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2.
Blood ; 140(10): 1119-1131, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-35759728

RESUMO

Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B-cell lymphoma (DLBCL). However, the premalignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to 4 hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1, and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivo promoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). As with MCD, these premalignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, displayed a de novo dependence on Tlr9, and were more sensitive to inhibition of Bruton's tyrosine kinase. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all 4 genetic lesions showed a >50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCBs as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.


Assuntos
Linfoma Difuso de Grandes Células B , Baço , Animais , Linfócitos B/patologia , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Mutação , Baço/patologia
3.
J Reprod Infant Psychol ; : 1-14, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591499

RESUMO

BACKGROUND: The 10-item Birth Satisfaction Scale-Revised (BSS-R) is a quick and easy survey instrument recommended by the International Consortium for Health Outcome Measures as the tool of choice for measuring women's birth satisfaction. AIM: To translate and validate a Vietnamese-language version of the BSS-R. METHOD: A quantitative cross-sectional method was used to gather data post translation and back-translation of a Vietnamese version of the BSS-R (VN-BSS-R). Data collected were psychometrically evaluated using key indices of validity and reliability. PARTICIPANTS: Vietnamese women who were within one month postpartum of birth (N = 383) took part in the study. RESULTS: Findings illustrate that a two-factor model offered excellent psychometric properties. With the two-factor VN-BSS-R, five items loaded onto a subscale 'Positive birth experiences' and the other five onto a second subscale 'Negative birth experiences'. This two-factor model offered a fit to data (root mean square error of approximation [RMSEA] = 0.07, 90% confidence interval [CI] [0.05, 0.09], root square mean residual [RMSE] = 0.04 and comparative fit index [CFI] = 0.97). Mean scores for the exploratory factor analysis [EFA]-derived 'positive' and 'negative' sub-scales were 17.12 (SD 2.34) and 8.40 (SD 4.18) respectively. CONCLUSION: The translated and validated VN-BSS-R is a psychometrically robust tool for measuring birth satisfaction in Vietnamese postpartum women.The VN-BSS-R is available for use to measure experiences and perceptions of intrapartum care received by Vietnamese women.

4.
Antimicrob Agents Chemother ; 67(10): e0042423, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37695304

RESUMO

We have previously reported promising in vivo activity of the first-generation 2-aminopyramidine robenidine analogue NCL195 against Gram-positive bacteria (GPB) when administered via the systemic route. In this study, we examined the efficacy of oral treatment with NCL195 (± low-dose colistin) in comparison to oral moxifloxacin in bioluminescent Staphylococcus aureus and Escherichia coli peritonitis-sepsis models. Four oral doses of 50 mg/kg NCL195, commencing immediately post-infection, were administered at 4 h intervals in the S. aureus peritonitis-sepsis model. We used a combination of four oral doses of 50 mg/kg NCL195 and four intraperitoneal doses of colistin at 0.125 mg/kg, 0.25 mg/kg, or 0.5 mg/kg in the E. coli peritonitis-sepsis model. Subsequently, the dose rates of four intraperitoneal doses of colistin were increased to 0.5 mg/kg, 1 mg/kg, or 2 mg/kg at 4 h intervals to treat a colistin-resistant E. coli infection. In the S. aureus infection model, oral treatment of mice with NCL195 resulted in significantly reduced S. aureus infection loads (P < 0.01) and longer survival times (P < 0.001) than vehicle-only treated mice. In the E. coli infection model, co-administration of NCL195 and graded doses of colistin resulted in a dose-dependent significant reduction in colistin-susceptible (P < 0.01) or colistin-resistant (P < 0.05) E. coli loads compared to treatment with colistin alone at similar concentrations. Our results confirm that NCL195 is a potential candidate for further preclinical development as a specific treatment for multidrug-resistant infections, either as a stand-alone antibiotic for GPB or in combination with sub-inhibitory concentrations of colistin for Gram-negative bacteria.


