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ABSTRACT We present the case of a 37-year-old woman who underwent bilateral penetrating keratoplasty for congenital hereditary endothelial dystrophy at the age of 10 years. Over the subsequent 27 years, the patient's vision slowly deteriorated. Our examination revealed decompensation of the right corneal graft. We addressed this with regraft surgery. We then learned that the patient had been suffering from progressive hearing loss since adolescence. Tonal audiometry revealed hearing per ceptive deafness of 25 dB, which was more prominent in the left ear. Because the patterns of progressive sensorineural hearing loss and congenital hereditary endothelial dystrophy have both been linked to the same gene, slc4a11, we tested our patient for mutations in this gene. The test was positive for a heterozygous slc4a11 gene fifth exon mutation on chromosome 20p13-p12, which causes a frameshift. A combined clinical and genetic evaluation confirmed a diagnosis of Harboyan syndrome. After the genetic diagnosis of the disease, she was evaluated for the need for a hearing aid due to her hearing loss. The patient was also informed about genetic counseling.
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OBJECTIVE: A hedgehog family ligand, namely, sonic hedgehog (SHH), was reported to be important in the development of bladder and ureter smooth muscle. In this prospective study, we aimed to determine protein expression of SHH in resected ureterovesical junction (UVJ) segments of children with vesicoureteral reflux (VUR). MATERIALS AND METHODS: The study group included 19 children; 12 (63%) girls, 7 (37%) boys, who had ureteroneocystostomy operation; 3 (15.7%) right sided, 7 (36.8%) left sided, 9 (47.3%) bilateral, due to primary VUR between years 2015 and 2018. Totally, 28 UVJ segments were examined for Western Blot analysis to determine related protein expression levels. RESULTS: The mean Western blot band area of SHH gene pathway related protein was 3880.69 (2059.55-13941.61) while the mean area of ß-Actin, the house-keeping gene, was 20180.25 (9530.39-26709.75) (p = 0.001). Correlation analyses between grade of reflux and protein expression of SHH gene pathways revealed no significant relation (p = 0.300). When the UV samples were grouped as low- and high-grade reflux and compared in terms of SHH protein expression levels, no statistically significant difference was found between groups (p = 0.818). CONCLUSION: We concluded that SHH signaling molecule which is effective in development of bladder and ureter smooth musculature might also be effective in etiopathology of reflux.
OBJETIVO: Se ha informado que el ligando sonic hedgehog (SHH) es importante en el desarrollo de los músculos lisos de la vejiga y el uréter. Nuestro objetivo fue determinar la expresión proteica de SHH en los segmentos de la unión ureterovesical de niños con reflujo vesicoureteral (RVU). MATERIALES Y MÉTODOS: El grupo de estudio incluyó a 19 niños; 12 (63%) niñas, 7 (37%) niños, que tuvieron operación de ureteroneocistostomía (UNC); 3 (15.7%) derecho, 7 (36.8%) izquierdo, 9 (47.3%) bilateral, por RVU primario entre los años 2015-2018. Se examinaron un total de 28 segmentos de la unión ureterovesical para análisis de transferencia Western para determinar los niveles de expresión de proteínas relacionadas en las muestras. RESULTADOS: El área media de la banda de transferencia Western de la proteína relacionada con la vía del gen SHH fue de 3880.69 (2059.55-13941.61), mientras que el área media de la ß-actina, el gen de limpieza, fue de 20180.25 (9530.39-26709.75) (p = 0.001). Los análisis de correlación entre el grado de reflujo y la expresión de proteínas de las vías del gen SHH no revelaron una relación significativa (p = 0.300). CONCLUSIÓN: Concluimos que la molécula de señalización SHH también podría ser efectiva en la etiopatología del reflujo vesicoureteral.
