Organ damage (OD) is an indicator of increased cardiovascular risk. Blood pressure variability (BPV) is related to greater incidence of events, regardless of the severity of hypertension. We ...investigated the relationship between ambulatory blood pressure monitoring (ABPM)-derived indices of BPV and the presence of multiple OD in primary hypertension (PH). One hundred and sixty-nine untreated patients with PH were evaluated. Systolic (SBP) and diastolic blood pressure (DBP) variability were assessed as the crude and weighted (w.) standard deviation (s.d.), and average real variability (ARV) of the mean value of 24-h, awake and asleep ABPM recordings. Left ventricular mass index, intima-media thickness, estimated-glomerular filtration rate and urinary albumin excretion were assessed as indices of cardiac, vascular and renal damage, respectively. Risk profile progressively increased starting from patients without OD to patients with only one sign of OD, and then to those with multiple OD. In addition to greater severity of the organ involvement, the only variables that were found to significantly differ between subjects with multiple and single OD were office SBP (160 ± 14 vs 154 ± 11 mm Hg, P=0.0423) and DBP (101 ± 7 vs 97 ± 8 mm Hg, P=0.0291), ambulatory arterial stiffness index (AASI) (0.60 ± 0.10 vs 0.50 ± 0.17, P=0.0158) and indices of BPV (24-h SBP s.d., 23 ± 5 vs 20 ± 6 mm Hg, P=0.0300; awake SBP s.d., 22 ± 6 vs 19 ± 6 mm Hg, P=0.0366; 24-h SBP w.s.d., 20 ± 5 vs 17 ± 5 mm Hg, P=0.0385; and 24-h SBP ARV, 18 ± 4 vs 15 ± 5 mm Hg, P=0.0420). All the above mentioned BPV parameters turned out to be determinants of multiple OD, regardless of several confounding variables, including BP levels. Therefore, in hypertensive patients increased SBP variability is associated with multiple signs of OD, regardless of BP values.
Summary
We analyzed polymorphism of the
ALPL
gene in patients with low serum levels of tissue-nonspecific alkaline phosphatase (TNAP). The presence of three or more of the less frequent alleles of
...ALPL
polymorphisms was associated with significantly lower TNAP serum level and higher frequencies of metatarsal fractures, which may help confirm a clinical suspicion of adult hypophosphatasia.
Introduction
Alkaline phosphatases (ALPs) are membrane-bound enzymes that hydrolyze monophosphate esters at a high pH (pH 8–10). Inorganic pyrophosphate, pyridoxal 5-phosphate, the activated form of vitamin B
6
(PLP), and phosphoethanolamine (PEA), are natural substrates of ALPs. Hypophosphatasia (HPP, OMIM 146300, 241500, 241510) is a heterogeneous rare metabolic bone disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase gene (
ALPL; MIM 171760
) with a deficiency of TNAP. Clinical presentation of HPP in adults demonstrated a wide range of manifestations, many of which are nonspecific. In the present study, we screened the polymorphic genetic variants of
ALPL
in 56 subjects presenting low serum levels of TNAP and/or other clinical signs of adult HPP in order to evaluate a possible role of polymorphic variants in the diagnosis and management of HPP in adults.
Methods
Genomic DNA was extracted from peripheral blood and
ALPL
gene was sequenced by PCR-based Sanger technique.
Results
Fourteen different polymorphic variants were found in the study population. A lower serum level of TNAP and higher frequencies of metatarsal fractures were observed in patients bearing three or more of the minor frequency alleles (MFAs) of the
ALPL
polymorphic variants. The presence of some MFAs, mostly as a contemporary presence of three or more of them, was found to be mainly represented in patients having both a significantly lower level of TNAP and a higher level of vitamin B6.
Conclusion
The genetic analysis and presence of some polymorphic variants may be an instrument to confirm clinical and biochemical data, consider adult HPP, and help clinicians be cautious in the administration of anti-reabsorption drugs.
Convective-scale ensemble simulations with perturbed initial and lateral boundary conditions are performed to investigate the mechanisms and sensitivities of a central European convection event from ...the Convective and Orographically Induced Precipitation Study (COPS). In this event, a "primary" squall line developed ahead of a decaying mesoscale convective system (MCS) upstream of the Vosges Mountains (France), weakened over the Rhine valley, then regenerated as a "secondary" squall line over the Black Forest Mountains (Germany). All ensemble members captured the squall-line evolution, but most suffered from a delay in the onset of convection and positional errors of 50-150 km over the COPS region. These errors in the secondary initiation were linked to errors in the primary initiation. Detailed analysis revealed a similar primary initiation mechanism in all members: in the ascending branch of a midlevel frontal circulation ahead of the MCS, convection initiated within a mesoscale moisture anomaly embedded within the prefrontal flow. The differences in the skill of the ensemble members were related to subtle differences in their initial upper-level representation of potential vorticity (PV). Members that verified well possessed a stronger PV gradient at the leading edge of an upper-level trough. This led to more rapid cyclogenesis over northern France and the United Kingdom and faster development and propagation of the midlevel front and the prefrontal moisture anomaly. As a consequence, the squall lines in these members developed earlier and closer to the COPS region. This case study provides an example of the subtle mechanisms by which errors on the larger scales may transfer to the convective scale and lead to errors in quantitative precipitation forecasts.
