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1.
Hypertension ; 77(2): 254-264, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33390042

RESUMO

This review portrays how ambulatory blood pressure (BP) monitoring was established and recommended as the method of choice for the assessment of BP and for the rational use of antihypertensive drugs. To establish much-needed diagnostic ambulatory BP thresholds, initial statistical approaches evolved into longitudinal studies of patients and populations, which demonstrated that cardiovascular complications are more closely associated with 24-hour and nighttime BP than with office BP. Studies cross-classifying individuals based on ambulatory and office BP thresholds identified white-coat hypertension, an elevated office BP in the presence of ambulatory normotension as a low-risk condition, whereas its counterpart, masked hypertension, carries a hazard almost as high as ambulatory combined with office hypertension. What clinically matters most is the level of the 24-hour and the nighttime BP, while other BP indexes derived from 24-hour ambulatory BP recordings, on top of the 24-hour and nighttime BP level, add little to risk stratification or hypertension management. Ambulatory BP monitoring is cost-effective. Ambulatory and home BP monitoring are complimentary approaches. Their interchangeability provides great versatility in the clinical implementation of out-of-office BP measurement. We are still waiting for evidence from randomized clinical trials to prove that out-of-office BP monitoring is superior to office BP in adjusting antihypertensive drug treatment and in the prevention of cardiovascular complications. A starting research line, the development of a standardized validation protocol for wearable BP monitoring devices, might facilitate the clinical applicability of ambulatory BP monitoring.

2.
Insect Sci ; 28(1): 77-92, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32039551

RESUMO

Swarming behavior facilitates pair formation, and therefore mating, in many eusocial termites. However, the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightless insect forms are still unclear. Here, we found that the dispersal flight of the eusocial termite Reticulitermes chinensis Snyder led to a gradual decrease in adenosine triphosphate supply from oxidative phosphorylation, as well as a reduction in the activities of critical mitochondrial respiratory enzymes from preflight to dealation. Correspondingly, using three-dimensional reconstruction and transmission electron microscopy (TEM), the flight muscles were found to be gradually deteriorated during this process. In particular, two tergo-pleural muscles (IItpm5 and III-tpm5) necessary to adjust the rotation of wings for wing shedding behavior were present only in flying alates. These findings suggest that flight muscle systems vary in function and morphology to facilitate the swarming flight procedure, which sheds light on the important role of swarming in successful extension and fecundity of eusocial termites.

3.
Asian J Surg ; 44(1): 164-168, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32513636

RESUMO

BACKGROUND: A few factors influence the feasibility of transrectal natural orifice specimen extraction (NOSE) surgery for colorectal cancers. However, little is known about the underlying factors of NOSE surgery. METHODS: Consecutive patients with rectal and sigmoid colon cancers treated laparoscopically between January 2014 and April 2017 were enrolled in this study. The transrectal NOSE performed laparoscopically was the first choice of all patients. When NOSE failed, the specimen was removed through a midline abdominal wall incision. Univariate and multivariate logistic regression analyses were performed to identify challenging factors influencing the intraoperative specimen extraction. RESULTS: Overall, 412 consecutive patients were included. NOSE performed laparoscopically was successful in 278 patients (75.5%) and unsuccessful in 90 patients (24.5%). The multivariate analyses indicated that body mass index (BMI; odds ratio [OR] = 3.510, 95% confidence interval [CI]: 1.333-9.243, p = 0.011), mesenteric thickness (OR = 1.069, 95% CI: 1.032-1.107, p < 0.001), maximum tumor diameter (OR = 2.827, 95% CI: 1.094-7.302, p = 0.032), and tumor T stage (OR = 2.831, 95% CI: 1.258-6.369, p = 0.012) were the factors influencing the feasibility of NOSE surgery. CONCLUSION: A successful transrectal NOSE surgery was associated with a lower BMI, thinner mesentery, lesser tumor diameter, and earlier tumor T stage.

