Salvage cryotherapy for prostate cancer.

BACKGROUND: Most men diagnosed with prostate cancer will be candidates for active treatment and 20 to 50% of patients treated with organ preserving strategies recur within the prostate. Optimal treatment of recurrence is controversial. Prostate cryosurgery has been increasingly used as primary, recurrence and focal treatment for prostate cancer. METHODS: We analysed 55 patients submitted to cryotherapy as salvage treatment after recurrence. RESULTS: Study population presented with a mean age of 70.9 ± 6.2 years, mean initial PSA of 7.6 ng/ml and average prostate volume by ultrasound of 43.2 ± 14.7 grams. Mean follow-up was of 18.0 months. Biochemical free survival at one year of follow-up was of 85%. CONCLUSIONS: Cryotherapy can be an effective and safe treatment for recurrence after primary curative treatment failure.

Mandibular morphology and the Mesolithic-Neolithic transition in Westernmost Iberia.

Neolithic farming and animal husbandry were first developed in the Near East ~ 10,000 BCE and expanded westwards, reaching westernmost Iberia no later than 5500 BCE. It resulted in major social, cultural, economic and dietary changes. Yet, the impact of this change on human mandibular morphology in Iberia is yet to be assessed, which is regrettable because mandible form is impacted by population history and diet. In this study we used Mesolithic to Chalcolithic Iberian samples to examine the impact of this transition on mandibular morphology. We also compared these samples with a Southern Levantine Chalcolithic population to assess their relationship. Lastly, we assessed dental wear to determine if the morphological differences identified were related to the material properties of the diet. We found differences between samples in mandibular shape but not size, which we attribute to contrasting population histories between Mesolithic and later populations. Some differences in the severity of dental wear were also found between Mesolithic and later Iberian samples, and smaller between the Mesolithic Iberians and southern Levantines. Little relationship was found between wear magnitude and mandibular shape. Altogether, our results show that the Mesolithic-Neolithic Iberian transition resulted in a meaningful change in mandibular morphology, which was likely driven more by population history than by dietary change.

Comparing extraction method efficiency for high-throughput palaeoproteomic bone species identification.

High-throughput proteomic analysis of archaeological skeletal remains provides information about past fauna community compositions and species dispersals in time and space. Archaeological skeletal remains are a finite resource, however, and therefore it becomes relevant to optimize methods of skeletal proteome extraction. Ancient proteins in bone specimens can be highly degraded and consequently, extraction methods for well-preserved or modern bone might be unsuitable for the processing of highly degraded skeletal proteomes. In this study, we compared six proteomic extraction methods on Late Pleistocene remains with variable levels of proteome preservation. We tested the accuracy of species identification, protein sequence coverage, deamidation, and the number of post-translational modifications per method. We find striking differences in obtained proteome complexity and sequence coverage, highlighting that simple acid-insoluble proteome extraction methods perform better in highly degraded contexts. For well-preserved specimens, the approach using EDTA demineralization and protease-mix proteolysis yielded a higher number of identified peptides. The protocols presented here allowed protein extraction from ancient bone with a minimum number of working steps and equipment and yielded protein extracts within three working days. We expect further development along this route to benefit large-scale screening applications of relevance to archaeological and human evolution research.

Changes in dental wear magnitude in the last ∼8000 years in southwestern Iberia.

OBJECTIVE: This study examines changes in dental wear magnitude in the past ∼8000 years, i.e., since Mesolithic until the 19th century, in southwestern Iberia. Thus, it encompasses the transition from hunting-gathering to agro-pastoralism, and then to the industrialization of food production and pre-processing. DESIGN: Dental wear magnitude was scored in a total of 191 individuals and 1557 teeth from Mesolithic (individuals=56; teeth=643), Neolithic (individuals=35; teeth=169), Chalcolithic (individuals =35; teeth=221), Modern Age (individuals=17; teeth=209), and Late Modern Age (individuals=48; teeth=315) samples originating in southwestern Iberia (i.e., present central and southern Portugal) and according to the 8 levels ordinal scale of Smith (1984). RESULTS: Results show a general trend for decreased wear magnitude in these two major transitions and during this timespan (although the hunting-gathering - agro-pastoralism transition had larger impact). The only meaningful differences in wear rate were found between the Late Modern Age and all remaining samples. CONCLUSION: Dental wear generally decreased during this timespan (although wear magnitude was less impacted by the industrialization of food production and pre-processing). Our results are consistent with studies documenting skull morphological gracilization associated with reduced masticatory demands due to the adoption of softer diets.

