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1.
Nat Commun ; 15(1): 2817, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561399

RESUMO

Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients' lives. However, our understanding of biomarkers driving OA risk remains limited. We developed a model predicting the five-year risk of OA diagnosis, integrating retrospective clinical, lifestyle and biomarker data from the UK Biobank (19,120 patients with OA, ROC-AUC: 0.72, 95%CI (0.71-0.73)). Higher age, BMI and prescription of non-steroidal anti-inflammatory drugs contributed most to increased OA risk prediction ahead of diagnosis. We identified 14 subgroups of OA risk profiles. These subgroups were validated in an independent set of patients evaluating the 11-year OA risk, with 88% of patients being uniquely assigned to one of the 14 subgroups. Individual OA risk profiles were characterised by personalised biomarkers. Omics integration demonstrated the predictive importance of key OA genes and pathways (e.g., GDF5 and TGF-ß signalling) and OA-specific biomarkers (e.g., CRTAC1 and COL9A1). In summary, this work identifies opportunities for personalised OA prevention and insights into its underlying pathogenesis.


Assuntos
Osteoartrite , Humanos , Estudos Retrospectivos , Osteoartrite/diagnóstico , Osteoartrite/genética , Osteoartrite/tratamento farmacológico , Biomarcadores , Anti-Inflamatórios não Esteroides/uso terapêutico , Aprendizado de Máquina , Proteínas de Ligação ao Cálcio
2.
Phys Rev E ; 109(1-2): 015207, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38366438

RESUMO

Three-dimensional magnetohydrodynamic simulations are able to model the generation of disk-shaped plasma, driven by laser ablation from a current-carrying rod in a pulsed-power machine producing azimuthal magnetic fields of 2-3 MG. The plasma at such extreme conditions is unique in that the parameter space for the plasma ß and Hall parameter χ transition from below unity to greater than unity at different stages of the plasma generation. In simulations, the formation of the plasma disk in the azimuthal direction is driven by heat flux from the laser spot and depends on the set of transport coefficients used in simulations. The most recent set of transport coefficients leads to the formation of plasma ejecta at the back end of the rod, which qualitatively matches experiments. Specifically, the cross-gradient Nernst effect, which twists the magnetic field, is shown to have a large effect on the shape of the back-end ejecta. In the direction along the axis of the rod, there is propagation of perturbations from the disk as observed in experiments. In simulations, the period of temperature perturbations is in good agreement with experimental results. An instability due to coupling of heat flux and the magnetic field advection provides a possible explanation for perturbation growth along the axis of the rod, and the instability growth rate is consistent with experimental results.

3.
Rev Bras Parasitol Vet ; 32(2): e016022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37132736

RESUMO

Stomoxys calcitrans causes losses to livestock, mainly to cattle. This study aimed to determine the pathogenic potential of Heterorhabditis bacteriophora HP88 and H. baujardi LPP7 against S. calcitrans larvae after being exposed to byproducts of the sugar and alcohol industry. The efficacy of EPNs on stable fly larvae was evaluated in bioassays with vinasse at three temperatures (16, 25 and 35 °C) and concentrations (0, 50 and 100%), as well as in relation to larva age (4, 6 and 8 days) in filter cake and EPNs concentration (100, 300 and 500 IJs/larva) in sugarcane bagasse. H. bacteriophora showed higher efficacy than H. baujardi at all temperatures. Vinasse did not have a negative effect on the virulence of H. bacteriophora. The age of fly larvae did not affect the mortality rates caused by the EPNs. In bagasse, H. bacteriophora presented higher mortality rates than the control group. It is concluded that EPNs can be a potential component in integrated strategies of stable fly control and outbreak prevention in areas of sugar and alcohol production.


Assuntos
Muscidae , Nematoides , Saccharum , Animais , Bovinos , Larva/parasitologia , Celulose , Açúcares , Virulência , Controle Biológico de Vetores
4.
Open Forum Infect Dis ; 9(11): ofac535, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36381625

RESUMO

Background: Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs). Methods: The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted. Results: Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response). Conclusions: Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

5.
Clin Infect Dis ; 74(1): 144-148, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32604407

RESUMO

We are learning that the host response to severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a "one size fits all" approach to immunomodulation in patients with coronavirus disease 2019 (COVID-19). We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anticytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.