4.
Hypertension ; 77(1): 39-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33296250

RESUMO

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33274751

RESUMO

Objectives Lead exposure causes neurocognitive dysfunction in children, but its association with neurocognition in adults at current occupational exposure levels is uncertain mainly due to the lack of longitudinal studies. In the Study for Promotion of Health in Recycling Lead (NCT02243904), we assessed the two-year responses of neurocognitive function among workers without previous known occupational exposure newly hired at lead recycling plants. Methods Workers completed the digit-symbol test (DST) and Stroop test (ST) at baseline and annual follow-up visits. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Statistical methods included multivariable-adjusted mixed models with participants modelled as random effect. Results DST was administered to 260 participants (11.9% women; 46.9%/45.0% whites/Hispanics; mean age 29.4 years) and ST to 168 participants. Geometric means were 3.97 and 4.13 µg/dL for baseline BL, and 3.30 and 3.44 for the last-follow-up-to-baseline BL ratio in DST and ST cohorts, respectively. In partially adjusted models, a doubling of the BL ratio was associated with a 0.66% [95% confidence interval (CI) 0.03-1.30; P=0.040] increase in latency time (DST) and a 0.35% (95% CI ­1.63-1.63; P=0.59) decrease in the inference effect (ST). In fully adjusted models, none of the associations of the changes in the DST and ST test results with the blood lead changes reached statistical significance (P≥0.12). Conclusions An over 3-fold increase in blood lead over two years of occupational exposure was not associated with a relevant decline in cognitive performance.

6.
Acta Neuropathol Commun ; 8(1): 191, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172502

RESUMO

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.

7.
Insects ; 11(11)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187256

RESUMO

Chitin synthase 1 (CHS1) is an essential gene regulating chitin during different developmental stages of arthropods. In the current study, we explored for the first time the role of CHS1 gene regulation in the citrus red mite, Panonychus citri (McGregor) (Acari: Tetranychidae), by silencing its expression using (RNA interference) RNAi-based strategies. The results reveal that P. citri tested in different developmental stages, including larvae, protonymphs, deutonymphs, and adults fed on sweet orange leaves dipped in various concentrations (200, 400, 600, and 800 ng/µL) of dsRNA-PcCHS1, resulted in a continuous reduction in their gene expression, and the extent of transcript knockdown was positively correlated with the concentration of dsRNA. Concentration-mortality response assays revealed a mortality of more than 50% among all the studied developmental stages, except for adulthood. Furthermore, the target gene dsRNA-PcCHS1 treatment of larvae, protonymphs, deutonymphs, and females at a treatment rate of 800 ng/mL of dsRNA significantly decreased the egg-laying rates by 48.50%, 43.79%, 54%, and 39%, respectively, and the hatching rates were also considerably reduced by 64.70%, 70%, 64%, and 52.90%, respectively. Moreover, using the leaf dip method, we found that the RNA interference effectively reduced the PcCHS1 transcript levels by 42.50% and 42.06% in the eggs and adults, respectively. The results of this study demonstrate that the RNAi of PcCHS1 can dramatically reduce the survival and fecundity of P. citri, but the dsRNA concentrations and developmental stages can significantly influence the RNAi effects. These findings indicate the potential utility of the PcCHS1 gene in causing developmental irregularities, which could aid in the development of effective and novel RNAi-based strategies for controlling P. citri.

8.
Hypertension ; 76(4): 1299-1307, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32903104

RESUMO

Lead exposure causing hypertension is the mechanism commonly assumed to set off premature death and cardiovascular complications. However, at current exposure levels in the developed world, the link between hypertension and lead remains unproven. In the Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of office blood pressure (average of 5 consecutive readings) and 24-hour ambulatory blood pressure to first occupational lead exposure in workers newly employed at lead recycling plants. Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 µg/dL). Hypertension was defined according to the 2017 American College of Cardiology/American Heart Association guideline. Statistical methods included multivariable-adjusted mixed models with participants modeled as a random effect and interval-censored Cox regression. Office blood pressure was measured in 267 participants (11.6% women, mean age at enrollment, 28.6 years) and ambulatory blood pressure in 137 at 2 follow-up visits. Geometric means were 4.09 µg/dL for baseline BL and 3.30 for the last-follow-up-to-baseline BL ratio. Fully adjusted changes in systolic/diastolic blood pressure associated with a doubling of the BL ratio were 0.36/0.28 mm Hg (95% CI, -0.55 to 1.27/-0.48 to 1.04 mm Hg) for office blood pressure and -0.18/0.11 mm Hg (-2.09 to 1.74/-1.05 to 1.27 mm Hg) for 24-hour ambulatory blood pressure. The adjusted hazard ratios of moving up across hypertension categories for a doubling in BL were 1.13 (0.93-1.38) and 0.84 (0.57-1.22) for office blood pressure and ambulatory blood pressure, respectively. In conclusion, the 2-year blood pressure responses and incident hypertension were not associated with the BL increase on first occupational exposure.

