Reconstructive surgery and adjuvant radiotherapy for the multimodal approach in oral cancer: a single cancer centre experience.

Introduction and importance: Ablative surgery for oral cancer, irrespective of the histological subtype, causes large tissue defects, functional and aesthetic damage. Microsurgical free flaps have been widely used in reconstruction after resection, with satisfactory success rates in conjunction with adjuvant radiotherapy (RT). This study aims to describe our clinical institutional experience based on the multimodal treatment performed in four cases diagnosed with oral squamous cell carcinoma with the use of different microvascular free flaps and RT. Case series presentation: Four patients underwent reconstructive microsurgery after surgical resection of oral cancer, using three types of free flap: radial forearm fasciocutaneous, osteomyocutaneous fibular, and anterolateral thigh musculocutaneous flaps; RT was performed in Case 2 and Case 3. In the period of 3 years after microsurgical reconstruction and RT, flaps remain clinically stable without failure signs in full patients submitted to multimodal treatment. Clinical discussion: After resection of oral carcinomas, extensive tissue defects can be successfully treated with reconstructive microsurgery using different types of microvascular free flaps. RT for locoregional control is a feasible option and did not seem to interfere with the survival of flaps. Conclusion: An enhance long-term follow-up to assess overall and disease-free survival rates and quality of life must be carried out; however, cohort studies would be necessary for better understanding of the role of each treatment in the multimodal scheme.

Bos indicus Carcasses Suspended by the Pelvic Bone Require a Shorter Aging Time to Meet Consumer Expectations Regarding Meat Quality.

This study evaluated the effects of hanging the carcass by the Achilles tendon (AS) versus pelvic suspension (PS) on meat quality traits. Bos indicus carcasses of two distinct biological types/sex categories comprised 10 young Brangus heifers and 10 Nellore bulls which were finished in a feedlot. Half-carcasses of each biological type/sex category were randomly hung using Achilles suspension (n = 20, AS) or pelvic suspension (n = 20, PS) for 48 h. At boning, longissimus samples were collected for evaluation by untrained consumers for tenderness, liking of flavor, juiciness and overall acceptability, after aging for 5 or 15 days. Objective samples were also tested for shear force (SF), Minolta meat colour, ultimate pH, cooking loss (CL) and purge loss (PL). There was a positive effect (p < 0.01) of PS on the sensory tenderness of Nellore bulls and Brangus heifers aged for 5 days compared to the AS method. At 15 days of aging, difference in sensory tenderness was observed (p < 0.05) in either group. Additionally, an interaction occurred between the suspension method and the aging of Nellore beef (p < 0.05) on liking of flavor, juiciness and overall acceptance, while the same effects were not observed for Brangus beef (p > 0.05). Nellore carcasses submitted to PS tended (p = 0.06) to produce more tender meat than those submitted to AS (SF = 44.62 ± 6.96 vs. 50.41 ± 8.04 N), and lower CL (p < 0.05) were found (27.7 vs. 30.9%). Carcass-suspension methods did not influence meat color, pH or PL in either group (p > 0.05). The PS contributes to improve the quality of Bos indicus bulls loins; in addition, this method allows a reduction in the aging time from 15 to 5 days, and it can be used to supply meat consumer markets which accept a certain level of eating quality.

Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review.

Although vitamin D deficiency resulting from insufficient sunlight exposure or inadequate dietary vitamin D intake is the most common cause of rickets, mutations in genes involved in vitamin D metabolism can cause genetic forms of rickets termed Vitamin D-Dependent Rickets (VDDR). In 2018, Roizen et al. described a new type of VDDR, named VDDR3, caused by a recurrent missense mutation in the CYP3A4 gene that leads to accelerated inactivation of vitamin D metabolites. Here, we describe the third case of VDDR3 due to the same CYP3A4 mutation in a 2-year-old boy with bone deformities associated with poor growth. As in the previously reported cases, this patient had no family history of rickets. Serial measurements of vitamin D metabolites after a single 150,000 IU dose of cholecalciferol demonstrated an accelerated inactivation of 25(OH)D and 1,25(OH)2D. Significant improvement in growth velocity and healing of bone deformities were achieved after a short period of treatment with 10.000 IU of cholecalciferol daily, showing the importance of early recognition and prompt precision therapy of this condition.

Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns. CONCLUSIONS: The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.

Radiation-induced Sarcoma in the Head and Neck: Clinical, Imaging, Histopathological, and Therapeutic Characterization.

Radiation-induced head and neck sarcoma (RIHNS) is a rare and serious long-term complication of radiotherapy (RT), with poor prognosis and high morbidity and mortality. Diagnosis is based on immunohistochemistry and molecular biomarker analysis, and therapy is usually surgical. Other adjuvant therapies might be considered. This case report aimed to describe the clinical, imaging, histopathological, and therapeutic characteristics of a rare case of RIHNS in the mandible after 21 years of RT. A 68-year-old male patient underwent a partial left parotidectomy in 1995, was diagnosed with pleomorphic adenoma, and after recurrence of the lesion in 2000, underwent an ipsilateral total parotidectomy with adjuvant RT. In May 2021, he complained of an ulcerated nodular lesion on the tongue that extended toward the lower gingiva, associated with oral bleeding and difficulties with swallowing. After biopsy in the gingival margin and histopathological analysis, the diagnosis of high-grade spindle-cell sarcoma was established. Complete surgical resection with microsurgical reconstruction using a fibular osteomusculocutaneous free flap was performed. RIHNS could appear after a period of almost 20 years after RT. Surgical resection with reconstructive surgery was a reliable and feasible therapeutic option that showed favorable clinical results after an appropriate follow-up.

Screening of family members of chronic kidney disease patients with Fabry disease mutations: a very important and underrated task / Triagem de familiares de pacientes com doença renal crônica com mutação na doença de Fabry: uma tarefa muito importante e subestimada

ABSTRACT Introduction: Fabry disease is a chronic, progressive, and multi-system hereditary condition, related to an Xq22 mutation in X chromosome, which results in deficiency of alpha-galactosidase enzyme, hence reduced capacity of globotriaosylceramide degradation. Objectives: to evaluate the prevalence of Fabry disease (FD) mutations, as well as its signs and symptoms, among relatives of chronic kidney disease (CKD) patients diagnosed with FD during a previously conducted study, named "Clinical and epidemiological analysis of Fabry disease in dialysis centers in Brazil". Methods: a cross-sectional study was carried out, and data was collected by interviewing the relatives of patients enrolled in the Brazil Fabry Kidney Project and blood tests for both Gb3 dosage and genetic testing. Results: Among 1214 interviewed relatives, 115 (9.47%) were diagnosed with FD, with a predominance of women (66.10%). The most prevalent comorbidities were rheumatologic conditions and systemic hypertension (1.7% each), followed by heart, neurological, cerebrovascular diseases, and depression in 0.9% of individuals. Intolerance to physical exercise and tiredness were the most observed symptoms (1.7%), followed by periodic fever, intolerance to heat or cold, diffuse pain, burn sensation or numbness in hands and feet, reduced or absent sweating, as well as abdominal pain after meals in 0.9%. Conclusion: We found a prevalence of Fabry disease in 9.47% of relatives of CKD patients with this condition, remarkably with a 66.1% predominance of women, which contrasts with previous reports. The screening of family members of FD patients is important, since it can lead to early diagnosis and treatment, thus allowing better quality of life and improved clinical outcomes for these individuals.