Assuntos
COVID-19 , Imunomodulação , Medicina de Precisão , COVID-19/imunologia , COVID-19/terapia , Citocinas , Humanos , Imunidade , Pulmão , SARS-CoV-2
6.
Rev Bras Parasitol Vet ; 30(3): e003721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431927

RESUMO

Stomoxys calcitrans is a hematophagous dipteran. Several agents are used in biological control, including entomopathogenic nematodes (EPNs). Bioassay I involved an evaluation of the effect of Heterorhabditis bacteriophora HP88 and Heterorhabditis baujardi LPP7 on S. calcitrans larvae in different periods of exposure. Groups of 10 larvae were placed in Petri dishes and 200 EPNs/larva were added, which were divided into groups according to the exposure times of 2, 4, 6, 12, 24 and 48 hours. The purpose of Bioassay II was to evaluate the efficacy of the EPNs in infecting S. calcitrans larvae when they were isolated from stable fly larvae in Bioassay I. Groups of 10 larvae were placed in Petri dishes and 200 EPNs/larva were added. In bioassay I, H. bacteriophora caused mortality rates of 51.7, 83.3 and 91.7% in 12, 24 and 48 hours, respectively, while H. baujardi caused mortality rates of 9.3 (12h), 35 (24h) and 35% (48h). In Bioassay II, H. bacteriophora and H. baujardi resulted in mortality rates of 35% and 25%, respectively. It was concluded that the longest exposure times presented the highest larval mortality and that EPNs isolated from S. calcitrans are not efficient in controlling the larvae fly.


Assuntos
Muscidae , Nematoides , Animais , Larva , Controle Biológico de Vetores , Reinfecção/veterinária
7.
Clin Immunol ; 228: 108731, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33892201

RESUMO

In hosts with damaged or impaired immune systems such as those undergoing hematopoietic cell transplant (HCT) or intensive chemotherapy, breakthrough fungal infections can be fatal. Risk factors for breakthrough infections include severe neutropenia, use of corticosteroids, extended use of broad-spectrum antibiotics, and intensive care unit admission. An individual's cumulative state of immunosuppression directly contributes to the likelihood of experiencing increased infection risk. Incidence of invasive fungal infection (IFI) after HCT may be up to 5-8%. Early intervention may improve IFI outcomes, although many infections are resistant to standard therapies (voriconazole, caspofungin, micafungin, amphotericin B, posaconazole or itraconazole, as single agents or in combination). We review herein several contributing factors that may contribute to the net state of immunosuppression in recipients of HCT. We also review a new approach for IFI utilizing adjunctive therapy with sargramostim, a yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF).


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Infecções Fúngicas Invasivas/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Transplante Homólogo , Resultado do Tratamento
8.
Front Pharmacol ; 12: 735443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35111042

RESUMO

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

9.
Rev. bras. parasitol. vet ; 30(3): e003721, 2021. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1288701

RESUMO

Abstract Stomoxys calcitrans is a hematophagous dipteran. Several agents are used in biological control, including entomopathogenic nematodes (EPNs). Bioassay I involved an evaluation of the effect of Heterorhabditis bacteriophora HP88 and Heterorhabditis baujardi LPP7 on S. calcitrans larvae in different periods of exposure. Groups of 10 larvae were placed in Petri dishes and 200 EPNs/larva were added, which were divided into groups according to the exposure times of 2, 4, 6, 12, 24 and 48 hours. The purpose of Bioassay II was to evaluate the efficacy of the EPNs in infecting S. calcitrans larvae when they were isolated from stable fly larvae in Bioassay I. Groups of 10 larvae were placed in Petri dishes and 200 EPNs/larva were added. In bioassay I, H. bacteriophora caused mortality rates of 51.7, 83.3 and 91.7% in 12, 24 and 48 hours, respectively, while H. baujardi caused mortality rates of 9.3 (12h), 35 (24h) and 35% (48h). In Bioassay II, H. bacteriophora and H. baujardi resulted in mortality rates of 35% and 25%, respectively. It was concluded that the longest exposure times presented the highest larval mortality and that EPNs isolated from S. calcitrans are not efficient in controlling the larvae fly.