9.
Front Microbiol ; 11: 1620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754145

RESUMO

As one of the most detrimental citrus pests worldwide, the citrus red mite, Panonychus citri (McGregor), shows extraordinary fecundity, polyphagia, and acaricide resistance, which may be influenced by microbes as other arthropod pests. However, the community structure and physiological function of microbes in P. citri are still largely unknown. Here, the high-throughput sequencing of 16S rDNA amplicons was employed to identify and compare the profile of bacterial communities across the larva, protonymph, deutonymph, and adult stages of P. citri. We observed a dominance of phylums Proteobacteria and Firmicutes, and classes α-, γ-, ß-Proteobacteria and Bacilli in the bacterial communities across the host lifespan. Based on the dynamic analysis of the bacterial community structure, a significant shift pattern between the immature (larva, protonymph, and deutonymph) and adult stages was observed. Accordingly, among the major families (and corresponding genera), although the relative abundances of Pseudomonadaceae (Pseudomonas), Moraxellaceae (Acinetobacter), and Sphingobacteriaceae (Sphingobacterium) were consistent in larva to deutonymph stages, they were significantly increased to 30.18 ± 8.76% (30.16 ± 8.75%), 20.78 ± 10.86% (18.80 ± 10.84%), and 11.71 ± 5.49% (11.68 ± 5.48%), respectively, in adult stage, which implied the important function of these bacteria on the adults' physiology. Actually, the functional prediction of bacterial communities and Spearman correlation analysis further confirm that these bacteria had positively correlations with the pathway of "lipid metabolism" (including eight sublevel pathways) and "metabolism of cofactors and vitamins" (including five sublevel pathways), which all only increased in adult stages. In addition, the bacterial communities were eliminated by using broad-spectrum antibiotics, streptomycin, which significantly suppressed the survival and oviposition of P. citri. Overall, we not only confirmed the physiological effects of bacteria community on the vitality and fecundity of adult hosts, but also revealed the shift pattern of bacterial community structures across the life stages and demonstrated the co-enhancements of specific bacterial groups and bacterial functions in nutritional metabolism in P. citri. This study sheds light on basic information about the mutualism between spider mites and bacteria, which may be useful in shaping the next generation of control strategies for spider mite pests, especially P. citri.

10.
J Am Heart Assoc ; 9(15): e014305, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32750311

RESUMO

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case-control study, we enrolled 55 children aged 11 years weighing <1000 g at birth and 71 matched controls (October 2014-November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure-based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer-assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, P<0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, P=0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, P<0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (-2.94 µm; 95% CI, -5.18 to -0.70 µm [P=0.011]) and forward (-2.57 µm; CI, -4.81 to -0.32 µm [P=0.026]) and backward (-3.20 µm; CI, -5.47 to -0.94 µm [P=0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, P=0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32811409

RESUMO

BACKGROUND: Resistance of Helicobacter pylori(H. pylori) to antibiotics is increasing worldwide. In order to understand the current situation of antibiotic resistance in Nanjing and provide a reasonable basis for clinical selection of antibiotics to cure H. Pylori. OBJECTIVE: To investigate the current status of H. Pylori antibiotics resistance in Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area. METHODS: During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by breath test or rapid urease test were collected for isolation and identify H. pylori. The agar dilution method was used for antibiotic resistance test. RESULTS: The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primary Vs post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% Vs 6.08%, 38.62% Vs 77.81%, 27.41% Vs 56.23%, 0.58% Vs 2.13%, 0.33% Vs 1.22%, 78.57% Vs 88.75%, respectively. CONCLUSIONS: Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in Nanjing area. For post-treatment eradication patients, clinicians should took into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects..

12.
Respir Res ; 21(1): 201, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727465

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. METHODS: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. RESULTS: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (ß = 0.397, p < 0.001) and PaO2/FiO2 (ß = - 0.434, p = 0.003). CONCLUSIONS: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Citocinas/sangue , Lesão Pulmonar/etiologia , Pneumonia Viral/complicações , Adulto , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Hypertension ; 76(2): 420-431, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32639887

