The mutational spectrum of FOXA2 in endometrioid endometrial cancer points to a tumor suppressor role.

BACKGROUND: Forkhead box protein A2 (FOXA2) plays an important in development, cellular metabolism and tumorigenesis. The Cancer Genome Atlas (TCGA) identified a modest frequency of FOXA2 mutations in endometrioid endometrial cancers (EEC). The current study sought to determine the relationship between FOXA2 mutation and clinicopathologic features in EEC and FOXA2 expression. METHODS: Polymerase chain reaction (PCR) amplification and sequencing were used to identify mutations in 542 EEC. Western blot, quantitative reverse transcriptase PCR (qRT-PCR) and immunohistochemistry (IHC) were used to assess expression. Methylation analysis was performed using combined bisulfite restriction analysis (COBRA) and sequencing. Chi-squared, Fisher's exact, Student's t- and log-rank tests were performed. RESULTS: Fifty-one mutations were identified in 49 tumors (9.4% mutation rate). The majority of mutations were novel, loss of function (LOF) (78.4%) mutations, and most disrupted the DNA-binding domain (58.8%). Six recurrent mutations were identified. Only two tumors had two mutations and there was no evidence for FOXA2 allelic loss. Mutation status was associated with tumor grade and not associated with survival outcomes. Methylation of the FOXA2 promoter region was highly variable. Most tumors expressed FOXA2 at both the mRNA and protein level. In those tumors with mutations, the majority of cases expressed both alleles. CONCLUSION: FOXA2 is frequently mutated in EEC. The pattern of FOXA2 mutations and expression in tumors suggests complex regulation and a haploinsufficient or dominant-negative tumor suppressor function. In vitro studies may shed light on how mutations in FOXA2 affect FOXA2 pioneer and/or transcription factor functions in EEC.

Social determinants of self-perceived discrimination in Spain.

OBJECTIVES: To analyse the association between self-perceived discrimination and social determinants (social class, gender, country of origin) in Spain, and further to describe contextual factors which contribute to self-perceived discrimination. METHODS: Cross-sectional design using data from the Spanish National Health Survey (2006). The dependent variable was self-perceived discrimination, and independent and stratifying variables were sociodemographic characteristics (e.g. sex, social class, country of origin, educational level). Logistic regression was used. RESULTS: The prevalence of self-perceived discrimination was 4.2% for men and 6.3% for women. The likelihood of self-perceived discrimination was higher in people who originated from low-income countries: men, odds ratio (OR) 5.59 [95% confidence interval (CI) 4.55-6.87]; women, OR 4.06 (95% CI 3.42-4.83). Women were more likely to report self-perceived discrimination by their partner at home than men [OR 8.35 (95% CI 4.70-14.84)]. The likelihood of self-perceived discrimination when seeking work was higher among people who originated from low-income countries than their Spanish counterparts: men, OR 13.65 (95% CI 9.62-19.35); women, OR 10.64 (95% CI 8.31-13.62). In comparison with Spaniards, male white-collar workers who originated from low-income countries [OR 11.93 (95% CI 8.26-17.23)] and female blue-collar workers who originated from low-income countries (OR 1.6 (95% CI 1.08-2.39)] reported higher levels of self-perceived discrimination. CONCLUSIONS: Self-perceived discrimination is distributed unevenly in Spain and interacts with social inequalities. This particularly affects women and immigrants.

Toothpaste use in Peruvian children during COVID-19 pandemic: results from a National Demographic and Health Survey.

PURPOSE: To determine the impact of COVID-19 pandemic on use of toothpaste in Peruvian children. METHODS: A national database of Peruvian children from 0 to 11 years old was used to develop a cross-sectional study, with a final sample of 51, 013 subjects. Data were obtained of results of the Demographic and Family Health Survey (ENDES); the questionnaire was self-reported. The use of toothpaste and fluoride concentration in toothpaste were dependent variables, and for the independent variable, the year was considered; in addition, other covariates were included. The statistical analyses applied were descriptive, bivariate, and multivariate tests. RESULTS: Use of toothpaste was 98.99% (n = 50,134), while fluoride toothpaste with < 1000 ppm was used by 77.29% (n = 27,366). For bivariate analysis, use of toothpaste was associated with place and area of residence, altitude, natural region, and age; for use of fluoride toothpaste with minimum 1000 ppm, there was an association with place and area of residence, natural region, wealth index, and age. In a multivariate manner, year only presented a positive association with use of fluoride toothpaste < 1000 ppm (RPa:1.04; 95%CI 1.01-1.07). CONCLUSIONS: Year 2020 of COVID-19 pandemic had a positive impact on the use of < 1000 ppm fluoride toothpaste in Peruvian children.

