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1.
Nucleic Acids Res ; 52(10): 5732-5755, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597682

RESUMO

Expansion of a G4C2 repeat in the C9orf72 gene is associated with familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). To investigate the underlying mechanisms of repeat instability, which occurs both somatically and intergenerationally, we created a novel mouse model of familial ALS/FTD that harbors 96 copies of G4C2 repeats at a humanized C9orf72 locus. In mouse embryonic stem cells, we observed two modes of repeat expansion. First, we noted minor increases in repeat length per expansion event, which was dependent on a mismatch repair pathway protein Msh2. Second, we found major increases in repeat length per event when a DNA double- or single-strand break (DSB/SSB) was artificially introduced proximal to the repeats, and which was dependent on the homology-directed repair (HDR) pathway. In mice, the first mode primarily drove somatic repeat expansion. Major changes in repeat length, including expansion, were observed when SSB was introduced in one-cell embryos, or intergenerationally without DSB/SSB introduction if G4C2 repeats exceeded 400 copies, although spontaneous HDR-mediated expansion has yet to be identified. These findings provide a novel strategy to model repeat expansion in a non-human genome and offer insights into the mechanism behind C9orf72 G4C2 repeat instability.


Assuntos
Proteína C9orf72 , Expansão das Repetições de DNA , Instabilidade Genômica , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Proteína C9orf72/genética , Modelos Animais de Doenças , Quebras de DNA de Cadeia Dupla , Expansão das Repetições de DNA/genética , Demência Frontotemporal/genética , Técnicas de Introdução de Genes , Instabilidade Genômica/genética , Proteína 2 Homóloga a MutS/genética
2.
J Biol Chem ; : 107884, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395809

RESUMO

Although COVID-19 pandemic was declared no longer a global emergency by the World Health Organization in May 2023, SARS-CoV-2 is still infecting people across the world. Many therapeutic oligonucleotides such as ASOs, siRNAs or CRISPR-based systems emerged as promising antiviral strategies for the treatment of SARS-CoV-2. In this work we explored the inhibitory potential on SARS-CoV-2 replication of Polypurine Reverse Hoogsteen Hairpins (PPRHs), CC1-PPRH and CC3-PPRH, targeting specific polypyrimidine sequences within the replicase and Spike regions, respectively, and previously validated for COVID-19 diagnosis. Both PPRHs bound to their target sequences in the viral genome with high affinity in the order of nM. In vitro, both PPRHs reduced viral replication by more than 92% when transfected into VERO-E6 cells 24 hours prior infection with SARS-CoV-2. In vivo intranasal administration of CC1-PPRH in K18-hACE2 mice expressing the human ACE receptor protected all the animals from SARS-CoV-2 infection. The properties of PPRHs position them as promising candidates for the development of novel therapeutics against SARS-CoV-2 and other viral infections.

3.
Eur J Clin Microbiol Infect Dis ; 43(6): 1139-1148, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613705

RESUMO

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.


Assuntos
Anticorpos Antivirais , Varicela , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Medições Luminescentes , Vírus do Sarampo , Sarampo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Sarampo/diagnóstico , Sarampo/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Medições Luminescentes/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Criança , Masculino , Feminino , Adulto , Adolescente , Varicela/diagnóstico , Varicela/imunologia , Vírus do Sarampo/imunologia , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Herpesvirus Humano 3/imunologia , Sensibilidade e Especificidade , Lactente , Idoso , Imunoensaio/métodos , Kit de Reagentes para Diagnóstico/normas
4.
Reprod Domest Anim ; 59(5): e14582, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715452

