Usefulness of ambulatory blood pressure monitoring in predicting the presence of autonomic neuropathy in type I diabetic patients.

This study investigated whether nondipping (defined as a day–night change in blood pressure (BP) <=0%) could be assumed as a diagnostic index for autonomic neuropathy, and assessed its accuracy in discriminating between type I diabetic patients with and without autonomic neuropathy. In 87 type I diabetic patients with normal renal function (age 36+-11, duration 17+-9 years, serum creatinine 67.2+-15.9 mcmol/l), four cardiovascular tests and 24-h BP monitoring were performed, and the percentage day–night change (Delta) in systolic (SBP) and diastolic BP (DBP) was calculated. Sixteen patients had Delta SBP and/or Delta DBP <=0%. In a multiple logistic regression with adjustment for sex, age, and body mass index, the odds ratio for having autonomic neuropathy was seven times higher in patients with DSBP <=0% as opposed to those without (odds ratio 6.97, CI 1.4–34.9, P=0.018). Using Receiver Operating Characteristic (ROC) analysis, DBP showed an acceptable accuracy in discriminating between patients with and without autonomic neuropathy (area under the ROC curve 0.69+-0.06 and 0.72+-0.05 for Delta SBP and Delta DBP, respectively). Adequate cutoff values were 0% for Delta SBP (sensitivity, 26%; specificity, 95%; positive predictive value, 87%) and 5% for Delta DBP (sensitivity, 26%; specificity, 92%; positive predictive value, 81%). In type I diabetic patients with normal renal function, a value of Delta SBP p0% identifies the presence of autonomic neuropathy with a very high chance. Nondipping at the cutoff proposed could be considered an adjunctive marker of autonomic neuropathy provided with a high specificity and low sensitivity

A meteorological–hydrological regional ensemble forecast for an early-warning system over small Apennine catchments in Central Italy

Abstract. The weather forecasts for precipitation have considerably improved in recent years thanks to the increase of computational power. This allows for the use of both a higher spatial resolution and the parameterization schemes specifically developed for representing sub-grid scale physical processes at high resolution. However, precipitation estimation is still affected by errors that can impact the response of hydrological models. To the aim of improving the hydrological forecast and the characterization of related uncertainties, a regional-scale meteorological–hydrological ensemble is presented. The uncertainties in the precipitation forecast and how they propagate in the hydrological model are also investigated. A meteorological–hydrological offline coupled ensemble is built to forecast events in a complex-orography terrain where catchments of different sizes are present. The Best Discharge-based Drainage (BDD; both deterministic and probabilistic) index, is defined with the aim of forecasting hydrological-stress conditions and related uncertainty. In this context, the meteorological–hydrological ensemble forecast is implemented and tested for a severe hydrological event which occurred over Central Italy on 15 November 2017, when a flood hit the Abruzzo region with precipitation reaching 200 mm (24 h)−1 and producing damages with a high impact on social and economic activities. The newly developed meteorological–hydrological ensemble is compared with a high-resolution deterministic forecast and with the observations (rain gauges and radar data) over the same area. The receiver operating characteristic (ROC) statistical indicator shows how skilful the ensemble precipitation forecast is with respect to both rain-gauge- and radar-retrieved precipitation. Moreover, both the deterministic and probabilistic configurations of the BDD index are compared with the alert map issued by Civil Protection Department for the event showing a very good agreement. Finally, the meteorological–hydrological ensemble allows for an estimation of both the predictability of the event a few days in advance and the uncertainty of the flood. Although the modelling framework is implemented on the basins of the Abruzzo region, it is portable and applicable to other areas

Epigenetic therapies for heart failure: Current insights and future potential

Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF

Reflectivity and velocity radar data assimilation for two flash flood events in central Italy: A comparison between 3D and 4D variational methods