Assessing host-parasite specificity through coprological analysis: a case study with species of Corynosoma (Acanthocephala: Polymorphidae) from marine mammals.

In this paper we report an investigation of the utility of coprological analysis as an alternative technique to study parasite specificity whenever host sampling is problematic; acanthocephalans from marine mammals were used as a model. A total of 252 scats from the South American sea lion, Otaria flavescens, and rectal faeces from 43 franciscanas, Pontoporia blainvillei, from Buenos Aires Province, were examined for acanthocephalans. Specimens of two species, i.e. Corynosoma australe and C. cetaceum, were collected from both host species. In sea lions, 78 out of 145 (37.9%) females of C. australe were gravid and the sex ratio was strongly female-biased. However, none of the 168 females of C. cetaceum collected was gravid and the sex ratio was not female-biased. Conversely, in franciscanas, 14 out of 17 (82.4%) females of C. cetaceum were gravid, but none of 139 females of C. australe was, and the sex ratio of C. cetaceum, but not that of C. australe, was female-biased. In putative non-hosts, the size of worms was similar to that from specimens collected from prey. Results suggest that both acanthocephalans contact sea lions and franciscanas regularly. However, C. australe and C. cetaceum cannot apparently reproduce, nor even grow, in franciscanas and sea lions, respectively. Coprological analysis may represent a useful supplementary method to investigate parasite specificity, particularly when host carcasses are difficult to obtain.

Impact of COVID-19 on the Knowledge and Attitudes of Dentists toward Teledentistry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has created a new scenario for dental practice, and teledentistry (TD) is a field of relevance for dentists. OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on the knowledge, practices, and expectations of dentists toward TD and its association with sociodemographic variables. METHODS: A cross-sectional survey was administered to dentists in Colombia as part of global research on the impact of COVID-19 on dentistry. The core questionnaire included 5 additional questions on TD that were added by the Colombian research team in 5 domains about TD: Q1, knowledge; Q2, practices; Q3, expectations; Q4, usefulness; and Q5, reimbursement. Sociodemographic variables were also measured. The questionnaire was validated in a pilot test and administered via digital media. Descriptive and bivariate analysis for sociodemographic and TD variables were done. For the evaluation of the chances of a determined answer, an ordinal multinomial logistic regression (Q1 and Q2) and binomial logistic regression (Q3 and Q5) analyses were made. RESULTS: In total, 5,370 dentists answered the survey (women: 3,878; mean age: 45 y). The response rate of the survey was 16.84%. Knowledge and practice of TD before the COVID-19 pandemic were both low (25.75% and 12.42%, respectively); however, since the beginning of the current pandemic, knowledge increased by 62.72% and practice by 42.53%. Some 93.1% of respondents considered that TD could be useful in their clinical practice, and 59.55% would consider practicing it after the pandemic. A high number of dentists (88.58%) did not charge for these services. Logistic regressions showed significant differences according to sociodemographic variables. CONCLUSIONS: The COVID-19 pandemic has had a great impact on TD, increasing knowledge and practice significantly. Dentists expect to continue practicing TD in the future. However, some geographical, technological, and attitudinal barriers need to be broken down to increase daily use of TD. KNOWLEDGE TRANSFER STATEMENT: This article provides an overview about the impact of COVID-19 pandemic in the knowledge and attitudes about teledentistry (TD) in general dentists and both clinical and nonclinical specialists. Although some barriers to the use of TD continue, this pandemic brought with it a new scenario for dental practice, which must be implemented through training for professionals to increase its use.

Periodontal treatment and glycaemic control in patients with diabetes and periodontitis: an umbrella review.

BACKGROUND: Studies suggest that non-surgical periodontal treatment improves glycaemic control in patients with diabetes and periodontitis. The aim of this umbrella review is to summarize the effects of periodontal treatment on glycaemic control in patients with periodontitis and diabetes. METHODS: A systematic review of systematic reviews with or without meta-analysis published between 1995 and 2015 was performed. Three independent reviewers assessed for article selection, quality and data extraction. RESULTS: Thirteen (13) systematic reviews/meta-analysis were included for qualitative synthesis. A reduction (0.23 to 1.03 percentage points) in the levels of HbA1c at 3 months after periodontal intervention was found. This reduction was statistically significant in 10/12 meta-analysis. One review with sufficiently large samples found a non-significant reduction (-0.014 percentage points; 95% CI -0.18 to 0.16; p = 0.87). Only three studies separated the use of adjunctive antibiotics and found a reduction of 0.36 percentage points but the difference was not statistically significant. CONCLUSIONS: Highly heterogeneous short-term studies with small sample size suggest that periodontal treatment could help improve glycaemic control at 3 months in patients with type 2 diabetes and periodontitis. However, longer term studies having sufficient sample size do not provide evidence that periodontal therapy improves glycaemic control in these patients.

