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1.
Ann Vasc Surg ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009131

RESUMO

OBJECTIVE: To investigate impact of Frozen Elephant Trunk (FET) on long-term distal aortic remodelling in acute AAD according to the latest recommended standards from the Society for Vascular Surgery (SVS)/Society of Thoracic Surgeons (STS). METHODS: Clinical data and imaging of patients undergone FET to treat acute AAD over the last 8 years were retrospectively reviewed. Patients were included if a pre- and post-operative Computed AngioTomographies at least 30-day from surgery was available for comparison. Contrasted postprocessed imaging were analysed with Aquarius iNtuition (TeraRecon Inc., Foster City, CA, USA) to analyse long-term positive aortic remodelling, FL thrombosis and aortic expansion according to the SVS/STS recommendations. Secondary endpoints were the rate of in-hospital and long-term mortality, spinal cord ischaemia and aortic-related reinterventions. RESULTS: Out of 75 patients who underwent FET for type A AAD, n=41(54.6%) were included. Significant positive aortic remodelling was reported in Ishimaru zone 1-4 but not in visceral/infrarenal aorta (p<0.001) and overall rate of FL thrombosis was 95.1% (n=39). Aortic expansion rates were: 4.9% in zones 1-4, 8.3% in zones 5-6 and 15% in zone 7. The rates of in-hospital mortality and long-term mortality were 7.3% (n=3) and 9.7% (n=4) respectively. At a median follow-up of 11 months (range 1-141, reintervention rate was 17.1%. CONCLUSIONS: We report positive aortic remodelling of the distal thoracic aorta in patients who underwent FET for acute AAD according to the SVS/STS reporting standards. The positive effect on the distal aorta is limited to the thoracic segments but not in the visceral aorta.

2.
J Am Chem Soc ; 145(36): 19832-19839, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37642292

RESUMO

Site-selective radical reactions of benzylic C-H bonds are now highly effective methods for C(sp3-H) functionalization and cross-coupling. The existing methods, however, are often ineffective with heterobenzylic C-H bonds in alkyl-substituted pyridines and related aromatic heterocycles that are prominently featured in pharmaceuticals and agrochemicals. Here, we report new synthetic methods that leverage polar, rather than radical, reaction pathways to enable the selective heterobenzylic C-H chlorination of 2- and 4-alkyl-substituted pyridines and other heterocycles. Catalytic activation of the substrate with trifluoromethanesulfonyl chloride promotes the formation of enamine tautomers that react readily with electrophilic chlorination reagents. The resulting heterobenzyl chlorides can be used without isolation or purification in nucleophilic coupling reactions. This chlorination-diversification sequence provides an efficient strategy to achieve heterobenzylic C-H cross-coupling with aliphatic amines and a diverse collection of azoles, among other coupling partners.

3.
Glob Chang Biol ; 29(6): 1530-1544, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36495084

RESUMO

Climate warming is leading to permafrost thaw in northern peatlands, and current predictions suggest that thawing will drive greater surface wetness and an increase in methane emissions. Hydrology largely drives peatland vegetation composition, which is a key element in peatland functioning and thus in carbon dynamics. These processes are expected to change. Peatland carbon accumulation is determined by the balance between plant production and peat decomposition. But both processes are expected to accelerate in northern peatlands due to warming, leading to uncertainty in future peatland carbon budgets. Here, we compile a dataset of vegetation changes and apparent carbon accumulation data reconstructed from 33 peat cores collected from 16 sub-arctic peatlands in Fennoscandia and European Russia. The data cover the past two millennia that has undergone prominent changes in climate and a notable increase in annual temperatures toward present times. We show a pattern where European sub-Arctic peatland microhabitats have undergone a habitat change where currently drier habitats dominated by Sphagnum mosses replaced wetter sedge-dominated vegetation and these new habitats have remained relatively stable over the recent decades. Our results suggest an alternative future pathway where sub-arctic peatlands may at least partly sustain dry vegetation and enhance the carbon sink capacity of northern peatlands.


