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This paper describes the application of a physically based agrohydrological model (named FLOWS), coupled with a kinematic wave approach model (named KWV) for water and solute runoff routing, for interpreting the fate of water and nutrients coming from cultivated fields to surface drainage network located in 'Piana del Sassu' in the Arborea plain, a hydraulically reclaimed area with shallow groundwater. Modelling was supported by a large complex database on soil, groundwater and surface drainage water, which was used for establishing the boundary conditions for simulations, as well as for calibrating and validating the model. The model FLOWS provided the water and nutrient fluxes to the surface water, which were passed to the KWV model for their routing along the elementary fields in the experimental area and from these to the ditches and finally to the drainage channel. The modelling approach effectively predicted the water and solute distribution along the soil profile, as well as the losses of water and nutrients to the surface water. The results showed a significant amount of water and dissolved nutrients to flow quickly from the soil uppermost layer to the surface drainage network during both the irrigation season and during rainfall events. During irrigation applications, losses were mostly due to rainfall intensity exceeding the maximum infiltration velocity of the shallow soil layer in the case of sprinkler irrigation and to subsurface lateral drainage in the case of exceeding irrigation water provided by drip irrigation. This makes the Sassu plain a significant contributor of nutrients (nitrate and phosphorus) to the surface water. Consequently, even though the agricultural activities might not be an important issue for the groundwater vulnerability, the management of water and nutrients should be significantly improved to avoid ecohydrological threats to the important coastal water bodies present in the area. [ABSTRACT FROM AUTHOR]

This research aims at studying the intrinsic vulnerability of groundwater to diffuse environmental pollutants in the Muravera coastal agricultural area of Sardinia, Italy. The area faces contamination risks arising from agricultural practices, especially the use of fertilizers, pesticides, and various chemicals that can seep into the groundwater. The study examined the interplay among hydrological elements, including soil characteristics, groundwater depth, climate conditions, land use, and aquifer properties. To do that, the outcomes of FLOWS 1D physically-based agrohydrological model were analyzed in parallel with those of the overlay-and-index model SINTACS, in a sort of reciprocal benchmarking. By using FLOWS, water movement and solute transport in the unsaturated zone were simulated by, respectively, solving the Richard Equation (RE) and the Advection-Dispersion equation (ADE). As such, this model allowed to account for the role of soil hydraulic and hydro-dispersive properties variability in determining the travel times of a conservative solute through the soil profile to the groundwater. For FLOWS simulations, a complete dataset was used as input, including soil horizons, soil physical and hydraulic properties of 36 soil profiles, average annual depth to groundwater table at each soil profile (ranging from 1 to 50 meters), and climatic temporal series data on rainfall and evapotranspiration. Detailed analyses of travel times for the movement of 25, 50, 75, and 100% of the solute mass to reach groundwater were conducted, revealing that the depth to groundwater predominantly influences vulnerability. This result was coherent with SINTACS vulnerability map due to the large impact of the depth to groundwater on SINTACS analysis. [ABSTRACT FROM AUTHOR]

Background/Objectives: A compartmental pharmacokinetics (PK) analysis of new extended half-life FVIII concentrates has never been performed in a large cohort of hemophilia patients. An improved PK analysis of individual outcomes may help to tailor hemophilia replacement treatment. Methods: PK outcomes after the infusion of a standard single dose of Efmoroctocog alfa were collected from 173 patients with severe/moderately severe hemophilia A in 11 Italian hemophilia centers. Factor VIII clotting activity (FVIII:C) was measured by one-stage clotting assay (OSA) in all patients, and chromogenic substrate assay (CSA) in a subgroup (n = 52). Fifty patients underwent a comparative PK assessment with standard half-life (SHL) recombinant FVIII (rFVIII) products. Non-compartmental analysis (NCA), one compartment model (OCM), and TCM were used to analyze the decay curves of all patients, and one-way paired ANOVA to compare the PK outcomes. Results: All 173 PKs conformed to the NCA and OCM, but only 106 (61%) conformed to the TCM based on the biphasic features of their decay curves. According to the TCM, the Beta HL and MRT of rFVIIIFc were 20.42 ± 7.73 and 25.64 ± 7.61 h, respectively. ANOVA analysis of the outcomes from the three PK models showed significant differences in clearance, half-life (HL), and mean residence time (MRT) (p < 0.001 for all parameters). As anticipated, the HL and MRT of rFVIIIFc were longer than those of SHL rFVIII. Comparing OSA with CSA outcomes, Cmax resulted higher when measured by CSA (p = 0.05) and, according to TCM, Beta HL resulted longer when measured by OSA (p = 0.03). FVIII:C trough levels obtained with SHL concentrates were significantly lower than those obtained with rFVIIIFc at each post-infusion time point. Conclusions: In a large group of hemophilia A (HA) patients, three different PK models confirmed the improved pharmacokinetic (PK) characteristics of rFVIIIFc, compared with standard half-life rFVIII concentrates. The TCM only fits two-thirds of the PKs, highlighting their biphasic decay and a long Beta half-life. In these patients, the TCM would be preferable to properly evaluate individual PK features. [ABSTRACT FROM AUTHOR]

Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. Treatment goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health‐related quality of life impacted by haemophilia and its treatment. Conclusion: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia‐imposed limitations. To achieve this—being supported by the data reviewed in this manuscript—the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) infection is linked to several cancers, including anal and oral cancers. The incidence of anal cancer is particularly high among HIV-positive men who have sex with men (MSM). DNA methylation markers have shown promise as biomarkers for identifying precancerous lesions and cancer in HPV-infected individuals. The aim of this study was to investigate the correlation of DNA methylation with HPV infection in oral samples and the correlation of DNA methylation with lesion degree in the anal samples of HIV-positive MSM. Methods: This study investigated DNA methylation in oral and anal samples from HIV-positive MSM at the National Institute for Infectious Diseases (INMI) in Rome, Italy. Exfoliated oral epithelial cells and anal samples were collected and analyzed for 28 HPV genotypes using the Allplex 28 HPV assay. DNA methylation was assessed with the PrecursorM+ kit for oral samples and the AnoGyn kit for anal samples, focusing on the promoter regions of specific genes. Results: The study included 63 participants, with a median age of 49 and a median CD4+ count of 705 cells/µL. The oral samples showed HPV16 as the most common type, with 22% testing positive for DNA methylation. The anal samples exhibited HPV-related methylation changes linked to cytological lesions, with a 30% increase in the observed ddCt ratio. Significant differences were found in both ASCL1 and ZNF582 genes, particularly for HSILvsNILM and HSILvsLSIL lesions. Of the samples with an increased ddCt ratio, 80% were from patients over 35 years old, and multiple HPV infections were common. Conclusions: DNA methylation markers could be valuable in identifying high-risk HPV infections in oral samples and detecting potential precancerous lesions in anal samples. These markers may enhance the early detection and prevention strategies for HPV-related cancers in high-risk populations, with follow-up data indicating potential for monitoring lesion progression. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted in Italy that evaluated the use of recombinant factor IX-albumin fusion protein (rIX-FP) as a treatment for adult patients with hemophilia B. The study found that rIX-FP prophylaxis was effective in reducing bleeding episodes and required fewer infusions compared to previous treatments. The most common dosing regimen was every 14-15 days, with one patient using a 21-day regimen. The study concluded that rIX-FP is a flexible and effective treatment option for adult patients with hemophilia B, but further research is needed to assess long-term outcomes. It is important to consider physical activity levels and lifestyle when personalizing prophylaxis regimens. [Extracted from the article]

Objectives: To evaluate pattern of use and clinical outcomes in pediatric/adolescent patients enrolled in the IDEAL study. Methods: This post‐hoc analysis of IDEAL retrospective‐prospective observational study focused on patients <18 years, 100% on prophylaxis during the entire observation period. Results: Thirteen subjects (median age 10.0 years; 61.5% ≤ 11 years) were analyzed. The infusion frequency changed from 2/week in 84.6% (N = 11) of patients with previous rFIX, to less than 1/weekly in 76.9% (N = 9) with rIX‐FP and the annualized number of infusions reduced of 57% (p =.002), from a mean ± SD of 95.1 ± 22.77 to 40.4 ± 6.79, respectively. Annualized mean consumption decreased of about 56% (p =.001), from 3748.4 ± 1155.40 IU/kg with previous rFIX, to 1656.8 ± 456.63 IU/kg of rIX‐FP. Mean FIX trough level changed from 3.0% ± 1.98% to 10.92% ± 3.6%. Low mean Annualized Bleeding Rate was maintained across all prophylaxis regimens (0.8 ± 1.69 vs. 0.3 ± 0.89) and zero bleeding patients moved from 69.2% (N = 9) with previous rFIX to 84.6% (N = 11) with rIX‐FP (p =.63). Two adverse events, none related to rIX‐FP, occurred in two patients. No inhibitors development was reported. Conclusions: The results in this pediatric/adolescent subgroup support rIX‐FP prophylaxis may reduce infusion frequency, while providing high FIX trough levels, stable annualized bleeding rate and a good safety profile. [ABSTRACT FROM AUTHOR]