SPIN enables high throughput species identification of archaeological bone by proteomics.

Species determination based on genetic evidence is an indispensable tool in archaeology, forensics, ecology, and food authentication. Most available analytical approaches involve compromises with regard to the number of detectable species, high cost due to low throughput, or a labor-intensive manual process. Here, we introduce "Species by Proteome INvestigation" (SPIN), a shotgun proteomics workflow for analyzing archaeological bone capable of querying over 150 mammalian species by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rapid peptide chromatography and data-independent acquisition (DIA) with throughput of 200 samples per day reduce expensive MS time, whereas streamlined sample preparation and automated data interpretation save labor costs. We confirm the successful classification of known reference bones, including domestic species and great apes, beyond the taxonomic resolution of the conventional peptide mass fingerprinting (PMF)-based Zooarchaeology by Mass Spectrometry (ZooMS) method. In a blinded study of degraded Iron-Age material from Scandinavia, SPIN produces reproducible results between replicates, which are consistent with morphological analysis. Finally, we demonstrate the high throughput capabilities of the method in a high-degradation context by analyzing more than two hundred Middle and Upper Palaeolithic bones from Southern European sites with late Neanderthal occupation. While this initial study is focused on modern and archaeological mammalian bone, SPIN will be open and expandable to other biological tissues and taxa.

Testing the reliability of CT scan-based dental wear magnitude scoring.

OBJECTIVES: Digital models are now frequently used in biological anthropology (bioanthropology) research. Despite several studies validating this type of research, none has examined if the assessment of dental wear magnitude based on Computerized Tomography (CT) scans is reliable. Thus, this study aims to fill this gap and assess if dental wear magnitude scoring based on CT scans provides results consistent with scoring based on direct observation of the physical specimens. MATERIALS AND METHODS: Dental wear magnitude from 412 teeth of 35 mandibles originating from the Portuguese Muge and Sado Mesolithic shell-middens was scored. The mandibles were also CT scanned and visualized using 3D Slicer. CT scan-based scoring of dental wear magnitude was then undertaken. Two scoring rounds were undertaken for each observation method (totaling four scoring rounds) and an intra-observer error test was performed. The averaged results of the two observation methods were compared via boxplots with paired cases. RESULTS: Intra-observer error was negligible and non-significant. Scoring results are comparable between the two observation methods. Notwithstanding, some differences were found, in which CT scan assessment generally overestimates dental wear when compared to direct observation. DISCUSSION: Our results generally validate the use of CT scans in studies of dental wear magnitude. Notwithstanding several caveats relating to CT scanning and visualization limitations should be considered to avoid over or under-estimation of dental wear.

Aptamer-based approaches to detect nucleolin in prostate cancer.

We have investigated the expression of nucleolin (NCL) in liquid biopsies of prostate cancer (PCa) patients and healthy controls to determine its correlation with tumor prognosis. To detect NCL we used a modified AS1411 aptamer designated by AS1411-N5. In presence of NCL, AS1411-N5 increases the fluorescence by assuming a G-quadruplex (G4) structure, while in the absence of NCL the fluorescence signal remains quenched. The structural characterization of AS1411-N5 was performed by biophysical studies, which demonstrated the formation of G4 parallel conformation in the presence of 100 mM K+ and the ability to recognize NCL with high affinity (KD = 138.1 ±â€¯5.5 nM). Furthermore, the clinical relevance of NCL in PCa liquid biopsies was assessed by using an NCL-based ELISA assay. The protein was measured in the peripheral blood mononuclear cells (PBMCs) cell lysate of 158 individuals, including PCa patients and healthy individuals. The results depicted a remarkable increase of NCL levels in the PBMC's lysate of PCa patients (mean of 626.1 pg/mL whole blood) when compared to healthy individuals (mean of 198.5 pg/mL whole blood). The ELISA results also provided evidence for the usefulness of determining NCL levels in advanced PCa stages. Furthermore, a microfluidic assay showed the ability of AS1411-N5 in recognizing NCL in spiked human plasma samples.

Giant Penis paraffinoma.

