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1.
BMC Genomics ; 23(1): 849, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550402

RESUMO

BACKGROUND: Modern human brains and skull shapes differ from other hominids. Brain growth disorders as micro- (ASPM, MCPH1) and macrocephaly (NFIX, GLI3) have been highlighted as relevant for the evolution in humans due to the impact in early brain development. Genes associated with macrocephaly have been reported to cause this change, for example NSD1 which causes Sotos syndrome. RESULTS: In this study we performed a systematic literature review, located the reported variants associated to Sotos syndrome along the gene domains, compared the sequences with close primates, calculated their similarity, Ka/Ks ratios, nucleotide diversity and selection, and analyzed the sequence and structural conservation with distant primates. We aimed to understand if NSD1 in humans differs from other primates since the evolution of NSD1 has not been analyzed in primates, nor if the localization of the mutations is limited to humans. Our study found that most variations causing Sotos syndrome are in exon 19, 22 and 10. In the primate comparison we did not detect Ka/Ks ratios > 1, but a high nucleotide diversity with non-synonymous variations in exons 10, 5, 9, 11 and 23, and sites under episodic selection in exon 5 and 23, and human, macaque/colobus/tarsier/galago and tarsier/lemur/colobus. Most of the domains are conserved in distant primates with a particular progressive development from a simple PWWP1 in O. garnetti to a complex structure in Human. CONCLUSION: NSD1 is a chromatin modifier that suggests that the selection could influence brain development during modern human evolution and is not present in other primates; however, nowadays the nucleotide diversity is associated with Sotos syndrome.


Assuntos
Hominidae , Megalencefalia , Síndrome de Sotos , Tarsiidae , Humanos , Animais , Síndrome de Sotos/genética , Histona Metiltransferases/genética , Histona-Lisina N-Metiltransferase/genética , Tarsiidae/genética , Colobus/genética , Proteínas Nucleares/genética , Mutação , Éxons/genética , Hominidae/genética , Megalencefalia/genética , Nucleotídeos , Proteínas do Citoesqueleto/genética , Proteínas de Ciclo Celular/genética
2.
Anal Chem ; 94(44): 15250-15260, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36197692

RESUMO

Rare cancers are a challenge for clinical practice, the treatment experience at major centers to which rare cancers are referred is limited and are the most difficult to diagnose. Research to identify causes or develop prevention and early detection strategies is extremely challenging. Anal cancer is an example of a rare cancer, with the human papillomavirus (HPV) infection being the most important risk factor associated. In the early stages, anal cancer does not exhibit evident symptoms. This disease is diagnosed by means of anoscopy, which diagnoses some cases of early cancer; nevertheless, sensitivity of this test ranges between 47 and 89%. Therefore, the development of new, effective, and evidence-based screening methodologies for the early detection of rare cancers is of great relevance. In this study, the potential of ATR-FTIR spectroscopy has been explored as a sensitive, nondestructive, and inexpensive analytical method for developing disease screening platforms in serum. Spectral differences were found in the regions of 1700-1100 and 1700-1400 cm-1 between the control group and the anal cancer group related to the presence of proteins and nucleic acids. The chemometric analysis presented differences in the spectral fingerprints for both spectral regions with a high sensitivity ranging from 95.2 to 99.9% and a specificity ranging from 99.2 to 100%. This is the first step that we report for a methodology that is fast, nondestructive, and easy to perform, and the high sensitivity and specificity of the method are the basis for extensive research studies to implement these technologies in the clinical field.


Assuntos
Neoplasias do Ânus , Infecções por Papillomavirus , Masculino , Humanos , Detecção Precoce de Câncer , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/etiologia , Fatores de Risco , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
3.
Hum Genomics ; 15(1): 49, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348791

RESUMO

BACKGROUND: The diagnostic process for uncommon disorders with similar manifestations is complicated and requires newer technology, like gene sequencing for a correct diagnosis. MAIN BODY: We described two brothers clinically diagnosed with Carpenter syndrome, which is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems, for which they underwent craniotomies. However, whole exome sequencing analysis concluded a novel pathological variation in the ATRX chromatin remodeler gene and protein remodeling demonstrated structural variations that decreased the function, giving a completely different diagnosis to these patients. CONCLUSION: Our study focuses on the importance of using newer technologies, such as whole exome sequencing analysis, in patients with ambiguous phenotypes.


