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Obesity is a risk factor for asthma. Individuals with asthma and obesity often have poor asthma control and do not respond as well to therapies such as inhaled corticosteroids and long-acting bronchodilators. Weight loss improves asthma control, with a 5%-10% loss in body mass necessary and sufficient to lead to clinically relevant improvements. Preclinical studies have demonstrated the pathogenic contribution of adipocytes from obese mice to the augmented production of proinflammatory cytokines from airway epithelial cells and the salutary effects of diet-induced weight loss to decrease these consequences. However, the effects of adipocyte-derived products on airway epithelial function in human obesity remain incompletely understood. We utilized samples collected from a 12-mo longitudinal study of subjects with obesity undergoing weight loss (bariatric) surgery including controls without asthma and subjects with allergic and nonallergic obese asthma. Visceral adipose tissue (VAT) samples were collected during bariatric surgery and from recruited normal weight controls without asthma undergoing elective abdominal surgery. Human bronchial epithelial (HBEC3-KT) cells were exposed to plasma or conditioned media from cultured VAT adipocytes with or without agonists. Human bronchial smooth muscle (HBSM) cells were similarly exposed to adipocyte-conditioned media. Proinflammatory cytokines were augmented in supernatants from HBEC3-KT cells exposed to plasma as compared with subsequent visits. Whereas exposure to obese adipocyte-conditioned media induced proinflammatory responses, there were no differences between groups in both HBEC3-KT and HBSM cells. These data show that bariatric surgery and subsequent weight loss beneficially change the circulating factors that augment human airway epithelial and bronchial smooth muscle cell proinflammatory responses.NEW & NOTEWORTHY This longitudinal study following subjects with asthma and obesity reveals that weight loss following bariatric surgery decreases the capacity for plasma to augment proinflammatory cytokine secretion by human bronchial epithelial cells, implicating that circulating but not adipocyte-derived factors are important modulators in obese asthma.
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Asma , Cirurgia Bariátrica , Animais , Camundongos , Humanos , Estudos Longitudinais , Meios de Cultivo Condicionados , Obesidade/cirurgia , Obesidade/complicações , Cirurgia Bariátrica/efeitos adversos , Brônquios/patologia , Citocinas , Células Epiteliais/patologia , Redução de Peso/fisiologiaRESUMO
Impaired baroreflex sensitivity (BRS) is partially responsible for erratic blood pressure fluctuations in End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD), which is related to autonomic nervous dysfunction. The sequence method with delayed signals allows for the measurement of BRS in a non-invasive fashion and the investigation of alterations in this physiological feedback system that maintains BP within healthy limits. Our objective was to evaluate the modified delayed signals in the sequence method for BRS assessment in ESRD patients without pharmacological antihypertensive treatment and compare them with those of healthy subjects. We recruited 22 healthy volunteers and 18 patients with ESRD. We recorded continuous BP to obtain a 15-min time series of systolic blood pressure and interbeat intervals during the supine position (SP) and active standing (AS) position. The time series with delays from 0 to 5 heartbeats were used to calculate the BRS, number of data points, number of sequences, and estimation error. The BRS from the ESRD patients was smaller than in healthy subjects (p < 0.05). The BRS estimation with the delayed sequences also increased the number of data points and sequences and decreased the estimation error compared to the original time series. The modified sequence method with delayed signals may be useful for the measurement of baroreflex sensitivity in ESRD patients with a shorter recording time and maintaining an estimation error below 0.01 in both the supine and active standing positions. With this framework, it was corroborated that baroreflex sensitivity in ESRD is decreased when compared with healthy subjects.