Assuntos
Sequestro de Carbono , Sphagnopsida , Ecossistema , Solo , Carbono
4.
Mol Biol Rep ; 50(2): 981-991, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36378419

RESUMO

PURPOSE: Oct3/4 a transcription factor is involved in maintaining the characteristics of cancer stem cells. Oct3/4 can be expressed differentially with respect to the progression of cervical cancer (CC). In addition, Oct3/4 can give rise to three isoforms by alternative splicing of the mRNA Oct3/4A, Oct3/4B and Oct3/4B1. The aim of this study was to evaluate the mRNA expression from Oct3/4A, Oct3/4B and Oct3/4B1 in low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), CC samples, and measure the effect of the HPV16 E7 oncoprotein on the mRNA expression from Oct3/4 isoforms in the C-33A cell line. METHODS: The expression levels of Oct3/4A, Oct3/4B and Oct3/4B1 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with LSILs, HSILs and CC. Additionally, C-33A cells that expressed the HPV16 E7 oncoprotein were established to evaluate the effect of E7 on the expression of Oct3/4 mRNA isoforms. RESULTS: Oct3/4A (p = 0.02), Oct3/4B (p = 0. 001) and Oct3/4B1 (p < 0. 0001) expression is significantly higher in patients with LSIL, HSIL and CC than in woman with non-IL. In the C-33A cell line, the expression of Oct3/4A mRNA in the presence of the E7 oncoprotein increased compared to that in nontransfected C-33A cells. CONCLUSION: Oct3/4B and Oct3/4B1 mRNA were expressed at similar levels among the different groups. These data indicate that only the mRNA of Oct3/4A is upregulated by the HPV16 E7 oncoprotein.


Assuntos
Papillomavirus Humano 16 , Fator 3 de Transcrição de Octâmero , Neoplasias do Colo do Útero , Feminino , Humanos , Processamento Alternativo/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo
5.
BMC Infect Dis ; 22(1): 917, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482326

RESUMO

BACKGROUND: Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. METHODS: A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. RESULTS: None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. CONCLUSIONS: At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.


Assuntos
COVID-19 , Ivermectina , Humanos , Progressão da Doença , Ivermectina/uso terapêutico , SARS-CoV-2 , Estados Unidos
6.
Brain Inj ; 36(8): 939-947, 2022 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-35904331

RESUMO

This prospective multicenter study evaluated differences in concussion severity and functional outcome using glial and neuronal biomarkers glial Fibrillary Acidic (GFAP) and Ubiquitin C-terminal Hydrolase (UCH-L1) in children and youth involved in non-sport related trauma, organized sports, and recreational activities. Children and youth presenting to three Level 1 trauma centersfollowing blunt head trauma with a GCS 15 with a verified diagnosis of a concussion were enrolled within 6 hours of injury. Traumatic intracranial lesions on CT scan and functional outcome within 3 months of injury were evaluated. 131 children and youth with concussion were enrolled, 81 in the no sports group, 22 in the organized sports group and 28 in the recreational activities group. Median GFAP levels were 0.18, 0.07, and 0.39 ng/mL in the respective groups (p = 0.014). Median UCH-L1 levels were 0.18, 0.27, and 0.32 ng/mL respectively (p = 0.025). A CT scan of the head was performed in 110 (84%) patients. CT was positive in 5 (7%), 4 (27%), and 5 (20%) patients, respectively. The AUC for GFAP for detecting +CT was 0.84 (95%CI 0.75-0.93) and for UCH-L1 was 0.82 (95%CI 0.71-0.94). In those without CT lesions, elevations in UCH-L1 were significantly associated with unfavorable 3-month outcome. Concussions in the 3 groups were of similar severity and functional outcome. GFAP and UCH-L1 were both associated with severity of concussion and intracranial lesions, with the most elevated concentrations in recreational activities .


