Age-related behavioural and striatal dysfunctions in Shank3ΔC/ΔC mouse model of autism spectrum disorder.

Autism spectrum disorders (ASDs) are defined as a set of neurodevelopmental disorders and a lifelong condition. In mice, most of the studies focused on the developmental aspects of these diseases. In this paper, we examined the evolution of motor stereotypies through adulthood in the Shank3ΔC/ΔC mouse model of ASD, and their underlying striatal alterations, at 10 weeks, 20 weeks, and 40 weeks. We highlighted that motor stereotypies worsened at 40 weeks possibly carried by earlier striatal medium spiny neurons (MSN) alterations in GABAergic transmission and morphology. Moreover, we report that 20 weeks could be a critical time-point in the striatal-related ASD physiopathology, and we suggest that MSN alterations may not be the direct consequence of developmental issues, but rather be a consequence of other impairments occurring earlier.

Genetic and environmental mouse models of autism reproduce the spectrum of the disease.

Genetic and environmental factors increase autism spectrum disorder (ASD) incidence, and this has led to the generation of corresponding animal models, with some showing strong construct and face validity. This short review focuses on results we have recently obtained with environmental and genetic mouse models of ASD and that are the valproic acid, the poly I:C and the Shank 3 models. This has allowed us to provide a comparative description of these widely used animal models providing an interesting perspective as to the pros and cons of each one of them, in our experimental settings. In these papers, we focused on motor and gait disorders which are currently not included in the diagnosis criteria, but which may provide new insights to ASD pathophysiology potentially leading to innovative therapies for a disease that currently has none. In all these models, we reported behavioral, cellular and molecular alterations related to the cerebellum. Motor and gait deficits were observed to various degrees in animal models and, when strongly present, they were correlated to the severity of social deficits as well as to the number of cerebellar Purkinje cells. Additionally, we also reported that, like in humans, males are more severely affected than females in these ASD models. These findings, along with an increasing body of literature, open new hopes in the ASD field pointing to brain regions, such the cerebellum, that are at the crossroads between cognitive, social and motor deficits. Targeting these brain regions and their underlying pathways and synaptic connections may prove of significant benefits.

Condylar Resorption After Orthognathic Surgery: A Review of Risk Factors With a Proposed Algorithm of Treatment.

This study aimed to critically reanalyze systematic reviews of patients suffering from condylar resorption (CR) and summarize the current scientific pieces of evidence with a focus on a possible relationship between CR and orthognathic surgery (OS). The work followed the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol" guidelines and was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42020168660). The search strategy produced 143 articles. After reading the abstracts, 113 articles were excluded, and the full-text articles in English of the remaining 30 studies were separately examined for eligibility by 2 authors, with 20 of them being excluded because they did not meet the inclusion criteria. Finally, 10 systematic reviews were processed for critical evaluation. Young female patients with a high mandibular plane angle, diminished posterior facial height, posteriorly inclined condylar neck, and a counter-clockwise jaw rotation, are more likely to develop CR after OS. The most common procedure associated with CR in the included systematic reviews was the bimaxillary OS followed by bilateral sagittal split osteotomy. Hence, extreme caution and surgical modification should be used in these high-risk conditions. There is still a need for more evidence on the risks of OS or iatrogenic factors during the fixation of various osteosynthesis devices because it is still inconclusive and requires further justification.

Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models.

Autism spectrum disorders (ASD) are complex conditions that stem from a combination of genetic, epigenetic and environmental influences during early pre- and postnatal childhood. The review focuses on the cerebellum and the striatum, two structures involved in motor, sensory, cognitive and social functions altered in ASD. We summarize clinical and fundamental studies highlighting the importance of these two structures in ASD. We further discuss the relation between cellular and molecular alterations with the observed behavior at the social, cognitive, motor and gait levels. Functional correlates regarding neuronal activity are also detailed wherever possible, and sexual dimorphism is explored pointing to the need to apprehend ASD in both sexes, as findings can be dramatically different at both quantitative and qualitative levels. The review focuses also on a set of three recent papers from our laboratory where we explored motor and gait function in various genetic and environmental ASD animal models. We report that motor and gait behaviors can constitute an early and quantitative window to the disease, as they often correlate with the severity of social impairments and loss of cerebellar Purkinje cells. The review ends with suggestions as to the main obstacles that need to be surpassed before an appropriate management of the disease can be proposed.