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Proteínas Hedgehog , Transdução de Sinais , Bexiga Urinária , Refluxo Vesicoureteral , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Humanos , Masculino , Feminino , Refluxo Vesicoureteral/genética , Estudos Prospectivos , Bexiga Urinária/metabolismo , Pré-Escolar , Criança , Ureter/metabolismo , LactenteRESUMO
BACKGROUND: Mobulidae is a monophyletic family within the Myliobatiformes that comprises pelagic species represented by manta and devil rays. Among the genus Mobula, the Atlantic Pygmy Devil Ray - Mobula hypostoma - is reported in coastal regions exclusively in tropical and subtropical Atlantic Ocean from 1 to 100 m deep. In Brazil, M. hypostoma is one of the least studied Mobula species. It is regularly misidentified, especially as Mobula thurstoni, and is commonly listed as bycatch, in fishery inventories, or related to opportunistic sightings in the national territory. METHODS AND RESULTS: Here, we describe the complete nucleotide sequence of the mitochondrial genome (mitogenome) from Mobula hypostoma, which is 18,141 bp in length and comprises 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes. The M. hypostoma mitochondrial genes organisation and mitochondrial genome length are similar to other Mobula species, and the phylogenetic reconstruction indicates M. hypostoma as closely related to Mobula munkiana. CONCLUSIONS: The Brazilian mitogenome of M. hypostoma is expected to be a valuable resource for molecular-based species identification, and evolutionary and phylogeography studies.
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Espécies em Perigo de Extinção , Genoma Mitocondrial , Filogenia , Rajidae , Animais , Genoma Mitocondrial/genética , Brasil , Rajidae/genética , Rajidae/classificação , RNA de Transferência/genética , DNA Mitocondrial/genética , Oceano Atlântico , RNA Ribossômico/genética , Análise de Sequência de DNA/métodosRESUMO
Human population growth constantly requires an increase in the production of food and products from the timber industry. To meet this demand, agriculture and planted forests are advancing over natural areas. In view of this, it is necessary to know the effects of land use for different purposes (grain production, pastures, planted forests, fruit production and among other uses) on the genetic diversity of populations of native species. This knowledge can assist in land use planning as well as in the development of conservation strategies for native species. In this study, we evaluated the effect of land use for agriculture (mainly for cereal production) and planted forests on the genetic diversity of Baccharis crispa Spreng., a herb native to South America. To achieve our goals, we compared population genetic data obtained with three molecular markers (microsatellites, inter-simple sequence repeat and isoenzymes) with data on land use for agriculture and planted forests from 15 different locations. Our results showed that regardless of the molecular marker used, the greater the use of land for agriculture and planted forests, the lower was the genetic diversity of B. crispa populations. Baccharis crispa is a semi-perennial species that needs at least one year to reach its reproductive period, which is prevented in agricultural areas due to the land being turned over or dissected with herbicides every 6 months. In the studied regions, the planted forests are of eucalypt and/or pine, which besides being species with a high production of allelopathic substances, produce strong shading and B. crispa is a species that inhabits open grassland that needs a high incidence of sunlight for development. The data obtained in our study can assist in the decision-making to use land in order to reconcile the production of supplies for humanity and for the conservation of nature.
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Background: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant syndrome characterized by medullary carcinoma of the early thyroid, pheochromocytoma, and non-endocrine manifestations, such as marfanoid habits and other skeletal abnormalities as well as mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract. Case Description: A 10-year-old male began follow-up at our service at 3 years of age through pediatric gastroenterology due to intestinal constipation. The mother also reported that the child had painless lesions on the tip of the tongue since birth with progressive worsening. The patient simultaneously began follow-up with pediatric endocrinology due to low gains in weight and height, between which only isolated low weight was found, and the onset of follow-up with the pediatric neurology team due to longstanding headache combined with vomiting, photophobia, and phonophobia as well as a specific reading and writing disorder. The patient was sent to clinical genetics. The child's karyotype was 46, XY (normal). Through a physical examination, the pediatric neurology team identified joint hypermobility, important muscle hypotrophy, gingival hypertrophy, and lipodystrophy. The patient was sent to neurogenetics, initiating a set of general laboratory exams for the investigation of the lipodystrophy and a panel of exams for lipodystrophy, neuropathy, and muscle hypotrophy as well as electroneuromyography. MEN2B due to genetic mutation was confirmed and the patient was sent to the pediatric endocrinology clinic for follow-up. Currently 10 years of age and again with the pediatric endocrinology team for the diagnosis of MEN2B, the investigation of pheochromocytoma and medullary thyroid cancer was initiated. Conclusions: An additional mutation occurs in most cases of MEN2B. The diagnosis is only established when the child or, in most cases, adolescent presents with medullary thyroid cancer in an advanced and even metastatic stage. However, non-endocrine manifestations, can lead to an early diagnosis and timely intervention. The diagnosis of MEN2B is made with the confirmation of the autosomal dominant genetic mutation or a mutation of the RET gene. In the absence of these mutations, the majority of clinical manifestations should be present.
