Search Results (17)

The Yanomami Indigenous Land (YIL) is heavily impacted by illegal gold mining, leading to significant contamination by methylmercury, a neurotoxin that poses severe risks to human health. The fetal brain is particularly susceptible to the neurotoxic effects of methylmercury, which can result in mild mental retardation (MMR). The goal of this study was to estimate the burden of disease (BoD) associated with methylmercury exposure in the YIL and its economic implications. The BoD calculations followed World Health Organization (WHO) methodologies. To estimate the local BoD, hair samples were collected from women of childbearing age in the Waikás, Mucajaí, Paapiu, and Maturacá regions. For broader estimates, data from the scientific literature were used. The average hair methylmercury concentrations in these investigated regions were 6.21 µg/g, 3.86 µg/g, 3.53 µg/g, and 2.96 µg/g, respectively. The MMR incidence rate (IR) in children ranged from 2.08 to 4.47 per 1000 in these regions. The Disability-Adjusted Life Years (DALYs) per 1000 births varied from 24.8 to 53.4. In the Worst-Case Scenario, MMR-IR reached 9 per 1000, with DALYs per 1000 births rising to 109.6. The estimated economic impact of methylmercury exposure ranged from USD 716,750 to USD 3,153,700. This study is the first to quantify the MMR incidence due to mercury in the YIL, highlighting the severe threat posed by gold mining to the health and survival of the Yanomami people. Full article

Floating–Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive language delays. It is caused by heterozygous mutations in the Snf2-related CREBBP activator protein (SRCAP) gene. The aim of this paper is to describe the case of a 14-year-old male with FHS, referring to a review of the literature, and to collect all reported symptoms. In addition, the orthodontic treatment of the patient is described. For this, the electronic databases PubMed and Scopus were searched using the keyword “Floating–Harbor syndrome”. Similar to previous cases in the literature, the patient presented with short stature; a triangular face with a large bulbous nose; deep-set eyes and narrow eyelid gaps; a wide mouth with a thin vermilion border of the upper lip; and dorsally rotated, small ears. They also presented some less-described symptoms, such as macrodontia and micrognathia. Moreover, mild mental retardation, microcephaly, and delayed psychomotor development were found. On the basis of an extraoral, intraoral examination, X-rays, and CBCT, he was diagnosed with overbite, canine class I and angle class III, on both sides. To the best of our knowledge, orthodontic treatment of this disease has not been assessed in detail so far, so this is the first case. Full article

This study investigates the psychological, educational, and technological difficulties faced by primary education students with special needs during online teaching. An interpretative phenomenological analysis was used for the qualitative analysis of data obtained through semi-structured interviews with twenty-two (22) teachers in primary education at a European country. The results revealed that their students showed negative emotions and behaviour. Those diagnosed with autism and learning disabilities had difficulty concentrating in class, while those with sensory disabilities had epileptic instances. Students with mild mental retardation in particular found it difficult to use digital tools. Many problems, however, are due to the lack of infrastructure and digital skills, as well as proper preparation of teachers for online teaching. Therefore, students and teachers should be equipped with the necessary digital skills, specialised digital tools and accessible open educational resources (OER) in order to effectively participate in online education. Full article

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs. Full article

Mutations in the tubulin-specific chaperon D (TBCD) gene, involved in the assembly and disassembly of the α/β-tubulin heterodimers, have been reported in early-onset progressive neurodevelopment regression, with epilepsy and mental retardation. We describe a rare homozygous variant in TBCD, namely c.881G>A/p.Arg294Gln, in a young woman with a phenotype dominated by distal motorneuronopathy and mild mental retardation, with neuroimaging evidence of corpus callosum hypoplasia. The peculiar phenotype is discussed in light of the molecular interpretation, enriching the literature data on tubulinopathies generated from TBCD mutations. Full article

The technological advances we are witnessing today have stimulated the creation of many 3D virtual environments for various purposes, from entertainment to industry to education. While the majority of these environments are perfectly suited for the healthy population, we should not forget about impaired people living among us. Regarding children’s education, one may wonder how impaired children handle them. Do they find them usable and attractive? How well do they handle basic activities in 3D environments, including orientation and interaction with objects? The experiment presented in this article provides answers to these questions within a specific setup. The experiment used a custom web application with several 3D virtual environments in a desktop virtual reality setting. The participants were 12 children, aged 8–14, with multiple impairments, predominantly hearing impairment, borderline and mild degree of mental retardation, and inferior communication skills. The answers can be regarded as positive and are based on results gathered in the form of completion times and the System Usability Scale questionnaire scores. The article also reports on a significant relation found between completion times and questionnaire scores. Future research directions, including those related to the Metaverse concept, are discussed, too. Full article