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Barorreflexo , Falência Renal Crônica , Humanos , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Diálise Renal , Frequência Cardíaca/fisiologiaRESUMO
Importance: Novel therapies for type 2 diabetes can reduce the risk of cardiovascular disease and chronic kidney disease progression. The equitability of these agents' prescription across racial and ethnic groups has not been well-evaluated. Objective: To investigate differences in the prescription of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) among adult patients with type 2 diabetes by racial and ethnic groups. Design, Setting, and Participants: Cross-sectional analysis of data from the US Veterans Health Administration's Corporate Data Warehouse. The sample included adult patients with type 2 diabetes and at least 2 primary care clinic visits from January 1, 2019, to December 31, 2020. Exposures: Self-identified race and self-identified ethnicity. Main Outcomes and Measures: The primary outcomes were prevalent SGLT2i or GLP-1 RA prescription, defined as any active prescription during the study period. Results: Among 1â¯197â¯914 patients (mean age, 68 years; 96% men; 1% American Indian or Alaska Native, 2% Asian, Native Hawaiian, or Other Pacific Islander, 20% Black or African American, 71% White, and 7% of Hispanic or Latino ethnicity), 10.7% and 7.7% were prescribed an SGLT2i or a GLP-1 RA, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 8.4% among American Indian or Alaska Native patients; 11.8% and 8% among Asian, Native Hawaiian, or Other Pacific Islander patients; 8.8% and 6.1% among Black or African American patients; and 11.3% and 8.2% among White patients, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 7.1% among Hispanic or Latino patients and 10.7% and 7.8% among non-Hispanic or Latino patients. After accounting for patient- and system-level factors, all racial groups had significantly lower odds of SGLT2i and GLP-1 RA prescription compared with White patients. Black patients had the lowest odds of prescription compared with White patients (adjusted odds ratio, 0.72 [95% CI, 0.71-0.74] for SGLT2i and 0.64 [95% CI, 0.63-0.66] for GLP-1 RA). Patients of Hispanic or Latino ethnicity had significantly lower odds of prescription (0.90 [95% CI, 0.88-0.93] for SGLT2i and 0.88 [95% CI, 0.85-0.91] for GLP-1 RA) compared with non-Hispanic or Latino patients. Conclusions and Relevance: Among patients with type 2 diabetes in the Veterans Health Administration system during 2019 and 2020, prescription rates of SGLT2i and GLP-1 RA medications were low, and individuals of several different racial groups and those of Hispanic ethnicity had statistically significantly lower odds of receiving prescriptions for these medications compared with individuals of White race and non-Hispanic ethnicity. Further research is needed to understand the mechanisms underlying these differences in rates of prescribing and the potential relationship with differences in clinical outcomes.
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Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Disparidades em Assistência à Saúde , Prescrições , Inibidores do Transportador 2 de Sódio-Glicose , Saúde dos Veteranos , Adulto , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etnologia , Etnicidade/estatística & dados numéricos , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Equidade em Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Prescrições/estatística & dados numéricos , Prática Profissional/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estados Unidos/epidemiologia , Saúde dos Veteranos/etnologia , Saúde dos Veteranos/estatística & dados numéricosRESUMO
BACKGROUND: Guidelines recommend estimating glomerular filtration rate (GFR) using creatinine-based equations (CBE). AIM: To evaluate the agreement between GFR measured using radionuclide imaging and estimated using creatinine-based equations. MATERIAL AND METHODS: In 421 patients aged 54 ± 17 years (47% women) GFR was estimated using the MDRD-4, CKD-EPI and the body surface adjusted Cockroft Gault equation. GFR was also measured using a radionuclide imaging method with 99mTc-DTPA. The concordance between estimated and measured GFR was calculated using Lin's concordance coefficient and Bland and Altman plots. RESULTS: Average GFR values obtained with CKD-EPI, MDRD-4, body surface adjusted Cockroft Gault equation and 99mTc-DTPA imaging were 75.9 ± 26.6, 76.3 ± 28.8, 77.1 ± 31.6 and 77.9 ± 28.4 ml/min/1.73 m2, respectively. There was no significant difference in means and 29% of participants had a GFR < 60 ml/min/1.73 m2 by CKD-EPI. The correlation was good between equations, but acceptable when compared with the 99mTc-DTPA imaging. The weighted kappa between CBEs was good, but low when comparing CBEs with measured GFR. The Lin's concordance coefficient between estimated and measured GFR was low. CONCLUSIONS: GFR measured by 99mTc-DTPA radionuclide imaging has a low correlation and poor concordance with estimations using CBE.
