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1.
Nat Mater ; 21(2): 188-194, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34857910

RESUMO

The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La0.7Sr0.3MnO3 combined with the superconducting cuprate YBa2Cu3O7. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.

2.
Mol Biol Rep ; 50(2): 1949-1952, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36385664

RESUMO

BACKGROUND: Lactoferrin (LTF) is an iron-binding glycoprotein found in milk and other exocrine secretion with antibacterial activity proposed as an alternative to mastitis treatment or prevention. LTF has been proposed as a candidate gene for mastitis resistance selection. The aim of this paper was to assess LTF promotor to explore variations with potential association to mastitis resistance in dairy cows from Honduras. METHODS: A resequencing of promotor and Exon I of LTF gene in extreme mastitis susceptibility cows (126 Holstein and Holstein crossbred) was performed. RESULTS: Eight polymorphisms were found in promotor region, four of them were novel variations. Two were important by frequency among extreme groups, but a polymorphism in - 421 A/T position was significantly (P = 0.0188) associated to mastitis susceptibility. CONCLUSION: Results support the key role of regulatory region of LTF gene. Some candidate genes are proposed in association with mastitis traits and implications are discussed.


Assuntos
Lactoferrina , Mastite Bovina , Feminino , Bovinos/genética , Animais , Humanos , Lactoferrina/genética , Genótipo , Polimorfismo Genético , Leite , Mastite Bovina/genética , Polimorfismo de Nucleotídeo Único/genética
3.
Surg Endosc ; 37(10): 8116-8122, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37658199

RESUMO

AIMS: Training programs are essential to introduce new methods for bile duct clearance. Visual examination via cholangioscopy is ideal to diagnose and treat biliary tract diseases such as cancer and choledocholithiasis. However, surgeons rarely use cholangioscopes. Specific training is required to master laparoscopic and percutaneous cholangioscopy. This study aims to assess skill acquisition and retention during cholangioscopy training in the Image-Guided Therapies Masterclass. METHODS: This prospective study enrolled 17 physicians undergoing training in interventional treatments of biliary diseases. A novel disposable cholangioscope and access kit were used with a biliary tract model including two simulated common bile duct (CBD) stones. The curriculum required visualization of all critical structures before removal of one stone with a Dormia basket. After informed consent, demographic data and time to exercise completion were recorded on each of two subsequent training days. Task-specific questions were measured at the completion of training using a Likert scale (strongly disagree to strongly agree, 1-5 points). RESULTS: All participants successfully completed the task (6F/11 M, age 36 ± 5 years; 13 surgeons, 4 interventional radiologists; median experience with percutaneous procedures 2 years, range 0-20). Significant improvement in mean task completion time was observed (day 1: 172 ± 59 s, day 2: 89 ± 45 s; P < 0.0001). All task-specific questions were answered with a median rating of 5/5: "The platform facilitates cholangioscopy" and "This training method accelerates gain in proficiency and is useful for residents/fellows" (IQR 5-5), "This platform is useful to measure the proficiency level" and "There is an application for simulation in percutaneous surgery training" (IQR 4.5-5), "The platform is user-friendly" and "The model quality recreates realistic scenarios" (IQR 4-5). CONCLUSION: Cholangioscopic bile duct exploration and stone retrieval were achieved by all participants using a dedicated training program and physical simulator. Significant skill progress was observed during 2 days of dedicated training.


Assuntos
Cálculos Biliares , Laparoscopia , Cirurgia Assistida por Computador , Humanos , Adulto , Estudos Prospectivos , Endoscopia do Sistema Digestório/métodos , Cálculos Biliares/cirurgia
4.
Surg Endosc ; 37(10): 7774-7783, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37580582

RESUMO

BACKGROUND: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases. METHODS: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023. RESULTS: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis. CONCLUSIONS: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients.