Resumo Stomoxys calcitrans é um díptero hematófago. Vários agentes são usados no controle biológico, incluindo nematoides entomopatogênicos (NEPs). O bioensaio I objetivou avaliar o efeito de Heterorhabditis bacteriophora HP88 e Heterorhabditis baujardi LPP7 sobre larvas de S. calcitrans em diferentes períodos de exposição. Grupos de 10 larvas foram colocados em placas de Petri, adicionou-se 200 NEPs/larva, e foram divididos de acordo com tempos de exposição de 2, 4, 6, 12, 24 e 48 horas. O objetivo do Bioensaio II foi avaliar a eficácia dos NEPs na infecção de larvas de S. calcitrans, quando esses foram isolados de larvas da mosca oriundos do Bioensaio I. Os grupos de 10 larvas foram colocados em placas de Petri e 200 NEPs/larva foram adicionados. No bioensaio I, H. bacteriophora causou taxas de mortalidade de 51,7%, 83,3% e 91,7% em 12, 24 e 48 horas, respectivamente, enquanto H. baujardi causou taxas de mortalidade de 9,3% (12h), 35% (24h) e 35% (48h). No Bioensaio II, H. bacteriophora e H. baujardi resultaram em taxas de mortalidade de 35% e 25%, respectivamente. Concluiu-se que os maiores tempos de exposição apresentaram as maiores mortalidades larvais e que NEPs isolados de S. calcitrans não são eficientes no controle das larvas mosca.


Assuntos
Animais , Muscidae , Nematoides , Controle Biológico de Vetores , Reinfecção/veterinária , Larva
10.
Mol Genet Genomic Med ; 8(6): e1248, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32307928

RESUMO

BACKGROUND: Severe hypercholesterolemia (HC, LDL-C > 4.9 mmol/L) affects over 30 million people worldwide. In this study, we validated a new polygenic risk score (PRS) for LDL-C. METHODS: Summary statistics from the Global Lipid Genome Consortium and genotype data from two large populations were used. RESULTS: A 36-SNP PRS was generated using data for 2,197 white Americans. In a replication cohort of 4,787 Finns, the PRS was strongly associated with the LDL-C trait and explained 8% of its variability (p = 10-41 ). After risk categorization, the risk of having HC was higher in the high- versus low-risk group (RR = 4.17, p < 1 × 10-7 ). Compared to a 12-SNP LDL-C raising score (currently used in the United Kingdom), the PRS explained more LDL-C variability (8% vs. 6%). Among Finns with severe HC, 53% (66/124) versus 44% (55/124) were classified as high risk by the PRS and LDL-C raising score, respectively. Moreover, 54% of individuals with severe HC defined as low risk by the LDL-C raising score were reclassified to intermediate or high risk by the new PRS. CONCLUSION: The new PRS has a better predictive role in identifying HC of polygenic origin compared to the currently available method and can better stratify patients into diagnostic and therapeutic algorithms.


Assuntos
Hipercolesterolemia/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Idoso , LDL-Colesterol/genética , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
11.
Clin Immunol ; 210: 108292, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676420

