). In Grade 4, number line estimation correlated significantly with math problem solving (r = -0.28) and numerical operations (r = -0.27). Dot estimation did not correlate significantly with any math task in Grades 2 and 4.The correlation coefficients among all variables in kindergarten, Grade 2, and Grade 4 are presented in Hierarchical regression analyses were subsequently conducted within each grade level to examine the unique contribution of the two ANS aspects to mathematics outcomes . In each model, age and gender were entered in the regression equation at step 1 as control variables. The general cognitive abilities  were entered in the regression equation at step 2, and number line estimation and dot estimation were entered at step 3 of the regression equation as a block.Tables 4–6 show the standardized beta coefficients, R2 changes, and significance levels of the regression models in each grade level. In kindergarten, the two ANS aspects accounted for unique variance in math problem solving , numerical operations , and TEMA-3 , after controlling for age, gender, nonverbal intelligence, inhibition, and working memory. In Grade 2, ANS accounted for unique variance in math problem solving , but not in numerical operation and math fluency. In Grade 4, ANS accounted for unique variance in math problem solving , but not in math fluency. The predictive effect of number line estimation on numerical operations was also significant .The aim of this study was to examine how two ANS aspects (symbolin) predict different mathematics skills in different grade levels in China. Overall, our findings showed that the relationship between ANS acuity and mathematics skills depends on the type of ANS aspect, the type of mathematics outcome assessed, and the grade level. Among kindergarteners, non-symbolic estimation uniquely predicted early mathematics skills, numerical operations, and mathematical problem solving. Symbolic estimation explained unique variance only in early mathematics skills. Symbolic estimation also predicted mathematical problem solving among the second- and fourth-graders, and numerical operations among the fourth-graders.In line with our expectation, non-symbolic estimation made unique contributions to mathematics skills only in kindergarten. This replicates the findings of earlier studies, which found that non-symbolic estimation played a unique role in early mathematics skills e.g., . As XeniSymbolic estimation made unique contributions to mathematical problem solving in Grades 2 and 4, and to numerical operations in Grade 4. The effect of number line estimation on numerical operations and mathematical problem solving is in line with the findings of previous studies e.g., . It was In contrast to our expectation, symbolic estimation uniquely explained only TEMA-3, but not numerical operations or mathematical problem solving among kindergartners. This might be due to the fact that early mathematics tasks included items such as number comparison, and number knowledge is closely connected with the performance on number line estimation. Children in kindergarten were learning to map symbolic digits onto pre-existing non-symbolic representations , and thuSymbolic estimation did not uniquely predict calculation fluency among school-age children, which was in line with the findings of previous studies . For exaSome limitations of the present study are worth mentioning. First, the cross-sectional design of this study does not allow us to draw conclusions about the causal relationships between the two ANS aspects and mathematics skills. The direction of their relation should be examined further since recent studies also showed that mathematics skills may enhance ANS acuity e.g., . Second,Taken together, our results showed that the two ANS aspects have different effects on mathematics skills at different learning periods: non-symbolic estimation was uniquely related to mathematics skills in kindergarten, while symbolic estimation was uniquely related to mathematics skills in elementary school years. These results suggest that different types of ANS acuity should be used to predict mathematic skills in different learning periods and perhaps to identify children at-risk for mathematics difficulties. Moreover, interventions to promote children’s mathematics skills should target different ANS aspects for young and school-age children.This study was carried out in accordance with the recommendations of Ethical Guidelines for the Protection of Human Subjects of Research, Academic Ethics Committee at Shanghai Normal University. The protocol was approved by Academic Ethics Committee at Shanghai Normal University. The parents of all children gave their written consent in accordance with the Declaration of Helsinki.DC, GG, WW, and YL designed the study. WW, DC, and LZ collected the data, prepared the data for analysis, and wrote the manuscript. GG, DC, WW, and YL revised the 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.