Clinical and laboratory findings of COVID-19: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: The aim of this study was to systematically review all COVID-19 publications to summarize the clinical features, assess comorbidities, prevalence, and disease outcomes. METHODS: Included were all COVID-19 published studies between January 1 to July 20, 2020. The random effect model was used to calculate the pooled prevalence and corresponding 95% confidence interval (CI). Publication bias was assessed using the funnel plot for the standard error by logit event. RESULTS: The mean age of the patients was 46.8 years (95% CI, 41.0-52.6) and males comprised 54.0% (95% CI, 51.3-56.7). Total co-morbidities prevalence was 29.5% (95% CI, 19.0-36.6), with diabetes mellitus being the most prevalent 13.8% (95% CI, 8.7-21.1), followed by hypertension 11.7% (95% CI, 5.7-22.6), and cardiovascular disease 9.7% (95% CI, 6.5-14.2). The most common clinical manifestations were fever, 82.0% (95% CI, 67.7-90.8), cough 54.3% (95% CI, 45.5-62.9), fatigue 30.2% (95% CI, 23.3-38.1), sputum 28.5% (95% CI, 21.2-37.2), sore throat 21.7% (95% CI, 14.6-31.0), and headache 11.0% (95% CI, 7.9-15.2). The most common COVID-19 serious complications were RNA Anemia 98.2% (95% CI, 96.2-99.2), hospitalization 83.7% (95% CI, 76.0-89.3), bilateral pneumonia 70.9% (95% CI, 58.2-81.0); of those hospitalized 43.5% (95% CI, 24.9-64.2) were discharged. Fatality accounted for 10.5% (95% CI 6.8-16.1). CONCLUSION: Patients infected with COVID-19 coronavirus showed a wide range of clinical presentation with non-specific symptoms.

Dopamine and addiction: what have we learned from 40 years of research.

Among the neurotransmitters involved in addiction, dopamine (DA) is clearly the best known. The critical role of DA in addiction is supported by converging evidence that has been accumulated in the last 40 years. In the present review, first we describe the dopaminergic system in terms of connectivity, functioning and involvement in reward processes. Second, we describe the functional, structural, and molecular changes induced by drugs within the DA system in terms of neuronal activity, synaptic plasticity and transcriptional and molecular adaptations. Third, we describe how genetic mouse models have helped characterizing the role of DA in addiction. Fourth, we describe the involvement of the DA system in the vulnerability to addiction and the interesting case of addiction DA replacement therapy in Parkinson's disease. Finally, we describe how the DA system has been targeted to treat patients suffering from addiction and the result obtained in clinical settings and we discuss how these different lines of evidence have been instrumental in shaping our understanding of the physiopathology of drug addiction.

A Delay between Motor Cortex Lesions and Neuronal Transplantation Enhances Graft Integration and Improves Repair and Recovery.

We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged motor cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. Here, we report that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, and proliferation of grafted cells. More importantly, the delay dramatically increases the density of projections developed by grafted neurons and improves functional repair and recovery as assessed by intravital dynamic imaging and behavioral tests. These findings open new avenues in cell transplantation strategies as they indicate successful brain repair may occur following delayed transplantation.SIGNIFICANCE STATEMENT Cell transplantation represents a promising therapy for cortical trauma. We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged cortical pathways. A critical barrier hindering the application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. We demonstrate that a 1 week delay between the lesion and transplantation significantly enhances graft vascularization, survival, proliferation, and the density of the projections developed by grafted neurons. More importantly, the delay has a beneficial impact on functional repair and recovery. These results impact the effectiveness of transplantation strategies in a wide range of traumatic injuries for which therapeutic intervention is not immediately feasible.

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods: Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received valproic acid (450 mg/kg) at embryonic day 12.5 and offspring underwent a battery of behavioral analyses before being killed for histological correlates in motor cortex, nigrostriatal pathway, and cerebellum. Results: We show that while valproic acid male mice show both social and motor impairments, female mice only show motor impairments. Prenatal valproic acid exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area. Conclusions: Our results suggest that motor dysfunction could contribute to social and communication deficits in autism spectrum disorders and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in autism spectrum disorders may potentially help the quantitative diagnosis of autism spectrum disorders and strategies aimed at improving motor behavior may provide a global therapeutic benefit.

Percutaneous Cryoablation of Renal Tumors: Is It Time for a New Paradigm Shift?