Assuntos
Bacteriemia , Infecções por Escherichia coli , Peritonite , Sepse , Infecções Estafilocócicas , Camundongos , Animais , Colistina/farmacologia , Colistina/uso terapêutico , Staphylococcus aureus , Escherichia coli , Robenidina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Administração Oral , Testes de Sensibilidade Microbiana
5.
PLoS Pathog ; 17(11): e1010026, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762705

RESUMO

Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with Trypanosoma evansi having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases, T. evansi can cause atypical Human Trypanosomosis. The success of this parasite is attributed to its capacity to evade and disable the mammalian defense response. To unravel the latter, we applied here for the first time a scRNA-seq analysis on splenocytes from trypanosome infected mice, at two time points during infection, i.e. just after control of the first parasitemia peak (day 14) and a late chronic time point during infection (day 42). This analysis was combined with flow cytometry and ELISA, revealing that T. evansi induces prompt activation of splenic IgM+CD1d+ Marginal Zone and IgMIntIgD+ Follicular B cells, coinciding with an increase in plasma IgG2c Ab levels. Despite the absence of follicles, a rapid accumulation of Aicda+ GC-like B cells followed first parasitemia peak clearance, accompanied by the occurrence of Xbp1+ expressing CD138+ plasma B cells and Tbx21+ atypical CD11c+ memory B cells. Ablation of immature CD93+ bone marrow and Vpreb3+Ly6d+Ighm+ expressing transitional spleen B cells prevented mature peripheral B cell replenishment. Interestingly, AID-/- mice that lack the capacity to mount anti-parasite IgG responses, exhibited a superior defense level against T. evansi infections. Here, elevated natural IgMs were able to exert in vivo and in vitro trypanocidal activity. Hence, we conclude that in immune competent mice, trypanosomosis associated B cell activation and switched IgG production is rapidly induced by T. evansi, facilitating an escape from the detrimental natural IgM killing activity, and resulting in increased host susceptibility. This unique role of IgM and its anti-trypanosome activity are discussed in the context of the dilemma this causes for the future development of anti-trypanosome vaccines.


Assuntos
Linfócitos B/imunologia , Citidina Desaminase/fisiologia , Switching de Imunoglobulina , Mutação , Análise de Célula Única/métodos , Trypanosoma/genética , Tripanossomíase/parasitologia , Animais , Anticorpos Antiprotozoários/imunologia , Feminino , Isotipos de Imunoglobulinas/imunologia , Ativação Linfocitária , Células B de Memória/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transcriptoma , Trypanosoma/imunologia , Tripanossomíase/genética , Tripanossomíase/imunologia
6.
J Pediatr ; 262: 113340, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36736584

RESUMO

Reconstruction for microtia decreased psychosocial morbidity; timely referral for surgery is crucial. We evaluated specialist referrals for microtia at a major academic medical center. Only one-half of patients were evaluated at any point by a reconstructive craniofacial surgeon. Patients followed early for audiologic concerns may not be receiving timely referred for reconstruction.


Assuntos
Microtia Congênita , Procedimentos de Cirurgia Plástica , Humanos , Criança , Microtia Congênita/cirurgia
7.
Environ Res ; 226: 115675, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906268

RESUMO

Low-cost adsorbents derived from agricultural by-products incorporated magnetic nanoparticles (NPs) are promising for wastewater treatment. They are always preferred due to their great performance and easy separation. This study reports cobalt superparamagnetic (CoFe2O4) nanoparticles (NPs) incorporated with triethanolamine (TEA) based surfactants from cashew nut shell liquid, namely TEA-CoFe2O4, for the removal of chromium (VI) ions from aqueous solutions. To have detailed characteristics of the morphology and structural properties, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometry (VSM) were employed. The fabricated TEA-CoFe2O4 particles exhibit soft and superparamagnetic properties, which make the nanoparticles easily recycled by using a magnet. Chromate adsorption on the TEA-CoFe2O4 nanomaterials reached an optimal efficiency of 84.3% at pH = 3 with the initial adsorbent dose of 10 g/L and chromium (VI) concentration of 40 mg/L. The TEA-CoFe2O4 nanoparticles can maintain the effective adsorption of chromium (VI) ion (by 29% of efficiency loss) and retain the magnetic separation using a magnet up to three cycles of the regeneration, which promise a high potential of this low-cost adsorbent for long-term treatment of heavy metal ions from polluted waters.


