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Homework is a debated issue in society and its relationship with academic achievement has been deeply studied in the last years. Nowadays, schools are multicultural stages in which students from different cultures and ethnicities work together. In this sense, the present study aims to compare homework involvement and academic achievement in a sample of native and immigrant students, as well as to study immigrant students’ relationship between homework involvement and Math achievement. The sample included 1328 students, 10 to 16 years old from Spanish families (85.6%) or are immigrant students or students of immigrant origin (14.4%) from South America, Europe, Africa, and Asia. The study was developed considering three informants: elementary and secondary students, their parents and their teachers.Results showed higher involvement in homework in native students than in immigrant. Between immigrants students, those who are more involved in homework have better academic achievement in Math at secondary grades. There weren’t found gender differences on homework involvement but age differences were reported. Immigrant students are less involved in homework at secondary grades that students in elementary grades. The study highlights the relevance of homework involvement in academic achievement in immigrant students.

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

BackgroundAdverse events in the primary care setting result in a direct cost equivalent to at least 2.5% of total healthcare spending. Across OECD countries, they lead to more than seven million avoidable hospital admissions annually. In this manuscript, we describe the protocol of a trial aimed at evaluating the effectiveness of SinergiAPS (a patient-centered audit and feedback intervention) in reducing avoidable hospital admission and explore the factors that may affect its implementation.MethodsWe will conduct a 24-month, parallel, open-label, multicenter, pragmatic, hybrid type 1 randomized clinical trial. 118 primary healthcare centers with wide geographical distribution in Spain will be randomly assigned (ratio 1:1) to two groups. The intervention group will receive two audits (baseline and intermediate at 12 months) based on information collected through the administration of the PREOS-PC questionnaire (a measure of patient-reported patient safety) to a convenience sample of 100 patients per center. The intervention group will receive reports on the results of both audits, along with educational resources aimed at facilitating the design and implementation of safety improvement plans. The control group will receive care as usual. The primary outcome will be the rate of avoidable hospitalizations (administrative data). Secondary outcomes: patient-reported patient safety experiences and outcomes (PREOS-PC questionnaire); patient safety culture as perceived by professionals (MOSPSC questionnaire); adverse events reported by healthcare professionals (ad hoc questionnaire); the number of safety improvement actions which the re has implemented (ad hoc questionnaire). Outcome data will be collected at baseline and 24 months follow-up. For the evaluation of the implementation of the SinergiAPS intervention, we will draw on the Consolidated Framework for Implementation Research (CFIR). We will collect and analyze qualitative and quantitative data (30 individual interviews, implementation logbooks; questionnaires for professionals from intervention centers, and level of use of the SinergiAPS web tool).DiscussionThis study will expand the scarce body of evidence existing regarding the effects and implementation of interventions aimed at promoting patient and family engagement in primary healthcare, specifically for enhancing patient safety. The study has the potential to produce an impact on clinical practice, healthcare systems, and population health.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05958108?term=sinergiAPS&rank=1 (NCT05958108).

BackgroundHealthcare-associated infection (HAI) remains a significant risk for hospitalized patients and a challenging burden for the healthcare system. This study presents a clinical decision support tool that can be used in clinical workflows to proactively engage secondary assessments of pre-symptomatic and at-risk infection patients, thereby enabling earlier diagnosis and treatment.MethodsThis study applies machine learning, specifically ensemble-based boosted decision trees, on large retrospective hospital datasets to develop an infection risk score that predicts infection before obvious symptoms present. We extracted a stratified machine learning dataset of 36,782 healthcare-associated infection patients. The model leveraged vital signs, laboratory measurements and demographics to predict HAI before clinical suspicion, defined as the order of a microbiology test or administration of antibiotics.ResultsOur best performing infection risk model achieves a cross-validated AUC of 0.88 at 1 h before clinical suspicion and maintains an AUC >0.85 for 48 h before suspicion by aggregating information across demographics and a set of 163 vital signs and laboratory measurements. A second model trained on a reduced feature space comprising demographics and the 36 most frequently measured vital signs and laboratory measurements can still achieve an AUC of 0.86 at 1 h before clinical suspicion. These results compare favorably against using temperature alone and clinical rules such as the quick sequential organ failure assessment (qSOFA) score. Along with the performance results, we also provide an analysis of model interpretability via feature importance rankings.ConclusionThe predictive model aggregates information from multiple physiological parameters such as vital signs and laboratory measurements to provide a continuous risk score of infection that can be deployed in hospitals to provide advance warning of patient deterioration.

Peripheral neuropathy with antibodies to myelin-associated glycoprotein (MAG) is an autoimmune demyelinating disorder of the peripheral nervous system caused by pathogenic IgM recognizing the human natural killer-1 glycoepitope expressed on MAG. This study aimed to analyze the performance of a new indirect immunofluorescence cell-based assay (CBA, EUROIMMUN) for the detection of anti-MAG IgM. Antibody reactivity was determined in sera from 95 patients with clinical and neurophysiological evidence of anti-MAG-associated neuropathy and in control samples from 55 patients with other forms of peripheral neuropathy. Compared to the results of the gold standard method (ELISA, Bühlmann) and using samples at a dilution of 1:100, the CBA had a sensitivity of 98.9% and a specificity of 100% (PPV 100%, NPV 98.2%). In conclusion, the CBA allows the detection of antibodies to MAG using an easy and standardized technique, and it presents a sensitive and specific alternative to the more time-consuming ELISA. Larger studies are needed to address anti-MAG titer monitoring in parallel with clinical activity.

