Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile.

In the dusk of the Mesozoic, advanced duck-billed dinosaurs (Hadrosauridae) were so successful that they likely outcompeted other herbivores, contributing to declines in dinosaur diversity. From Laurasia, hadrosaurids dispersed widely, colonizing Africa, South America, and, allegedly, Antarctica. Here, we present the first species of a duck-billed dinosaur from a subantarctic region, Gonkoken nanoi, of early Maastrichtian age in Magallanes, Chile. Unlike duckbills further north in Patagonia, Gonkoken descends from North American forms diverging shortly before the origin of Hadrosauridae. However, at the time, non-hadrosaurids in North America had become replaced by hadrosaurids. We propose that the ancestors of Gonkoken arrived earlier in South America and reached further south, into regions where hadrosaurids never arrived: All alleged subantarctic and Antarctic remains of hadrosaurids could belong to non-hadrosaurid duckbills like Gonkoken. Dinosaur faunas of the world underwent qualitatively different changes before the Cretaceous-Paleogene asteroid impact, which should be considered when discussing their possible vulnerability.

The evolutionary consequences of epigenesis and neutral change: A conceptual approach at the organismal level.

Living beings are autopoietic systems with highly context-dependent structural dynamics and interactions, that determine whether a disturbance in the genotype or environment will lead or not to phenotypic change. The concept of epigenesis entails how a change in the phenotype may not correspond to a change in the structure of an earlier developmental stage, including the genome. Disturbances of embryonic structure may fail to change the phenotype, as in regulated development, or when different genotypes are associated to a single phenotype. Likewise, the same genotype or early embryonic structure may develop different phenotypes, as in phenotypic plasticity. Disturbances that fail to trigger phenotypic change are considered neutral, but even so, they can alter unexpressed developmental potential. Here, we present conceptual diagrams of the "epigenic field": similar to Waddington's epigenetic landscapes, but including the ontogenic niche (organism/environment interactional dynamics during ontogeny) as a factor in defining epigenic fields, rather than just selecting among possible pathways. Our diagrams illustrate transgenerational changes of genotype, ontogenic niche, and their correspondence (or lack thereof) with changes of phenotype. Epigenic fields provide a simple way to understand developmental constraints on evolution, for instance: how constraints evolve as a result of developmental system drift; how neutral changes can be involved in genetic assimilation and de-assimilation; and how constraints can evolve as a result of neutral changes in the ontogenic niche (not only the genotype). We argue that evolutionary thinking can benefit from a framework for evolution with conceptual foundations at the organismal level.

No Evidence of Rabies Exposure in Wild Marmosets (Callithrix jacchus) of Northeast Brazil.

Rabies transmitted by wildlife is the main source of human rabies mortality in Latin America and considered an emerging disease. The common marmoset Callithrix jacchus of Brazil is the only known primate reservoir of rabies worldwide. We tested whether alive free-ranging C. jacchus were exposed to rabies in four northeast states that have previously reported rabies-positive dead C. jacchus (Pernambuco and Bahia) or not (Paraíba and Rio Grande do Norte). Our results show no evidence of rabies antibodies or infection in the sampled C. jacchus, suggesting that apparently healthy marmosets are not widely exposed to rabies over their natural range.

Description of human anti-rabies post-exposure prophylaxis care notifications in Brazil, 2014-2019. / Descrição das notificações de atendimento antirrábico humano para profilaxia pós-exposição no Brasil, 2014-2019.

OBJECTIVE: To analyze human anti-rabies post-exposure prophylaxis notifications in Brazil. METHODS: This was a descriptive study using data from the Notifiable Diseases Information System in Brazil, from 2014 to 2019. RESULTS: A total of 4,033,098 anti-rabies medical consultations were notified, averaging 672,183 a year. Percentage care was higher among males (n = 2,111,369; 52.4%), those under 19 years old (n = 1,423,433; 35.3%), living in urban areas (n = 3,386,589; 88.1%), attacked by dogs (n = 3,281,190; 81.5%) and bitten (n = 3,575,717; 81.9%), mainly on the hands and feet (n = 1,541,201; 35.3%). The most frequent prophylactic procedure was observation plus vaccination (n = 1,736,036; 44.2%). Prophylactic procedure was appropriate in 57.8% (n = 2,169,689) of cases and inappropriate in 42.2% (n = 1,582,411) of cases. CONCLUSION: Although there were appropriate prophylactic procedures, we also found procedures that were inappropriate and which, when insufficient, can result in cases of human rabies and, when unnecessary, can result in waste, including shortage of immunobiological products.

Spatio-temporal dynamics of rabies and habitat suitability of the common marmoset Callithrix jacchus in Brazil.

Rabies transmitted by wildlife is now the main source of human rabies in the Americas. The common marmoset, Callithrix jacchus, is considered a reservoir of rabies causing sporadic and unpredictable human deaths in Brazil, but the extent of the spillover risk to humans remains unknown. In this study, we described the spatiotemporal dynamics of rabies affecting C. jacchus reported to Brazil's Ministry of Health passive surveillance system between 2008 and 2020, and combined ecological niche modelling with C. jacchus occurrence data to predict its suitable habitat. Our results show that 67 outbreaks (91 cases) of rabies affecting C. jacchus were reported by 41 municipalities between January 2008 and October 2020, with a mean of 5 outbreaks/year [range: 1-14]. The maximum number of outbreaks and municipalities reporting cases occurred in 2018, coinciding with higher surveillance of primate deaths due to Yellow Fever. A mean of 3 [1-9] new municipalities reported outbreaks yearly, suggesting potential spatial expansions of the C. jacchus variant in northeastern Brazil and emerging rabies spillover from vampire bat Desmodus rotundus to C. jacchus in the north and south. Outbreaks were concentrated in the states of Ceará (72%) and Pernambuco (16%) up to 2012, but are now reported in Piauí since 2013, in Bahia since 2017 (D. rotundus' antigenic variant, AgV3) and in Rio de Janeiro since 2019 (AgV3). Besides confirming suitable habitat for this primate in the northeast and the east coast of Brazil, our Maximum Entropy model also predicted suitable habitat on the north and the west states of the country but predicted low habitat suitability among inland municipalities of the Caatinga biome reporting rabies. Our findings revealed new areas reporting rabies infecting C. jacchus, highlighting the need to implement strategies limiting spillover to humans and to better understand the drivers of C. jacchus rabies dynamics.