Our understanding of Parkinson's disease (PD) has significantly accelerated over the last few years, but predominant advances have been made in developed, Western countries. Little is known about PD in the Central Asian (CA) and Transcaucasian (TC) countries. Here, we review the clinical characteristics, treatments used, epidemiology, and genetics of PD in CA and TC countries via a methodological search in MEDLINE, EMBASE, Scopus, Web of Science, and Google Scholar databases. For the acquisition of PD care-related data, the search was extended to the local web resources. Our findings showed that PD prevalence in the region is averaging 62 per 100,000 population. The mean age of onset is 56.4 ± 2.8 in females and 63.3 ± 3.5 in males. Large-scale national studies on PD prevalence from the region are currently lacking. A limited number of genetic studies with small cohorts and inconclusive results were identified. The G2019S LRRK2 mutation, the commonest mutation in PD worldwide, was found in 5.7% of patients with idiopathic PD and 17.6% of familial cases in 153 Uzbek patients. Our review highlighted systematic deficiencies in PD health care in the region including lacks of neurologists specializing in PD, delays in PD diagnosis, absence of specialized PD nurses and PD rehab services, limited access to PD medications and surgery, and the unavailability of PD infusion therapies. Overall, this article demonstrated the paucity of data on this common neurological disorder in CA and TC countries and identified a number of healthcare areas that require an urgent consideration. We conclude that well-designed large-scale epidemiological, genetic, and clinical studies are desperately needed in this region. Healthcare professionals, local and national institutions, and stakeholders must come together to address deficiencies in PD healthcare systems in CA and TC countries. Central Asian (CA) and Transcaucasian (TC) countries consist of a number of independent, upper-middle- and low-middle-income post-Soviet Union countries, populated with diverse ethnic groups. While Central Asia with overall population of 70 million is formed of five countries including Kazakhstan, Uzbekistan, Kyrgyzstan, Turkmenistan, and Tajikistan, Transcaucasian countries include Azerbaijan, Armenia, and Georgia with overall regional population of 16 million , Table 1This review encompassed all available population, outpatient clinic, and in-patient-based studies focusing on the clinical, genetic, epidemiologic, and care-related issues of PD in CA and TC regions published up to November 2018. The review included studies focusing only on idiopathic PD using the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank  or MovemPublications that did not focus on the frequency, clinical presentation, genetics, and care-related aspects of PD were excluded. Review articles were excluded, with the exception of their references.Abstracts and poster presentations published in the abstract books of the MDS, International Association of Parkinsonism and Related Disorders (IAPRD), and European Federation of Neurological Societies (EFNS) meetingsReference lists of all the available review articles and primary studiesMEDLINE, EMBASE, Scopus, Web of Science, and Google Scholar databases were searched for available research articles. “The name of the relevant country within the regions” and “Parkinson's disease” terms were used as keywords for the search, e.g., “Kazakhstan and Parkinson's disease”. With the purpose of including all the pertinent publications, the search was extended to the following resources:If data reporting the available PD treatment and care in CA and TC countries were not found in the listed databases, the search was extended to the official web resources belonging to the Health Ministries of each country, World Bank (WB) and World Health Organization (WHO) statistics concerning healthcare facilities, MDS website, and any available local reports on PD-related services. PRISMA flow diagram was used to report the data search procedure .The titles and abstracts of obtained publications were reviewed, and studies irrelevant to the aims of this review were excluded. The relevant publications were obtained in full copy and thoroughly reviewed. The following information was systematically sought from the reviewed literature: country, authors, publication year, study design, study year and duration, number of recruited PD patients, basic demographic and clinical characteristics including age at study period, age at onset, disease duration, family history of PD, response to levodopa, MDS UPDRS  score, and clinical subtype of PD. Age-adjusted and crude prevalence figures were recorded from the prevalence studies. For the genetic studies, the reported genes and mutations, as well as methods for genetic analysis, were extracted. Microsoft Excel 2010 was used for data analysis. The ensuing results were presented in the text and tables.P = 0.0005), well water consumption (P = 0.001), and working in the chemical industry (P = 0.04) [No large-scale community-based cross-sectional PD prevalence studies have been identified in CA and TC regions. Only outpatient and inpatient registry-based PD prevalence and frequency data have been hardly elicited from one Kazakhstani doctoral thesis  publishe = 0.04) . The stu = 0.04) .Four research papers have been found to report genetics of PD in CA and TC regions. The important ones are two doctoral thesis reports published in Russian language in Kazakhstan and Uzbekistan in 