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Insuficiência Renal Crônica , Creatinina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Cintilografia , Insuficiência Renal Crônica/diagnóstico por imagemRESUMO
Monomeric, dimeric, and trimeric derivatives of the triphenylmethane dye crystal violet (1a-1f) have been synthesized for the purpose of evaluating their affinity and sequence selectivity for duplex DNA. Competitive ethidum displacement assays indicate that 1a-1f have apparent association constants for CT DNA in the range of 1.80-16.2â¯×â¯107â¯M-1 and binding site sizes of 10-14â¯bp. Viscosity experiments performed on ligand 1f confirmed that these dyes associate with duplex DNA by a non-intercalative mode of binding. Circular dichroism and competition binding studies of the tightest binding ligand 1e with known major and minor groove binding molecules suggest that these dye derivatives likely occupy the major groove of DNA. Data from the binding of 1e to polynucleotides indicate close to an order of magnitude preference for associating with AT rich homopolymers over GC rich homopolymers, suggesting a shape-selective match of the sterically bulky ligand with DNA containing a wider major groove.
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DNA/metabolismo , Violeta Genciana/metabolismo , Animais , Sítios de Ligação , Bovinos , DNA/química , Violeta Genciana/síntese química , Violeta Genciana/química , Ligantes , Simulação de Acoplamento Molecular , Eletricidade EstáticaRESUMO
The inter beat interval (IBI) duration and systolic blood pressure (SBP) are cardiovascular variables related through several feedback mechanisms. We propose the analysis of diagonal lines in cross recurrence plots (CRPs) from IBI and SBP embedded within the same phase space to identify events where trajectories of both variables concur. The aim of the study was to describe the relationship between IBI and SBP of healthy subjects using CRP and diagonal analysis during baseline condition-supine position (SP)-and how the relationship changes during the physiological stress of active standing (AS). IBI and SBP time series were obtained from continuous blood pressure recordings during SP and AS (15 min each) in 19 young healthy subjects. IBI and SBP time series were embedded within a five-dimensional phase space using an embedding delay estimated from cross correlation between IBI and SBP. During SP, mean CRP showed high determinism (≥85%) and also brief but repeated events where both variables stay within a reduced space. Most quantitative recurrences analysis indexes of CRP increased significantly (p < 0.05) during AS. CRP analysis showed short diagonals indicating a very strong deterministic relationship between IBI and SBP with intermittent unlocking periods. The strength of IBI and SBP relationship increased during the physiological stress of AS. The CRP method allowed a rigorous quantitative description of the deterministic association between these two variables. Diagonal lines were intermittent and not always parallel, showing that there is not a defined and unique rhythm. This suggests the activation of different influences at different times and with different precedence between the heart rate and blood pressure in response to AS.
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Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Modelos Cardiovasculares , Feminino , Humanos , Masculino , Decúbito Dorsal/fisiologia , Adulto JovemRESUMO
BACKGROUND: Non-critical care Hospital-Acquired Acute Kidney Injury (Non-ICU HA-AKI) is a preventable common complication. AIM: To analyze its risk factors and outcomes in a general hospital ward. MATERIAL AND METHODS: A retrospective paired case-control 1:2 study was carried out from April to December 2014. Non-ICU HA-AKI was defined as those patients who experienced a 1.5-fold, or 0.3 mg/dl rise in serum creatinine after 24 hours of hospitalization. Controls were randomly selected, paired by date of hospital admission and specialty causing the admission. We analyzed short-term outcomes and risk factors. RESULTS: We included 101cases aged 65 ± 16 years (55% women). Mean length of stay at the time of diagnosis of AKI was 7.9 ± 8.9 days. Hospital length of stay was longer in patients with AKI (p < 0.01), The risk for intensive care unit (ICU) admission and mortality were also higher (odds ratio [OR], 2.43 [95% confidence intervals (CI), 1.24 to 4.75)p < 0.01 and OR, 26.2 [95% CI, 8.8 to 104, P < 0.01). In a multivariate analysis, sepsis (OR, 3.64 [95% CI, 1.30 to 10.16] p = 0.013), dehydration (OR, 14.4 [95% CI, 4.49 to 46.19), baseline glomerular filtration (OR, 0.96 [95% CI, 0.94-0.98), contrast medium exposure (OR, 4.33 [95% CI, 1.60 to 11.66), recent exposure to Nonsteroidal Anti-inflammatory Drugs (OR 3.23 [95% CI, 1.22 to 8.52 (p = 0.02)] and Charlson comorbidity index (OR, 1.23 [95% CI, 1.05 to 1.43 (p < 0.01) were independent risk factors for Non-ICU HA-AKI. CONCLUSIONS: Non-ICU HA-AKI is associated with a longer hospital stay and higher risk of ICU admission and mortality. Most risk factors are potentially preventable.
