Exome Sequencing Identifies Multiple Genetic Diagnoses in Children with Syndromic Growth Disorders.

OBJECTIVE: To evaluate the presence of multiple genetic diagnoses in syndromic growth disorders. STUDY DESIGN: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders. RESULTS: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes. CONCLUSION: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.

Two new patients with acromesomelic dysplasia, PRKG2 type-identification and characterization of the first missense variant.

Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelia, mild metaphyseal widening of the long bones and mild spondylar dysplasia. To date, only four variants have been reported; one nonsense, one splice-site, and two frameshifts in five AMDP families. Here, we report the first missense variant and a second splice-site variant in PRKG2 in two patients with clinical and radiological features of acromesomelic dysplasia. Furthermore, functional studies of the novel missense variant, p.Val470Gly, revealed that it was unable to down-regulate FGF2-induced MAPK signaling and, thus, would be predicted to cause growth delay. Hence, this report expands the mutational spectrum in skeletal dysplasias associated with PRKG2 variants. In addition, we propose recognizable facial features with acromesomelic dysplasia, PRKG2 type.

Identification of a second genetic alteration in patients with SHOX deficiency individuals: a potential explanation for phenotype variability.

OBJECTIVE: Our study aimed to assess the impact of genetic modifiers on the significant variation in phenotype that is observed in individuals with SHOX deficiency, which is the most prevalent monogenic cause of short stature. DESIGN AND METHODS: We performed a genetic analysis in 98 individuals from 48 families with SHOX deficiency with a target panel designed to capture the entire SHOX genomic region and 114 other genes that modulate growth and/or SHOX action. We prioritized rare potentially deleterious variants. RESULTS: We did not identify potential deleterious variants in the promoter or intronic regions of the SHOX genomic locus. In contrast, we found eight heterozygous variants in 11 individuals from nine families in genes with a potential role as genetic modifiers. In addition to a previously described likely pathogenic (LP) variant in CYP26C1 observed in two families, we identified LP variants in PTHLH and ACAN, and variants of uncertain significance in NPR2, RUNX2, and TP53 in more affected individuals from families with SHOX deficiency. Families with a SHOX alteration restricted to the regulatory region had a higher prevalence of a second likely pathogenic variant (27%) than families with an alteration compromising the SHOX coding region (2.9%, P = .04). CONCLUSION: In conclusion, variants in genes related to the growth plate have a potential role as genetic modifiers of the phenotype in individuals with SHOX deficiency. In individuals with SHOX alterations restricted to the regulatory region, a second alteration could be critical to determine the penetrance and expression of the phenotype.

Factors associated with worsening in the self-rated health status of Brazilian women who lived with dependent elderly people during the first wave of COVID-19. / Fatores associados à piora da autoavaliação da saúde das brasileiras que residiam com idosos dependentes durante a primeira onda da COVID-19.

The objective is to analyze the factors associated with the worsening of the self-rated health (SRH) of Brazilian women who live with elderly people with functional dependence (EFD) during the first wave of COVID-19. ConVid - Behavior Research was used as a data source. For the analysis, the group of women who lived with EFD was compared with those who lived with the elderly without any dependence. Hierarchical prevalence ratio (PR) models were estimated to test the associations between sociodemographic characteristics, changes in income, routine activities and health in the pandemic, with the outcome of worsening SRH. This worsening was more frequent in the group of women living with EFD. After adjusting for hierarchical factors, being black (PR=0.76; 95%CI 0.60-0.96) and having a per capita income lower than minimum wage (PR=0.78; 95%CI 0.64- 0.96) were shown to be protective factors for SRH worsening among EFD co-residents. Indisposition, emergence/worsening of back problems, affected sleep, poor SRH, feeling loneliness and difficulty in carrying out routine activities during the pandemic were positively associated factors. The study demonstrates that living with EFD was associated with a worsening in the health status of Brazilian women during the pandemic, especially among those of higher social status.