Assuntos
Concussão Encefálica , Traumatismos Cranianos Fechados , Adolescente , Biomarcadores , Concussão Encefálica/diagnóstico por imagem , Criança , Proteína Glial Fibrilar Ácida , Humanos , Estudos Prospectivos
7.
Opt Express ; 29(15): 23500-23507, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34614614

RESUMO

We apply an InGaAs quantum dot based single-photon source for the absolute detection efficiency calibration of a silicon single-photon avalanche diode operating in Geiger mode. The single-photon source delivers up to (2.55 ± 0.02) × 106 photons per second inside a multimode fiber at the wavelength of 929.8 nm for above-band pulsed excitation with a repetition rate of 80 MHz. The purity of the single-photon emission, expressed by the value of the 2nd order correlation function g(2)(τ = 0), is between 0.14 and 0.24 depending on the excitation power applied to the quantum dot. The single-photon flux is sufficient to be measured with an analog low-noise reference detector, which is traceable to the national standard for optical radiant flux. The measured detection efficiency using the single-photon source remains constant within the measurement uncertainty for different photon fluxes. The corresponding weighted mean thus amounts to 0.3263 with a standard uncertainty of 0.0022.

8.
J Card Surg ; 36(3): 848-856, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33442890

RESUMO

BACKGROUND: A significant restructuring of the healthcare services has taken place since the declaration of the coronavirus disease 2019 (COVID-19) pandemic, with elective surgery put on hold to concentrate intensive care resources to treat COVID-19 as well as to protect patients who are waiting for relatively low risk surgery from exposure to potentially infected hospital environment. METHODS: Multicentre study, with 19 participating centers, to define the impact of the pandemic on the provision of aortovascular services and patients' outcomes after having adapted the thresholds for intervention to guarantee access to treatment for emergency and urgent conditions. Retrospective analysis of prospectively collected data, including all patients with aortovascular conditions admitted for surgical or conservative treatment from the 1st March to the 20th May 2020. RESULTS: A total of 189 patients were analyzed, and 182 underwent surgery. Diagnosis included: aneurysm (45%), acute aortic syndrome (44%), pseudoaneurysm (4%), aortic valve endocarditis (4%), and other (3%). Timing for surgery was: emergency (40%), urgent (34%), or elective (26%). In-hospital mortality was 12%. Thirteen patients were diagnosed with COVID-19 during the peri-operative period, and this subgroup was not associated with a higher mortality. CONCLUSIONS: There was a significant change in service provision for aortovascular patients in the UK. Although the emergency and urgent surgical activity were maintained, elective treatment was minimal during early months of the pandemic. The preoperative COVID-19 screening protocol, combined with self-isolation and shielding, contributed to the low incidence of COVID-19 in our series and a mortality similar to that of pre-pandemic outcomes.


Assuntos
Doenças da Aorta/cirurgia , COVID-19/epidemiologia , Emergências , Pandemias , SARS-CoV-2 , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/epidemiologia , Comorbidade , Serviço Hospitalar de Emergência , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido/epidemiologia
9.
J Card Surg ; 36(1): 199-202, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33169430

RESUMO

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has restructured the healthcare systems, prioritizing resources to treat COVID-19 patients. The aim of this study was to establish if patients affected by acute aortic syndrome (AAS) had unrestricted access to emergency treatment and evaluate outcome of these patients during the peak of the pandemic. METHODS: This is a retrospective analysis of prospectively collected data between March and June 2020 from 19 participating cardiac surgery centers in the United Kingdom. RESULTS: Among 95 patients who presented with an AAS in the participating centers; 85 (89%) underwent surgery, 7 (7%) were turned down for surgery because of their profile of comorbidities, and 3 (3%) died on transfer. Among the patients treated conservatively, three of them (43%) were alive at 30 days. We observed no significant restriction in access to treatment for AAS during the early months of the pandemic. CONCLUSION: Services for life-threatening aortic surgery patients were maintained during the COVID-19 period through patient selection and timing of surgery. The rate of surgical turn-down was comparable to published figures despite the challenges faced during the COVID-19 pandemic.