Description of human anti-rabies post-exposure prophylaxis care notifications in Brazil, 2014-2019 / Descripción de notificaciones de atención antirrábica humana para la profilaxis posexposición en Brasil, 2014-2019 / Descrição das notificações de atendimento antirrábico humano para profilaxia pós-exposição no Brasil, 2014-2019

Objective: To analyze human anti-rabies post-exposure prophylaxis notifications in Brazil. Methods: This was a descriptive study of human anti-rabies post-exposure prophylaxis care notified on the Notifiable Health Conditions Information System in Brazil between 2014 and 2019. Results: A total of 4,033,098 anti-rabies medical consultations were notified, averaging 672,183 a year. Percentage care was higher among males (n=2,111,369; 52.4%), those under 19 years old (n=1,423,433; 35.3%), living in urban areas (n=3,386,589; 88.1%), attacked by dogs (n=3,281,190; 81.5%) and bitten (n=3,575,717; 81.9%), mainly on the hands and feet (n=1,541,201; 35.3%). The most frequent prophylactic procedure was observation plus vaccination (n=1,736,036; 44.2%). Prophylactic procedure was appropriate in 57.8% (n=2,169,689) of cases and inappropriate in 42.2% (n=1,582,411) of cases. Conclusion: Although there were appropriate prophylactic procedures, we also found procedures that were inappropriate and which, when insufficient, can result in cases of human rabies and, when unnecessary, can result in waste, including shortage of immunobiological products

Objetivo: Analizar la atención antirrábica humana de profilaxis post exposición en Brasil, de 2014 a 2019. Métodos: Estudio descriptivo de la atención antirrábica humana de profilaxis post exposición, notificados en el Sistema de Información de Agravamientos de Notificación en Brasil, de 2014 a 2019. Resultados: Se notificaron 4.033.098 atendimientos antirrábicos, con un promedio de 672.183 al año. Hubo mayor porcentual de atención a personas del sexo masculino (n=2.111.369; 52,4%), menores de 19 años (n=1.423.433; 35,3%), residentes en área urbana (n=3.386.589; 88,1%), agredidas por perros (n=3.281.190; 81,5%) y con mordidas (n=3.575.717; 81,9%), principalmente en las manos y pies (n=1.541.201; 35,3%). La conducta profiláctica más frecuente fue la observación y vacuna (n=1.736.036; 44,2%). La conducta profiláctica fue adecuada en 57,8% (n=2.169.689) e inadecuada en 42,2% (n=1.582.411) de los casos. Conclusión: A pesar de las conductas profilácticas adecuadas, se observaron indicaciones inadecuadas que, cuando insuficientes, pueden resultar en casos de rabia humana y, cuando desnecesarias, desperdicios, incluso desabastecimiento de inmunobiológicos.

Objetivo: Analisar os atendimentos antirrábicos humanos de profilaxia pós-exposição no Brasil. Métodos: Estudo descritivo dos atendimentos antirrábicos humanos de profilaxia pós-exposição notificados no Sistema de Informação de Agravos de Notificação no Brasil, de 2014 a 2019. Resultados: Foram notificados 4.033.098 atendimentos antirrábicos, com média de 672.183 ao ano. Houve maior percentual de atendimentos em pessoas do sexo masculino (n=2.111.369; 52,4%), menores de 19 anos de idade (n=1.423.433; 35,3%), residentes em área urbana (n=3.386.589; 88,1%), agredidas por cães (n=3.281.190; 81,5%) e com mordeduras (n=3.575.717; 81,9%), principalmente em mãos e pés (n=1.541.201; 35,3%). A conduta profilática mais frequente foi observação e vacina (n=1.736.036; 44,2%). A conduta profilática foi adequada em 57,8% (n=2.169.689) e inadequada em 42,2% (n=1.582.411) dos casos. Conclusão: Apesar das condutas profiláticas adequadas, foram observadas indicações inadequadas que, quando insuficientes, podem acarretar casos de raiva humana e, quando desnecessárias, desperdícios, inclusive desabastecimento de imunobiológicos.

Developmental evolution of the distal ankle in the dinosaur-bird transition.

The adult ankle of early reptiles had five distal tarsal (dt) bones, but in Dinosauria, these were reduced to only two: dt3 and dt4, articulated to metatarsals (mt) mt3 and mt4. Birds have a single distal tarsal ossification center that fuses to the proximal metatarsals to form a new adult skeletal structure: the composite tarsometatarsus. This ossification center develops within a single large embryonic cartilage, but it is unclear if this cartilage results from fusion of earlier cartilages. We studied embryos in species from four different bird orders, an alligatorid, and an iguanid. In all embryos, cartilages dt2, dt3, and dt4 are formed. In the alligatorid and the iguanid, dt2 failed to ossify: only dt3 and dt4 develop into adult bones. In birds, dt2, dt3, and dt4 fuse to form the large distal tarsal cartilage; the ossification center then develops above mt3, in cartilage presumably derived from dt3. During the entire dinosaur-bird transition, a dt2 embryonic cartilage was always formed, as inferred from the embryology of extant birds and crocodilians. We propose that in the evolution of the avian ankle, fusion of cartilages dt3 and dt2 allowed ossification from dt3 to progress into dt2, which began to contribute bone medially, while fusion of dt3 to dt4 enabled the evolutionary loss of the dt4 ossification center. As a result, a single ossification center expands into a plate-like unit covering the proximal ends of the metatarsals, that is key to the development of an integrated tarsometatarsus.