RESUMO

To identify potential application of GLP1-RAs (glucagon-like peptide-1 receptor agonists) and SGLT2-Is (sodium-dependent glucose cotrasnsporter-2 inhibitors) in cardiovascular medicine, we performed PubMed search until March 31, 2020 and selected placebo-controlled randomized trials (RCTs) in patients with type 2 diabetes mellitus. Twenty-four hour ambulatory and office blood pressure (BP), major adverse cardiovascular events (MACE), progression of chronic kidney disease (CKD), and changes in glycated hemoglobin and body weight were aggregated across RCTs using random-effect models. In 2238 patients (7 RCTs), SGLT2-Is lowered 24-hour systolic/diastolic BP by 4.4/1.9 mm Hg (95% CI, 3.4-5.5/1.2-2.6 mm Hg), whereas 2 GLP1-RAs RCTs produced contradictory BP results. Over 1.3 to 5.4 years of follow-up of 56 004 patients (7 RCTs), aggregate hazard ratios associated with GLP1-RA treatment were 0.88 (0.84-0.93) for MACE, 0.84 (0.74-0.89) for CKD, and ranged from 0.84 to 0.90 for individual MACE end points (P≤0.01). Across 5 SGLT2-Is RCTs, including 43 467 patients with 1.5 to 4.2 years follow-up, hazard ratios were 0.87 (0.82-0.93) for MACE, 0.68 (0.62-0.75) for HF, 0.82 (0.72-0.93) for cardiovascular death, 0.87 (0.79-0.96) for myocardial infarction, and 0.61 (0.56-0.67) for worsening CKD. The risk of HF and CKD, but not MACE, decreased with more BP lowering. Stricter glycemic control was associated with higher HF risk, but unrelated to MACE or CKD. The aggregate effect sizes on systolic BP, body weight, and glycated hemoglobin were -1.61 mm Hg, -2.40 kg, and -0.69% for GLP1-RAs, and -2.53 mm Hg, -1.15 kg and -0.24%, for SGLT2-Is (P<0.001). In conclusion, GLP1-RAs and SGLT2-Is reduced cardiovascular risk with differential benefit profiles.

14.
Hypertension ; 76(2): 350-358, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32639894

RESUMO

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalized R2 increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.

15.
FEBS Open Bio ; 10(8): 1568-1576, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533762

RESUMO

Preeclampsia (PE) is a hypertensive disorder of pregnancy. Early diagnosis of PE is currently contingent on regular prenatal physical examinations and may be facilitated by identification of novel diagnostic markers. Transthyretin (TTR), also known as prealbumin, is primarily responsible for maintaining the normal levels of thyroxine and retinol binding protein. The expression of TTR is lower in patients with severe PE as compared with healthy controls. Here, we examined the suitability of TTR as a diagnostic marker in pregnant hypertensive rats. N'-nitro-l-arginine-methylesterhydrochloride (l-NAME) was used to generate a rat model of hypertension during pregnancy. Rat placental trophoblast cells were divided into control and TTR groups for in vitro experiments. Systolic blood pressure, diastolic blood pressure, mean blood pressure and urinary protein of hypertensive pregnant rats were higher than those of healthy pregnant rats, but these effects could be reversed by TTR treatment. There were no significant changes in blood pressure and urinary protein in healthy pregnant rats before or after TTR treatment. TTR levels in the serum and placental tissues of pregnant hypertensive rats were significantly reduced compared with those of healthy pregnant rats. Changes in placental and fetal weights in the hypertensive model could also be rescued by TTR treatment. TTR treatment significantly increased the level of matrix metalloproteinase-2/9 in hypertensive rats. Finally, in vivo and in vitro experiments demonstrated that TTR effectively increased the migration and invasion of rat placental trophoblast cells, as well as matrix metalloproteinase-2/9 levels in these cells. In conclusion, our data from a rat model suggest that TTR may have potential as a novel marker for PE diagnosis.

