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Abstract Aims We report the results of a real‐world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life. Methods and results We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ‐5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e′ (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High‐Sensitivity Kit determined elevated interleukin‐6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period. Conclusions This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs.

We consider degenerate Kolmogorov-Fokker-Planck operators ℒu=∑i,j=1qaij(x,t)uxixj+∑k,j=1Nbjkxkuxj−ut,{\mathcal{ {\mathcal L} }}u=\mathop{\sum }\limits_{i,j=1}^{q}{a}_{ij}\left(x,t){u}_{{x}_{i}{x}_{j}}+\mathop{\sum }\limits_{k,j=1}^{N}{b}_{jk}{x}_{k}{u}_{{x}_{j}}-{u}_{t}, such that the corresponding model operator having constant aij{a}_{ij} is hypoelliptic, translation invariant w.r.t. a Lie group operation in RN+1{{\mathbb{R}}}^{N+1} and 2-homogeneous w.r.t. a family of nonisotropic dilations. We assume that the aij{a}_{ij}’s are globally bounded and Hölder continuous in xx (w.r.t. some intrinsic distance induced by ℒ{\mathcal{ {\mathcal L} }}); the matrix {aij}i,j=1q{\{{a}_{ij}\}}_{i,j=1}^{q} is symmetric and uniformly positive on Rq{{\mathbb{R}}}^{q}. We prove “partial Schauder a priori estimates” on a bounded open set Ω⊂RN+1\Omega \subset {{\mathbb{R}}}^{N+1}, of the kind ∑i,j=1q([uxixj]∗,α,2x+[uxixj]∗,2)≤c{[ℒu]∗,α,2x+[ℒu]∗,2+supΩ∣u∣}\mathop{\sum }\limits_{i,j=1}^{q}({\left[{u}_{{x}_{i}{x}_{j}}]}_{\ast ,\alpha ,2}^{x}+{\left[{u}_{{x}_{i}{x}_{j}}]}_{\ast ,2})\le c\left\{{\left[{\mathcal{ {\mathcal L} }}u]}_{\ast ,\alpha ,2}^{x}+{\left[{\mathcal{ {\mathcal L} }}u]}_{\ast ,2}+\mathop{\sup }\limits_{\Omega }| u| \right\} for suitable functions uu, where [u]∗,α,2x=sup(x,t)≠(y,t)∈Ωd(x,t),(y,t)2+α∣u(x,t)−u(y,t)∣‖x−y‖α[u]∗,2=supξ∈Ωdξ2∣u(ξ)∣.\begin{array}{rcl}{\left[u]}_{\ast ,\alpha ,2}^{x}& =& \mathop{\sup }\limits_{\left(x,t)\ne (y,t)\in \Omega }{d}_{\left(x,t),(y,t)}^{2+\alpha }\frac{| u\left(x,t)-u(y,t)| }{\Vert x-y{\Vert }^{\alpha }}\\ {{[}u]}_{\ast ,2}& =& \mathop{\sup }\limits_{\xi \in \Omega }{d}_{\xi }^{2}| u\left(\xi )| .\end{array} Here ‖⋅‖\Vert \cdot \Vert is a homogeneous norm in RN{{\mathbb{R}}}^{N}, while dξ=dist(ξ,∂Ω){d}_{\xi }={\rm{dist}}\left(\xi ,\partial \Omega ) and dξ,η=min{dξ,dη}{d}_{\xi ,\eta }=\min \left\{{d}_{\xi },{d}_{\eta }\right\}. We also prove that the derivatives uxixj{u}_{{x}_{i}{x}_{j}} are locally Hölder continuous in space and time.

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Background: Cognitive loss is one of the biggest health problems for older people. The incidence of dementia increases with age, so Alzheimer’s disease (AD), the most prevalent type of dementia, is expected to increase. Patients with dementia find it difficult to cope with their daily activities and resort to family members or caregivers. However, aging generally leads to a loss of orientation and navigation skills. This phenomenon creates great inconvenience for autonomous walking, especially in individuals with Mild Cognitive Impairment (MCI) or those suffering from Alzheimer’s disease. The loss of orientation and navigation skills is most felt when old people move from their usual environments to nursing homes or residential facilities. This necessarily involves a person’s constant presence to prevent the patient from moving without a defined destination or incurring dangerous situations. Methods: A navigation system is a support to allow older patients to move without resorting to their caregivers. This application meets the need for helping older people to move without incurring dangers. The aim of the study was to verify the possibility of applying the technology normally used for video games for the development of an indoor navigation system. There is no evidence of this in the literature. Results: We have developed an easy-to-use solution that can be extended to patients with MCI, easing the workload of caregivers and improving patient safety. The method applied was the use of the Unity Vuforia platform, with which an augmented reality APK application was produced on a smartphone. Conclusions: The model differs from traditional techniques because it does not use arrows or labels to identify the desired destination. The solution was tested in the laboratory with staff members. No animal species have been used. The destinations were successfully reached, with an error of 2%. A test was conducted against some evaluation parameters on the use of the model. The values are all close to the maximum expected value. Future developments include testing the application with a predefined protocol in a real-world environment with MCI patients.

