Low-dose aspirin for primary prevention of cardiovascular events in postmenopausal women with type-2 diabetes: The prescriptive approach in the real world

Background: The long-Term efficacy of low-dose aspirin for primary prevention of cardiovascular (CV) events in postmenopausal women with type-2 diabetes is controversial. Therefore, it is recommended only on an individual basis, recommendation of grade C. Methods: We enrolled 275 consecutive postmenopausal women with type-2 diabetes, without an increased bleeding risk and without preexisting CV disease as coronary artery disease, stroke, and peripheral vascular disease, but with a high risk assessed by score >10%, aged 60-69 years. All were receiving aspirin (75-100 mg daily), aspirin group (AG). 170 postmenopausal women with type-2 diabetes and without preexisting cardiovascular (CV) disease, but not on aspirin treatment, despite a high risk assessed by score >10%, were control group (CG). Mean age was 66 ± 4 years for AG and 65 ± 7 years for CG. Our goal was to identify the prevalence of low-dose aspirin prescriptions in these populations according to different clinical conditions. Results: Women with only high risk were 41/275 (15%) on AG and 72/170 (42.3%) on CG, Chi-squared 41, Odds ratio 0.2, c.i. 95%, P < 0.0001. Women affected by metabolic syndrome were 105/275 (38.1%) on AG and 47/170 (27.6%) on CG, Chi-squared 5.1, Odds ratio 1.6, c.i. 95%, P < 0.02. Women affected by metabolic cardiomyopathy were 111/275 (40.3%) on AG and 44/170 (25.9%) on CG, Chi-squared 8, Odds ratio 1.8, c.i. 95%, P < 0.004. Women affected by diabetic cardiomyopathy were 18/275 (6.6%) on AG and 7/170 (4.2%) on CG, Chi-squared 1.2, Odds ratio 16, c.i. 95%, P < 0.2 n.s. Conclusions: Low-dose aspirin in our population is prescribed preferentially in postmenopausal women with type-2 diabetes when affected by metabolic syndrome or metabolic cardiomyopathy, at the opposite women with only high risk have lower chance to receive aspirin

Near-optimal combination of disparity across a log-polar scaled visual field

The human visual system is foveated: we can see fine spatial details in central vision, whereas resolution is poor in our peripheral visual field, and this loss of resolution follows an approximately logarithmic decrease. Additionally, our brain organizes visual input in polar coordinates. Therefore, the image projection occurring between retina and primary visual cortex can be mathematically described by the log-polar transform. Here, we test and model how this space-variant visual processing affects how we process binocular disparity, a key component of human depth perception. We observe that the fovea preferentially processes disparities at fine spatial scales, whereas the visual periphery is tuned for coarse spatial scales, in line with the naturally occurring distributions of depths and disparities in the real-world. We further show that the visual system integrates disparity information across the visual field, in a near-optimal fashion. We develop a foveated, log-polar model that mimics the processing of depth information in primary visual cortex and that can process disparity directly in the cortical domain representation. This model takes real images as input and recreates the observed topography of human disparity sensitivity. Our findings support the notion that our foveated, binocular visual system has been moulded by the statistics of our visual environment

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

Immune checkpoint mechanisms are important molecular cell systems that maintain tolerance toward autoantigens in order to prevent immunity-mediated accidental damage. It is well known that cancer cells may exploit these molecular and cellular mechanisms to escape recognition and elimination by immune cells. Programmed cell death protein-1 (PD-1) and its natural ligand programmed cell death ligand-1 (PD-L1) form the PD-L1/PD-1 axis, a well-known immune checkpoint mechanism, which is considered an interesting target in cancer immunotherapy. In fact, the expression of PD-L1 was found in various solid malignancies and the overactivation of PD-L1/PD-1 axis results in a poor patient survival rate. Breaking PD-L1/PD-1 axis, by blocking either the cancer side or the immune side of the axis, is currently used as anti-cancer strategy to re-establish a tumor-specific immune response. For this purpose, several blocking antibodies are now available. To date, three anti-PD-L1 antibodies have been approved by the FDA, namely atezolizumab, durvalumab and avelumab. The main advantages of anti-PD-L1 antibodies arise from the overexpression of PD-L1 antigen by a high number of tumor cells, also deriving from different tissues; this makes anti-PD-L1 antibodies potential pan-specific anti-cancer molecules. Despite the good results reported in clinical trials with anti-PD-L1 antibodies, there is a significant number of patients that do not respond to the therapy. In fact, it should be considered that, in some neoplastic patients, reduced or absent infiltration of cytotoxic T cells and natural killer cells in the tumor microenvironment or presence of other immunosuppressive molecules make immunotherapy with anti-PD-L1 blocking antibodies less effective. A strategy to improve the efficacy of antibodies is to use them as carriers for toxic payloads (toxins, drugs, enzymes, radionuclides, etc.) to form immunoconjugates. Several immunoconjugates have been already approved by FDA for treatment of malignancies. In this review, we focused on PD-L1 targeting antibodies utilized as carrier to construct immunoconjugates for the potential elimination of neoplastic cells, expressing PD-L1. A complete examination of the literature regarding anti-PD-L1 immunoconjugates is here reported, describing the results obtained in vitro and in vivo. The real potential of anti-PD-L1 antibodies as carriers for toxic payload delivery is considered and extensively discussed