RESUMO

Crossbred cattle are commonly used for milk production in the tropics, combining the potential benefits of pure breeds with the heterosis effects of the offspring. However, no comprehensive assessment of lifetime productivity for crossbred versus purebred cattle in low-altitude tropical environments has been carried out. The present study compares the lifetime productivity of purebred Holstein (HO, n = 17,269), Gyr (GY4, n = 435), and Brahman (BR4, n = 622) with crossbreds Gyr × Holstein (GY × HO, n = 5521) and Brahman×Holstein (BR × HO, n = 5429) cows from dairy farms located in low and medium altitude tropical regions in Costa Rica. The production traits of interest were age at first calving (AFC), days open (DO), milk production per lactation (TMP), lactation length (LLEN), age at culling (ACUL), and number of lactations (NLAC). Estimates of heterosis were also calculated. The AFC for GY × HO crosses (33-34 months) was not significantly different (p > .05) from HO (33.8 months). For BR × HO crosses, a significant (p < .05) decrease in AFC (BR3HO1 35.6 months, BR2HO2 34.5 months, and BR1H03 33.3 months) was observed as the fraction of HO breed increased. Estimates of heterosis for AFC were favourable for both crosses, of a magnitude close to 3%. The DO for F1 crosses (GY2HO2 94 days; BR2HO2 96 days) was significantly (p < .05) lower than HO (123 days). Estimates of heterosis for DO were also favourable and above 15% for both crosses. The TMP and LLEN were higher for HO (TMP = 5003 kg; LLEN = 324 days) compared with GY × HO (TMP = 4428 to 4773 kg; LLEN = 298 to 312 days) and BR × HO (TMP = 3950 to 4761 kg; LLEN = 273 to 313 days) crosses. Heterosis for TMP was favourable but low for both crosses, with a magnitude below 3.0%. The NLAC for HO (4.6 lactations) was significantly (p < .05) lower than F1 (GY2HO2, 5.8 lactations; BR2HO2, 5.4 lactations). Heterosis for NLAC was above 6.0% for both crosses. Overall, estimates of lifetime income over feed costs per cow on average were USD 2637 (30.3%) and USD 734 (8.4%) higher in F1 GY × HO and BR × HO, respectively, compared to HO. In conclusion, crossbred animals, specifically those with Gyr and Brahman genetics, extend the productive lifespan, increasing economic returns.


Assuntos
Vigor Híbrido , Lactação , Leite , Clima Tropical , Animais , Bovinos/genética , Bovinos/fisiologia , Lactação/genética , Lactação/fisiologia , Feminino , Costa Rica , Cruzamento , Hibridização Genética , Altitude , Cruzamentos Genéticos
5.
Molecules ; 29(16)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39202912

RESUMO

In this research work, we examined the decomposition mechanisms of N-substituted diacetamides. We focused on the substituent effect on the nitrogen lone-pair electron delocalization, with electron-withdrawing and electron donor groups. DFT functionals used the following: B1LYP, B3PW91, CAMB3LYP, LC-BLYP, and X3LYP. Dispersion corrections (d3bj) with Becke-Johnson damping were applied when necessary to improve non-covalent interactions in the transition state. Pople basis sets with higher angular moments and def2-TZVP basis sets were also applied and were crucial for obtaining consistent thermodynamic parameters. The proposed mechanism involves a six-membered transition state with the extraction of an α hydrogen. Several conformers of N-diacetamides were used to account for the decrease in entropy in the transition state in the rate-determining state. All calculations, including natural bond orbital (NBO) analyses, were performed using the Gaussian16 computational package and its GaussView 6.0 visualizer, along with VMD and GNUPLOT software. The isosurfaces and IBSIs were calculated using MultiWFN and IGMPlot, respectively.