O objetivo do artigo é analisar os fatores associados à piora da autoavaliação da saúde (AAS) de brasileiras que residiam com idosos com dependência funcional (IDF) durante a primeira onda da pandemia de COVID-19. Utilizou-se a ConVid - Pesquisa de Comportamentos como fonte de dados. Para a análise comparou-se o grupo de mulheres que moravam com IDF com aquelas que moravam com idosos sem dependência. Estimou-se modelos hierárquicos de razão de prevalência (RP) para testar as associações entre as características sociodemográficas, mudanças na renda, atividades de rotina e saúde na pandemia, tendo como desfecho a piora da AAS. A piora da AAS foi mais frequente no grupo de mulheres que moravam com IDF. Após o ajuste dos fatores hierárquicos, ser negra (RP=0,76; IC95% 0,60-0,96) e ter renda per capita menor que um salário-mínimo (RP=0,78; IC95% 0,64-0,96) foram fatores inversamente associados à piora da AAS entre corresidentes de IDF. O estado de ânimo ruim, o surgimento/piora de problema de coluna, o sono afetado, a AAS ruim, o sentimento de solidão e a dificuldade na realização de atividades rotineiras durante a pandemia foram fatores positivamente associados. O estudo demonstra que morar com IDF esteve associado à piora da saúde das brasileiras na pandemia, especialmente entre aquelas em posição de maior status social.

Fatores associados à piora da autoavaliação da saúde das brasileiras que residiam com idosos dependentes durante a primeira onda da COVID-19 / Factors associated with worsening in the self-rated health status of Brazilian women who lived with dependent elderly people during the first wave of COVID-19

Resumo O objetivo do artigo é analisar os fatores associados à piora da autoavaliação da saúde (AAS) de brasileiras que residiam com idosos com dependência funcional (IDF) durante a primeira onda da pandemia de COVID-19. Utilizou-se a ConVid - Pesquisa de Comportamentos como fonte de dados. Para a análise comparou-se o grupo de mulheres que moravam com IDF com aquelas que moravam com idosos sem dependência. Estimou-se modelos hierárquicos de razão de prevalência (RP) para testar as associações entre as características sociodemográficas, mudanças na renda, atividades de rotina e saúde na pandemia, tendo como desfecho a piora da AAS. A piora da AAS foi mais frequente no grupo de mulheres que moravam com IDF. Após o ajuste dos fatores hierárquicos, ser negra (RP=0,76; IC95% 0,60-0,96) e ter renda per capita menor que um salário-mínimo (RP=0,78; IC95% 0,64-0,96) foram fatores inversamente associados à piora da AAS entre corresidentes de IDF. O estado de ânimo ruim, o surgimento/piora de problema de coluna, o sono afetado, a AAS ruim, o sentimento de solidão e a dificuldade na realização de atividades rotineiras durante a pandemia foram fatores positivamente associados. O estudo demonstra que morar com IDF esteve associado à piora da saúde das brasileiras na pandemia, especialmente entre aquelas em posição de maior status social.

Abstract The objective is to analyze the factors associated with the worsening of the self-rated health (SRH) of Brazilian women who live with elderly people with functional dependence (EFD) during the first wave of COVID-19. ConVid - Behavior Research was used as a data source. For the analysis, the group of women who lived with EFD was compared with those who lived with the elderly without any dependence. Hierarchical prevalence ratio (PR) models were estimated to test the associations between sociodemographic characteristics, changes in income, routine activities and health in the pandemic, with the outcome of worsening SRH. This worsening was more frequent in the group of women living with EFD. After adjusting for hierarchical factors, being black (PR=0.76; 95%CI 0.60-0.96) and having a per capita income lower than minimum wage (PR=0.78; 95%CI 0.64- 0.96) were shown to be protective factors for SRH worsening among EFD co-residents. Indisposition, emergence/worsening of back problems, affected sleep, poor SRH, feeling loneliness and difficulty in carrying out routine activities during the pandemic were positively associated factors. The study demonstrates that living with EFD was associated with a worsening in the health status of Brazilian women during the pandemic, especially among those of higher social status.

Factors Associated With Influenza Vaccination During the COVID-19 Pandemic in Older Adults Residing in Brazil.

The current study aimed to assess influenza vaccination coverage and explore factors related to vaccine uptake in older adults in 2020 amid the coronavirus disease 2019 pandemic. A cross-sectional study using an online questionnaire was performed with 380 older adults (aged ≥60 years), living in Brazil, from May 26 to June 29, 2020. Data regarding sociodemographic, health, and social support variables were collected. Data were analyzed using Poisson regression with robust variance. Influenza vaccination coverage in the sample was 85.5% (95% confidence interval [81.6, 88.7]). Older adults with increased age had higher vaccination coverage, whereas those who were smokers, not wearing masks, and sometimes and never/almost never received professional support had lower vaccination rates. Data show that vaccine coverage for influenza in 2020 was below that recommended by Brazilian authorities. We reinforce the importance of information about the influenza vaccine, especially for younger older adults, smokers, and those who do not wear masks. Reliable information from health care professionals and the media is essential for vaccination during a pandemic. [Journal of Gerontological Nursing, 49(5), 31-38.].

Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature.

Objective: Most children with short stature remain without an etiologic diagnosis after extensive clinical and laboratory evaluation and are classified as idiopathic short stature (ISS). This study aimed to determine the diagnostic yield of a multigene analysis in children classified as ISS. Design and methods: We selected 102 children with ISS and performed the genetic analysis as part of the initial investigation. We developed customized targeted panel sequencing, including all genes already implicated in the isolated short-stature phenotype. Rare and deleterious single nucleotide or copy number variants were assessed by bioinformatic tools. Results: We identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%). Three patients had more than one P/LP genetic alteration. Most of the findings were in genes associated with the growth plate differentiation: IHH (n = 4), SHOX (n = 3), FGFR3 (n = 2), NPR2 (n = 2), ACAN (n = 2), and COL2A1 (n = 1) or involved in the RAS/MAPK pathway: NF1 (n = 2), PTPN11 (n = 1), CBL (n = 1), and BRAF (n = 1). None of these patients had clinical findings to guide a candidate gene approach. The diagnostic yield was higher among children with severe short stature (35% vs 12.2% for height SDS ≤ or > -3; P = 0.034). The genetic diagnosis had an impact on clinical management for four children. Conclusion: A multigene sequencing approach can determine the genetic etiology of short stature in up to one in six children with ISS, removing the term idiopathic from their clinical classification.

[Homecare of elderly Brazilians with functional dependency: inequalities and challenges during the first wave of the COVID-19 pandemic]. / O cuidado domiciliar de idosos com dependência funcional no Brasil: desigualdades e desafios no contexto da primeira onda da pandemia de COVID-19.

The article aims to analyze the pandemic's effect on the burden of care for elderly persons with functional dependency according to the presence of hired caregivers and socioeconomic conditions in the year 2020. Data were obtained from the ConVid - Behavior Survey of 2020. We calculated the percentage distribution and prevalence of the population living with elderly persons with functional dependency during the COVID-19 pandemic according to sex, race/color, and income. We estimated the Pearson chi-square test and prevalence ratio for the increase in household work, fitting Poisson regression models with robust variance and using 95% confidence intervals (95%CI). Among adults living with elderly individuals, 8.1% (95%CI: 7.1-9.4) had at least one elderly person with functional dependency. During the pandemic, 11.7% (95%CI: 8.5-16.0) stopped hiring third-party caregivers, which can be explained by social distancing to reduce risk of transmission and/or by the decline in families' purchasing power. Those who lost hired caregivers during the pandemic were more likely to experience an increase in the burden of care, regardless of their socioeconomic status. There was an unequal distribution of caregiving work in the population, intensified by the arrival of the COVID-19 pandemic. The heavier load of care for elderly persons with functional dependency was sharper in more socioeconomically privileged groups such as whites and those with higher income. One hypothesis is that more vulnerable groups already bore a high burden of care before the pandemic. The crisis in care has been aggravated by the dismantling of primary healthcare in Brazil, a reduction in social support for Brazilian families during the pandemic, and rising unemployment, decreasing families' capacity to hire caregivers.

O artigo tem o objetivo de analisar o efeito da pandemia na carga de cuidado da pessoa idosa com dependência funcional, segundo a presença de cuidador contratado e condições socioeconômicas no ano de 2020. Utilizou-se a ConVid - Pesquisa de Comportamentos de 2020 como fonte de dados. Calculou-se a distribuição percentual e a prevalência da população que mora com idoso com dependência funcional durante a pandemia da COVID-19, segundo sexo, raça/cor da pele e renda. Estimou-se o teste de qui-quadrado de Pearson e a razão da prevalência de aumento do trabalho doméstico, ajustando-se modelos de regressão de Poisson com a variância robusta. Utilizou-se o intervalo de 95% de confiança (IC95%). Entre adultos que moravam com idoso, 8,1% (IC95%: 7,1-9,4) tinham pelo menos um idoso com dependência funcional. Durante a pandemia, 11,7% (IC95%: 8,5-16,0) deixaram de ter cuidador, o que se explica pelo distanciamento social para redução de risco de contágio e/ou pela diminuição da capacidade aquisitiva das famílias. Aqueles que perderam cuidador remunerado durante a pandemia tiveram maior probabilidade de aumento da carga do cuidado, independentemente da condição socioeconômica. Verificou-se a distribuição desigual do trabalho de cuidar na população, que se intensificou com a chegada da pandemia da COVID-19. A piora da carga de cuidado de idoso com dependência funcional foi mais acentuada entre os grupos mais privilegiados, como brancos e de maior renda. Uma hipótese é a de que os grupos mais vulneráveis já tivessem uma alta carga de cuidado antes da pandemia. A crise no cuidado se agrava diante do desmonte da atenção básica, redução do suporte social às famílias brasileiras no contexto de pandemia e aumento do desemprego, diminuindo a capacidade de contratação de cuidador.