Assuntos
Nanopartículas de Magnetita , Poluentes Químicos da Água , Cromatos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas de Magnetita/química , Adsorção , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Cinética
8.
Dig Dis Sci ; 68(8): 3254-3258, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37268795

RESUMO

INTRODUCTION: Discordance between gastrointestinal (GI) symptoms and endoscopic inflammation in patients with ulcerative colitis (UC) is known. However, the correlations between symptoms and endoscopic and histologic (endo-histologic) mucosal healing and remains unknown. METHODS: We performed a secondary analysis of prospectively collected clinical, endoscopic, and histologic data on 254 colonoscopies from 179 unique adults at a tertiary referral center from 2014 to 2021. Spearman's rank was used to assess the correlation between patient reported outcomes and objective assessments of disease activity, as measured by validated instruments: Two-item patient-reported outcome measure (PRO-2) for stool frequency and rectal bleeding, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for endoscopic inflammation, and the Geboes score for histologic inflammation. The predictive value of objective assessments of inflammation and clinical symptoms was described using sensitivity, specificity, and positive/negative predictive value. RESULTS: One-quarter (28%, 72/254) of cases were in endo-histologic remission; of these, 25% (18/72) report GI symptoms (22% diarrhea; 6% rectal bleeding). Endo-histologically active disease had higher sensitivity (95% rectal bleeding; 87% diarrhea) and negative predictive value (94% rectal bleeding, 78% diarrhea) for clinically active disease compared to active disease on endoscopic (77%) or histologic assessment only (80%). The specificity of endo/histologic inflammation for GI symptoms was < 65%. PRO-2 was positively correlated with endoscopic disease activity (Spearman's rank 0.57, 95% CI 0.54-0.60, p < 0.0001) and histologic disease activity (Spearman's rank 0.49, 0.45-0.53, p < 0.0001). CONCLUSION: One-quarter of patients with ulcerative colitis in endo-histologic (deep) remission have gastrointestinal symptoms, more commonly with diarrhea than rectal bleeding. Endo-histologic inflammation has high sensitivity (≥ 87%) for diarrhea/rectal bleeding.


Assuntos
Colite Ulcerativa , Humanos , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Colonoscopia , Inflamação/patologia , Mucosa/patologia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/patologia , Diarreia/etiologia , Diarreia/patologia , Índice de Gravidade de Doença
9.
Proc Natl Acad Sci U S A ; 117(42): 26318-26327, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33020271

RESUMO

Epstein-Barr virus (EBV) infects human B cells and reprograms them to allow virus replication and persistence. One key viral factor in this process is latent membrane protein 2A (LMP2A), which has been described as a B cell receptor (BCR) mimic promoting malignant transformation. However, how LMP2A signaling contributes to tumorigenesis remains elusive. By comparing LMP2A and BCR signaling in primary human B cells using phosphoproteomics and transcriptome profiling, we identified molecular mechanisms through which LMP2A affects B cell biology. Consistent with the literature, we found that LMP2A mimics a subset of BCR signaling events, including tyrosine phosphorylation of the kinase SYK, the calcium initiation complex consisting of BLNK, BTK, and PLCγ2, and its downstream transcription factor NFAT. However, the majority of LMP2A-induced signaling events markedly differed from those induced by BCR stimulation. These included differential phosphorylation of kinases, phosphatases, adaptor proteins, transcription factors such as nuclear factor κB (NF-κB) and TCF3, as well as widespread changes in the transcriptional output of LMP2A-expressing B cells. LMP2A affected apoptosis and cell-cycle checkpoints by dysregulating the expression of apoptosis regulators such as BCl-xL and the tumor suppressor retinoblastoma-associated protein 1 (RB1). LMP2A cooperated with MYC and mutant cyclin D3, two oncogenic drivers of Burkitt lymphoma, to promote proliferation and survival of primary human B cells by counteracting MYC-induced apoptosis and by inhibiting RB1 function, thereby promoting cell-cycle progression. Our results indicate that LMP2A is not a pure BCR mimic but rather rewires intracellular signaling in EBV-infected B cells that optimizes cell survival and proliferation, setting the stage for oncogenic transformation.


