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Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and occurs in ~1 of every 700 live births. Individuals with DS present craniofacial abnormalities, specifically an undersized, dysmorphic mandible which may lead to difficulty with eating, breathing, and speech. Using the Ts65Dn DS mouse model, which mirrors these phenotypes and contains three copies of ~50% Hsa21 homologues, our lab has traced the mandibular deficit to a neural crest cell (NCC) deficiency in the first pharyngeal arch (PA1 or mandibular precursor) at embryonic day 9.5 (E9.5). At E9.5, the PA1 is reduced in size and contains fewer cells due to fewer NCC populating the PA1 from the neural tube (NT) as well as reduced cellular proliferation in the PA1. We hypothesize that both the deficits in NCC migration and proliferation may cause the reduction in size of the PA1. To identify potential genetic mechanisms responsible for trisomic PA1 deficits, we generated RNA-sequence (RNA-seq) data from euploid and trisomic E9.25 NT and E9.5 PA1 (time points occurring before and after observed deficits) using a next-generation sequencing platform. Analysis of RNA-seq data revealed differential trisomic expression of 53 genes from E9.25 NT and 364 genes from E9.5 PA1, five of which are present in three copies in Ts65Dn. We also further analyzed the data to find that fewer alternative splicing events occur in trisomic tissues compared to euploid tissues and in PA1 tissue compared to NT tissue. In a subsequent study, to test gene-specific treatments to rescue PA1 deficits, we targeted Dyrk1A, an overexpressed DS candidate gene implicated in many DS phenotypes and predicted to cause the NCC and PA1 deficiencies. We hypothesize that treatment of pregnant Ts65Dn mothers with Epigallocatechin gallate (EGCG), a known Dyrk1A inhibitor, will correct NCC deficits and rescue the undersized PA1 in trisomic E9.5 embryos. To test our hypothesis, we treated pregnant Ts65Dn mothers with EGCG from either gestational day 7 (G7) to G8 or G0 to G9.5. Our study found an increase in PA1 volume and NCC number in trisomic E9.5 embryos after treatment on G7 and G8, but observed no significant improvements in NCC deficits following G0-G9.5 treatment. We also observed a developmental delay of embryos from trisomic mothers treated with EGCG from G0-G9.5. Together, these data show that timing and sufficient dosage of EGCG treatment is most effective during the developmental window the few days before NCC deficits arise, during G7 and G8, and may be ineffective or harmful when administered at earlier developmental time points. Together, the findings of both studies offer a better understanding of potential mechanisms altered by trisomy as well as preclinical evidence for EGCG as a potential prenatal therapy for craniofacial disorders linked to DS.

The evolution of jaws in cichlid fishes of the East African Great Lakes is a textbook example of adaptive radiation in vertebrates. Karl Liem postulated that this adaptive radiation has been possible due to the functional decoupling of two cichlid functional units – the pharyngeal jaw (PJ) and the oral jaw (OJ). This functional decoupling of the jaws has enabled the OJ to be relieved of its dual role of prey capturing and processing and has allowed the PJ to take on the role of prey processing. As a result, African cichlids have adapted the morphology of their functional units (i.e., oral jaws) to specialize in a feeding mechanism best suited for their habitat. However, global morphological changes (across the OJ and PJ) are understudied, especially, at the genetic level. In this study, two rock dwelling species of African Cichlids from Lake Malawi were used - Labeotropheus fuelleborni (LF) and Tropheops “red cheek” (TRC). Both species have distinct craniofacial morphologies for specialized benthic feeding (LF) and for generalized feeding (TRC). This morphological variation allowed us to investigate the functional decoupling of the jaws by studying differences in bone shape and muscle volumes in an F5 hybrid population. Strong phenotypic correlations were observed between and within the tissues of the OJ and PJ. Further, to identify phenotype to genotype associations, a Quantitative Locus (QTL) analysis and a fine mapping analysis was conducted. The results show some evidence of overlapping genetic control (i.e., pleiotropy) suggesting some genetic coupling between the two jaws.