Descrição das notificações de atendimento antirrábico humano para profilaxia pós-exposição no Brasil, 2014-2019 / Descripción de notificaciones de atención antirrábica humana para la profilaxis post-exposición en Brasil, 2014-2019 / Description of human anti-rabies post-exposure prophylaxis care notifications in Brazil, 2014-2019

Objetivo: Analisar os atendimentos antirrábicos humanos de profilaxia pós-exposição no Brasil. Métodos: Estudo descritivo utilizando dados do Sistema de Informação de Agravos de Notificação no Brasil, de 2014 a 2019. Resultados: Foram notificados 4.033.098 atendimentos antirrábicos, com média de 672.183 ao ano. Houve maior percentual de atendimentos em pessoas do sexo masculino (n = 2.111.369; 52,4%), menores de 19 anos de idade (n = 1.423.433; 35,3%), residentes em área urbana (n = 3.386.589; 88,1%), agredidas por cães (n = 3.281.190; 81,5%) e com mordeduras (n = 3.575.717; 81,9%), principalmente em mãos e pés (n = 1.541.201; 35,3%). A conduta profilática mais frequente foi observação e vacina (n = 1.736.036; 44,2%). A conduta profilática foi adequada em 57,8% (n = 2.169.689) e inadequada em 42,2% (n = 1.582.411) dos casos. Conclusão: Apesar das condutas profiláticas adequadas, foram observadas indicações inadequadas que, quando insuficientes, podem acarretar casos de raiva humana e, quando desnecessárias, desperdícios, inclusive desabastecimento de imunobiológicos.

Objetivo: Analizar la atención antirrábica humana de profilaxis post exposición en Brasil, de 2014 a 2019. Métodos: Estudio descriptivo utilizando datos del Sistema de Información de Agravamientos de Notificación en Brasil, de 2014 a 2019. Resultados: Se notificaron 4.033.098 atendimientos antirrábicos, con un promedio de 672.183 al año. Hubo mayor porcentual de atención a personas del sexo masculino (n = 2.111.369; 52,4%), menores de 19 años (n = 1.423.433; 35,3%), residentes en área urbana (n = 3.386.589; 88,1%), agredidas por perros (n = 3.281.190; 81,5%) y con mordidas (n = 3.575.717; 81,9%), principalmente en las manos y pies (n = 1.541.201; 35,3%). La conducta profiláctica más frecuente fue la observación y vacuna (n = 1.736.036; 44,2%). La conducta profiláctica fue adecuada en 57,8% (n = 2.169.689) e inadecuada en 42,2% (n = 1.582.411) de los casos. Conclusión: A pesar de las conductas profilácticas adecuadas, se observaron indicaciones inadecuadas que, cuando insuficientes, pueden resultar en casos de rabia humana y, cuando desnecesarias, desperdicios, incluso desabastecimiento de inmunobiológicos.

Objective: To analyze human anti-rabies post-exposure prophylaxis notifications in Brazil. Methods: This was a descriptive study using data from the Notifiable Diseases Information System in Brazil, from 2014 to 2019. Results: A total of 4,033,098 anti-rabies medical consultations were notified, averaging 672,183 a year. Percentage care was higher among males (n = 2,111,369; 52.4%), those under 19 years old (n = 1,423,433; 35.3%), living in urban areas (n = 3,386,589; 88.1%), attacked by dogs (n = 3,281,190; 81.5%) and bitten (n = 3,575,717; 81.9%), mainly on the hands and feet (n = 1,541,201; 35.3%). The most frequent prophylactic procedure was observation plus vaccination (n = 1,736,036; 44.2%). Prophylactic procedure was appropriate in 57.8% (n = 2,169,689) of cases and inappropriate in 42.2% (n = 1,582,411) of cases. Conclusion: Although there were appropriate prophylactic procedures, we also found procedures that were inappropriate and which, when insufficient, can result in cases of human rabies and, when unnecessary, can result in waste, including shortage of immunobiological products.

Bizarre tail weaponry in a transitional ankylosaur from subantarctic Chile.

Armoured dinosaurs are well known for their evolution of specialized tail weapons-paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs1. Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria2-4. Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur from the late Cretaceous period of Magallanes in southernmost Chile, a region that is biogeographically related to West Antarctica5. Stegouros elengassen gen. et sp. nov. evolved a large tail weapon unlike any dinosaur: a flat, frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail. Stegouros shows ankylosaurian cranial characters, but a largely ancestral postcranial skeleton, with some stegosaur-like characters. Phylogenetic analyses placed Stegouros in Ankylosauria; specifically, it is related to Kunbarrasaurus from Australia6 and Antarctopelta from Antarctica7, forming a clade of Gondwanan ankylosaurs that split earliest from all other ankylosaurs. The large osteoderms and specialized tail vertebrae in Antarctopelta suggest that it had a tail weapon similar to Stegouros. We propose a new clade, the Parankylosauria, to include the first ancestor of Stegouros-but not Ankylosaurus-and all descendants of that ancestor.

New cladotherian mammal from southern Chile and the evolution of mesungulatid meridiolestidans at the dusk of the Mesozoic era.