Assuntos
Neoplasias dos Ductos Biliares , Doenças da Vesícula Biliar , Laparoscopia , Litíase , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Litíase/patologia , Estudos Retrospectivos , Endoscopia do Sistema Digestório/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Ductos Biliares/patologia , Doenças da Vesícula Biliar/patologia , Neoplasias dos Ductos Biliares/patologia
5.
Lett Appl Microbiol ; 74(3): 444-451, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34862647

RESUMO

The most alarming aspect of the Sudanese toombak smokeless tobacco is that it contains high levels of highly toxic tobacco-specific nitrosamines (TSNAs). Understanding the microbiology of toombak is of relevance because TSNAs are an indirect result of microbial-mediated nitrate reductions. We conducted shotgun metagenomic sequencing on a toombak product for which relevant features are presented here. The microbiota was composed of over 99% Bacteria. The most abundant taxa included Actinobacteria, specifically the genera Enteractinococcus and Corynebacterium, while Firmicutes were represented by the family Bacillaceae and the genus Staphylococcus. Selected gene targets were nitrate reduction and transport, antimicrobial resistance, and other genetic transference mechanisms. Canonical nitrate reduction and transport genes (i.e. nar) were found for Enteractinococcus and Corynebacterium while various species of Staphylococcus exhibited a notable number of antimicrobial resistance and genetic transference genes. The nitrate reduction activity of the microbiota in toombak is suspected to be a contributing factor to its high levels of TSNAs. Additionally, the presence of antimicrobial resistance and transference genes could contribute to deleterious effects on oral and gastrointestinal health of the end user. Overall, the high toxicity and increased incidences of cancer and oral disease of toombak users warrants further investigation into the microbiology of toombak.


Assuntos
Nitrosaminas , Tabaco sem Fumaça , Metagenoma , Metagenômica , Nicotiana
6.
Georgian Med News ; (330): 99-105, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36427851

RESUMO

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.


Assuntos
Tratamento Farmacológico da COVID-19 , Peptídeos , Humanos , Honduras , Estimativa de Kaplan-Meier , Peptídeos/efeitos adversos , Modelos de Riscos Proporcionais
7.
Appl Microbiol Biotechnol ; 105(12): 4843-4853, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34110473

RESUMO

Smokeless tobacco products (STP) contain diverse microbial communities that contribute to the formation of harmful chemical byproducts. This is concerning since 300 million individuals around the globe are users of smokeless tobacco. Significant evidence has shown that microbial metabolic activities mediate the formation of carcinogens during manufacturing. In recent years, studies have revealed a series of additional health impacts that include lesions and inflammation of the oral mucosa and the gastrointestinal tract, as well as alterations of the endogenous microbiota. These findings are due to recent developments in molecular technologies that allowed researchers to better examine the microbial component of these products. This new information illustrates the scale of the STP microbiota and its diversity in the finished product that is sold for consumption. Additionally, the application of metagenomics and metatranscriptomics has provided the tools to look at phylogenies across bacterial, viral, and eukaryotic groups, their functional capacities, and viability. Here we present key examples of tobacco microbiology research that utilizes newer approaches and strategies to define the microbial component of smokeless tobacco products. We also highlight challenges in these approaches, the knowledge gaps being filled, and those gaps that warrant further study. A better understanding of the microbiology of STP brings vast public health benefits. It will provide important information for the product consumer, impact manufacturing practices, and provide support for the development of attainable and more meaningful regulatory goals. KEY POINTS: Newer technologies allowed quicker and more comprehensive identification of microbes in tobacco samples, encapsulating microorganisms difficult or impossible to culture. Current research in smokeless tobacco microbiology is filling knowledge gaps previously unfilled due to the lack of suitable approaches. The microbial ecology of smokeless tobacco presents a clearer picture of diversity and variability not considered before.