El artículo tiene como objetivo analizar el efecto de la pandemia en la carga de cuidado de la persona anciana con dependencia funcional, según la presencia del cuidador contratado y condiciones socioeconómicas, durante el año 2020. Se utilizó la ConVid - Encuesta de Comportamientos de 2020 como fuente de datos. Se calculó la distribución porcentual y la prevalencia de la población que vive con anciano con dependencia funcional durante la pandemia de COVID-19, según sexo, raza/color de piel y renta. Se estimó el test de chi-cuadrado de Pearson y la razón de la prevalencia de aumento del trabajo doméstico, ajustándose a modelos de regresión de Poisson con variancia robusta. Se utilizó el intervalo de 95% de confianza (IC95%). Entre adultos que vivían con ancianos, un 8,1% (IC95%: 7,1-9,4) tenían por lo menos un anciano con dependencia funcional. Durante la pandemia, un 11,7% (IC95%: 8,5-16,0) dejaron de tener cuidador, lo que se explica por el distanciamiento social para la reducción del riesgo de contagio y/o por la disminución de la capacidad adquisitiva de las familias. Aquellos que perdieron un cuidador remunerado durante la pandemia tuvieron una mayor probabilidad de aumento de la carga del cuidado, independientemente de la condición socioeconómica. Se verificó la distribución desigual del trabajo de cuidar en la población, que se intensificó con la llegada de la pandemia de COVID-19. El empeoramiento de la carga de cuidado de anciano con dependencia funcional fue más acentuada entre los grupos más privilegiados, como blancos y de mayor renta. Una hipótesis es la de que los grupos más vulnerables ya tuvieran una alta carga de cuidado antes de la pandemia. La crisis en el cuidado se agrava ante el desmantelamiento de la Atención Básica, reducción del apoyo social a las familias brasileñas en el contexto de pandemia y aumento del desempleo, disminuyendo la capacidad de contratación de cuidadores.

Adult Height of Patients with SHOX Haploinsufficiency with or without GH Therapy: A Real-World Single-Center Study.

INTRODUCTION: Isolated SHOX haploinsufficiency is a common monogenic cause of short stature. Few studies compare untreated and rhGH-treated patients up to adult height (AH). Our study highlights a growth pattern from childhood to AH in patients with SHOX haploinsufficiency and analyzes the real-world effectiveness of rhGH alone or plus GnRH analog (GnRHa). METHODS: Forty-seven patients (18 untreated and 29 rhGH-treated) with SHOX haploinsufficiency were included in a longitudinal retrospective study. Adult height was attained in 13 untreated and 18 rhGH-treated (rhGH alone [n = 8] or plus GnRHa [n = 10]) patients. RESULTS: The untreated group decreased height SDS from baseline to AH (-0.8 [-1.1; -0.4]), with an increase in the prevalence of short stature from 31% to 77%. Conversely, the rhGH-treated group had an improvement in height SDS from baseline to AH (0.6 [0.2; 0.6]; p < 0.001), with a reduction in the prevalence of short stature (from 61% to 28%). AH in the rhGH-treated patients was 1 SD (6.3 cm) taller than in untreated ones. Regarding the use of GnRHa, the subgroups (rhGH alone or plus GnRHa) attained similar AH, despite the higher prevalence of pubertal patients and worse AH prediction at the start of rhGH treatment in patients who used combined therapy. CONCLUSION: The use of rhGH treatment improves AH in patients with SHOX haploinsufficiency, preventing the loss of height potential during puberty. In peripubertal patients, the addition of GnRHa to rhGH allows AH attainment similar to the AH of patients who start rhGH alone in the prepubertal age.