Assuntos
Doenças da Aorta/etiologia , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/epidemiologia , COVID-19/complicações , Feminino , Humanos , Incidência , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Síndrome , Reino Unido/epidemiologia
10.
J Card Surg ; 36(8): 2692-2696, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33982333

RESUMO

OBJECTIVE: The coronavirus disease (COVID-19) increases the respiratory complications and carries a higher mortality in the immediate postoperative period. The aim of this study was to analyze the outcomes of patients with type A acute aortic syndromes (AAS) diagnosed with COVID-19 in the perioperative period. METHODS: Retrospective analysis of prospectively collected data between March and August 2020 from 20 participating cardiac surgery centers in the United Kingdom. RESULTS: Among 122 patients who underwent emergency surgical repair for type A AAS at the participating centers, 3 patients (2.5%) tested positive for COVID-19 in the preoperative screeing, and 4 cases turned to be positive in the postoperative period having been operated on an unknown COVID-19 status. Another patient was diagnosed of COVID-19 disease based on radiological features. These eight patients had increased postoperative complications, including respiratory failure, longer ventilation times, and Intensive Therapy Unit (ITU) stay and increased mortality when compared with COVID-19 negative patients. CONCLUSION: COVID-19 disease in the perioperative period of type A AAS poses a challenge. Despite the increasing morbidity and mortality associated with the virus, the prognosis of the aortic disease is poorer and emergency surgery should not be contraindicated based on the COVID-19 diagnosis alone.


Assuntos
Teste para COVID-19 , COVID-19 , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Síndrome , Reino Unido/epidemiologia
11.
Glob Chang Biol ; 26(4): 2435-2448, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31961026

RESUMO

Northern boreal peatlands are important ecosystems in modulating global biogeochemical cycles, yet their biological communities and related carbon dynamics are highly sensitive to changes in climate. Despite this, the strength and recent direction of these feedbacks are still unclear. The response of boreal peatlands to climate warming has received relatively little attention compared with other northern peatland types, despite forming a large northern hemisphere-wide ecosystem. Here, we studied the response of two ombrotrophic boreal peatlands to climate variability over the last c. 200 years for which local meteorological data are available. We used remains from plants and testate amoebae to study historical changes in peatland biological communities. These data were supplemented by peat property (bulk density, carbon and nitrogen content), 14 C, 210 Pb and 137 Cs analyses and were used to infer changes in peatland hydrology and carbon dynamics. In total, six peat cores, three per study site, were studied that represent different microhabitats: low hummock (LH), high lawn and low lawn. The data show a consistent drying trend over recent centuries, represented mainly as a change from wet habitat Sphagnum spp. to dry habitat S. fuscum. Summer temperature and precipitation appeared to be important drivers shaping peatland community and surface moisture conditions. Data from the driest microhabitat studied, LH, revealed a clear and strong negative linear correlation (R2  = .5031; p < .001) between carbon accumulation rate and peat surface moisture conditions: under dry conditions, less carbon was accumulated. This suggests that at the dry end of the moisture gradient, availability of water regulates carbon accumulation. It can be further linked to the decreased abundance of mixotrophic testate amoebae under drier conditions (R2  = .4207; p < .001). Our study implies that if effective precipitation decreases in the future, the carbon uptake capacity of boreal bogs may be threatened.

12.
Gastric Cancer ; 23(4): 754-759, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32086651

RESUMO

In women, serum levels of CTSB, GKN2, LIPF, LIPFG, AZGP1, TOP2A and PGA4 are proposed as predictive markers of gastric cancer. It is unknown whether GKN1 expression varies with the sex of patients with chronic gastritis or gastric cancer. We studied 36 patients with histopathological diagnosis of chronic gastritis from the state of Guerrero, Mexico. PCR was performed for H. pylori detection and GKN1 expression was determined by RT-qPCR and western blot. GKN1 mRNA expression was significantly lower in patients with chronic follicular gastritis than in those with chronic chemical gastritis (p = 0.00071). The mRNA and protein level of expression of GKN1 were significantly lower in women with chronic follicular gastritis than in men with the same condition (p = 0.0279 and p = 0.0014, respectively); the lowest levels of GKN1 were detected in women with H. pylori-positive follicular gastritis (p = 0.0175 and p = 0.0111, respectively). Through a bioinformatic analysis, estrogen response elements were identified in the GKN1 promoter.


