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1.
Sci Rep ; 11(1): 4215, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603102

RESUMO

Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5' end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0.05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81.7%), which determined a reduction in HBV DNA release of up to 1.5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.

2.
J Infect Dis ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528501

RESUMO

BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, can be transmitted to the offspring of infected women, which constitutes an epidemiologically significant parasite transmission route in non-endemic areas. It is relevant to evaluate differentially expressed factors in T. cruzi-infected pregnant women as potential markers of Chagas congenital transmission. METHODS: Circulating levels of twelve cytokines and chemokines were measured by ELISA or cytometric bead array in T. cruzi-infected and uninfected pregnant women in their second trimester of pregnancy, and control groups of T. cruzi-infected and uninfected non-pregnant women. RESULTS: T. cruzi-infected women showed a pro-inflammatory Th1-biased profile, with increased levels of TNF-α, IL-12p70, IL-15 and MIG. Uninfected pregnant women presented a biased response towards Th2/Th17/Treg profiles, with increased plasma levels of IL-5, IL-6, IL-1ß, IL-17A and IL-10. Finally, we identified that high parasitemia together with low levels of TNF-α, IL-15, and IL-17, low TNF-α/IL-10 ratio, and high IL-12p70 levels are factors associated with an increased probability of Chagas congenital transmission. CONCLUSIONS: T. cruzi-infected pregnant women who did not transmit the infection to their babies exhibited a distinct pro-inflammatory cytokine profile that might serve as a potential predictive marker of congenital transmission.

3.
Genes (Basel) ; 11(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255299

RESUMO

Microorganisms used for the biohydrometallurgical extraction of metals from minerals must be able to survive high levels of metal and oxidative stress found in bioleaching environments. The Acidihalobacter genus consists of four species of halotolerant, iron-sulfur-oxidizing acidophiles that are unique in their ability to tolerate chloride and acid stress while simultaneously bioleaching minerals. This paper uses bioinformatic tools to predict the genes and mechanisms used by Acidihalobacter members in their defense against a wide range of metals and oxidative stress. Analysis revealed the presence of multiple conserved mechanisms of metal tolerance. Ac. yilgarnensis F5T, the only member of this genus that oxidizes the mineral chalcopyrite, contained a 39.9 Kb gene cluster consisting of 40 genes encoding mobile elements and an array of proteins with direct functions in copper resistance. The analysis also revealed multiple strategies that the Acidihalobacter members can use to tolerate high levels of oxidative stress. Three of the Acidihalobacter genomes were found to contain genes encoding catalases, which are not common to acidophilic microorganisms. Of particular interest was a rubrerythrin genomic cluster containing genes that have a polyphyletic origin of stress-related functions.

4.
Alzheimers Dement (N Y) ; 6(1): e12092, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33283036

RESUMO

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks.

6.
Exp Parasitol ; 220: 108044, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33253715

RESUMO

Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic in Latin America and around the world through mother to child transmission. The heart is the organ most frequently affected in the chronic stage of the human infection and depends on mitochondria for the required energy for its activity. Cyclophilins are involved in protein folding and the mitochondrial isoform, Cyclophilin D (CyPD), has a crucial role in the opening of the mitochondrial permeability transition pore. In the present study, we infected CyPD deficient mice, with ablation of the Ppif gene, with T. cruzi parasites and the course of the infection was analyzed. Parasite load, quantified by PCR, was significantly lower in skeletal and cardiac tissues of Ppif-/- mice compared to wild type mice. In vitro cultured cardiomyocytes and macrophages from mice lacking CyPD exhibited lower percentage of infected cells and number of intracellular parasites than those observed for wild type mice. Although histopathological analysis of heart and mRNA of heart cytokines showed differences between T. cruzi-infected mice compared to the uninfected animals, no significant differences were found mice due to the ablation of the Ppif gene. Our results suggest that cells deficient for mitochondrial CyPD, inhibited for the mitochondrial membrane potential collapse, reduces the severity of parasite aggression and spread of cellular infection.

7.
Food Chem ; : 128355, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33077286

RESUMO

Malnutrition is a serious problem in the elderly while understanding flavour perception could be a tool for controlling appetite or food choices. To increase our knowledge, we characterised the health and oral physiology (oral volume, swallowing tongue force, number of teeth and salivary flow rate, protein content and antioxidant capacity) of a cohort of 54 community-dwelling French elderly as well as their individual retronasal release of five aroma compounds (2-pentanone, 2-nonanone, 2,3-hexanedione, octanal and linalool) by proton-transfer-reaction mass spectrometry (PTR-MS). In general, large variability across participants was observed in both oral physiological (>40%) and retronasal aroma release (>56%) parameters. Multivariate analyses revealed a relationship between physiological parameters (mostly salivary antioxidant capacity) and retronasal aroma release that explained up to 46% of the variability observed. This study provides new insights to understand retronasal aroma release in the elderly that could contribute to the development of personalised nutrition strategies.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33112221

