Social cognition in two brothers with Becker muscular dystrophy: an exploratory study revealing divergent behavioral phenotypes.

BACKGROUND AND OBJECTIVE: Only few studies investigated social cognition in Becker muscular dystrophy (BMD). However, brain dystrophin deficiency could be a neural substrate for cognitive, emotional, and neuropsychological features in BMD. METHODS: We compared interoceptive accuracy and interpersonal comfort distance in two brothers with BMD presenting with the same genetic deletion and a healthy control. When possible, we collected neuropsychological and psychopathological assessments. RESULTS: Our BMD patients were significantly different in interoceptive accuracy, with patient 1 being extremely accurate and patient 2 being significantly less accurate than his brother but more accurate than the control. Interestingly, they presented opposite patterns of interpersonal distance. Patient 1 was comfortable with very short interpersonal distance (≤50 cm from the confederate/object) vs the control and patient 2. By contrast, patient 2 preferred larger distance vs the control and patient 1. Patient 1 also presented difficulties in social and emotional skills on the psychopathological assessment. CONCLUSIONS: We are aware this is a small sample; nonetheless, this is also the first description of such aspects in BMD and the first report ever of such divergent behavioral pattern. As impaired social cognition affects the quality of life and social relationship, further studies are needed for a closer understanding of involved mechanisms.

Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

Response of Coccomyxa cimbrica sp.nov. to Increasing Doses of Cu(II) as a Function of Time: Comparison between Exposure in a Microfluidic Device or with Standard Protocols.

In this study, we explore how the in vitro conditions chosen to cultivate and observe the long-term (up to 72 h) toxic effect of Cu(II) on the freshwater microalga Coccomyxa cimbrica sp.nov. can affect the dose response in time. We test three different cultivation protocols: (i) under static conditions in sealed glass cells, (ii) in a microfluidic device, where the sample is constantly circulated with a peristaltic pump, and (iii) under continuous agitation in plastic falcons on an orbital shaker. The advantage and novelty of this study resides in the fact that each condition can mimic different environmental conditions that alga cells can find in nature. The effect of increasing dose of Cu(II) as a function of time (24, 48, and 72 h) is monitored following chlorophyll a fluorescence intensity from single cells. Fluorescence lifetime imaging experiments are also explored to gain information on the changes induced by Cu(II) in the photosynthetic cycle of this microalga.

Formation of Catalytic Hotspots in ATP-Templated Assemblies.

The self-assembly of surfactant-based structures that rely for their formation on the combination of a thermodynamically controlled and a dissipative pathway is described. Adenosine triphosphate (ATP) acts as a high-affinity template and triggers assembly formation at low surfactant concentrations. The presence of these assemblies creates the conditions for the activation of a dissipative self-assembly process by a weak-affinity substrate. The substrate-induced recruitment of additional surfactants leads to the spontaneous formation of catalytic hotspots in the ATP-stabilized assemblies that cleave the substrate. As a result of the two self-assembly processes, catalysis can be observed at a surfactant concentration at which low catalytic activity is observed in the absence of ATP.

Supporting Caregivers Remotely During a Pandemic: Comparison of WHO Caregiver Skills Training Delivered Online Versus in Person in Public Health Settings in Italy.

Feasibility, acceptability and effectiveness data of a virtual adaptation of the WHO Caregiver Skills Training (CST; n = 25) were compared with those of a pilot RCT of CST delivered in person (n = 43) against treatment as usual (TAU; n = 43). Virtual CST was delivered with high levels of integrity, but received lower ratings in some caregiver- and facilitator-rated acceptability and feasibility dimensions. Qualitative analysis identified both benefits (flexibility, convenience, clinical usefulness) and challenges, (technological issues, distraction from family members, emotional distance). Virtual and in-person CST improved significantly more on caregiver competence than TAU; there were no other significant effects. Potential for use of virtual CST as a clinical response in contexts where in-person delivery is not possible is discussed.

Neuromuscular disorders and transition from pediatric to adult care in a multidisciplinary perspective: a narrative review of the scientific evidence and current debate.