2015 and 2017, respectively. In addition, two small genetic reports by other authors also come from these two countries .Akanova , in her Several studies from Kazakhstan and Uzbekistan reported demographic and clinical details of PD patients in their regions. Three independent studies with relatively large cohorts, up to 595, reported mean age at disease onset 56.4 ± 2.8 in females and 63.3 ± 3.5 in males. The age of the patients at the study periods ranged from 20 to 91 years. All three studies reported female predominance in their cohorts with female-to-male ratio of 1.6 : 1 , 18 Sup).It was challenging to find a systematic study on the availability of PD care in CA and TC countries. This review explores the state of neurology and neurosurgery workforce, availability of PD medication, and physiotherapy in these countries searching local websites.CA and TC countries are in the European regions of WHO classification . TherefoNo trained PD nurses are available in these regions. One study on 545 patients shows that there is a delay in PD diagnosis after the onset symptoms for 3–3.5 years in Kazakhstan. Moreover, 80% of patients in this cohort were diagnosed with PD only in the advanced stage . This miThere have not been any studies systematically investigating the availability of antiparkinsonian medications in the regions. However, the official websites of the health ministries in Uzbekistan, Georgia, and Kazakhstan display the list of antiparkinsonian drugs registered with the State Pharmaceutical Registries –26. In tWhile this review did not find any information on the availability of the advanced PD treatments as infusion therapies with Duodopa and apomorphine, there are some reports on the application of deep brain stimulation (DBS) in movement disorders including PD in Kazakhstan from 2013. The conference abstract report by Shashkin et al.  states tSeveral web resources suggest that there are some rehabilitation centers specializing on PD physiotherapy in Kazakhstan and Uzbekistan , 32. TheThe outpatient registry-based PD prevalence studies showed low prevalence rates of about 62 per 100,000 population in CA. However, the global burden of PD article by Dorsey, Elbaz, and colleagues from the GBD 2016 Parkinson's Disease Collaborators shows higher figures based on ICD-10 state registry . This diThis review discovered 4 small-scale studies investigating the genetics of PD in the CA and TC countries. The major finding appears to be a high proportion of LRRK2 G2019S mutation among Uzbeks. This adds new data to Asian PD cohorts, since G2019S mutation has previously been very rarely reported among Asian PD patients . The UzbPositive findings on Parkin and SNCA mutations in a small cohort of Uzbek studies suggest that genetic investigations involving larger PD cohorts in CA and TC countries may yield more valuable data on the genetic determinants of PD in these regions. The lack of PD genetic studies in these countries might be attributable to insufficient financial resources, facilities for genetic investigations, and field staff to conduct large-scale studies locally. However, collaboration with world leading genetic institutions with an expertise in PD genetics could potentially provide a good opportunity for CA and TC countries to explore the genetics of PD in their population.The review showed the lack of access to a specialized PD-related care in CA and TC countries. There are very few neurologists specializing in PD with no available PD nurses, SLT, and occupational therapy specialists. There are appear to be two centers practicing PD rehabilitation, one in Kazakhstan and one in Uzbekistan; however, more PD rehabilitations centers need to be established in the regions. Although PD drugs are available for purchase, high prices for dopamine agonists and MAO inhibitors significantly affect access to these medications. DBS in PD has been successfully practiced in the capital of Kazakhstan. However, the large territories of TC and especially of CA countries probably require several DBS centers for adequate access and postsurgical follow-up. The aforementioned discussion points might reflect the quality of PD service in the concerned regions and highlight the important needs and potential actions for the improvement of PD-related care. The latter would be educational activities and training a number of PD specialists. Improving public awareness would also be of importance in the early diagnosis of PD and effective management. There is a need in introduction of PD infusion therapies to improve the management of patients with the advanced PD in the region.This review highlights several issues related to PD epidemiology, genetics, and care in CA and TC countries. Data on PD prevalence and genetics are sparse and available only in a couple of CA countries, whereas no data are present in the remaining countries of the regions. The available studies report a relatively young onset of PD suggesting a need for well-designed large-scale epidemiological and genetic studies. Very limited number of neurologists specializing in PD, absence of PD nurses, SLT and rehab specialists, and limited access to PD medication and surgery, devoid of PD infusion therapies, might reflect the inadequate level of PD care in CA and TC countries. Therefore, a major effort from active local medical specialists supported by the world PD experts and movement disorders organizations is warranted to increase public awareness of PD, train field staff, and improve PD-related care in these countries.