RESUMO

The genus Acidihalobacter has three validated species, Acidihalobacter ferrooxydans, Acidihalobacter prosperus and Acidihalobacter aeolinanus, all of which were isolated from Vulcano island, Italy. They are obligately chemolithotrophic, aerobic, acidophilic and halophilic in nature and use either ferrous iron or reduced sulphur as electron donors. Recently, a novel strain was isolated from an acidic, saline drain in the Yilgarn region of Western Australia. Strain F5T has an absolute requirement for sodium chloride (>5 mM) and is osmophilic, growing in elevated concentrations (>1 M) of magnesium sulphate. A defining feature of its physiology is its ability to catalyse the oxidative dissolution of the most abundant copper mineral, chalcopyrite, suggesting a potential role in biomining. Originally categorized as a strain of A. prosperus, 16S rRNA gene phylogeny and multiprotein phylogenies derived from clusters of orthologous proteins (COGS) of ribosomal protein families and universal protein families unambiguously demonstrate that strain F5T forms a well-supported separate branch as a sister clade to A. prosperus and is clearly distinguishable from A. ferrooxydans DSM 14175T and A. aeolinanus DSM14174T. Results of comparisons between strain F5T and the other Acidihalobacter species, using genome-based average nucleotide identity, average amino acid identity, correlation indices of tetra-nucleotide signatures (Tetra) and genome-to-genome distance (digital DNA-DNA hybridization), support the contention that strain F5T represents a novel species of the genus Acidihalobacter. It is proposed that strain F5T should be formally reclassified as Acidihalobacter yilgarnenesis F5T (=DSM 105917T=JCM 32255T).

9.
Eur J Cancer Care (Engl) ; : e13346, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037849

RESUMO

OBJECTIVE: The aim of this study was to examine how the burden of caregivers of patients with an advanced oncological illness mediates the relationship between positive aspects of care, depression and anxiety. METHODS: Quantitative study with a cross-sectional design. One hundred informal adult caregivers of patients with advanced oncological illness who attended the pain and palliative care unit or the psychological unit at the Instituto de Cancerologia Clinica las Americas (Medellin, Colombia) completed self-report assessments including positive aspects of care (PAC), burden and anxiety/depression measured using the HADS (Hospitalized Anxiety Depression Scale). The partial least squares Structural Equation Modelling (PLS-SEM) approach was selected to validate the hypotheses of the study. RESULTS: Most of the participants were women (86%), with a mean age of 46.52 years (SD=15.05). Most of the participants reported experiencing both PAC and anxiety. They also scored low for burden. PAC exerted a negative effect on Burden, whereas Burden contributed positively to Anxiety and Depression. The indirect impact of PAC on Anxiety and Depression was significant p < .00. CONCLUSIONS: Positive aspects of care in advanced cancer caregivers constitutes a protective factor against caregiver's burden, depression and anxiety. Health staff can promote caregivers' adaptation and wellbeing emphasizing these PAC.

10.
BMJ Case Rep ; 13(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028572

RESUMO

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.


Assuntos
Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumonia Viral/diagnóstico , Sarcoma de Ewing , Tomografia Computadorizada por Raios X/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Exame de Medula Óssea/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Masculino , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
11.
Pathogens ; 9(8)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751557

RESUMO

In this study, we assessed the presence of Epstein-Barr virus (EBV) in gastric samples derived from pediatric patients with dyspeptic symptoms, aiming to understand whether EBV participates in the development of early gastric lesions influencing chronic inflammation, in conjunction with the Helicobacter pylori (Hp) bacterium. We analyzed EBV load in 236 gastric biopsies derived from 186 pediatric patients with chronic dyspepsia and compared it with EBV serology, Hp load and serology, and with immune cell infiltration. We found that 7.5% of patients were positive for EBV load, ranging from 240 to 29,685 genomic copies/µg of DNA. Hp genomic sequences were found in 24.7% of patients. EBV positive samples did not correlate with Hp status and were characterized by absent to moderate immune cell infiltration. To our knowledge, this is the first study addressing EBV load in the stomach in a large cohort of pediatric patients with dyspeptic symptoms, providing evidence of EBV localization in the gastric mucosa in early inflammatory lesions. The lack of correlation between EBV and both Hp infection and inflammation is perhaps explained by independent pathogenic mechanisms or because of the randomness of the gastritis sampling. This is also supported by a moderate association between EBV load and serology.