Objective: Standards of care and new genetic and molecular therapies have contributed to increasing life expectancy of patients with neuromuscular diseases (NMDs). This review presents the clinical evidence for an adequate transition from pediatric to adult care in patients with NMDs considering both physical and psychosocial aspects and attempts at identifying a general pattern of transition in the literature that can be used for all patients with NMDs. Method: A search was performed on PubMed, Embase and Scopus using generic terms that could be referred to the transition construct specifically related to NMDs. A narrative approach was used to summarise the available literature. Results: Our review shows that few or no studies explored the transition process from pediatric to adult care in neuromuscular diseases and tried to identify a general pattern of transition applicable to all NMDs. Conclusions: A transition process taking into consideration physical, psychological, social needs of patient and caregiver could produce positive outcomes. However, there is still no unanimous agreement in the literature on what it consists of and how to achieve an optimal and effective transition.

Acceptability and feasibility of the World Health Organization's Caregiver Skills Training implemented in the Italian National Health System.

LAY ABSTRACT: Across the globe, children with neurodevelopmental disorders, including autism, have limited access to care through public services. To improve access to care the World Health Organization developed a novel, open-access programme: the Caregiver Skills Training programme. The Caregiver Skills Training consists of nine group sessions and three individual home visits, focused on training the caregiver on how to use everyday play and home routines as opportunities for learning and development. We implemented Caregiver Skills Training in public child neuropsychiatry services in Italy and examined with questionnaires and focus groups how feasible it was to deliver the programme in public health settings and how acceptable and relevant it was for caregiver users. We found that the Caregiver Skills Training was largely considered acceptable and relevant for families and feasible to deliver. We discuss potential solutions to address the specific implementation challenges that were identified, such as strategies to improve training of interventionists and overcome barriers to caregiver participation.

Systematic Review and Meta-analysis: The Science of Early-Life Precursors and Interventions for Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To evaluate which early neurocognitive and behavioral precursors are associated with the development of attention-deficit/hyperactivity disorder (ADHD) and whether these are currently targeted in early interventions. METHOD: We conducted 2 systematic reviews and meta-analyses of empirical studies to examine the following: (1) early-life (0-5 years) neurocognitive and behavioral precursors associated with familial likelihood for ADHD, an early ADHD diagnosis/elevated ADHD symptoms, and/or the presence of later-childhood ADHD; and (2) interventions delivered to children aged 0 to 5 years targeting the identified precursors or measuring these as outcomes. Standardized mean differences (Hedges' g) and pre-post-treatment change scores (SMD) were computed. RESULTS: A total of 149 studies (165,095 participants) investigating 8 neurocognitive and behavioral domains met inclusion criteria for part 1. Multi-level random-effects meta-analyses on 136 studies revealed significant associations between ADHD and poorer cognitive (g = -0.46 [95% CIs: -0.59, -0.33]), motor (g = -0.35 [CIs: -0.48, -0.21]) and language (g = -0.43 [CIs: -0.66, -0.19]) development, social (g = 0.23 [CIs: 0.03, 0.43]) and emotional (g = 0.46 [CIs: 0.33, 0.58]) difficulties, early regulatory (g = 0.30 [CIs: 0.18, 0.43]) and sleep (g = 0.29 [CIs: 0.14, 0.44]) problems, sensory atypicalities (g = 0.52 [CIs: 0.16, 0.88]), elevated activity levels (g = 0.54 [CIs: 0.37, 0.72]), and executive function difficulties (g = 0.34 [CIs: 0.05, 0.64] to -0.87 [CIs: -1.35, -0.40]). A total of 32 trials (28 randomized, 4 nonrandomized, 3,848 participants) testing early interventions that targeted the identified precursors met inclusion criteria for part 2. Multi-level random-effects meta-analyses on 22 studies revealed significant intervention-related improvements in ADHD symptoms (SMD = 0.43 [CIs: 0.22, 0.64]) and working memory (SMD = 0.37 [CIs: 0.06, 0.69]). CONCLUSION: Children aged 0 to 5 years with current or later-emerging ADHD are likely to experience difficulties in multiple neurocognitive/behavioral functions. Early interventions show some effectiveness in reducing ADHD symptoms, but their effects on neurocognitive/behavioral difficulties require further study.

