Genetic mechanisms of multiciliated cell development: from fate choice to differentiation in zebrafish and other models.

Multiciliated cells (MCCS) form bundles of cilia and their activities are essential for the proper development and physiology of many organ systems. Not surprisingly, defects in MCCs have profound consequences and are associated with numerous disease states. Here, we discuss the current understanding of MCC formation, with a special focus on the genetic and molecular mechanisms of MCC fate choice and differentiation. Furthermore, we cast a spotlight on the use of zebrafish to study MCC ontogeny and several recent advances made in understanding MCCs using this vertebrate model to delineate mechanisms of MCC emergence in the developing kidney.

(Zebra)fishing for nephrogenesis genes.

Kidney disease is a devastating condition affecting millions of people worldwide, where over 100,000 patients in the United States alone remain waiting for a lifesaving organ transplant. Concomitant with a surge in personalized medicine, single-gene mutations, and polygenic risk alleles have been brought to the forefront as core causes of a spectrum of renal disorders. With the increasing prevalence of kidney disease, it is imperative to make substantial strides in the field of kidney genetics. Nephrons, the core functional units of the kidney, are epithelial tubules that act as gatekeepers of body homeostasis by absorbing and secreting ions, water, and small molecules to filter the blood. Each nephron contains a series of proximal and distal segments with explicit metabolic functions. The embryonic zebrafish provides an ideal platform to systematically dissect the genetic cues governing kidney development. Here, we review the use of zebrafish to discover nephrogenesis genes.

Selenium increases photosynthetic capacity, daidzein biosynthesis, nodulation and yield of peanuts plants (Arachis hypogaea L.).

This study aimed to investigate the roles of selenium (Se) application on the profile of photosynthetic pigments, oxidant metabolism, flavonoids biosynthesis, nodulation, and its relation to agronomic traits of peanut plants. Two independent experiments were carried out: one conducted in soil and the other in a nutrient solution. When the plants reached the V2 growth stage, five Se doses (0, 7.5, 15, 30, and 45 µg kg-1) and four Se concentrations (0, 5, 10, and 15 µmol L-1) were supplied as sodium selenate. The concentration of photosynthetic pigments, activity of antioxidant enzymes and the concentration of total sugars in peanut leaves increased in response to Se fertilization. In addition, Se improves nitrogen assimilation efficiency by increasing nitrate reductase activity which results in a higher concentration of ureides, amino acids and proteins. Se increases the synthesis of daidzein and genistein in the root, resulting in a greater number of nodules and concentration and transport of ureides to the leaves. Se-treated plants showed greater growth, biomass accumulation in shoots and roots, yield and Se concentration in leaves and grains. Our results contribute to food security and also to increase knowledge about the effects of Se on physiology, biochemistry and biological nitrogen fixation in legume plants.

Can the application of low doses of paraquat induce the hormesis effect in upland rice?

This study aimed to verify the effects of the application of paraquat low doses on the agronomic traits of upland rice in two different application modes. The treatments consisted of a combination of 6 low doses of the paraquat (0; 20; 40; 60; 80 and 120 g a.i. ha-1) and 2 application modes of low doses a) single application performed between active tillering and floral differentiation b) application split into four applications, the first being carried out at the beginning of active tillering, the second being carried out between active tillering and floral differentiation, the third application carried out after floral differentiation and the fourth application carried out after flowering with 25% of the dose in each application. The application of low doses of paraquat does not promote the hormesis effect of upland rice. The increase in the frequency of the plant to the herbicide caused by the splitting of applications negatively affected the plant height, number of spikelets per panicle, yield, leaf nitrogen and sulfur as the low doses levels were increased. On the other hand, there is no influence of paraquat low doses levels when single applied to the agronomic traits of upland rice.

Does the glufosinate-ammonium herbicide have the potential to induce the hormesis effect in upland rice?

This study aimed to evaluate the effects of low doses of the herbicide glufosinate-ammonium in different application modes in the vegetative development of upland rice. The treatment consisted of a combination of five low doses (0; 15; 30; 60; and 100 g a.i. ha-1) of the herbicide glufosinate-ammonium and four application modes of the low doses: single between active tillering (AT) and floral differentiation (FD); single after FD; split in two (the first at the beginning of the AT and the second between AT and FD; split in three (the first at the beginning of the AT, the second between the AT and the FD and the third after the FD, with. There was no hormesis effect on rice crop due to low doses of glufosinate-ammonium. The vegetative development of rice plants was reduced by the application of low doses in all application modes with lower plant height, dry weight, number of panicles, and effective tiller.