Rapid urbanization and evolving dietary preferences have heightened the demand for durum wheat and its derivatives in developing nations like Nepal. This study represents the first comprehensive exploration and evaluation of durum wheat genotypes in Nepal, addressing the escalating need for high-yielding varieties. The primary objective was to identify stable and prolific durum wheat lines for release, enhancing Nepal’s durum wheat breeding program. Utilizing genotypes from CIMMYT’s disease screening and yield nurseries from 2011/12 to 2020/21, a total of 132 genotypes, including international checks, underwent evaluation over ten years under the Alpha Lattice design. Results revealed significant variation among genotypes for grain yield and other traits, identifying high-yielding and stable lines suitable for Nepal. Heritability analysis highlighted moderate heritability for grain number per spike, thousand-grain weight, and grain yield. Cluster analysis identified distinct clusters with high grain yield and desirable agronomic traits. Disease incidence facilitated the selection of resistant lines, with DWK38 emerging as the highest grain yielder (4416.04 kg/ha). Overall, durum wheat lines from CIMMYT exhibited robust performance in Nepal, enabling the identification of superior lines with potential benefits for farmers and consumers. The study’s implications include developing and releasing superior durum lines in Nepal, providing farmers with profitable alternatives amidst evolving food habits. In conclusion, the findings from this study provide a valuable foundation for future durum wheat breeding efforts in Nepal, guiding the selection of genotypes that are well-suited to the diverse environmental challenges of the region.

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

BackgroundIn recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI).ObjectiveThe aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU).ResultsAn improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis. Results Treatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 μM and 5 μM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers β-galactosidase, γH2Ax and Klotho-beta. Conclusions In conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects. Graphical Abstract

Background: A Special Health Care Need (SHCN) is characterized by any type of physical, mental, sensorial, cognitive, emotional, or developmental condition that requires medical treatment, specialized services, or healthcare interventions. These conditions can negatively impact oral health as SHCN children can hardly cooperate or communicate and experience higher levels of dental fear/anxiety, which interfere with regular appointments. The present narrative review aims to analyze the use of audiovisual (AV) tools in dental setting for the management of SHCN children during dental treatment and to evaluate their effectiveness in anxiety/behavior control from the child, dentist, and care-giver perspectives. This analysis leads to the proposal of a new multi-session model for the behavioral management of SHCN pediatric subjects. Methods: An electronic search on the MEDLINE/Pubmed, Scopus, and Web of Science databases was carried out and through this analysis, a new model was proposed, the “UNISA-Virtual Stepwise Distraction model”, a multi-session workflow combining traditional behavior management and the progressive introduction of AV media to familiarize the SHCN child with dental setting and manage behavior. Results: AV tools helped in most cases to manage SHCN behavior and decreased stress in both the dentist and child during dental treatments. Care-givers also welcomed AV distractors, reporting positive feedback in using them during future treatments. Conclusions: The present narrative review found increasing evidence of the use of AV media for SHCN pediatric subjects as distraction tools during dental treatment. In the majority of the studies, AV tools proved to be effective for the management of anxiety, dental fear, and behavior in dental setting.

IntroductionCarmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy. NEC mortality may be up to 30%–50%. In our study, we compared NEC incidence, symptoms, mortality, and transplant outcome in terms of overall survival (OS) and progression-free survival (PFS) in the BEAM vs. FEAM groups. Furthermore, we compared the cost of hospitalization of patients who did vs. patients who did not experience a NEC episode (NECe).MethodsA total of 191 patients were enrolled in this study (N = 129 and N = 62 were conditioned with BEAM and FEAM, respectively). All patients received bed-side high-resolution ultrasound (US) for NEC diagnosis.Results and discussionNEC incidence and NEC-related mortality were similar in the BEAM and FEAM groups (31% and 40.3%, p = 0.653, and 5% and 8%, p = 0.627, respectively). At a median follow-up of 116 months, no difference was noted between BEAM vs. FEAM groups in terms of OS and PFS (p = 0.181 and p = 0.978, respectively). BEAM appeared equivalent to FEAM in terms of NEC incidence and efficacy. The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos vs. patients NECneg. The cost analysis of NECpos vs. NECneg has been also performed.