RESUMO

Granulocyte-macrophage-colony stimulating factor (GM-CSF), can direct the activation, proliferation and differentiation of myeloid-derived cells. It is also responsible for maturation and function of professional antigen presenting cells thereby impacting adaptive immune responses, while assisting to maintain epithelial barrier function. GM-CSF in combination with other endogenous cytokines and secondary stimuli, such as tumor necrosis factor can modulate pro-inflammatory monocyte priming via chromatin remodeling and enhanced transcriptional responses, a concept termed "trained immunity". An increase in the incidence of opportunistic fungal infections was recently reported in patients with hematological cancers receiving treatment with the BTK inhibitor, Ibrutinib. Tec Kinase BTK is known to influence the expression of GM-CSFRα and regulates downstream signaling pathways, suggesting a role for GM-CSF in maintenance of defense against fungal infections in immune competent hosts. Further examination of the potential mechanism(s) of action for naturally occurring GM-CSF and recombinant human GM-CSF (rhu-GM-CSF) expressed in yeast (sargramostim) are reviewed.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Imunoterapia/métodos , Infecções/terapia , Saccharomyces cerevisiae/metabolismo , Animais , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Imunidade/efeitos dos fármacos , Imunomodulação , Infecções/imunologia , Inflamação , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Saccharomyces cerevisiae/genética , Fator de Necrose Tumoral alfa/uso terapêutico
12.
Data Brief ; 26: 104408, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31534990

RESUMO

Electrocoagulation consists of the in-situ generation of the coagulant by the electro dissolution of sacrificial electrodes (Mg and Al). This technique, besides being normally used for water treatment, can be used to synthesize Layered Double Hydroxides (LDH) or Hydrotalcites (HT) such as green rust, MgAlCl/LDH, and other oxides as Magnetite. The HT has a high tendency for water in the interlayer to be replaced by anions, these exchange characteristics generate a high interest in the fields of drug administration, photodegradation, catalyst supports, supercapacitors, and water oxidation. There are several routes of synthesis for these compounds such as co-precipitation, hydrolysis of urea, hydrothermal treatment and a novel route by electrocoagulation (EC). This work discloses the data of the energy consumption at laboratory-scale production in the synthesis of hydrotalcite (HT) or Layered Double Hydroxides (LDH) by electrocoagulation, the values obtained through these experiments are intended to provide support due to the lack of information on the energy consumption of this novel production method. Aluminum and AZ31 electrodes were used as a cations source during two- and four-hours operation, at 50 °C with 5 mA cm-2 of current density, and 5 minutes of polarity change for Aluminum and 8 minutes for AZ31 (Magnesium alloy).

13.
Genome Biol Evol ; 11(9): 2633-2652, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400207

RESUMO

In species with genetic sex determination, dosage compensation can evolve to equal expression levels of sex-linked and autosomal genes. Current knowledge about dosage compensation has mainly been derived from male-heterogametic (XX/XY) model organisms, whereas less is understood about the process in female-heterogametic systems (ZZ/ZW). In moths and butterflies, downregulation of Z-linked expression in males (ZZ) to match the expression level in females (ZW) is often observed. However, little is known about the underlying regulatory mechanisms, or if dosage compensation patterns vary across ontogenetic stages. In this study, we assessed dynamics of Z-linked and autosomal expression levels across developmental stages in the wood white (Leptidea sinapis). We found that although expression of Z-linked genes in general was reduced compared with autosomal genes, dosage compensation was actually complete for some categories of genes, in particular sex-biased genes, but equalization in females was constrained to a narrower gene set. We also observed a noticeable convergence in Z-linked expression between males and females after correcting for sex-biased genes. Sex-biased expression increased successively across developmental stages, and male-biased genes were enriched on the Z-chromosome. Finally, all five core genes associated with the ribonucleoprotein dosage compensation complex male-specific lethal were detected in adult females, in correspondence with a reduction in the expression difference between autosomes and the single Z-chromosome. We show that tuning of gene dosage is multilayered in Lepidoptera and argue that expression balance across chromosomal classes may predominantly be driven by enrichment of male-biased genes on the Z-chromosome and cooption of available dosage regulators.


