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Background Spinal muscular atrophy (SMA-5q) is a neurodegenerative disease characterized by progressive muscle atrophy, hypotonia, and weakness, with SMA 1 presenting symptoms within the first 6 months of life. Disease-modifying therapies have been approved, with better outcomes with earlier treatment.

Spinal muscular atrophy (SMA) is a genetic neuromuscular progressive disorder that is currently treatable. The sooner the disease-modifying therapies are started, the better the prognosis. Newborn screening for SMA, which is already performed in many countries, has been scheduled to begin in the near future. The development of a well-organized program is paramount to achieve favorable outcomes for the child who is born with the disease and for the costs involved in health care. We herein present a review paper hoping to point out that SMA neonatal screening is urgent and will not increase the cost of its care.

Spinal muscular atrophy linked to chromosome 5 (SMA-5q) is an autosomal recessive genetic disease caused by mutations in the SMN1. SMA-5q is characterized by progressive degeneration of the spinal cord and bulbar motor neurons, causing severe motor and respiratory impairment with reduced survival, especially in its more severe clinical forms. In recent years, highly effective disease-modifying therapies have emerged, either acting by regulating the splicing of exon 7 of the SMN2 gene or adding a copy of the SMN1 gene through gene therapy, providing a drastic change in the natural history of the disease. In this way, developing therapeutic guides and expert consensus becomes essential to direct the use of these therapies in clinical practice. This consensus, prepared by Brazilian experts, aimed to review the main available disease-modifying therapies, critically analyze the results of clinical studies, and provide recommendations for their use in clinical practice for patients with SMA-5q. This consensus also addresses aspects related to diagnosis, genetic counseling, and follow-up of patients under drug treatment. Thus, this consensus provides valuable information regarding the current management of SMA-5q, helping therapeutic decisions in clinical practice and promoting additional gains in outcomes.

LIPID NANOPARTICLES (LNPS) are used to administer mRNA vaccines against Covid-19 and are considered as a crucial factor in ending the pandemic. Moreover, these nanoparticles are being researched as a [...]

OBJECTIVE: Help the pediatrician in the suspicion of neuromuscular diseases when the child has complaints or altered findings in neuropsychomotor development, presenting one review on the topic. METHODOLOGY: Non-systematic literature review using articles published between 2015 and 2021 obtained with the terms “neuromuscular disorders” and “children”; “neuromuscular disorders” and “pediatric”; “milestones” and “delay”; “motor development” and “delay”; “development”and “neuromuscular disorders”; “neuromuscular disorder” and “evaluation”; “neuromuscular disorders” and “examination” in the Lilacs, Medline, Paho, Wholis and Scielo research bases. RESULTS: Data found in the review were compiled and divided into three topics: (1) Warning signs for neuromuscular diseases: how history and physical examination help define hypotonia and signs of muscle weakness; (2) Differential Etiological Diagnoses: most common clinical presentations and brief description of the main diseases with available therapies; and (3) Investigation of Neuromuscular Diseases: examples of situations divided between those with central or peripheral hypotonia, the use of creatine phosphokinase dosage in cases of muscle weakness and motor delay and examples of confirmatory tests of neuromuscular diseases with therapeutic possibilities. CONCLUSION: Although neuromuscular diseases are individually rare, they may have specific treatment that modifies their natural history, then the important differential diagnosis when there is a delay in neuropsychomotor development. It is imperative that the pediatrician, as a reference professional for families, have a high degree of suspicion and knowledge that allows initial assessment and referral to a specialized service.

Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface "self-associated molecular patterns" that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2-3 Ma, possibly contributing to the origins of the genus Homo. The mutation likely altered human self-associated molecular patterns, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some gene-encoding Sia-sensing proteins suggested a "hotspot" in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human-Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal-human divergence ∼0.6 Ma. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, Natural Killer(NK) cells, and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6 and 2 Ma, potentially affecting human evolution.