Assuntos
Acrocefalossindactilia/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteínas Nucleares/genética , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética , Acrocefalossindactilia/patologia , DNA Helicases/genética , Exoma/genética , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Mutação/genética , Fenótipo , Sequenciamento do Exoma , Talassemia alfa/patologia
5.
BMC Evol Biol ; 17(1): 10, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28077068

RESUMO

BACKGROUND: The evolutionary dynamics of repeat sequences is quite complex, with some duplicates never having differentiated from each other. Two models can explain the complex evolutionary process for repeated genes-concerted and birth-and-death, of which the latter is driven by duplications maintained by selection. Copy number variations caused by random duplications and losses in repeat regions may modulate molecular pathways and therefore affect phenotypic characteristics in a population, resulting in individuals that are able to adapt to new environments. In this study, we investigated the filaggrin gene (FLG), which codes for filaggrin-an important component of the outer layers of mammalian skin-and contains tandem repeats that exhibit copy number variation between and within species. To examine which model best fits the evolutionary pathway for the complete tandem repeats within a single exon of FLG, we determined the repeat sequences in crab-eating macaque (Macaca fascicularis), orangutan (Pongo abelii), gorilla (Gorilla gorilla), and chimpanzee (Pan troglodytes) and compared these with the sequence in human (Homo sapiens). RESULTS: In this study we compared concerted and birth-and-death evolution models, commonly used for gene copies. We found that there is high nucleotide diversity between filaggrin repeat regions, which fits the birth-and-death model. Phylogenetic analyses also suggested that independent duplication events created the repeat sequences in crab-eating macaques and orangutans, while different duplication and loss events created the repeats in gorillas, chimpanzees, and humans. Comparison of the repeat sequences detected purifying selection within species and lineage-specific duplications across species. We also found variation in the length of the repeated region within species such as chimpanzee and crab-eating macaque. CONCLUSIONS: We conclude that the copy number variation in the repeat sequences of FLG between primates may be a consequence of species-specific divergence and expansion.


Assuntos
Evolução Molecular , Proteínas de Filamentos Intermediários/genética , Primatas/genética , Adaptação Biológica/genética , Animais , Evolução Biológica , Variações do Número de Cópias de DNA , Proteínas Filagrinas , Duplicação Gênica , Humanos , Proteínas de Filamentos Intermediários/química , Filogenia , Alinhamento de Sequência , Especificidade da Espécie
6.
Invest Clin ; 58(1): 34-43, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29939001

RESUMO

The article examines the association between psychological stress (PS) and prehypertension (PH) in 690 adolescents, 260 males and 430 females, whose average age was 15.2 years (SD = 1.5). Their blood pressure (BP) was measured on separate days at school, by the oscillometric method (Dinamap) in a seating position. All of them completed a survey assessing life events and social readjustment (both scales associated with life stressors in adolescence). Participants were classified according to BP levels in prehypertensive (PH) and normotensive (N). The presence of PS was evaluated as severe stressful life events. The Chi-square test was used to study the association between PS and the presence of PH. The results showed the presence of PH in 9.2% (n = 24) in males and 3.5% (n = 15) in females, while the presence of PS ocurred in 70 males (26.9%) and 155 females (36.0%).When applied to the whole data, the Chi-square statistical test showed no association between PS and the condition of prehypertension [PH with PS = 15 vs. N with PS = 24, (P= 0.42)]. However, when subjects were classified by gender, there was a significant association between PS and PH in female adolescents [PH with PS = 9 vs N with PS = 6 (P = 0.04)]. This result suggests that, at early ages, female adolescents may be more vulnerable than males to PS as a determining factor to the condition of PH.


Assuntos
Pré-Hipertensão/etiologia , Estresse Psicológico/complicações , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino
7.
Heliyon ; 10(15): e35333, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170343

RESUMO

Miyoshi Muscular Dystrophy Type 1 is a rare autosomal recessive myopathy caused by mutations in the dysferlin (DYSF) gene. This disease presents with progressive distal lower limb weakness, such as gastrocnemius and soleus muscles resulting in difficulty standing on tiptoes, walking, and climbing stairs. We describe a family consisting of 6 siblings, 2 affected males, 1 affected female, 1 affected-death female, and 2 unaffected females. The affected members of this family have lived without an appropriate diagnosis for more than 20 years. Our patients have a homozygous nonsense pathogenic variant of the DYSF gene with 0 frequency in the Genome Aggregation Database. Our study shows that genetic testing provides a crucial aid to doctors when the physical examination and the clinical history are insufficient. It also emphasizes that a precise and accurate diagnosis prompts the correct management of a complex case.