Impact of the periodontal phenotype in premolar and molar sites on bone loss following full-thickness mucoperiosteal flap: A 1-year prospective clinical trial.

BACKGROUND: Full-thickness mucoperiosteal flap (FTF) elevation could potentially affect the periodontium of the involved teeth; it is not clear if the periodontal phenotype of teeth involved in a FTF may influence these changes. The aim of this study was to evaluate the impact of FTF on teeth periodontium, as well as assessing the impact of periodontal phenotype on bone remodeling. METHODS: In this single arm prospective clinical trial, 26 subjects and a total of 52 adjacent teeth were included. Patients receiving implant surgery in the posterior area, at the time of implant site preparation, an FTF was extended one tooth mesial and distal to the planned site, and the flap was elevated both facially and lingually. Vertical and horizontal bone linear changes were measured on both adjacent teeth, using superimposed cone-beam computerized tomography (CBCT) images taken prior to implant placement (T0) and at 12 months (T1). Baseline digital scans of models and DICOM files were superimposed to assess the periodontal phenotype. RESULTS: Vertical bone changes from T0 to T1 were statistically significant (P = 0.013), with changes were significantly higher at the mesial (-0.31 ± 0.30 mm) and facial (P < 0.05) sites. Horizontal dimensional changes 5 mm subcrestally were similar among different locations (P = 0.086) and the bone width loss was higher closest to the crest (P = 0.001). No correlation was found between soft tissue thickness and bone changes. However, bone thickness at baseline appears to influence the extent of horizontal bone remodeling. Overall, the magnitude of bone loss either vertically or horizontally was clinically insignificant (≤0.4 mm). A preventive effect against bone loss maybe expected with bone thickness > 2 mm. CONCLUSION(S): Marginal bone changes in maxillary and mandibular posterior teeth following FTF at 12 months are very minimal, and mainly influenced by bone rather than soft tissue thickness. Overall, FTF does not seem to have deleterious effects on adjacent teeth periodontium.

Delayed Puberty Phenotype Observed in Noonan Syndrome Is More Pronounced in Girls than Boys.

INTRODUCTION: Pubertal delay is described as one of the clinical features in Noonan syndrome (NS) and it may be one of the factors causing short adult height in those patients. The present study aimed at characterizing pubertal development in NS and identifying pubertal delay predictors. METHODS: We analyzed 133 individuals with a molecular diagnosis of NS and clinical puberty evaluation. We characterized delayed puberty as pubertal onset after 12 years in girls and 13.5 years in boys, according to parameters of the Brazilian population. To investigate its predictors, we correlated the age at onset of puberty with several characteristics and genotype in a multilevel regression model. For comprehending pubertal development in NS, we assessed age and anthropometric measures at each Tanner stage and adult age. RESULTS: The mean age at puberty onset for girls was 11.9 ± 1.9 years and for boys, 12.5 ± 1.7 years, significantly later than the Brazilian population (p = 0.025; p < 0.001). Girls (49.1%) presented delayed puberty more frequently than boys (27.9%, p = 0.031). Body mass index standard deviation scores (SDS) and insulin growth factor 1 SDS at puberty onset significantly predicted later puberty entry. Height gain from the onset of puberty to adult height was lower in children with pubertal delay. CONCLUSION: Pubertal delay is characteristically found in children with NS, more frequently in females. The low weight of patients with NS could modulate the age of puberty, just as the increase in overweight/obesity in the general population has shown an effect on reducing the age of onset of puberty.

Factors associated with depressive and anxiety symptoms in older adults during the COVID-19 pandemic: a Brazilian study.

Objectives: Older adults are one of the most vulnerable age groups to the social distance measures imposed by the COVID-19 pandemic. This study aimed to assess factors associated with depressive and anxiety symptoms in Brazilian older adults during the pandemic.Method: This cross-sectional online study assessed 380 older adults (over 60 years of age) living in Brazil, from 26th May 2020 to 29th June 2020. A self-reported questionnaire included sociodemographic data, lifestyle, health characteristics, and the COVID-19 related variables. The Geriatric Depression Scale (GDS) and the Geriatric Anxiety Inventory (GAI) were also applied. Data were analyzed via logistic regression models, using a hierarchical approach.Results: The prevalence of depressive symptoms according to GDS was 28.7% (95% CI = 24.4%, 33.4%) and the prevalence of anxiety symptoms according to GAI was 26.1% (95% CI = 21.9%, 30.7%). Physically inactive older adults, the ones who were in social isolation for more days, feel much vulnerable to contracting COVID-19, and never or almost never receive support from family/friends were more likely to have depressive symptoms. Being female, physically inactive or physically active 1-3 times/week, feel very vulnerable to contracting COVID-19 and never or almost never receive support from family/friends were associated with the anxiety symptoms.Conclusion: A high prevalence of depressive and anxious symptoms was identified in Brazilian older adults. The data can help in planning interventions aimed at older adults, also including their families, health professionals, and the whole society.

