Working Memory and Language Relate to Report of Socio-Emotional Functioning in Children with Hearing Loss.

Background: Children with hearing loss have been found to have significantly more behavioral and emotional challenges than their typically hearing peers, though these outcomes are variable at the individual level. Working memory deficits have been found to relate to executive functioning and overall emotion regulation, leading to behavior challenges. Language development is essential for development of social relationships and communicating one's needs and this may lead to distress when children cannot communicate effectively. Based on prior findings in children with hearing loss and their typically hearing peers, working memory and language skills were hypothesized to be related to parent and teacher report of socio-emotional functioning. Methods: Participants were 35 children with hearing loss (66% female, M = 5.17 years old, SD = ±1.97) whose language, working memory, and socio-emotional functioning were evaluated during the course of treatment and educational planning. Results: Bivariate analyses indicated that working memory was related to a number of socio-emotional domains (e.g., functional communication, atypicality, withdrawal), as were language scores (e.g., social skills, inattention). The direction of these associations was such that stronger working memory and language skills were related to more regulated socio-emotional functioning. Conclusions: This study is limited in generalizability by size and the relative homogeneity of the sample. A call to action of the current study includes more education with regard to profiles and presentations of children with hearing loss, and an early focus on socio-emotional learning to foster the development of regulatory skills.

Language and academic outcomes of children with cochlear implants in an inclusive setting: Evidence from 18 years of data.

OBJECTIVE: This study examined outcomes in core and pragmatic language, receptive vocabulary, and academic skills in children with cochlear implants (CIs) enrolled in an inclusive educational setting. METHODS: Eighty-eight children with CIs were included in the analyses. Data was collected over an 18-year period, at six-month intervals for core language, vocabulary, and pragmatic skills and in kindergarten and second grade for academic skills. Kaplan-Meier analyses were used to estimate the median time to achieve age-appropriate scores. RESULTS: Results indicated the median time to obtain age-appropriate skills for children with CIs enrolled in our program was less than three years for core language and pragmatic skills and less than two years for vocabulary. Over 90% of the sample had academic skills in the average range in both kindergarten and second grade. DISCUSSION: This study shares outcomes of children with CIs who received consistent and intensive transdisciplinary intervention in an inclusive educational setting, revealing the trajectory required to obtain age-appropriate skills, when compared to normative data. CONCLUSION: Results were favorable, indicating that children with CIs in an inclusive program, with intensive intervention and strong language and social models, can develop skills commensurate with typically developing peers across a variety of core skills.

The feasibility and reliability of measuring forearm muscle thickness by ultrasound in a geriatric inpatient setting: a cross-sectional pilot study.

BACKGROUND: Given the potential benefits of introducing ultrasound in the clinical assessment of muscle disorders, this study aimed to assess the feasibility and reliability of measuring forearm muscle thickness by ultrasound in a geriatric clinical setting. METHODS: Cross-sectional pilot study in 25 participants (12 patients aged ≥ 70 years in an acute geriatric ward and 13 healthy volunteers aged 25-50 years), assessed by three raters. Muscle thickness measurement was estimated as the distance between the subcutaneous adipose tissue-muscle interface and muscle-bone interface of the radius at 30% proximal of the distance between the styloid process and distal insertion of the biceps brachii muscle of the dominant forearm. Examinations were repeated three times by each rater and intra- and inter-rater reliability was calculated. Feasibility analysis included consideration of technological, economic, legal, operational, and scheduling (TELOS) components. RESULTS: Mean muscle-thickness measurement difference between groups was 4.4 mm (95% confidence interval [CI] 2.4 mm to 6.3 mm], p < 0.001). Intra-rater reliability of muscle-thickness assessment was excellent, with intraclass correlation coefficient (ICC) of 0.947 (95%CI 0.902 to 0.974), 0.969 (95%CI 0.942 to 0.985), and 0.950 (95%CI 0.907 to 0.975) for observer A, B, and C, respectively. Inter-rater comparison showed good agreement (ICC of 0.873 [95%CI 0.73 to 0.94]). Four of the 17 TELOS components considered led to specific recommendations to improve the procedure's feasibility in clinical practice. CONCLUSION: Our findings suggest that US is a feasible tool to assess the thickness of the forearm muscles with good inter-rater and excellent intra-rater reliability in a sample of hospitalized geriatric patients, making it a promising option for use in clinical practice.

Pathways in the association between added sugar consumption, obesity in mother-child dyads, and chronic oral disease burden in early childhood.