8.
Heliyon ; 10(6): e28024, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545186

RESUMO

Introduction: In resource-limited settings, patients with uncommon phenotypes often face prolonged diagnostic journeys and potential misdiagnoses. Coloboma, heart defects, atresia choanae, restricted growth and development, genital and ear abnormalities syndrome (CHARGE) syndrome, a congenital condition affecting various body parts such as the heart, ears, eyes, and genitals, exemplifies this challenge. Case presentation: We present the case of a 21-year-old male patient from Ecuador who exhibited hypogonadism, facial deformities, and stunted growth. Due to the scarcity of genetic specialists and limited access to genetic testing in Ecuador, the patient received a misdiagnosis of Noonan syndrome. However, a correct diagnosis of CHARGE syndrome was ultimately reached after eight years, facilitated by genetic sequencing that identified a novel mutation in the Chromodomain helicase DNA binding protein 7 gene. Conclusion: This case highlights the critical role of meticulously assessing patients' symptoms and emphasizes the necessity for enhanced collaboration among physicians and researchers. Such efforts are pivotal in advancing healthcare access and equity for individuals in developing nations.

9.
Front Neurol ; 15: 1376643, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689878

RESUMO

Epilepsy, characterized by recurrent seizures, impacts 70-80% of patients, leading to cognitive deficits. The intricate relationship between seizure control and cognitive impairment remains complex. Epileptic encephalopathy (EE), an intensified form often rooted in genetic factors, is detectable through next-generation sequencing, aiding in precise diagnoses, family counseling, and potential treatment strategies. We present a case involving two sisters with refractory generalized seizures evolving into dysarthria, dysphagia, ataxia, and cognitive decline. Despite normal physical exams, abnormal electroencephalogram results consistent with epilepsy were noted. Whole Exome Sequencing identified heterozygous variants in the alanyl-tRNA synthetase (AARS) and Calcium Voltage-Gated Channel Subunit Alpha 1 (CACNA1A) genes. The AARS variant (c.C2083T, p.R695*) was maternal, while the CACNA1A variant (c.G7400C, p.R2467P) was paternal. Patients A and B exhibited a unique blend of neurological and psychiatric conditions, distinct from common disorders that begin adolescence, like Juvenile Myoclonic Epilepsy. Whole Exome Sequencing uncovered an AARS gene and CACNA1A gene, linked to various autosomal dominant phenotypes. Presence in both parents, coupled with familial reports of migraines and seizures, provides insight into accelerated symptom progression. This study underscores the importance of genetic testing in decoding complex phenotypes and emphasizes the value of documenting family history for anticipating related symptoms and future health risks.

10.
Hum Immunol ; 85(3): 110771, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38443236

RESUMO

The Waorani, an isolated indigenous tribe in Ecuador, have long been characterized by limited genetic diversity, with few studies delving into their genetic background. Human Leukocyte Antigen (HLA) genes which are located in the human major histocompatibility complex (MHC) provides valuable insights into population evolution due to its highly polymorphic nature. However, little is known about the HLA diversity and ancestry of the Waorani population. In this study, we sequenced eight HLA genes using Next Generation Sequencing (NGS) from 134 Waorani individuals and obtained up to four-field HLA allele resolution. Cluster and phylogenetic analysis show that the Waorani are genetically distant from other Ecuador populations, but instead show genetic affinities with the Puyanawa and Terena tribes from Brazil, as well as the Mixe tribe from Mexico. The identification of alleles common within the Waorani population, previously linked to specific health conditions, notably paves the way for future association analyses. This extensive study, employing Next-Generation Sequencing (NGS) technology, significantly enriches the sparse and segmented understanding of HLA diversity in the South American region. Our findings enhance the global comprehension of human genetic diversity and underscore the value of studying indigenous populations. Such research is vital for deepening our insights into human migration patterns and evolutionary processes.