Assuntos
Borboletas/genética , Compensação de Dosagem (Genética) , Animais , Borboletas/crescimento & desenvolvimento , Feminino , Masculino , Cromossomos Sexuais/genética
14.
Bioinformatics ; 35(24): 5182-5190, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31070705

RESUMO

MOTIVATION: Integration of different omics data could markedly help to identify biological signatures, understand the missing heritability of complex diseases and ultimately achieve personalized medicine. Standard regression models used in Genome-Wide Association Studies (GWAS) identify loci with a strong effect size, whereas GWAS meta-analyses are often needed to capture weak loci contributing to the missing heritability. Development of novel machine learning algorithms for merging genotype data with other omics data is highly needed as it could enhance the prioritization of weak loci. RESULTS: We developed cNMTF (corrected non-negative matrix tri-factorization), an integrative algorithm based on clustering techniques of biological data. This method assesses the inter-relatedness between genotypes, phenotypes, the damaging effect of the variants and gene networks in order to identify loci-trait associations. cNMTF was used to prioritize genes associated with lipid traits in two population cohorts. We replicated 129 genes reported in GWAS world-wide and provided evidence that supports 85% of our findings (226 out of 265 genes), including recent associations in literature (NLGN1), regulators of lipid metabolism (DAB1) and pleiotropic genes for lipid traits (CARM1). Moreover, cNMTF performed efficiently against strong population structures by accounting for the individuals' ancestry. As the method is flexible in the incorporation of diverse omics data sources, it can be easily adapted to the user's research needs. AVAILABILITY AND IMPLEMENTATION: An R package (cnmtf) is available at https://lgl15.github.io/cnmtf_web/index.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Estudo de Associação Genômica Ampla , Aprendizado de Máquina , Redes Reguladoras de Genes , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único
15.
World J Surg ; 43(1): 67-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30145672

RESUMO

BACKGROUND: Although many studies have compared outcomes of laparoscopic appendectomy (LA) and open appendectomy (OA), some clinical and economic outcomes continue to be controversial, particularly in low-medium-income countries. We aimed at determining clinical and economic outcomes associated with LA versus OA in adult patients in Colombia. METHODS: Retrospective, cohort study based on administrative healthcare records included all patients who underwent LA or OA in Colombia's contributory regime between July 1, 2013, and September 30, 2015. Outcomes were 30-day mortality rates, ICU admissions rates, length of stay (LOS), and hospital costs provided until discharge. Propensity score matching techniques were used to balance the baseline characteristics of patients (age, sex, comorbidities based on the Charlson index, insurer, and geographic location) and to estimate the average treatment effect (ATE) of LA as compared to OA over outcomes. RESULTS: A total of 65,625 subjects were included, 92.9% underwent OA and 7.1% LA. For the entire population, 30-day mortality was 0.74 per 100 appendectomies (95% CI 0.67-0.81), the mean and median LOS were 3.83 days and 1 day, respectively, and the ICU admissions rate during the first 30 days was 7.92% (95% CI 7.71-8.12). The ATE shows an absolute difference in the mortality rate after 30 days of -0.35 per 100 appendectomies (p = 0.023), in favor of LA. No effects on ICU admissions or LOS were identified. LA was found to increase costs by 514.13 USD on average, with total costs of 772.78 USD for OA and 1286.91 USD for LA (p < 0.001). CONCLUSIONS: In Colombia's contributory regime, LA is associated with lower 30-day mortality rate and higher hospital costs as compared to OA. No differences are found in ICU admissions or LOS.


Assuntos
Apendicectomia/estatística & dados numéricos , Países em Desenvolvimento , Custos de Cuidados de Saúde/estatística & dados numéricos , Laparoscopia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Adulto , Apendicectomia/economia , Apendicectomia/métodos , Apendicectomia/mortalidade , Apendicite/cirurgia , Colômbia/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Laparoscopia/economia , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Cobertura Universal do Seguro de Saúde , Adulto Jovem
16.
Mol Ecol ; 27(4): 935-948, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29411442