Assuntos
Microbiota , Tabaco sem Fumaça , Carcinógenos , Humanos , Metagenômica , Nicotiana , Estados Unidos
8.
Appl Microbiol Biotechnol ; 104(2): 751-763, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31820070

RESUMO

Smokeless tobacco (ST) products are used worldwide and are a major public health concern. In addition to harmful chemicals found in these products, microbes found in ST products are believed to be responsible for generating harmful tobacco-specific nitrosamines (TSNAs), the most abundant carcinogens in ST. These microbes also contribute endotoxins and other pro-inflammatory components. A greater understanding of the microbial constituents in these products is sought in order to potentially link select design aspects or manufacturing processes to avoidable increases in harmful constituents. Previous studies looked primarily at bacterial constituents and had not differentiated between viable vs nonviable organisms, so in this study, we sought to use a dual metatranscriptomic and metagenomic analysis to see if differences exist. Using high-throughput sequencing, we observed that there were differences in taxonomic abundances between the metagenome and metatranscriptome, and in the metatranscriptome, we also observed an abundance of plant virus RNA not previously reported in DNA-only studies. We also found in the product tested, that there were no viable bacteria capable of metabolizing nitrate to nitrite. Therefore, the product tested would not be likely to increase TSNAs during shelf storage. We tested only a single product to date using the strategy presented here, but succeeded in demonstrating the value of using of these methods in tobacco products. These results present novel findings from the first combined metagenome and metatranscriptome of a commercial tobacco product.


Assuntos
Perfilação da Expressão Gênica , Metagenômica , Microbiota , Tabaco sem Fumaça/microbiologia , Bactérias/metabolismo , Biotransformação , DNA Bacteriano/genética , Sequenciamento de Nucleotídeos em Larga Escala , Nitratos/metabolismo , Nitritos/metabolismo , RNA Bacteriano/análise , RNA Bacteriano/genética , RNA Viral/análise , RNA Viral/genética
9.
Appl Microbiol Biotechnol ; 104(24): 10613-10629, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33180172

RESUMO

Smokeless tobacco products (STP) contain bacteria, mold, and fungi due to exposure from surrounding environments and tobacco processing. This has been a cause for concern since the presence of microorganisms has been linked to the formation of highly carcinogenic tobacco-specific nitrosamines. These communities have also been reported to produce toxins and other pro-inflammatory molecules that can cause mouth lesions and elicit inflammatory responses in STP users. Moreover, microbial species in these products could transfer to the mouth and gastrointestinal tract, potentially altering the established respective microbiotas of the consumer. Here, we present the first metagenomic analysis of select smokeless tobacco products, specifically US domestic moist and dry snuff. Bacterial, eukaryotic, and viral species were found in all tobacco products where 68% of the total species was comprised of Bacteria with 3 dominant phyla but also included 32% Eukarya and 1% share abundance for Archaea and Viruses. Furthermore, 693,318 genes were found to be present and included nitrate and nitrite reduction and transport enzymes, antibiotic resistance genes associated with resistance to vancomycin, ß-lactamases, their derivatives, and other antibiotics, as well as genes encoding multi-drug transporters and efflux pumps. Additional analyses showed the presence of endo- and exotoxin genes in addition to other molecules associated with inflammatory responses. Our results present a novel aspect of the smokeless tobacco microbiome and provide a better understanding of these products' microbiology. KEY POINTS: • The findings presented will help understand microbial contributions to overall STP chemistries. • Gene function categorization reveals harmful constituents outside canonical forms. • Pathway genes for TSNA precursor activity may occur at early stages of production. • Bacteria in STPs carry antibiotic resistance genes and gene transfer mechanisms.