In this study, we modeled the pathways in the association of socioeconomic status, frequency of added sugar consumption, and obesity in mother-child dyads with chronic oral disease burden in early childhood using structural equation modeling. A population-based study was conducted on preschoolers from public daycare centers in São Luís, Brazil (n = 674) and their mothers. Chronic oral disease burden in early childhood was a latent variable, representing the shared variance of the following indicators: visible plaque index, gingivitis, and dental caries. A higher consumption frequency of added sugars by children [standardized regression coefficient (SC) = 0.219] explained the chronic oral disease burden. A higher consumption frequency of added sugars by mothers was associated with greater consumption of sugar by children (SC = 0.236), and indirectly with a greater chronic oral disease burden (SC = 0.052). Maternal obesity was associated with obesity in the offspring (SC = 0.130). The chronic oral disease burden is already present in early childhood and can be explained by the higher consumption of added sugars by the mother-child dyad. Approaches to preventing chronic oral diseases should focus on common risk factors, start early in life, and promote family involvement in this process.

Reabilitação bucal com prótese obturadora maxilar após excisão de carcinoma adenoide cístico / Mouth rehabilitation with maxillary obturator prosthesis after excision of adenoid cystic carcinoma / Rehabilitación bucal con prótesis obturadora maxilar tras excision de carcinoma adenoide quístico

A prótese obturadora constitui o principal método para a reabilitação de grandes defeitos maxilares. Tem como objetivo fechar o defeito, separar a cavidade oral da cavidade nasal, prevenir a fala anasalada e a regurgitação nasal de alimentos e líquidos e dar sustentação ao perfil facial. Este artigo visa relatar um caso de reabilitação com prótese obturadora maxilar após maxilectomia parcial. Paciente do gênero feminino, 72 anos, diagnosticada com carcinoma adenoide cístico na região de palato, foi submetida a maxilectomia parcial que resultou em extenso defeito maxilar e comunicação bucosinusal. Após anamnese, exames extra, intraorais e radiográfico, foi planejado para o período cicatricial e de uso da sonda nasogástrica, a confecção de uma placa obturadora para melhorar a deglutição e fala. Em seguida, confecção de uma prótese total obturadora superior e prótese parcial removível inferior. A placa obturadora foi confeccionada e utilizada até a remoção da sonda e instalação das próteses. Após moldagem das duas arcadas, foram obtidos modelos funcionais que foram montados em articulador após os ajustes dos planos de orientação e registro das relações intermaxilares. Foram realizadas provas estéticas e funcionais dos dentes artificiais e ajustes necessários. Posteriormente à acrilização, as próteses foram instaladas e o ajuste oclusal executado. Para obter retenção e estabilidade satisfatórias durante a utilização da prótese obturadora superior foi sugerido o uso de adesivo para dentadura. Três proservações foram realizadas. A prótese obturadora reabilitou a estética, fonética, função mastigatória e deglutição restabelecendo a autoestima e a ressocialização da paciente(AU)

The obturator prosthesis is the main method for the rehabilitation of large maxillary defects. With the purpose to closethe defect, separate the oral cavity from the nasal cavity, prevent hypernasal speech, nasal regurgitation of food and liquids and provide support for the facial profile. This article aims to report a case of rehabilitation with maxillary obturator prosthesis after partial maxillectomy. A 72-year-old female patient, diagnosed with adenoid cystic carcinoma in the palate region, underwent partial maxillectomy that resulted in extensive maxillary defect and bucco-sinus communication. After anamnesis, extra, intraoral and radiographic exams, the construction of a palatal plate was planned to be used with the nasogastric tube and during the healing process, to improve swallowing and speech. Then, the manufacture of a maxillary obturator prosthesis and a lower removable partial prosthesis. The palatal plate was made and used until the tube was removed and the insertion of the prostheses. After the impressions, master casts were made and mounted on an articulator after adjustment of wax occlusion rims and registration of the maxillo-mandibular relations. Functional elements of speech, occlusion, and appearance were evaluated during the try-in of the provisional set-up and adjusts were made.After the acrylization, the prostheses were inserted and the occlusal adjustment performed. To obtain satisfactory retention and stability when using the maxillary obturator prosthesis, it was suggested to use denture adhesive. Three post-insertions visits were carried out. The obturator prosthesis rehabilitated aesthetics, phonetics, masticatory function and swallowing, restoring the patient's self-esteem and improving social life(AU)