In the last decades, several discoveries have uncovered the complexity of mammalian evolution during the Mesozoic Era, including important Gondwanan lineages: the australosphenidans, gondwanatherians, and meridiolestidans (Dryolestoidea). Most often, their presence and diversity is documented by isolated teeth and jaws. Here, we describe a new meridiolestidan mammal, Orretherium tzen gen. et sp. nov., from the Late Cretaceous of southern Chile, based on a partial jaw with five cheek teeth in locis and an isolated upper premolar. Phylogenetic analysis places Orretherium as the earliest divergence within Mesungulatidae, before other forms such as the Late Cretaceous Mesungulatum and Coloniatherium, and the early Paleocene Peligrotherium. The in loco tooth sequence (last two premolars and three molars) is the first recovered for a Cretaceous taxon in this family and suggests that reconstructed tooth sequences for other Mesozoic mesungulatids may include more than one species. Tooth eruption and replacement show that molar eruption in mesungulatids is heterochronically delayed with regard to basal dryolestoids, with therian-like simultaneous eruption of the last premolar and last molar. Meridiolestidans seem endemic to Patagonia, but given their diversity and abundance, and the similarity of vertebrate faunas in other regions of Gondwana, they may yet be discovered in other continents.

A giant soft-shelled egg from the Late Cretaceous of Antarctica.

Egg size and structure reflect important constraints on the reproductive and life-history characteristics of vertebrates1. More than two-thirds of all extant amniotes lay eggs2. During the Mesozoic era (around 250 million to 65 million years ago), body sizes reached extremes; nevertheless, the largest known egg belongs to the only recently extinct elephant bird3, which was roughly 66 million years younger than the last nonavian dinosaurs and giant marine reptiles. Here we report a new type of egg discovered in nearshore marine deposits from the Late Cretaceous period (roughly 68 million years ago) of Antarctica. It exceeds all nonavian dinosaur eggs in volume and differs from them in structure. Although the elephant bird egg is slightly larger, its eggshell is roughly five times thicker and shows a substantial prismatic layer and complex pore structure4. By contrast, the new fossil, visibly collapsed and folded, presents a thin eggshell with a layered structure that lacks a prismatic layer and distinct pores, and is similar to that of most extant lizards and snakes (Lepidosauria)5. The identity of the animal that laid the egg is unknown, but these preserved morphologies are consistent with the skeletal remains of mosasaurs (large marine lepidosaurs) found nearby. They are not consistent with described morphologies of dinosaur eggs of a similar size class. Phylogenetic analyses of traits for 259 lepidosaur species plus outgroups suggest that the egg belonged to an individual that was at least 7 metres long, hypothesized to be a giant marine reptile, all clades of which have previously been proposed to show live birth6. Such a large egg with a relatively thin eggshell may reflect derived constraints associated with body shape, reproductive investment linked with gigantism, and lepidosaurian viviparity, in which a 'vestigial' egg is laid and hatches immediately7.

Assesment and interpretation of negative forelimb allometry in the evolution of non-avian Theropoda.

BACKGROUND: The origin of birds is marked by a significant decrease in body size along with an increase in relative forelimb size. However, before the evolution of flight, both traits may have already been related: It has been proposed that an evolutionary trend of negative forelimb allometry existed in non-avian Theropoda, such that larger species often have relatively shorter forelimbs. Nevertheless, several exceptions exist, calling for rigorous phylogenetic statistical testing. RESULTS: Here, we re-assessed allometric patterns in the evolution of non-avian theropods, for the first time taking into account the non-independence among related species due to shared evolutionary history.We confirmed a main evolutionary trend of negative forelimb allometry for non-avian Theropoda, but also found support that some specific subclades (Coelophysoidea, Ornithomimosauria, and Oviraptorosauria) exhibit allometric trends that are closer to isometry, losing the ancestral negative forelimb allometry present in Theropoda as a whole. CONCLUSIONS: Explanations for negative forelimb allometry in the evolution of non-avian theropods have not been discussed, yet evolutionary allometric trends often reflect ontogenetic allometries, which suggests negative allometry of the forelimb in the ontogeny of most non-avian theropods. In modern birds, allometric growth of the limbs is related to locomotor and behavioral changes along ontogeny. After reviewing the evidence for such changes during the ontogeny of non-avian dinosaurs, we propose that proportionally longer arms of juveniles became adult traits in the small-sized and paedomorphic Aves.

Human rabies in Brazil: a descriptive study, 2000-2017. / Raiva humana no Brasil: estudo descritivo, 2000-2017.

OBJECTIVE: to describe the epidemiological profile of human rabies in Brazil. METHODS: this is a descriptive study of human rabies cases reported in 2000-2017, with an estimate of incidence and spatial distribution. RESULTS: 188 cases were studied, mostly males (66.5%), rural residents (67.0%), children under 15 years (49.6%), with biting being the most frequent form of exposure (81.9%); frequency was highest in the period 2000-2008 (85.6%), with 46.6% of cases involving dogs and 45.9% bats; median incubation was 50 days, followed by, predominantly, symptoms of fever (92.6%), agitation (85.2%), paresthesia (66.7%), and dysphagia/paralysis (51.9%); the majority (70.2%) did not have prophylaxis and for the rest (29.8%) who did have prophylaxis, it was untimely and/or incomplete; 13 patients were treated according to the Recife Protocol, and two survived. CONCLUSION: human rabies incidence reduced and its epidemiological profile changed, with predominance of cases transmitted by bats; we suggest that secondary cases be investigated, and that pre-exposure prophylaxis be made available to populations at greater risk of accidents involving bats.