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Abstract Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a "dilapidated brick wall", with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment.
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Much knowledge about bacteriophages has been obtained via genomics and metagenomics over the last decades. However, most studies dealing with prophage diversity have rarely conducted phage species delimitation (aspect 1) and have hardly integrated the population structure of the host (aspect 2). Yet, these two aspects are essential in assessing phage diversity. Here, we implemented an operational definition of phage species (clustering at 95% identity, 90% coverage) and integrated the host's population structure to understand prophage diversity better. Gathering the most extensive data set of Acinetobacter baumannii phages (4,152 prophages + 122 virulent phages, distributed in 46 countries in the world), we show that 91% (875 out of 963) of the prophage species have four or fewer prophages per species, and just five prophage species have more than 100 prophages. Most prophage species have a narrow host range and are geographically restricted; yet, very few have a broad host range being well spread in distant lineages of A. baumannii. These few broad host range prophage species are not only cosmopolitan but also the most abundant species. We also noted that polylysogens had very divergent prophages, belonging to different prophage species, and prophages can easily be gained and lost within the bacterial lineages. Finally, even with this extensive data set, the prophage diversity has not been fully grasped. Our study highlights how integrating the host population structure and a solid operational definition of phage species allows us to better appreciate phage diversity and its transmission dynamics. IMPORTANCE: Much knowledge about bacteriophages has been obtained via genomics and metagenomics over the last decades. However, most studies dealing with prophage diversity have rarely conducted phage species delimitation (aspect 1) and have hardly integrated the population structure of the host (aspect 2). Yet, these two aspects are essential in assessing phage diversity. Here, we implemented an operational definition of phage species (clustering at 95% identity, 90% coverage) and integrated the host's population structure to understand prophage diversity better. Gathering the most extensive data set of Acinetobacter baumannii phages, we show that most prophage species have four or fewer prophages per species, and just five prophage species have more than 100 prophages. Most prophage species have a narrow host range and are geographically restricted; yet, very few have a broad host range being well spread in distant lineages of A. baumannii. These few broad host range prophage species are cosmopolitan and the most abundant species. Prophages in the same bacterial genome are very divergent, and prophages can easily be gained and lost within the bacterial lineages. Finally, even with this extensive data set, the prophage diversity has not been fully grasped. This study shows how integrating the host population structure and clustering at the species level allows us to better appreciate phage diversity and its transmission dynamics.
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Especificidade de Hospedeiro , Prófagos , Prófagos/genética , Prófagos/fisiologia , Prófagos/classificação , Acinetobacter baumannii/virologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/classificação , Metagenômica , Filogenia , Genoma Viral , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificaçãoRESUMO
Thyrinteina arnobia (Lepidoptera: Geometridae) is a native American species. Despite its historical importance as an insect pest in Eucalyptus plantations, more information is needed regarding the population diversity, demography, and climatic variables associated with its distribution in different regions of Brazil. We used a phylogeographic approach to infer the genetic diversity, genetic structure, and demographic parameters of T. arnobia. We also conducted an ecological niche modeling (ENM) to predict suitable areas for T. arnobia occurrence in Brazil and other countries worldwide. Although T. arnobia populations have low genetic diversity in Brazil, we identified mitochondrial haplogroups predominating in different Brazilian regions and high ФST and ФCT values in AMOVA, suggesting a low frequency of insect movement among these regions. These results indicate that outbreaks of T. arnobia in Eucalyptus areas in different regions of Brazil are associated with local or regional populations, with no significant contribution from long-distance dispersal from different regions or biomes, suggesting that pest management strategies would be implemented on a regional scale. In Brazil, the demographic and spatial expansion signals of T. arnobia seem to be associated with the history of geographical expansion of Eucalyptus plantations, a new sustainable host for this species. ENM indicated that isothermality and annual rainfall are critical climatic factors for the occurrence of T. arnobia in tropical and subtropical areas in the Americas. ENM also suggested that T. arnobia is a potential pest in Eucalyptus areas in all Brazilian territory and in regions from Africa, Asia, and Oceania.