Can the application of low doses of glyphosate induce the hormesis effect in upland rice?

The aim of this research was to verify the effect of glyphosate low doses on leaf macronutrient levels and vegetative traits of upland rice in two growth stages. The treatments were arranged in 2 × 6 factorial scheme. The first factor consisted of applications in two growth stages of rice crop (tillering and floral differentiation) and the second factor was the low doses of glyphosate (0, 10, 20, 40, 70 and 100 g e.a. ha-1). In full bloom, the chlorophyll content was determined in a sample of 30 flag leaves. In these leaves, the contents of macronutrients were determined. At the maturity of the rice plant, the stem count was performed per m2, effective tiller and the plant height was measured. The low doses did not influence the leaf content of macronutrients. The plant height was reduced with an increase in the low doses of glyphosate, having a greater effect on the floral differentiation stage. When applied low doses of glyphosate at the floral differentiation stage, chlorophyll content increases and when applied to tillering there is a linear decrease in chlorophyll content. The number of stems increases with the application of low doses at floral differentiation.

Metachronic Breast and Cerebellar Neoplasm in a Young Patient.

Several factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.

Diversos fatores desencadeiam o desenvolvimento de mutações genéticas que são responsáveis por originar uma neoplasia. O meduloblastoma é uma neoplasia cerebelar maligna e invasiva que acomete crianças e adultos jovens. O carcinoma mucinoso é um tipo de câncer de mama especial por ser um subtipo atípico de carcinoma invasivo, que acomete com maior frequência mulheres de idade avançada e representa entre 1 a 7% do total de neoplasias mamárias. O caso relatado tem como objetivo mostrar a raridade da ocorrência do meduloblastoma desmoplásico e carcinoma mucinoso mamário em uma paciente jovem em um curto período de tempo, em diferentes sítios sem ligação anatômica direta e sem ocorrência de metástase. Inicialmente, esta paciente possuía um meduloblastoma desmoplásico e foi tratada com tumorectomia e radioterapia. Após 13 meses, a paciente foi diagnosticada com carcinoma mucinoso de mama, sendo submetida a mastectomia, quimioterapia adjuvante e atualmente está sendo tratada com endocrinoterapia. Concluímos, com base na característica metacrônica da neoplasia e características clínicas, que a paciente apresenta a síndrome de Li-Fraumeni, doença autossômica dominante com mutação do gene TP53, que é o principal gene envolvido nesta síndrome. Por não apresentar as características completas do fenótipo da síndrome, a paciente pode assim ser classificada como portadora de uma variante da síndorme de Li-Fraumeni ou síndrome do tipo Li-Fraumeni.

Primary extraperitoneal rectum lymphoma in AIDS patient / Linfoma primário de reto extraperitoneal em paciente SIDA

ABSTRACT Introduction The gastrointestinal lymphoma can be classified in primary or secondary, and this is important regarding diagnosis and subsequent treatment. Primary gastrointestinal lymphoma of the rectum is rare and therefore lacks data in medical literature. Its incidence has been increasing and that fact may be related to a higher incidence in immunosuppressive therapy and immunosuppressive diseases (such as AIDS). Metodology 19 articles have been reviewed, searched online on the Scielo and PubMed databases. The goal was to increase data available regarding this pathology and improve its therapy. Discussion Primary GI lymphoma of the rectum presents as hematochezia, rectal pain, change in bowel habits. PET/CT is the first choice exam to pursue investigation; however abdominal CT and MRI reveal sufficient information and are much more available in daily practice. Plasmablastyc lymphoma is an aggressive subtype and is usually associated with AIDS patients. There are no available treatment protocols for this specific type of lymphoma and colonic lymphoma's therapy is usually used for this patient (such as ECHOP and CHOP). Conclusion As rare as this pathology is, this article aims to improve the available data and provide useful information regarding diagnosis and therapy.