Introdução: Apneia Obstrutiva do Sono (AOS) é prevalente em estados edematosos, especialmente em pacientes em hemodiálise (HD). Uma vez que o deslocamento noturno de fluidos (DNF) acarreta piora da AOS, nós elaboramos a hipótese de que a interferência na redistribuição de fluidos pelo uso de meias elásticas compressivas (MEC) atenuaria a gravidade da AOS, por mecanismos diferentes em comparação à terapia padrão para AOS, a pressão positiva em vias aéreas (CPAP). Métodos: este é um estudo randomizado e cross-over, que incluiu 14 pacientes dialíticos com AOS (índice de apneia/hipopneia - IAH > 5 eventos/hora) em exame de polissonografia (PSG), que era realizada em três momentos: basal, titulação de CPAP e após uma semana de uso diário de MEC. Circunferência cervical (CC), bioimpedância elétrica segmentar e variabilidade de frequência cardíaca (VFC) foram avaliadas antes e após cada exame de PSG. Resultados: A idade média foi 53±9 anos (57% de homens) e o índice de massa corporal foi 29,7±6,8 Kg/m². O IAH foi reduzido de 20,8 (14,2; 39,6) no exame basal para 7,9 (2,8; 25,4) durante titulação de CPAP e para 16,7 (3,5; 28,9) eventos/hora após uso de MEC (CPAP vs. basal, p=0,004; MEC vs. basal, p=0,017; e CPAP vs. MEC, p=0.017). Comparando basal, CPAP e MEC, o conteúdo de água noturna em membros inferiores foi menor com MEC (p=0,04), enquanto a água intracelular noturna em tronco foi maior (p=0,03). DNF basal, com CPAP e MEC foi de -183±72, -343±220, e -290±213ml, respectivamente (p=0,006). Houve aumento da circunferência cervical durante a noite durante o exame basal (0,7±0,4 cm), mas houve redução dessa circunferência após titulação com CPAP (-1,0±0,4 cm) e após uso de MEC (-0,4±0,8 cm) (CPAP vs. basal, p<0.0001; MEC vs. basal, p=0.001; CPAP vs. MEC, p=0.01). VFC, avaliada pelos componentes de alta e baixa frequência, demonstrou menor ativação simpática durante o exame de titulação de CPAP: OR: 11 (95% CI: 1,06 - 114,2), p=0,025, mas não com MEC: OR: 7,8 (95% CI: 0,75 - 82,2), p=0,059. Conclusões: tanto o CPAP quanto MEC melhoraram AOS em pacientes em HD, mas por mecanismos distintos: enquanto o CPAP reduziu o edema de vias aéreas superiores, ao exercer pressão local, o uso de MEC reduziu o DNF, ao evitar retenção de fluidos em membros inferiores, acumulando água no componente intracelular do tronco. Ativação simpática foi somente reduzida com uso de CPAP. / Background: Obstructive Sleep Apnea (OSA) is prevalent in edematous states, notably in hemodialysis (HD) patients. Once overnight fluid shift (OFS) augments OSA, we hypothesized that interfering in fluid redistribution by wearing compression stockings (CS) would attenuate OSA severity by different mechanisms in comparison to the standard treatment to OSA, the positive airway pressure (CPAP). Methods: This is a randomized crossover study that included 14 dialytic patients with OSA (apnea/hypopnea index - AHI >5 events/hour) by polysomnography (PSG), which was performed in three moments: at baseline, for CPAP titration, and one week after daily wearing of CS. Neck circumference (NC), segmental bioelectrical impedance and heart rate variability (HRV) were assessed before and after each PSG. Results: Mean age was 53±9 years (57% men) and body mass index was 29.7±6.8 kg/m2. AHI decreased from 20.8 (14.2; 39.6) at baseline to 7.9 (2.8; 25.4) during CPAP titration and to 16.7 (3.5; 28.9) events/hour after wearing CS (CPAP vs. baseline, p=0.004; CS vs. baseline, p=0.017; and CPAP vs. CS, p=0.017). Comparing baseline, CPAP and CS, nocturnal lower limbs water content was lower with CS (p=0.04), while nocturnal intracellular trunk water was higher (p=0.03). OFS at baseline, CPAP and CS was -183±72, -343±220, and -290±213ml, respectively (p=0.006). Overnight NC variation increased at baseline (0.7±0.4 cm), but decreased after CPAP titration (-1.0±0.4 cm) and while wearing CS (-0.4±0.8 cm) (CPAP vs. baseline, p<0.0001; CS vs. baseline, p=0.001; CPAP vs. CS, p=0.01). HRV, assessed by both high and low frequency components, showed a lower sympathetic activation during CPAP titration: OR: 11 (95% CI: 1.06 - 114.2), p=0.025, but not with CS: OR: 7,8 (95% CI: 0.75 - 82.2), p=0.059 Conclusions: Both CPAP and CS improved OSA in HD patients by different mechanisms: while CPAP reduced edema in upper airways by exerting local pressure, wearing CS reduced OFS by avoiding fluid retention in the legs, accumulating water in the intracellular component of the trunk. Sympathetic activation was decreased only with CPAP.