Assuntos
Herpesvirus Humano 4/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Proteínas da Matriz Viral/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/fisiologia , Linfócitos B/metabolismo , Humanos , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Fosforilação , Transdução de Sinais , Quinase Syk/metabolismo
10.
Aesthetic Plast Surg ; 47(3): 1104-1110, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36097080

RESUMO

BACKGROUND: Patients with dentofacial anomalies may undergo orthognathic surgery to address functional and aesthetic concerns. Past works have evaluated determinants affecting length of stay (LOS) in patients undergoing upper and/or lower jaw surgery alone. No studies have assessed the addition of genioplasty to double-jaw (Lefort I, bilateral sagittal split osteotomy (BSSO))) surgery and its effect on LOS and other outcomes. This study investigates whether the addition of genioplasty incurs additional morbidity to patients undergoing complex orthognathic surgery. METHODS: This was a retrospective cohort study of patients undergoing orthognathic surgery at Yale-New Haven Hospital. Clinical and demographic information were compared across the "double"- and "triple"-jaw cohorts with t tests and Chi-squared analyses. Multivariable linear and logistic regression analyses were utilized to assess the impact of genioplasty when controlling for baseline patient differences. RESULTS: A total of 27 patients received Lefort I and BSSO (double-jaw), and 224 received Lefort I, BSSO, and genioplasty (triple-jaw). Six (22.2%) double-jaw patients were segmental and fifty-eight (25.9%) triple-jaw patients were segmental (p > 0.05), during the study period. Triple-jaw surgery was associated with increased operative time (+ 41.1 min, p < 0.01). There was no increase in LOS, postoperative nausea and vomiting, opioid use, hematoma, or infection (p > 0.05). CONCLUSIONS: This study attempted to determine if triple-jaw surgery could influence patients' LOS and other surgical outcomes compared to double-jaw surgery. Only the operative time was significantly affected. This indicates that incorporation of a genioplasty can provide aesthetic benefit without incurring significant additional morbidity to the patient. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Mentoplastia , Estudos Retrospectivos , Morbidade
11.
J Autoimmun ; 128: 102814, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35298976

RESUMO

Inflammatory bowel disease (IBD) is a serious public health problem in Western society with a continuing increase in incidence worldwide. Safe, targeted medicines for IBD are not yet available. Autophagy, a vital process implicated in normal cell homeostasis, provides a potential point of entry for the treatment of IBDs, as several autophagy-related genes are associated with IBD risk. We conducted a series of experiments in three distinct mouse models of colitis to test the effectiveness of therapeutic P140, a phosphopeptide that corrects autophagy dysfunctions in other autoimmune and inflammatory diseases. Colitis was experimentally induced in mice by administering dextran sodium sulfate and 2,4,6 trinitrobenzene sulfonic acid. Transgenic mice lacking both il-10 and iRhom2 - involved in tumor necrosis factor α secretion - were also used. In the three models investigated, P140 treatment attenuated the clinical and histological severity of colitis. Post-treatment, altered expression of several macroautophagy and chaperone-mediated autophagy markers, and of pro-inflammatory mediators was corrected. Our results demonstrate that therapeutic intervention with an autophagy modulator improves colitis in animal models. These findings highlight the potential of therapeutic peptide P140 for use in the treatment of IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Autofagia , Proteínas de Transporte , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/metabolismo , Lisossomos/metabolismo , Camundongos
12.
Photosynth Res ; 153(1-2): 43-57, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35092556