PURPOSE: To retrospectively assess long-term outcomes of percutaneous renal cryoablation, including factors affecting complications and local recurrence rates. MATERIALS AND METHODS: A total of 357 computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation procedures were performed for 382 masses in 302 outpatients; 347 were biopsy-proven renal-cell carcinoma (RCC) or Bosniak category > III masses (n = 28). Benign pathologic conditions (n = 18) or metastatic non-RCC disease (n = 17) were included to analyze procedural complication rate, but recurrence rates, tumor staging, and nephrometry score were limited to RCCs. The average tumor diameter was 2.9 cm (range, 1-10.3 cm), and median nephrometry score for RCC was 8 (mean, 7.4). Protection of adjacent vital structures was performed in 34% of procedures (n = 121), and ureteral stent placement was performed for 9.2% (n = 33). All major complications were graded per surgical Clavien-Dindo criteria. RESULTS: The average CT-visible cryoablation zone diameter was 5 cm (range, 2.5-10.5 cm). Grade ≥ 3 complications occurred in 2.8% of procedures (n = 10), and appeared related to only high nephrometry scores (P = .0086) and larger tumors (P = .0034). No significant changes in renal function before and after the procedure were noted (P = .18). At a mean follow-up of 31.8 months, the local tumor recurrence rate was 3.2% (11 of 347) for RCC, and no significant difference was noted between tumors larger or smaller than 3 cm (P = .15). The difference reached significance only among the small number of stage ≥ T2 RCC tumors (P = .0039). CONCLUSIONS: Long-term follow-up of percutaneous renal cryoablation demonstrates low recurrence rates with preserved renal function, even for patients with high nephrometry scores and body mass index, assuming thorough cytotoxic technique and protection measures.

Knowledge, Practices, and Nasal Carriage Rate of MRSA Amongst Dental Professionals.

OBJECTIVE: Resistance of Staphylococcus aureus (S. aureus) against common antibiotics has been increasing given the rampant use of antibiotics. Methicillin-resistant S. aureus (MRSA) is particularly important because it has been reported to present in hospital-acquired as well as community-acquired infections. Our aim was to study the types and subtypes of MRSA isolated from nasal swabs taken from volunteering dental school students and to assess and analyse the knowledge of dental health care workers (DHCWs) on MRSA and prevention of its infection. METHODS: A total of 100 participants, which included staff, students, and dental auxiliaries, from the School of Dental Sciences, Krishna Institute of Medical Sciences, Deemed to Be University, Karad, India, were included in the study which was conducted from June 2020 to 1 June 2021. All the participants completed a survey and underwent collection of nasal swabs. The samples were cultured and underwent microbiological and molecular analysis for MRSA. The questionnaire was sent out electronically via SurveyMonkey. RESULTS: Sixty-three percent of the participants were female. The majority were undergraduate students (66%) and younger than 25 years (77%). The prevalence of MRSA in the sample was the MRSA type SCCmec type V (54.8%). The survey reports a lack of knowledge amongst dental students on MRSA and prevention of its infection. The majority (69%) of participants had not heard of MRSA infection and had inadequate knowledge of MRSA infection. Only 29% of the participants think that a healthy person may have MRSA without feeling ill. Eighty-five percent of the participants reported that they have written polices and guidelines to control MRSA. Eighty-five percent of the participants indicated that they are less confident in their knowledge on MRSA infection control protocols, and 94% mentioned that the dental clinics have written guidelines for hand hygiene. CONCLUSIONS: DHCWs have limited knowledge of MRSA infection, emphasising the need for appropriate clinical training. Academic institutions should promote effective infection control training to protect students, faculty, and other employees.

Comparative evaluation of nasolabial flap and buccal fat pad flap in the surgical management of oral submucous fibrosis: a systematic review and meta-analysis.