Cognitive studies generally report impaired autobiographical memory in individuals with autism spectrum disorder (ASD), but mostly using verbal paradigms. In the present study, we therefore investigated the properties of both past and future autobiographical productions using visual cues in 16 boys with ASD and 16 typically developing (TD) participants aged between 10 and 18 years. We focused on sensory properties, emotional properties, and recollection, probing past and future productions for both near and distant time periods. Results showed that the ASD group performed more poorly than controls on free recall for recent periods, but performed like them when provided with visual cues. In addition, the ASD group reported fewer sensory details than controls and exhibited difficulties in the experience of recollection for the most remote events. These data suggest a combination of consolidation and binding deficits. Finally, our findings reveal the relevance of using visual cues to probe autobiographical memory, with possible perspectives for memory rehabilitation. Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by deficits in social communication, with restricted and repetitive behaviors. There is growing evidence that people with ASD have atypical memory functioning , even ifpre-experience a possible scenario  and to imagine possible future experiences (episodic future thinking) . Both epscenario . This prscenario . Moreovescenario . This nescenario  to more scenario  and sociscenario , while oscenario . Hence, scenario .happy, scared), cognitive , and sensory  terms than TD children  than episodic . Ciaramechildren . This dichildren  or futurchildren . On the children  and earlchildren . Hence, weak central coherence evoked by Thinking in Pictures   . All theductions .Hence, and as suggested by Temple Grandin’s testimony, pictures could be a valuable tool for studying AM, by providing a visual aid to overcome the language constraints associated with the free recall paradigm. Therefore, pictures would constitute a more appropriate mean of testing the properties of episodic memories in ASD. In addition, these visual supports would provide an opportunity to test different kinds of properties, including sensory details, and investigate the possible impact on AM of the impairments in sensory processing observed in ASD .The main aim of the present study was to investigate the properties of episodic memories and future thinking in high-functioning adolescents with ASD using visual cues. We focused on the sensory and emotional properties and the quality of the experience of recollection associated with autobiographical productions for four time periods: two in the past  and two in the future . First, given the known retrieval deficit in ASD and possible difficulties in scene construction, we predicted that free recall performance would be impaired, but performance would normalize when visual cues were provided. We added a general neuropsychological assessment focusing on cognitive functions involved in AM retrieval, i.e., executive functions, short-term memory, and verbal episodic memory, to discuss our results. Based on the cognitive profile of ASD, we expected to find baseline differences in verbal episodic memory, planning and short-term memory. Second, given the perceptual bias reported in ASD  and the SD = 2.4)  . They weD = 2.4)  criteriaD = 2.4)  and/or AD = 2.4) . The ADID = 2.4) . These tEach child also underwent a neuropsychological assessment focusing on the cognitive abilities involved in AM production . This asFinally, all participants underwent a brief investigation of personal semantic knowledge, in order to exclude a possible major deficit that might interfere with the AM task. This consisted of a questionnaire coupled with visual cues about general personal information on three different topics, adapted from This task explored specific past personal events and future thinking for the day before (recent past), last summer vacation (remote past), next day (near future), and forthcoming summer vacation (distant future). For each period, visual cues were provided to support production . All reswho content, there was a person of every age  and gender. In addition, five types of perceptions were illustrated with drawings. For example, colors were associated with a color chart, while smells were indicated with a trash can or a flower; sounds with a musical note or bell; tastes with a lemon or a sweet; and tactile feelings with a finger placed on a pillow (mushy) or on ice (cold) . Contents could refer to temporal situations, spatial locations , modes of transport , activities  and people present . All the pictures were drawn by a professional illustrator who ensured that each type of content