Raiva humana no Brasil: estudo descritivo, 2000-2017 / La rabia humana en Brasil: estudio descriptivo, 2000-2017 / Human rabies in Brazil: a descriptive study, 2000-2017

Objetivo: descrever o perfil epidemiológico da raiva humana no Brasil. Métodos: estudo descritivo dos casos de raiva humana notificados em 2000-2017; estimou-se a incidência e distribuição espacial. Resultados: 188 casos humanos observados, na maioria homens (66,5%), residentes rurais (67,0%), menores de 15 anos de idade (49,6%), com exposição mais frequente por mordedura (81,9%); o período 2000-2008 apresentou maior frequência (85,6%), com 46,6% dos casos envolvendo cães e 45,9% morcegos; incubação mediana de 50 dias, seguida de sintomatologia predominante de febre (92,6%), agitação (85,2%), parestesia (66,7%) e disfagia/paralisia (51,9%); a maioria (70,2%) não fez profilaxia, os demais (29,8%) realizaram-na de forma inoportuna e/ou incompleta; 13 pacientes foram tratados pelo Protocolo de Recife e dois sobreviveram. Conclusão: houve redução na incidência de raiva humana e mudança no perfil epidemiológico, predominando casos transmitidos por morcegos; sugere-se investigar casos secundários e viabilizar a profilaxia pré-exposição em populações sob maior risco de acidentes com morcegos.

Objetivo: describir el perfil epidemiológico de la rabia humana en Brasil. Métodos: descripción de los casos en 2000-2017, con estimación de la incidencia y distribución espacial. Resultados: se observaron 188 casos humanos, la mayoría de hombres (66,5%), residentes rurales (67,0%), menores de 15 años de edad (49,6%), con exposición más frecuente por mordedura (81,9%); el período 2000-2008 presentó mayor frecuencia (85,6%), con un 46,6% de los casos involucrando a perros y 45,9% a murciélagos; la incubación promedio fue de 50 días, seguida de sintomatología predominante de fiebre (92,6%), agitación (85,2%), parestesia (66,7%) y disfagia/parálisis (51,9%); la mayoría (70,2%) no hizo profilaxis y los demás (29,8%) la realizaron de forma inoportuna y/o incompleta; se trataron 13 pacientes con el Protocolo de Recife y dos sobrevivieron. Conclusión: hubo reducción en la incidencia de rabia humana y cambio en el perfil epidemiológico, predominando casos transmitidos por murciélagos; se sugiere investigar casos secundarios y viabilizar la profilaxis preexposición en poblaciones de mayor riesgo a accidentes por murciélagos.

Objective: to describe the epidemiological profile of human rabies in Brazil. Methods: this is a descriptive study of human rabies cases reported in 2000-2017, with an estimate of incidence and spatial distribution. Results: 188 cases were studied, mostly males (66.5%), rural residents (67.0%), children under 15 years (49.6%), with biting being the most frequent form of exposure (81.9%); frequency was highest in the period 2000-2008 (85.6%), with 46.6% of cases involving dogs and 45.9% bats; median incubation was 50 days, followed by, predominantly, symptoms of fever (92.6%), agitation (85.2%), paresthesia (66.7%), and dysphagia/paralysis (51.9%); the majority (70.2%) did not have prophylaxis and for the rest (29.8%) who did have prophylaxis, it was untimely and/or incomplete; 13 patients were treated according to the Recife Protocol, and two survived. Conclusion: human rabies incidence reduced and its epidemiological profile changed, with predominance of cases transmitted by bats; we suggest that secondary cases be investigated, and that pre-exposure prophylaxis be made available to populations at greater risk of accidents involving bats.

Dinosaur ossification centres in embryonic birds uncover developmental evolution of the skull.

Radical transformation of the skull characterizes bird evolution. An increase in the relative size of the brain and eyes was presumably related to the loss of two bones surrounding the eye, the prefrontal and postorbital. We report that ossification centres of the prefrontal and postorbital are still formed in bird embryos, which then fuse seamlessly to the developing nasal and frontal bones, respectively, becoming undetectable in the adult. The presence of a dinosaur-like ossification pattern in bird embryos is more than a trace of their evolutionary past: we show how persistent modularity of ossification centres has allowed for evolutionary re-organization of skull architecture in evolution. Our findings also demonstrate that enigmatic mesodermal cells forming the posterior region of the avian frontal correspond to the ossification centre of the postorbital, not the parietal, and link its failure to develop into an adult bone to its incorporation into the expanded braincase of birds.

[Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015]. / Anafilaxia relacionada à vacina sarampo, caxumba e rubéola, Santa Catarina, Brasil, 2014 e 2015.

The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. RECOMMENDATIONS: the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Os objetivos consistiram em descrever os casos e verificar a frequência de anafilaxia relacionada à vacina sarampo, caxumba e rubéola (SCR) do produtor A, bem como avaliar os possíveis fatores de risco associados. Estudo de caso-controle (1:4), em Santa Catarina, Brasil, de 14 de julho de 2014 a 12 de janeiro de 2015, em crianças de um a menores de cinco anos, vacinadas com SCR e notificadas com anafilaxia, sendo os controles sem anafilaxia. Utilizou-se, como medida de associação, odds ratio (OR) com intervalo de 95% de confiança (IC95%) e os testes qui-quadrado e exato de Fisher. Calcularam-se taxas de anafilaxia por doses distribuídas/aplicadas. Entrevistaram-se 15 casos e 60 controles, em 12 municípios. As taxas de anafilaxia foram 2,46 e 5,05 por doses distribuídas e aplicadas, respectivamente. Dentre os casos de anafilaxia, oito (53,4%) eram do sexo masculino, e dentre os controles, 36 (60%), com p = 0,64. Na análise bivariada referente à anafilaxia e alergia à proteína do leite de vaca (APLV), verificou-se OR = 51,62, com p = 0,00002 e IC95%: 5,59-476,11. As variáveis alergia alimentar familiar, aleitamento materno, evento adverso pós-vacinação (EAPV) anterior e vacinação simultânea não foram estatisticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Taxas de anafilaxia por doses distribuídas/aplicadas ficaram acima de 1/100 mil doses aplicadas (taxa esperada). Anafilaxia e APLV apresentaram associação estatisticamente significativa. Não foram encontradas associações estatísticas referentes à vacinação simultânea, aleitamento materno, alergia alimentar familiar e EAPV anterior. Recomendou-se ao produtor informar na bula todos os componentes do produto e que crianças com história pregressa de APLV não sejam vacinadas com essa vacina.