IntroductionThe association of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) and tumors has seldom been reported. We aim to investigate the occurrence of tumors in a cohort of patients with MOGAD and to describe their clinical features, in addition to previously reported cases.MethodsWe retrospectively identified patients with MOGAD (i.e., compatible clinical phenotype and positive MOG antibodies analysed with a live cell-based assay) from 1/1/2015 to 1/1/2023 who had a neoplasm diagnosed within 2 years from MOGAD onset. Furthermore, we performed systematic review of literature to identify previously reported cases. Clinical, paraclinical and oncological findings were collected and reported as median (range) or number (percentage).ResultsTwo of 150 MOGAD patients (1%) had a concomitant neoplasm in our cohort. Fifteen additional cases were retrieved from literature. Median age was 39 (16–73) years-old, 12 patients were female. ADEM (n = 4;23.5%), encephalomyelitis (n = 3;17.6%), and monolateral optic neuritis (n = 2;11.8%) were the most frequent phenotypes. Median number of treatments was 1 (range 1–4), improvement was reported in 14/17 cases (82.4%). Oncological accompaniments were teratoma (n = 4), CNS (n = 3), melanoma (n = 2), lung (n = 2), hematological (n = 2), ovary (n = 1), breast (n = 1), gastrointestinal (n = 1), and thymic (n = 1) neoplasms. Median time from tumor diagnosis to MOGAD onset was 0 (range − 60 to 20) months. MOG expression in neoplastic tissue was reported in 2/4 patients. Median PNS-CARE score was 3 (range 0–7): 11 patients were classified as “non-PNS,” 5 as “possible PNS,” and 1 as “probable PNS.”DiscussionOur study confirms that MOG is a low-risk antibody for paraneoplastic neurological syndromes and that the clinical presentation and oncological accompaniments are extremely variable. Most of these patients were classified as non-PNS, whereas only a minority was diagnosed with possible/probable PNS, frequently in association with ovarian teratoma. These findings support the notion that MOGAD is not a paraneoplastic disease.

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON.Trial registrationClinicalTrials.gov, identifier: NCT05605951.

IntroductionDespite advances in treating high-risk neuroblastoma, 50-60% of patients still suffer relapse, necessitating new treatment options. Bispecific trifunctional antibodies (trAbs) are a promising new class of immunotherapy. TrAbs are heterodimeric IgG-like molecules that bind CD3 and a tumor-associated antigen simultaneously, whereby inducing a TCR-independent anti-cancer T cell response. Moreover, via their functional Fc region they recruit and activate cells of the innate immune system like antigen-presenting cells potentially enhancing induction of adaptive tumor-specific immune responses.MethodsWe used the SUREK trAb, which is bispecific for GD2 and murine Cd3. Tumor-blind trAb and the monoclonal ch14.18 antibody were used as controls. A co-culture model of murine dendritic cells (DCs), T cells and a neuroblastoma cell line was established to evaluate the cytotoxic effect and the T cell effector function in vitro. Expression of immune checkpoint molecules on tumor-infiltrating T cells and the induction of an anti-neuroblastoma immune response using a combination of whole cell vaccination and trAb therapy was investigated in a syngeneic immunocompetent neuroblastoma mouse model (NXS2 in A/J background). Finally, vaccinated mice were assessed for the presence of neuroblastoma-directed antibodies. We show that SUREK trAb-mediated effective killing of NXS2 cells in vitro was strictly dependent on the combined presence of DCs and T cells. ResultsUsing a syngeneic neuroblastoma mouse model, we showed that vaccination with irradiated tumor cells combined with SUREK trAb treatment significantly prolonged survival of tumor challenged mice and partially prevent tumor outgrowth compared to tumor vaccination alone. Treatment led to upregulation of programmed cell death protein 1 (Pd-1) on tumor infiltrating T cells and combination with anti-Pd-1 checkpoint inhibition enhanced the NXS2-directed humoral immune response.ConclusionHere, we provide first preclinical evidence that a tumor vaccination combined with SUREK trAb therapy induces an endogenous anti-neuroblastoma immune response reducing tumor recurrence. Furthermore, a combination with anti-Pd-1 immune checkpoint blockade might even further improve this promising immunotherapeutic concept in order to prevent relapse in high-risk neuroblastoma patients.

Antibody-mediated central nervous system (CNS) disorders including those associated with aquaporin-4 or myelin oligodendrocyte glycoprotein IgG and autoimmune encephalitis often affect women of childbearing age. Pathogenic antibodies of these diseases can potentially alter reproductive functions and influence fetal development. Hormonal changes occurring during pregnancy may modify the course of autoimmune diseases by influencing relapse risk, attack severity, and affect the delivery and postpartum period. Moreover, balancing treatment related safety issues with the risk of potentially disabling relapses during pregnancy and breastfeeding are major challenges. Intentional prenatal, gestational, and post-partum counseling is paramount to address these issues and mitigate these risks. Fortunately, new insights on risk factors for adverse pregnancy outcomes and possible preventive strategies are emerging. This review aims to summarize the interplay between antibody-mediated CNS disorders and pregnancy during the prenatal, gestational, and postpartum periods, highlight current treatment recommendations, and discuss future areas of research.