A fifty-year-old healthy, Portuguese male, with prior history of paraffin injections into the penis 30 years ago, was referred for urological consultation because of a large, hardened ulcerated mass on the base of the penis causing deformity and pain. The patient underwent a biopsy that showed a benign granulomatous lesion, and then excision of the mass and penile plasty with a scrotum flap in the same surgical time. Histology confirmed the diagnosis of paraffinoma. Three months after surgery, the patient is satisfied with the functional (urinary function and erectile function) and aesthetic results. Penile paraffinoma is a rare disease (most common in Asia and Eastern Europe) and results from an inflammatory response to the subcutaneous injection of paraffin, Vaseline or other mineral oils. Treatment is usually surgery.

Assessing the reliability of virtual reconstruction of mandibles.

OBJECTIVES: Mandibular morphological variation is often used to examine various aspects of human palaeobiology. However, fossil and archeological skeletal remains are often fragmented/distorted and so are frequently excluded from studies. This leads to decreased sample sizes and, potentially, to biased results. Thus, it is of interest to restore the original anatomy of incomplete/distorted specimens. Thin plate splines (TPS), commonly used in Geometric Morphometrics (GM), offer the prospect of reconstruction of missing parts and particularly of interest here, missing landmarks. MATERIALS AND METHODS: Here, the reliability of TPS based mandibular reconstruction is tested. To that end missing landmarks were simulated in originally complete hemimandibles. TPS was then used to restore the location of simulated missing data and the predicted landmarks were compared to the original ones. RESULTS: Results show that error varies according to the number and location of estimated landmarks. Notwithstanding, estimation error is usually considerably smaller than the morphological differences between individuals from the same species. DISCUSSION: TPS based reconstruction allows fragmentary mandibles to be used in studies of whole mandibular variation, provided the above mentioned caveats are considered.

Prognostic value of p16INK4a overexpression in penile cancer.

INTRODUCTION: Penile cancer is rare, accounting for less than 1% of all male cancers in industrialized countries. It is most common in areas of high prevalence of HPV, being a third of cases attributed to the carcinogenic effect of HPV. Tumour cells infected with HPV overexpress p16INK4a, as such p16INK4a has been used as a surrogate of HPV infections. OBJECTIVE: To evaluate the prognostic factor of p16INK4a overexpression in penile cancer. METHODS: Retrospective analysis of patients diagnosed with penile cancer, submitted to surgery in a Portuguese Oncological Institution in the last 20 years (n = 35). Histological review of surgical pieces and immunohistochemical identification of p16INK4a. Relation between p16INK4a and the following factors were studied: age, histological subtype, tumour dimensions, grade, TNM stage, perineural invasion, perivascular invasion, disease free survival (DFS) and cancer specific survival (CSS). RESULTS: p16INK4a was positive in 8 patients (22.9%). Identification of p16INK4a did not correlate with none of the histopathological factors. In this work we identified a better DFS and CSS in patients positive for p16INK4a (DFS at 36 months was 100.0% vs. 66.7%; CSS at 36 months was 100.0% vs. 70.4%), although without statistical significance (p > 0.05). In multivariate analysis of histopathological factors studied, only N staging correlated with DFS and CSS (p = 0.017 and p = 0.014, respectively). DISCUSSION: the percentage of cases positive for p16INK4a is smaller than the one found in literature, which can suggest a less relevant part of HPV infection in the oncogenesis of penile cancer in the studied population. Identification of p16INK4a did not relate with other clinicopathological factors. Tendency for a more favourable prognosis in patients with p16INK4a agrees with results found in literature. The most relevant factor for prognosis is nodal staging. CONCLUSIONS: penile cancer positive for p16INK4a shows a trend for better survival, although the most relevant factor is nodal staging.

Influence of sociodemographic factors on treatment's choice for localized prostate cancer in Portugal.

