A Novel Flexible and Steerable Probe for Minimally Invasive Soft Tissue Intervention

Current trends in surgical intervention favour a minimally invasive (MI) approach, in which complex procedures are performed through increasingly small incisions. Specifically, in neurosurgery, there is a need for minimally invasive keyhole access, which conflicts with the lack of maneuverability of conventional rigid instruments. In an attempt to address this fundamental shortcoming, this thesis describes the concept design, implementation and experimental validation of a novel flexible and steerable probe, named “STING” (Soft Tissue Intervention and Neurosurgical Guide), which is able to steer along curvilinear trajectories within a compliant medium. The underlying mechanism of motion of the flexible probe, based on the reciprocal movement of interlocked probe segments, is biologically inspired and was designed around the unique features of the ovipositor of certain parasitic wasps. Such insects are able to lay eggs by penetrating different kinds of “host” (e.g. wood, larva) with a very thin and flexible multi-part channel, thanks to a micro-toothed surface topography, coupled with a reciprocating “push and pull” motion of each segment. This thesis starts by exploring these foundations, where the “microtexturing” of the surface of a rigid probe prototype is shown to facilitate probe insertion into soft tissue (porcine brain), while gaining tissue purchase when the probe is tensioned outwards. Based on these findings, forward motion into soft tissue via a reciprocating mechanism is then demonstrated through a focused set of experimental trials in gelatine and agar gel. A flexible probe prototype (10 mm diameter), composed of four interconnected segments, is then presented and shown to be able to steer in a brain-like material along multiple curvilinear trajectories on a plane. The geometry and certain key features of the probe are optimised through finite element models, and a suitable actuation strategy is proposed, where the approach vector of the tip is found to be a function of the offset between interlocked segments. This concept of a “programmable bevel”, which enables the steering angle to be chosen with virtually infinite resolution, represents a world-first in percutaneous soft tissue surgery. The thesis concludes with a description of the integration and validation of a fully functional prototype within a larger neurosurgical robotic suite (EU FP7 ROBOCAST), which is followed by a summary of the corresponding implications for future work

Focusing and orienting spatial attention differently modulate crowding in central and peripheral vision

The allocation of attentional resources to a particular location or object in space involves two distinct processes: an orienting process and a focusing process. Indeed, it has been demonstrated that performance of different visual tasks can be improved when a cue, such as a dot, anticipates the position of the target (orienting), or when its dimensions (as in the case of a small square) inform about the size of the attentional window (focusing). Here, we examine the role of these two components of visuo-spatial attention (orienting and focusing) in modulating crowding in peripheral (Experiment 1 and Experiment 3a) and foveal (Experiment 2 and Experiment 3b) vision. The task required to discriminate the orientation of a target letter "T,'' close to acuity threshold, presented with left and right "H'' flankers, as a function of target-flanker distance. Three cue types have been used: a red dot, a small square, and a big square. In peripheral vision (Experiment 1 and Experiment 3a), we found a significant improvement with the red dot and no advantage when a small square was used as a cue. In central vision (Experiment 2 and Experiment 3b), only the small square significantly improved participants' performance, reducing the critical distance needed to recover target identification. Taken together, the results indicate a behavioral dissociation of orienting and focusing attention in their capability of modulating crowding. In particular, we confirmed that orientation of attention can modulate crowding in visual periphery, while we found that focal attention can modulate foveal crowdin

Serotype epidemiology and multidrug resistance patterns of Salmonella enterica infecting humans in Italy

BACKGROUND: Salmonella enterica is the zoonotic agent most frequently responsible for foodborne infections in humans worldwide. In this work the presence of S. enterica was investigated in 734 unique enteropathogenic isolates collected from human patients between 2011 and 2012. RESULTS: All Salmonella spp. isolates were subjected to serotyping and antimicrobial susceptibility testing. Isolates displaying phenotypes and antimicrobial susceptibility profiles different from the reference strains were genotipically characterized. Several plasmid-embedded resistance determinants were identified and characterized. Non-typhoidal serotypes were most frequently diagnosed; monophasic Salmonella typhimurium 1,4 [5],12:i- and S. typhimurium represented the most prevalent serovars. Five isolates displayed phenotypes with extremely reduced susceptibility to antimicrobials: we detected multidrug resistance elements belonging to Ambler class A and class C in two non-typhoidal S. enterica serovars, i.e. Rissen and monophasic S. typhimurium 1,4 [5],12:i-, and in one typhoidal serovar, i.e., Paratyphi B. These resistance determinants have been so far almost exclusively associated with non-Salmonella members of the Enterobacteriaceae family. Alarmingly, two colistin resistant Salmonella enteritidis were also found. CONCLUSIONS: This work draws the attention to the still low, but rising, percentage of multidrug resistant Salmonella isolates infecting humans in Italy. Our results suggest that prompt monitoring of Salmonella serovar dissemination and resistance to antimicrobials is highly required