Foi realizado estudo caso-controle de base hospitalar, envolvendo pacientes diagnosticados com câncer de cabeça e pescoço e que participaram do \"Estudo Multicêntrico Latino-americano de Fatores Ambientais, Vírus e Câncer da Cavidade Oral e Laringe\" do projeto \"Genoma Clínico do Câncer\". Foram incluídos pacientes atendidos no Hospital Heliópolis, no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Instituto do Câncer Arnaldo Vieira de Carvalho entre novembro de 1998 e dezembro de 2005. Consideraram-se casos os pacientes com diagnóstico histologicamente confirmado de câncer de boca, faringe ou laringe e controles pessoas atendidas nos mesmos hospitais por outros motivos que não neoplasia maligna e doenças associadas com os fatores de risco do câncer de cabeça e pescoço. A análise empregou regressão logística não-condicional baseada em modelo hierárquico de determinação. No nível mais distal foram incluídas as variáveis demográficas (sexo, cor de pele e idade), seguidas pela escolaridade (série mais elevada que a pessoa cursou) e ocupação (exercida por mais tempo). No nível mais proximal, foram considerados o consumo de tabaco e de álcool. Também foi investigado se a associação de instrução e ocupação com câncer de cabeça e pescoço se mediava apenas por padrões diferenciais de consumo de álcool e tabaco entre os estratos sociais, ou se havia variação residual que excedia esses dois fatores. Todas as análises conduzidas para câncer de cabeça e pescoço foram replicadas de modo específico para as localizações topográficas da boca, faringe e laringe em separado. O estudo foi aprovado pelo Comitê de Ética da Faculdade de Odontologia da Universidade de São Paulo sob parecer no. 68/07 e os procedimentos estatísticos foram realizados no programa Stata 9. A amostra foi composta por 1017 casos e 951 controles. A análise hierárquica identificou maior chance de câncer de cabeça e pescoço entre os homens (OR=2,01; IC95% 1,57-2,59), pessoas entre 48 e 55 anos (OR=1,82; IC95% 1,42-2,33), pessoas sem estudo ou apenas alfabetizados (2,48; IC95% 1,73-3,52), entre pessoas com primeiro grau completo ou incompleto (1,31; IC95% 1,05-1,63) e entre as pessoas que exerceram durante mais tempo profissão manual (1,38; IC95% 1,10-1,74). Além disso, fumantes e consumidores de bebidas alcoólicas apresentaram maior razão de chances em relação àqueles que nunca consumiram os produtos. No modelo não hierárquico, mesmo após o ajuste por tabagismo e ingestão de álcool, maior chance foi verificada para o grupo de menor escolaridade em todas as localizações topográficas (exceto para os tumores de boca), e para pessoas com ocupações manuais (exceto para os tumores de boca e faringe). A identificação desse efeito residual indica haver fatores adicionais, além da exposição ao álcool e tabaco, operando na distribuição desigual do câncer de cabeça e pescoço entre os estratos sociais. / This is a hospital-based case-control study involving patients diagnosed with head and neck cancer. Such patients have participated in the \"Latin American Multicentric Study from Environmental Factors, Virus and Oral Cavity and Larynx Cancer\", and in the \"Clinical Genome of Cancer Project\", from November 1998 to December 2005, and were attended at the Hospital Heliópolis, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer Arnaldo Vieira de Carvalho. The case group comprised patients histologically diagnosed with mouth, pharynx or larynx cancer; the control group comprised patients treated at the same hospitals for other diseases than malignant neoplasms or conditions related to head and neck cancer risk factors. Data analysis used non-conditional logistic regression based on a hierarchical model of determination. At the most distal level, demographic variables were included (e.g. sex, skin color and age), followed by education level (e.g. highest grade or degree completed) and occupation (i.e. the one performed the longest period). Alcohol and tobacco consumption were included at the most proximal level. The investigation also assessed whether the association between education level and occupation with mouth and neck cancer was only mediated by differential patterns of alcohol and tobacco consumption among social strata, or there was residual variation that exceeded those two factors. All analyses for mouth and neck cancer were specifically replicated for each topographic location (mouth, pharynx and larynx). The study was approved by the University of Sao Paulo School of Dentistry\'s Ethics Committee, report number 68/07, and statistical analyses used the Stata 9 program. The sample was composed of 1017 cases and 951 controls. Hierarchical analysis identified a greater chance of head and neck cancer for men (OR=2,01; CI95% 1,57-2,59), patients aged 48 to 55 years old (OR=1,82; CI95% 1,42-2,33), uneducated or semi-literate patients (2,48; CI95% 1,73-3,52), subjects with elementary education (8 years) (1,31; IC95% 1,05-1,63) and those performing manual occupations (1,38; CI95% 1,10-1,74). In addition, tobacco smokers and alcohol users presented a higher odds than those non-exposed to these conditions. In the non-hierarchical model, even after the adjustment for tobacco and alcohol use, a higher odds was identified for the less-schooled strata in every topographic location (except for mouth tumors), and for subjects with manual labor occupations (except for mouth and pharynx tumors). Identification of such residual effect indicates that there are other factors than alcohol and tobacco consumption, which mediate the uneven distribution of head and neck cancer across the socioeconomic strata.