Los objetivos consistieron en describir los casos y verificar la frecuencia de anafilaxia, relacionada con la vacuna del sarampión, paperas y rubeola (SCR) del productor A, así como evaluar los posibles factores de riesgo asociados. Estudio de caso-control (1:4), en Santa Catarina, Brasil, de 14 de julio de 2014 a 12 de enero de 2015, en niños de uno a menores de cinco años, vacunadas con SCR y notificadas con anafilaxia, siendo los controles sin anafilaxia. Se utilizó, como medida de asociación, odds ratio (OR) con un intervalo de 95% de confianza (IC95%) y los testes chi-cuadrado y exacto de Fisher. Se calcularon las tasas de anafilaxia por dosis distribuidas/aplicadas. Se entrevistaron 15 casos y 60 controles, en 12 municipios. Las tasas de anafilaxia fueron 2,46 y 5,05 por dosis distribuidas y aplicadas, respectivamente. Entre los casos de anafilaxia, ocho (53,4%) eran del sexo masculino, y entre los controles, 36 (60%), con p = 0,64. En el análisis bivariado referente a la anafilaxia y alergia a la proteína de leche de vaca (APLV), se verificó OR = 51,62, con p = 0,00002 e IC95%: 5,59-476,11. Las variables alergia alimentaria familiar, lactancia materna , evento adverso pos-vacunación (EAPV) anterior y vacunación simultánea no fueron estadísticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Tasas de anafilaxia por dosis distribuidas/aplicadas se situaron encima de 1/100.000 dosis aplicadas (tasa esperada). Anafilaxia y APLV presentaron una asociación estadísticamente significativa. No fueron encontradas asociaciones estadísticas referentes a la vacunación simultánea, lactancia materna, alergia alimentaria familiar y EAPV anterior. Se recomendó al productor informar en el prospecto sobre todos los componentes del producto, y que los niños con historial anterior de APLV no sean vacunados con esa vacuna.

[Investigation of an outbreak of acute Chagas disease outside the Amazon Region, in Rio Grande do Norte State, Brazil, 2016]. / Investigação de surto de doença de Chagas aguda na região extra-amazônica, Rio Grande do Norte, Brasil, 2016.

The aim of this article was to confirm and describe an outbreak of acute Chagas disease involving oral transmission in the western region of Rio Grande do Norte State, Brazil. This was a descriptive case series study in which the data sources were medical records and interviews with suspected cases from September 16 to November 19, 2015. An entomological investigation was conducted in the probable sites of infection for acute Chagas disease cases. Eighteen cases of acute Chagas disease were confirmed in residents of four municipalities (counties) in Rio Grande do Norte State. The most frequently reported signs and symptoms were fever and weakness (n = 18), followed by myalgia (n = 17), prostration, loss of appetite, and edema of the lower limbs (n = 15). Median duration of fever was 20 days (range: 6 to 45 days). Fifteen cases were confirmed by the laboratory criterion and three by epidemiological link with consistent clinical characteristics. All confirmed cases reported having consumed sugar cane juice from the same mill. A total of 110 triatomines were captured on the plantation where the sugar cane had been crushed for juice. The insects were found in the peridomicile, in stacks of firewood and close to the sugar cane mill. The majority of the captured specimens were Triatoma brasiliensis and showed a natural infection rate of 63%. The Chagas disease outbreak was confirmed with oral transmission via ingestion of sugar cane juice contaminated with infected triatomines, as evidenced by the epidemiological link between the investigated cases and the entomological survey in the probable site where the infection occurred.

O objetivo do artigo foi confirmar e descrever um surto da doença de Chagas aguda por transmissão oral na mesorregião Oeste Potiguar, Rio Grande do Norte, Brasil. Trata-se de um estudo descritivo do tipo série de casos, tendo como fonte de dados os registros de atendimentos médicos e entrevistas com os casos suspeitos entre 16 de setembro e 19 de novembro de 2015. Realizou-se pesquisa entomológica nas prováveis localidades de infecção dos casos de doença de Chagas aguda. Foram confirmados 18 casos de doença de Chagas aguda em residentes de quatro municípios do Rio Grande do Norte. Os sinais e sintomas mais relatados foram febre e fraqueza (n = 18), seguidos de mialgia (n = 17), prostração, inapetência e edema de membros inferiores (n = 15). A mediana de duração da febre foi de 20 dias (intervalo: 6 a 45 dias). Quinze casos foram confirmados por critério laboratorial e três por vínculo epidemiológico com clínica compatível. Todos os casos confirmados relataram ter consumido caldo de cana da mesma procedência. Foram capturados 110 triatomíneos na fazenda onde ocorreu a moagem da cana consumida. Os insetos estavam no peridomicílio, em amontoados de lenha e próximos ao engenho. A maioria dos exemplares capturados era da espécie Triatoma brasiliensis, e apresentou um índice de infecção natural de 63%. Foi confirmado surto da doença de Chagas de transmissão oral por ingestão de caldo de cana contaminado por triatomíneo infectado, evidenciado pelo vínculo epidemiológico entre os casos investigados e a pesquisa entomológica no local provável de infecção.