Dual Digitally Guided Crown Lengthening in Esthetic Area Compromised by Disharmonic Implant Crown.

INTRODUCTION: A disharmonious smile results from excessive gingival exposure or gingival margin misalignment is a frequent finding in patients. The most common cause is altered passive eruption; however, in the case presented here, the esthetics of the smile is compromised also due to an inadequate implant placement and crown fabrication. CASE PRESENTATION: This case presented a combination of altered passive eruption and a buccally as well as deeply placed implant crown (#10) that led to disproportionate dimensions of an upper lateral incisor. Dual digitally guided crown lengthening surgical procedure for teeth #5 to #12 was performed aiming a better harmony of the smile. Treatment also included placement of tooth veneers and re-made of implant crown. A pleasant smile with appropriate colors and proportions was achieved. All esthetic and periodontal health parameters were maintained throughout the follow-up period (1 year). CONCLUSION: The use of dual digitally guided crown lengthening help to accomplish precision and stability of esthetic outcome, as it guides for both, bone and soft tissue removal. Particularly, in challenging cases with high esthetic demand and complicated factors present, such as the case presented here, the digital approach provides tools to attain excellent treatment outcome.

O cuidado domiciliar de idosos com dependência funcional no Brasil: desigualdades e desafios no contexto da primeira onda da pandemia de COVID-19 / Homecare of elderly Brazilians with functional dependency: inequalities and challenges during the first wave of the COVID-19 pandemic / El cuidado domiciliario de ancianos con dependencia funcional en Brasil: desigualdades y desafíos en el contexto de la primera ola de la pandemia de COVID-19

O artigo tem o objetivo de analisar o efeito da pandemia na carga de cuidado da pessoa idosa com dependência funcional, segundo a presença de cuidador contratado e condições socioeconômicas no ano de 2020. Utilizou-se a ConVid - Pesquisa de Comportamentos de 2020 como fonte de dados. Calculou-se a distribuição percentual e a prevalência da população que mora com idoso com dependência funcional durante a pandemia da COVID-19, segundo sexo, raça/cor da pele e renda. Estimou-se o teste de qui-quadrado de Pearson e a razão da prevalência de aumento do trabalho doméstico, ajustando-se modelos de regressão de Poisson com a variância robusta. Utilizou-se o intervalo de 95% de confiança (IC95%). Entre adultos que moravam com idoso, 8,1% (IC95%: 7,1-9,4) tinham pelo menos um idoso com dependência funcional. Durante a pandemia, 11,7% (IC95%: 8,5-16,0) deixaram de ter cuidador, o que se explica pelo distanciamento social para redução de risco de contágio e/ou pela diminuição da capacidade aquisitiva das famílias. Aqueles que perderam cuidador remunerado durante a pandemia tiveram maior probabilidade de aumento da carga do cuidado, independentemente da condição socioeconômica. Verificou-se a distribuição desigual do trabalho de cuidar na população, que se intensificou com a chegada da pandemia da COVID-19. A piora da carga de cuidado de idoso com dependência funcional foi mais acentuada entre os grupos mais privilegiados, como brancos e de maior renda. Uma hipótese é a de que os grupos mais vulneráveis já tivessem uma alta carga de cuidado antes da pandemia. A crise no cuidado se agrava diante do desmonte da atenção básica, redução do suporte social às famílias brasileiras no contexto de pandemia e aumento do desemprego, diminuindo a capacidade de contratação de cuidador.