6.
Medicina (Kaunas) ; 60(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674288

RESUMO

Background and Objectives: Dementia grief in family caregivers of people with dementia refers to grieving prior to the death of the care recipient. It is related to psychosocial risk factors that may have a negative impact on the health of these family caregivers. This study aimed to describe the relationship between depressive symptoms, caregiver strain, and social support with dementia grief in family caregivers of people with dementia. Materials and Methods: A descriptive correlational cross-sectional study was conducted. A total of 250 family caregivers of people with dementia participated. Dementia grief was the main variable, and depressive symptoms, caregiver strain, and social support were assessed. Additionally, socio-demographic data were collected. Descriptive statistics were calculated, and a bivariate correlation analysis and a multiple linear regression analysis were performed for dementia grief. Results: Higher scores for dementia grief were found in women, in family caregivers of patients at advanced stages of dementia, and in family caregivers with a low level of education. High levels of depressive symptoms and caregiver strain and low levels of social support indicated greater intensity of dementia grief. Depressive symptomatology was the variable with the greatest influence on dementia grief. Caregiver strain and social support also related to dementia grief, but to a lesser extent. Conclusions: In family caregivers, depressive symptoms, caregiver strain, and social support are related to the intensity of dementia grief, with a greater influence of depressive symptoms. Moreover, being female, having a low level of education, and caring for a care recipient at an advanced stage of dementia are factors associated with increased dementia grief. Concerning study limitations, the sample was restricted, belonging to a specific region of Spain and to a Provincial Federation of associations. It is necessary to exercise caution in generalizing results due to the sociodemographic and geographical characteristics of the sample.


Assuntos
Cuidadores , Demência , Depressão , Pesar , Apoio Social , Humanos , Feminino , Masculino , Cuidadores/psicologia , Demência/psicologia , Estudos Transversais , Idoso , Depressão/psicologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto , Inquéritos e Questionários , Estresse Psicológico/psicologia , Estresse Psicológico/etiologia
7.
J Biol Chem ; 298(6): 101984, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35487246

RESUMO

A major challenge in eukaryotic cells is the proper distribution of nuclear-encoded proteins to the correct organelles. For a subset of mitochondrial proteins, a signal sequence at the N terminus (matrix-targeting sequence [MTS]) is recognized by protein complexes to ensure their proper translocation into the organelle. However, the early steps of mitochondrial protein targeting remain undeciphered. The cytosolic chaperone nascent polypeptide-associated complex (NAC), which in yeast is represented as the two different heterodimers αß-NAC and αß'-NAC, has been proposed to be involved during the early steps of mitochondrial protein targeting. We have previously described that the mitochondrial outer membrane protein Sam37 interacts with αß'-NAC and together promote the import of specific mitochondrial precursor proteins. In this work, we aimed to detect the region in the MTS of mitochondrial precursors relevant for their recognition by αß'-NAC during their sorting to the mitochondria. We used targeting signals of different mitochondrial proteins (αß'-NAC-dependent Oxa1 and αß'-NAC-independent Mdm38) and fused them to GFP to study their intracellular localization by biochemical and microscopy methods, and in addition followed their import kinetics in vivo. Our results reveal the presence of a positively charged amino acid cluster in the MTS of select mitochondrial precursors, such as Oxa1 and Fum1, which are crucial for their recognition by αß'-NAC. Furthermore, we explored the presence of this cluster at the N terminus of the mitochondrial proteome and propose a set of precursors whose proper localization depends on both αß'-NAC and Sam37.


Assuntos
Proteínas de Membrana/metabolismo , Proteínas Mitocondriais , Chaperonas Moleculares/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Aminoácidos/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética
8.
J Virol ; 96(18): e0124022, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36094317

RESUMO

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.


Assuntos
Células Dendríticas , Ativação Linfocitária , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Animais , Antivirais , Diferenciação Celular , Concanavalina A/genética , Concanavalina A/imunologia , Células Dendríticas/citologia , Células Dendríticas/virologia , Cabras , Terapia de Imunossupressão , Ativação Linfocitária/imunologia , Mitógenos/imunologia , Peste dos Pequenos Ruminantes/imunologia , Peste dos Pequenos Ruminantes/virologia , Fenótipo , Ovinos , Linfócitos T/imunologia , Linfócitos T/virologia
9.
Nephrol Dial Transplant ; 38(4): 969-981, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36423334

RESUMO

BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Estudos Prospectivos , SARS-CoV-2 , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Anticorpos Antivirais
10.
Int J Food Sci Nutr ; 74(4): 532-543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37369137

RESUMO

Phenolic catabolites excreted by fasting subjects with a functioning colon and ileostomists on a low (poly)phenol diet have been investigated. Urine was collected over a 12 h fasting period after adherence to a low (poly)phenol diet for 36 h. UHPLC-HR-MS quantified 77 phenolics. Some were present in the urine of both groups in similar trace amounts and others were excreted in higher amounts by participants with a colon indicating the involvement of the microbiota. Most were present in sub- or low-µmol amounts, but hippuric acid dominated accounting on average for 60% of the total for both volunteer categories indicating significant production from sources other than non-nutrient dietary (poly)phenols. The potential origins of the phenolics associated with the low (poly)phenol diet, include endogenous catecholamines, surplus tyrosine and phenylalanine, and washout of catabolites derived from pre-study intakes of non-nutrient dietary (poly)phenols.