In this study we focus on the application of standardized tests aimed at evaluating the functional degree of independence in children (client 1, WeeFIM test; and client 2, FIM test) in special education diagnostics. The target group consisted of two clients with a diagnosis of mental functional diversity (n = 2; client 1: mild mental retardation, according to ICD-10: F70, aged 6.5 years; and client 2: moderate mental retardation, according to ICD-10: F71, aged 13.4 years). Special pedagogical intervention was primarily applied to the clients, focusing on identified deficits in the areas of cognitive, motor, and social skills. The presented results demonstrate the importance of the application of these tests in special pedagogy. An improvement in the observed indicators of the given tests was demonstrated for both probands after the intervention. The aim of this article was to draw attention to the suitability of using functional independence tests in special pedagogical practices. The authors discuss the further implications of this application for future practice. Full article

The K-homology (KH) domains are small, structurally conserved domains found in proteins of different origins characterized by a central conserved βααβ “core” and a GxxG motif in the loop between the two helices of the KH core. In the eukaryotic KHI type, additional αβ elements decorate the “core” at the C-terminus. Proteins containing KH domains perform different functions and several diseases have been associated with mutations in these domains, including those in the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein crucial for the control of RNA metabolism whose lack or mutations lead to fragile X syndrome (FXS). Among missense mutations, the R138Q substitution is in the KH0 degenerated domain lacking the classical GxxG motif. By combining equilibrium and kinetic experiments, we present a characterization of the folding mechanism of the KH0 domain from the FMRP wild-type and of the R138Q variant showing that in both cases the folding mechanism implies the accumulation of an on-pathway transient intermediate. Moreover, by exploiting a battery of biophysical techniques, we show that the KH0 domain has the propensity to form amyloid-like aggregates in mild conditions in vitro and that the R138Q mutation leads to a general destabilization of the protein and to an increased fibrillogenesis propensity. Full article

Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1. Full article

Artisanal small-scale gold mining (ASGM) in the Amazon results in the dumping of tons of mercury into the environment annually. Despite consensus on the impacts of mercury on human health, there are still unknowns regarding: (i) the extent to which mercury from ASGM can be dispersed in the environment until it becomes toxic to humans; and (ii) the economic value of losses caused by contamination becomes evident. The main objective of this study is to propose a methodology to evaluate the impacts of ASGM on human health in different contexts in the Brazilian Amazon. We connect several points in the literature based on hypotheses regarding mercury dispersion in water, its transformation into methylmercury, and absorption by fish and humans. This methodology can be used as a tool to estimate the extent of environmental damage caused by artisanal gold mining, the severity of damage to the health of individuals contaminated by mercury and, consequently, can contribute to the application of fines to environmental violators. The consequences of contamination are evaluated by dose-response functions relating to mercury concentrations in hair and the development of the following health outcomes: (i) mild mental retardation, (ii) acute myocardial infarction, and (iii) hypertension. From disability-adjusted life years and statistical life value, we found that the economic losses range from 100,000 to 400,000 USD per kilogram of gold extracted. A case study of the Yanomami indigenous land shows that the impacts of mercury from illegal gold mining in 2020 totaled 69 million USD, which could be used by local authorities to compensate the Yanomami people. Full article

Background: There is an urgent need to systematically analyze the growing body of literature on the effect of motor imagery (MI) training in children and adolescents. Methods: Seven databases and clinicaltrials.gov were searched. Two reviewers independently screened references and full texts, and extracted data (studies’ methodology, MI elements, temporal parameters). Two studies were meta-analyzed providing the standard mean difference (SDM). Selected studies were evaluated with the risk of bias (RoB) and GRADE tools. Results: A total of 7238 references were retrieved. The sample size of the 22 included studies, published between 1995 and 2021, ranged from 18 to 136 participants, totaling 934 (nine to 18 years). Studies included healthy pupils, mentally retarded adolescents, children with motor coordination difficulties or with mild mental disabilities. The motor learning tasks focused on upper, lower and whole body movements. SMDs for the primary outcome of pooled studies varied between 0.83 to 1.87 (95% CI, I², T² varied 0.33–3.10; p = 0.001; 0–74%; 0–0.59). RoB varied between some concerns and high risk. GRADE rating was low. Conclusions: MI combined with physical practice (PP) might have a high potential for healthy and impaired children and adolescents. However, important reporting recommendations (PETTLEP, TIDieR, CONSORT) should be followed. The systematic review was registered with PROSPERO: CRD42021237361. Full article

Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) is a fatty acid elongase responsible for very long-chain fatty acid biosynthesis in the brain, retina, and skin. Heterozygous mutations in ELOVL4 gene cause Stargardt-like macular dystrophy and spinocerebellar ataxia type-34, while different homozygous mutations have been associated with ichthyosis, spastic quadriplegia, and mental retardation syndrome in three kindred. We report the first two Italian children affected with neuro-ichthyosis due to the previously undescribed ELOVL4 homozygous frameshift variant c.435dupT (p.Ile146TyrfsTer29), and compound heterozygous variants c.208C>T (p.Arg70Ter) and c.487T>C (p.Cys163Arg), respectively. Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy. Visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces. Our findings contribute to expanding the phenotypic and genotypic features of ELOVL4-related neuro-ichthyosis. Full article

SHANK3 encodes a scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+ inhibitory neurons—the key players in the generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response (ASSR). However, 40-Hz ASSR was not studied in relation to SHANK3 functioning. Here, we present a 15-year-old girl (SH01) with previously unreported duplication of the first seven exons of the SHANK3 gene (22q13.33). SH01’s electroencephalogram (EEG) during 40-Hz click trains of 500 ms duration binaurally presented with inter-trial intervals of 500–800 ms were compared with those from typically developing children (n = 32). SH01 was diagnosed with mild mental retardation and learning disabilities (F70.88), dysgraphia, dyslexia, and smaller vocabulary than typically developing (TD) peers. Her clinical phenotype resembled the phenotype of previously described patients with 22q13.33 microduplications (≈30 reported so far). SH01 had mild autistic symptoms but below the threshold for ASD diagnosis and microcephaly. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential (ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. The absence of 40-Hz ASSR in patients with microduplication, which affected the SHANK3 gene, indicates deficient temporal resolution of the auditory system, which might underlie language problems and represent a neurophysiological biomarker of SHANK3 abnormalities. Full article

Methyl-CpG binding protein 2 (MeCP2) is a transcriptional regulator and a chromatin-binding protein involved in neuronal development and maturation. Loss-of-function mutations in MeCP2 result in Rett syndrome (RTT), a neurodevelopmental disorder that is the main cause of mental retardation in females. MeCP2 is an intrinsically disordered protein (IDP) constituted by six domains. Two domains are the main responsible elements for DNA binding (methyl-CpG binding domain, MBD) and recruitment of gene transcription/silencing machinery (transcription repressor domain, TRD). These two domains concentrate most of the RTT-associated mutations. R106W and R133C are associated with severe and mild RTT phenotype, respectively. We have performed a comprehensive characterization of the structural and functional impact of these substitutions at molecular level. Because we have previously shown that the MBD-flanking disordered domains (N-terminal domain, NTD, and intervening domain, ID) exert a considerable influence on the structural and functional features of the MBD (Claveria-Gimeno, R. et al. Sci Rep. 2017, 7, 41635), here we report the biophysical study of the influence of the protein scaffold on the structural and functional effect induced by these two RTT-associated mutations. These results represent an example of how a given mutation may show different effects (sometimes opposing effects) depending on the molecular context. Full article

Iodine, a micronutrient that plays a pivotal role in thyroid hormone synthesis, is essential for proper health at all life stages. Indeed, an insufficient iodine intake may determine a thyroid dysfunction also with goiter, or it may be associated to clinical features such as stunted growth and mental retardation, referred as iodine deficiency disorders (IDDs). Iodine deficiency still remains an important public health problem in many countries, including Italy. The effective strategy for the prevention and control of IDDs is universal salt iodization, which was implemented in Italy in 2005 as a nationwide program adopted after the approval of an Italian law. Despite an improvement in the iodine intake, many regions in Italy are still characterized by mild iodine deficiency. In this review, we provide an overview of the historical evolution of the iodine status in the Calabria region, located in the South of Italy, during the past three decades. In particular, we have retraced an itinerary from the first epidemiological surveys at the end of the 1980s to the establishment of the Regional Observatory of Endemic Goiter and Iodine Prophylaxis, which represents an efficient model for the surveillance of IDDs and monitoring the efficacy of iodine prophylaxis. Full article