A multimethod approach to assessing motor skills in boys and girls with autism spectrum disorder.

LAY ABSTRACT: Motor peculiarities are often reported in children with autism spectrum disorder and may predict subsequent adaptive functioning and quality of life. Although the sex bias in the prevalence of the disorder is well documented, little is known about differences in motor profile in males and females with autism spectrum disorder. Our goal was to study differences in motor functioning of boys and girls with autism spectrum disorder aged 3-11 years compared with typically developing children. Their motor performances were evaluated using a multimethod approach, including standardized motor tests, caregiver reports, and a detailed motion capture analysis of a simple reach-to-drop movement. We found that, irrespective of sex, children with autism spectrum disorder had worse scores than typically developing children on standardized tests and on caregiver reports. Interestingly, girls with autism spectrum disorder, but not boys, presented altered motor anticipation in reach-to-drop. Our findings emphasize the need for more sex-specific assessment of motor function in autism spectrum disorder.

Fundamental Motor Skills Intervention for Children with Autism Spectrum Disorder: A 10-Year Narrative Review.

In the past decade, converging evidence has suggested that motor impairment is one of the most consistent markers, alongside sociocommunicative difficulties, for autism spectrum disorder (ASD). Indeed, widespread anomalies of movement have been described in the ASD context. These motor abnormalities could have critical implications for subsequent cognitive and social development. Nevertheless, this area of development is particularly underexamined in the autism-related context, and early intervention programs commonly focus on the core symptoms of the condition. In the present work, we review and discuss the findings from recent studies that investigated the effect of interventions regarding fundamental motor skills in autistic children. Although the limited nature of the literature prevents researchers from drawing definitive conclusions, the results from the studies discussed here demonstrated potentially significant improvements in the motor abilities of autistic children after the interventions. Only a subset of the reviewed studies explored possible changes in the sociocommunicative domain after the motor skills improvements, and they had not concordant, although promising, conclusions. Overall, in consideration of the well-documented motor impairment people with the condition, the present findings highlight the importance of including motor skills training within the rehabilitation programs designed for autistic children. Furthermore, this narrative review encourages future interventional trials to consider motor skills as a possible target for reducing activity limitations and participation restrictions of autistic children.

Time-gated fluorescence signalling under dissipative conditions.

Precise control over specific functions in the time domain is ubiquitous in biological systems. Here, we demonstrate time-gated fluorescence signalling under dissipative conditions exploiting an ATP-fueled self-assembly process. A temporal ATP-concentration gradient allows the system to pass through three states, among which only the intermediate state generates a fluorescent signal from a hydrophobic dye entrapped in the assemblies. The system can be reactivated by adding a new batch of ATP. The results indicate a strategy to rationally programme the temporal emergence of functions in complex chemical systems.

Interictal Heart Rate Variability Analysis Reveals Lateralization of Cardiac Autonomic Control in Temporal Lobe Epilepsy.