PURPOSE: Oral submucous fibrosis (OSMF) is a chronic, potentially malignant condition affecting any part of the oral cavity and is prevalent in Southeast Asia and the Indian subcontinent. The aim of this study is to compare the efficacy of buccal fat pad flap with the nasolabial flap in the management of OSMF. METHODS: We systematically compared two commonly used constructive techniques in the management of OSMF: the buccal pad of fat flap and the nasolabial flap. We performed a comprehensive search in four databases for all articles published between 1982 and November 2021. We assessed the risk of bias using the Cochrane Handbook and Newcastle-Ottawa Scale. We used the mean difference (MD) for pooling the data with 95% confidence intervals (CIs) and evaluated the heterogeneity between pooled studies using χ2 and I2 tests. RESULTS: Out of 917 studies, six were included in this review. The meta-analysis significantly favored conventional nasolabial flap over buccal fat pad flap in improving the maximal mouth opening (MD, - 2.52; 95% CI, - 4.44 to - 0.60; P = 0.01; I2 = 0%) after OSMF reconstructive surgery. Conversely, when it comes to esthetic outcomes, these studies favored buccal fat pad flap. CONCLUSION: Our meta-analysis found that nasolabial flap was better than buccal fat pad flap in terms of mouth opening restoration after OSMF reconstructive surgery. Also, the included studies found better results, favoring nasolabial flap over buccal fat pad flap in terms of oral commissural width restoration. Also, these studies reported better outcomes in terms of esthetics, favoring buccal fat pad flap. Further studies with larger sample sizes and different populations/races are needed to confirm our findings.

Risk Factors Contributing to Symptomatic Miniplate Removal following Orthognathic Surgery: Systematic Review and Meta-Analysis.

Background/Objectives: The use of miniplates for stabilizing bones post orthognathic surgery has surged in popularity due to their efficacy in ensuring stability and hastening recovery. However, controversy exists regarding what should be done with these miniplates after surgery. Some surgeons advocate for their removal, while others suggest leaving them in place. This study sought to assess the frequency, causes, and potential risk factors linked with miniplate removal in orthognathic procedures. Methods: A thorough meta-analysis was conducted by scrutinizing studies from various databases including PubMed, Google Scholar, Embase, and Scopus, focusing on publications spanning from 1989 to 2023. Results: Ten studies meeting the inclusion criteria, encompassing 1603 patients, were chosen for inclusion in the meta-analysis. The male-to-female ratio varied from 0.7:1 to 4:1. Overall, 5595 miniplates were inserted, with 294 (5.3%) being subsequently removed. Primary reasons for miniplate removal included infection (161 cases, 2.9%), exposure of miniplates (34 cases, 0.6%), and palpable plates (23 cases, 0.4%). Other indications comprised pain, patient preference, and temperature sensitivity. Less frequent causes for miniplate removal included sinusitis, secondary surgery, and dental pathology. The mean duration of miniplate removal was 5.5 months, with the majority (56.1%) being removed from the mandible rather than the maxilla. In conclusion, this meta-analysis underscores the importance of miniplate removal when hardware causes complications and physical discomfort. The primary reasons for removing miniplates were infection and plate exposure, with the mandible being the most common removal site. Conclusions: These findings emphasize the need for continued monitoring to assess the fate of miniplates in orthognathic surgery and provide valuable information for future clinical decision-making.

SRY gene isolation from teeth for forensic gender identification-An observational study.

Personal identification in forensics is possible with gender determination using DNA (deoxyribonucleic acid) analysis. DNA isolation from teeth samples subjected to extreme temperatures has been shown to predict the gender of the deceased. However, the literature lacks studies on DNA extracted from tooth samples exposed to freezing temperatures. This study aimed to isolate the SRY gene from the extirpated pulp of teeth that were subjected to varying temperatures for gender identification. Thirty teeth with vital pulps, divided into 3 groups were included in the study. Each group consisted of 5 male and 5 female tooth samples. The groups were exposed to diverse environmental factors for three weeks. Group 1: room temperature (R group); Group 2: high temperature (H group) and Group 3: freezing temperature (F group). Later, DNA was isolated from the pulp tissue, and the SRY gene was amplified using PCR (Polymerase Chain Reaction). The Sensitivity and Specificity of the results were analyzed. SRY gene detected in the study samples identified accurate gender with a 46.70% Sensitivity and 93.30% Specificity. Significant difference was found in the correlation between gene expression and gender among the three groups (p = 1.000). The study validates that dental pulp tissue can be a reliable source for DNA extraction. And SRY gene amplification from teeth exposed to diverse environmental conditions. Further investigations are required to validate its application in forensics.

Correction: SRY gene isolation from teeth for forensic gender identification-An observational study.

[This corrects the article DOI: 10.1371/journal.pone.0294751.].

Adenoid Cystic Carcinoma of the Minor Salivary Glands: A Systematic Review and Meta-Analysis of Clinical Characteristics and Management Strategies.