La prótesis obturadora es el método principal para la rehabilitación de grandes defectos maxilares. Tiene por objetivo cerrarel defecto, separar la cavidad bucal de la cavidad nasal, prevenir el habla nasal, la regurgitación nasal de alimentos y líquidos,dando apoyo al perfil facial. Este artículo tiene objetivo de reportar un caso de rehabilitación con prótesis obturadora maxilar tras maxilectomía parcial. Una paciente de 72 años, diagnosticada de carcinoma adenoide quístico en región del palato, fué sometida a maxilectomía parcial que resultó en extenso defecto maxilar y comunicación bucosinusal. Después de anamnesis, exámenes extra, intraorales y radiográficos, se planificó para el período de cicatrización y el uso de la sonda nasogástrica,la construcción de una placa obturadora para mejorar la deglución y el habla. Luego, la fabricación de una prótesis obturadora total superior y una prótesis parcial inferior removible. La placa obturadora se hizo y se utilizó hasta que se retiró la sonda y se instalaron las prótesis. Se realizón la impresión de ambos arcos, obtuvieron modelos funcionales que se montaron en articulador, tras ajustes de los planos de orientación y registro de relaciones intermaxilares. Se realizaron pruebas estéticas y funcionales en dientes artificiales y ajustes necesarios. Después de la acrilización se instalaron las prótesis y se realizó ajuste oclusal. Para obtener una retención y estabilidad satisfactoria al utilizar la prótesis obturadora superior, fue sugirió utilizar un adesivo para prótesis. Se realizaron tres proservaciones. La prótesis obturatriz rehabilitó estética, fonética, función masticatoria y deglución, devolviendo autoestima y resocialización al paciente(AU)

Caesarean delivery and early childhood caries: Estimation with marginal structural models in Brazilian pre-schoolers.

OBJECTIVE: This study analysed the association between caesarean section and early childhood caries (ECC), estimating the effects using regression and causal inference models. METHODS: This was a historical cohort study of 697 mother-child dyads, conducted in São Luís, Brazil. The caesarean section was the exposure, and the severity of ECC (dmft) was the outcome. Covariates household income, maternal schooling, maternal hypertension, maternal obesity and birth weight were adjusted for in the models. The effects were estimated by Poisson regression (Means Ratio-MR) and causal inference using a marginal structural model (MSM) (MR and Average Treatment Effect-ATE coefficients), weighted by the inverse probability (IPW) of exposure. RESULTS: Caesarean section was protective against caries in the bivariate (MR 0.81; CI 0.70-0.94; P = 0.005) and multivariate (MR 0.78; CI 0.67-0.91; P = 0.002) models. In MSM analyses, the caesarean section had no effect on ECC (ATE = -0.35; P = 0.107), controlling for IPW of exposure. CONCLUSION: The apparent association between caesarean section and ECC severity seems spurious, as it did not persist after employing a superior approach to estimating causality.

Synthesis of Deoxyradicinin, an Inhibitor of Xylella fastidiosa and Liberibacter crescens, a Culturable Surrogate for Candidatus Liberibacter asiaticus.

Pierce's disease of grapevine and citrus huanglongbing are caused by the bacterial pathogens Xylella fastidiosa and Candidatus Liberibacter asiaticus (CLas), respectively. Both pathogens reside within the plant vascular system, occluding water and nutrient transport, leading to a decrease in productivity and fruit marketability and ultimately death of their hosts. Field observations of apparently healthy plants in disease-affected vineyards and groves led to the hypothesis that natural products from endophytes may inhibit these bacterial pathogens. Previously, we showed that the natural product radicinin from Cochliobolus sp. inhibits X. fastidiosa. Herein we describe a chemical synthesis of deoxyradicinin and establish it as an inhibitor of both X. fastidiosa and Liberibacter crescens, a culturable surrogate for CLas. The key to this three-step route is a zinc-mediated enolate C-acylation, which allows for direct introduction of the propenyl side chain without extraneous redox manipulations.

Parent-Child Interaction Therapy as a Behavior and Spoken Language Intervention for Young Children With Hearing Loss.

Purpose The importance of early intervention for fostering language in children with hearing loss has been well documented; those that facilitate parent engagement are particularly effective. Listening and spoken language outcomes among children with hearing loss continue to fall short compared to hearing peers, despite improvements in hearing technologies. The current study evaluated the effectiveness of parent-child interaction therapy (PCIT) as a behavioral intervention for children with hearing loss and its applicability as a language intervention. Method PCIT effectiveness was evaluated for children with hearing loss (PCIT treatment group: N = 18). For a subset of the treatment group (matched experimental group: n = 6), pretreatment and posttreatment language samples were compared to a matched control group ( n = 6). Results Significant changes were observed in parent skills and child behavior from pretreatment to posttreatment for the PCIT treatment group. A subset of the treatment group (matched experimental group) with available matched controls (matched control group) demonstrated a significant increase in utterances and a trend toward significant increase in receptive vocabulary compared to the control group. Conclusion PCIT is a promising intervention for children with hearing loss that empowers parents to engage in optimal indirect language stimulation, improves parent-child interactions, improves child behavior, and promotes spoken language skills.

The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.

The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain (TMD) lengths and hydrophobicity. Features in transmembrane domains such as charged residues in ion channels are often functionally important, but could pose a challenge during cotranslational membrane insertion and folding. Our systematic proteomic approaches in both yeast and human cells revealed that the ER membrane protein complex (EMC) binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally and immediately following clusters of TMDs enriched for charged residues. The EMC can remain associated after completion of translation, which both protects clients from premature degradation and allows recruitment of substrate-specific and general chaperones. Thus, the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade-off between function and stability.