Assuntos
Microbiota , Tabaco sem Fumaça , Bactérias/genética , Metagenoma , Metagenômica , Nicotiana
10.
Anaerobe ; 66: 102279, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33022384

RESUMO

The relationship between the gut microbiota and Clostridioides difficile, and its role in the severity of C. difficile infection in humans is an area of active research. Intestinal carriage of toxigenic and non-toxigenic C. difficile strains, with and without clinical signs, is reported in animals, however few studies have looked at the risk factors associated with C. difficile carriage and the role of the host gut microbiota. Here, we isolated and characterized C. difficile strains from different animal species (predominantly canines (dogs), felines (cats), and equines (horses)) that were brought in for tertiary care at North Carolina State University Veterinary Hospital. C. difficile strains were characterized by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16S rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts. Here, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes including ones known to cause CDI in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridium hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.


Assuntos
Clostridioides difficile/fisiologia , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/veterinária , Fezes/microbiologia , Microbioma Gastrointestinal , Interações Microbianas , Animais , Antibacterianos/farmacologia , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Técnicas de Tipagem Bacteriana , Gatos , Chlorocebus aethiops , Clostridioides difficile/classificação , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/microbiologia , Técnicas de Cocultura , Cães , Feminino , Cavalos , Hospitais Veterinários , Interações Hospedeiro-Patógeno , Masculino , Testes de Sensibilidade Microbiana , North Carolina , Reação em Cadeia da Polimerase , Prevalência , RNA Ribossômico 16S , Ribotipagem , Fatores de Risco , Atenção Terciária à Saúde , Células Vero
11.
Eur J Neurol ; 26(9): 1200-1204, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30977955

RESUMO

BACKGROUND AND PURPOSE: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. METHODS: This was a prospective, longitudinal, single-center study. sNfL concentration was assessed using a highly sensitive single-molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P-MS). Twenty-one healthy pregnant women (HPW) served as a control group. Eight P-MS suffered relapses during pregnancy (P-MS-R) in the first or second trimesters. RESULTS: No differences in pregnancy and delivery data were observed between P-MS and HPW. P-MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P-MS-R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P-MS-R showed higher sNfL values than those with no relapses during gestation (P = 0.02). CONCLUSION: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.


Assuntos
Esclerose Múltipla/sangue , Proteínas de Neurofilamentos/sangue , Complicações na Gravidez/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Gravidez
12.
Med Oral Patol Oral Cir Bucal ; 24(5): e588-e594, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433390

RESUMO

BACKGROUND: Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. MATERIAL AND METHODS: descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. RESULTS: 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p <0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). CONCLUSIONS: the profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records.


Assuntos
Acidentes de Trânsito , Traumatismos Maxilofaciais , Adolescente , Idoso , Chile , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Violência
13.
Mol Psychiatry ; 22(12): 1735-1745, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28194001

RESUMO

Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca2+ channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established. In the present study, we directly manipulated Cav1.3 channels in Cav1.2 dihydropyridine insensitive mutant mice and found that ventral tegmental area (VTA) Cav1.3 channels mediate cocaine-related and depressive-like behavior through a common nucleus accumbens (NAc) shell calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) mechanism that requires GluA1 phosphorylation at S831. Selective activation of VTA Cav1.3 with (±)-BayK-8644 (BayK) enhanced cocaine conditioned place preference and cocaine psychomotor activity while inducing depressive-like behavior, an effect not observed in S831A phospho-mutant mice. Infusion of the CP-AMPAR-specific blocker Naspm into the NAc shell reversed the cocaine and depressive-like phenotypes. In addition, activation of VTA Cav1.3 channels resulted in social behavioral deficits. In contrast to the cocaine- and depression-related phenotypes, GluA1/A2 AMPARs in the NAc core mediated social deficits, independent of S831-GluA1 phosphorylation. Using a candidate gene analysis approach, we also identified single-nucleotide polymorphisms in the CACNA1D gene associated with cocaine dependence in human subjects. Together, our findings reveal novel, overlapping mechanisms through which VTA Cav1.3 mediates cocaine-related, depressive-like and social phenotypes, suggesting that Cav1.3 may serve as a target for the treatment of neuropsychiatric symptoms.