RESUMO Introdução O linfoma do TGI pode ser dividido entre primário e secundário, com importância diagnóstica e terapêutica. O linfoma primário de reto é patologia rara, pouco relatada em literatura médica. Sua incidência tem aumentado e possivelmente esse fenômeno esteja associado ao aumento no numero de pacientes com imunossupressão (seja por SIDA ou drogas imunossupressoras). Metodologia Foram revisados 19 artigos nas bases de dados Scielo e PubMed, com o objetivo de aumentar o número de relatos dessa patologia e consequentemente expandir o conhecimento disponível, visando melhorar a terapêutica e, principalmente, o diagnóstico desse tipo de linfoma. Discussão Quando o linfoma tem seu sítio primário no reto, as principais manifestações são sangramento, dor retal, tenesmo e mudança nos hábitos intestinais (diarreia ou constipação). O exame de investigação de escolha é o PET/CT, porém a TC e RNM fornecem as informações necessárias e são mais disponíveis na prática clínica. O linfoma plasmablástico é um subtipo bastante agressivo e associado aos pacientes com SIDA. Não existem ainda protocolos definidos para o tratamento do linfoma primário de reto, sendo optado por seguir a mesma terapêutica dos linfomas de cólon com esquemas EPOCH e CHOP. Conclusão Por se tratar de patologia rara e pouco descrita na literatura, espera-se que este relato contribua na formação de protocolos de tratamento específicos.

Metachronic breast and cerebellar neoplasm in a young patient / Neoplasias mamária e cerebelar metacrônicas em uma paciente jovem

Abstract Several factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.

Resumo Diversos fatores desencadeiam o desenvolvimento de mutações genéticas que são responsáveis por originar uma neoplasia. O meduloblastoma é uma neoplasia cerebelar maligna e invasiva que acomete crianças e adultos jovens. O carcinoma mucinoso é um tipo de câncer de mama especial por ser um subtipo atípico de carcinoma invasivo, que acomete com maior frequência mulheres de idade avançada e representa entre 1 a 7% do total de neoplasias mamárias. O caso relatado tem como objetivo mostrar a raridade da ocorrência do meduloblastoma desmoplásico e carcinoma mucinoso mamário em uma paciente jovem em um curto período de tempo, em diferentes sítios sem ligação anatômica direta e sem ocorrência de metástase. Inicialmente, esta paciente possuía um meduloblastoma desmoplásico e foi tratada com tumorectomia e radioterapia. Após 13 meses, a paciente foi diagnosticada com carcinoma mucinoso de mama, sendo submetida a mastectomia, quimioterapia adjuvante e atualmente está sendo tratada com endocrinoterapia. Concluímos, com base na característica metacrônica da neoplasia e características clínicas, que a paciente apresenta a síndrome de Li-Fraumeni, doença autossômica dominante com mutação do gene TP53, que é o principal gene envolvido nesta síndrome. Por não apresentar as características completas do fenótipo da síndrome, a paciente pode assim ser classificada como portadora de uma variante da síndorme de Li-Fraumeni ou síndrome do tipo Li-Fraumeni.

Surface parameters of as-built additive manufactured metal for intraosseous dental implants.

STATEMENT OF PROBLEM: To improve osseointegration, current machined implants are submitted to different surface treatments such as airborne-particle abrasion and acid etching. Although additive manufacturing has allowed the fabrication of implants with custom design, porosity, and roughness, whether good osseointegration can be achieved without subsequent surface treatments is still unclear. PURPOSE: The purpose of this in vitro study was to investigate the feasibility of using additive manufacturing technology for dental implants without the use of subsequent surface treatments. MATERIAL AND METHODS: The roughness, wettability, and surface energy of a flat test stainless-steel specimen produced from a 3D printer were evaluated. The roughness measurements were obtained by using a mechanical contact profilometer. The wettability was characterized by the sessile drop method by using deionized water and ethylene glycol. The surface energy values were calculated by using the Owens, Wendt, Rabel, and Kaeble (OWRK) computational method. RESULTS: The experimental data obtained were Ra=4.55 µm, Rq=5.64 µm, RSm=0.235 mm, Rsk=-0.071, Rku=3.740, Rdq=13 degrees; water contact angle=66 degrees; ethylene glycol contact angle=57 degrees; surface energy=38 mN/m. The measured values were compared with data reported in the literature for commercially available implants. The parameter Ra, which is the most used parameter to describe the surface of dental implants, was 50%, 270%, and 329% higher than that reported in the literature for commercial dental implants. The surface energy was 10% and 19% lower than the representative values in the literature for commercial dental implants. CONCLUSIONS: The results indicate that specimens fabricated by additive manufacturing had higher roughness and lower surface energy than reported results in the literature. Therefore, additive manufacturing was found to produce suitable surface parameters for dental implants, and subsequent surface treatments could be removed from the manufacturing process.