was included. For example, for the e (cold) . Each quwhat), temporal situation (when), spatial location (where), course of the event (how), and people present (who)  and the future . These questions allowed us to manipulate orientation (past vs. future) and temporal distance, either close (yesterday or tomorrow) or remote (last or next summer vacation). For past events, participants were instructed to remember real events that had happened to them . For future events, participants were instructed to imagine an event that could happen in their lives or else was completely invented . If 1 min went by without an answer, the interviewer gave the children an open-ended prompt . If they were still not able to provide different contents associated with an episodic event, after a further minute, they were helped with visual cues for each of these components. Cues concerned activities (nt (who) . Episodint (who) .No image) to 6 (Lot of distinctive images)”; Completely blurry) to 6 (Very precise)?”; No feeling of reliving) to 6 (Very intense feeling)?”  to 6 (Very important)”), its frequency of evocation  to 6 (Very often)”) for past and future events. For future events only, we asked whether they wished them to happen  to 6 (Very much)”), and the probability of occurrence  to 6 (Certainly)”) ?” . Finallyainly)”) . To ensuStatistical analyses were performed using Statistica Version 10 software . The reported values are means and standard deviations.p < 0.05 in one or both groups), we conducted non-parametric analyses (Friedman ANOVAs and Wilcoxon for within comparisons and Mann-Whitney for between comparisons with Z adjusted).Due to the limited number of participants and some non-normally distributed variables , and planning , but none of the other comparisons including working memory, yielded significant differences , near future  and a marginally significant effect for the distant future . The ASD group produced fewer event memories and projections than the TD group . The control group reported less details for the distant future period compared to the recent past (p = 0.03) and near future periods (p = 0.03) (see Mann–Whitney .03) see .2 = 13.13, p = 0.004, η2 = 0.84). The arousal associated to memories for the recent past was lower compared to the remote past (p = 0.02) and distant future periods (p = 0.008). Friedman ANOVA analyses conducted in the ASD group showed a period effect for valence . Memories associated with the remote past had a more positive valence than the recent past (p = 0.01).The analyses of emotion  revealed no significant differences between groups . Howeverz = 2.74, p = 0.006, η2 = 0.23). Analyses of each perceptual modality revealed significant differences between the ASD and control group on color for recent past  and for remote past . We also observed differences on smell for remote past period , on sound , and tactile feeling for remote past . Except for sounds for the distant future, the ASD group produced fewer information associated with less intensity than the TD group for all modalities and periods cited above : both scores associated with the near future were reduced compared to the remote past  and distant future . Second and concerning the ASD group, analyses showed a period effect on the intensity of colors : the intensity of colors associated with the recent past was reduced compared to the remote past (p = 0.01). We also observed in this group a period effect on the intensity of sounds : sound intensity associated with the remote past was reduced compared to the distant future (p = 0.02).Friedman ANOVA analyses were conducted within each group on each category of sensory perceptual details. First and concerning the TD group, analyses showed a period effect on both the number and intensity of smell , subjective recollection , and frequency of evocation . Friedman ANOVA analyses conducted in the TD group showed a period effect on mental imagery . Number of mental imagery associated with recent past was more important than near (p = 0.05) and distant (p = 0.008) future periods. Accuracy of mental imagery associated with recent past was better than for the remote past (p = 0.008) and distant future periods (p = 0.008) and accuracy of mental imagery associated with near future was better than distant future period (p = 0.05).Mann–Whitney comparisons revealed no significant difference for the measures of perspective, personal relevance, wish for it to happen, or probability of occurrence . HoweverThe aim of this study was to analyze the properties of past memories and future thinking produced by adolescents with ASD, compared with their TD peers, using a visual cues paradigm. As hypothesized, results revealed difficulty with free recall in the ASD group that contrasted with typical