INTRODUCTION: Patients with localized prostate cancer (PCa) are active participants in the choice of treatment. OBJECTIVES: To access the effects of social and demographic factors in the choice of treatment in cases of localized PCa, in a Portuguese population. METHODS: Identification of all patients with the diagnosis of localized PCa in the last four years in an oncological centre. Evaluation of the effects of sociodemographic factors (age, profession, literacy, marital status, district and number of inhabitants of the place of residence) in the choice of treatment. RESULTS: 300 patients with localized PCa were evaluated: 17.3% (n = 52) opted for radical prostatectomy (RP); 39,3% had (n = 118) external radiotherapy; brachytherapy in 29.3% (n = 88) and other options (active surveillance, cryotherapy and hormonal therapy) in 14.1% (n = 42). In relation to surgical treatment (RP) the following results were obtained: a) > 70 years: 3.9% (n = 5); ≤ 70 years: 27.5% (n = 47), p < 0.001; b) primary sector: 10.3% (n = 3); secondary sector: 16.2% (n = 27); tertiary sector: 24.1% (n = 21); quaternary sector: 8.3% (n = 1), p = 0.296; c) marital status married: 17.9% (n = 47); single: 0% (n = 0); divorced: 25.0% (n = 5); widow: 0% (n = 0), p = 0.734; d) residency in a city: 14.1% (n = 13); city > 4000 habitants: 22.7% (n = 15); city ≤ 4000 habitants: 16.9% (n = 24), p = 0.701. Using multinomial regression with age (p = 0.001), district (p = 0.035), marital status (p = 0.027) and profession (0.179), this model explained 17.2%-28.4% of therapeutic choices (p < 0.001). CONCLUSIONS: The main socioeconomical factor that influence treatment choice was age. Unmarried patients over 70 years choose less radical prostatectomy. Other sociodemographic factors have minor influence in the choice of the treatment.

A lunate-triquetral coalition from a commingled funerary context from the Chalcolithic Perdigões ditched enclosures of Portugal.

Carpal coalitions, resulting from a failure of separation of the cartilaginous precursors of the carpal bones during gestation, may be osseous or non-osseous. Even though lunate-triquetral coalitions are the most common of all carpal coalitions there is only one previous palaeopathological report of such a coalition. This study presents a non-osseous lunate-triquetral coalition found amongst the mostly cremated commingled bones from a Chalcolithic pit at Perdigões (Portugal). The cremated bones show evidence of burning at varying but mostly at generally high temperatures. The perfect articulation between these right bones and pinpoint pitting in the lunate-triquetral joint were crucial for the identification of this congenital condition. Carpal coalitions are more frequent in African than European populations. Artifacts produced from ivory of African origin were found in Perdigões, however it is not possible to establish the ancestry of this individual.

Cleft lip and palate associated hearing loss in Brazilian children.

INTRODUCTION: Cleft lip and palate children have chronic otitis media related to Eustachian Tube dysfunction and associated conductive hearing loss. In this group of children, communicative skill development limitations, in association with orofacial aesthetics and functional disorders, can lead to behavioral, educational and social problems. METHODS: We evaluated the minimum hearing threshold and the air-bone gap (ABG) in a range from 500 to 4000 Hz for 4-14 years old cleft lip and palate children (CLPC). This cross-sectional study took place in a multiprofessional tertiary care center and involved 89 CLPC with bilateral or unilateral postforamen or transforamen malformation, divided into two groups: those aged 4-7 and 8-14 years. The hearing tests of 89 children were evaluated: 53 (group I) aged from 4 to 7 years (67.9% male) and 36 (group II) aged from 8 to 14 years (55.6% female). RESULTS: The minimum hearing threshold 500-4 KHz mean (MHT 500-4 KHz) was 19.4 dB for all children. MHT 500-4 KHz was 21.2 dB and 17.5 dB respectively for the group I and group II. Both groups demonstrated a minimum hearing threshold of up to 70 dB at certain frequencies. The global ABG 500-4 KHz average was 16.6 dB (SD 12.5): 19.7 dB (SD 12.9) in group I and 13.2 dB (SD 11.1) in group II. CONCLUSION: The worst hearing thresholds were found in children of 4-7 years old: 21.2 dB MHT 500-4 KHz and 19.7 ABG 500-4 KHz, what is a disadvantage for them, as the normal hearing thresholds are up to 15 dB. The children of 8-14 years old had MHT 500-4 KHz of 17.5 dB, and ABG 500-4KHZ OF 13.2 with up to 70 dB of hearing loss.

Supraorbital morphology and social dynamics in human evolution.