RESUMO Introdução: A doença de Fabry é uma condição hereditária crônica, progressiva e multissistêmica, relacionada a uma mutação Xq22 no cromossomo X, que resulta em deficiência da enzima alfa-galactosidase, diminuindo a capacidade de degradação da globotriaosilceramida. Objetivos: avaliar a prevalência de mutações na doença de Fabry, bem como seus sinais e sintomas, em familiares de pacientes com doença renal crônica (DRC) diagnosticados com DF durante um estudo realizado anteriormente, denominado "Análise clínica e epidemiológica da doença de Fabry em centros de diálise no Brasil". Métodos: foi realizado um estudo transversal e os dados foram coletados através da entrevista com familiares de pacientes inscritos no Projeto Rim Fabry Brasil e exames de sangue para dosagem de Gb3 e testes genéticos. Resultados: Dos 1,214 familiares entrevistados, 115 (9,47%) foram diagnosticados com DF, com predomínio de mulheres (66,10%). As comorbidades mais prevalentes foram condições reumatológicas e hipertensão arterial sistêmica (1,7% cada), seguidas por doenças cardíacas, neurológicas, cerebrovasculares e depressão em 0,9% dos indivíduos. Intolerância ao exercício físico e cansaço foram os sintomas mais observados (1,7%), seguidos de febre periódica, intolerância ao calor ou ao frio, dor difusa, sensação de queimação ou dormência nas mãos e nos pés, sudorese reduzida ou ausente, além de dor abdominal após refeições em 0,9%. Conclusão: Encontramos uma prevalência da doença de Fabry em 9,47% dos familiares de pacientes com DRC com essa condição, notadamente com uma predominância de 66,1% de mulheres, o que contrasta com relatos anteriores. A triagem de familiares de pacientes com DF é importante, pois pode levar ao diagnóstico e tratamento precoces, permitindo melhor qualidade de vida e melhores resultados clínicos para esses indivíduos.

Screening of family members of chronic kidney disease patients with Fabry disease mutations: a very important and underrated task.

INTRODUCTION: Fabry disease is a chronic, progressive, and multi-system hereditary condition, related to an Xq22 mutation in X chromosome, which results in deficiency of alpha-galactosidase enzyme, hence reduced capacity of globotriaosylceramide degradation. OBJECTIVES: to evaluate the prevalence of Fabry disease (FD) mutations, as well as its signs and symptoms, among relatives of chronic kidney disease (CKD) patients diagnosed with FD during a previously conducted study, named "Clinical and epidemiological analysis of Fabry disease in dialysis centers in Brazil". METHODS: a cross-sectional study was carried out, and data was collected by interviewing the relatives of patients enrolled in the Brazil Fabry Kidney Project and blood tests for both Gb3 dosage and genetic testing. RESULTS: Among 1214 interviewed relatives, 115 (9.47%) were diagnosed with FD, with a predominance of women (66.10%). The most prevalent comorbidities were rheumatologic conditions and systemic hypertension (1.7% each), followed by heart, neurological, cerebrovascular diseases, and depression in 0.9% of individuals. Intolerance to physical exercise and tiredness were the most observed symptoms (1.7%), followed by periodic fever, intolerance to heat or cold, diffuse pain, burn sensation or numbness in hands and feet, reduced or absent sweating, as well as abdominal pain after meals in 0.9%. CONCLUSION: We found a prevalence of Fabry disease in 9.47% of relatives of CKD patients with this condition, remarkably with a 66.1% predominance of women, which contrasts with previous reports. The screening of family members of FD patients is important, since it can lead to early diagnosis and treatment, thus allowing better quality of life and improved clinical outcomes for these individuals.

Tough aged meat presents greater expression of calpastatin, which presents postmortem protein profile and tenderization related to Nellore steer temperament.

Eighteen Nellore steers were classified as either excitable (high index) or calm (low index) temperament, and high or low WB Shear Force (SF) in Longissimus lumborum at 16 days postmortem, with a subset assigned to four groups: HTHS-high temperament and SF (n = 5); HTLS-high temperament and low SF (n = 4); LTHS-low temperament and high SF (n = 4); LTLS-low temperament and SF (n = 5). Only the second calpastatin peak was detected at 48 h in the all samples, and the calpastatin activity only differed (P < .05) between shear force groups. High WBSF groups had greater expression of CAST gene (P < .05) in the high and low temperament. Western blots showed a calpastatin fragmentation pattern very particular to each group with high molecular weight bands present in the HTHS. Temperament was not a determinant factor in postmortem proteolysis variation. However, greater WBSF aged meat from high temperament animals had greater calpastatin activity and less calpastatin fragments formed during the postmortem period analyzed.