Non-canonical proteolytic activation of human prothrombin by subtilisin from Bacillus subtilis may shift the procoagulant\ue2\u80\u93anticoagulant equilibrium toward thrombosis

Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active -thrombin (T). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive precursor pre-thrombin-2 (Pre2), which is further attacked at Arg-320 \u2013Ile-321 to yield mature T. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation. This knowledge gap is particularly concerning, as bacterial infections are frequently complicated by severe coagulopathies. Here, we show that addition of subtilisin (50 nM to 2 M), a serine protease secreted by the non-pathogenic bacterium Bacillus subtilis, induces plasma clotting by proteolytically converting ProT into active Pre2, a nicked Pre2 derivative with a single cleaved Ala-470 \u2013Asn-471 bond. Notably, we found that this non-canonical cleavage at Ala-470 \u2013Asn-471 is instrumental for the onset of catalysis in Pre2, which was, however, reduced about 100 \u2013200-fold compared with T. Of note, Pre2 could generate fibrin clots from fibrinogen, either in solution or in blood plasma, and could aggregate human platelets, either isolated or in whole blood. Our findings demonstrate that alternative cleavage of ProT by proteases, even by those secreted by non-virulent bacteria such as B. subtilis, can shift the delicate procoagulant\u2013anticoagulant equilibrium toward thrombosis

Otoacoustic emissions and medial olivocochlear system: patients with tinnitus and no hearing loss

BACKGROUND: tinnitus. AIM: to compare the results of otoacoustic emissions for transitory stimulus (TEOAE) and the functioning of the olivocochlear medial system, in individuals with normal hearing sensibility, with and without tinnitus. METHOD: participants of this study were 60 subjects, with tonal thresholds and acoustic imitance measurements within normal standards, distributed in two groups: group one - 30 subjects with tinnitus and group two - 30 subjects without tinnitus, paired up by gender and age. Both groups were submitted to the TEOAE test, with and without the presence of white contralateral white noise at 60dB NPS. For the 19 subjects who presented unilateral tinnitus, TEOAE and suppression results were compared regarding the variables of side, taking in consideration the presence of tinnitus. RESULTS: in the group comparison, with and without tinnitus, there was no significant statistical difference for the incidence of TEOAE, response levels, and incidence of the suppression effect. Significant statistical difference was not observed between the right and left ears in the group with tinnitus. For the 19 subjects with unilateral tinnitus, a higher amplitude of the responses and a higher suppression incidence were observed for the right ear, as well as a higher incidence of tinnitus and a lower incidence of suppression for the left ear. CONCLUSION: there was no significant statistical difference for both TEOAE incidence and response levels, as well as for the functioning of the olivocochlear medial system between the subjects, with normal hearing sensibility, with and without tinnitus. For the subjects who presented unilateral tinnitus, the overall TEOAE reponse levels was significantly higher in the ear with no tinnitus and the olivocochlear medial system was significantly less efficient in the ear with tinnitus.TEMA: zumbido. OBJETIVO: comparar os resultados das emissões otoacústicas transitório por estímulo (EOAT) e do funcionamento do sistema olivococlear medial, em indivíduos com sensibilidade auditiva normal, com e sem zumbido. MÉTODO: a casuística deste estudo foi composta por 60 sujeitos, com limiares tonais e medidas da imitância acústica dentro dos padrões da normalidade distribuídos em dois grupos: grupo um formado por 30 sujeitos com zumbido e grupo dois por 30 sujeitos sem zumbido, pareados por gênero e idade. Os dois grupos foram submetidos ao teste das EOAT com e sem ruído branco contralateral a 60dB NPS. Em 19 sujeitos que apresentavam zumbido unilateral comparou-se os resultados das EOAT e supressão em relação à variável lado, considerando-se o lado do zumbido. RESULTADOS: na comparação entre os grupos com e sem zumbido não houve diferença estatisticamente significante quanto à ocorrência das EOAT, à amplitude de resposta, e à ocorrência do efeito de supressão. Não se observou diferença estatisticamente significante entre as orelhas direita (OD) e esquerda (OE) no grupo com zumbido. Nos 19 sujeitos com zumbido unilateral, observou-se maior amplitude de resposta e maior ocorrência de supressão à direita e maior ocorrência de zumbido e menor ocorrência de supressão à esquerda. CONCLUSÃO: não houve diferença estatisticamente significante tanto na ocorrência e amplitude de respostas das EOAT quanto no funcionamento do sistema olivococlear medial entre os sujeitos, com sensibilidade auditiva normal, com e sem zumbido. Nos sujeitos que apresentaram zumbido unilateral, observou-se que a amplitude geral das EOAT foi maior na orelha sem zumbido e que o sistema olivococlear medial foi menos eficiente na orelha com zumbido de forma estatisticamente significante.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaAudiologia do Centro de Especialização em Fonoaudiologia ClínicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Otorrinolaringologia e Distúrbios da Comunicação HumanaSciEL