Purpose: The temporal lobe, a critical hub for cognition, also plays a central role in the regulation of autonomic cardiovascular functions. Lesions in this area are usually associated with abnormalities in the regulation of heart rate (HR) and blood pressure (BP). The analysis of the heart rate variability (HRV) is useful to evaluate the cardiac parasympathetic nervous system activity. This study aims at comparing HRV changes occurring in two groups of patients suffering from Temporal Lobe Epilepsy (TLE). To that aim, we evaluated patients differentiated by the right or left location of the epileptic foci. Materials and Methods: Fifty-two adult patients with a diagnosis of TLE were enrolled. Each patient underwent a 20-min EEG + EKG recording in resting state. According to the localization of epileptic focus, patients were divided into two subgroups: right TLE (R-TLE) and left TLE (L-TLE). HRV parameters were calculated with a short-lasting analysis of EKG recordings. Time-domain and frequency domain-related, as well as non-linear analysis, parameters, were compared between the two groups. Results: Compared to the R-TLE group, L-TLE subjects showed a significant decrease in low frequency (LF) (p < 0.01) and low frequency/high-frequency ratio (LF/HF) (p < 0.001) as well as increased HF values (p < 0.01), a parameter indicative of the presence of an increased cardiac vagal tone. These results were also confirmed in the subgroup analysis that took into account the seizure types, responses to antiepileptic drugs, seizure frequencies, and etiology. Conclusions: The main finding of the study is that, compared to R-TLE, L-TLE is associated with increased cardiac vagal tone. These results indicate that patients with TLE exhibit a lateralized cardiac autonomic control. L-TLE patients may have a lower risk of developing cardiac dysfunctions and less susceptible to develop Sudden Death for Epilepsy (SUDEP).

Nucleotide-Selective Templated Self-Assembly of Nanoreactors under Dissipative Conditions.

Nature adopts complex chemical networks to finely tune biochemical processes. Indeed, small biomolecules play a key role in regulating the flux of metabolic pathways. Chemistry, which was traditionally focused on reactions in simple mixtures, is dedicating increasing attention to the network reactivity of highly complex synthetic systems, able to display new kinetic phenomena. Herein, we show that the addition of monophosphate nucleosides to a mixture of amphiphiles and reagents leads to the selective templated formation of self-assembled structures, which can accelerate a reaction between two hydrophobic reactants. The correct matching between nucleotide and the amphiphile head group is fundamental for the selective formation of the assemblies and for the consequent up-regulation of the chemical reaction. Transient stability of the nanoreactors is obtained under dissipative conditions, driven by enzymatic dephosphorylation of the templating nucleotides. These results show that small molecules can play a key role in modulating network reactivity, by selectively templating self-assembled structures that are able to up-regulate chemical reaction pathways.

Maternal input to children with sex chromosome trisomies.

BACKGROUND: Although language difficulties are one of the most distinctive characteristics of the neuropsychological profile of children with sex chromosome trisomies (SCT), the analysis of the maternal input addressed to them is a neglected topic. AIMS: The present study aims to analyse the lexical, morphosyntactic, and functional features of the input addressed to children with SCT comparing them with those of the input directed to typically developing children (TD). METHODS & PROCEDURES: Participants were 38 mothers and their 8-month-old children, 19 with SCT and 19 TD children. Maternal utterances, collected during video-recorded play sessions, have been transcribed and coded. OUTCOMES & RESULTS: No significant differences between groups have been found in the lexical and syntactic characteristics of maternal input. However, considering the input functional features, the proportion of directives and questions was significantly higher in the maternal input addressed to children with SCT than in the input addressed to TD children whereas the opposite pattern was found in the proportion of affect-salient speech. CONCLUSIONS & IMPLICATIONS: The awareness of a possible delay in their children's language development could influence the way the mothers speak to them. In particular, the functional features of maternal input could be affected. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development. What this paper adds What is already known on the subject Studies in the literature identified a high percentage of language delays or impairments in children with SCT. To date, according to our knowledge, there are no studies that analyse the linguistic input addressed to these children. What this study adds The lexical and syntactic features of maternal input addressed to 8-month-old children with SCT are adequate to the children's communicative skills. However, the mothers of children with SCT seem to provide additional scaffolding in their verbal input, using a lower proportion of affect-salient speech and a higher proportion of questions. In addition, a higher proportion of directives suggests the use of a more demanding style. Clinical implications of this study The awareness of possible language delays could influence the functional features of input leading mothers to use a more supportive and demanding input. Support groups for parents of children with SCT at the preverbal stage could be useful to reassure the mothers about their role in their children's language development.

Psychogenic Non-epileptic Seizures and Pseudo-Refractory Epilepsy, a Management Challenge.