performance on the visually cued task. We found differences between the groups on the total number of sensory details provided only for the remote past period. These differences also appeared when we considered each perceptual modality separately, with the ASD group reporting fewer color, smell, sound, and tactile feeling details and intensity than the TD group. Finally, we did not observe any impairment on the measures of emotion and quality of the experience of recollection, except for number of mental imagery, subjective recollection and frequency of evocation for the remote past.Our results showed a significant benefit from visual cues in the production of both past and future episodic autobiographical events. This enhanced performance is in line with the task support hypothesis developed by The impaired performances of participants with ASD on the free recall task were in accordance with their story recall performances , and mirror previous findings in individuals with ASD ,b. Our dper se, they found impaired performance for colors compared with shapes. Two years later, Contrary to our prediction, the episodic memories provided by the participants with ASD contained just as many sensory details as those produced by controls for three periods. These results are in accordance with When our participants with ASD were prompted by visual cues, we did not find any difference in the processing of either the valence or intensity of emotions: they produced memories that were just as positive as those of controls. These results further justify the use of visual cues at retrieval to compensate for the difficulty that individuals with ASD have understanding verbally expressed emotions. Moreover, Concerning the other properties, we observed differences between the two groups only for the remote past. The ASD group had reduced mental imagery, subjective recollection and frequency of evocation. Participants with ASD produced memories lacking in details and associated with reduced episodic properties, compared to controls. Once more, this result is in accordance with abnormal forgetting previously reported in ASD. These data replicate those of other experimental studies that used anterograde memory paradigms . Our parSurprisingly, we did not observe the same pattern of performance for projections into the future. Performance was poorer for future versus past periods in the control group for number and accuracy of mental imagery, as previously demonstrated by This work presents certain limits. First, the sample size is relatively small, preventing us from generalizing to the ASD population. In addition, since we had the opportunity to include only boys, inclusion of a group of girls would extend our conclusions to ASD as a whole. Second, our groups do not differ in age but have a wide age range. Given the major influence of age on cognitive development, it would be particularly interesting to investigate the relationship between AM development and other cognitive abilities, such as theory of mind which is impaired in ASD. Third, given the interaction between AM development and social interactions, environment and lifestyle , largely neglected in previous studies, it is crucial to consider these factors in future research. Fourth, each personal event was manually transcribed and scored according to a grid coding for five components of episodic memory . Scoring was obtained separately by the interviewer and a psychologist until a consensus was reached. In future work, recording verbatim productions would refine the analysis in providing a more detailed investigation of each component. Finally, the interviewer was one of the two coders and was thus not blind to groups. It would be relevant to replicate our results with two coders blind to the diagnoses and verify their inter-rater reliability.Our study suggests that AM impairment may result from a combination of a consolidation deficit for the most remote events associated with a binding deficit and demonstrates the relevance of using visual cues to facilitate AM retrieval. These results are in keeping with other studies and may be relevant to other cognitive abilities, as recently suggested by Families were given a comprehensive description of the research. The study was approved by the relevant ethics committees, and written consent was obtained from the participants  in line with their guidelines.MA, JLV, FE, and BG-G contributed to the conception and design of the study. MA, JLV, JM, LB, FG, EM, CB, FB-B, and J-MB organized the database. MA, PW, JLV, and BG-G conducted the statistical analysis. MA, PW, and BG-G wrote the first draft of the manuscript. All authors contributed to the manuscript revision, and read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.