Autoantibody-associated demyelinating diseases of the central nervous system such as myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) and aquaporin 4-antibody positive neuromyelitis optica spectrum disorders (AQP4+ NMOSD) are rare diseases but can cause severe disability. In both diseases, associated neuroinflammation is accompanied by blood and cerebrospinal fluid cytokine and chemokine signatures, which were shown to be distinct from those observed in patients with multiple sclerosis (MS). In this study, we aimed to confirm and extend these findings by analyzing a larger number of serum cytokines, chemokines and related molecules in patients with MOGAD or AQP4+ NMOSD in comparison to MS, to better understand the pathophysiology and to identify biomarkers potentially useful in clinical practice for diagnostic and treatment purposes. A total of 65 serum cytokines, chemokines and related molecules like growth factors and soluble receptors were measured by Procartaplex multiplex immunoassays in 40 MOGAD, 40 AQP4+ NMOSD and 54 MS patients at baseline. Furthermore, follow-up samples of 25 AQP4+ NMOSD and 40 MOGAD patients were measured after 6-12 months. Selected analytes were validated in a subgroup of samples using other bead-based assays and ELISA. At baseline, 36 analytes in MOGAD and 30 in AQP4+ NMOSD were significantly increased compared to MS. K-means cluster analysis of all significantly altered molecules revealed three distinct groups: Cluster I, including 12 MOGAD, 2 AQP4+ NMOSD and 3 MS patients, had a specific association with 11 IL-6/IL-17A associated cytokines. In this cluster, 9/17 (53%) patients were children. Cluster II with 13 MOGAD, 24 AQP4+ NMOSD and 1 MS patient was associated with 31 upregulated analytes. Cluster III contained 15 MOGAD, 14 AQP4+ NMOSD and 50 MS patients. In cluster II and III the majority were adults (82% and 92%). Most measured analytes remained stable over time. Validation of selected cytokines and chemokines using other analytical methods revealed moderate to high correlation coefficients, but absolute values differed between assays. In conclusion, these results obtained by bead-based multiplex assays highlight a significant association of biomarkers of peripheral inflammation in patients with antibody-associated demyelinating diseases in comparison with MS.

BackgroundStroke represents the second preventable cause of death after cardiovascular disease and the third global cause of disability. In countries where national registries of the clinical quality of stroke care have been established, the publication and sharing of the collected data have led to an improvement in the quality of care and survival of patients. However, information on rehabilitation processes and outcomes is often lacking, and predictors of functional outcomes remain poorly explored. This paper describes a multicenter study protocol to implement a Stroke rehabilitation Registry, mainly based on a multidimensional assessment proposed by the Italian Society of Physical and Rehabilitation Medicine (PMIC2020), in a pilot Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation, to provide a systematic assessment of processes and outcomes and develop data-driven prediction models of functional outcomes.MethodsAll patients with a diagnosis of ischemic or haemorrhagic stroke confirmed by clinical assessment, admitted to intensive rehabilitation units within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled. Measures will be taken at admission (T0), at discharge (T1), and at follow-up, 3 months (T2) and 6 months (T3) after the stroke. Assessment variables include anamnestic data, clinical and nursing complexity information and measures of body structures and function, activity and participation (PMIC2020), rehabilitation interventions, adverse events and discharge data. The modified Barthel Index will be our primary outcome. In addition to classical biostatistical analysis, learning algorithms will be cross-validated to achieve data-driven prognosis prediction models.ConclusionsThis study will test the feasibility of a stroke rehabilitation registry in the Italian health context and provide a systematic assessment of processes and outcomes for quality assessment and benchmarking. By the development of data-driven prediction models in stroke rehabilitation, this study will pave the way for the development of decision support tools for patient-oriented therapy planning and rehabilitation outcomes maximization.Clinical tial registrationThe registration on ClinicalTrials.gov is ongoing and under review. The identification number will be provided when the review process will be completed.

Objectives: The COVID-19 pandemic caused risks and burdens for health professionals and might result in job leaving intentions. To assess the potential risks, we explored the association of the job leaving intentions with exposure to COVID-19 risk, impact of pandemic management on professional and personal life, and personal coping resources among Slovak dentists in the first wave of the outbreak.Methods: We obtained data from 500 dentists (66.8% females, M/SD = 43.8) registered with the Slovak Chamber of Dentists using an online questionnaire. Data were analysed using logistic regression models adjusted for age and gender.Results: Nearly 40% of dentists reported job leaving intentions after the first wave of the pandemic outbreak. Job leaving intentions were associated with exposure to COVID-19 risks (odds ratios, ORs, varying from 1.6 to 4.7), impact of pandemic management on professional and personal life (Ors from 1.6 to 2.9), and personal coping resources (Ors from 0.4 to 0.6).Conclusion: Better management of exposures to risks and impact on professional and personal life, as well as building better personal coping resources may prevent the loss of a valuable workforce in dental care.