RESUMO

Coralline algae (CA) are globally distributed and fulfil many important roles within coastal ecosystems. In this study, photosynthetically active radiation (PAR) measured for 616 days at 2 and 10 m in a temperate subtidal kelp forest in southern New Zealand provided context to photosynthesis vs. irradiance relationships for, and pigment concentrations of, an articulated coralline alga, Arthrocardia sp. and a crustose coralline species assemblage within the Hapalidiales order. The maximum photosynthetic rate Pmax of the Arthrocardia sp. (20.38 ± 2.38 µmol O2. gDW-1 h-1) was significantly higher than the Pmax of crustose coralline spp. (3.72 ± 0.74 µmol O2. gDW-1 h-1) at the same 2 m stratum. Pigment concentration of Arthrocardia sp. was significantly higher than that of crustose coralline spp. at the same depth, while pigment concentration of crustose coralline spp. at 2 and 10 m were not significantly affected by depth. The photosynthetic characteristics of these coralline algae represent a shade acclimated organism with low saturation irradiance (all Ek < 100 µmol photons m-2 s-1). Despite sevenfold difference in average daily dose between 2 and 10 m there was no significant effect of depth on the photosynthetic performance of crustose coralline algae measured. The lack of evidence for acclimation to low light could be because periods of clear water provide enough light to maintain photosynthesis, lower energetic requirements of species found at depth or constraints on the synthesis of photosynthetic pigments at greater depth.


Assuntos
Kelp , Rodófitas , Ecossistema , Kelp/efeitos da radiação , Luz , Fotossíntese/fisiologia , Água
13.
Environ Res ; 211: 113037, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35248562

RESUMO

Sediment humins are extremely important for binding hydrophobic organic contaminants in rivers and lakes. Nonetheless, little is known about their structure and binding. We, therefore, examined the structure and phenanthrene sorption affinity of sediment humin samples upstream, midstream, and downstream from two artificial lakes in South Korea by using the elemental 13C-NMR analysis, Freundlich model, and Langmuir model. The characteristics and phenanthrene sorption affinity of sediment humins were also compared with those of sediment humic acids from similar origins as well as soil humins/humic acids in South Korea from previous studies by using principal component analysis. In both lakes, downstream sediment humins exhibited lower N/C, O/C, and (N + O)/C ratios, lower internal oxidation, and higher aliphaticity due to the presence of long-chain aliphatic compounds generated during anaerobic decomposition. The principal component analysis results also showed that C,H-alkyl, O-alkyl, and polar organic carbon contents were significantly different when comparing the up-mid stream and downstream sediment samples in Daecheong Lake. In addition, midstream sediment humin in Andong Lake presented higher C,H-alkyl and lower polar organic carbon contents compared to those of up-downstream samples. In both lakes, the sorption coefficient and adsorption isotherm linearity were positively correlated with the C,H-alkyl content and negatively correlated with the O-aryl content. Similar to C,H-alkyl and POC, C,H-alkyl, and (N + O)/C had an extremely high correlation coefficient when predicting the sorption coefficient (Freundlich model) and the maximum adsorption capacity (Langmuir model) of sediment humins. Sediment humins had higher C,H-alkyl contents and lower sorption coefficients than those of sediment humic acids and soil humins/humic acids. These findings provide key information for monitoring water quality and polycyclic aromatic hydrocarbon contamination in South Korean lake sediments.