Valor pronóstico de los instrumentos de evaluación de enfermedad avanzada y de final de vida en ancianos ingresados en un centro sociosanitario / Prognostic value of assessment tools on elderly patients with chronic advanced disease and end of life, admitted to an intermediate care centre

Objetivo. Aplicar 3instrumentos de evaluación de enfermedad avanzada en ancianos ingresados en un centro sociosanitario y evaluar su relación con la mortalidad. Métodos. Se aplicaron los instrumentos NECPAL, índice PROFUND e índice de comorbilidad de Charlson a 87 pacientes. Resultados. El instrumento NECPAL identificó a 31 pacientes (35,6%) en situación de necesidad de atención paliativa; según el índice PROFUND, 45 (54,7%) tenían riesgo alto/muy alto de mortalidad (≥7 puntos) y según el índice de Charlson, 31 (35,6%) tenían carga de morbilidad alta (≥4 puntos). Pacientes NECPAL positivos: el 80,5% tenían puntuación ≥7 en índice PROFUND y 48,3% un Charlson ≥ 4; dichas proporciones fueron 34,4 y 28,5% en los NECPAL negativos (p<0,001 y p≤0,06, respectivamente). Correlaciones entre los 3instrumentos: cuantitativas (Spearman): número de respuestas NECPAL con PROFUND (r=0,57; p<0,001); con Charlson (r=0,214; p=0,047) y entre PROFUND y Charlson (r=0,157; p=0,148). Cualitativas (kappa) NECPAL (positivo/negativo) con PROFUND (corte 6/7) (0,40; p<0,001), con Charlson (corte 3/4) (0,19; p=0,080) y entre PROFUND y Charlson (0,08; p=0,399). Predicción de mortalidad (área bajo la curva): NECPAL 3 meses 0,81 (IC: 0,62-1,00); 6 meses 0,71 (IC: 0,53-0,89) y 12 meses 0,67 (IC: 0,52-0,82). PROFUND 3 meses 0,71 (IC: 0,50-0,91); 6 meses 0,73 (IC: 0,58-0,87) y 12 meses 0,69 (IC: 0,57-0,81). Charlson 3 meses 0,72 (IC: 0,52-0,91); 6 meses 0,62 (IC: 0,45-0,80) y 12 meses 0,64 (IC: 0,50-0,78). Conclusiones. Los 3instrumentos se relacionaron de forma significativa con una mayor mortalidad. La concordancia entre los resultados de los distintos instrumentos fue baja (AU)

Objective. To apply 3advanced chronic disease evaluation tools in elderly patients admitted to an intermediate and long-term care centre, and evaluate its relationship with mortality. Methods. The NECPAL tool, PROFUND prognostic index, and Charlson comorbidity index were applied to 87 patients. Results. The NECPAL tool identified 31 patients (35.6%) in need of palliative care, and according to the PROFUND index, 45 (54.7%) had high/very high risk of mortality (≥7 points), and according to Charlson index, 31 (35.6%) had high comorbidity (≥4 points). Of the NECPAL positive patients, 80.5% had a PROFUND index score ≥7, and 48.3% a Charlson index ≥ 4. These percentages were 34.4% and 28.5% in negative NECPAL patients (P<.001 and P≤.06, respectively). Correlations between the 3tools: quantitative (Spearman) number of responses in NECPAL with PROFUND (r=.57; P<.001); with Charlson (r=.214; P<.047) and between PROFUND and Charlson (r=.157; P=.148). Qualitative (kappa) NECPAL (positive/negative) with PROFUND (cut-off 6/7) (0.40; P<.001), and Charlson (cut-off 3/4) (0.19; P=.080) and between PROFUND and Charlson (0.08; P=.399). Mortality prediction (area under the curve): NECPAL 3 months 0.81 (95% CI: 0.62-1.00); 6 months 0.71 (95% CI: 0.53-0.89) and 12 months 0.67 (95% CI: 0.52-0.82). PROFUND 3 months 0.71 (95% CI: 0.50-0.91); 6 months 0.73 (95% CI: 0.58-0.87), and 12 months 0.69 (95% CI: 0.57-0.81). Charlson 3 months 0.72 (95% CI: 0.52-0.91); 6 months 0.62 (95% CI: 0.45-0.80), and 12 months 0.64 (95% CI: 0.50-0.78). Conclusions. The 3tools were significantly associated with high mortality. A low concordance was found between the results of the different tools (AU)

Defining the physiological role of SRP in protein-targeting efficiency and specificity.