Assuntos
Frequência do Gene , Variação Genética , Genética Populacional , Antígenos HLA , Filogenia , Humanos , Alelos , Equador , Etnicidade/genética , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos HLA/genética , Migração Humana
11.
Front Nutr ; 11: 1390133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988862

RESUMO

Introduction: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder resulting from phenylalanine hydroxylase deficiency, which impacts neurodevelopment. Lifelong low-phenylalanine diets and multidisciplinary care are pivotal for managing PKU. Latin American challenges in PKU care include diverse newborn screening programs, limited specialized healthcare, and resource scarcity. Methods: A systematic literature review was conducted (2010-2023) on PKU management following PRISMA guidelines. Inclusion criteria encompassed English/Spanish articles focusing on PKU management guidelines approved by an organization as well as articles focusing on PKU management in Latin America. After screening 127,276 results, 6 articles were included. Results: Six articles were analyzed, highlighting shared principles like multidisciplinary care, lifelong dietary adherence, personalized plans, and regular monitoring. Guides emphasized regional variations, breastfeeding complexities, and challenges for pregnant women with PKU. Discussion: Multidisciplinary care emerges as critical, incorporating physicians, psychologists, dietitians, nurses, and genetic counselors. Lifelong adherence to low-phenylalanine diets and personalized strategies for different life stages are emphasized. Challenges in Latin America include healthcare gaps, scarce resources, and reliance on international guidance. The importance of breastfeeding, preconception care, and comprehensive support for pregnant women with PKU is underscored. Conclusion: Collaborative efforts are essential to address PKU challenges in Latin America. Advocacy for awareness, specialized training, regional databases, and international collaborations can enhance diagnosis and management, ensuring a better quality of life for PKU individuals in the region. Embracing lessons from existing guides will contribute to improved PKU care and overall well-being.

12.
Front Cardiovasc Med ; 11: 1387063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38938651

RESUMO

This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old male patient presenting with early-onset heart failure and reduced ejection fraction. DCM is a nonischemic heart condition characterized by left biventricular dilation and systolic dysfunction, with approximately one-third of cases being familial and often linked to genetic mutations. The TTN gene, encoding the largest human protein essential for muscle contraction and sarcomere structure, is implicated in about 25% of DCM cases through mutations, especially truncating variants. Our investigation revealed a previously unreported G > C mutation at the splice acceptor site in intron 356 of TTN, confirmed by Sanger sequencing and not found in population databases, suggesting a novel contribution to the understanding of DCM etiology. The case emphasizes the critical role of the TTN gene in cardiac function and the genetic complexity underlying DCM. A comprehensive literature review highlighted the prevalence and significance of splice variants in the TTN gene, particularly those affecting the titin A-band, which is known for its role in muscle contraction and stability. This variant's identification underscores the importance of genetic screening in patients with DCM, offering insights into the disease's familial transmission and potential therapeutic targets. Our findings contribute to the expanding knowledge of genetic factors in DCM, demonstrating the necessity of integrating genetic diagnostics in cardiovascular medicine. This case supports the growing evidence linking splicing mutations in specific regions of the TTN gene to DCM development and underscores the importance of genetic counseling and testing in managing heart disease.

13.
Eur J Pharm Biopharm ; 195: 114178, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38195049

RESUMO

The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.


Assuntos
Metacrilatos , Impressão Molecular , Polímeros Molecularmente Impressos , Preparações de Ação Retardada , Ciprofloxacina/farmacologia , Polímeros , Impressão Molecular/métodos , Escherichia coli , Adsorção
14.
Front Public Health ; 11: 1248260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822540

RESUMO

Background: Patients, families, the healthcare system, and society as a whole are all significantly impacted by rare diseases (RDs). According to various classifications, there are currently up to 9,000 different rare diseases that have been recognized, and new diseases are discovered every month. Although very few people are affected by each uncommon disease individually, millions of people are thought to be impacted globally when all these conditions are considered. Therefore, RDs represent an important public health concern. Although crucial for clinical care, early and correct diagnosis is still difficult to achieve in many nations, especially those with low and middle incomes. Consequently, a sizeable amount of the overall burden of RD is attributable to undiagnosed RD (URD). Existing barriers and policy aspects impacting the care of patients with RD and URD remain to be investigated. Methods: To identify unmet needs and opportunities for patients with URD, the Developing Nations Working Group of the Undiagnosed Diseases Network International (DNWG-UDNI) conducted a survey among its members, who were from 20 different nations. The survey used a mix of multiple choice and dedicated open questions covering a variety of topics. To explore reported needs and analyze them in relation to national healthcare economical aspects, publicly available data on (a) World Bank ranking; (b) Current health expenditure per capita; (c) GDP per capita; (d) Domestic general government health expenditure (% of GDP); and (e) Life expectancy at birth, total (years) were incorporated in our study. Results: This study provides an in-depth evaluation of the unmet needs for 20 countries: low-income (3), middle-income (10), and high-income (7). When analyzing reported unmet needs, almost all countries (N = 19) indicated that major barriers still exist when attempting to improve the care of patients with UR and/or URD; most countries report unmet needs related to the availability of specialized care and dedicated facilities. However, while the countries ranked as low income by the World Bank showed the highest prevalence of referred unmet needs across the different domains, no specific trend appeared when comparing the high, upper, and low-middle income nations. No overt trend was observed when separating countries by current health expenditure per capita, GDP per capita, domestic general government health expenditure (% of GDP) and life expectancy at birth, total (years). Conversely, both the GDP and domestic general government health expenditure for each country impacted the presence of ongoing research. Conclusion: We found that policy characteristics varied greatly with the type of health system and country. No overall pattern in terms of referral for unmet needs when separating countries by main economic or health indicators were observed. Our findings highlight the importance of identifying actionable points (e.g., implemented orphan drug acts or registries where not available) in order to improve the care and diagnosis of RDs and URDs on a global scale.