12.
Biomedicines ; 8(8)2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32726912

RESUMO

Radiotherapy is one of the treatments of choice in many types of cancer. Adjuvant treatments to radiotherapy try, on one hand, to enhance the response of tumor cells to radiation and, on the other hand, to reduce the side effects to normal cells. Radiosensitizers are agents that increase the effect of radiation in tumor cells by trying not to increase side effects in normal tissues. Melatonin is a hormone produced mainly by the pineal gland which has an important role in the regulation of cancer growth, especially in hormone-dependent mammary tumors. Different studies have showed that melatonin administered with radiotherapy is able to enhance its therapeutic effects and can protect normal cells against side effects of this treatment. Several mechanisms are involved in the radiosensitization induced by melatonin: increase of reactive oxygen species production, modulation of proteins involved in estrogen biosynthesis, impairment of tumor cells to DNA repair, modulation of angiogenesis, abolition of inflammation, induction of apoptosis, stimulation of preadipocytes differentiation and modulation of metabolism. At this moment, there are very few clinical trials that study the therapeutic usefulness to associate melatonin and radiotherapy in humans. All findings point to melatonin as an effective adjuvant molecule to radiotherapy in cancer treatment.

13.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521599

RESUMO

The Special Issue entitled "New Strategies in Cancer Pharmacotherapy: Development of Hormonal Antineoplastic Drugs, Cytotoxic Drugs and Targeted Therapies" was conceived with the idea of compiling information on the latest advances in the treatment of both hormone-dependent and hormone-independent cancers [...].

15.
World J Gastroenterol ; 26(20): 2584-2598, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32523313

RESUMO

BACKGROUND: Since it is currently not possible to eradicate hepatitis B virus (HBV) infection with existing treatments, research continues to uncover new therapeutic strategies. HBV core protein, encoded by the HBV core gene (HBC), intervenes in both structural and functional processes, and is a key protein in the HBV life cycle. For this reason, both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies. Moreover, alterations in the protein sequence could serve as potential markers of disease progression. AIM: To detect, by next-generation sequencing, HBC hyper-conserved regions that could potentially be prognostic factors and targets for new therapies. METHODS: Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage [chronic hepatitis B infection without liver damage (CHB, n = 16), liver cirrhosis (LC, n = 5), and hepatocellular carcinoma (HCC, n = 17)]. HBV DNA was extracted from patients' plasma. A region between nucleotide (nt) 1863 and 2483, which includes HBC, was amplified and analyzed by next-generation sequencing (Illumina MiSeq platform). Sequences were genotyped by distance-based discriminant analysis. General and intergroup nt and amino acid (aa) conservation was determined by sliding window analysis. The presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus sequences. RESULTS: Three nt (nt 1900-1929, 2249-2284, 2364-2398) and 2 aa (aa 117-120, 159-167) hyper-conserved regions were shared by all the clinical groups. All groups showed a similar pattern of conservation, except for five nt regions (nt 1946-1992, 2060-2095, 2145-2175, 2230-2250, 2270-2293) and one aa region (aa 140-160), where CHB and LC, respectively, were less conserved (P < 0.05). Some group-specific conserved regions were also observed at both nt (2306-2334 in CHB and 1935-1976 and 2402-2435 in LC) and aa (between aa 98-103 in CHB and 28-30 and 51-54 in LC) levels. No differences in insertion and deletions frequencies were observed. An aa substitution (P79Q) was observed in the HCC group with a median (interquartile range) frequency of 15.82 (0-78.88) vs 0 (0-0) in the other groups (P < 0.05 vs CHB group). CONCLUSION: The differentially conserved HBC and HBV core protein regions and the P79Q substitution could be involved in disease progression. The hyper-conserved regions detected could be targets for future therapeutic and diagnostic strategies.

16.
Food Res Int ; 135: 109286, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32527481

RESUMO

The present work evaluated for the first time the influence of wine matrix composition on oral ester persistence. To do that, the in mouth behaviour (oral retention and persistence) of six esters was followed in nine individuals after they rinsed their mouths with four rosé wines presenting two levels (low and moderate) of ethanol (0.5% or 10% v/v) and polyphenols (402 ± 10 or 661 ± 33 mg gallic acid/L). Overall, polyphenols and specially, ethanol, affected the oral retention of esters and their subsequent oral persistence, in an individual, compound and concentration dependent manner. The wine with moderate ethanol and low polyphenol content and the wine with low ethanol and moderate polyphenol content presented an increased oral ester persistence respect to the control wine (low ethanol/polyphenol content). However, the wine with moderate ethanol/polyphenol content showed most likely a lower oral ester persistence compared to the rest of the wines. Thus, an interaction between ethanol and polyphenols at specific concentrations could reduce oral ester persistence, and likely the fruity character of wines. The information generated in this research can be used by winemakers to understand how different winemaking techniques, which might alter wine ethanol and polyphenol content, may also affect wine aroma quality.