Assuntos
Microbioma Gastrointestinal , Fenol , Humanos , Catecolaminas , Aminoácidos , Fenóis/metabolismo , Dieta
11.
Int J Food Sci Nutr ; 74(1): 33-50, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36450698

RESUMO

Disruption of microvascular architecture is a common pathogenic mechanism in the progression of Alzheimer's disease (AD). Given the anti-angiogenic activity of berry (poly)phenols, we investigated whether long-term feeding of Rubus idaeus (raspberries) could ameliorate cerebral microvascular pathology and improve cognition in the APP/PS-1 mouse model of AD. Male C57Bl/6J mice (50 wild type, 50 APP/PS-1) aged 4-months were fed for 24-weeks, with a normal diet enriched with either 100 mg/day glucose (control diet) or supplemented with glucose and freeze-dried anthocyanin-rich (red) or -poor (yellow) raspberries (100 mg/day) and assessed/sampled post intervention. Cerebral microvascular architecture of wild-type mice was characterised by regularly spaced capillaries with uniform diameters, unlike APP/PS-1 transgenic mice which showed dysregulated microvascular architecture. Long-term feeding of raspberries demonstrated limited modulation of microbiota and no substantive effect on microvascular architecture or cognition in either mice model although changes were evident in endogenous cerebral and plasmatic metabolites.


Assuntos
Doença de Alzheimer , Rubus , Masculino , Camundongos , Animais , Frutas , Antocianinas , Camundongos Transgênicos , Suplementos Nutricionais , Cognição
12.
Int J Mol Sci ; 24(5)2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36902411

RESUMO

The aim of this study was to evaluate the impact of in vitro gastrointestinal digestion and colonic fermentation on the polyphenol compounds from different varieties of pistachio by UHPLC-HRMS analysis. The total polyphenol content decreased significantly, mostly during oral (recoveries of 27 to 50%) and gastric digestion (recoveries of 10 to 18%), with no significant changes after the intestinal phase. After in vitro digestion, the hydroxybenzoic acids and the flavan-3-ols were the main compounds found in pistachio, with respective total polyphenol contents of 73 to 78% and 6 to 11%. More specifically, the main compounds determined after in vitro digestion were 3,4,5-trihydroxybenzoic acid, vanillic hexoside and epigallocatechin gallate. The colonic fermentation affected the total phenolic content of the six varieties studied, with a recovery range of 11 to 25% after 24 h of fecal incubation. A total of twelve catabolites were identified after fecal fermentation, the main compounds being the 3-(3'-hydroxyphenyl)propanoic, 3-(4'-hydroxyphenyl)propanoic, 3-(3',4'-dihydroxyphenyl)propanoic, 3-hydroxyphenylacetic acids and 3,4-dihydroxyphenyl-É£-valerolactone. Based on these data, a catabolic pathway for colonic microbial degradation of phenolic compounds is proposed. The catabolites identified at the end of the process are potentially responsible for the health properties attributed to pistachio consumption.


Assuntos
Pistacia , Polifenóis , Polifenóis/metabolismo , Pistacia/metabolismo , Fermentação , Colo/metabolismo , Fenóis/metabolismo , Digestão
13.
Rev Esp Enferm Dig ; 115(4): 211-212, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36779461

RESUMO

Aortoesophageal fistula is a very rare cause of upper gastrointestinal bleeding, however its interest lies in the high mortality rate associated with it. Due to this, early diagnosis and treatment of this entity is essential to increase survival. The typical symptoms known as the Chiari´s triad are only present in 45% of reported cases. We present the case of a patient with upper gastrointestinal bleeding due to an aortoesophageal fistula as well as the importance of endoscopic use for its differential diagnosis.