The article comments on a research by A. W. Bruckner on the population decline of red coral Corallium rubrum in the Mediterranean area. The main concerns regarding Bruckner's research are outlined including the use of different sampling methodologies, insufficient population data from deep water, and limited sampling data on area and density of colonies. The sampling methods used in assessing Corallium rubrum populations are detailed such as in situ counts, photographs and video. The author's conclusion on changes in size structure and reproductive output is presented.

The recruitment process is a fundamental step in population life cycles that determines survival, population demographic structure, and dynamics. The success of recruitment events repeated over successive years greatly affects the survival of long-lived gorgonian populations. Here, we report the recruitment process of the precious, heavily harvested Mediterranean gorgonian Corallium rubrum (red coral) on both settlement tiles and natural substrates over different Mediterranean areas. Red coral is a gonochoric internal brooder that reproduces in early summer. Lecithotrophic planulae settle 15–30 days after release in semi-dark environments at depths between 15 and 800 m. In autumn, 0.58–0.68 mm-wide recruits can be observed on the vaults of small crevices and caves and on rocky cliffs and boulders. Owing to their small size, there is limited knowledge of C. rubrum recruitment in the field. In this study, we examined the recruitment density and distribution in Canadells (Banyuls sur Mer, France) and Calafuria (Livorno, Italy) and compared these findings with those collected over different Mediterranean areas. Red coral exhibited high recruitment values ranging from 0.43 to 13.19 recruits dm−2. The distribution pattern of recruits, examined at a small spatial scale via nearest-neighbor distance analysis, revealed a significantly higher patch frequency on the natural substrate than on settlement tiles, presumably because of the scarcely available spots of free space on the former substrate, which are crowded by competitor species.

Factors that contribute to food allergenicity is still unknown. To determine food intrinsic properties that contribute to L. vannamei and A. granosa allergenicity or allergy like symptoms this study identify total protein and metal profiles, histamine contents, and protein heat stability. Histamine content is measured colorimetrically. Protein heat-stability is observed with sodium dodecyl sulfate – polyacrylamide gel electrophoresis (SDS-PAGE). Allergy-related metal concentration are determined with Atomic Absorption Spectroscopy (AAS). Fresh L. vannamei and A. granosa contained ~100 and ~25 ppm histamine, respectively. Storage at -20 oC for 3 days relatively did not changed histamine content of both foods. Storage at 4-8 oC for 3 days increased histamine content in L. vannamei, but not in A. granosa. Protein sized

Objective Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. We examine barriers and enablers to BC sampling in three Southeast Asian countries.Design A Theoretical Domains Framework (TDF)-based survey, comprising a case scenario of a patient presenting with community-acquired sepsis and all 14 TDF domains of barriers/enablers to BC sampling.Setting Hospitals in Indonesia, Thailand and Viet Nam, December 2021 to 30 April 2022.Participants 1070 medical doctors and 238 final-year medical students were participated in this study. Half of the respondents were women (n=680, 52%) and most worked in governmental hospitals (n=980, 75.4%).Outcome measures Barriers and enablers to BC sampling.Results The proportion of respondents who answered that they would definitely take BC in the case scenario was highest at 89.8% (273/304) in Thailand, followed by 50.5% (252/499) in Viet Nam and 31.3% (157/501) in Indonesia (p

Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a therapeutic option to cure patients affected by hematologic malignancies. The kinetics and the quality of immune-reconstitution (IR) impact the clinical outcome of h-HSCT and limit the onset of life-threatening Human Cytomegalovirus (HCMV) infection/reactivation. Natural Killer (NK) cells are the first lymphocytes that recover after h-HSCT and they can provide rapid innate immune responses against opportunistic pathogens. By performing a longitudinal single-cell analysis of multiparametric flow-cytometry data, we show here that the persistence at high frequencies of CD158b1b2jneg/NKG2Apos/NKG2Cneg/NKp30pos/NKp46pos (KIRneg) NK cells is associated with HCMV infection/reactivation control. These KIRneg NK cells are “unlicensed”, and are not terminal-differentiated lymphocytes appearing early during IR and mainly belonging to CD56bright/CD16neg and CD56bright/CD16pos subsets. KIRneg NK cells are enriched in oxidative and glucose metabolism pathways, produce interferon-γ, and are endowed with potent antiviral activity against HCMV ex vivo. Decreased frequencies of KIRneg NK cells early during IR are associated with clinically relevant HCMV replication. Taken together, our findings indicate that the prolonged persistence of KIRneg NK cells after h-HSCT could serve as a biomarker to better predict HCMV infection/reactivation. This phenomenon also paves the way to optimize anti-viral immune responses by enriching post-transplant donor lymphocyte infusions with KIRneg NK cells.