The article aims to analyze the pandemic's effect on the burden of care for elderly persons with functional dependency according to the presence of hired caregivers and socioeconomic conditions in the year 2020. Data were obtained from the ConVid - Behavior Survey of 2020. We calculated the percentage distribution and prevalence of the population living with elderly persons with functional dependency during the COVID-19 pandemic according to sex, race/color, and income. We estimated the Pearson chi-square test and prevalence ratio for the increase in household work, fitting Poisson regression models with robust variance and using 95% confidence intervals (95%CI). Among adults living with elderly individuals, 8.1% (95%CI: 7.1-9.4) had at least one elderly person with functional dependency. During the pandemic, 11.7% (95%CI: 8.5-16.0) stopped hiring third-party caregivers, which can be explained by social distancing to reduce risk of transmission and/or by the decline in families' purchasing power. Those who lost hired caregivers during the pandemic were more likely to experience an increase in the burden of care, regardless of their socioeconomic status. There was an unequal distribution of caregiving work in the population, intensified by the arrival of the COVID-19 pandemic. The heavier load of care for elderly persons with functional dependency was sharper in more socioeconomically privileged groups such as whites and those with higher income. One hypothesis is that more vulnerable groups already bore a high burden of care before the pandemic. The crisis in care has been aggravated by the dismantling of primary healthcare in Brazil, a reduction in social support for Brazilian families during the pandemic, and rising unemployment, decreasing families' capacity to hire caregivers.

El artículo tiene como objetivo analizar el efecto de la pandemia en la carga de cuidado de la persona anciana con dependencia funcional, según la presencia del cuidador contratado y condiciones socioeconómicas, durante el año 2020. Se utilizó la ConVid - Encuesta de Comportamientos de 2020 como fuente de datos. Se calculó la distribución porcentual y la prevalencia de la población que vive con anciano con dependencia funcional durante la pandemia de COVID-19, según sexo, raza/color de piel y renta. Se estimó el test de chi-cuadrado de Pearson y la razón de la prevalencia de aumento del trabajo doméstico, ajustándose a modelos de regresión de Poisson con variancia robusta. Se utilizó el intervalo de 95% de confianza (IC95%). Entre adultos que vivían con ancianos, un 8,1% (IC95%: 7,1-9,4) tenían por lo menos un anciano con dependencia funcional. Durante la pandemia, un 11,7% (IC95%: 8,5-16,0) dejaron de tener cuidador, lo que se explica por el distanciamiento social para la reducción del riesgo de contagio y/o por la disminución de la capacidad adquisitiva de las familias. Aquellos que perdieron un cuidador remunerado durante la pandemia tuvieron una mayor probabilidad de aumento de la carga del cuidado, independientemente de la condición socioeconómica. Se verificó la distribución desigual del trabajo de cuidar en la población, que se intensificó con la llegada de la pandemia de COVID-19. El empeoramiento de la carga de cuidado de anciano con dependencia funcional fue más acentuada entre los grupos más privilegiados, como blancos y de mayor renta. Una hipótesis es la de que los grupos más vulnerables ya tuvieran una alta carga de cuidado antes de la pandemia. La crisis en el cuidado se agrava ante el desmantelamiento de la Atención Básica, reducción del apoyo social a las familias brasileñas en el contexto de pandemia y aumento del desempleo, disminuyendo la capacidad de contratación de cuidadores.

Infective endocarditis caused by Enterobacteriaceae: phenotypic and molecular characterization of Escherichia coli and Klebsiella pneumoniae in Rio de Janeiro, Brazil.

The etiological agent for infective endocarditis (IE), a life-threatening disease, is usually gram-positive bacteria. However, gram-negative bacteria can rarely cause IE and 4% of cases are associated with morbidity and mortality. This study aimed to characterize Escherichia coli and Klebsiella pneumoniae isolates from the blood of patients with IE. The characteristics of blood isolates were compared with those of urinary isolates from patients with urinary tract infections (UTIs). The results of this study revealed that K. pneumoniae isolates from patients with IE were phylogenetically related to those from patients with UTI. Additionally, the resistance phenotype, resistance gene, virulence gene, and plasmid profiles were similar between the blood and urinary isolates. The isolates belonging to the sequence types (STs) 76, 36, 101 (K. pneumoniae), and 69 (E. coli) are reported to be associated with drug resistance. The Enterobacteriaceae isolates from patients with IE did not produce extended-spectrum ß-lactamase or carbapenemase. Additionally, this study investigated the virulence phenotype, biofilm formation ability, and the ability to adhere to the epithelial cells in vitro of the isolates. The isolates from patients with IE exhibited weaker biofilm formation ability than the urinary isolates. All isolates from patients with IE could adhere to the renal epithelial cells. However, three isolates from patients with UTIs could not adhere to the epithelial cells. The closely related K. pneumoniae isolates (648, KP1, KP2, KP3, and KP4) could not form biofilms or adhere to the epithelial cells. In summary, the molecular analysis revealed that the genetic characteristics of IE-causing K. pneumoniae and E. coli were similar to those of UTI-causing isolates. These isolates belonged to the STs that are considered treatable. Genetically similar isolates did not exhibit the same virulence phenotype. Thus, these non-hypervirulent clones must be monitored as they can cause complex infections in susceptible hosts.