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Ecossistema , Eucalyptus , Variação Genética , Filogeografia , Animais , Eucalyptus/parasitologia , Brasil , Lepidópteros/genética , Lepidópteros/fisiologia , Mariposas/fisiologia , Mariposas/genética , FilogeniaRESUMO
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with clinical heterogeneity and a high association with hereditary disease, affecting approximately 30 % of the cases. Differences in the presentation and genetic etiologies of PPGLs have been demonstrated between Chinese and European patients. The frequency of germline genetic diagnosis was remarkably higher in Brazilian patients (â¼50 %) compared with other cohorts (Chinese 21 %, European 31 %, and The Cancer Genome Atlas Program cohort 27 %). Interestingly, germline SDHB genetic defects were also more prevalent in Brazilian patients (17 %) with PPGLs when compared with other cohorts (3-9 %). The SDHB exon 1 deletion was responsible for approximately 50 % of the SDHB pathogenic/likely pathogenic variants in Brazilian patients with PPGLs due to a founder effect. The germline SDHB exon 1 deletion represents â¼10 % of the germline drivers in Brazilian patients (and possibly in Latin America). Therefore, a single diagnostic PCR for the SDHB exon 1 deletion might be very useful in clinical practice for genetic testing and counseling of patients with PPGLs in Latin America.
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COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001), MTHFR gene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.
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Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Fator de von Willebrand , Humanos , COVID-19/sangue , Feminino , Masculino , Biomarcadores/sangue , Pessoa de Meia-Idade , Prognóstico , Fator de von Willebrand/metabolismo , Fator de von Willebrand/análise , Adulto , Idoso , SARS-CoV-2/isolamento & purificação , Fator VIII/metabolismo , Fator VIII/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismoRESUMO
Neonatal epileptic syndromes are part of the genetic and metabolic epilepsies in this age group. Although they are not the most frequent cause of neonatal seizures, their early recognition allows for better diagnostic and therapeutic approaches. These syndromes can be classified into self-limited neonatal syndromes and early infantile epileptic and developmental encephalopathies (EIDEE). While they may share semiology in some types of seizures, such as sequential, and even share alterations in common genes in their etiology, their evolution is very different. In self-limited neonatal syndromes, seizures typically resolve within the first months of life with normal psychomotor development, giving rise to the term self-limited. However, the term benign should not be used as some may present recurrence of seizures, movement disorders, or learning disorders. In the case of EIDEE, seizures are usually refractory to treatment, affecting brain functions and neurodevelopment. In this review, our aim was to describe the electroclinical phenotype of neonatal epileptic syndromes, the most frequently involved genes and their clinical spectrum, their diagnostic approach, as well as the recommended treatments.
Los síndromes epilépticos neonatales hacen parte de las epilepsias de origen genético y metabólico en este grupo edad y aunque no son la causa más frecuente de crisis neonatales, su reconocimiento temprano permite dirigir mejor su enfoque diagnóstico y tratamiento. Pueden clasificarse en síndromes neonatales autolimitados y encefalopatías epilépticas y del desarrollo infantil temprano (EIDEE). Aunque pueden mostrar semiología similar en algunos tipos de crisis, como las secuenciales, e incluso comparten alteraciones en genes comunes en su etiología, su evolución es muy diferente. En los síndromes autolimitados, las crisis remiten en los primeros meses de vida alcanzando un desarrollo psicomotor normal, lo que da su nombre de autolimitado; sin embargo, el término benigno no debe utilizarse dado que algunos pueden presentar recurrencia de crisis, trastornos del movimiento o trastornos del aprendizaje. En las EIDEE las crisis suelen ser refractarias al tratamiento y se comprometen funciones cerebrales y el neurodesarrollo. En esta revisión describiremos el fenotipo electroclínico de los síndromes epilépticos neonatales, los genes más frecuentemente involucrados y su espectro clínico, su enfoque diagnóstico, así como los tratamientos recomendados.