The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes amino-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the amino terminus. By contrast, many proteins containing cleavable amino-terminal signal peptides were efficiently cotranslationally targeted in SRP's absence. We also reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to the ER were mistargeted to mitochondria, leading to mitochondrial defects. These results elucidate SRP's essential roles in maintaining the efficiency and specificity of protein targeting.

[Prognostic value of assessment tools on elderly patients with chronic advanced disease and end of life, admitted to an intermediate care centre]. / Valor pronóstico de los instrumentos de evaluación de enfermedad avanzada y de final de vida en ancianos ingresados en un centro sociosanitario.

OBJECTIVE: To apply 3advanced chronic disease evaluation tools in elderly patients admitted to an intermediate and long-term care centre, and evaluate its relationship with mortality. METHODS: The NECPAL tool, PROFUND prognostic index, and Charlson comorbidity index were applied to 87 patients. RESULTS: The NECPAL tool identified 31 patients (35.6%) in need of palliative care, and according to the PROFUND index, 45 (54.7%) had high/very high risk of mortality (≥7 points), and according to Charlson index, 31 (35.6%) had high comorbidity (≥4 points). Of the NECPAL positive patients, 80.5% had a PROFUND index score ≥7, and 48.3% a Charlson index ≥ 4. These percentages were 34.4% and 28.5% in negative NECPAL patients (P<.001 and P≤.06, respectively). Correlations between the 3tools: quantitative (Spearman) number of responses in NECPAL with PROFUND (r=.57; P<.001); with Charlson (r=.214; P<.047) and between PROFUND and Charlson (r=.157; P=.148). Qualitative (kappa) NECPAL (positive/negative) with PROFUND (cut-off 6/7) (0.40; P<.001), and Charlson (cut-off 3/4) (0.19; P=.080) and between PROFUND and Charlson (0.08; P=.399). Mortality prediction (area under the curve): NECPAL 3 months 0.81 (95% CI: 0.62-1.00); 6 months 0.71 (95% CI: 0.53-0.89) and 12 months 0.67 (95% CI: 0.52-0.82). PROFUND 3 months 0.71 (95% CI: 0.50-0.91); 6 months 0.73 (95% CI: 0.58-0.87), and 12 months 0.69 (95% CI: 0.57-0.81). Charlson 3 months 0.72 (95% CI: 0.52-0.91); 6 months 0.62 (95% CI: 0.45-0.80), and 12 months 0.64 (95% CI: 0.50-0.78). CONCLUSIONS: The 3tools were significantly associated with high mortality. A low concordance was found between the results of the different tools.

Proinflammatory cytokines in early childhood caries: Salivary analysis in the mother/children pair.

HYPOTHESIS: Proinflammatory cytokines are increased in saliva of mother/children pairs with caries. DESIGN: Case-control study involving caries-free children (n = 20) and children with early childhood caries (ECC) (n = 20), and their mothers (n = 40). The maternal variables analyzed were waist circumference (WC), decayed, missing and filled teeth (DMFT) and sugar intake; and in the children were body mass index (BMI), def-t and sugar intake. Salivary levels of VEGF, IL-6 and TNF-α were analyzed of mother/children pairs. RESULTS: In the mothers, salivary VEGF levels were correlated with DMFT (r = 0.35; p = .03), WC (r = 0.35; p = .02), and sugar intake (r = 0.32; p = .04). Higher salivary IL-6 levels were also correlated with maternal DMFT (r = 0.45; p = .004) and WC (r = 0.32; p = .04). In the children, higher salivary VEGF levels were correlated with higher def-t scores (r = 0.42; p = .008). Children with caries had a 63% higher median salivary VEGF and twofold higher mean IL-6 levels compared to caries-free children. Mothers of children with ECC showed higher mean of salivary IL-6 levels compared to those of children without ECC (p = .03). CONCLUSION: Salivary proinflammatory cytokines are correlated with the severity of caries in the mother-children pair. Obesity and excessive sugar consumption seem to underlie the associations between proinflammatory cytokines and caries in the family environment.

Streptococcus mutans in Mother-Child Dyads and Early Childhood Caries: Examining Factors Underlying Bacterial Colonization.

This study investigated the association between colonization of mother-child dyads with Streptococcus mutans (SM) and early childhood caries (ECC), with consideration of the mediator and confounders, using a theoretical model. Four hundred mothers and their children from São Luís, Brazil, were included in the study. A diagram based on directed acyclic graphs was elaborated to analyze the association between SM colonization of the mother, mediated by child SM, and ECC. Other maternal (socioeconomic, waist circumference, sugar consumption, DMFT index, and visible plaque) and child factors (sugar consumption, visible plaque, and child age) composed the theoretical model. A total effect model (maternal SM on ECC) and a direct effect model, adjusted by the mediation effect of child SM (maternal SM via child SM) on ECC, were analyzed. The outcome of interest in this study was ECC (number of teeth with caries experience, dmft), which was analyzed as a discrete variable by Poisson regression. The Paramed test was used to analyze mediation. The following variables were associated with ECC in the total effect model: maternal SM, maternal waist circumference ≥80 cm, DMFT, maternal visible plaque, child age ≥4 years, and increased sugar consumption of the child (>3 times/day). In the direct effect model, high maternal SM levels remained associated with ECC, while moderate and high colonization of the child with SM was also associated with ECC. Child SM colonization just partially mediated the effect of maternal SM on ECC (33%). Thus, factors other than the mechanism of bacterial colonization should be considered in mother-child dyads, including eating habits, oral hygiene practices, and a family history of caries.