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Injúria Renal Aguda/mortalidade , Infecção Hospitalar/mortalidade , Idoso , Estudos de Casos e Controles , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model.
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Envelhecimento/metabolismo , Envelhecimento/patologia , Proteínas do Olho/metabolismo , Ventrículos Laterais/metabolismo , Ventrículos Laterais/patologia , Fatores de Crescimento Neural/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Serpinas/metabolismo , Envelhecimento/genética , Animais , Bromodesoxiuridina/metabolismo , Contagem de Células , Proteínas do Olho/genética , Camundongos , Modelos Animais , Modelos Neurológicos , Fatores de Crescimento Neural/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Serpinas/genética , Transdução de Sinais , Nicho de Células-TroncoRESUMO
OBJECTIVES: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system. METHODS: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons. RESULTS: In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE. CONCLUSIONS: The base-case results for all evidence groups are consistent with the different sensitivity analyses.
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Análise Custo-Benefício , Imunossupressores , Transplante de Rim , Humanos , Transplante de Rim/economia , Colômbia , Análise Custo-Benefício/métodos , Análise Custo-Benefício/estatística & dados numéricos , Imunossupressores/economia , Imunossupressores/uso terapêutico , Adulto , Ciclosporina/uso terapêutico , Ciclosporina/economia , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/economia , Tacrolimo/economia , Tacrolimo/uso terapêutico , Azatioprina/uso terapêutico , Azatioprina/economia , Cadeias de Markov , Árvores de Decisões , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/economia , Sirolimo/uso terapêutico , Sirolimo/economia , Transplantados/estatística & dados numéricos , Corticosteroides/uso terapêutico , Corticosteroides/economia , Análise de Custo-EfetividadeRESUMO
The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.
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BACKGROUND: The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. METHODS: We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients; survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. RESULTS: Among 165 confirmed cases, 28 died (17%); the risk factors for mortality identified in univariate analysis were age older than 60 years (p=.003) diabetes (p=.001), immunosuppression based on calcineurin inhibitors (CNI) (p=.025) and patients receiving steroids (p=.041). In multivariable analysis, hypoxemia (p=.000) and calcineurin inhibitors regimen (p=.002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p=.036). CONCLUSIONS: Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection.
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COVID-19 , Transplante de Rim , Humanos , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Colômbia/epidemiologia , Rejeição de Enxerto , SARS-CoV-2 , Terapia de Imunossupressão/métodosRESUMO
PROBLEM: The occurrence of preterm birth is associated with multiple factors including bleeding, infection and inflammation. Platelets are mediators of hemostasis and can modulate inflammation through interactions with leukocytes. TREM like Transcript 1 (TLT-1) is a type 1 single Ig domain receptor on activated platelets. In adults, it plays a protective role by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. TLT-1 is expressed in human placenta and found in cord blood. We thus hypothesized that TLT-1 deficiency is associated with prematurity and fetal inflammation. METHOD OF STUDY: To test this hypothesis, we examined cord blood levels of soluble TLT-1 (sTLT) in premature and term infants and compared the inflammatory response in C57BL/6 (WT) and TLT-1-/- (treml1-/- , KO) mice given intraperitoneal LPS mid-gestation RESULTS: The preterm infant cord blood level of sTLT was significantly lower than that found at term. On exposure to LPS, histology of KO (as compared to WT) placenta and decidua showed increased hemorrhage, and KO decidual RNA expression of IL-10 was significantly lower. KO fetal interface tissues (placenta, membranes, amniotic fluid) over time showed increased expression of inflammatory cytokines such as IL-6, IFN-γ, and TNF, but not MCP-1. However, fetal organs showed similar levels. CONCLUSION: There is a potential association between insufficient TLT-1 expression and increased fetal inflammatory responses in the setting of prematurity. The data support further study of TLT-1 in the mechanistic link between bleeding, inflammation and preterm birth, and perhaps as a biomarker in human pregnancy.