Assuntos
Doenças não Diagnosticadas , Recém-Nascido , Humanos , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Saúde Global , Atenção à Saúde , Gastos em Saúde
15.
Front Public Health ; 11: 1079601, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935719

RESUMO

Introduction: Rare diseases (RD) are a health priority worldwide, overall affecting hundreds of millions of people globally. Early and accurate diagnosis is essential to support clinical care but remains challenging in many countries, especially the low- and medium-income ones. Hence, undiagnosed RD (URD) account for a significant portion of the overall RD burden. Methods: In October 2020, the Developing Nations Working Group of the Undiagnosed Diseases Network International (DNWG-UDNI) launched a survey among its members, belonging to 20 countries across all continents, to map unmet needs and opportunities for patients with URD. The survey was based on questions with open answers and included eight different domains. Conflicting interpretations were resolved in contact with the partners involved. Results: All members responded to the survey. The results indicated that the scientific and medical centers make substantial efforts to respond to the unmet needs of patients. In most countries, there is a high awareness of RD issues. Scarcity of resources was highlighted as a major problem, leading to reduced availability of diagnostic expertise and research. Serious equity in accessibility to services were highlighted both within and between participating countries. Regulatory problems, including securing informed consent, difficulties in sending DNA to foreign laboratories, protection of intellectual property, and conflicts of interest on the part of service providers, remain issues of concern. Finally, most respondents stressed the need to strengthen international cooperation in terms of data sharing, clinical research, and diagnostic expertise for URD patients in low and medium income countries. Discussion: The survey highlighted that many countries experienced a discrepancy between the growing expertise and scientific value, the level of awareness and commitment on the part of relevant parties, and funding bodies. Country-tailored public health actions, including general syllabus of medical schools and of the education of other health professionals, are needed to reduce such gaps.


Assuntos
Doenças não Diagnosticadas , Humanos , Doenças Raras/diagnóstico , Inquéritos e Questionários
16.
Rev Argent Microbiol ; 44(1): 10-5, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-22610291

RESUMO

Bacteremia is an important cause of morbimortality. This study describes the episodes of community-acquired bacteremia in adult patients registered at our hospital. Between January 2005, and December 2009, 271 episodes were studied. The diagnostic yield of blood cultures was 13.5 %. A total of 52 % of patients were male and 48 % female. The mean age was 60. The most frequent comorbidities were: diabetes (21 %), neoplasia (18 %), cardiopathy (11 %), and HIV infection (8 %). The focus was- respiratory (21 %), urinary (15 %), cutaneous (9 %), and others (13 %). Gram-positive bacteria prevailed (51.4%). The most frequent microorganisms were Escherichia coli (25 %), Streptococcus pneumoniae (22.9 %), and Staphylococcus aureus (12.3 %). Bacteremia was polymicrobial in 7 % of the cases. Thirty three percent of E. coli isolates were resistant to ciprofloxacin and 6 % to ceftazidime. Fourteen percent of S. aureus strains were resistant to oxacillin whereas only 7 % of S. pneumoniae expressed high resistance to penicillin with MICs = 2 ug/ml, according to meningitis breakpoints.