Blood transfusion-acquired hemoglobin C.

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

Case report. Diagnosis of early HIV-1 infection.

The diagnosis of acute infection with human immunodeficiency virus (HIV) presents a challenge for the primary care provider. We present a case of early HIV infection and discuss the limitations of the currently established diagnostic algorithm for HIV infection. We conclude that alternative diagnostic testing for human immunodeficiency virus type 1 (HIV-1) RNA is warranted in certain clinical settings. Appropriate, early diagnosis of HIV infection may improve the patient's outcome and provide additional public health benefits by reducing transmission of disease.

[Small cell pulmonary carcinoma, nephrotic syndrome and kidney failure of rapid evolution]. / Carcinoma pulmonar de peoueñas células, síndrome nefrótico e insuficiencia renal rápidamente evolutiva.

There are different clinical manifestations and various types of glomerular damages associated to neoplasias. The association to nephrotic syndrome is a relatively frequent event. However, rapidly evolutive renal insufficiency with extensive crescentic glomerulonephritis in more than 50% of the glomeruli is not usually thought to be linked to malignant diseases. We present the case of a previously healthy 55 year old man, who suffered a nephrotic syndrome and renal failure of rapid evolution, in whom a small cell lung cancer was detected. He died in three months and at autopsy mesangial proliferation and enlargement of basal membranes with crescents in 90% of the glomeruli were observed. Electronic microscopy also showed enlargement of the basal membrane. Structures consistent with immune-complex depositions were not seen. We reviewed the reported cases of glomerular lesions and neoplasias, and described the 20 cases published with this particular type of glomerular lesions described for the first time in 1976. None of these 20 cases belongs to this variety of lung cancer. Only in 5 patients, rapidly evolutive renal insufficiency was accompanied by nephrotic syndrome, as in the present case. The presence of immunocomplexes is not frequent and it was mentioned in only four cases. The only three cases of small cell lung carcinoma with nephrotic syndrome described in the literature were associated with membranous glomerulonephritis.

[Kabuki syndrome]. / Síndrome de Kabuki.

INTRODUCTION: Kabuki syndrome (OMIM: #147 920) presents as large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, dysplastic ears and in most cases, with mental retardation. Patients have minor and major abnormalities in different systems. Its genetic basis is heterogeneous, but recently has been associated with mutations in gen MLL2. CASE REPORTS: We present two patients with clinical features compatibles with the syndrome, mainly: large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, flat nose, persistent fingertip pads, cardiopathies and renal anomalies. COMMENTARY: The diagnosis of this condition is clinical. The characteristics in the cases are compared with the patients reported in the literature. The importance of early diagnosis is to provide preventive management and an appropriate genetic counseling for the family.

Placental dysferlin expression is reduced in severe preeclampsia.

Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE (n=10) and normotensive controls (n=10). DYSF and MYOF expression were examined using quantitative real-time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level (p=0.03) and 38% lower at the protein level (p=0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villi was observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE.

Carcinoma pulmonar de pequeñas células, síndrome nefrótica e insuficiencia renal rápidamente evolutiva / Small cell pulmonar carcinoma, nephrotic syndrome and kidney failure of rapid evolution

La asociación de síndrome nefrótico con neoplasias es un hecho relativamente frecuente. Por el contrario, la insuficiencia renal rápidamente evolutiva con glomerulonefritis con semilunas extensas como consecuencia de una neoplasia es infrecuente. Presentamos el caso de un hombre de 55 años, previamente sano, que sufrió un síndrome nefrótico y una insuficiencia renal de rápida evolución en quien se detectó un cáncer pulmonar de pequeñas células. En la autopsia, se observaron proliferación mesangial y engrosamiento de las membranas basales con semilunas en el 90 por ciento de los glomérulos. La microscopia electrónica también demonstró engrosamiento de la membrana basal. No se evidenciaron estructuras compatibles con depósitos de inmunocomplejos. Realizamos una revisión de los casos comunicados de asociación de lesiones glomerulares y neoplasias y detallamos los 20 casos publicados con este tipo particular de lesión glomerular. Ninguno pertenece a esta variedad de cáncer de pulmón; los únicos tres casos de carcinoma pulmonar de pequeñas células con síndrome nefrótico referidos en la literatura se asociaron a glomerulonefritis membranosa