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Recém-Nascido Prematuro , Nascimento Prematuro , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Camundongos , Gravidez , Líquido Amniótico , Inflamação , Lipopolissacarídeos , Camundongos Endogâmicos C57BLRESUMO
Using cytotoxic reducing and stabilizing agents in the synthesis of gold nanoparticles (AuNPs) limits their use in biomedical applications. One strategy to overcome this problem is using "green" synthesis methodologies using polysaccharides. In the present study, we propose a green methodology for synthetizing AuNPs with mesquite gum (MG) as a reducing agent and steric stabilizer in Gold(III) chloride trihydrate aqueous solutions to obtain biocompatible nanoparticles that can be used for biomedical applications. Through this method, AuNPs can be produced without using elevated temperatures or pressures. For synthetizing gold nanoparticles coated with mesquite gum (AuNPs@MG), Gold(III) chloride trihydrate was used as a precursor, and mesquite gum was used as a stabilizing and reducing agent. The AuNPs obtained were characterized using UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, scanning transmission electron microscopy, and FT-IR spectroscopy. The stability in biological media (phosphate buffer solution), cytotoxicity (MTT assay, hematoxylin, and eosin staining), and hemocompatibility (Hemolysis assay) were measured at different concentrations and exposure times. The results showed the successful synthesis of AuNPs@MG with sizes ranging from 3 to 30 nm and a zeta potential of -31 mV. The AuNPs@MG showed good colloidal stability in PBS (pH 7.4) for up to 24 h. Finally, cytotoxicity assays showed no changes in cell metabolism or cell morphology. These results suggest that these gold nanoparticles have potential biomedical applications because of their low cytotoxicity and hemotoxicity and improved stability at a physiological pH.
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PURPOSE: Association between variants rs1047972 and rs8173 of the AURKA gene in healthy women and breast cancer (BC) in a Mexican population. METHODS: Genomic DNA samples from 409 healthy women and 572 patients with BC were analyzed for variants rs1047972 and rs8173 of the AURKA gene by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: TT genotype (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.22-5.11; p = 0.0015) and the T allele (OR, 1.16; 95% CI, 1.23-2.12; p = 0.0007) of the rs1047972 variant were associated as risk susceptibility for BC relative to the control group. Contrarily, the GG genotype (OR, 0.64; 95% CI, 0.43-0.94; p = 0.029) was associated as a protective factor of susceptibility of BC of the variant rs8173 of the AURKA gene. Differences were observed in the patients with BC who were carriers of the CT genotype of the rs1047972 variant with overweight, obesity, estrogen receptor-positive plus obesity, Ki-67 (≥ 20%) plus history familial positive of cancer; and for variant rs8173 the BC patients who were CG carriers and presented chemotherapy gastric toxicity, hormonal receptor positive plus chemotherapy gastric toxicity, and menopause status plus chemotherapy gastric toxicity (p < 0.05). Two common haplotypes were identified in the study groups: CG and TC genotypes, were associated as a protective and risk factor, respectively (p < 0.05). CONCLUSION: Variants rs1047972 and rs8173 of the AURKA gene and the TC haplotype were associated as risk susceptibility factors for BC in this population.