Summary
Rationale: Calcidiol can be employed to correct vitamin D deficiency. Main results: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully ...raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. Significance: Calcidiol supplementation is effective and safe.
Introduction
The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D
3
) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D
3
) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D 25(OH)D. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested.
Methods
A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 μg/day, 40 μg/day, and 125 μg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety.
Results
In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound.
Conclusions
The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.
Papillomas are uncommon tumors of the sinonasal tract histologically derived from the Schneiderian membrane. Three distinctive variants are described, the exophytic, the inverting and the oncocytic ...types. On physical examination, their appearance varies from exophytic-fungiform seen in the exophytic variant, to polypoid-papillary in both the inverting and oncocytic variant. The presence of an asymptomatic mass or epistaxis and unilateral nasal obstruction are the typical presenting symptoms. Clinically they tend to recur and, although benign, they may erode the bone laminas by pressure, especially the inverting type, causing proptosis and other co-morbidities. Malignant transformation is seen both synchronously, on a pre-existing papilloma, and metachronously after several recurrences of papilloma. Schneiderian papillomas are at a date a topic of controversy regarding their etiology, pathogenesis and biological behavior. Furthermore, histologic criteria to assess dysplasia and malignant transformation are ill-defined. The present study aims to comparatively review the histologic types of papillomas, their etiology, the currently available criteria for malignant transformation, their treatment and prognosis.
Background
Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that may relapse. ...Histological assessment is informative, but no single scoring system is widely adopted. We previously proposed an eight-item histological scheme for the easy, fast reporting of disease activity in the intestine. The aim of the present study was to evaluate the performance of our Simplified Histologic Mucosal Healing Scheme (SHMHS).
Methods
Between April and May 2021 pathologists and gastroenterologists in Italy were invited to contribute to this multicenter study by providing data on single endoscopic–histological examinations for their IBD patients undergoing treatment. Disease activity was expressed using SHMHS (maximum score, 8) and either Simple Endoscopic Score for Crohn’s Disease (categorized into grades 0–3) or Mayo Endoscopic Subscore (range 0–3).
Results
Thirty hospitals provided data on 597 patients (291 Crohn’s disease; 306 ulcerative colitis). The mean SHMHS score was 2.96 (SD = 2.42) and 66.8% of cases had active disease (score ≥ 2). The mean endoscopic score was 1.23 (SD = 1.05), with 67.8% having active disease (score ≥ 1). Histologic and endoscopic scores correlated (Spearman’s ρ = 0.76), and scores for individual SHMHS items associated directly with endoscopic scores (chi-square
p
< 0.001, all comparisons). Between IBD types, scores for SHMHS items reflected differences in presentation, with cryptitis more common and erosions/ulcerations less common in Crohn’s disease, and the distal colon more affected in ulcerative colitis.
Conclusions
SHMHS captures the main histological features of IBD. Routine adoption may simplify pathologist workload while ensuring accurate reporting for clinical decision making.
Objectives
The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ...ventricular (LV) structure and function in community‐dwelling subjects without heart disease.
Design
The relationship between concentrations of 25‐hydroxyvitamin D 25(OH)D, a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease.
Results
Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL−1; only 15.5% of subjects had moderate or severe vitamin D deficiency 25(OH)D < 20 ng mL−1. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (β 0.095, SE 0.039, P < 0.05) and LV mass index (β 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels <30 ng mL−1 odds ratio (OR) 1.24; 95% confidence interval (CI) 0.83–1.85 or ≥38 ng mL−1 (OR 1.73; 95% CI 1.13–2.65), compared with those with 30–37 ng mL−1 25(OH)D. Consistently, LV relative wall thickness was significantly lower (P for trend=0.05), and LV diastolic internal diameter index (P for trend<0.05) and end‐diastolic volume index (P for trend<0.05) were significantly higher in subjects with 30–37 ng mL−1 25(OH)D compared to the rest of the study population. There was a significant interaction between 25(OH)D and hypertension on the risk of LV hypertrophy (P < 0.05).
Conclusions
In a population‐based sample of predominantly vitamin D‐sufficient subjects without heart disease, LV geometry was most favourable at intermediate 25(OH)D concentrations.
This work contributes to the development of a multi-vector flexibility management platform, combining electric, heat and gas optimization at district level. The multi-vector flexibility management ...platform will be validated both experimentally and by simulation, on a set of demonstration scenarios. Each scenario refers to an eco-district topology with a given distribution network of energy, a consumer side and a multi-source heat production plant, consisting of a gas boiler, a solar collector, and a heat pump. In addition, a thermal storage in the form of a water tank is connected to the network. A key aspect is the ability to optimize such a system at district level, with the performance of the individual components depending on operating temperatures and environmental conditions, and varying primary energy prices. By simulating the distribution network with a dynamic model, the non-linear influence of various parameters on the system can be investigated.
In particular, the current study focuses on the operation of the multi-source heat production system and thermal storage. A 1D model of the multi-source heat production (gas, solar and heat pump), the thermal storage, and a global consumer is performed using the equation-based object-oriented language Modelica along with the simulation platform Dymola. The model is run with standard controls from district heating provider, i.e. constant or linear controls. For a given consumer load, a set of key performance indicators (KPI) are used to assess the performance of the system, e.g. energy share from renewables and storage utilization rate. The sensitivity to the model’s input is analyzed as well. The results can be used as reference to apply optimal control schemes and study the influence on the corresponding KPIs.
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