Introdução: A parede lateral da faringe tem importante papel no colapso da via aérea superior nos episódios de apneia obstrutiva do sono (AOS). Os dois principais músculos que formam esta região são o músculo palatofaríngeo (MPF) e o músculo constritor superior da faringe (MCSF). Estes músculos são classificados como esqueléticos e não possuem um padrão histológico de normalidade estabelecido. Os objetivos do estudo foram verificar a estrutura histológica das fibras do MPF e do MCSF em indivíduos controles sem síndrome da apneia obstrutiva do sono (SAOS), e avaliar se indivíduos portadores de SAOS apresentam alterações histológicas nestes músculos em comparação aos controles. Métodos: Foram avaliados 28 indivíduos adultos (faixa etária entre 18 e 55 anos de idade), sendo 17 portadores de SAOS grave e 11 controles. Destes 11 controles, 7 eram portadores de ronco primário, e 4 não apresentavam roncos e AOS. Coletaram-se fragmentos de MPF e de MCSF em cirurgia de faringoplastia lateral para os roncadores primários e apneicos graves, e em cirurgia de tonsilectomia das palatinas para os indivíduos com tonsilite crônica caseosa. Os espécimes musculares coletados foram congelados em nitrogênio líquido em até 3 horas após o procedimento cirúrgico. Por meio de colorações histológicas e imuno-histoquímicas, avaliou-se a histologia das fibras musculares no que tange a sua morfologia, a distribuição dos tipos de fibras, as dimensões do espaço intercelular, e a prevalência de fibras híbridas nos 2 músculos e em ambos os grupos. Resultados: O grupo-controle apresenta predomínio de fibras do tipo II, de contração rápida e alta fatigabilidade, nos MPF e MCSF, não havendo diferença estatística entre os dois músculos. Encontramos prevalência elevada de fibras híbridas no grupo-controle (45,45% no MPF e 27,27% no MCSF), sem diferença estatística entre os dois músculos. Quanto à comparação entre os grupos controle e SAOS, verificamos redução do percentual de fibras do tipo II do MCSF nos indivíduos com SAOS (p=0,04) quando comparados aos controles. Não houve diferença estatística na distribuição dos tipos de fibras musculares entre os 2 grupos no MPF. Conclusões: Os MPF e MCSF possuem composição histológica com predomínio de fibras do tipo II e prevalência elevada de fibras híbridas nos indivíduos sem SAOS. Os indivíduos portadores de SAOS possuem redução do percentual de fibras do tipo II no MCSF em comparação aos indivíduos sem SAOS, e isso pode ter implicações na redução da eficiência desta musculatura, podendo contribuir na etiopatogenia da AOS / Introduction: The lateral pharyngeal muscular wall plays an important role in upper airway collapse in obstructive sleep apnea (OSA) episodes. The two main muscles that form this anatomical site are the palatopharyngeal muscle (PPM) and the superior pharyngeal constrictor muscle (SPCM). These muscles are classified as skeletal and do not have an established normal histological pattern in literature. The objectives of the study were: verify the histological structure of PPM and SPCM fibers in control subjects without obstructive sleep apnea syndrome (OSAS), and evaluate whether OSAS individuals demonstrate histological changes in these muscles compared to controls. Methods: Twenty-eight adults (age range between 18 to 55 years old) were evaluated, 17 with severe OSAS and 11 controls. On the control group, 7 had primary snoring and 4 had no snoring or OSA. PPM and SPCM fragments were collected in lateral pharyngoplasty surgery for the primary snoring and severe OSAS patients and a palatine tonsillectomy was executed in individuals with chronic caseous tonsillitis. The collected muscles specimens were frozen in liquid nitrogen within 3 hours after the surgical procedure. Histological and immunohistochemical staining were used to evaluate the histology of muscle fibers concerning their morphology, the distribution of fiber types, the size of the intercellular space and the prevalence of hybrid fibers in the two muscles in both groups. Results: The control group showed predominance of type II fibers (fast contraction and high fatigability) in PPM and SPCM, without statistical difference between the two muscles. We found a high prevalence of hybrid fibers in the control group (45.45% in PPM and 27.27% in SPCM), without statistical difference between the two