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OBJECTIVE: To evaluate a modified sequence method with delayed time series for baroreflex sensitivity (BRS) estimation during supine position and orthostatism in healthy human beings. METHODS: Nineteen clinically healthy volunteers (12 men, age 28.4 ± 6.2 years old) were included. Blood pressure recordings were obtained during supine position and orthostatism (15 min each) with a Finometer. Systolic blood pressure (SBP) and inter beat intervals (IBI) measured from all heartbeats were used to estimate BRS in both positive and negative sequences, with SBP delayed between 0 and 5 heartbeats. BRS estimations were compared by ANOVA, p < 0.05 was considered significant. Optimal recording time based on fixed BRS error estimation was calculated for each time series. RESULTS: BRS estimation was similar between positive and negative sequences in all conditions (BRS = 12.0 ± 2.0 ms/mmHg in supine position, delay 0). BRS with no delay was similar to BRS with delays between 1 and 5 heartbeats. Compared to supine position, BRS was smaller in orthostatism in all delays (BRS = 8.0 ± 2.0 ms/mmHg with delay 0). The shortest optimal recording time with delayed time series was similar in supine position and orthostatism (4.3 ± 1.7 vs. 3.74 ± 0.07 min, respectively). Estimation error was linearly correlated to IBI, regardless of the delay. CONCLUSION: BRS estimation with sequence method improves with delayed time series, during supine position and orthostatism. Reduced BRS estimation error and recording time from this method could benefit studies with large populations or patients with low tolerance to orthostatism.
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Algoritmos , Barorreflexo/fisiologia , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Postura/fisiologia , Adaptação Fisiológica , Adulto , Determinação da Pressão Arterial/instrumentação , Feminino , Humanos , Masculino , Valores de Referência , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Optic neuritis (ON) causes several sequela. Aggressive treatment with plasma exchange (TPE) is an option. This study describes improvement and safety outcomes with TPE. METHODS: We recruited adults with ON in neuromyelitis optica spectrum disorders (NMOSD) patients treated with TPE. The primary outcome was an improvement in the visual acuity scale (VOS). We described the data and used multivariate logistic regression to identify factors associated with response. RESULTS: Eighty-three patients received 558 TPE sessions. Mean age was 40.9 years (±13.7 years); 73.5% were women, 50.1% were first attack, and 10.7% were bilateral. Median VOS: 5 (range [R], 2-7). Median time between onset and TPE was 8 days (R, 1-32). By Keegan's criteria, 82.4% experience improvement and 78.3% improve in at least 1 point in VOS. Age and pre-TPE VOS were related to improvement. Low fibrinogen occurs in 26% sessions. CONCLUSION: TPE is effective and safety for ON in NMOSD patients. There is a need for a clinical trial using a therapeutic equivalent.
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Neuromielite Óptica , Neurite Óptica , Adulto , Feminino , Humanos , Masculino , Aquaporina 4 , Modelos Logísticos , Neuromielite Óptica/terapia , Neurite Óptica/terapia , Troca Plasmática , Plasmaferese , Pessoa de Meia-IdadeRESUMO
Problem: Fieldwork is a vital component of public health emergency response, yet little has been published on undertaking fieldwork safely. Safety is of particular importance with emerging pandemic viruses, which can pose additional risks to public health fieldwork staff. Context: During a pandemic, surge health staff may be drawn from diverse professional backgrounds; they may have limited experience in fieldwork or be unfamiliar with the risks posed by a novel virus. Novel pathogens pose dangers to fieldwork staff, particularly when there are global or local shortages of personal protective equipment. Action: During the coronavirus disease 2019 (COVID-19) pandemic, New South Wales (NSW) Health's Public Health Emergency Operations Centre (PHEOC) deployed staff for fieldwork in a range of settings. The PHEOC developed a protocol to systematize planning, risk assessment and management for COVID-19 fieldwork. The protocol was accompanied by training, discussion exercises and debriefs to support PHEOC fieldwork staff. Lessons learned: Effective fieldwork is an essential component of outbreak investigation and management, including stakeholder management. Here, we share and discuss key elements of the NSW Health protocol to support fieldwork during outbreak responses for emerging communicable diseases across various resource contexts. Limited understanding of novel viruses, particularly in the early phases of a pandemic, must be considered in decisions to deploy fieldwork staff and implement precautionary risk mitigation approaches. Planning is essential to protect staff and ensure ethical allocation of resources. Through appropriate selection of teams and training, surge staff can be supported to effectively conduct fieldwork.
Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , New South Wales/epidemiologia , Pandemias/prevenção & controle , Saúde Pública , SARS-CoV-2RESUMO
Background: Individuals with allergic asthma exhibit lung inflammation and remodeling accompanied by methacholine hyperresponsiveness manifesting in proximal airway narrowing and distal lung tissue collapsibility, and they can present with a range of mild-to-severe disease amenable or resistant to therapeutic intervention, respectively. There remains a need for alternatives or complements to existing treatments that could control the physiologic manifestations of allergic asthma. Objectives: Our aim was to examine the hypothesis that because ketone bodies elicit anti-inflammatory activity and are effective in mitigating the methacholine hyperresponsiveness associated with obese asthma, increasing systemic concentrations of ketone bodies would diminish pathologic outcomes in asthma-relevant cell types and in mouse models of allergic asthma. Methods: We explored the effects of ketone bodies on allergic asthma-relevant cell types (macrophages, airway epithelial cells, CD4 T cells, and bronchial smooth muscle cells) in vitro as well as in vivo by using preclinical models representative of several endotypes of allergic asthma to determine whether promotion of ketosis through feeding a ketogenic diet or providing a ketone precursor or a ketone ester dietary supplement could affect immune and inflammatory parameters as well as methacholine hyperresponsiveness. Results: In a dose-dependent manner, the ketone bodies acetoacetate and ß-hydroxybutyrate (BHB) decreased proinflammatory cytokine secretion from mouse macrophages and airway epithelial cells, decreased house dust mite (HDM) extract-induced IL-8 secretion from human airway epithelial cells, and decreased cytokine production from polyclonally and HDM-activated T cells. Feeding a ketogenic diet, providing a ketone body precursor, or supplementing the diet with a ketone ester increased serum BHB concentrations and decreased methacholine hyperresponsiveness in several acute HDM sensitization and challenge models of allergic asthma. A ketogenic diet or ketone ester supplementation decreased methacholine hyperresponsiveness in an HDM rechallenge model of chronic allergic asthma. Ketone ester supplementation synergized with corticosteroid treatment to decrease methacholine hyperresponsiveness in an HDM-driven model of mixed-granulocytic severe asthma. HDM-induced morphologic changes in bronchial smooth muscle cells were inhibited in a dose-dependent manner by BHB, as was HDM protease activity. Conclusions: Increasing systemic BHB concentrations through dietary interventions could provide symptom relief for several endotypes of allergic asthmatic individuals through effects on multiple asthma-relevant cells.
RESUMO
In the present study, the modification of branched polyethyleneimine (b-PEI) was carried out using mesquite gum (MG) to improve its hemocompatibility to be used in biomedical applications. In the copolymer synthesis process (carboxymethylated mesquite gum grafted polyethyleneimine copolymer (CBX-MG-PEI), an MG carboxymethylation reaction was initially carried out (carboxymethylated mesquite gum (CBX-MG). Subsequently, the functionalization between CBX-MG and b-PEI was carried out using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as crosslinking agents. The synthesis products were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). Thermogravimetric analysis showed that CBX-MG and CBX-MG-PEI presented a lower decomposition temperature than MG. The CBX-MG-PEI has a high buffer capacity in the pH range of 4 to 7, similar to the b-PEI. In addition, the CBX-MG-PEI showed an improvement in hemocompatibility in comparison with the b-PEI. The results showed a non-hemolytic property at doses lower than 0.1 µg/mL (CBX-MG-PEI). These results allow us to propose that this copolymer be used in transfection, polymeric nanoparticles, and biomaterials due to its physicochemical and hemocompatibility properties.