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Síndromes Epilépticas , Humanos , Recém-Nascido , Síndromes Epilépticas/genética , Síndromes Epilépticas/diagnóstico , Síndromes Epilépticas/terapia , Fenótipo , EletroencefalografiaRESUMO
BACKGROUND: The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood. OBJECTIVE: To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia. METHODS: In individuals with plasma TG≥880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1. For each variant we ascertained its location, zygosity, allelic frequency and pathogenicity classification according to American College of Medical Genetics (ACMG) criteria. RESULTS: The study included 166 participants (62 % male, mean age 50), peak TG levels ranged between 894 and 11,000 mg/dL. We identified 92 variants: 19 in LPL, 7 in APOC2, 11 in GPIHBP1, 38 in LMF1, and 17 in APOA5. Eighteen of these variants had not been reported. We identified a new pathogenic variant in LMF1 (c.41C>A; p.Ser14*), a new likely pathogenic variant in LMF1 (c.1527 C > T; p.Pro509=, also expressed as c.1447C>T; p.Gln483*), and a known pathogenic variant in LMF1 (c.779G>A; p.Trp260*). Four participants were heterozygous for variant c.953A>G; p.Asn318Ser in LPL, a known risk factor for hypertriglyceridemia. Participants with variants of unknown significance (VUS) in LMF1 had significantly higher peak TG than those with VUS in other genes. Peak TG were 4317 mg/dL in participants with a history of pancreatitis, and 1769 mg/dL in those without it (p = 0.001). CONCLUSION: Our study identified variants associated with sHTG among Latinos, and showed that genetic variation in LMF1 may be frequently associated with sHTG in this population.
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Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson's disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain.
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OBJECTIVES: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. DESIGN: An open-label, multicentre, non-randomised clinical trial. SETTING: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico. PARTICIPANTS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases. INTERVENTIONS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured. PRIMARY AND SECONDARY OUTCOMES: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001). CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups. TRIAL REGISTRATION NUMBER: NCT03419325.
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Algoritmos , Clopidogrel , Hispânico ou Latino , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Ticagrelor , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Clopidogrel/uso terapêutico , Porto Rico , Idoso , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/terapia , Sistemas de Apoio a Decisões Clínicas , Genótipo , Farmacogenética , Citocromo P-450 CYP2C19/genética , Medição de Risco , Região do Caribe/etnologia , Hemorragia/induzido quimicamenteRESUMO
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.
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Xyleborus beetles, a diverse group of ambrosia beetles, present challenges to forestry and agriculture due to their damaging burrowing behavior and symbiotic relationships with fungi. This review synthesizes current knowledge on the biology, ecology, and management of Xyleborus. We explore the beetles' life cycle, reproductive strategies, habitat preferences, and feeding habits, emphasizing their ecological and economic impacts. Control and management strategies, including preventive measures, chemical and biological control, and integrated pest management (IPM), are critically evaluated. Recent advances in molecular genetics and behavioral studies offer insights into genetic diversity, population structure, and host selection mechanisms. Despite progress, managing Xyleborus effectively remains challenging. This review identifies future research needs and highlights innovative control methods, such as biopesticides and pheromone-based trapping systems.
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The seascape comprises multiple environmental variables that interact with species biology to determine patterns of spatial genetic variation. The environment imposes spatially variable selective forces together with homogenizing and diverging drivers that facilitate or restrict dispersal, which is a complex, time-dependent process. Understanding how the seascape influences spatial patterns of genetic variation remains elusive, particularly in coastal upwelling systems. Here, we combine genome-wide SNP data, Lagrangian larval dispersal simulated over a hydrodynamic model, and ocean environmental information to quantify the relative contribution of ocean circulation and environmental heterogeneity as drivers of the spatial genetic structure of two congeneric intertidal limpets, Scurria scurra and S. araucana, along the central coast of Chile. We find that a genetic break observed in both limpet species coincides with a break in connectivity shown by the Lagrangian dispersal, suggesting that mean ocean circulation is an important seascape feature, in particular for S. scurra. For S. araucana, environmental variation appears as a better predictor of genetic structure than ocean circulation. Overall, our study shows broad patterns of seascape forcing on genetic diversity and contributes to our understanding of the complex ecological and evolutionary interactions along coastal upwelling systems.