RESUMO

In temperate latitudes, many insects enter diapause (dormancy) during the cold season, a period during which developmental processes come to a standstill. The wood white (Leptidea sinapis) is a butterfly species distributed across western Eurasia that shows photoperiod-induced diapause with variation in critical day-length across populations at different latitudes. We assembled transcriptomes and estimated gene expression levels at different developmental stages in experimentally induced directly developing and diapausing cohorts of a single Swedish population of L. sinapis to investigate the regulatory mechanisms underpinning diapause initiation. Different day lengths resulted in expression changes of developmental genes and affected the rate of accumulation of signal molecules, suggesting that diapause induction might be controlled by increased activity of monoamine neurotransmitters in larvae reared under short-day light conditions. Expression differences between light treatment groups of two monoamine regulator genes (DDC and ST) were observed already in instar III larvae. Once developmental pathways were irreversibly set at instar V, a handful of genes related to dopamine production were differentially expressed leading to a significant decrease in expression of global metabolic genes and increase in expression of genes related to fatty acid synthesis and sequestration. This is in line with a time-dependent (hour-glass) model of diapause regulation where a gradual shift in the concentration of monoamine neurotransmitters and their metabolites during development of larvae under short-day conditions leads to increased storage of fat, decreased energy expenditures, and ultimately developmental stasis at the pupal stage.


Assuntos
Borboletas/genética , Borboletas/fisiologia , Diapausa/genética , Perfilação da Expressão Gênica , Madeira , Animais , Borboletas/efeitos da radiação , Relógios Circadianos/genética , Análise por Conglomerados , Diapausa/efeitos da radiação , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Ontologia Genética , Luz
17.
Hum Mutat ; 39(3): 365-370, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29197136

RESUMO

We analyzed 563,099 common (minor allele frequency, MAF≥0.01) and rare (MAF < 0.01) genetic variants annotated in ExAC and UniProt and 26,884 disease-causing variants from ClinVar and UniProt occurring in the coding region of 17,975 human protein-coding genes. Three novel sets of genes were identified: those enriched in rare variants (n = 32 genes), in common variants (n = 282 genes), and in disease-causing variants (n = 800 genes). Genes enriched in rare variants have far greater similarities in terms of biological and network properties to genes enriched in disease-causing variants, than to genes enriched in common variants. However, in half of the genes enriched in rare variants (AOC2, MAMDC4, ANKHD1, CDC42BPB, SPAG5, TRRAP, TANC2, IQCH, USP54, SRRM2, DOPEY2, and PITPNM1), no disease-causing variants have been identified in major, publicly available databases. Thus, genetic variants in these genes are strong candidates for disease and their identification, as part of sequencing studies, should prompt further in vitro analyses.


Assuntos
Genes , Variação Genética , Doença/genética , Genes Essenciais , Humanos , Mutação/genética
18.
Int J Dermatol ; 57(2): 131-138, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28653769

RESUMO

Onychomycosis is a fungal nail infection caused primarily by dermatophytes. Several other nail disorders, including psoriasis, can simulate onychomycosis. Accurate diagnosis is therefore vital for the ongoing treatment and management of onychomycosis and to avoid misdiagnosis and treatment delay, which can be both lengthy and costly. Often, a combination of histologic and laboratory techniques is used to obtain an accurate diagnosis. The potential diagnostic challenges associated with the differential diagnosis of onychomycosis caused by dermatophytes and the most common techniques used to confirm the diagnosis are discussed.


Assuntos
Micologia/métodos , Onicomicose/diagnóstico , Onicomicose/patologia , Benzenossulfonatos , Biópsia , Diagnóstico Diferencial , Corantes Fluorescentes , Humanos , Hidróxidos , Técnicas Microbiológicas , Unhas/microbiologia , Unhas/patologia , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Reação do Ácido Periódico de Schiff , Reação em Cadeia da Polimerase , Compostos de Potássio , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
Rev. bras. parasitol. vet ; 26(4): 451-456, Oct.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-899298