The SND proteins constitute an alternative targeting route to the endoplasmic reticulum.

In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.

Comparison phenotypic and genotypic identification of Staphylococcus species isolated from bovine mastitis / Comparação da identificação fenotípica e genotípica de espécies do gênero Staphylococcus isoladas de mastite bovina

In addition to Staphylococcus aureus nowadays other coagulase-positive staphylococci (CoPS) and coagulase-negative staphylococci (CoNS), earlier considered of minor importance, are now accepted as relevant pathogens for humans and animals. The involvement of these microorganisms in bovine mastitis etiology and the possibility their transmission through milk to humans justify the requirement of developing reliable methods for identification of the most frequent species among them. The purpose of this study was to compare the phenotypic techniques with the genotypic method carried out by sequencing of the rpoB gene in identification of several species of the genus Staphylococcus isolated from bovine mastitis. A total of 300 staphylococci isolates of bovine mastitis cases from several Brazilian dairy herds were studied by phenotypic and genotypic techniques, respectively: 150 CoPS and 150 CoNS strains. A total of 18 CoNS different species and 4 CoPS species were identified. Among the CoNS the following species were recognized: 48 (32%) Staphylococcus warneri, 22(15%) S. epidermidis, 20(13%) S. hyicus, 10(7%) S. xylosus, 7(5%) S. haemolyticus, 6(4%) S. simulans, 6(4%) S. schleiferi subsp schleiferi, 6(4%) S. hominis, 5(3%) S. pasteuri, 4(2.7%) S. cohnii, 3(2%) S. saprophyticus subsp. saprophyticus 3(2%) S. chromogenes 3(2%) S. sciuri, 2(1%) S. saccharolyticus, 2(1%) S. lugdunensi, 1(0,7%) S. auricularis, 1(70%) S. saprophyticus subsp. bovis, 1(0.7%) S. capitis. And among the 150 CoPS were identified respectively: 105 (70%) S. aureus, 21(14%), S. hyicus, 19(13%) S. intermedius e 5(3%) S. schleiferi subsp coagulans. Considering the 150 CoNS isolates, the identifications performed by phenotypic and genotypic tests presented 96.7% of concordance, kappa coefficient of agreement = 0.933, SE (standard error) of kappa=0.021 (95% confidence interval: 0.893 to 0.974), Pearson's correlation coefficient (r) = 0.9977, (confidence interval 95%: 0.9938 a 0.9992) and in relation to 150 CPS isolates it was detected an agreement of 98.7%, kappa = 0.960, SE of kappa = 0.016, (95% confidence interval: 0.929 to 0.992) Pearson's correlation coefficient (r) = 0.9994 (95% confidence interval: 0.9681 to 1.0000). The verified agreement strength between the identification methods can be considered as excellent. These results assure that according to laboratory resources any of them will be suitable to perform the staphylococci identification.(AU)