Screening for Fabry Disease in Kidney Disease: a Cross-Sectional Study in Males and Females.

BACKGROUND/AIMS: Evaluate the prevalence of Fabry disease in men and women with kidney disease; and observe the presence and importance of the main signs and symptoms in patients with kidney disease. METHODS: A cross-sectional analysis of secondary data from a multicenter project of Clinical and Epidemiological Analysis of Fabry Disease in 854 Dialysis Centers. A total of 36,442 patients underwent the questionnaire and algorithm; of them, 28,284 were discarded for not presenting signs and symptoms of Fabry disease, while the other 8,087 submitted to blood collection and analysis. All participants signed a Free and Informed Consent Form and a questionnaire was applied. The questionnaire data were analyzed using a computerized algorithm. This program/algorithm analyzes and separates patients into: discarded, patients unlikely to have Fabry disease; suspect, patients who submitted to blood collection. The blood of suspect patients was collected on filter paper for enzyme measurement and genetic testing. A descriptive data analysis was performed and the likelihood ratio was determined. RESULTS: The general prevalence was 0.19% and after use of algorithm was 0.87%. Although more men were screened (59.3%), the prevalence was higher in women (65.1%). The most prevalent signs and symptoms were: heart disease (60.6%), decreased or lack of sweating (42.3%), heat and cold intolerance (28.2%), and pain crises spreading throughout the body (26.8%). CONCLUSION: The prevalence was higher in women, and the most prevalent symptom was heart diseases.

Divergent temperaments are associated with beef tenderness and the inhibitory activity of calpastatin.

Ninety-six feedlot-finished Nellore steers were used to verify the relationship between temperament indicators and meat tenderization. Temperament index (TI), chute score (CS), and average of exit velocity (EV) with CS (AT) presented low positive correlations (P≤0.05) with shear force, either at 2 or 16days postmortem (WBSF-16). The rectal temperature was consistently correlated with temperament indicators (TI, CS, and AT) and WBSF-16. Two groups (n=12) representing the most tender (39.2±4.9N) and most tough meat (94.1±11.8N), based on WBSF-16, were compared for temperament, and calpastatin activity (CASTa) was determined 48h postmortem. The tender group presented lower EV, TI, and AT (P≤0.05). The tender group exhibited lower (P≤0.05) CASTa in the triceps brachii muscle, but there was no difference in CASTa in the longissimus lumborum muscle between WBSF groups. Meat tenderness and inhibitory activity of calpastatin may be associated with divergent temperament indices in zebu cattle.

Eradication of Plant Pathogens in Forest Nursery Irrigation Water.

Interest in rational use and reuse of water has increased in recent years, especially in forest nurseries. However, before water can be reused in nurseries, it must be properly treated to eradicate plant pathogens to reduce risks of pathogen dispersal and losses to disease. In the present study, the efficacy of irrigation water treatment by ultrafiltration and conventional physical-chemical treatment was studied to eliminate Botrytis cinerea, Cylindrocladium candelabrum, Ralstonia solanacearum, and Xanthomonas axonopodis, the pathogens most commonly found in Brazilian forest nurseries. Ultrafiltration eradicated over 99% of R. solanacearum, X. axonopodis, and B. cinerea and 100% of C. candelabrum. The few remaining cells or conidia of R. solanacearum and B. cinerea did not induce disease in irrigated rooted cuttings. Flocculation and fast sand filtration used in physical-chemical treatment completely eliminated C. candelabrum but the other pathogens were only removed after chlorination of the filtered water. Both forms of treatment are viable, practical, and safe methods for plant pathogen removal from irrigation water.

