Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

IntroductionCurrent evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice.AimThe aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics.MethodsA total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study.ResultsModel-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2(-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed.ConclusionIn conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.     

siMS Score: Simple Method for Quantifying Metabolic Syndrome

Objective

To evaluate siMS score and siMS risk score, novel continuous metabolic syndrome scores as methods for quantification of metabolic status and risk.

Materials and Methods

Developed siMS score was calculated using formula: siMS score = 2*Waist/Height + Gly/5.6 + Tg/1.7 + TA_systolic/130—HDL/1.02 or 1.28 (for male or female subjects, respectively). siMS risk score was calculated using formula: siMS risk score = siMS score * age/45 or 50 (for male or female subjects, respectively) * family history of cardio/cerebro-vascular events (event = 1.2, no event = 1). A sample of 528 obese and non-obese participants was used to validate siMS score and siMS risk score. Scores calculated as sum of z-scores (each component of metabolic syndrome regressed with age and gender) and sum of scores derived from principal component analysis (PCA) were used for evaluation of siMS score. Variants were made by replacing glucose with HOMA in calculations. Framingham score was used for evaluation of siMS risk score.

Results

Correlation between siMS score with sum of z-scores and weighted sum of factors of PCA was high (r = 0.866 and r = 0.822, respectively). Correlation between siMS risk score and log transformed Framingham score was medium to high for age groups 18+,30+ and 35+ (0.835, 0.707 and 0.667, respectively).

Conclusions

siMS score and siMS risk score showed high correlation with more complex scores. Demonstrated accuracy together with superior simplicity and the ability to evaluate and follow-up individual patients makes siMS and siMS risk scores very convenient for use in clinical practice and research as well.     

Massive excretion of calcium oxalate from late prepupal salivary glands of Drosophila melanogaster demonstrates active nephridial‐like anion transport

The Drosophila salivary glands (SGs) were well known for the puffing patterns of their polytene chromosomes and so became a tissue of choice to study sequential gene activation by the steroid hormone ecdysone. One well‐documented function of these glands is to produce a secretory glue, which is released during pupariation to fix the freshly formed puparia to the substrate. Over the past two decades SGs have been used to address specific aspects of developmentally‐regulated programmed cell death (PCD) as it was thought that they are doomed for histolysis and after pupariation are just awaiting their fate. More recently, however, we have shown that for the first 3–4 h after pupariation SGs undergo tremendous endocytosis and vacuolation followed by vacuole neutralization and membrane consolidation. Furthermore, from 8 to 10 h after puparium formation (APF) SGs display massive apocrine secretion of a diverse set of cellular proteins. Here, we show that during the period from 11 to 12 h APF, the prepupal glands are very active in calcium oxalate (CaOx) extrusion that resembles renal or nephridial excretory activity. We provide genetic evidence that Prestin, a Drosophila homologue of the mammalian electrogenic anion exchange carrier SLC26A5, is responsible for the instantaneous production of CaOx by the late prepupal SGs. Its positive regulation by the protein kinases encoded by fray and wnk lead to increased production of CaOx. The formation of CaOx appears to be dependent on the cooperation between Prestin and the vATPase complex as treatment with bafilomycin A₁ or concanamycin A abolishes the production of detectable CaOx. These data demonstrate that prepupal SGs remain fully viable, physiologically active and engaged in various cellular activities at least until early pupal period, that is, until moments prior to the execution of PCD.     

Foot insensitivity is associated with renal function decline in patients with type 2 diabetes: a cohort study

Background

Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes.

Methods

A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol.

Results

Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR?≥?60 ml/min/1.73 m². Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R² 0.87), baseline foot insensitivity was associated with study-end eGFR (B?=??3.551, p?=?0.036).

Conclusions

Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.

     

Performance of the eclipse monitor unit objective tool utilizing volumetric modulated arc therapy for rectal cancer

AimTo assess the performance of the monitor unit (MU) Objective tool in Eclipse treatment planning system (TPS) utilizing volumetric modulated arc therapy (VMAT) for rectal cancer.BackgroundEclipse VMAT planning module includes a tool to control the number of MUs delivered: the MU Objective tool. This tool could be utilized to reduce the total number of MUs in rectal cancer treatments.Materials and methods20 rectal cancer patients were retrospectively studied using VMAT and the MU Objective tool. The baseline plan for each patient was selected as the one with no usage of the MU Objective tool. The number of MUs of this plan was set to be the reference number of MUs (MU_ref). Five plans were re-optimized for each patient only varying the Max MU parameter. The selected values were 30%, 60%, 90%, 120% and 150% of MU_ref for each patient. Differences with respect to the baseline plan were evaluated regarding MU number and parameters for PTVs coverage evaluation, PTVs homogeneity and OARs doses assessment. A two-tailed, paired-samples t-test was used to quantify these differences.ResultsAverage relative differences in MU number obtained was 10% for Max MU values of 30% and 60% of MU_ref, respectively (p < 0.03). PTVs coverage and homogeneity were not compromised and discrepancies obtained with respect to baseline plans were not significant. Furthermore, maximum OARs doses deviations were also not significant.ConclusionsA 10% reduction in the MU number could be obtained without an alteration of PTV coverage and OARs doses for rectal cancer.     

Leaf wax n‐alkane patterns of six tropical montane tree species show species‐specific environmental response

It remains poorly understood how the composition of leaf wax n‐alkanes reflects the local environment. This knowledge gap inhibits the interpretation of plant responses to the environment at the community level and, by extension, inhibits the applicability of n‐alkane patterns as a proxy for past environments. Here, we studied the n‐alkane patterns of five Miconia species and one Guarea species, in the Ecuadorian Andes (653–3,507 m a.s.l.). We tested for species‐specific responses in the average chain length (ACL), the C₃₁/(C₃₁ + C₂₉) ratio (ratio), and individual odd n‐alkane chain lengths across an altitudinally driven environmental gradient (mean annual temperature, mean annual relative air humidity, and mean annual precipitation). We found significant correlations between the environmental gradients and species‐specific ACL and ratio, but with varying magnitude and direction. We found that the n‐alkane patterns are species‐specific at the individual chain length level, which could explain the high variance in metrics like ACL and ratio. Although we find species‐specific sensitivity and responses in leaf n‐alkanes, we also find a general decrease in “shorter” (<C₂₉) and an increase in “longer” (>C₃₁) chain lengths with the environmental gradients, most strongly with temperature, suggesting n‐alkanes are useful for reconstructing past environments.     

Allozyme diversity in pheasants (<Emphasis Type="Italic">Phasianus</Emphasis> spp.) from breeding stations in Serbia

The pheasant breeds are widely used for restocking of natural populations depleted by hunting. The pheasant population number decline was detected during the 1970s in many hunting areas of Europe. One of its possible reasons might be the loss of adaptability in populations originating from breeding stations, which was caused by inbreeding depression. The aim of this paper was the analysis of genetic variability in pheasant populations from three breeding stations in Vojvodina province (Serbia) by means of allozyme diversity detection. The allozyme variability analysis of pheasants from all three breeding stations revealed polymorphisms at nine loci: Ldh-1, Mor-1, Mor-2, Es-1, Mod-2, Pgd, Gpi-2, Odh, and Sod. The analysis of individuals from three different breeding stations showed mean values of observed heterozygosity of H _o=0.137, polymorphism P _95%=30%, and H/P ratio H/P=0.430, which indicate a normal level of genetic variability for bird populations. Comparative analysis of three pheasant populations showed a high level of interpopulation differentiation.