The disintegration of complex Classic Maya population centres may have been driven by a decline in seasonal rainfall predictability in addition to protracted drought, suggests a dated speleothem record from Yok Balum cave, Belize.

In the last few decades, there have been considerable improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy. International guidelines have been published and recently reviewed. A group of Brazilian experts has developed a standard of care based on a literature review with evidence-based graded recommendations in a two-part publication. Implementing best practice management has helped change the natural history of this chronic progressive disorder, in which the life expectancy for children of the male sex in the past used to be very limited. Since the previous publication, diagnosis, steroid treatment, rehabilitation, and systemic care have gained more significant insights with new original work in certain fields. Furthermore, the development of new drugs is ongoing, and some interventions have been approved for use in certain countries. Therefore, we have identified the need to review the previous care recommendations for Brazilian patients with DMD. Our objective was to create an evidence-based document that is an update on our previous consensus on those topics.

The influence of climate on premodern civil conflict and societal instability is debated. Here, the authors combine archeological, historical, and paleoclimatic datasets to show that drought between 1400-1450 cal. CE escalated civil conflict at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula.

The genetic prehistory of central America has not been well explored. Here, the authors find evidence from ancient DNA from twenty individuals who lived in Belize 9,600 to 3,700 years ago of a migration from the south that coincided with the first evidence for forest clearing and the spread of maize horticulture.

We report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions.

Objective: Duchenne muscular dystrophy, an X-linked genetic disease, leads to progressive muscle weakness mainly in the lower limbs. Motor function tests help to monitor disease progression. Can low-cost, simple assessments help in the diagnostic suspicion of Duchenne muscular dystrophy? The authors aim to define the sensitivity of time to rise from the floor, time to walk 10 meters, and time to run 10 meters, evaluating them as eventual diagnostic screening tools. Methods: This is an analytical, observational, retrospective (1998–2015), and prospective study (2015–2018). Cases were recruited from the database of the pediatric neurology department and the healthy, from child care consultations, with normal gait development (up to 15 months) and without other comorbidities (neuromuscular, pulmonary, heart diseases) from the same university hospital. Results: 128 Duchenne muscular dystrophy patients and 344 healthy children were analyzed, equally distributed in age groups. In Duchenne muscular dystrophy, there is a progressive increase in the means of the times to perform the motor tests according to the age group, which accelerates very abruptly after 7 years of age. Healthy children acquire maximum motor capacity at 6 years and stabilize their times. The time to rise showed a p-value 0.8) in all age groups (except at 12 years), with time to walk 10 meters from 9 years, and with time to run 10 meters, from 5 years. The 100% sensitivity points were defined as follows: time to rise, at 2 s; time to walk 10 meters, 5 s; time to walk 10 meters, 4 s. Conclusions: Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy, a previously incurable disease with new perspectives for treatment. Resumo: Objetivo: A distrofia muscular de Duchenne, doença genética ligada ao X, determina fraqueza muscular progressiva principalmente em membros inferiores. Os testes de função motora ajudam a monitorar a progressão da doença. Avaliações simples de baixo custo podem ajudar na suspeita diagnóstica da distrofia muscular de Duchenne? Objetivamos definir a sensibilidade do tempo levantar, tempo andar 10 metros e tempo correr 10 metros, avaliando-os como eventuais ferramentas de triagem diagnóstica. Métodos: Estudo analítico, observacional, retrospectivo (1998 até 2015) e prospectivo (2015 até 2018). Os casos foram recrutados do banco de dados do serviço de neurologia infantil e os saudáveis, de consultas de puericultura, com desenvolvimento de marcha normal (até os 15 meses) e sem outras comorbidades (neuromusculares, pneumopatias, cardiopatias), do mesmo hospital universitário. Resultados: Foram analisados 128 pacientes com distrofia muscular de Duchenne e 344 saudáveis, distribuídos igualmente em faixas etárias. Na distrofia muscular de Duchenne ocorre aumento progressivo das médias dos tempos para realizar as provas motoras, de forma acentuada a partir dos 7 anos. Os saudáveis estabilizam os tempos a partir dos 6 anos, adquirindo capacidade motora máxima. O tempo de levantar apresentou p-valor 0,8) em todas as faixas etárias (exceto aos 12 anos), tempo de andar 10 metros a partir de 9 anos e o tempo de correr 10 metros, dos 5 anos. Os pontos de 100% sensibilidade foram definidos: tempo de levantar aos 2 segundos; tempo de andar, 5 segundos e tempo de correr 10 metros, 4 segundos. Conclusões: O tempo de levantar é útil e simples na triagem de doenças neuromusculares como a distrofia muscular de Duchenne, doença antes incurável com novas perspectivas de tratamento.