RESUMO

Abstract The present study verified the pathogenic potential of entomopathogenic nematodes (EPNs) of the genus Heterorhabditis (Heterorhabditis bacteriophora, isolate HP88 and Heterorhabditis baujardi isolate LPP7) to immature stages of Stomoxys calcitrans in the laboratory. All EPN concentrations of the H. bacteriophora HP88 strain caused mean larval mortality greater than 90% after four days. Higher concentrations of the H. baujardi LPP7 isolate (≥50 EPNs/larva) eliminated more than 70% of larvae after six days with the concentration 200 EPNs/larva reaching mortality levels of 93.3%. The larval mortality at all concentrations of EPNs (25, 50, 100, 150, and 200 EPNs/larva) for both strains was significant (p<0.05) when compared to the respective control groups. Concentrations of H. bacteriophora HP88 yielded an LC50 of 0.36 EPN/larva and LC90 of 29.1; while H. baujardi LPP7 yielded an LC50 of 39.85 and LC90 of 239.18. H. bacteriophora HP88 provided greater inhibition of the emergence of adults when compared to the response obtained with H. baujardi LPP7. EPNs did not cause considerable mortality when applied directly to pupae. The set of observed results suggests that the EPNs of the genus Heterorhabditis, isolates HP88 and LPP7, are a promising alternative in the control of the stable fly.


Resumo O presente estudo verificou o potencial patogênico de nematoides (NEP) do gênero Heterorhabditis (H. bacteriophora - isolado HP88 e H. baujardi - isolado LPP7) para estágios imaturos de Stomoxys calcitrans em laboratório. Todas as concentrações de NEPs da cepa HP88 causaram mortalidade larval média maior que 90% após quatro dias. Concentrações mais elevadas da cepa LPP7 (≥50 NEPs/larva) eliminaram mais de 70% após seis dias, com a concentração 200 NEPs/larva atingindo níveis de 93,3%. A mortalidade larval em todas as concentrações de NEPs (25, 50, 100, 150, and 200 NEPs/larva) para ambas as cepas foi significativa (p<0,05), quando comparadas aos respectivos grupos controle. Concentrações de H. bacteriophora HP88 obtiveram LC50 de 0,36 NEP/larva e LC90 de 29,1; enquanto H. baujardi LPP7 obteve LC50 de 39,85 e LC90 de 239,18. O isolado H. bacteriophora HP88 propiciou maior inibição da emergência de adultos, quando comparado à resposta obtida com H. baujardi LPP7. NEPs não provocaram mortalidade considerável quando aplicados diretamente sobre pupas. O conjunto de resultados observados indica os nematoides entomopatogênicos do gênero Heterorhabditis (estirpes HP88 e LPP7) como uma alternativa promissora no controle da mosca dos estábulos.


Assuntos
Muscidae/parasitologia , Controle Biológico de Vetores/métodos , Rabditídios/patogenicidade , Infecções por Rhabditida , Larva
20.
Rev Bras Parasitol Vet ; 26(4): 451-456, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29160358

RESUMO

The present study verified the pathogenic potential of entomopathogenic nematodes (EPNs) of the genus Heterorhabditis (Heterorhabditis bacteriophora, isolate HP88 and Heterorhabditis baujardi isolate LPP7) to immature stages of Stomoxys calcitrans in the laboratory. All EPN concentrations of the H. bacteriophora HP88 strain caused mean larval mortality greater than 90% after four days. Higher concentrations of the H. baujardi LPP7 isolate (≥50 EPNs/larva) eliminated more than 70% of larvae after six days with the concentration 200 EPNs/larva reaching mortality levels of 93.3%. The larval mortality at all concentrations of EPNs (25, 50, 100, 150, and 200 EPNs/larva) for both strains was significant (p<0.05) when compared to the respective control groups. Concentrations of H. bacteriophora HP88 yielded an LC50 of 0.36 EPN/larva and LC90 of 29.1; while H. baujardi LPP7 yielded an LC50 of 39.85 and LC90 of 239.18. H. bacteriophora HP88 provided greater inhibition of the emergence of adults when compared to the response obtained with H. baujardi LPP7. EPNs did not cause considerable mortality when applied directly to pupae. The set of observed results suggests that the EPNs of the genus Heterorhabditis, isolates HP88 and LPP7, are a promising alternative in the control of the stable fly.


Assuntos
Muscidae , Controle Biológico de Vetores/métodos , Rabditídios/patogenicidade , Animais , Larva , Muscidae/parasitologia , Infecções por Rhabditida
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