Assuntos
Doenças da Aorta , Fístula Esofágica , Perfuração Esofágica , Fístula Vascular , Humanos , Perfuração Esofágica/diagnóstico por imagem , Perfuração Esofágica/etiologia , Fístula Vascular/complicações , Fístula Vascular/diagnóstico por imagem , Fístula Esofágica/etiologia , Fístula Esofágica/complicações , Hemorragia Gastrointestinal/complicações , Doenças da Aorta/etiologia , Doenças da Aorta/complicações
14.
Rev Med Chil ; 151(6): 797-800, 2023 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-38801389

RESUMO

Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.


Assuntos
Anticoagulantes , Rodenticidas , Tentativa de Suicídio , Humanos , Masculino , Adulto , Rodenticidas/intoxicação , Anticoagulantes/intoxicação , 4-Hidroxicumarinas/intoxicação , Vitamina K/uso terapêutico
15.
Rev Med Chil ; 151(7): 941-946, 2023 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-39093184

RESUMO

Lawsonella clevelandensis is a gram-positive anaerobic bacillus, partially acid-fast, belonging to the order Corynebacteriales and is considered commensal of the skin and oral cavity. In recent years, few cases of infection by this microorganism have been reported, generally in immunosuppressed patients, with the most reported clinical presentation being the generation of abscesses. The isolation of this bacterium is difficult since it does not grow in traditional cultures, so its identification usually requires the use of molecular biology. We present the case of a 29-year-old patient with a kidney transplant and progressive worsening of kidney function in the context of a pauci-immune vasculitis which required greater immunosuppression. During the investigation, it was identified an asymptomatic leukocyturia, with a negative urine culture, for which six urine smear microscopy tests were performed of which 3 were positive, but with a negative Koch culture. Sequencing of the gene that codes for the 16s RNA of the bacterial ribosome was performed from a urine sample, obtaining a sequence compatible with Lawsonella clevelandensis. After the result, therapy with amoxicillin-clavulanic acid was indicated with resolution of the leukocyturia and negative smear microscopy, and immunosuppression could be indicated without inconvenience. To the authors' knowledge, this is the twelfth case of Lawsonella clevelandensis infection described in the medical literature in the world and the first to report the isolation of the pathogen in urine.


Assuntos
Transplante de Rim , Humanos , Adulto , Masculino , Transplante de Rim/efeitos adversos , América Latina , Antibacterianos/uso terapêutico
16.
Respir Res ; 23(1): 168, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751068

RESUMO

BACKGROUND: Studies of the respiratory tract microbiome primarily focus on airway and lung microbial diversity, but it is still unclear how these microbial communities may be affected by intubation and long periods in intensive care units (ICU), an aspect that today could aid in the understanding of COVID19 progression and disease severity. This study aimed to explore and characterize the endotracheal tube (ETT) microbiome by analyzing ETT-associated microbial communities. METHODS: This descriptive study was carried out on adult patients subjected to invasive mechanical ventilation from 2 to 21 days. ETT samples were obtained from 115 patients from ICU units in two hospitals. Bacteria isolated from endotracheal tubes belonging to the ESKAPE group were analyzed for biofilm formation using crystal violet quantification. Microbial profiles were obtained using Illumina sequencing of 16S rRNA gene. RESULTS: The ETT microbiome was mainly composed by the phyla Proteobacteria, Firmicutes and Bacteroidetes. Microbiome composition correlated with the ICU in which patients were hospitalized, while intubation time and diagnosis of ventilator-associated pneumonia (VAP) did not show any significant association. CONCLUSION: These results suggest that the ICU environment, or medical practices, could be a key to microbial colonization and have a direct influence on the ETT microbiomes of patients that require mechanical ventilation.


