Publications

Objective: Recent guidelines suggest relying on the ambulatory blood pressure (BP) monitoring (ABPM) derived awake mean to corroborate the diagnosis of hypertension suspected by elevated clinic BP measurement. However, several prospective ABPM studies have found elevated sleep-time BP is a better predictor of cardiovascular disease (CVD) risk than awake BP mean, also in diabetes. We evaluated the combined contribution to CVD risk of clinic, awake, and asleep BP among patients with diabetes participants in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of Northwest Spain. Design and method: This study involved 2632 patients with type 2 diabetes, 1589 men/1043 women, 65.1 ± 11.6 years of age, with baseline BP ranging from normotension to sustained hypertension according to ABPM criteria, prospectively evaluated throughout a 4.1-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed at night and awakening in the morning. Results: The hazard ratios (HR) of total CVD events for each 1-SD elevation in clinic, awake, and asleep systolic BP (SBP) analyzed separately (adjusted for the significant influential characteristics of age, sex, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event) were 1.25 [95%CI: 1.17–1.35]; 1.39 [1.30–1.50], and 1.51 [1.41–1.62], respectively (always P < 0.001). Exploration of the combined contribution of all three BP measurements revealed elevation in asleep SBP (HR = 1.55 [1.38–1.75], P < 0.001) but not in clinic BP (1.08 [0.99–1.18], P = 0.082) or awake BP (0.93 [0.82–1.06], P = 0.270) was the only independent BP parameter significantly associated with increased CVD risk. Conclusions: In patients with diabetes, sleep-time SBP mean, but not daytime clinic BP measurement or ABPM-derived awake BP mean, is the only significant and independent prognostic marker of CVD morbidity and mortality. These findings indicate ABPM, but not conventional clinic BP so far mistakenly used to diagnose hypertension and establish therapeutic targets, is a clinical necessity to accurately detect abnormal sleep-time BP and assess CVD risk in diabetes.

Abstract — — To recognize the highly statistically significant circadian variability of blood pressure in pregnancy is to admit that the diagnosis of gestational hypertension or preeclampsia should be based not just on whether a casual blood pressure value is too high or too low, but rather on more pertinent questions: How long is blood pressure elevated above a given time-varying threshold? What is the excess blood pressure? When does most of the excess occur? Answers to these questions may be obtained by establishing (1) an adequate reference threshold for blood pressure and (2) a proper measurement of blood pressure elevation. Accordingly, we derived time-specified reference standards for blood pressure as a function of gestational age. We analyzed 1408 blood pressure series systematically sampled by ambulatory monitoring for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 235 women with uncomplicated pregnancies. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual to avoid differences among women in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each trimester of pregnancy, in keeping with the trends in blood pressure along gestation previously documented. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data, and therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results not only reflect expected changes in the tolerance limits as a function of gestational age, but also upper limits markedly below the thresholds currently used for diagnosing hypertension in pregnancy. The use of these time-qualified tolerance limits for the computation of a hyperbaric index as a measure of BP excess has already been show to provide high sensitivity and specificity in the early identification of gestational hypertension and preeclampsia.

Boosting or suppressing our immune system represents an attractive adjunct in the treatment of infections including SARS-CoV-2, cancer, AIDS, malnutrition, age related problems and some inflammatory disorders. Thus, there has been a growing interest in exploring and developing novel drugs, natural or synthetic, that can manipulate our defence mechanism. Many of such studies, reported till date, have been designed to explore effect of the therapeutic on function of macrophages, being a key component in innate immune system. Indeed, RAW264.7, J774A.1, THP-1 and U937 cell lines act as ideal model systems for preliminary investigation and selection of dose for in vivo studies. Several bioassays have been standardized so far where many techniques require high throughput instruments, cost effective reagents and technical assistance that may hinder many scholars to perform a method demanding compilation of available protocols. In this review, we have taken an attempt for the first time to congregate commonly used in vitro immune-modulating techniques explaining their principles. The study detected that among about 40 different assays and more than 150 sets of primers, the methods of cell proliferation by MTT, phagocytosis by neutral red, NO detection by Griess reaction and estimation of expression of TLRs, COX-2, iNOS, TNF-α, IL-6 and IL-1β by PCR have been the most widely used to screen the therapeutics under investigation.

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 +/- 16.5 (mean +/- SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.

Objective This study evaluated the diagnostic value of different combinations of five commonly used tumour markers and screened the best combination of tumour markers. Methods Regression analysis was used to evaluate 185 patients with suspected breast cancer admitted to Mianyang Central Hospital from January 2020 to December 2021. The differences of five tumour markers between a breast cancer group and a benign lesion group were analysed. The sensitivity and specificity of five tumour markers were compared. Results Of 185 patients with suspected breast cancer, 108 patients had breast cancer and 77 patients had benign breast tumours. The detection results of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153) in patients with breast cancer were significantly higher than those in patients with benign breast tumours. In the analysis of the single-detection results of tumour markers, CEA had the highest sensitivity (23.94%), CA153 had the highest specificity (96.43%), AFP had the highest accuracy (47.66%) and CA153 had the highest area under the curve (AUC) value (0.727). With the increase of parallel indicators, the sensitivity, accuracy and AUC value increased in turn, and the increase was obvious in the front. The increase began to slow down after the three parallel indicators. Among the different combinations of three parallel detections of breast cancer tumour markers, the highest sensitivity was AFP + CEA + CA153 (83.46%), the highest accuracy was AFP + CEA + CA153 and AFP + CA153 + CA125 (80.25%), and the highest AUC was CEA + CA125 + CA199 (0.922). Conclusion AFP, CA153 and CA199 are recommended for clinical diagnosis of breast cancer. In routine physical examination and early breast cancer screening, the optimal combination of AFP + CEA + CA153 three parallel tests is recommended.

The study of organisms with restricted dispersal abilities and presence in the fossil record is particularly adequate to understand the impact of climate changes on the distribution and genetic structure of species. Trochoidea geyeri (Soos 1926) is a land snail restricted to a patchy, insular distribution in Germany and France. Fossil evidence suggests that current populations of T. geyeri are relicts of a much more widespread distribution during more favourable climatic periods in the Pleistocene. Results: Phylogeographic analysis of the mitochondrial 16S rDNA and nuclear ITS-1 sequence variation was used to infer the history of the remnant populations of T. geyeri. Nested clade analysis for both loci suggested that the origin of the species is in the Provence from where it expanded its range first to Southwest France and subsequently from there to Germany. Estimated divergence times predating the last glacial maximum between 25-17 ka implied that the colonization of the northern part of the current species range occurred during the Pleistocene. Conclusion: We conclude that T. geyeri could quite successfully persist in cryptic refugia during major climatic changes in the past, despite of a restricted capacity of individuals to actively avoid unfavourable conditions.