Assuntos
Biomarcadores/análise , Gastrite/patologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Hormônios Peptídicos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Seguimentos , Gastrite/epidemiologia , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Hormônios Peptídicos/genética , Prognóstico , Adulto Jovem
13.
J Card Surg ; 35(6): 1351-1353, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32531128

RESUMO

The novel coronavirus, now termed SARS-CoV-2, has caused a significant global impact in the space of 4 months. Almost all elective cardiac surgical operations have been postponed in order to reduce transmission and to allocate resources adequately. Urgent and emergency cardiac surgery is still taking place during the pandemic. The decision to operate in urgent patients with active/recent COVID-19 infection is difficult to make, particularly as it is still an unknown disease entity in the setting of emergent cardiac surgery. We present a case series of three patients who underwent urgent cardiac surgery and who have had recent or active COVID-19 infection.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Infecções por Coronavirus/complicações , Procedimentos Cirúrgicos Eletivos/métodos , Segurança do Paciente , Pneumonia Viral/complicações , Adulto , Idoso , COVID-19 , Teste para COVID-19 , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Serviço Hospitalar de Emergência , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/cirurgia , Humanos , Masculino , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/cirurgia , Pandemias/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Prognóstico , Medição de Risco , Gestão da Segurança , Estudos de Amostragem , Tempo para o Tratamento , Resultado do Tratamento
14.
J Card Surg ; 35(7): 1563-1569, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32598501

RESUMO

Over the last 4 months, the novel coronavirus, SARS-CoV-2, has caused a significant economic, political, and public health impact on a global scale. The natural history of the disease and surge in the need for invasive ventilation has required the provision of intensive care beds in London to be reallocated. NHS England have proposed the formation of a Pan-London Emergency Cardiac surgery (PLECS) service to provide urgent and emergency cardiac surgery for the whole of London. In this initial report, we outline our experience of setting up and delivering a pan-regional service for the delivery of urgent and emergency cardiac surgery with a focus on maintaining a COVID-free in-hospital environment. In doing so, we hope that other regions can use this as a starting point in developing their own region-specific pathways if the spread of coronavirus necessitates similar measures be put in place across the United Kingdom.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Infecções por Coronavirus/epidemiologia , Atenção à Saúde/organização & administração , Controle de Infecções/organização & administração , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Emergências , Feminino , Humanos , Londres , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Medição de Risco , Gestão da Segurança/métodos , Resultado do Tratamento , Reino Unido
15.
J Am Chem Soc ; 140(38): 11906-11910, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30153728

RESUMO

We report the synthesis and reactivity of Zr complexes supported by a 9,10-anthracenediyl-linked bisphenoxide ligand, L. ZrIVLBn2 (1) undergoes facile photolytic reduction with concomitant formation of bibenzyl and ZrIVL(THF)3 (2), which displays a two-electron reduced anthracene moiety. Leveraging ligand-stored reducing equivalents, 2 promotes the oxidative coupling of internal and terminal alkynes to isolable zirconacyclopentadiene complexes, demonstrating the reversible utilization of anthracene as a redox reservoir. With diphenylacetylene under CO, cyclopentadienone is formed stoichiometrically. 2 is competent for the catalytic formation of pyrimidines from alkynes and nitriles. Mechanistic studies suggest that selectivity for pyrimidine originates from preferred formation of an azazirconacyclopentadiene intermediate, which reacts preferentially with nitriles over alkynes.


Assuntos
Alcinos/química , Antracenos/química , Complexos de Coordenação/química , Nitrilas/química , Pirimidinas/síntese química , Zircônio/química , Catálise , Ciclização , Ligantes , Acoplamento Oxidativo
16.
BMC Cancer ; 18(1): 349, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587669

RESUMO

BACKGROUND: Cervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers. METHODS: Immunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot. RESULTS: High Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer. CONCLUSIONS: Ezrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.


Assuntos
Biomarcadores Tumorais , Caderinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Caderinas/genética , Proteínas do Citoesqueleto/genética , Progressão da Doença , Feminino , Expressão Gênica , Genótipo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prognóstico , Transporte Proteico , Fatores de Risco , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/mortalidade , Adulto Jovem
17.
Lett Math Phys ; 108(1): 225-247, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29353958

RESUMO

The un-reduction procedure introduced previously in the context of classical mechanics is extended to covariant field theory. The new covariant un-reduction procedure is applied to the problem of shape matching of images which depend on more than one independent variable (for instance, time and an additional labelling parameter). Other possibilities are also explored: nonlinear [Formula: see text]-models and the hyperbolic flows of curves.