BACKGROUND: Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This study aimed to comprehensively review ACC of MSGs, focusing on clinical characteristics, imaging modalities, treatment approaches, and long-term outcomes. METHODS: A systematic search was conducted in PubMed, Web of Science, and MEDLINE databases to identify relevant articles reporting cases of ACC of MSGs between January 1997 and March 2023. The study was registered in PROSPERO (ID: CRD42023449478). A total of 10 studies that met the inclusion criteria were selected for critical review. In total, 902 patients were diagnosed with ACC of MSGs with an age range of 44.3 to 63 years, and an average age of 56.6 years. The female to male ratio ranges from 1:1 to 2.4:1. Regarding the primary site of ACC, the palate was the most common location, accounting for 30.5% to 83.3%, followed by the buccal mucosa, floor of the mouth, and lip and the retromolar area. For histology, the solid mass pattern was the most prevalent, seen in 95.2% of patients, followed by the cribriform pattern. Regarding treatment modalities, surgery was the most common approach, applied in 76.3% of cases, with a combination of surgery and radiotherapy used in 29.0% of cases. A smaller fraction, 3.2%, received a combination of surgery, chemotherapy, and radiotherapy, and 8.3% underwent radiotherapy alone. Local recurrence rates varied between 1% and 28.5%, and distant metastasis occurred in 18.2% to 33.3% of cases, predominantly to lymph nodes (14.5%). An analysis of overall survival across various stages and patient numbers indicated a 5-year survival rate of 68.0%. The findings of this study provide valuable insights for physicians in making treatment decisions and emphasize the need for ongoing research and collaborative clinical efforts to improve the management and outcomes of this challenging disease. CONCLUSION: ACC of MSGs is a multifaceted condition typically manifesting as asymptomatic enlargement and ulceration. This disease is marked by distinct histopathological patterns and perineural invasion (PNI). Recognizing these distinctive aspects is key in shaping the treatment plan, which can range from surgical procedures to radiation therapy, chemotherapy, and evolving targeted treatments. Continuous research and collaborative clinical efforts remain critical for ongoing progress in the treatment and management of this challenging condition.

Long-Term Evaluation of Tooth Transplantation: An Umbrella Review.

Aim/Objective: This umbrella review of systematic reviews aims to summarize the available data regarding both success and survival rates of tooth autotransplantation, in addition to analyzing the risk factors that are connected to those rates. Methods: This umbrella review was performed according to the evaluation of various meta-analyses and systematic reviews following AMSTAR2 guidelines. A systematic search of literature on PubMed, Scopus, MEDLINE, EMBASE, and the Cochrane Database. Six systematic reviews were included. Explicit inclusion and exclusion criteria were applied. It is registered in PROSPERO under the registration number (CRD-42023415623). Results: The studies reviewed were written from 2014 to 2018, which extracted the information from various studies spanning from 1968 to 2014. According to the selected studies regarding autotransplanted teeth in humans, they showed the following: A survival rate overall of 87.39% and a success rate overall of 90.29%. These factors were the most common in relation to the success of the autotransplanted teeth: age, gender, and stage of root development. On the other hand, common unfavorable results linked to the transplanted teeth in these studies were failure, ankylosis, and internal root resorption, followed by extraction and hypermobility. Conclusions: The wide body of evidence gathered illustrates that autotransplantation is an operation that dispenses high rates of survival and success. Furthermore, risk factors like root development stage, recipient site, and donor tooth type established a remarkable association with the negative outcomes of the procedure. For successful tooth autotransplantation, patient selection is crucial. Younger patients and those with donor teeth at an optimal stage of root development typically experience better outcomes. Preoperative planning should include comprehensive evaluations and advanced imaging techniques to accurately assess both the donor tooth and the recipient site. Nonetheless, on account of heterogeneity and the quality of the studies included in this investigation, caution should be taken when interpreting the mentioned results.

The Patterns of Impacted Third Molars and Their Associated Pathologies: A Retrospective Observational Study of 704 Patients.