El objetivo de este artículo fue confirmar y describir un brote de la enfermedad de Chagas aguda por transmisión oral en la mesorregión oeste de Rio Grande do Norte, Brasil. Se trata de un estudio descriptivo del tipo serie de casos, contando como fuente de datos los registros de atención médica y entrevistas en los casos sospechosos entre el 16 de septiembre y el 19 de noviembre de 2015. Se realizó una investigación entomológica en las probables localidades de infección de los casos de enfermedad de Chagas aguda. Fueron confirmados 18 casos de enfermedad de Chagas aguda en residentes de cuatro municipios de Rio Grande do Norte. Los signos y síntomas más informados fueron fiebre y debilidad (n = 18), seguidos de mialgia (n = 17), postración, inapetencia y edema de miembros inferiores (n = 15). La media de duración de la fiebre fue de 20 días (intervalo: 6 a 45 días). Quince casos fueron confirmados por criterio de laboratorio y tres por vínculo epidemiológico con clínica compatible. Todos los casos confirmados informaron haber consumido caldo de caña de la misma procedencia. Fueron capturados 110 triatominos en la hacienda donde se produjo la molienda de la caña consumida. Los insectos estaban en el peridomicilio, en montones de leña y cerca del ingenio azucarero. La mayoría de los ejemplares capturados era de la especie Triatoma brasiliensis, y presentó un índice de infección natural de un 63%. Se confirmó un brote de la enfermedad de Chagas de transmisión oral por ingestión de caldo de caña contaminado por triatomino infectado, evidenciado por el vínculo epidemiológico entre los casos investigados y la investigación entomológica en el lugar probable de infección.

Anafilaxia relacionada à vacina sarampo, caxumba e rubéola, Santa Catarina, Brasil, 2014 e 2015 / Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015 / Anafilaxia relacionada a la vacuna sarampión, paperas y rubeola, Santa Catarina, Brasil, 2014 y 2015

Resumo: Os objetivos consistiram em descrever os casos e verificar a frequência de anafilaxia relacionada à vacina sarampo, caxumba e rubéola (SCR) do produtor A, bem como avaliar os possíveis fatores de risco associados. Estudo de caso-controle (1:4), em Santa Catarina, Brasil, de 14 de julho de 2014 a 12 de janeiro de 2015, em crianças de um a menores de cinco anos, vacinadas com SCR e notificadas com anafilaxia, sendo os controles sem anafilaxia. Utilizou-se, como medida de associação, odds ratio (OR) com intervalo de 95% de confiança (IC95%) e os testes qui-quadrado e exato de Fisher. Calcularam-se taxas de anafilaxia por doses distribuídas/aplicadas. Entrevistaram-se 15 casos e 60 controles, em 12 municípios. As taxas de anafilaxia foram 2,46 e 5,05 por doses distribuídas e aplicadas, respectivamente. Dentre os casos de anafilaxia, oito (53,4%) eram do sexo masculino, e dentre os controles, 36 (60%), com p = 0,64. Na análise bivariada referente à anafilaxia e alergia à proteína do leite de vaca (APLV), verificou-se OR = 51,62, com p = 0,00002 e IC95%: 5,59-476,11. As variáveis alergia alimentar familiar, aleitamento materno, evento adverso pós-vacinação (EAPV) anterior e vacinação simultânea não foram estatisticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Taxas de anafilaxia por doses distribuídas/aplicadas ficaram acima de 1/100 mil doses aplicadas (taxa esperada). Anafilaxia e APLV apresentaram associação estatisticamente significativa. Não foram encontradas associações estatísticas referentes à vacinação simultânea, aleitamento materno, alergia alimentar familiar e EAPV anterior. Recomendou-se ao produtor informar na bula todos os componentes do produto e que crianças com história pregressa de APLV não sejam vacinadas com essa vacina.

Abstract: The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. Recommendations: the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Resumen: Los objetivos consistieron en describir los casos y verificar la frecuencia de anafilaxia, relacionada con la vacuna del sarampión, paperas y rubeola (SCR) del productor A, así como evaluar los posibles factores de riesgo asociados. Estudio de caso-control (1:4), en Santa Catarina, Brasil, de 14 de julio de 2014 a 12 de enero de 2015, en niños de uno a menores de cinco años, vacunadas con SCR y notificadas con anafilaxia, siendo los controles sin anafilaxia. Se utilizó, como medida de asociación, odds ratio (OR) con un intervalo de 95% de confianza (IC95%) y los testes chi-cuadrado y exacto de Fisher. Se calcularon las tasas de anafilaxia por dosis distribuidas/aplicadas. Se entrevistaron 15 casos y 60 controles, en 12 municipios. Las tasas de anafilaxia fueron 2,46 y 5,05 por dosis distribuidas y aplicadas, respectivamente. Entre los casos de anafilaxia, ocho (53,4%) eran del sexo masculino, y entre los controles, 36 (60%), con p = 0,64. En el análisis bivariado referente a la anafilaxia y alergia a la proteína de leche de vaca (APLV), se verificó OR = 51,62, con p = 0,00002 e IC95%: 5,59-476,11. Las variables alergia alimentaria familiar, lactancia materna , evento adverso pos-vacunación (EAPV) anterior y vacunación simultánea no fueron estadísticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Tasas de anafilaxia por dosis distribuidas/aplicadas se situaron encima de 1/100.000 dosis aplicadas (tasa esperada). Anafilaxia y APLV presentaron una asociación estadísticamente significativa. No fueron encontradas asociaciones estadísticas referentes a la vacunación simultánea, lactancia materna, alergia alimentaria familiar y EAPV anterior. Se recomendó al productor informar en el prospecto sobre todos los componentes del producto, y que los niños con historial anterior de APLV no sean vacunados con esa vacuna.