Assuntos
Afeto/fisiologia , Canais de Cálcio Tipo L/metabolismo , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Núcleo Accumbens/metabolismo , Área Tegmentar Ventral/metabolismo , Afeto/efeitos dos fármacos , Animais , Canais de Cálcio Tipo L/genética , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Depressão/metabolismo , Modelos Animais de Doenças , Estudos de Associação Genética , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Densidade Pós-Sináptica/efeitos dos fármacos , Densidade Pós-Sináptica/metabolismo , Receptores de AMPA/metabolismo , Comportamento Social , Área Tegmentar Ventral/efeitos dos fármacos
14.
J Endocrinol Invest ; 41(7): 755-764, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29204916

RESUMO

BACKGROUND: In a previous work, we found linkage and association of type 1 diabetes (T1D) to a 12 known gene region at chromosome 2p25 in Colombian families. Here, we present further work on this candidate region. MATERIALS AND METHODS: Seventeen SNPs located on the 12 candidate genes, in 100 familial trios set, were tested by ARMS-tetraprimer-PCR or PCR-RFLP. Five extra SNPs in the vicinity of rs10186193 were typed. A replica phase included 97 novel familial trios, in whom diabetes-related auto-antibodies (AABs) were tested in sera of the patients. In addition to transmission disequilibrium tests, haplotype analyses were carried out using the unphased software. RESULTS: SNP rs10186193 (at RNASEH1 gene) showed association with T1D (P = 0.005). The additional five SNPs revealed that rs7607888 (P = 2.03 × 10-7), rs55981318 (P = 0.018), and rs1136545 (P = 1.93 × 10-9) were also associated with T1D. Haplotype analysis showed association for rs55981318-rs10186193 (P = 0.0005), rs7563960-rs7607888 (P = 0.0007), rs7607888-rs1136545 (P = 9.21 × 10-10), and rs1136545-rs11538545 (P = 6.67 × 10-8). In contrast, the new set of 97 familial trios tested for SNPs rs55981318, rs10186193, and rs7607888 did not support the previous finding; however, by combining the sample (197 trios), evidence of association of T1D with rs55981318 and rs7607888 was conclusive. In addition, a two-loci haplotype analysis of the combined sample showed significant association of RNASEH1 with T1D (P = 3.1 × 10-5). CONCLUSION: In conclusion, our analyses suggest that RNASEH1 gene variants associate with susceptibility/protection to T1D in Colombia.


Assuntos
Diabetes Mellitus Tipo 1/genética , Polimorfismo de Nucleotídeo Único , Ribonuclease H/genética , Adulto , Criança , Colômbia/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Família , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição
15.
Clin Genet ; 91(4): 640-646, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27874174

RESUMO

〈 We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non-asphyxiating), trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.-11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer-Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.


Assuntos
Proteínas de Transporte/genética , Ciliopatias/genética , Craniossinostoses/genética , Predisposição Genética para Doença , Deficiência Intelectual/genética , Ciliopatias/diagnóstico , Ciliopatias/fisiopatologia , Craniossinostoses/diagnóstico , Craniossinostoses/fisiopatologia , Exoma/genética , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Masculino , Linhagem , Sítios de Splice de RNA/genética , Deleção de Sequência/genética
16.
Mar Drugs ; 15(12)2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29194350