Clinical characteristics of alopecia areata in Down syndrome.

This study was undertaken to better understand clinical characteristics, environmental and physical events in Down syndrome (DS) and alopecia areata (AA). This cross-sectional study included 18 DS patients who were currently presenting or had presented AA. We evaluated gender, age, location and type of AA, presence of autoimmune disease or atopy, AA in first-degree relatives, and environmental, physical, and clinical intercurrences. The mean age of study subjects was 11.6 (SD ± 5.5) years and mean age at AA onset 7.2 (2.5 to 15.2) years. The duration of alopecia episodes varied, with a mean of 2.7 (0.1 to 18.7) years. Recurrence of AA was reported in 27.7% (5/18) of subjects, with a mean number of recurrences of 3.6. Localized type AA was seen in 83.4% of individuals, with the most frequent location on the scalp (100%). Seven of the individuals presented atopy. Fourteen individuals had undergone environmental and/or clinical intercurrences. In conclusion, the most frequent presentation of AA in DS is the non-recurrent, localized form on the scalp, with a varied period of duration. Changes in the individuals' routine occurred in more than half of the study group. We suggest further studies of the psychology and immunogenetics in the etiopathology of AA in DS.

Alopecia areata: aspectos imunogenéticos / Areata alopecia: immunogenetic aspects

A alopecia areata (AA) é um tipo de queda súbita de cabelos, temporária, por vezes recorrente, não cicatricial que pode afetar qualquer área portadora de pêlos; que vem sendo descrita como uma doença auto-imune. Três fatores de suscetibilidade/gravidade têm sido identificados. Alelos HLA foram os primeiros a mostrar uma forte associação com a AA e alguns alelos DQB e DR demonstraram conferir alto risco para doença em estudo de casos-controle e estudos baseados em famílias. Cluster de genes da interleucinas (IL-1), principalmente receptores antagonista da IL-1, mostrou uma forte associação com a gravidade da doença na AA e várias outras doenças inflamatórias e auto-imunes. Finalmente, a associação da AA com a síndrome de Down, a alta freqüência da síndrome poliglandular do tipo 1, devido a mutações no gene auto-imune regulador no cromossomo 21q22.3, e a associação com MX1, outro gene localizado na região da síndrome de Down do cromossomo 21. Conclui-se que existem várias hipóteses possíveis que podem elucidar a patogênese da AA e compreender a presença do infiltrado inflamatório de células imunes. Estas hipóteses podem ser classificadas em três grupos principais: 1) atividade de um terceiro fator: tal como a infecção que induziria a queda do cabelo e da resposta imune; 2) a auto-imunidade induziria à doença: o sistema imune agiria anormalmente contra um folículo capilar em funcionamento normal; 3) a doença induziria a auto-imunidade: o sistema imune agiria normalmente contra um folículo capilar que funciona anormalmente.

DataGenno: building a new tool to bridge molecular and clinical genetics.

Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information. Therefore, it is very challenging for health care professionals and researchers to translate the latest advances in science and medicine into effective clinical interventions and new treatments. In order to overcome this obstacle and promote networking, we are building DataGenno, an online medical and scientific portal. DataGenno has been developed to be a source of information on genetic diseases and syndromes for the needs of all heath care professionals and researchers. Our database will be able to integrate both clinical and molecular aspects of genetic diseases in a fully interactive environment. DataGenno's system already contains clinical and molecular information for 300 diseases, with approximately 6,000 signs and symptoms of these diseases in a database combined with a search engine. Our main goal is to cover all genetic diseases described to date, providing not only clinical information such as morphological and anatomical features but also the most comprehensive molecular genetics/genomics features and available testing information. We are also developing ways to connect DataGenno's portal with Electronic Health Records in order to improve the efficiency of patient care. Additionally, DataGenno's system and search engine will be able to provide tools that will facilitate the discovery and description of new genetic syndromes. In conclusion, we believe that DataGenno's portal will be a helpful and innovative tool for health care professionals, scientists, genetic counselors, and other professionals in the clinical genetics field.