Gender equality in Italian soil science is still far from being a reality although an in-depth investigation has never been carried out. In this work we analyse data on women soil scientists working in public research institutions and universities as well as on those affiliated with soil science societies, considering the changes in gender balance with time. We also recall three female pioneers in Italian soil science who played a key role in both research and scientific societies. An analysis of the impact of papers authored by Italian women is finally provided to gauge the contribution of Italian women to soil science in the last 20 years. The results show that the National Research Institutions reached a more equal balance between genders compared to universities. With regard to scientific societies, we observed a strong lack of female inclusion in the first years of the Italian Soil Science Society, founded in 1952, and the Italian Society of Pedology, even if it was founded much later in 1998. The Italian Society of Agricultural Chemistry was less discriminant, likely due to the presence of different sub-disciplines traditionally more open to women, although always far from real equality. With time, in all societies and research institutions we registered a positive trend with a better balance and a pro-active participation of women. However, we observed a persistent loss of highly qualified women resources from the training phase to the beginning of the career as well as under-representation of women in top roles and in the research centre leaderships. However, when we evaluated the scientific production, no statistical differences appear between women and men at all career levels, confirming the key contribution of women to soil science, despite facing major professional difficulties and disparities. These results show that, notwithstanding the marked progress in the number of women entering and working in Italian soil science, beyond the hard numbers, gender equality still remains a challenge and requires greater investments in resources and research toward structural and systemic interventions that may successfully lead to a more gender-balanced society.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

The term neuromyelitis optica spectrum disorder (NMOSD) describes a group of clinical-MRI syndromes characterized by longitudinally extensive transverse myelitis, optic neuritis, brainstem dysfunction and/or, less commonly, encephalopathy. About 80% of patients harbor antibodies directed against the water channel aquaporin-4 (AQP4-IgG), expressed on astrocytes, which was found to be both a biomarker and a pathogenic cause of NMOSD. More recently, antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), have been found to be a biomarker of a different entity, termed MOG antibody-associated disease (MOGAD), which has overlapping, but different pathogenesis, clinical features, treatment response, and prognosis when compared to AQP4-IgG-positive NMOSD. Despite important refinements in the accuracy of AQP4-IgG and MOG-IgG testing assays, a small proportion of patients with NMOSD still remain negative for both antibodies and are called “seronegative” NMOSD. Whilst major advances have been made in the diagnosis and treatment of these conditions, biomarkers that could help predict the risk of relapses, disease activity, and prognosis are still lacking. In this context, a number of serum and/or cerebrospinal fluid biomarkers are emerging as potentially useful in clinical practice for diagnostic and treatment purposes. These include antibody titers, cytokine profiles, complement factors, and markers of neuronal (e.g., neurofilament light chain) or astroglial (e.g., glial fibrillary acidic protein) damage. The aim of this review is to summarize current evidence regarding the role of emerging diagnostic and prognostic biomarkers in patients with NMOSD and MOGAD.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder caused by the conformational conversion of the prion protein (PrPC) into an abnormally folded form, named prion (or PrPSc). The combination of the polymorphism at codon 129 of the PrP gene (coding either methionine or valine) with the biochemical feature of the proteinase-K resistant PrP (generating either PrPSc type 1 or 2) gives rise to different PrPSc strains, which cause variable phenotypes of sCJD. The definitive diagnosis of sCJD and its classification can be achieved only post-mortem after PrPSc identification and characterization in the brain. By exploiting the Real-Time Quaking-Induced Conversion (RT-QuIC) assay, traces of PrPSc were found in the olfactory mucosa (OM) of sCJD patients, thus demonstrating that PrPSc is not confined to the brain. Here, we have optimized another technique, named protein misfolding cyclic amplification (PMCA) for detecting PrPSc in OM samples of sCJD patients. OM samples were collected from 27 sCJD and 2 genetic CJD patients (E200K). Samples from 34 patients with other neurodegenerative disorders were included as controls. Brains were collected from 26 sCJD patients and 16 of them underwent OM collection. Brain and OM samples were subjected to PMCA using the brains of transgenic mice expressing human PrPC with methionine at codon 129 as reaction substrates. The amplified products were analyzed by Western blot after proteinase K digestion. Quantitative PMCA was performed to estimate PrPSc concentration in OM. PMCA enabled the detection of prions in OM samples with 79.3% sensitivity and 100% specificity. Except for a few cases, a predominant type 1 PrPSc was generated, regardless of the tissues analyzed. Notably, all amplified PrPSc were less resistant to PK compared to the original strain. In conclusion, although the optimized PMCA did not consent to recognize sCJD subtypes from the analysis of OM collected from living patients, it enabled us to estimate for the first time the amount of prions accumulating in this biological tissue. Further assay optimizations are needed to faithfully amplify peripheral prions whose recognition could lead to a better diagnosis and selection of patients for future clinical trials.