muscles. Regarding the comparison between the control and OSAS groups, we verified a reduction in the percentage of SPCM type II fibers in individuals with OSAS (p = 0.04) when compared to controls. There was no statistical difference in the percentage of muscle fiber types between the 2 groups in PPM. Conclusions: PPM and SPCM have histological composition with predominance of type II fibers and high prevalence of hybrid fibers in individuals without OSAS. Patients with OSAS have a reduction in the percentage of type II fibers in SPCM compared to controls, and this may have implications in the efficiency of this muscular function, which may contribute to the etiopathogenesis of OSAS

Introdução: A parede lateral da faringe tem importante papel no colapso da via aérea superior nos episódios de apneia obstrutiva do sono (AOS). Os dois principais músculos que formam esta região são o músculo palatofaríngeo (MPF) e o músculo constritor superior da faringe (MCSF). Estes músculos são classificados como esqueléticos e não possuem um padrão histológico de normalidade estabelecido. Os objetivos do estudo foram verificar a estrutura histológica das fibras do MPF e do MCSF em indivíduos controles sem síndrome da apneia obstrutiva do sono (SAOS), e avaliar se indivíduos portadores de SAOS apresentam alterações histológicas nestes músculos em comparação aos controles. Métodos: Foram avaliados 28 indivíduos adultos (faixa etária entre 18 e 55 anos de idade), sendo 17 portadores de SAOS grave e 11 controles. Destes 11 controles, 7 eram portadores de ronco primário, e 4 não apresentavam roncos e AOS. Coletaram-se fragmentos de MPF e de MCSF em cirurgia de faringoplastia lateral para os roncadores primários e apneicos graves, e em cirurgia de tonsilectomia das palatinas para os indivíduos com tonsilite crônica caseosa. Os espécimes musculares coletados foram congelados em nitrogênio líquido em até 3 horas após o procedimento cirúrgico. Por meio de colorações histológicas e imuno-histoquímicas, avaliou-se a histologia das fibras musculares no que tange a sua morfologia, a distribuição dos tipos de fibras, as dimensões do espaço intercelular, e a prevalência de fibras híbridas nos 2 músculos e em ambos os grupos. Resultados: O grupo-controle apresenta predomínio de fibras do tipo II, de contração rápida e alta fatigabilidade, nos MPF e MCSF, não havendo diferença estatística entre os dois músculos. Encontramos prevalência elevada de fibras híbridas no grupo-controle (45,45% no MPF e 27,27% no MCSF), sem diferença estatística entre os dois músculos. Quanto à comparação entre os grupos controle e SAOS, verificamos redução do percentual de fibras do tipo II do MCSF nos indivíduos com SAOS (p=0,04) quando comparados aos controles. Não houve diferença estatística na distribuição dos tipos de fibras musculares entre os 2 grupos no MPF. Conclusões: Os MPF e MCSF possuem composição histológica com predomínio de fibras do tipo II e prevalência elevada de fibras híbridas nos indivíduos sem SAOS. Os indivíduos portadores de SAOS possuem redução do percentual de fibras do tipo II no MCSF em comparação aos indivíduos sem SAOS, e isso pode ter implicações na redução da eficiência desta musculatura, podendo contribuir na etiopatogenia da AOS / Introduction: The lateral pharyngeal muscular wall plays an important role in upper airway collapse in obstructive sleep apnea (OSA) episodes. The two main muscles that form this anatomical site are the palatopharyngeal muscle (PPM) and the superior pharyngeal constrictor muscle (SPCM). These muscles are classified as skeletal and do not have an established normal histological pattern in literature. The objectives of the study were: verify the histological structure of PPM and SPCM fibers in control subjects without obstructive sleep apnea syndrome (OSAS), and evaluate whether OSAS individuals demonstrate histological changes in these muscles compared to controls. Methods: Twenty-eight adults (age range between 18 to 55 years old) were evaluated, 17 with severe OSAS and 11 controls. On the control group, 7 had primary snoring and 4 had no snoring or OSA. PPM and SPCM fragments were collected in lateral pharyngoplasty surgery for the primary snoring and severe OSAS patients and a palatine tonsillectomy was executed in individuals with chronic caseous tonsillitis. The collected