Purpose Given that intellectual disability affects 15% to 63% of boys with Duchenne muscular dystrophy (DMD), it is relevant to evaluate if the Mini-Mental State Examination (MMSE) is a reliable test for screening in these cognitively impaired boys. Methods A descriptive study of 74 DMD boys was performed. Age, years of schooling, genotype, and performance in the MMSE and Wechsler Intelligence Scale for Children (WISC)-IV were verified. Results Sixty-seven patients, with a mean of age 12.1±3 years were enrolled. Verbal comprehension (76.9±13.9) and working memory (71.2±16.7) indexes showed the highest impairment. Correlation between the MMSE (20.3±6.1) and WISC-IV (74.4±15.6) was moderate (r=0.556). Conclusion The MMSE is a good cognitive screening test for DMD patients of 9 years and older, particularly in countries where the public health system does not provide expensive neuropsychological batteries, and has 78% accuracy and 82% sensitivity for scores ≤21. Subtests of the MMSE with better discriminatory power (for orientation, attention, and calculation) can help educators, teachers, and families to develop simple activities or academic games that enhance such mental skills.

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method—combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups—to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization.

Analyses of terminal long count dates from stone monuments in the Maya lowlands have played a central role in characterizing the rise and “collapse” of polities during the Late and Terminal Classic periods (a.d. 730–910). Previous studies propose a directional abandonment of large political centers from west-to-east. We retest the west-to-east hypothesis, using Geographic Information Systems (GIS) and spatial statistics to analyze an updated dataset of 89 terminal dates from the Maya Hieroglyphic Database (MHD). Our results do not support a directional collapse, but instead suggest a contraction of Terminal Classic polities around seven core areas in the Maya lowlands. Three regions demonstrate distinct subregional abandonments of monument carving over a period of 24 to 127 years, consistent with independent archaeological data for each region. Advances in GIS, spatial statistics, and related methods applied to an increasingly detailed and comprehensive epigraphic and archaeological database provide a foundation for examining long-term sociopolitical dynamics in the Maya lowlands.

Archaeologists have begun to understand that many of the challenges facing our technologically sophisticated, resource dependent, urban systems were also destabilizing factors in ancient complex societies. The focus of IHOPE-Maya is to identify how humans living in the tropical Maya Lowlands in present-day Central America responded to and impacted their environments over the past three millennia, and to relate knowledge of those processes to modern and future coupled human-environment systems. To better frame variability in ancient lowland Maya development and decline, the area that they once occupied may be subdivided into a series of geographical regions in which the collected archaeological data can be correlated with environmental differences. Although beginning as small agricultural communities occupying a variety of ecological niches in the humid tropics of Mesoamerica, the ancient Maya became an increasingly complex set of societies involved in intensive and extensive resource exploitation. Their development process was not linear, but also involved periods of rapid growth that were punctuated by contractions. Thus, the long-term development and disintegration of Maya geopolitical institutions presents an excellent vantage from which to study resilience, vulnerability, and the consequences of decision-making in ancient complex societies.