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

Corticosteroid-Sparing Effect of Chromoglycate Sodium and Nedocromil

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 μg/day. Values for FEV1, PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 μ/day). Authors conclude that NED could have a steroidsparing effect over long-term use

Sequence, structure, and binding site analysis of kirkiin in comparison with ricin and other type 2 rips

Kirkiin is a new type 2 ribosome-inactivating protein (RIP) purified from the caudex of Adenia kirkii with a cytotoxicity compared to that of stenodactylin. The high toxicity of RIPs from Adenia genus plants makes them interesting tools for biotechnology and therapeutic applications, particularly in cancer therapy. The complete amino acid sequence and 3D structure prediction of kirkiin are here reported. Gene sequence analysis revealed that kirkiin is encoded by a 1572 bp open reading frame, corresponding to 524 amino acid residues, without introns. The amino acid sequence analysis showed a high degree of identity with other Adenia RIPs. The 3D structure of kirkiin preserves the overall folding of type 2 RIPs. The key amino acids of the active site, described for ricin and other RIPs, are also conserved in the kirkiin A chain. Sugar affinity studies and docking experiments revealed that both the 1α and 2γ sites of the kirkiin B chain exhibit binding activity toward lactose and D-galactose, being lower than ricin. The replacement of His246 in the kirkiin 2γ site instead of Tyr248 in ricin causes a different structure arrangement that could explain the lower sugar affinity of kirkiin with respect to ricin

Psychology and hereditary angioedema: A systematic review

Background: Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(SERPING1), which results in either the decreased synthesis of normal C1-INH (C1-INH–HAE type I) or expression of unfunctional C1-INH (C1-INH–HAE type II). In recent studies, emotional stress was reported by patients as the most common trigger factor for C1-INH–HAE attacks. Moreover, patients reported considerable distress over the significant variability and uncertainty with which the disease manifests, in addition to the impact of physical symptoms on their overall quality of life. Objective: We did a systematic review of the literature to shed light on the advancements made in the study of how stress and psychological processes impact C1-INH–HAE. Methods: All of the articles on C1-INH–HAE were analyzed up to December 2019. Both medical data bases and psychological data bases were examined. The keywords (KWs) used for searching the medical and psychological data bases were the following: “hereditary angioedema,” “psychology,” “stress,” “anxiety,” and “depression.” Results: Of a total of 2549 articles on C1-INH–HAE, 113 articles were retrieved from the literature search by using the related KWs. Twenty-one of these articles were retrieved, examined, and classified. Conclusion: Although the literature confirmed that stress may induce various physical diseases, it also warned against making simplistic statements about its incidence that did not take into account the complexity and multicausality of factors that contribute to C1-INH–HAE expression

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

Impact of radar data assimilation for the simulation of a heavy rainfall case in central Italy using WRF–3DVAR

Abstract. The aim of this study is to investigate the role of the assimilation of Doppler weather radar (DWR) data in a mesoscale model for the forecast of a heavy rainfall event that occurred in Italy in the urban area of Rome from 19 to 22 May 2008. For this purpose, radar reflectivity and radial velocity acquired from Monte Midia Doppler radar are assimilated into the Weather Research Forecasting (WRF) model, version 3.4.1. The general goal is to improve the quantitative precipitation forecasts (QPF): with this aim, several experiments are performed using the three-dimensional variational (3DVAR) technique. Moreover, sensitivity tests to outer loops are performed to include non-linearity in the observation operators. In order to identify the best initial conditions (ICs), statistical indicators such as forecast accuracy, frequency bias, false alarm rate and equitable threat score for the accumulated precipitation are used. The results show that the assimilation of DWR data has a large impact on both the position of convective cells and on the rainfall forecast of the analyzed event. A positive impact is also found if they are ingested together with conventional observations. Sensitivity to the use of two or three outer loops is also found if DWR data are assimilated together with conventional data