Além de Staphylococcus aureus atualmente outros estafilococos coagulase positiva (SCP) e estafilococos coagulase-negativos (SCN), anteriormente considerados de menor relevância, são reconhecidos como importantes patógenos para humanos e animais. O envolvimento desses micro-organismos na etiologia da mastite bovina e a possibilidade da sua transmissão através do leite aos humanos justifica a utilização de métodos confiáveis para a identificação das espécies mais frequentes. O objetivo deste estudo foi comparar as técnicas fenotípicas com o método genotípico realizada por sequenciamento do gene rpoB na identificação de espécies do gênero Staphylococcus spp. isolados de mastite bovina. Um total de 300 estafilococos isolados de casos de mastite bovina em diferentes rebanhos leiteiros brasileiros foram estudados por técnicas fenotípicas e genotípicas, respectivamente: 150 linhagens de SCP e 150 linhagens de SCN. Foram identificados um total de 18 espécies de SCN e 4 espécies SCP. Entre os SCN as seguintes espécies identificadas: 48 (32%) Staphylococcus warneri, 22 (15%) S. epidermidis, 20 (13%) S. hyicus, 10 (7%) S. xylosus, 7 (5%) S. haemolyticus, 6 (4%) S. simulans, 6 (4%) S. schleiferi subsp schleiferi, 6 (4%) S. hominis, 5 (3%) S. pasteuri, 4 (2,7%) S. cohnii, 3 (2%) S. saprophyticus subsp. saprophyticus, 3 (2%) S. chromogenes, 3 (2%) S. sciuri, 2 (1%) S. saccharolyticus, 2 (1%) S. lugdunensi, 1 (0,7%) S. auricularis, 1 (70 %) S. saprophyticus subsp. bovis, 1 (0,7%) S. capitis. E entre as 150 SCP foram identificados, 105 (70%) S. aureus, 21 (14%), S. hyicus, 19 (13%) S. intermedius e 5 (3%) S. schleiferi subsp coagulans. Considerando-se os 150 SCN isolados, as identificações realizadas por testes fenotípicos e genotípicos apresentaram 96,7% de concordância, coeficiente de concordância kappa = 0,933, SE (erro padrão) de kappa = 0,021 (95% intervalo de confiança: 0,893-0,974), coeficiente de correlação de Pearson (r) = 0,9977, (intervalo de confiança de 95%: 0,9938 a 0,9992) e em relação a 150 SCP isolados foi observado uma concordância de 98,7%, kappa = 0,960, sE de kappa = 0,016, (95% de intervalo de confiança: 0,929 a 0,992) coeficiente de correlação de Pearson (r) = 0,9994 (95% intervalo de confiança: 0,9681-1,0000). A correlação entre os métodos de identificação pode ser considerada como excelente. Esses resultados demonstraram que de acordo com os recursos disponíveis no laboratório, poderia ser utilizada qualquer uma das metodologias.(AU)

Identifying beliefs about smoking in patients with peripheral vascular disease.

Peripheral vascular disease (PVD) is a chronic disabling illness that frequently results in the occlusion of arteries in lower limbs and may cause ischemia, gangrene, or infection. The single most significant factor contributing to both the onset and progression of PVD is smoking, which has addictive properties. Once smoking becomes a habitual behavior, combined with the atherosclerotic process, a disastrous pathway ensues. The aim of this project was to gain an understanding of the beliefs of patients with PVD who smoked. A nonexperimental, descriptive design was used. Data were obtained from a sample of participants with a known history of PVD who have had a previous vascular intervention and who are established patients in a vascular surgeon's private office N = 50. The majority of participants were male (n = 31; 63%) 65-74 years of age (n = 18; 36%), were unemployed (n = 30; 60%), and have smoked for greater than 51+ years (n = 13; 26%). A scale that was developed guided by the behavioral beliefs subscale revealed that PVD patients enjoyed smoking, smoking helped them to relax, and they believed that they were addicted to smoking. Results from the normative beliefs subscale indicated that the spouse or significant other, children or those whom they lived with, did not approve of their smoking and also that their healthcare provider had discussed smoking cessation with them. The control beliefs subscale results demonstrated that most patients had attempted to quit smoking and believed that it would be a difficult behavior to stop and they would require the assistance of a patch or medication and feared the withdrawal symptoms. In conclusion, exploring the beliefs and thought process of patients who smoked provided a rich body of knowledge which can afford the healthcare professional with the ability to better understand the smoking experience as seen through the patients' eyes.

Celularidade do leite e unidades formadoras de colônias nas mastites causadas por Staphylococcus coagulase positiva e coagulase negativa / Milk cellularity and colony forming units in mastitis caused by coagulase-positive staphylococci and coagulase negative

A mastite é a principal afecção do gado destinado à produção leiteira, que impacta significativamente a cadeia produtiva do leite, com reflexos ainda para a saúde pública. Estudou-se aspectos relacionados à etiologia, celularidade e de contagem bacteriana em 10 propriedades leiteiras, localizadas no Estado de São Paulo. Foram examinadas 1148 vacas em lactação, totalizando 4584 glândulas mamárias. Foram considerados os casos, em que houve isolamento de estafilococos coagulase positiva (SCP) e estafilococos coagulase negativa (SCN). Os resultados revelaram microbiota com vários patógenos e diferentes espécies de SCN (128 casos) e SCP (45), Staphylococcus aureus(90), Streptococcus agalactiae(70), Streptococcus dysgalactiae (69), Streptococcus uberis(29), Corynebacteriumspp. (230), Klebsiella pneumoniae(28), Klebsiella oxytoca(2), Escherichia coli(15), Enterobactersp. (3). Os resultados de contagem de células somáticas (CCS) relacionados aos SCP e SCN não mostraram diferenças entre as propriedades avaliadas, entretanto com diferenças significantes ao se avaliar a CCS entre os dois grupos de estafilococos, como pode ser evidenciado ao comparar SCN Discreto e SCP exuberante (P<0,01), SCP Discreto e SCP exuberante (P<0,001) e SCN moderado e SCP exuberante (P<0,01). A avaliação da CCS relacionada à intensidade da infecção, considerando-se como crescimento discreto o isolamento de até nove colônias, moderado de dez a 29 colônias e exuberante, com 30 ou mais colônias, revelou para ambos os grupos de estafilococos que quanto maior o número de unidades formadoras de colônias (UFC), a CCS é mais elevada, sendo sempre maior nos casos de SCP. Conclui-se que quando há maior número de UFC, há concomitantemente maior CCS/mL de leite, no caso dos SCP e SCN...