The aim of this study is to provide an evaluation of the impact of two largely used data assimilation techniques, namely three- and four-dimensional variational data assimilation systems (3D-Var and 4D-Var), on the forecasting of heavy precipitation events using the Weather Research and Forecasting (WRF) model. For this purpose, two flash flood events in central Italy are analysed. The first occurred on September 14, 2012 during an Intensive Observation Period of the Hydrological cycle in the Mediterranean experiment (HyMeX) campaign, while the other occurred on May 3, 2018. Radial velocity and reflectivity acquired by C-band weather radars at Mt. Midia (central Italy) and San Pietro Capofiume (northern Italy), as well as conventional observations (SYNOP and TEMP), are assimilated into the WRF model to simulate these damaging flash flood events. In order to evaluate the impact of the 3D-Var and 4D-Var assimilation systems on the estimation of short-term quantitative precipitation forecasts, several experiments are carried out using conventional observations with and without radar data. Rainfall evaluation is performed by means of point-by-point and filtering methodologies. The results point to a positive impact of the 4D-Var technique compared to results without assimilation and with 3D-Var experiments. More specifically, the 4D-Var system produces an increase of up to 22% in terms of the Fractions Skill Score compared to 3D-Var for the first flash flood event, while an increase of about 5% is achieved for the second event. The use of a warm start initialization results in a considerable reduction in the spin-up time and a significant improvement in the rainfall forecast, suggesting that the initial precipitation spin-up problem still occurs when using 4D-Var

Does autonomic neuropathy play a role in erythropoietin regulation in non-proteinuric Type 2 diabetic patients?

Aims Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy. Methods In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO. Results Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001). Conclusion This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation

Pharmacokinetic and metabolism determinants of fluoropyrimidines and oxaliplatin activity in treatment of colorectal patients

Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary to develop an effective therapy adapted to the patient's molecular profile, while minimizing life-threatening toxicities. In this review, we discuss literature data, defining predictive and prognostic markers actually identified in the treatment of CRC. We analyzed predictive markers of fluoropyrimidines effectiveness, principally for 5-Fluorouracil (5-FU) and also for oral fluoropyrimidines, as thymidylate Synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), methylenetetrahydrofolate reductase (MTHFR), deoxyuridine triphosphate nucleotidohydrolase (dUTPase), micro-satellite instability. DPD represent the more studied 5-FU toxicity marker, followed by TS and OPRT. Oxaliplatin effectiveness is principally regulated by nucleotide excision repair (NER) pathway, including excision repair cross-complementation group 1 (ERCC1), X-ray cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XDP). The major oxaliplatin toxicity marker is represented by glutathione S-transferase (GST). All these results are based principally on retrospective studies. The future challenge became to validate molecular markers and their association with clinical outcomes in prospective trials, refining technologic platforms and bioin-formatics to accommodate the complexity of the multifaceted molecular map that may determine outcome, and determining CRC patients most likely to benefit from therapeutic interventions tailored specifically for them

Correlation between diastolic impairment and lipid metabolism in mild-to-moderate hypertensive postmenopausal women1

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Folfiri versus xeliri in untreated advanced colorectal cancer: A phase II randomised trial of the Gruppo Oncologico dell' Italia Meridionale (prot. GOIM 2405)

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Assessment of DNA Damage and Telomerase Activity in Exfoliated Urinary Cells as Sensitive and Noninvasive Biomarkers for Early Diagnosis of Bladder Cancer in Ex-Workers of a Rubber Tyres Industry

The aim of the present study was to identify sensitive and noninvasive biomarkers of early carcinogenic effect at target organ to use in biomonitoring studies of workers at risk for previous occupational exposure to potential carcinogens. Standard urine cytology (Papanicolaou staining test), comet assay, and quantitative telomerase repeat amplification protocol (TRAP) assay were performed in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects. In TRAP positive cases, a second level analysis using FISH (Urovysion) was done. Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet positive resulted in infiltrating UBC to the biopsy and with hyperplasia and slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition, and 2 TRAP positive showed in one case a phlogosis condition. The results evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of procarcinogenic effect confirmed by the dysplastic condition and UBC found by cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be potentially more accurate than conventional cytology in monitoring workers exposed to mixture of bladder potential carcinogens