muscles specimens were frozen in liquid nitrogen within 3 hours after the surgical procedure. Histological and immunohistochemical staining were used to evaluate the histology of muscle fibers concerning their morphology, the distribution of fiber types, the size of the intercellular space and the prevalence of hybrid fibers in the two muscles in both groups. Results: The control group showed predominance of type II fibers (fast contraction and high fatigability) in PPM and SPCM, without statistical difference between the two muscles. We found a high prevalence of hybrid fibers in the control group (45.45% in PPM and 27.27% in SPCM), without statistical difference between the two muscles. Regarding the comparison between the control and OSAS groups, we verified a reduction in the percentage of SPCM type II fibers in individuals with OSAS (p = 0.04) when compared to controls. There was no statistical difference in the percentage of muscle fiber types between the 2 groups in PPM. Conclusions: PPM and SPCM have histological composition with predominance of type II fibers and high prevalence of hybrid fibers in individuals without OSAS. Patients with OSAS have a reduction in the percentage of type II fibers in SPCM compared to controls, and this may have implications in the efficiency of this muscular function, which may contribute to the etiopathogenesis of OSAS

Oral and pharyngeal cancer is commonly treated with a combination of radiotherapy and surgery. It is a clinical knowledge that patients often experience severe swallowing disorders following treatment. Since surgical sequelae are instantaneous and obvious, little attention has been paid to other concurrent effects of the treatment. To shed light on this subject, the aim of this thesis was twofold (i) to make a retrospective inventory of the sequelae following treatment and (ii) to perform a prospective, inceptive examination at diagnosis, and to follow-up after radiotherapy, six months and 12 months after surgery. The files of ninety-nine patients revealed that following treatment one-third had to use gastric fistulas and more than nine of ten patients had restricted swallowing capacity. Every second patient could only swallow puréed or liquid food. Adequate intra-oral sensation and discrimination ability is essential for bolus preparation and bolus control, for appropriate elicitation of the swallowing reflex and, hence, for the oral phase of swallowing. At the inceptive examination, the prospective part of the study demonstrated intra-oral discrimination ability in patients was equal to that in healthy controls but was impaired six months after treatment and there was no significant improvement after 12 months. It had been expected that the patient’s healthy, non-tumor side would compensate but it did not. An explanation was found when it was revealed that radiotherapy induced a delayed decline in intra-oral sensation. Sensory decline was not demonstrated within a month after radiotherapy but was manifest six months later. Since the radiotherapy field includes the neck, because of the risk for metastasis, it is highly plausible that pharyngeal sensation declines in a manner corresponding to that found intra-orally when the healthy side is irradiated. In accord with this presumption, pharyngeal swallowing function deteriorated in patents with oral tumors. Cineradiographic evaluation of oral and pharyngeal swallowing function disclosed a significant association between the degree of swallowing dysfunction and the degree of sensory decline and with the degree of impairment of shape recognition. Conclusions: Delayed intra-oral sensory decline, found to be induced by radiotherapy, can be expected to appear in the entire radiation field, including the oral cavity and the pharynx, with adverse effect on swallowing. Testing intra-oral sensation close to the last radiotherapy session is not advisable, because sensory decline does not develop immediately after radiotherapy but manifests after six months. Spontaneous sensory rehabilitation cannot be expected after six months. The significant association between degree of swallowing dysfunction and degree of intra-oral sensory decline and impaired discrimination ability must be considered in the quest for functional rehabilitation of patients treated for oral or pharyngeal cancer.