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Ecossistema , Variação Genética , Animais , Oceanografia , Gastrópodes/genética , Gastrópodes/fisiologia , Chile , Oceanos e Mares , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Meningiomas (MGs), which arise from meningothelial cells of the dura mater, represent a significant proportion of primary tumours of the central nervous system (CNS). Despite advances in treatment, the management of malignant meningioma (MMG) remains challenging due to diagnostic, surgical, and resection limitations. Cancer stem cells (CSCs), a subpopulation within tumours capable of self-renewal and differentiation, are highlighted as key markers of tumour growth, metastasis, and treatment resistance. Identifying additional CSC-related markers enhances the precision of malignancy evaluations, enabling advancements in personalised medicine. The review discusses key CSC biomarkers that are associated with high levels of expression, aggressive tumour behaviour, and poor outcomes. Recent molecular research has identified CSC-related biomarkers, including Oct-4, Sox2, NANOG, and CD133, which help maintain cellular renewal, proliferation, and drug resistance in MGs. This study highlights new therapeutic strategies that could improve patient prognosis with more durable tumour regression. The use of combination therapies, such as hydroxyurea alongside diltiazem, suggests more efficient and effective MG management compared to monotherapy. Signalling pathways such as NOTCH and hedgehog also offer additional avenues for therapeutic development. CRISPR/Cas9 technology has also been employed to create meningioma models, uncovering pathways related to cell growth and proliferation. Since the efficacy of traditional therapies is limited in most cases due to resistance mechanisms in CSCs, further studies on the biology of CSCs are warranted to develop therapeutic interventions that are likely to be effective in MG. Consequently, improved diagnostic approaches may lead to personalised treatment plans tailored to the specific needs of each patient.
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Introdução: O trabalho conjunto da genética médica e da fonoaudiologia é essencial, contribuindo para o desenvolvimento de procedimentos que auxiliam no tratamento de pacientes com distúrbios da comunicação. Objetivo: Analisar as características fonoaudiológicas de pacientes pediátricos atendidos por um serviço de genética clínica. Método: Estudo transversal observacional, realizado com pacientes atendidos pelo serviço de genética de um hospital em Porto Alegre. Para a coleta de dados, aplicou-se um questionário relacionado as áreas de audição, deglutição, motricidade orofacial, voz e linguagem. Resultados: A amostra foi constituída por 54 participantes com idades entre 8 meses e 17 anos (média de idade 6 anos e 5 meses). 24,07% (n=13) dos pacientes apresentaram diagnóstico de síndrome, e 59,26% (n=32) tinham atraso no desenvolvimento neuropsicomotor. Com relação ao perfil fonoaudiológico, 81,48% (n=44) apresentaram algum hábito oral deletério durante a infância. 16,67% (n=9) percebiam alguma dificuldade para ouvir e 29,62% (n=16) para deglutir. 85,19% (n=46) dos participantes manifestaram a linguagem oral desenvolvida e, destes, 71,74% (n=33) apresentavam trocas na fala. 33,33% (n=18) já estavam em atendimento fonoaudiológico, e outros 24,07% (n=13) estavam na fila de espera para este atendimento. Conclusões: Uma parte significativa dos pacientes apresentou queixas e/ou manifestações nas áreas da comunicação humana, principalmente em relação à linguagem, à fala e aos hábitos orais deletérios. Esses dados destacam a importância do encaminhamento para a equipe de fonoaudiologia. (AU)