Mastitis is the main affection of cattle intended for dairy production, which significantly impacts the milk production chain, with consequences yet to public health. It was studied aspects related to etiology, cellularity and bacterial count in 10 dairy farms, in the State of São Paulo. There were examined 1148 milking cows, totaling 4584 mammary glands. Cases in which there was isolation coagulase positive staphylococci (CPS) and coagulase-negative staphylococci (CNS) were considered. The results showed microbiota with various different pathogens and CNS (128 cases) and CPS (45), Staphylococcus aureus (90), Streptococcus agalactiae (70), Streptococcus dysgalactiae (69), Streptococcus uberis (29), Corynebacterium spp . (230), Klebsiella pneumoniae (28), Klebsiella oxytoca (2), Escherichia coli (15), Enterobacter spp. (3). The somatic cell count (SCC) related to CPS and CNS showed no differences among the evaluated properties, although with significant differences when evaluating the SCC between both groups of staphylococci, as evidenced by comparing discreet CNS and exuberant CPS (P <0.01), discreet CPS and exuberant CPS (P <0.001) and moderate SCN and exuberant SCP (P <0.01). The evaluation of SCC was related to the intensity of infection, considering how slight growth isolation of up to nine colonies, moderate ten to 29 colonies and lush, with 30 or more colonies, revealed for both groups of staphylococci that the higher the number of colony forming units (CFU), SCC is higher being larger in cases of CPS. The results indicate that the importance of both CPS and CNS when considering the high occurrence of the evaluated properties and the fact that it raises the SCC, which compromises the quality of milk. We conclude that when there is a larger number of CFU, is concomitantly higher SCC/ml of milk, in the case of CPS and CNS...

Association between early childhood caries and maternal caries status: A cross-section study in São Luís, Maranhão, Brazil.

OBJECTIVE: This study aims to evaluate the association between early childhood caries (ECC) and maternal caries status, and the maternal perception of ECC risk factors. MATERIALS AND METHODS: A cross-sectional study was carried out with 77 mother-child pairs, the children ranging from 12 to 36 months of age and their mothers, who were seeking dental care at a health center in São Luís, Maranhão, Brazil. Data collection was conducted using a specific questionnaire for mothers. Oral clinical examination of the mother-child binomial to assess caries incidence, gingival bleeding (GB) and visible plaque was done. Home visits were performed in 10% of the sample in order to observe the environmental conditions, dietary habits and dental hygiene practices. RESULTS: The findings showed that the caries prevalence in children was 22.5 times higher in the mother who had decayed tooth (prevalence ratio [PR] = 22.5, confidence interval [CI] 95% = 3.2-156.6, P < 0.001). GB also was observed in 14 mothers and children, the PR in pair was 12.2 (CI95% = 1.6-88.9, P < 0.001). The variables are related for the mother-child binomial in regression linear analysis. CONCLUSION: The maternal caries status was associated with ECC.

Utilization of a free fitness center-based exercise referral program among women with chronic disease risk factors.

Physical activity (PA) reduces the risk for a number of chronic diseases including heart disease, hypertension, hyperlipidemia, and diabetes mellitus type 2. However, most Americans do not meet expert recommendations for exercise, and minorities and low-income persons are the most inactive. Community-based approaches to promoting PA include primary care exercise referral programs. This study examines patient characteristics associated with utilization of a community health center-based exercise referral program. Adult female patients of a community health center with an affiliated fitness center, in Boston, MA, were included in the study if they received a referral to the fitness center from their primary care provider. Demographic and medical information was abstracted from the medical chart, and fitness records were abstracted to measure activation of a fitness center membership (creation of an account denoting at least an initial visit) and utilization over time. Overall, 503 (40%) of the 1,254 referred women in the study sample activated their membership. Black women were almost 60% more likely to activate their membership (adjusted OR 1.6, 95% CI 1.2-2.2), and women with higher co-morbidity counts were almost 45% more likely to activate (adjusted OR 1.4, 95% CI 1.0-2.0). Once activated, a minority of women participated at levels likely to improve cardiometabolic fitness. Of the 503 activations, 96 (19%) had no participation, 359 (71%) had low participation, and only 48 (10%) had high participation. No independent predictors of participation were identified. These findings suggest that program design may benefit from developing activation, initial participation, and retention strategies that address population-specific barriers.