Assuntos
COVID-19 , Microbiota , Adulto , Biofilmes , Hospitais , Humanos , Intubação Intratraqueal/efeitos adversos , RNA Ribossômico 16S/genética , Respiração Artificial/efeitos adversos
17.
Nephrol Dial Transplant ; 37(10): 1868-1878, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34788858

RESUMO

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Insuficiência Renal Crônica , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , SARS-CoV-2
18.
Cell Mol Life Sci ; 78(4): 1423-1444, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33084946

RESUMO

Antiviral responses of interferons (IFNs) are crucial in the host immune response, playing a relevant role in controlling viralw infections. Three types of IFNs, type I (IFN-α, IFN-ß), II (IFN-γ) and III (IFN-λ), are classified according to their receptor usage, mode of induction, biological activity and amino acid sequence. Here, we provide a comprehensive review of type I IFN responses and different mechanisms that viruses employ to circumvent this response. In the first part, we will give an overview of the different induction and signaling cascades induced in the cell by IFN-I after virus encounter. Next, highlights of some of the mechanisms used by viruses to counteract the IFN induction will be described. And finally, we will address different mechanism used by viruses to interference with the IFN signaling cascade and the blockade of IFN induced antiviral activities.


Assuntos
Interações Hospedeiro-Patógeno/genética , Imunidade Inata/genética , Interferons/genética , Viroses/genética , Humanos , Evasão da Resposta Imune/genética , Interferon-alfa/genética , Interferon-alfa/imunologia , Interferons/classificação , Interferons/imunologia , Transdução de Sinais , Viroses/imunologia
19.
Sensors (Basel) ; 22(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35590910

RESUMO

The research presents the inter-comparison of atmospheric variables measured by 9 automatic weather stations. This set of data was compared with the measurements of other weather stations in order to standardize the values that must be adjusted when taken to different areas. The data of a set of a total of 9 GMX500, which measures conventional meteorological variables, and 10 WS100 sensors, which measures precipitation parameters. The automatic stations were set up at the Huancayo Observatory (Geophysical Institute of Peru) for a period of 5 months. The data set of GMX500 were evaluated comparing with the average of the 9 sensors and the WS100 was compared with an optical disdrometer Parsivel2. The temperature, pressure, relative humidity, wind speed, rainfall rate, and drop size distribution were evaluated. A pair of GMX500 sensors presented high data dispersion; it was found found that the errors came from a bad configuration; once this problem was solved, good agreement was archived, with low RMSE and high correlation. It was found that the WS100 sensors overestimate the precipitation with a percentage bias close to 100% and the differences increase with the greater intensity of rain. The drop size distribution retrieved by WS100 have unrealistic behavior with higher concentrations in diameters of 1 mm and 5 mm, in addition to a flattened curve.


Assuntos
Chuva , Tempo (Meteorologia) , Umidade , Peru , Temperatura , Vento
20.
Int J Food Sci Nutr ; 73(4): 531-537, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34933644

RESUMO

The impact of ß-glucan on the bioavailability of orange juice (OJ) flavanones was investigated in a randomised controlled trial. Volunteers consumed 500 mL of OJ without or with either 3 g (OB-3) or 6 g (OB-6) of ß-glucan. Urine samples, collected 12 h before and over a 0-24 h period post-supplementation, were analysed by high-performance liquid chromatography-high resolution mass spectrometry. The overall 0-24 h urinary excretion of the 17 flavanone metabolites identified and quantified in urine after OJ ingestion corresponded to 29.7 µmol, and 25.0 and 9.3 µmol, respectively, after OB-3 and OB-6 intake. This corresponds to 9.3, 7.9, and 2.9% recoveries of the 318 µmol of the ingested flavanones. The acute ingestion of OJ with 6 g, but not 3 g of ß-glucan led to a significant reduction (p < 0.05) in the excretion of flavanone metabolites compared with consumption of OJ alone.


Assuntos
Citrus sinensis , Flavanonas , Hesperidina , beta-Glucanas , Bebidas/análise , Disponibilidade Biológica , Citrus sinensis/química , Flavanonas/análise , Hesperidina/análise , Humanos
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