Introduction: The collaborative efforts of medical genetics and speech therapy are essential, contributing to the development of procedures that assist in treating patients with communication disorders. Objective: To analyze the speech therapy characteristics of pediatric patients seen by a clinical genetics service. Methods: Observational cross-sectional study conducted with patients seen at the genetics service of a hospital in Porto Alegre. A questionnaire related to hearing, swallowing, orofacial motricity, voice, and language areas was used for data collection. Results: The sample consisted of 54 participants aged between 8 months and 17 years, with an average age of 6 years and 5 months. 24.07% (n=13) of the patients had a diagnosis of syndrome, and 59.26% (n=32) had delayed neuropsychomotor development. Regarding the speech therapy profile, 81.48% (n=44) had some harmful oral habit during childhood. 16.67% (n=9) reported some difficulty in hearing, and 29.62% (n=16) in swallowing. 85.19% (n=46) of the participants showed developed oral language, and of these, 71.74% (n=33) made speech substitutions. 33.33% (n=18) of the patients were already undergoing speech therapy, and another 24.07% (n=13) were on the waiting list for this treatment. Conclusions: A significant portion of the patients presented complaints and/or manifestations in the areas of human communication, especially regarding language, speech, and harmful oral habits. These data highlight the importance of referral to the speech therapy team. (AU)
Introducción: La colaboración entre genética médica y foniatría es esencial para desarrollar procedimientos que ayuden en el tratamiento de pacientes con trastornos de la comunicación. Objetivo:Analizar las características de patología del habla y lenguaje de pacientes pediátricos atendidos por un servicio de genética clínica. Método: Estudio transversal observacional con pacientes atendidos por el servicio de genética de un hospital en Porto Alegre. Se aplicó un cuestionario sobre audición, deglución, motricidad orofacial, voz y lenguaje. Resultados: La muestra consistió en 54 participantes con edades comprendidas entre 8 meses y 17 años (media: 6 años y 5 meses). El 24,07% (n=13) de los pacientes tenían un diagnóstico de síndrome, y el 59,26% (n=32) presentaron retraso en el desarrollo neuropsicomotor. En cuanto al perfil foniatra, el 81,48% (n=44) presentaron algún hábito oral perjudicial durante la infancia. El 16,67% (n=9) reportaron dificultades para oír, y el 29,62% (n=16) para tragar. El 85,19% (n=46) manifestaron lenguaje oral desarrollado y, de ellos, el 71,74% (n=33) realizaban intercambios en el habla. El 33,33% (n=18) de los pacientes ya estaban en tratamiento foniatra y el 24,07% (n=13) estaban en lista de espera para este tratamiento. Conclusiones: Una parte significativa de los pacientes presentó quejas y/o manifestaciones en las áreas de la comunicación humana, especialmente en relación con el lenguaje, el habla y los hábitos orales perjudiciales, enfatizando la importancia de la derivación al equipo de foniatría. (AU)
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Serviços de Saúde , Transtornos do Desenvolvimento da Linguagem/genética , Fonoterapia , Síndrome , Estudos Transversais , Inquéritos e Questionários , Genética Médica , Doenças Genéticas InatasRESUMO
Over the last 10 years, global raspberry production has increased by 47.89%, based mainly on the red raspberry species (Rubus idaeus). However, the black raspberry (Rubus occidentalis), although less consumed, is resistant to one of the most important diseases for the crop, the late leaf rust caused by Acculeastrum americanum fungus. In this context, genetic resistance is the most sustainable way to control the disease, mainly because there are no registered fungicides for late leaf rust in Brazil. Therefore, the aim was to understand the genetic architecture that controls resistance to late leaf rust in raspberries. For that, we used an interspecific multiparental population using the species mentioned above as parents, 2 different statistical approaches to associate the phenotypes with markers [GWAS (genome-wide association studies) and copula graphical models], and 2 phenotyping methodologies from the first to the 17th day after inoculation (high-throughput phenotyping with a multispectral camera and traditional phenotyping by disease severity scores). Our findings indicate that a locus of higher effect, at position 13.3 Mb on chromosome 5, possibly controls late leaf rust resistance, as both GWAS and the network suggested the same marker. Of the 12 genes flanking its region, 4 were possible receptors, 3 were likely defense executors, 1 gene was likely part of signaling cascades, and 4 were classified as nondefense related. Although the network and GWAS indicated the same higher effect genomic region, the network identified other different candidate regions, potentially complementing the genetic control comprehension.