Objective: The present study aimed to evaluate the prevalence of traumatic experienced seizures (TES) and of postepileptic seizure PTSD (PS-PTSD) in patients with pharmacoresistant focal epilepsy and to explore the determining factors of TES.Methods: We conducted an observational study enrolling 107 adult refractory epilepsy patients. We used the DSM-5 criteria of traumatic events and PTSD to define TES and PS-PTSD. We assessed all traumatic life events unrelated to epilepsy, general and specific psychiatric comorbidities, and quality of life.Results: Nearly half (n = 48) of the 107 participants reported at least one TES (44.85%). Among these, one-third (n = 16) developed PS-PTSD. The TES group was more likely to experience traumatic events unrelated to epilepsy (p < 0.001), to have generalized anxiety disorder (p = 0.019), and to have specific psychiatric comorbidities [e.g., interictal dysphoric disorder (p = 0.024) or anticipatory anxiety of seizures (p = 0.005)]. They reported a severe impact of epilepsy on their life (p = 0.01). The determining factors of TES according to the multifactorial model were the experience of trauma (p = 0.008), a history of at least one psychiatric disorder (p = 0.03), and a strong tendency toward dissociation (p = 0.03).Significance: Epileptic seizures may be a traumatic experience in some patients who suffer from pharmacoresistant epilepsy and may be the source of the development of PS-PTSD. Previous trauma unrelated to epilepsy and psychiatric history are determining factors of TES. These clinical entities should be explored systematically.

Neural-interfaced prostheses aim to restore sensorimotor limb functions in amputees. They rely on bidirectional neural interfaces, which represent the communication bridge between nervous system and neuroprosthetic device by controlling its movements and evoking sensory feedback. Compared to extraneural electrodes (i.e., epineural and perineural implants), intraneural electrodes, implanted within peripheral nerves, have higher selectivity and specificity of neural signal recording and nerve stimulation. However, being implanted in the nerve, their main limitation is represented by the significant inflammatory response that the body mounts around the probe, known as Foreign Body Reaction (FBR), which may hinder their rapid clinical translation. Furthermore, the mechanical mismatch between the consistency of the device and the surrounding neural tissue may contribute to exacerbate the inflammatory state. The FBR is a non-specific reaction of the host immune system to a foreign material. It is characterized by an early inflammatory phase eventually leading to the formation of a fibrotic capsule around intraneural interfaces, which increases the electrical impedance over time and reduces the chronic interface biocompatibility and functionality. Thus, the future in the reduction and control of the FBR relies on innovative biomedical strategies for the fabrication of next-generation neural interfaces, such as the development of more suitable designs of the device with smaller size, appropriate stiffness and novel conductive and biomimetic coatings for improving their long-term stability and performance. Here, we present and critically discuss the latest biomedical approaches from material chemistry and tissue engineering for controlling and mitigating the FBR in chronic neural implants.

In the last 20 years, several modalities of neuromodulation, mainly based on non-invasive brain stimulation (NIBS) techniques, have been tested as a non-pharmacological therapeutic approach to slow disease progression in amyotrophic lateral sclerosis (ALS). In both sporadic and familial ALS cases, neurophysiological studies point to motor cortical hyperexcitability as a possible priming factor in neurodegeneration, likely related to dysfunction of both excitatory and inhibitory mechanisms. A trans-synaptic anterograde mechanism of excitotoxicity is thus postulated, causing upper and lower motor neuron degeneration. Specifically, motor neuron hyperexcitability and hyperactivity are attributed to intrinsic cell abnormalities related to altered ion homeostasis and to impaired glutamate and gamma aminobutyric acid gamma-aminobutyric acid (GABA) signaling. Several neuropathological mechanisms support excitatory and synaptic dysfunction in ALS; additionally, hyperexcitability seems to drive DNA-binding protein 43-kDA (TDP-43) pathology, through the upregulation of unusual isoforms directly contributing to ASL pathophysiology. Corticospinal excitability can be suppressed or enhanced using NIBS techniques, namely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as well as invasive brain and spinal stimulation. Experimental evidence supports the hypothesis that the after-effects of NIBS are mediated by long-term potentiation (LTP)-/long-term depression (LTD)-like mechanisms of modulation of synaptic activity, with different biological and physiological mechanisms underlying the effects of tDCS and rTMS and, possibly, of different rTMS protocols. This potential has led to several small trials testing different stimulation interventions to antagonize excitotoxicity in ALS. Overall, these studies suggest a possible efficacy of neuromodulation in determining a slight reduction of disease progression, related to the type, duration, and frequency of treatment, but current evidence remains preliminary. Main limitations are the small number and heterogeneity of recruited patients, the limited “dosage” of brain stimulation that can be delivered in the hospital setting, the lack of a sufficient knowledge on the excitatory and inhibitory mechanisms targeted by specific stimulation interventions, and the persistent uncertainty on the key pathophysiological processes leading to motor neuron loss. The present review article provides an update on the state of the art of neuromodulation in ALS and a critical appraisal of the rationale for the application/optimization of brain stimulation interventions, in the light of their interaction with ALS pathophysiological mechanisms.