Assuntos
Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Bacteriemia/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/microbiologia , Comorbidade , Grupos Diagnósticos Relacionados , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais Estaduais/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
17.
Front Surg ; 9: 986372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338653

RESUMO

Background: Osteogenesis imperfecta (OI) is a rare heterogeneous genetic disorder commonly autosomal dominant with variants in the COL1A1 and COL1A2 genes. It is characterized by bone fragility and deformity, recurrent fractures, blue sclera, dentinogenesis imperfecta, short stature, and progressive deafness. Case presentation: We present a novel splicing mutation in the COL1A1 gene (c.2398-1G > C) in a 6-year-old Ecuadorian girl with fractures after light pressure and blue sclera. We identified the pathogenic variant, performed a literature review of splice variants, and recognized their location in the COL1A1 functional domains. Conclusion: We describe the first clinical description of a patient with OI type 1 caused by a splice variant in intron 34 of COL1A1 gene and identify that most of them are localized in the triple-helical region domain. We suggest that the splice variant in signal peptide, von Willebrand factor type C, and nonhelical regions maintain their functionality or that individuals affected with severe cases die early in development and are not reported.

18.
Front Oncol ; 12: 899579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756649

RESUMO

Multiple non-related neoplasia does not have an established approach or benefits for performing whole-exome sequencing (WES) analysis. We report on a 46-year-old woman who developed astrocytoma, thyroid, and breast cancer within 10 years. The WES analysis found a novel missense variant in the ACSL6 gene, and the protein modeling showed altered secondary and tertiary structures, which modify the binding to cofactors and substrates. ACSL6 is involved in lipid metabolism, expressed in the brain, thyroid, and breast tissues, and is associated with diverse types of cancer. Our study demonstrates the benefit of WES analysis compared with commercial panels in patients with non-related neoplasia.

19.
Front Pediatr ; 10: 975947, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467484

RESUMO

Background: Campomelic dysplasia (CD) is a rare disorder that involves the skeletal and genital systems. This condition has been associated with a diverse set of mutations in the SRY-box transcription factor 9 (SOX9) gene. Case presentation: We herein report a case involving a 4-year-old female patient with CD, female sex reversal, type 1 Arnold-Chiari malformation, and bilateral conductive hearing loss and investigate the causal mutation. Whole-exome sequencing analysis detected a novel Trp115X* variant in the SOX9 gene. We performed a literature review of the reported cases and demonstrated that the missense variants were located only in the self-dimerization domain (DIM) and high-mobility group box domains. We also reported that variants in the DIM domain do not cause sex reversal and identified that the amino acid sequences that were mutated in the patients with campomelic dysplasia are evolutionarily conserved among primates. Conclusions: We suggest that missense variants cannot be located in the K2, PQA, and PQS given that these domains function critically for transcriptional activation or repression of target genes and evolve under purifying selection.

20.
Environ Sci Pollut Res Int ; 29(30): 45885-45902, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35149949

RESUMO

In this study, a series of molecularly imprinted polymers (MIPs) have been synthesized using separately diclofenac, naproxen, and ibuprofen as templates with three different polymerization approaches. Two functional monomers, methacrylic acid (MAA) and 2-vinylpyridine (2-VP), were tested and ethylene glycol dimethacrylate (EGDMA) was used as crosslinker; also, template-free polymers (NIPs) were synthesized. It was found that the MIP with the highest retention percentage for diclofenac was the one prepared by the emulsion approach and with MAA (98.3%); for naproxen, the one prepared by the bulk polymerization with MAA (99%); and for ibuprofen, the one synthesized by bulk with 2-VP (97.7%). These three MIPs were characterized by scanning electron microscopy, thermogravimetric test, Fourier transform infrared, specific area measurements, and surface charge. It was found that the emulsion method allowed particle size control, while the bulk method gave heterogeneous particles. The three evaluated MIPs exhibited thermal stability up to 300 °C, and it was observed that 2-VP confers greater stability to the material. From the BET analysis, it was demonstrated that the MIPs and NIPs evaluated are mesoporous materials with a pore size between 10 and 20 nm. In addition, the monomer influenced the surface charge of the material, since the MAA conferred an acidic point of zero charge (PZC), while the 2-VP conferred a PZC of basic character. Through adsorption isotherms, it was determined  that there is a higher adsorption capacity of the MIPs at acidic pH following a pseudo-second-order kinetic model. Finally, the MIPs were used to determine the non-steroidal anti-inflammatory drugs (NSAIDs) understudy in San Luis Potosí, México, wastewater, finding concentrations of 0.642, 0.985, and 0.403 mg L-1 for DCF, NPX, and IBP, respectively.


Assuntos
Impressão Molecular , Adsorção , Anti-Inflamatórios não Esteroides/análise , Diclofenaco/análise , Emulsões , Ibuprofeno , Impressão Molecular/métodos , Polímeros Molecularmente Impressos , Naproxeno/análise , Águas Residuárias/análise
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