RESUMO

Fish oil is used in the production of feed for cultured fish owing to its high polyunsaturated fatty acid content (PUFA). The over-exploitation of fisheries and events like "El Niño" are reducing the fish oil supply. Some marine microorganisms are considered potentially as alternative fatty acid sources. This study assesses a strain of Rhodotorula sp. (strain CNYC4007; 27% docosahexaenoic acid (DHA) of total fatty acids), as feed for fish larvae. The total length and ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) ratio of Danio rerio larvae was determined at first feeding at six and 12 days old (post-yolk absorption larvae). Larvae fed with microencapsulated Rhodotorula sp. CNYC4007 had a significantly higher RNA/DNA ratio than control group (C1). At six days post-yolk absorption group, the RNA/DNA ratio of larvae fed with Rhodotorula sp. bioencapsulated in Brachionus sp. was significantly higher than control group fed with a commercial diet high in DHA (C2-DHA). Finally, at 12 days post-yolk absorption, the RNA/DNA ratio was significantly higher in larvae fed with Rhodotorula sp. CNYC4007 and C2-DHA (both bioencapsulated in Artemia sp. nauplii) than in control group (C1). These results suggest that Rhodotorula sp. CNYC4007 can be an alternative source of DHA for feeding fish at larval stage, providing a sustainable source of fatty acids.


Assuntos
Ração Animal , Peixes , Rhodotorula , Animais , Organismos Aquáticos , Larva
18.
N C Med J ; 78(4): 230-236, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28724669

RESUMO

Seeds of HOPE (Health, Opportunities, Partnerships, and Empowerment) was a community-based participatory research project designed to implement an evidence-based weight loss and empowerment intervention aimed at increasing self-efficacy through peer support. HOPE Works, its model, has yielded significant weight loss and increases in participants' ability to set and achieve goals, including in consumption of fruits and vegetables and in physical activity.METHODS The Seeds of HOPE project was implemented through 3 peer leader recruitment approaches using Circle Leaders. Study participants met in hope circles to discuss various topics aimed at developing healthier lifestyles. Changes at 6-month intervals were assessed in health behaviors, weight, and hope. One-way ANOVA was used to test differences in mean change in weight and hope across the 3 recruitment approaches.RESULTS Study participants (N = 146) lost weight (-3.3 pounds, P = 0.003, 95% CI: -5.40 - -1.27). Fruit consumption significantly increased (P = 0.04, 95% CI: 0.01-0.41) while no changes in vegetable consumption or physical activity were observed. No differences based on different leader recruitment approaches were found.LIMITATIONS There were limitations in the power to fully detect differences across Circle Leader recruitment approaches; loss-to-follow up and representativeness of the sample were present. Further research is needed to determine if these approaches would be successful in other rural counties, with different genders, or with individuals in urban and/or higher socioeconomic populations.CONCLUSIONS Participants found modest success in weight loss and fruit consumption. Authors find that community engagement strategies are helpful in finding mutually acceptable adaptations to implement interventions such as Seeds of HOPE in diverse communities.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Programas de Redução de Peso , Dieta , Feminino , Frutas , Humanos , Pessoa de Meia-Idade , North Carolina , Avaliação de Programas e Projetos de Saúde , Autoeficácia , Apoio Social , Redução de Peso
19.
Eur J Clin Microbiol Infect Dis ; 35(12): 1997-2003, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27549108

RESUMO

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC ß-lactamases (AmpC-Ec-BSI). In a multi-centre case-control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p < 0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p = 0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p = 0.03; LOS 17.5 days vs. 6 in controls, p = 0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p < 0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/patologia , Proteínas de Bactérias/metabolismo , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/patologia , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Estudos de Casos e Controles , DNA Bacteriano/química , DNA Bacteriano/genética , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Análise de Sequência de DNA , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Appl Opt ; 55(8): 2002-10, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26974795

RESUMO

Ray tracing in spherical Luneburg lenses has always been represented in 2D. All propagation planes in a 3D spherical Luneburg lens generate the same ray tracing, due to its radial symmetry. A geometry without radial symmetry generates a different ray tracing. For this reason, a new ray tracing method in 3D through spherical and elliptical Luneburg lenses using 2D methods is proposed. The physics of the propagation is shown here, which allows us to make a ray tracing associated with a vortex beam. A 3D ray tracing in a composite modified Luneburg lens that represents the human eye lens is also presented.


Assuntos
Imageamento Tridimensional/métodos , Cristalino/anatomia & histologia , Lentes , Humanos , Refratometria
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