16.
Hypertension ; 75(4): 1133-1139, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32114854

RESUMO

The association of blood pressure (BP) with manganese-an essential trace element required for human health-remains poorly studied. In 734 randomly recruited Swiss participants (mean age, 47.5 years; 51.4% women), we related ambulatory BP to 2 biomarkers, plasma manganese (pMn) and the urinary manganese (uMn) excretion. To allow for diurnal variation, we assessed BP and uMn over 24 hours and during wakefulness and sleep, using split urine samples. Twenty-four-hour, daytime, and nighttime systolic/diastolic BPs averaged 119.8/78.1, 123.8/81.2, and 107.0/68.3 mm Hg; the corresponding median uMn were 199.5, 83.0, and 51.5 µmol and median pMn, 0.52 µg/L. In analyses dichotomized by the median of the biomarkers, greater pMn was associated with higher 24-hour systolic/diastolic BP (+4.1/+2.3 mm Hg; P≤0.0003), greater daytime uMn with lower daytime BP (-3.5/-1.9 mm Hg; P≤0.0067), and greater nighttime uMn with higher nighttime BP (+2.9/+1.2 mm Hg; P≤0.046). In multivariable-adjusted analyses, significance (P≤0.030) was retained for the positive association of 24-hour and daytime diastolic BP with pMn and for systolic BP in relation to uMn at night. The association sizes for a 2-fold increment in the biomarkers amounting to 0.77 mm Hg (95% CI, 0.08-1.47 mm Hg), 0.97 (CI, 0.20-1.76) and 1.33 (CI, 0.20-2.50 mm Hg), respectively. In conclusion, there were positive associations between diastolic BP and pMn over 24 hours and during daytime and between systolic BP and uMn at night.

17.
Hypertension ; 75(3): 603-614, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008462

RESUMO

Our objective was to gain insight in the calculation and interpretation of population health metrics that inform disease prevention. Using as model environmental exposure to lead (ELE), a global pollutant, we assessed population health metrics derived from the Third National Health and Nutrition Examination Survey (1988 to 1994), the GBD (Global Burden of Disease Study 2010), and the Organization for Economic Co-operation and Development. In the National Health and Nutrition Examination Survey, the hazard ratio relating mortality over 19.3 years of follow-up to a blood lead increase at baseline from 1.0 to 6.7 µg/dL (10th-90th percentile interval) was 1.37 (95% CI, 1.17-1.60). The population-attributable fraction of blood lead was 18.0% (10.9%-26.1%). The number of preventable ELE-related deaths in the United States would be 412 000 per year (250 000-598 000). In GBD 2010, deaths and disability-adjusted life-years globally lost due to ELE were 0.67 million (0.58-0.78 million) and 0.56% (0.47%-0.66%), respectively. According to the 2017 Organization for Economic Co-operation and Development statistics, ELE-related welfare costs were $1 676 224 million worldwide. Extrapolations from the foregoing metrics assumed causality and reversibility of the association between mortality and blood lead, which at present-day ELE levels in developed nations is not established. Other issues limiting the interpretation of ELE-related population health metrics are the inflation of relative risk based on outdated blood lead levels, not differentiating relative from absolute risk, clustering of risk factors and exposures within individuals, residual confounding, and disregarding noncardiovascular disease and immigration in national ELE-associated welfare estimates. In conclusion, this review highlights the importance of critical thinking in translating population health metrics into cost-effective preventive strategies.

18.
Crit Care ; 24(1): 10, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918764

RESUMO

RATIONALE: The urinary proteome reflects molecular drivers of disease. OBJECTIVES: To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality. METHODS: In 1243 patients, the urinary proteome was measured on ICU admission, using capillary electrophoresis coupled with mass spectrometry along with clinical variables, circulating biomarkers (BNP, hsTnT, active ADM, and NGAL), and urinary albumin. Methods included support vector modeling to construct the classifier, Cox regression, the integrated discrimination (IDI), and net reclassification (NRI) improvement, and area under the curve (AUC) to assess predictive accuracy, and Proteasix and protein-proteome interactome analyses. MEASUREMENTS AND MAIN RESULTS: In the discovery (deaths/survivors, 70/299) and test (175/699) datasets, the new classifier ACM128, mainly consisting of collagen fragments, yielding AUCs of 0.755 (95% CI, 0.708-0.798) and 0.688 (0.656-0.719), respectively. While accounting for study site and clinical risk factors, hazard ratios in 1243 patients were 2.41 (2.00-2.91) for ACM128 (+ 1 SD), 1.24 (1.16-1.32) for the Charlson Comorbidity Index (+ 1 point), and ≥ 1.19 (P ≤ 0.022) for other biomarkers (+ 1 SD). ACM128 improved (P ≤ 0.0001) IDI (≥ + 0.50), NRI (≥ + 53.7), and AUC (≥ + 0.037) over and beyond clinical risk indicators and other biomarkers. Interactome mapping, using parental proteins derived from sequenced peptides included in ACM128 and in silico predicted proteases, including/excluding urinary collagen fragments (63/35 peptides), revealed as top molecular pathways protein digestion and absorption, lysosomal activity, and apoptosis. CONCLUSIONS: The urinary proteomic classifier ACM128 predicts the 1-year post-ICU mortality over and beyond clinical risk factors and other biomarkers and revealed molecular pathways potentially contributing to a fatal outcome.