Investigação de surto de doença de Chagas aguda na região extra-amazônica, Rio Grande do Norte, Brasil, 2016 / Investigation of an outbreak of acute Chagas disease outside the Amazon Region, in Rio Grande do Norte State, Brazil, 2016 / Investigación del brote de la enfermedad de Chagas aguda en la región extra-amazónica, Rio Grande do Norte, Brasil, 2016

Resumo: O objetivo do artigo foi confirmar e descrever um surto da doença de Chagas aguda por transmissão oral na mesorregião Oeste Potiguar, Rio Grande do Norte, Brasil. Trata-se de um estudo descritivo do tipo série de casos, tendo como fonte de dados os registros de atendimentos médicos e entrevistas com os casos suspeitos entre 16 de setembro e 19 de novembro de 2015. Realizou-se pesquisa entomológica nas prováveis localidades de infecção dos casos de doença de Chagas aguda. Foram confirmados 18 casos de doença de Chagas aguda em residentes de quatro municípios do Rio Grande do Norte. Os sinais e sintomas mais relatados foram febre e fraqueza (n = 18), seguidos de mialgia (n = 17), prostração, inapetência e edema de membros inferiores (n = 15). A mediana de duração da febre foi de 20 dias (intervalo: 6 a 45 dias). Quinze casos foram confirmados por critério laboratorial e três por vínculo epidemiológico com clínica compatível. Todos os casos confirmados relataram ter consumido caldo de cana da mesma procedência. Foram capturados 110 triatomíneos na fazenda onde ocorreu a moagem da cana consumida. Os insetos estavam no peridomicílio, em amontoados de lenha e próximos ao engenho. A maioria dos exemplares capturados era da espécie Triatoma brasiliensis, e apresentou um índice de infecção natural de 63%. Foi confirmado surto da doença de Chagas de transmissão oral por ingestão de caldo de cana contaminado por triatomíneo infectado, evidenciado pelo vínculo epidemiológico entre os casos investigados e a pesquisa entomológica no local provável de infecção.

Abstract: The aim of this article was to confirm and describe an outbreak of acute Chagas disease involving oral transmission in the western region of Rio Grande do Norte State, Brazil. This was a descriptive case series study in which the data sources were medical records and interviews with suspected cases from September 16 to November 19, 2015. An entomological investigation was conducted in the probable sites of infection for acute Chagas disease cases. Eighteen cases of acute Chagas disease were confirmed in residents of four municipalities (counties) in Rio Grande do Norte State. The most frequently reported signs and symptoms were fever and weakness (n = 18), followed by myalgia (n = 17), prostration, loss of appetite, and edema of the lower limbs (n = 15). Median duration of fever was 20 days (range: 6 to 45 days). Fifteen cases were confirmed by the laboratory criterion and three by epidemiological link with consistent clinical characteristics. All confirmed cases reported having consumed sugar cane juice from the same mill. A total of 110 triatomines were captured on the plantation where the sugar cane had been crushed for juice. The insects were found in the peridomicile, in stacks of firewood and close to the sugar cane mill. The majority of the captured specimens were Triatoma brasiliensis and showed a natural infection rate of 63%. The Chagas disease outbreak was confirmed with oral transmission via ingestion of sugar cane juice contaminated with infected triatomines, as evidenced by the epidemiological link between the investigated cases and the entomological survey in the probable site where the infection occurred.

Resumen: El objetivo de este artículo fue confirmar y describir un brote de la enfermedad de Chagas aguda por transmisión oral en la mesorregión oeste de Rio Grande do Norte, Brasil. Se trata de un estudio descriptivo del tipo serie de casos, contando como fuente de datos los registros de atención médica y entrevistas en los casos sospechosos entre el 16 de septiembre y el 19 de noviembre de 2015. Se realizó una investigación entomológica en las probables localidades de infección de los casos de enfermedad de Chagas aguda. Fueron confirmados 18 casos de enfermedad de Chagas aguda en residentes de cuatro municipios de Rio Grande do Norte. Los signos y síntomas más informados fueron fiebre y debilidad (n = 18), seguidos de mialgia (n = 17), postración, inapetencia y edema de miembros inferiores (n = 15). La media de duración de la fiebre fue de 20 días (intervalo: 6 a 45 días). Quince casos fueron confirmados por criterio de laboratorio y tres por vínculo epidemiológico con clínica compatible. Todos los casos confirmados informaron haber consumido caldo de caña de la misma procedencia. Fueron capturados 110 triatominos en la hacienda donde se produjo la molienda de la caña consumida. Los insectos estaban en el peridomicilio, en montones de leña y cerca del ingenio azucarero. La mayoría de los ejemplares capturados era de la especie Triatoma brasiliensis, y presentó un índice de infección natural de un 63%. Se confirmó un brote de la enfermedad de Chagas de transmisión oral por ingestión de caldo de caña contaminado por triatomino infectado, evidenciado por el vínculo epidemiológico entre los casos investigados y la investigación entomológica en el lugar probable de infección.

The Origin and Evolutionary Consequences of Skeletal Traits Shaped by Embryonic Muscular Activity, from Basal Theropods to Modern Birds.

Embryonic muscular activity (EMA) is involved in the development of several distinctive traits of birds. Modern avian diversity and the fossil record of the dinosaur-bird transition allow special insight into their evolution. Traits shaped by EMA result from mechanical forces acting at post-morphogenetic stages, such that genes often play a very indirect role. Their origin seldom suggests direct selection for the trait, but a side-effect of other changes such as musculo-skeletal rearrangements, heterochrony in skeletal maturation, or increased incubation temperature (which increases EMA). EMA-shaped traits like sesamoids may be inconstant, highly conserved, or even disappear and then reappear in evolution. Some sesamoids may become increasingly influenced in evolution by genetic-molecular mechanisms (genetic assimilation). There is also ample evidence of evolutionary transitions from sesamoids to bony eminences at tendon insertion sites, and vice-versa. This can be explained by newfound similarities in the earliest development of both kinds of structures, which suggest these transitions are likely triggered by EMA. Other traits that require EMA for their formation will not necessarily undergo genetic assimilation, but still be conserved over tens and hundreds of millions of years, allowing evolutionary reduction and loss of other skeletal elements. Upon their origin, EMA-shaped traits may not be directly genetic, nor immediately adaptive. Nevertheless, EMA can play a key role in evolutionary innovation, and have consequences for the subsequent direction of evolutionary change. Its role may be more important and ubiquitous than currently suspected.