18.
J Gene Med ; 18(10): 302-311, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27672733

RESUMO

BACKGROUND: Although herpes simplex virus type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of approximately 15.4 kb of DNA sequences that are duplicated in the HSV-1 genome, complicating vector construction and stability. METHODS: As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired. We used this ΔIR mutant to subsequently investigate whether the insertion of tetracycline-responsive tetO elements into the ICP34.5-ICP0 gene region can be used to control HSV-1 lytic replication. RESULTS: The results of the present study show that ΔIR mutants deleted for ICP34.5 are viable for replication but not when the ICP0 promoter is also disrupted, thus indicating that regulation of infected cell protein 0 (ICP0) levels in the absence of ICP34.5 could be a viable means for controlling growth of HSV-1 vectors. Surprisingly, however, the tetO elements inserted into the ICP0 promoter did not confer ligand responsiveness to growth or ICP0 expression. Further analysis by transfection experiments revealed that ICP0 itself interferes with the tetracycline switch and reduces the the inducibility of this system. CONCLUSIONS: Our new haploid HSV-1 BAC is a useful platform for building multiply deleted HSV-1 vectors. Deletion of the gene for ICP34.5 in this backbone renders viral growth dependent on ICP0, although ICP0 expression could not be regulated by tet-responsive transcriptional regulators.


Assuntos
Vetores Genéticos/genética , Genoma Viral/genética , Haploidia , Herpesvirus Humano 1/genética , Linhagem Celular Tumoral , Deleção de Genes , Regulação Viral da Expressão Gênica , Humanos , Proteínas Imediatamente Precoces/genética , Mutação , Regiões Promotoras Genéticas , Elementos de Resposta/genética , Tetraciclinas/farmacologia , Ubiquitina-Proteína Ligases/genética , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
19.
Proteome Sci ; 14(1): 10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27601940

RESUMO

BACKGROUND: Cervical cancer (CC) is the fourth most common cancer in women worldwide with an estimated 528,000 new cases in 2012. The same year México had an incidence of 13,960 and a mortality of 4769 cases. There are several diagnosis methods of CC; among the most frequents are the conventional Pap cytology (Pap), colposcopy, and visual inspection with acetic acid (VIA), histopathological examination, tests of imaging and detection of high-risk papilloma virus (HR-HPV) with molecular tests (PCR, hybridization, sequencing). Proteomics is a tool for the detection of new biomarkers that can be associated with clinical stage, histological type, prognosis, and/or response to treatment. In this study we performed a comparative analysis of CC cells with normal cervical cells. The proteomic analysis was carried out with the fluorescent two-dimensional electrophoresis (2D-DIGE) technique to subsequently identify differential protein profiles using Decyder Software, and the selected proteins were identified by Mass Spectrometry (MALDI-TOF). RESULTS: The proteins that showed an increased expression in cervical cancer in comparison with normal cervix cells were: Mimecan, Actin from aortic smooth muscle and Lumican. While Keratin, type II cytoskeletal 5, Peroxiredoxin-1 and 14-3-3 protein sigma showed a decrease in their protein expression level in cervical cancer in comparison with normal cervix cells. CONCLUSIONS: Thus, this study was successful in identifying biomarker signatures for cervical cancer, and might provide new insights into the mechanism of CC progression.

20.
Virol J ; 12: 29, 2015 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-25889023

RESUMO

BACKGROUND: HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma. METHODS: This study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n = 97), low-grade squamous intraepithelial lesion (n = 123), high-grade squamous intraepithelial lesion (n = 19) and cervical carcinoma (n = 91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares. RESULTS: Twenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR = 69.01, CI = 7.57-628.96), followed by E-A176/G350 (OR = 39.82, CI = 4.11-386.04), AA-c (OR = 21.16, CI 2.59-172.56), E-G350 (OR = 13.25, CI = 2.02-87.12) and E-C188/G350 (OR = 10.48, CI = 1.39-78.92). CONCLUSIONS: The variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.


Assuntos
Carcinoma/virologia , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Carcinoma/patologia , Feminino , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiologia , Humanos , México , Dados de Sequência Molecular , Infecções por Papillomavirus/patologia , Filogenia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
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