Morbihan disease: a therapeutic challenge

Abstract: Morbihan disease is a rare condition characterized by chronic and persistent erythematous solid edema localized on the face. It is believed to be a complication of rosacea and may occur at any stage of the disease. Features of this condition include variable therapeutic response and great refractoriness. We report a case of a 61-year-old man with rosacea history diagnosed with Morbihan disease, who showed excellent therapeutic response with the combination of deflazacort and oral isotretinoin but developed recurrence after corticosteroid discontinuation. We believe that in severe cases of lymphedema of the face this combination is effective and corticosteroid suspension should be done slowly and gradually.

Morbihan disease: a therapeutic challenge.

Morbihan disease is a rare condition characterized by chronic and persistent erythematous solid edema localized on the face. It is believed to be a complication of rosacea and may occur at any stage of the disease. Features of this condition include variable therapeutic response and great refractoriness. We report a case of a 61-year-old man with rosacea history diagnosed with Morbihan disease, who showed excellent therapeutic response with the combination of deflazacort and oral isotretinoin but developed recurrence after corticosteroid discontinuation. We believe that in severe cases of lymphedema of the face this combination is effective and corticosteroid suspension should be done slowly and gradually.

18F-FET PET Uptake Characteristics in Patients with Newly Diagnosed and Untreated Brain Metastasis.

In patients with brain metastasis, PET using labeled amino acids has gained clinical importance, mainly regarding the differentiation of viable tumor tissue from treatment-related effects. However, there is still limited knowledge concerning the uptake characteristics in patients with newly diagnosed and untreated brain metastases. Hence, we evaluated the uptake characteristics in these patients using dynamic O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET. Methods: Patients with newly diagnosed brain metastases without prior local therapy and 18F-FET PET scanning were retrospectively identified in 2 centers. Static and dynamic PET parameters (maximal/mean tumor-to-brain-ratio [TBRmax/TBRmean], biologic tumor volume [BTV], and time-activity curves with minimal time to peak [TTPmin]) were evaluated and correlated with MRI parameters (maximal lesion diameter, volume of contrast enhancement) and originating primary tumor. Results: Forty-five brain metastases in 30 patients were included. Forty of 45 metastases (89%) had a TBRmax ≥ 1.6 and were classified as 18F-FET-positive (median TBRmax, 2.53 [range, 1.64-9.47]; TBRmean, 1.86 [range, 1.63-5.48]; and BTV, 3.59 mL [range, 0.04-23.98 mL], respectively). In 39 of 45 brain metastases eligible for dynamic analysis, a wide range of TTPmin was observed (median, 22.5 min; range, 4.5-47.5 min). All 18F-FET-negative metastases had a diameter of ≤ 1.0 cm, whereas metastases with a > 1.0 cm diameter all showed pathologic 18F-FET uptake, which did not correlate with lesion size. The highest variability of uptake intensity was observed within the group of melanoma metastases. Conclusion: Untreated metastases predominantly show increased 18F-FET uptake, and only a third of metastases < 1.0 cm were 18F-FET-negative, most likely because of scanner resolution and partial-volume effects. In metastases > 1.0 cm, 18F-FET uptake intensity was highly variable and independent of tumor size (even intraindividually). 18F-FET PET might provide additional information beyond the tumor extent by reflecting molecular features of a metastasis and might be a useful tool for future clinical applications, for example, response assessment.

Multiple cutaneous melanomas associated with gastric and brain metastases

Abstract The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.

Multiple cutaneous melanomas associated with gastric and brain metastases.

The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

INTRODUCTION: Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. METHODOLOGY: Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. RESULTS: It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. CONCLUSIONS: We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.