Recent preclinical and clinical evidence suggest that immune system has a role in the progression and prognosis of Amyotrophic Lateral Sclerosis (ALS), but the identification of a clear mechanism and immune players remains to be elucidated. Here, we have investigated, in 30 and 60 days (presymptomatic) and 120 days (symptomatic) old SOD1-G93A mice, systemic, peripheral, and central innate and adaptive immune and inflammatory response, correlating it with the progression of the neurodegeneration in neuromuscular junction, sciatic nerves, and spinal cord. Surprisingly, we found a very initial (45–60 days) presence of IgG in sciatic nerves together with a gradual enhancement of A20/TNFAIP3 (protein controlling NF-κB signalling) and a concomitantly significant increase and activation of circulating mast cells (MCs) as well as MCs and macrophages in sciatic nerve and an enhancement of IL-6 and IL-10. This immunological frame coincided with a myelin aggregation. The 30–60 days old SOD1-G93A mice didn’t show real elements of neuroinflammation and neurodegeneration in spinal cord. In 120 days old mice macrophages and monocytes are widely diffused in sciatic nerves, peripheral neurodegeneration reaches the tip, high circulating levels of TNFα and IL-2 were found and spinal cord exhibits clear signs of neural damage and infiltrating immune cells. Our results underpin a clear immunological disorder at the origin of ALS axonopathy, in which MCs are involved in the initiation and sustaining of inflammatory events. These data cannot be considered a mere epiphenomenon of motor neuron degeneration and reveal new potential selective immune targets in ALS therapy.

Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affected by LRBA deficiency. We describe a 7-year old female with an acute cervical longitudinally extensive transverse myelitis (LETM) as a feature of LRBA deficiency. This is the first case of LETM associated with LRBA deficiency described in literature.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.

Cephalopods are highly evolved marine invertebrates that colonized almost all the oceans of the world at all depths. This imposed the occurrence of several modifications of their brain and body whose muscle component represents the major constituent. Hence, studying their muscle physiology may give important hints in the context of animal biology and environmental adaptability. One major pathway involved in muscle metabolism in vertebrates is the evolutionary conserved mTOR-signaling cascade; however, its role in cephalopods has never been elucidated. mTOR is regulating cell growth and homeostasis in response to a wide range of cues such as nutrient availability, body temperature and locomotion. It forms two functionally heteromeric complexes, mTORC1 and mTORC2. mTORC1 regulates protein synthesis and degradation and, in skeletal muscles, its activation upon exercise induces muscle growth. In this work, we characterized Octopus vulgaris mTOR full sequence and functional domains; we found a high level of homology with vertebrates’ mTOR and the conservation of Ser2448 phosphorylation site required for mTORC1 activation. We then designed and tested an in vitro protocol of resistance exercise (RE) inducing fatigue in arm samples. We showed that, upon the establishment of fatigue, a transient increase in mTORC1 phosphorylation reaching a pick 30 min after exercise was induced. Our data indicate the activation of mTORC1 pathway in exercise paradigm and possibly in the regulation of energy homeostasis in octopus and suggest that mTORC1 activity can be used to monitor animal response to changes in physiological and ecological conditions and, more in general, the animal welfare.

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries.

The metallic impregnation invented by Camillo Golgi in 1873 has allowed the visualization of individual neurons in their entirety, leading to a breakthrough in the knowledge on the structure of the nervous system. Professor of Histology and of General Pathology, Golgi worked for decades at the University of Pavia, leading a very active laboratory. Unfortunately, most of Golgi's histological preparations are lost. The present contribution provides an account of the original slides on the nervous system from Golgi's laboratory available nowadays at the Golgi Museum and Historical Museum of the University of Pavia. Knowledge on the organization of the nervous tissue at the time of Golgi's observations is recalled. Notes on the equipment of Golgi's laboratory and the methodology Golgi used for his preparations are presented. Images of neurons from his slides (mostly from hippocampus, neocortex and cerebellum) are here shown for the first time together with some of Golgi's drawings. The sections are stained with the Golgi impregnation and Cajal stain. Golgi-impregnated sections are very thick (some more than 150 μm) and require continuous focusing during the microscopic observation. Heterogeneity of neuronal size and shape, free endings of distal dendritic arborizations, axonal branching stand out at the microscopic observation of Golgi-impregnated sections and in Golgi's drawings, and were novel findings at his time. Golgi also pointed out that the axon only originates from cell bodies, representing a constant and distinctive feature of nerve cells which distinguishes them from glia, and subserving transmission at a distance. Dendritic spines can be seen in some cortical neurons, although Golgi, possibly worried about artifacts, did not identify them. The puzzling intricacy of fully impregnated nervous tissue components offered to the first microscopic observations still elicit nowadays the emotion Golgi must have felt looking at his slides.

The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis. It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response. The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4+ and CD8+ T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD). Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1). Higher frequencies of antigen-specific TNAIVE cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (TEM for CD4+ T cells and TEMRA for CD8+ T cells). The amount of antigen-specific CD57+/CD8+ TEMRA cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects. Regarding functionality, a more robust multifunctional CD8+ T cell response was detected in cured patients than in those with active cutaneous leishmaniasis. Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ+/granzyme-B/+perforin+). Patients with an active leishmaniosis process had a significantly higher frequency of CD8+ T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients. The expression profile observed in cured patients could be indicative of an imbalance toward a CD8+ Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis. The results also suggest a possible exhaustion process of CD8+ T cells associated with the evolution of Leishmania infection.

The rapidly growing field of mechanobiology demands for robust and reproducible characterization of cell mechanical properties. Recent achievements in understanding the mechanical regulation of cell fate largely rely on technological platforms capable of probing the mechanical response of living cells and their physico–chemical interaction with the microenvironment. Besides the established family of atomic force microscopy (AFM) based methods, other approaches include optical, magnetic, and acoustic tweezers, as well as sensing substrates that take advantage of biomaterials chemistry and microfabrication techniques. In this review, we introduce the available methods with an emphasis on the most recent advances, and we discuss the challenges associated with their implementation.