Assuntos
Biomarcadores/análise , Biomarcadores/urina , Mortalidade , Alta do Paciente/estatística & dados numéricos , Idoso , Análise de Variância , Área Sob a Curva , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC
19.
Blood Press ; 29(1): 39-46, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31352838

RESUMO

Purpose: Previous studies that addressed whether left ventricular hypertrophy is more closely associated with central than peripheral blood pressure (BP) have been inconsistent. Radial artery wave generated by applanation tonometry and calibrated with brachial BP in 162 adult Nigerians were analysed by using generalized transfer function to derive central BP.Materials and methods: We compared the associations of ECG voltages and left ventricular hypertrophy (ECG-LVH) as continuous and binary variables respectively with central and brachial BP indices.Results: In a multivariable adjusted analysis, 1 standard deviation (SD) increase in brachial systolic, diastolic, pulse and mean arterial pressures increased the Sokolow-Lyon QRS voltage by 0.34 (CI, 0.21-0.48; p < 0.0001), 0.21 (CI, 0.07-0.36; p < 0.05); 0.22 (CI, 0.9-0.34; p < 0.001) and 0.29 (CI, 0.14-0.43) similar to (p > 0.05) corresponding Sokolow-Lyon QRS increase of 0.26 (0.12-0.40, p < 0.001); 0.14 (0.00-0.28, p < 0.05); 0.24 (0.11-0.39; p < 0.001) and 0.19 (0.05-0.34, p < 0.05) respectively observed for 1 SD increment in central pressures. The odds ratio (OR) relating ECG-LVH to 1 SD increase in brachial systolic, pulse, and mean arterial pressures were 2.62 (CI, 1.49-4.65, p < 0.001); 1.88 (CI, 1.19-2.95, p < 0.01) and 2.16 (CI, 1.22-3.82, p < 0.01) was similar to (p > 0.05) corresponding OR of 2.41 (1.33-4.36, p < 0.01); 2.04 (1.23-3.37, p < 0.01); 2.00 (1.11-3.63, p < 0.001) observed for I SD increment in central pressures.Conclusion: Central and peripheral BP are similarly associated with Sokolow-Lyon ECG voltage and hypertrophy.


Assuntos
Pressão Sanguínea/fisiologia , Eletrocardiografia/métodos , Hipertrofia Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Índice Tornozelo-Braço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria
20.
Brain Pathol ; 30(3): 541-553, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31733156

RESUMO

In the 2016, WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) mutation is a main classifier for lower grade astrocytomas and IDH-mutated astrocytomas is now regarded as a single group with longer survival. However, the molecular and clinical heterogeneity among IDH mutant lower grade (WHO Grades II/III) astrocytomas have only rarely been investigated. In this study, we recruited 160 IDH mutant lower grade (WHO Grades II/III) astrocytomas, and examined PDGFRA amplification, CDKN2A deletion and CDK4 amplification by FISH analysis, TERT promoter mutation by Sanger sequencing and ATRX loss and p53 expression by immunohistochemistry. We identified PDGFRA amplification, CDKN2A homozygous deletion and CDK4 amplification in 18.8%, 15.0% and 18.1% of our cohort respectively, and these alterations occurred in a mutually exclusive fashion. PDGFRA amplification was associated with shorter PFS (P = 0.0003) and OS (P < 0.0001). In tumors without PDGFRA amplification, CDKN2A homozygous deletion or CDK4 amplification was associated with a shorter OS (P = 0.035). Tumors were divided into three risk groups based on the presence of molecular alterations: high risk (PDGFRA amplification), intermediate risk (CDKN2A deletion or CDK4 amplification) and low risk (neither CDKN2A deletion and CDK4 amplification nor PDGFRA amplification). These three risk groups were significantly different in overall survival with mean survivals of 40.5, 62.9 and 71.5 months. The high-risk group also demonstrated a shorter PFS compared to intermediate- (P = 0.036) and low-risk (P < 0.0001) groups. One limitation of this study is the relatively short follow-up period, a common confounding factor for studies on low-grade tumors. Our data illustrate that IDH mutant lower grade astrocytomas is not a homogeneous group and should be molecularly stratified for risk.

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