18.
Arch. argent. pediatr ; 118(3): e338-e341, jun. 2020. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1117378

RESUMO

La invaginación intestinal ocurre cuando un segmento proximal de intestino se repliega dentro de la luz de un segmento distal adyacente y provoca obstrucción intestinal. Es una causa común de abdomen agudo en los dos primeros años de la vida, pero raro en niños mayores. Un varón de 16 años, con diagnóstico de fibrosis quística, se presentó con un cuadro compatible con síndrome de oclusión intestinal distal. Consultó a la clínica con dolor abdominal y una masa palpable en el hipocondrio derecho. Se realizó ecografía abdominal y tomografía de abdomen contrastada, que demostraron invaginación íleo-colónica con signos de isquemia intestinal, necrosis y neumatosis de la pared intestinal. Fue intervenido: se realizó resección del íleon terminal y hemicolon derecho, y se detectó una tumoración en ciego. La invaginación íleo-colónica es una causa rara de abdomen agudo en pacientes adolescentes con fibrosis quística y puede estar asociada a una causa orgánica subyacente.


Intestinal intussusception occurs when a proximal segment of the intestine telescopes into the lumen of an adjacent distal segment, causing intestinal obstruction. It is a common cause of acute abdomen in the first two years of life, but rare in older children. A 16-year-old male with a diagnosis of cystic fibrosis presented with symptoms compatible with distal intestinal occlusion syndrome. He came at the cystic fibrosis clinic with a 5-day evolution of abdominal pain and a palpable mass in the right hypochondrium. Abdominal ultrasound and abdominal contrasted tomography were performed demonstrating ileo-colonic invagination with signs of intestinal ischemia, necrosis and pneumatosis of the intestinal wall. He underwent surgery with resection of the terminal ileum and right hemicolon, ana tumor in the caecum was found. This is a rare cause of acute abdomen in young patients with cystic fibrosis and may be associated with an underlying organic cause.


Assuntos
Humanos , Masculino , Adolescente , Fibrose Cística , Intussuscepção/diagnóstico por imagem , Dor Abdominal , Íleo/cirurgia , Obstrução Intestinal , Intussuscepção/cirurgia
19.
J Dent ; 98: 103374, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32413383

RESUMO

OBJECTIVES: Evidence of the cost-effectiveness of fluoride varnish in the prevention of caries is not yet fully conclusive. The aim of this study was to assess the incremental cost-effectiveness ratio (ICER) of the community-wide application of fluoride varnish in the prevention of early childhood caries (ECC) in non-fluoridated areas. MATERIALS AND METHODS: A cost-effectiveness analysis was carried out based on a clinical decision tree from the payer's perspective. The effectiveness and cost of the varnish were determined from a two-year follow-up triple-blind randomized control trial in 275 two- to three-year-old children. Costs and benefits were discounted at 3% per year. Only direct costs were evaluated, expressed in Chilean pesos (CLP) valued in July, 2019 (exchange rate USD = CLP686.06). A univariate deterministic sensitivity analysis was carried out. RESULTS: Incidence of ECC was 45 % for the varnish group and 55.6 % for the placebo group with a two-year follow-up. The weighted cost to intervene and treat the consequences of ECC was CLP 67,757 (USD98.76) for the fluoride varnish and CLP 67,739 (USD98.74) for the control group. The ICER was CLP 173 (USD0.25) for each extra healthy child in favor of fluoride varnish. The sensitivity analysis showed that the increase in caries was the variable which most influenced the ICER. CONCLUSIONS: The protocol that included fluoride varnish is more effective and less costly in the prevention of ECC in non-fluoridated areas, compared with a placebo. CLINICAL SIGNIFICANCE: Findings support the application of fluoride varnish as a cost-effective community strategy to prevent ECC in non-fluoridated areas.

20.
Arch Argent Pediatr ; 118(3): e338-e341, 2020 06.
Artigo em Espanhol | MEDLINE | ID: mdl-32470278

RESUMO

Intestinal intussusception occurs when a proximal segment of the intestine telescopes into the lumen of an adjacent distal segment, causing intestinal obstruction. It is a common cause of acute abdomen in the first two years of life, but rare in older children. A 16-year-old male with a diagnosis of cystic fibrosis presented with symptoms compatible with distal intestinal occlusion syndrome. He came at the cystic fibrosis clinic with a 5-day evolution of abdominal pain and a palpable mass in the right hypochondrium. Abdominal ultrasound and abdominal contrasted tomography were performed demonstrating ileocolonic invagination with signs of intestinal ischemia, necrosis and pneumatosis of the intestinal wall. He underwent surgery with resection of the terminal ileum and right hemicolon, and a tumor in the caecum was found. This is a rare cause of acute abdomen in young patients with cystic fibrosis and may be associated with an underlying organic cause.

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