Introdução: Apneia Obstrutiva do Sono (AOS) é prevalente em estados edematosos, especialmente em pacientes em hemodiálise (HD). Uma vez que o deslocamento noturno de fluidos (DNF) acarreta piora da AOS, nós elaboramos a hipótese de que a interferência na redistribuição de fluidos pelo uso de meias elásticas compressivas (MEC) atenuaria a gravidade da AOS, por mecanismos diferentes em comparação à terapia padrão para AOS, a pressão positiva em vias aéreas (CPAP). Métodos: este é um estudo randomizado e cross-over, que incluiu 14 pacientes dialíticos com AOS (índice de apneia/hipopneia - IAH > 5 eventos/hora) em exame de polissonografia (PSG), que era realizada em três momentos: basal, titulação de CPAP e após uma semana de uso diário de MEC. Circunferência cervical (CC), bioimpedância elétrica segmentar e variabilidade de frequência cardíaca (VFC) foram avaliadas antes e após cada exame de PSG. Resultados: A idade média foi 53±9 anos (57% de homens) e o índice de massa corporal foi 29,7±6,8 Kg/m². O IAH foi reduzido de 20,8 (14,2; 39,6) no exame basal para 7,9 (2,8; 25,4) durante titulação de CPAP e para 16,7 (3,5; 28,9) eventos/hora após uso de MEC (CPAP vs. basal, p=0,004; MEC vs. basal, p=0,017; e CPAP vs. MEC, p=0.017). Comparando basal, CPAP e MEC, o conteúdo de água noturna em membros inferiores foi menor com MEC (p=0,04), enquanto a água intracelular noturna em tronco foi maior (p=0,03). DNF basal, com CPAP e MEC foi de -183±72, -343±220, e -290±213ml, respectivamente (p=0,006). Houve aumento da circunferência cervical durante a noite durante o exame basal (0,7±0,4 cm), mas houve redução dessa circunferência após titulação com CPAP (-1,0±0,4 cm) e após uso de MEC (-0,4±0,8 cm) (CPAP vs. basal, p<0.0001; MEC vs. basal, p=0.001; CPAP vs. MEC, p=0.01). VFC, avaliada pelos componentes de alta e baixa frequência, demonstrou menor ativação simpática durante o exame de titulação de CPAP: OR: 11 (95% CI: 1,06 - 114,2), p=0,025, mas não com MEC: OR: 7,8 (95% CI: 0,75 - 82,2), p=0,059. Conclusões: tanto o CPAP quanto MEC melhoraram AOS em pacientes em HD, mas por mecanismos distintos: enquanto o CPAP reduziu o edema de vias aéreas superiores, ao exercer pressão local, o uso de MEC reduziu o DNF, ao evitar retenção de fluidos em membros inferiores, acumulando água no componente intracelular do tronco. Ativação simpática foi somente reduzida com uso de CPAP. / Background: Obstructive Sleep Apnea (OSA) is prevalent in edematous states, notably in hemodialysis (HD) patients. Once overnight fluid shift (OFS) augments OSA, we hypothesized that interfering in fluid redistribution by wearing compression stockings (CS) would attenuate OSA severity by different mechanisms in comparison to the standard treatment to OSA, the positive airway pressure (CPAP). Methods: This is a randomized crossover study that included 14 dialytic patients with OSA (apnea/hypopnea index - AHI >5 events/hour) by polysomnography (PSG), which was performed in three moments: at baseline, for CPAP titration, and one week after daily wearing of CS. Neck circumference (NC), segmental bioelectrical impedance and heart rate variability (HRV) were assessed before and after each PSG. Results: Mean age was 53±9 years (57% men) and body mass index was 29.7±6.8 kg/m2. AHI decreased from 20.8 (14.2; 39.6) at baseline to 7.9 (2.8; 25.4) during CPAP titration and to 16.7 (3.5; 28.9) events/hour after wearing CS (CPAP vs. baseline, p=0.004; CS vs. baseline, p=0.017; and CPAP vs. CS, p=0.017). Comparing baseline, CPAP and CS, nocturnal lower limbs water content was lower with CS (p=0.04), while nocturnal intracellular trunk water was higher (p=0.03). OFS at baseline, CPAP and CS was -183±72, -343±220, and -290±213ml, respectively (p=0.006). Overnight NC variation increased at baseline (0.7±0.4 cm), but decreased after CPAP titration (-1.0±0.4 cm) and while wearing CS (-0.4±0.8 cm) (CPAP vs. baseline, p<0.0001; CS vs. baseline, p=0.001; CPAP vs. CS, p=0.01). HRV, assessed by both high and low frequency components, showed a lower sympathetic activation during CPAP titration: OR: 11 (95% CI: 1.06 - 114.2), p=0.025, but not with CS: OR: 7,8 (95% CI: 0.75 - 82.2), p=0.059 Conclusions: Both CPAP and CS improved OSA in HD patients by different mechanisms: while CPAP reduced edema in upper airways by exerting local pressure, wearing CS reduced OFS by avoiding fluid retention in the legs, accumulating water in the intracellular component of the trunk. Sympathetic activation was decreased only with CPAP.