Assuntos
Substâncias Húmicas , Fenantrenos , Adsorção , Carbono , Sedimentos Geológicos/análise , Substâncias Húmicas/análise , Lagos/análise , Solo
14.
Environ Res ; 214(Pt 4): 114130, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35998691

RESUMO

The present work focused on the synthesis of novel ZnLaxFe2-xO4 catalysts (x = 0, 0.01, 0.03, 0.05) and their utilization for the photocatalytic degradation of Rhodamine B dye. Structurally, the band gap energy of the catalysts tended to decrease (1.94-1.70 eV) with increasing the amount of La3+ dopant. ZnLa0.05Fe1.95O4 had an average particle size (40 nm), high surface area (41.07 m2 g-1) and large pore volume (0.186 cm3 g-1). Moreover, the effect of doping ratio, reaction time, H2O2 concentration, catalyst loading on the treatment performance of La3+ substituted ZnFe2O4 nanocomposites was investigated. ZnLa0.05Fe1.95O4/H2O2 system exhibited the highest degradation efficiency of 99.5% and nonlinear pseudo first-order kinetic reaction rate (14.8 × 10-3 min-1) in the presence of visible light irradiation. The key role of reactive oxygen species involving •O2- and •OH radicals was well explained through the scavenger study. A plausible mechanism of the degradation of Rhodamine B dye was also proposed. Due to two advantageous points including high recyclability (up to 4 cycles) and stability, La3+ substituted ZnFe2O4 nanocomposites can be an effective and competitive catalyst for the visible light-driven photodegradation of toxic dyes in the real wastewaters.

15.
BMC Nephrol ; 23(1): 291, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999520

RESUMO

BACKGROUND: Hyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction. METHODS: We conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain. RESULTS: There were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r = 0.3, p = .04; r = 0.4, p = .002; r = 0.5, p < .0001; and r = 0.5, p = .0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p = .01), 0.4 (p = .007), and 0.3 (p = .04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (ß = 4.33, p = .0002; log transformed ß = 0.05, p = .005; reciprocal transformed ß = -0.03, p = .047). CONCLUSIONS: Serum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification. TRIAL REGISTRATION: The study was part of a registered clinical trial, NCT01862497 (May 24, 2013).


Assuntos
Hiperfosfatemia , Hipertensão , Falência Renal Crônica , Calcificação Vascular , Pressão Sanguínea/fisiologia , Estudos Transversais , Células Endoteliais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Falência Renal Crônica/complicações , Hormônio Paratireóideo , Fosfatos , Diálise Renal/efeitos adversos , Calcificação Vascular/complicações , Vasoconstrição , Aumento de Peso
16.
Plant Dis ; 106(3): 960-965, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34705489

RESUMO

Since the protective activity of the Bordeaux mixture against plant disease caused by oomycetes was discovered, copper compounds have been used for more than a century as an effective plant protection strategy. However, the application of excessive copper can cause adverse effects through long-term heavy metal accumulation in soils. Therefore, it is necessary to develop new strategies to reduce or replace copper in pesticides based on organic and low-input farming systems. Organic acids are eco-friendly. In this study, we tested the antifungal and anti-oomycete activity of maleic acid (MA) and copper sulfate (CS) against 13 plant pathogens. Treatment with a mixture of MA and CS showed strong anti-oomycetes activity against Phytophthora xcambivora, P. capsici, and P. cinnamomi. Moreover, the concentration of CS in the activated mixture of MA and CS was lower than that in the activated CS only, and the mixture showed synergy or partial synergy effects on the anti-oomycete activity. Application of a wettable powder formulation of MA and CS mixture (MCS 30WP; 26.67% MA and 3.33% CS) had excellent protective activity in pot experiments with control values of 73% Phytophthora blight on red pepper, 91% damping-off on cucumber, and 84% Pythium blight on creeping bentgrass, which are similar to those of the CS wettable powder formulation (6.67% CS) containing two times the CS content of MCS 30WP. These observations suggest that the synergistic effect of the MA and CS combination is a sustainable alternative for effective management of destructive oomycete diseases.