Perfil antropométrico y alimentar de los alumnos de la Universidad de Integración Latinoamericana (UNILA)

Anais do V Encontro de Iniciação Científica e I Encontro Anual de Iniciação ao Desenvolvimento Tecnológico e Inovação – EICTI 2016 - 05 e 07 de outubro de 2016 – Sessão BiológicasLa obesidad es caracterizada por aumento de masa adiposa del organismo, estando comúnmente relacionada a disturbios nutricionales y metabólicos. También es considerada una condición clínica sería y prevalente, pudiendo tornarse el principal problema de salud del siglo XXI y es la primera causa de enfermedades crónicas del mundo (Ramos y Barros Filho, 2003). El siguiente trabajo fue realizado con el fin de reconocer los factores relacionados a las condiciones socio-culturales y ambientales con respecto a posibles alteraciones metabólicas y nutricionales en función de la inserción de los alumnos en un nuevo espacio geográfico, conocer mediante los parámetros alimentares y el estado nutricional de los alumnos de la UNILA, sus hábitos alimentares, relación con sus valores culturales y verificar los efectos pos-adaptación de estos individuos. Así también conocer el perfil alimentar de los estudiantes, comprender como los mismos conducen su alimentación y cuales son aquellos factores que podrían influenciar su nutrición

Visual reinforcement audiometry with different sound stimuli in children

BACKGROND: hearing evaluation in children. AIM: to verify the Minimum Response Levels (MRL) through the use of Visual Reinforcement Audiometry (VRA) in the sound field, in 50 normal hearing children and in 25 children with hearing loss, taking into account the following variables: side of sound presentation, gender, age and type of stimulus. METHOD: VRA was performed using pure tone frequency modulation (warble) and the Sonar System. The modulated tones were produced by the Pediatric Audiometer, in the frequencies of 500, 1000, 2000 and 4000Hz and at the intensities of 80, 60, 40 and 20dBNA. The modulated tones were presented in a decreasing sequence of intensity and by using the stimulus-reply-visual reinforcement conditioning. The assessment procedure and analysis of response were the same when using the stimuli of the Sonar System. However, on this occasion, a sound amplification box was used. Each loudspeaker with the visual reinforcement was positioned approximately at 90º azimuth to the right and the left of the child, and at a distance of approximately 50 cm. Visual reinforcement was an illuminated clown. RESULTS: no statistically significant difference was found between the MNL and the side of sound presentation. The MRL at 500Hz and 2000Hz, when using the Sonar System, were lower for normal hearing males. In this group, there was a decrease in the MRL with the increase in age for both stimuli. When comparing the MRL with two stimuli, there was a statistically significant difference in favor of the Sonar System, but only for the group of normal hearing children below two years of age. CONCLUSION: the MRL decrease with age independently of the stimulus and are lower when using the Sonar System. For the group of children with hearing loss no significant difference was found for any of the studied variables.TEMA: avaliação auditiva infantil. OBJETIVO: verificar os Níveis Mínimos de Resposta (NMR) por meio de Audiometria de Reforço Visual (ARV) em campo livre, em 50 crianças ouvintes e 25 deficientes auditivas, considerando as variáveis: lado de apresentação sonora, sexo, idade e tipo de estímulo. MÉTODO: realizou-se ARV com tons puros modulados em freqüência (warble) e com estímulos do Sistema Sonar nas crianças selecionadas. Os tons modulados foram produzidos pelo Audiômetro Pediátrico, nas freqüências de 500, 1000, 2000 e 4000Hz e nas intensidades de 80, 60, 40 e 20dBNA. Sendo estes apresentados em ordem decrescente de intensidade e utilizando o condicionamento estímulo-resposta-reforço visual. Utilizando os estímulos Sistema Sonar, o procedimento de avaliação e a apreciação das respostas foram os mesmos, porém para a apresentação destes foi utilizada uma caixa de amplificação sonora. Cada alto-falante com o reforço visual foi posicionado a aproximadamente a 90 azimute à direita e à esquerda da criança, em uma distância de aproximadamente 50cm. O reforço visual usado foi um palhaço iluminado. RESULTADOS: não houve diferença estatisticamente significante entre MNR em relação ao lado de apresentação. Os NMRs em 500 e 2000Hz do Sistema Sonar, foram menores no sexo masculino nos ouvintes. Neste grupo houve diminuição dos NMR com aumento da idade, para ambos estímulos. Ao comparar NMRs com dois estímulos houve diferença estatisticamente significante a favor do Sistema Sonar apenas para ouvintes com menos de dois anos. CONCLUSÃO: em ouvintes os NMRs reduzem com avanço da idade independente do estímulo e são inferiores com o Sistema Sonar. Nas deficientes auditivas não houve diferença significativa em relação a nenhuma variável estudada.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Departamento de Fonoaudiologia Núcleo Integrado de Atendimento, Pesquisa e Ensino em AudiçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de FonoaudiologiaUNIFESP, EPMUNIFESP, Depto. de Fonoaudiologia Núcleo Integrado de Atendimento, Pesquisa e Ensino em AudiçãoUNIFESP, Depto. de FonoaudiologiaSciEL