Essential oils, which are mixtures of terpenes, frequently show stronger insecticide activity, i.e., lower lethal dose 50 (LC50), than their most abundant terpenes. Synergy between terpenes provides a plausible explanation, but its demonstration has been elusive. In the present work, we look for an alternative explanation, by considering the influence of insect metabolic detoxification. Basically, we propose a model (metabolic model, MM) in which the LC50 of the major terpene in a mixture is expected to include a fraction that is detoxified by the insect, whereas a minor terpene would act unimpeded, showing a lower LC50 than when acting alone. In order to test this idea, we analyzed the effects of inhibiting the cytochrome P450 detoxification system with piperonyl butoxide (PBO), on the lethal concentration of terpenes as fumigants against Musca domestica. We found that, within a group of 10 terpenes [linalool, citronellal, (R)-α-pinene, 1,8-cineole, γ-terpinene, limonene, α-terpinene, (S)-β-pinene, thymol and (R)-pulegone], seven showed the LC50PBO (the lethal concentration for PBO-treated flies) between 1.7 and 12.4 times lower than the corresponding LC50 when P450 was not inhibited. Only in one case, that of (R)-pulegone, was the LC50PBO greater than the LC50, while two terpenes [(S)-β-pinene and thymol] showed no changes in toxicity. The increased activity of most terpenes (particularly linalool and citronellal) in PBO-treated flies supports our hypothesis that normally the LC50 includes a fraction of inactive compound, due to detoxification. Having previously determined that M. domestica preferentially oxidizes the most abundant terpene in a mixture, while terpenes in smaller proportions are poorly or not detoxified by the P450 system, we assessed whether the toxicity of minority terpenes in a mixture is similar to their activity under P450 inhibition. We chose suitable binary combinations in such a way that one terpene (in greater proportion) should be the target of P450 while the other (in smaller proportion) should intoxicate the fly with LC50PBO or similar. Combinations of 1,8-cineole-citronellal, 1,8-cineole-linalool, linalool-citronellal, (R)-pulegone-linalool, (R)-pulegone-1,8-cineole and (R)-pulegone-citronellal were assayed against M. domestica, and the LC50 of each mixture was determined and compared to values predicted by MM (considering the LC50PBO for minor component) or by the classical approach (LC50 for both components). The MM showed the best fit to the data, suggesting additive rather than synergistic effects, except for the combination of (R)-pulegone-citronellal that was clearly synergistic. Thus, the experimental data indicate that the insect preferentially oxidizes the major component in a mixture, while the terpene in lesser proportion acts as a toxicant, with higher toxicity than when it was assayed alone. These findings contribute to a deeper understanding of the higher toxicity of essential oils compared to their component terpenes and provide important information for the design of effective insecticides based on essential oils or terpenes.

In Brazil, canine visceral leishmaniasis (CVL) is caused by Leishmania infantum, presenting a broad spectrum of clinical manifestations. Dogs are the main parasite reservoir in urban areas and canine cases precede human infection. Currently, A2 protein based Leish-Tec® vaccine is the only vaccine commercially available against CVL in Brazil. Considering that the main screening and confirmatory tests of canine infection are serological, it is possible that the antibody response elicited after vaccination interfere with diagnosis, leading to the inability to distinguish between vaccinated and infected animals. In order to identify the specific B-cell response induced after vaccination, A2 protein sequence was screened for main linear B-cell epitopes using in silico prediction (Bepipred) and immunological confirmation by ELISA. Three amino acid sequences were described as potential B-cell epitopes (SV11-SAEPHKAAVDV, PP16-PQSVGPLSVGPQSVGP, and VQ34-VGPLSVGPQSVGPLSVGPLSVGPQAVGPLSVGPQ). Specific IgG ELISAs were performed in sera of 12 immunized dogs living in non-endemic areas, followed for up to 1 year after immunization. The results were compared with those obtained in a group of 10 symptomatic and 10 asymptomatic CVL dogs. All predicted epitopes were confirmed as linear B-cell epitopes broadly recognized by sera from studied dogs. Total IgG ELISAs demonstrated distinct patterns of response between peptides in the immunized and CVL groups. VQ34 peptide was recognized by the majority of sera from vaccinated and symptomatic dogs, and increases after vaccination. PP16 induced low levels of specific IgG that increased 1 year after immunization. Interestingly, a low frequency of reactivity was found against SV11 in naturally infected dogs (symptomatic and asymptomatic), while 83.3% of vaccinated dogs presented positive responses 1 year after immunization. The two animals in the vaccinated group that did not respond to SV11 1 year after immunization presented positive serology both 30 days and 6 months after immunization. In summary, we identified three main linear B-cell epitopes in A2 based vaccine. Moreover, the humoral response against SV11 presented marked differences between infected and Leish-Tec vaccinated dogs, and should be further investigated, in large trials, to confirm its potential as a serological marker able to distinguish between infected and vaccinated dogs.