Assuntos
Sulfato de Cobre , Phytophthora , Sulfato de Cobre/farmacologia , Maleatos/farmacologia , Phytophthora/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
17.
Environ Monit Assess ; 194(Suppl 2): 765, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36255568

RESUMO

Can Tho city in the Mekong Delta is in the top ten areas affected by climate change. Therefore, assessing climate change impacts, social and economic activities require proposed solutions to respond to climate change. This study aims to (i) apply the MIKE 11 model (Hydrodynamic module and Advection-Dispersion module) to simulate the impacts of climate change scenarios on water resources in Can Tho city; (ii) calculate water balance in Can Tho city; and (iii) suggest climate change adaptation plan for sustainable social-economic activities of the city. The results show that when the rainfall changes due to climate change, the flow rate tends to decrease at high tide and increase at low tide. When the sea level rises due to climate change, the flow rate tends to increase at high tide and decrease at low tide. For 2030, the flow will decrease up to 15.6% and 14.3% at the low tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The flow will increase up to 63.5% and 58.9% at the high tide period for RCP 2.6 and RCP 8.5 compared to the present, respectively. The water demand evaluation shows that the water resource reserve in Can Tho city meets water demands in current and future scenarios under climate change. While rainwater and groundwater can provide enough water in the rainy season, the city has to use surface water during the dry season due to a lack of rainwater. Of these, agriculture contributes the most water demands (85%). Eight adaptation measures to climate change for Can Tho city are developed from 2021 to 2050.


Assuntos
Mudança Climática , Recursos Hídricos , Vietnã , Monitoramento Ambiental , Água
18.
Gastroenterology ; 158(5): 1373-1388, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31917256

RESUMO

BACKGROUND & AIMS: Colibactin-producing Escherichia coli (CoPEC) colonize the colonic mucosa of a higher proportion of patients with vs without colorectal cancer (CRC) and promote colorectal carcinogenesis in susceptible mouse models of CRC. Autophagy degrades cytoplasmic contents, including intracellular pathogens, via lysosomes and regulates intestinal homeostasis. We investigated whether inhibiting autophagy affects colorectal carcinogenesis in susceptible mice infected with CoPEC. METHODS: Human intestinal epithelial cells (IECs) (HCT-116) were infected with a strain of CoPEC (11G5 strain) isolated from a patient or a mutant strain that does not produce colibactin (11G5ΔclbQ). Levels of ATG5, ATG16L1, and SQSTM1 (also called p62) were knocked down in HCT-116 cells using small interfering RNAs. ApcMin/+ mice and ApcMin/+ mice with IEC-specific disruption of Atg16l1 (ApcMin/+/Atg16l1ΔIEC) were infected with 11G5 or 11G5ΔclbQ. Colonic tissues were collected from mice and analyzed for tumor size and number and by immunohistochemical staining, immunoblot, and quantitative reverse transcription polymerase chain reaction for markers of autophagy, DNA damage, cell proliferation, and inflammation. We analyzed levels of messenger RNAs (mRNAs) encoding proteins involved in autophagy in colonic mucosal tissues from patients with sporadic CRC colonized with vs without CoPEC by quantitative reverse-transcription polymerase chain reaction. RESULTS: Patient colonic mucosa with CoPEC colonization had higher levels of mRNAs encoding proteins involved in autophagy than colonic mucosa without these bacteria. Infection of cultured IECs with 11G5 induced autophagy and DNA damage repair, whereas infection with 11G5ΔclbQ did not. Knockdown of ATG5 in HCT-116 cells increased numbers of intracellular 11G5, secretion of interleukin (IL) 6 and IL8, and markers of DNA double-strand breaks but reduced markers of DNA repair, indicating that autophagy is required for bacteria-induced DNA damage repair. Knockdown of ATG5 in HCT-116 cells increased 11G5-induced senescence, promoting proliferation of uninfected cells. Under uninfected condition, ApcMin/+/Atg16l1ΔIEC mice developed fewer and smaller colon tumors than ApcMin/+ mice. However, after infection with 11G5, ApcMin/+/Atg16l1ΔIEC mice developed more and larger tumors, with a significant increase in mean histologic score, than infected ApcMin/+ mice. Increased levels of Il6, Tnf, and Cxcl1 mRNAs, decreased level of Il10 mRNA, and increased markers of DNA double-strand breaks and proliferation were observed in the colonic mucosa of 11G5-infected ApcMin/+/Atg16l1ΔIEC mice vs 11G5-infected ApcMin/+ mice. CONCLUSION: Infection of IECs and susceptible mice with CoPEC promotes autophagy, which is required to prevent colorectal tumorigenesis. Loss of ATG16L1 from IECs increases markers of inflammation, DNA damage, and cell proliferation and increases colorectal tumorigenesis in 11G5-infected ApcMin/+ mice. These findings indicate the importance of autophagy in response to CoPEC infection, and strategies to induce autophagy might be developed for patients with CRC and CoPEC colonization.