Uniquely, with respect to Middle Pleistocene hominins, anatomically modern humans do not possess marked browridges, and have a more vertical forehead with mobile eyebrows that play a key role in social signalling and communication. The presence and variability of browridges in archaic Homo species and their absence in ourselves have led to debate concerning their morphogenesis and function, with two main hypotheses being put forward: that browridge morphology is the result of the spatial relationship between the orbits and the brain case; and that browridge morphology is significantly impacted by biting mechanics. Here, we virtually manipulate the browridge morphology of an archaic hominin (Kabwe 1), showing that it is much larger than the minimum required to fulfil spatial demands and that browridge size has little impact on mechanical performance during biting. As browridge morphology in this fossil is not driven by spatial and mechanical requirements alone, the role of the supraorbital region in social communication is a potentially significant factor. We propose that conversion of the large browridges of our immediate ancestors to a more vertical frontal bone in modern humans allowed highly mobile eyebrows to display subtle affiliative emotions.

The biting performance of Homo sapiens and Homo heidelbergensis.

Modern humans have smaller faces relative to Middle and Late Pleistocene members of the genus Homo. While facial reduction and differences in shape have been shown to increase biting efficiency in Homo sapiens relative to these hominins, facial size reduction has also been said to decrease our ability to resist masticatory loads. This study compares crania of Homo heidelbergensis and H. sapiens with respect to mechanical advantages of masticatory muscles, force production efficiency, strains experienced by the cranium and modes of deformation during simulated biting. Analyses utilize X-ray computed tomography (CT) scan-based 3D models of a recent modern human and two H. heidelbergensis. While having muscles of similar cross-sectional area to H. heidelbergensis, our results confirm that the modern human masticatory system is more efficient at converting muscle forces into bite forces. Thus, it can produce higher bite forces than Broken Hill for equal muscle input forces. This difference is the result of alterations in relative in and out-lever arm lengths associated with well-known differences in midfacial prognathism. Apparently at odds with this increased efficiency is the finding that the modern human cranium deforms more, resulting in greater strain magnitudes than Broken Hill when biting at the equivalent tooth. Hence, the facial reduction that characterizes modern humans may not have evolved as a result of selection for force production efficiency. These findings provide further evidence for a degree of uncoupling between form and function in the masticatory system of modern humans. This may reflect the impact of food preparation technologies. These data also support previous suggestions that differences in bite force production efficiency can be considered a spandrel, primarily driven by the midfacial reduction in H. sapiens that occurred for other reasons. Midfacial reduction plausibly resulted in a number of other significant changes in morphology, such as the development of a chin, which has itself been the subject of debate as to whether or not it represents a mechanical adaptation or a spandrel.

The biomechanical significance of the frontal sinus in Kabwe 1 (Homo heidelbergensis).

Paranasal sinuses are highly variable among living and fossil hominins and their function(s) are poorly understood. It has been argued they serve no particular function and are biological 'spandrels' arising as a structural consequence of changes in associated bones and/or soft tissue structures. In contrast, others have suggested that sinuses have one or more functions, in olfaction, respiration, thermoregulation, nitric oxide production, voice resonance, reduction of skull weight, and craniofacial biomechanics. Here we assess the extent to which the very large frontal sinus of Kabwe 1 impacts on the mechanical performance of the craniofacial skeleton during biting. It may be that the browridge is large and the sinus has large trabecular struts traversing it to compensate for the effect of a large sinus on the ability of the face to resist forces arising from biting. Alternatively, the large sinus may have no impact and be sited where strains that arise from biting would be very low. If the former is true, then infilling of the sinus would be expected to increase the ability of the skeleton to resist biting loads, while removing the struts might have the opposite effect. To these ends, finite element models with hollowed and infilled variants of the original sinus were created and loaded to simulate different bites. The deformations arising due to loading were then compared among different models and bites by contrasting the strain vectors arising during identical biting tasks. It was found that the frontal bone experiences very low strains and that infilling or hollowing of the sinus has little effect on strains over the cranial surface, with small effects over the frontal bone. The material used to infill the sinus experienced very low strains. This is consistent with the idea that frontal sinus morphogenesis is influenced by the strain field experienced by this region such that it comes to lie entirely within a region of the cranium that would otherwise experience low strains. This has implications for understanding why sinuses vary among hominin fossils.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis, / IV Consenso Brasileiro sobre Rinite - atualização em rinite alérgica,

Abstract Introduction The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. Objective To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. Methods We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. Results The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. Conclusion A flowchart for allergic rhinitis treatment has been proposed.