Salivary glands are a target for SARS-CoV-2: a source for saliva contamination.

The ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8-83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70-100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivary glands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID-19 and highlight this biological fluid's role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Survival of salivary gland cancer stem cells requires mTOR signaling.

Advanced salivary gland mucoepidermoid carcinoma (MEC) is a relentless cancer that exhibits resistance to conventional chemotherapy. As such, treatment for patients with advanced MEC is tipically radical surgery and radiotherapy. Facial disfigurement and poor quality of life are frequent treatment challenges, and many patients succumb to loco-regional recurrence and/or metastasis. We know that cancer stem-like cells (CSC) drive MEC tumorigenesis. The current study tests the hypothesis that MEC CSC are sensitive to therapeutic inhibition of mTOR. Here, we report a correlation between the long-term clinical outcomes of 17 MEC patients and the intratumoral expression of p-mTOR (p = 0.00294) and p-S6K1 (p = 0.00357). In vitro, we observed that MEC CSC exhibit constitutive activation of the mTOR signaling pathway (i.e., mTOR, AKT, and S6K1), unveiling a potential strategy for targeted ablation of these cells. Using a panel of inhibitors of the mTOR pathway, i.e., rapamycin and temsirolimus (mTOR inhibitors), buparlisib and LY294002 (AKT inhibitors), and PF4708671 (S6K1 inhibitor), we observed consistently dose-dependent decrease in the fraction of CSC, as well as inhibition of secondary sphere formation and self-renewal in three human MEC cell lines (UM-HMC-1,-3A,-3B). Notably, therapeutic inhibition of mTOR with rapamycin or temsirolimus induced preferential apoptosis of CSC, when compared to bulk tumor cells. In contrast, conventional chemotherapeutic drugs (cisplatin, paclitaxel) induced preferential apoptosis of bulk tumor cells and accumulation of CSC. In vivo, therapeutic inhibition of mTOR with temsirolimus caused ablation of CSC and downregulation of Bmi-1 expression (major inducer of stem cell self-renewal) in MEC xenografts. Transplantation of MEC cells genetically silenced for mTOR into immunodeficient mice corroborated the results obtained with temsirolimus. Collectively, these data demonstrated that mTOR signaling is required for CSC survival, and unveiled the therapeutic potential of targeting the mTOR pathway for elimination of highly tumorigenic cancer stem-like cells in salivary gland mucoepidermoid carcinoma.

Challenges and Decision Making for the Classification of Two Complex Periodontal Cases.

FOCUSED CLINICAL QUESTION: What are the fundamental debates and questions related to the newly developed two-vector system for classification of periodontal diseases that have emerged as to how to accurately assign, stage, and grade periodontitis cases? The aim of the present manuscript is to demonstrate the essential thought processes that are needed in utilizing the new periodontitis classification system to diagnose two gray zone cases. SUMMARY: Clinical case 1 includes an 83-year-old male diagnosed with periodontitis and classified as Stage III Generalized Grade B periodontitis, while clinical case 2, a 73-year-old male was classified as presenting Stage IV Generalized Grade B periodontitis. Although clinical and radiographic evaluations revealed similarities between the cases, the thought process that includes clinical judgment is described to guide a more accurate diagnosis following the guidelines of the new classification system. CONCLUSION: The two cases demonstrated here offer an opportunity for clinicians to recognize the essential role of sound clinical judgment in certain cases when applying the new periodontal disease classification system and also clarify questions emerging from implementing this classification system.

Salivary glands are a target for SARS-CoV-2: a source for salivacontamination

The ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed innasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples ofsalivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immu-nohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qual-itative and quantitative viral proles in salivary glands. The study included 13 female and 11 male patients, with amean age of 53.12 years (range 8­83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70­100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm,acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of acluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showedmorphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as wellas nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei.Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cellsof major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivaryglands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate theuse of saliva as a diagnostic method for COVID-19 and highlight this biological uid's role in spreading the disease.© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.