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders. Although not a diagnostic feature, motor impairments have been recently acknowledged as prevalent and significant, such that these children have difficulties planning, organizing and coordinating movements. This study aimed to further investigate anticipatory motor planning in children with ASD by means of assessing end- and beginning-state comfort, considering inconsistent reports of end-state comfort in independent action, and the study of beginning-state comfort being limited to one study with young adults. Five- to 11-year-old children with ASD, and chronologically age- and sex matched typically-developing children picked-up a glass and (1) poured a cup of water; and (2) passed it to the researcher to pour a cup of water. End-state comfort was deemed evident if participants grasped the glass thumb-down followed by a 180° rotation; therefore ending with a thumb-up posture. Beginning-state comfort was deemed evident if participants passed the glass to the researcher oriented upright. Findings revealed less end-state comfort in children with ASD, attributed to motor planning deficits. Beginning-state comfort did not differ, ascribed to the habitual nature of the task; therefore reflecting a stimulus-driven response as opposed to an action which reflects anticipatory planning. Findings support difficulties with motor planning and control for children with ASD in an independent task. However, when acting with a familiar object in joint action, behaviour does not differ, likely indicative of a habitual, stimulus-driven response.

As numerous movement options are available in reaching and grasping, of particular interest are what factors influence an individual’s choice of action. In the current study a preferential reaching task was used to assess the propensity for right handers to select their preferred hand and grasp a coffee mug by the handle in both independent and joint action object manipulation contexts. Mug location (right-space, midline and left-space) and handle orientation (towards, away, to left and to right of the participant) varied in four tasks that differed as a function of intention: (1) pick-up (unimanual, independent); (2) pick-up and pour (bimanual, independent); (3) pick-up and pass (unimanual, joint action); and (4) pick-up, pour and pass (bimanual, joint action). In line with previous reports, a right-hand preference for unimanual tasks was observed. Furthermore, extending existing literature to a preferential reaching task, role differentiation between the hands in bimanual tasks (i.e., preferred hand mobilizing, non-preferred hand stabilizing) was displayed. Finally, right-hand selection was greatest in right space, albeit lower in bimanual tasks compared to what is typically reported in unimanual tasks. Findings are attributed to the desire to maximize biomechanical efficiency in reaching. Grasp postures were also observed to reflect consideration of efficiency. More specifically, within independent object manipulation (pick-up; pick-up and pour) participants only grasped the mug by the handle when it afforded a comfortable posture. Furthermore, in joint action (pick-up and pass; pick-up, pour and pass), the confederate was only offered the handle if the intended action of the confederate was similar or required less effort than that of the participant. Together, findings from the current study add to our knowledge of hand and grasp selection in unimanual and bimanual object manipulation, within the context of both independent and joint action tasks.

Despite a lack of agreement concerning the age at which adult-like patterns of handedness emerge, it is generally understood that hand preference presents early in life and development is variable. Young children (ages 3-5 years) are described as having weak hand preference; however, older children (ages 7-10 years) display stronger patterns. Here, strength of hand preference refers to reliable use of the preferred hand. In comparison to their typically-developing (TD) peers, individuals with Autism Spectrum Disorder (ASD) are described as having a weak hand preference. This study aimed to extend the literature to assess three measures of handedness (Waterloo Handedness Questionnaire – WHQ, Annett Pegboard – AP and WatHand Cabinet Test – WHCT) in two repeated sessions. The first research question aimed to delineate if the strength of hand use changes across testing sessions as a function of age in typical development. Right-handed children reported a reliable preference for the right hand on the WHQ, similar to adults. A marginally significant difference was revealed between 3- to 4- and 5- to 6-year-olds on the AP. This was attributed to weak lateralization in 3- to 4-year-olds, where the establishment of hand preference by age 6 leads to superior performance with the preferred hand in 5- to 6-year-olds. Finally, for the WHCT, 3- to 4-year-olds had the highest bimanual score, indicating use of the same hand to lift the cabinet door and retrieve an object. It is likely that the task was not motorically complex enough to drive preferred hand selection for older participants. The second research question sought to determine if there is difference between typically-developing children and children with ASD. No differences were revealed; however, children with ASD did display variable AP performance, providing partial support for previous literature. Findings will be discussed in light of relevant literature.

It is widely know that the pattern of human handedness is such that approximately 90% of the population is right handed with the remainder being left handed, at least in the adult population. What is less well understood is how handedness develops and at what age adult-like handedness patterns emerge. Quantified in terms of both preference and performance, a plethora of different behavioural assessments are currently in use with both children and adults. Handedness questionnaires are commonly used; however, these possess inherent limitations, considering their subjective nature. Hand performance measures have also been implemented; however, such tasks appear to measure different components of handedness. In addition to these traditional measures, handedness has been successfully assessed through observation of hand selection in reaching, which has proven to be a unique and effective manner in understanding the development of handedness in children. Research over the past several decades has demonstrated that young children display weak, inconsistent hand preference tendencies and are slower with both hands. Performance differences between the hands are larger for young children, and consistency improves with age. However, there remains some controversy surrounding the age at which hand preference and hand performance abilities can be considered fully developed. The following paper will provide a review of the literature pertaining to hand preference, performance abilities and hand selection in children in an attempt to ascertain the age at which adult-like patterns of hand preference and performance emerge.