Background: The study aims to investigate parameters in patients attending Fujairah Dental Center, including assessing the prevalence of impacted teeth, determining the frequency of associated pathological conditions, and evaluating the patterns and angulations of impacted third molars. Methods: It is a retrospective descriptive study of the panoramic radiographs of patients who attended Fujairah Dental Center for dental care between January 2011 and December 2017. The minimum age for inclusion was 17 years. Clinical records were used to obtain the demographic details of patients, such as age, gender, nationality, medical history, and smoking history. Seven hundred and four panoramic radiographs and clinical records of patients were analyzed. The age range was between 17 and 112 years old, with a mean age of 34 years (S.D 13.5). Results: Of the 704 panoramic radiographs evaluated, 236 (33.6%) X-rays showed teeth impaction with a total of 562 impacted teeth in the upper and lower jaws. Five hundred and twenty-five (93.4%) were impacted third molars, and 37 (6.5%) teeth were other kinds of impacted teeth. Females showed a higher frequency of impacted teeth (62.6%) compared to males (37.4%). The highest prevalence of impacted teeth was found in the 17-25 year age group (61%), and the prevalence declined with advancing age. Impacted third molars were more likely to occur in the mandible (57.3%) than in the maxilla (42.7%). Most of the impacted third molars were in the mesioangular position, followed by the vertical position. The evaluation of the depth of impacted third molars demonstrated that level C impaction was the most frequently seen, followed by level B impaction. Impacted third-molar teeth often presented with two roots (60.7%), followed by a single root (31.3%). An evaluation of the relationship between lower third molars and the inferior dental canal (IDC) revealed that the most frequently observed relation was interrupted (61.5%), followed by a distant relation to the ID canal, and 13% were superimposed. The most common morphological pattern of roots of the impacted third molars was either straight-type or curved and dilacerated roots (5.7%). Additionally, the most noticed pathological conditions associated with impacted teeth were carious second molars adjacent to impacted third molars (42%), which was more likely to be seen in the 17-25-year age group, with females having a higher prevalence than males.

Female mice prenatally exposed to valproic acid exhibit complex and prolonged social behavior deficits.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized mainly by deficits in social communication and stereotyped and restricted behavior and interests with a male to female bias of 4.2/1. Social behavior in ASD animal models is commonly analyzed in males, and seldomly in females, using the widely implemented three-chambers test procedure. Here, we implemented a novel procedure, the Live Mouse Tracker (LMT), combining artificial intelligence, machine learning procedures and behavioral measures. We used it on mice that were prenatally exposed to valproic acid (VPA) (450 mg/kg) at embryonic day 12.5, a widely recognized and potent ASD model that we had previously extensively characterized. We focused on female mice offspring, in which social deficits have been rarely documented when using the 3-CT procedure. We recorded several parameters related to social behavior in these mice, continuously for three days in groups of four female mice. Comparisons were made on groups of 4 female mice with the same treatment (4 saline or 4 VPA) or with different treatments (3 saline and 1 VPA). We report that VPA females show several types of social deficits, which are different in nature and magnitude in relation with time. When VPA mice were placed in the LMT alongside saline mice, their social deficits showed significant improvement as early as 1 h from the start of the experiment, lasting up to 3 days throughout the duration of the experiment. Our findings suggest that ASD may be underdiagnosed in females. They also imply that ASD-related social deficits can be ameliorated by the presence of typical individuals.

Anthracycline-induced cardiotoxicity on regional myocardial work and left ventricular mechanical dispersion in adolescents and young adults in post-lymphoma remission.

BACKGROUND: Myocardial work (MW) is a new echocardiographic tool with a high sensitivity to detect early and subtle alterations of myocardial function. We aimed to evaluate the late effects of anthracyclines by assessing the global and segmental MW and intraventricular mechanical dispersion from speckle tracking echocardiography in childhood lymphoma survivors (CLS). METHODS: Thirty-one young adults including CLS and age-matched healthy controls were enrolled. All underwent echocardiography including an evaluation of left ventricular (LV) morphology and regional function. We assessed LV longitudinal (differentiating sub-endocardial and sub-epicardial layers), circumferential strains and twist, global and regional MW index (MWI). LV mechanical dispersion was assessed from the time dispersion of LV longitudinal strain, from myocardial wasted work (MWW) and myocardial work efficiency (MWE). RESULTS: The longitudinal strains both at the level of the sub-endocardium and sub-epicardium were reduced in CLS compared to controls. The global MWI was also decreased (1668 ± 266 vs 1870 ± 264%.mmHg in CLS patients and controls, respectively, p < 0.05), especially on the apical segments. An increase of LV intraventricular mechanical dispersion was observed in CLS. MWW and MWE remained unchanged compared to controls. CONCLUSION: Our results strongly support that cardiac remodeling is observed in CLS, characterized by a decrease in MW and an increase in LV mechanical dispersion. The apex is specifically altered, but its clinical significance remains uncertain. MW as a complement to strain seems interesting in cancer survivors to detect myocardial dysfunction at early stage and adapt their follow-up.