Psychogenic nonepileptic seizures (PNES) are neurobehavioral conditions positioned in a gray zone, not infrequently a no-man land, that lies in the intersection between Neurology and Psychiatry. According to the DSM 5, PNES are a subgroup of conversion disorders (CD), while the ICD 10 classifies PNES as dissociative disorders. The incidence of PNES is estimated to be in the range of 1.4-4.9/100,000/year, and the prevalence range is between 2 and 33 per 100,000. The International League Against Epilepsy (ILAE) has identified PNES as one of the 10 most critical neuropsychiatric conditions associated with epilepsy. Comorbidity between epilepsy and PNES, a condition leading to "dual diagnosis," is a serious diagnostic and therapeutic challenge for clinicians. The lack of prompt identification of PNES in epileptic patients can lead to potentially harmful increases in the dosage of anti-seizure drugs (ASD) as well as erroneous diagnoses of refractory epilepsy. Hence, pseudo-refractory epilepsy is the other critical side of the PNES coin as one out of four to five patients admitted to video-EEG monitoring units with a diagnosis of pharmaco-resistant epilepsy is later found to suffer from non-epileptic events. The majority of these events are of psychogenic origin. Thus, the diagnostic differentiation between pseudo and true refractory epilepsy is essential to prevent actions that lead to unnecessary treatments and ASD-related side effects as well as produce a negative impact on the patient's quality of life. In this article, we review and discuss recent evidence related to the neurobiology of PNES. We also provide an overview of the classifications and diagnostic steps that are employed in PNES management and dwell on the concept of pseudo-resistant epilepsy.

mCerulean3-Based Cameleon Sensor to Explore Mitochondrial Ca2+ Dynamics In Vivo.

Genetically Encoded Ca2+ Indicators (GECIs) are extensively used to study organelle Ca2+ homeostasis, although some available probes are still plagued by a number of problems, e.g., low fluorescence intensity, partial mistargeting, and pH sensitivity. Furthermore, in the most commonly used mitochondrial Förster Resonance Energy Transfer based-GECIs, the donor protein ECFP is characterized by a double exponential lifetime that complicates the fluorescence lifetime analysis. We have modified the cytosolic and mitochondria-targeted Cameleon GECIs by (1) substituting the donor ECFP with mCerulean3, a brighter and more stable fluorescent protein with a single exponential lifetime; (2) extensively modifying the constructs to improve targeting efficiency and fluorescence changes caused by Ca2+ binding; and (3) inserting the cDNAs into adeno-associated viral vectors for in vivo expression. The probes have been thoroughly characterized in situ by fluorescence microscopy and Fluorescence Lifetime Imaging Microscopy, and examples of their ex vivo and in vivo applications are described.

Brainstem evoked potentials and magnetic resonance imaging abnormalities in differential diagnosis of intracranial hypotension.

OBJECTIVE: To compare brainstem acoustic evoked potentials (BAEP) and magnetic resonance imaging (MRI) in the differential diagnosis of intracranial hypotension (IH), Chiari malformation (CM) and sensorineural hearing loss (SNHL). METHODS: BAEP were recorded in 18 IH, 18 CM, 20 SNHL patients and 52 controls. MRI were acquired in all IH and CM patients. RESULTS: Abnormal BAEP were observed in 94% of IH patients, in 33% of CM and 70% of SNHL patients. After recovery from IH, BAEP abnormalities disappeared. Internal auditory canal (IAC) MRI abnormalities were described in 88% of IH patients. MRI signs of IH were observed in 33-78% in IH patients, but the most frequent MRI sign was 8th nerve T2 hyperintensity, with contrast enhancement in T1 sequences. This finding, combined with wave I latency, yielded highest specificity and sensitivity for IH diagnosis. CONCLUSIONS: Our study points out how IH can be effectively distinguished from CM and SNHL through the contribution of neurophysiology and MRI; in particular, evaluation of the 8th nerve achieves a high sensitivity and specificity in patients with IH. Further studies are required to examine the combined use of BAEP recordings ad MRI in diagnosis and monitoring of patients affected by IH.