False-positive results in newborn universal hearing screening: possible causes

PURPOSE: to investigate the rate of false positive responses in a hospital - based newborn hearing screening program (NHS), their possible causes and solutions. METHODS: during the period we evaluated 1,110 regular nursery newborns, age 6 to 48 hours with Transient Evoked Otoacoustic Emissions (TEOAEs), Echocheck, Ilodynamics Ltd model., at the nurseries, before discharge. In case of absence of response, the ear canal was manipulated. Infants that failed the screening were retested fifteen days after birth. RESULTS: 50.09% failed the first trial, then the ear canal was manipulated, and it decreased to 24.41%. This group showed normal TEOAEs at the retest time; Mean time of hospital discharge was 42,27h, thought 93% cesarian delivery; 98% double room and 2% single room status. The mean age of the pass group was 24.14 h (± 10.21) and the fail group 19.19 hours (± 8.43). 66.12% had less than 24 hours on the moment of the test. 4.9% were occluded with vernix. CONCLUSION: hospital trend toward early discharge after routine deliveries forces the audiologist to carry out the screening before 48 hours. High number of false-positives in NHS, must be seen as a Hospital Administrative Problem not only as a biologic cause, like the vernix caseosum, and it is not related to the professional experience. Ear manipulation is strongly recommended.OBJETIVO: avaliar a ocorrência de respostas falso-positivas na Triagem Auditiva dentro de uma maternidade particular, suas possíveis causas e soluções. MÉTODOS: foram avaliados 1.110 recém-nascidos eutróficos entre 6 e 48 horas de vida no berçário, com o analisador de Emissões Otoacústicas Evocadas Transientes (EOATE) modelo Echochek da Ilodynamics Ltd. Na ausência de resposta, foi realizada a manipulação do meato acústico externo (Manobra Facilitadora) e colhido novo resultado. Os que falharam foram retestados em 15 dias. RESULTADOS: 50,09% dos RN falhou na primeira tentativa. Após a manobra facilitadora, 24,41% continuou falhando, mas demonstraram EOATE presentes no reteste. O tempo médio de internação foi de 42,27 h, sendo 93,42% oriundos de cesareana. Pertenciam a convênios particulares padrão enfermaria 98% e 2% quarto individual. A idade média do grupo que passou foi de 24,14 h (± 10,21) e a do grupo que falhou 19,19 horas (±8,43). Possuíam menos de 24 horas de vida no momento do teste 66,12% dos RN, foi constatado vérnix obliterante em 4.9%. CONLUSÃO: face a alta precoce hospitalar, é necessário que o Fonoaudiólogo realize o teste antes das 48 horas de vida do RN. Desta forma, além das causas biológicas inerentes a faixa etária, detectou-se um problema estrutural de administração hospitalar, que independe da habilidade ou experiência do Fonoaudiólogo. A Manobra Facilitadora é altamente recomendada.Instituto Nacional de Educação de SurdosUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Distúrbios da Comunicação HumanaSciEL

Formation of a Unique Cluster of G-Quadruplex Structures in the HIV-1 nef Coding Region: Implications for Antiviral Activity

G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich sequences. Their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they have been proposed to be directly involved in gene regulation at the level of transcription. Because the HIV-1 Nef protein is a fundamental factor for efficient viral replication, infectivity and pathogenesis in vitro and in vivo, we investigated G-quadruplex formation in the HIV-1 nef gene to assess the potential for viral inhibition through G-quadruplex stabilization. A comprehensive computational analysis of the nef coding region of available strains showed the presence of three conserved sequences that were uniquely clustered. Biophysical testing proved that G-quadruplex conformations were efficiently stabilized or induced by G-quadruplex ligands in all three sequences. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. These data constitute the first evidence of the possibility to regulate HIV-1 gene expression and infectivity through G-quadruplex targeting and therefore open a new avenue for viral treatment. © 2013 Perrone et al