Resumo Introdução As diretrizes sobre rinite alergica visam atualizar os conhecimentos sobre a doença e os cuidados para com esses pacientes. A iniciativa designada "Rinite Alergica e seu Impacto na Asma", cujo relatorio inicial foi publicado em 2001 e atualizada em 2008 e 2010, tem sido muito bem sucedida na disseminaçao de informaçoes e evidencias, bem como na formulaçao da classificaçao de gravidade e proposta de sistematizaçao do tratamento. Entretanto, visando a participaçao de outros profissionais medicos no atendimento da rinite alergica, e importante o desenvolvimento de algoritmos que indiquem com precisao o que deve e pode ser feito regionalmente. Objetivo Atualizar o III Consenso Brasileiro sobre Rinites-2012, com elaboraçao de algoritmo para conduta da rinite alergica. Método Foram convidados 24 especialistas indicados pelas Associaçao Brasileira de Alergia e Imunologia, Associaçao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial e Sociedade Brasileira de Pediatria para atualizaçao do documento de 2012. Resultados A atualizaçao do ultimo Consenso Brasileiro sobre Rinites, incorporou e adaptou para a realidade brasileira as informaçoes relevantes publicadas em todos os documentos da Iniciativa "Rinite Alergica e seu Impacto na Asma", trazendo novos conceitos como a rinite alergica local, novos medicamentos e metodos de avaliaçao de tratamento. Conclusão Proposto um fluxograma de tratamento para a rinite alergica.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis.

INTRODUCTION: The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. OBJECTIVE: To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. METHODS: We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. RESULTS: The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. CONCLUSION: A flowchart for allergic rhinitis treatment has been proposed.

Ontogeny of the maxilla in Neanderthals and their ancestors.

Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived.

Alterações auditivas em crianças portadoras de fissuras labiopalatinas / Hearing impairment in children with cleft lip and cleft palate

As fissuras labiopalatinas são malformações congênitas que têm como características a deformidade estética facial, alterações de fala e disacusia condutiva ocasionada pela disfunção crônica da tuba auditiva. Existem protocolos de tratamento para a reparação do lábio e do palato, que habitualmente são realizados dos três e aos 18 meses de idade,respectivamente. A reparação do palato tem como funções restabelecer a anatomia do palato e assoalho da cavidade nasal e promover o funcionamento adequado da tuba auditiva. A correta inserção dos músculos tensor e elevador do véu palatino no palato duro pode promover abertura mais eficiente da tuba auditiva, durante a deglutição,mantendo a aeração da orelha média, minimizando o risco do desenvolvimento da otite média com efusão. Os protocolos definem bem o que fazer em relação ao momento da palatoplastia, entretanto, não existe consenso sobre o tratamento da disfunção da tuba auditiva. Vários estudos têm surgido com o intuito de orientar o tratamento e definiro melhor momento para a resolução dessa doença, tendo como escolha a realização de timpanotomia com colocação de tubos de ventilação. A timpanotomia precoce, aos quatro meses de idade, é indicada por alguns pesquisadores, entretanto, outros são conservadores e aguardam o surgimento dos sintomas para intervir cirurgicamente. Neste trabalho, verifica-se o que existe de atual no tratamento das otites médias comefusão, os estudos com modelos computacionais, a história natural das alterações auditivas em pacientes com fissuras labiopalatinas não operadas e o resultado das introduções de tubos de ventilação no desenvolvimento auditivo e de fala dessa população.

Cleft lip and cleft palate are congenital malformations that are characterized by cosmetic facial deformity, speech disorders, and conductive hearing loss caused by chronic Eustachian tube dysfunction. There are treatment protocols for the repair of lip and palate that are usually performed between three and 18 months of age, respectively. Palate repairrestores palate functions and anatomy, and the floor of the nasal cavity-promoting proper functioning of the Eustachian tube. The correct insertion of tensor muscles and soft palate lift in the hard palate can promote more efficient opening of the Eustachian tube during swallowing, keeping aeration in the middle ear, minimizing the risk of developing otitismedia with effusion. The protocols are well-defined about the timing for palatoplasty. However, there is no consensus on the treatment of Eustachian tube dysfunction. Several studies have emerged in order to guide treatment and determine the best time to resolve the disease, choosing to carry out tympanostomy with the placement of ventilation tubes. Early tympanostomy, at four months of age, is indicated by some researchers; however, others are conservative and await the onset of symptoms to intervene surgically. In this study, the current treatment of otitis media with effusion, studies with computer models, the natural history of hearing loss in patients with non-operated cleft lip and cleft palate,and results of ventilation tubes placement on auditory development and speech of this population are evaluated.