Diferentes modelos de gestão de serviços de saneamento produzem os mesmos resultados? Um estudo comparativo em Minas Gerais com base em indicadores / Different management models for water supply and sanitation services produce the same outcomes? A comparative study in Minas Gerais, Brazil, based on indicators

O trabalho compara grupos de 600 municípios de Minas Gerais, segundo as diferentes categorias de gestores dos serviços de saneamento: (1) aqueles em que a sede tem os sistemas administrados por autarquia municipal, conveniada com a FUNASA; (2) em que a autarquia fora outrora conveniada com a FUNASA; (3) sistemas sob responsabilidade de autarquia municipal; (4) sistemas de abastecimento de água administrados pela COPASA e de esgotamento sanitário pelo município; (5) ambos os serviços administrados pela COPASA; (6) serviços administrados diretamente pela prefeitura e (7) novos municípios, criados após 1989. A pesquisa foi realizada para o ano base de 1998, empregando dados secundários. Foram construídos indicadores operacionais, epidemiológicos e sociais para cada um dos municípios. As comparações foram realizadas por meio de diversas técnicas estatísticas, incluindo multivariadas. Os resultados indicam diferenças entre os gestores e que, além do bom desempenho da COPASA em alguns aspectos, o conjunto de municípios com serviços administrados por autarquias destaca-se positivamente.

The paper compares groups from 600 municipalities, according to different categories of management models: (1) water supply and sanitation (WSS) managed by a municipal autarchy, through cooperation with FUNASA; (2) WSS managed by a municipal autarchy that had had a cooperation agreement with FUNASA; (3) WSS managed by a municipal autarchy; (4) water supply managed by COPASA and sanitation directly by the municipality; (5) both water supply and sanitation managed by COPASA; (6) WSS directly managed by the municipality; (7) new municipalities, created after 1989. The research used data of 1998 from secondary sources. Operational, epidemiological, and social indicators were created for each municipality. The comparisons were performed by several statistical techniques, including multivariate ones. The results indicate differences between the management models and, besides the good performance of COPASA regarding some specific aspects, highlight the positive performance of the models based on the autarchy organization.

Democracias Andinas: chegando tarde à festa? / Andean democracies: late to the party?

After a centuries-old history of oligarchic, populist, and authoritarian institutionality, in recent decades South America has begun the transition to a liberal democratic state model. This new state model harbors the contradiction of being both more democratic and less capable. Namely, it allows public participation and dissent, but with more limited conditions to respond, a role that has been largely transferred to the market, which has become globalized and more complex, while experiencing difficulties in meeting social demands. The tension between democracy and economic limitations, combined with endogenous institutional problems, has sustained a climate of permanent political instability in parts of South America, reproducing fragmentations and conflicts, which are the focus of this study, a comparative analysis of five Andean countries: Bolivia, Peru, Ecuador, Colombia, and Venezuela.

Après une histoire centenaire sous la primauté des institutions oligarchiques, populistes et autoritaires, l'Amérique du Sud semble, depuis quelques décennies, aller vers un État démocratique et libéral. Ce nouveau modèle d'État présente le paradoxe d'être plus démocratique sous certains aspects, tout en étant moins efficace, c'est-à-dire qu'il permet la participation et la contestation publique sans pour autant disposer de moyens pour les satisfaire; ceci car presque tous ces moyens ont été cédés au marché économique, qui s'est mondialisé et devenu plus complexe, n'ayant plus la possibilité de répondre aux demandes sociales. La tension entre démocratie et restrictionsé conomiques, associée à des problèmes institutionnels endogènes, provoque un climat d'instabilité politique permanent dans certains endroits de la région, reproduisant des cassures et des conflits, sujet étudié dans cet article sous la forme d'une analyse comparative de cinq pays andins: Bolivie, Pérou, Équateur, Colombie et Vénézuéla.