Assuntos
Autofagia , Carcinogênese/imunologia , Colo/microbiologia , Neoplasias do Colo/imunologia , Mucosa Intestinal/microbiologia , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/imunologia , Proteínas Relacionadas à Autofagia/metabolismo , Carcinogênese/efeitos dos fármacos , Proliferação de Células , Colo/imunologia , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/patologia , Escherichia coli/imunologia , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Células HeLa , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Transgênicos , Peptídeos/toxicidade , Policetídeos/toxicidade , RNA Interferente Pequeno/metabolismo
19.
J Clin Microbiol ; 59(10): e0093621, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34319801

RESUMO

We developed a novel real-time PCR assay that simultaneously evaluates 11 major nucleos(t)ide antiviral (NA) drug resistance mutations (mt) in chronic hepatitis B patients (CHB), including L180M, M204I/V, and V207M (lamivudine [LMV] resistance), N/H238A/T (adefovir [ADF] resistance), which are circulating in Vietnam; and T184G/L, S202I, and M250V (entecavir [ETV] resistance) and A194T (tenofovir resistance), which have been recently reported in several studies across the globe. We detected drug-resistant mt in hepatitis B virus (HBV) samples using our predesigned panel of allele-specific locked-nucleic acid (LNA) probes. Our assay had a high sensitivity of 5% in a low-HBV DNA population of ≥5 × 103 IU/ml and was validated in a cohort of 130 treatment-naive children and 98 NA-experienced adults with CHB. Single-point mt for LMV and ADF resistance were detected in 57.7% and 54.1% of the child and adult samples, respectively, with rtV207M (children, 42.3%; adults, 36.7%) and rtN238T/A (children, 15.4%; adults, 16.3%) being the most frequent mt in these populations. Multiple-point mt, including rtL180M-rtM204V- rtN238A and rtL180M-rtM204I, were identified in only two children, resulting in LMV-ADF resistance and reduced ETV susceptibility. In conclusion, this assay accurately identified the mt profile of children (98.4%) and adults (91.2%) with CHB, which is comparable to established methods. This fast and sensitive screening method can be used for the detection of major NA-resistant mt circulating in developing countries, as well as providing a model for the development of similar mt-detection assays, especially for use in nonhospitalized patients who need their results within half a day, before starting treatment.


Assuntos
Hepatite B Crônica , Adulto , Antivirais/farmacologia , Antivirais/uso terapêutico , Criança , DNA Viral/genética , Farmacorresistência Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Mutação , Reação em Cadeia da Polimerase em Tempo Real
20.
J Med Virol ; 93(9): 5660-5665, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34042186

RESUMO

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.


Assuntos
COVID-19/virologia , Variação Genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/transmissão , Busca de Comunicante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Quarentena , Análise de Regressão , Vietnã/epidemiologia , Sequenciamento Completo do Genoma , Adulto Jovem
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