Foi realizado estudo caso-controle de base hospitalar, envolvendo pacientes diagnosticados com câncer de cabeça e pescoço e que participaram do \"Estudo Multicêntrico Latino-americano de Fatores Ambientais, Vírus e Câncer da Cavidade Oral e Laringe\" do projeto \"Genoma Clínico do Câncer\". Foram incluídos pacientes atendidos no Hospital Heliópolis, no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Instituto do Câncer Arnaldo Vieira de Carvalho entre novembro de 1998 e dezembro de 2005. Consideraram-se casos os pacientes com diagnóstico histologicamente confirmado de câncer de boca, faringe ou laringe e controles pessoas atendidas nos mesmos hospitais por outros motivos que não neoplasia maligna e doenças associadas com os fatores de risco do câncer de cabeça e pescoço. A análise empregou regressão logística não-condicional baseada em modelo hierárquico de determinação. No nível mais distal foram incluídas as variáveis demográficas (sexo, cor de pele e idade), seguidas pela escolaridade (série mais elevada que a pessoa cursou) e ocupação (exercida por mais tempo). No nível mais proximal, foram considerados o consumo de tabaco e de álcool. Também foi investigado se a associação de instrução e ocupação com câncer de cabeça e pescoço se mediava apenas por padrões diferenciais de consumo de álcool e tabaco entre os estratos sociais, ou se havia variação residual que excedia esses dois fatores. Todas as análises conduzidas para câncer de cabeça e pescoço foram replicadas de modo específico para as localizações topográficas da boca, faringe e laringe em separado. O estudo foi aprovado pelo Comitê de Ética da Faculdade de Odontologia da Universidade de São Paulo sob parecer no. 68/07 e os procedimentos estatísticos foram realizados no programa Stata 9. A amostra foi composta por 1017 casos e 951 controles. A análise hierárquica identificou maior chance de câncer de cabeça e pescoço entre os homens (OR=2,01; IC95% 1,57-2,59), pessoas entre 48 e 55 anos (OR=1,82; IC95% 1,42-2,33), pessoas sem estudo ou apenas alfabetizados (2,48; IC95% 1,73-3,52), entre pessoas com primeiro grau completo ou incompleto (1,31; IC95% 1,05-1,63) e entre as pessoas que exerceram durante mais tempo profissão manual (1,38; IC95% 1,10-1,74). Além disso, fumantes e consumidores de bebidas alcoólicas apresentaram maior razão de chances em relação àqueles que nunca consumiram os produtos. No modelo não hierárquico, mesmo após o ajuste por tabagismo e ingestão de álcool, maior chance foi verificada para o grupo de menor escolaridade em todas as localizações topográficas (exceto para os tumores de boca), e para pessoas com ocupações manuais (exceto para os tumores de boca e faringe). A identificação desse efeito residual indica haver fatores adicionais, além da exposição ao álcool e tabaco, operando na distribuição desigual do câncer de cabeça e pescoço entre os estratos sociais. / This is a hospital-based case-control study involving patients diagnosed with head and neck cancer. Such patients have participated in the \"Latin American Multicentric Study from Environmental Factors, Virus and Oral Cavity and Larynx Cancer\", and in the \"Clinical Genome of Cancer Project\", from November 1998 to December 2005, and were attended at the Hospital Heliópolis, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer Arnaldo Vieira de Carvalho. The case group comprised patients histologically diagnosed with mouth, pharynx or larynx cancer; the control group comprised patients treated at the same hospitals for other diseases than malignant neoplasms or conditions related to head and neck cancer risk factors. Data analysis used non-conditional logistic regression based on a hierarchical model of determination. At the most distal level, demographic variables were included (e.g. sex, skin color and age), followed by education level (e.g. highest grade or degree completed) and occupation (i.e. the one performed the longest period). Alcohol and tobacco consumption were included at the most proximal level. The investigation also assessed whether the association between education level and occupation with mouth and neck cancer was only mediated by differential patterns of alcohol and tobacco consumption among social strata, or there was residual variation that exceeded those two factors. All analyses for mouth and neck cancer were specifically replicated for each topographic location (mouth, pharynx and larynx). The study was approved by the University of Sao Paulo School of Dentistry\'s Ethics Committee, report number 68/07, and statistical analyses used the Stata 9 program. The sample was composed of 1017 cases and 951 controls. Hierarchical analysis identified a greater chance of head and neck cancer for men (OR=2,01; CI95% 1,57-2,59), patients aged 48 to 55 years old (OR=1,82; CI95% 1,42-2,33), uneducated or semi-literate patients (2,48; CI95% 1,73-3,52), subjects with elementary education (8 years) (1,31; IC95% 1,05-1,63) and those performing manual occupations (1,38; CI95% 1,10-1,74). In addition, tobacco smokers and alcohol users presented a higher odds than those non-exposed to these conditions. In the non-hierarchical model, even after the adjustment for tobacco and alcohol use, a higher odds was identified for the less-schooled strata in every topographic location (except for mouth tumors), and for subjects with manual labor occupations (except for mouth and pharynx tumors). Identification of such residual effect indicates that there are other factors than alcohol and tobacco consumption, which mediate the uneven distribution of head and neck cancer across the socioeconomic strata.