Aim
In Italy, the ISPED CARD initiative was launched to measure and improve quality of care in children and adolescents with type 1 diabetes.
Methods
Process and outcome indicators and the related ...information derived from electronic medical records were identified. A network of pediatric diabetes centers was created on a voluntary basis.
Results
Overall, 20 centers provided data on 3284 patients aged < = 18 years. HbA1c was monitored ≥ 2/year in 81.2% of the cases. BMI was monitored ≥ 1/year in 99.0%, lipid profile in 45.3%, and blood pressure in 91.7%. Pubertal status, albuminuria, eye examination, and screening of celiac disease and thyroiditis were underreported. From 2017 to 2021, average HbA1c levels decreased from 7.8 ± 1.2 to 7.6 ± 1.3%, while patients with LDL cholesterol > 100 mg/dl increased from 18.9 to 36.7%. Prevalence of patients with elevated blood pressure and BMI/SDS values also increased. In 2021, 44.7% of patients were treated with the newest basal insulins, while use of regular human insulin had dropped to 7.7%. Use of insulin pump remained stable (37.9%).
Conclusions
This report documents the feasibility of the ISPED CARD initiative and shows lights and shadows in the care provided. Improving care, increasing number of centers, and ameliorating data recording represent future challenges.
American tegumentary leishmaniasis (ATL) is considered a neglected disease, for which an effective vaccine or an efficient diagnosis is not yet available and whose chemotherapeutic arsenal is ...threatened by the emergence of resistance by etiological agents such as Leishmania amazonensis. ATL is endemic in poor countries and has a high incidence in Brazil. Vaccines developed from native parasite fractions have led to the identification of defined antigenic subunits and the development of vaccine adjuvant technology. The purpose of the present study was to develop and compare preparations based on membrane antigens from L. amazonensis, as a biotechnological prototype for the immunoprophylaxis of the disease in a murine experimental model. For this purpose, batches of biodegradable polymeric micro/nanoparticles were produced, characterized and compared with other parasite's antigens in solution. All preparations containing membrane antigens presented low toxicity on murine macrophages. The in vivo evaluation of immunization efficacy was performed against a challenge with L. amazonensis, along with an evaluation of the immune response profile generated in BALB/C mice. The animals were followed for sample processing and quantification of serum-specific cytokines, nitrites and antibodies. The sera of animals immunized with the non-encapsulated antigen formulations showed higher intensities of nitrites and total IgGs. This approach evidenced the importance of the biological studies involving the immune response of the host against the parasite being interconnected and related to the subfractionation of its proteins in the search for more effective vaccine candidates.
•Membrane antigens were encapsulated in a polymeric micro/nanostructed particles with adequate diameters•All preparations containing membrane antigens presented low toxicity on murine macrophages•Non-encapsulated protein antigens showed higher NO and total IgGs serum production than encapsulated ones
Transgenic Balb/c mice expressing the transforming rat HER-2/neu oncogene develop early and multifocal mammary carcinomas. Within the first 5 months of life the tissue-specific expression of ...HER-2/neu causes a progression in all their 10 mammary glands from atypical hyperplasia to invasive carcinoma. It was previously observed that chronic administration of interleukin (IL)-12 increased tumor latency, but every mouse eventually succumbed to multiple carcinomas. A significant improvement in tumor prevention was sought by administering allogeneic mammary carcinoma cells expressing HER-2/neu combined with systemic IL-12. This treatment reduced tumor incidence by 90% and more than doubled mouse lifetime. For the maximum prevention p185(neu) antigen must be expressed by allogeneic cells. IL-12 treatment strongly increased the cell vaccine efficacy. The mammary glands of mice receiving the combined treatment displayed a markedly reduced epithelial cell proliferation, angiogenesis, and HER-2/neu expression, while the few hyperplastic foci were heavily infiltrated by granulocytes, macrophages, and CD8(+) lymphocytes. Specific anti-HER-2/neu antibodies were produced and a nonpolarized activation of CD4(+) and CD8(+) cells secreting IL-4 and interferon (IFN)-gamma were evident. A central role for IFN-gamma in the preventive effect was proven by the lack of efficacy of vaccination in IFN-gamma gene knockout HER-2/neu transgenic Balb/c mice. A possible requirement for IFN-gamma is related to its effect on antibody production, in particular on IgG2a and IgG2b subclasses, that were not induced in IFN-gamma knockout HER-2/neu mice. In conclusion, our data show that an allogeneic HER-2/neu-expressing cell vaccine combined with IL-12 systemic treatment can prevent the onset of genetically determined tumors.
Functional mitral regurgitation (FMR) is a common finding in patients with heart failure (HF), but its effect on outcome is still uncertain, mainly because in previous studies sample sizes were ...relatively small and semiquantitative methods for FMR grading were used.
To evaluate the prognostic value of FMR in patients with HF.
Patients with HF due to ischaemic and non-ischaemic dilated cardiomyopathy (DCM) were retrospectively recruited. The clinical end point was a composite of all-cause mortality and hospitalisation for worsening HF. FMR was quantitatively determined by measuring vena contracta (VC) or effective regurgitant orifice (ERO) or regurgitant volume (RV). Severe FMR was defined as ERO >0.2 cm(2) or RV >30 ml or VC >0.4 cm. Restrictive mitral filling pattern (RMP) was defined as E-wave deceleration time <140 ms. The study population comprised 1256 patients (mean age 67 ± 11; 78% male) with HF due to DCM: 27% had no FMR, 49% mild to moderate FMR and 24% severe FMR. There was a powerful association between severe FMR and prognosis (HR = 2.0, 95% CI 1.5 to 2.6; p<0.0001) after adjustment of left ventricular ejection fraction and RMP. The independent association of severe FMR with prognosis was confirmed in patients with ischaemic DCM (HR = 2.0, 95% CI 1.4 to 2.7; p<0.0001) and non-ischaemic DCM (HR = 1.9, 95% CI 1.3 to 2.9; p = 0.002).
In a large patient population it was shown that a quantitatively defined FMR was strongly associated with the outcome of patients with HF, independently of LV function.
A deflection efficiency of about 61% was observed for 400 GeV/c protons due to channeling, most strongly along the 〈110〉 axis of a bent silicon crystal. It is comparable with the deflection ...efficiency in planar channeling and considerably larger than in the case of the 〈111〉 axis. The measured probability of inelastic nuclear interactions of protons in channeling along the 〈110〉 axis is only about 10% of its amorphous level whereas in channeling along the (110) planes it is about 25%. High efficiency deflection and small beam losses make this axial orientation of a silicon crystal a useful tool for the beam steering of high energy charged particles.
Peripheral T cell lymphomas (PTCL) account for about 12% of lymphoid tumours worldwide. Almost half show such morphological and molecular variability as to hamper any further classification, and to ...justify their inclusion in a waste-basket category termed "not otherwise specified (NOS)". The latter term is used for neoplasms with aggressive presentation, poor response to therapy and dismal prognosis. In contrast to B cell lymphomas, PTCL have been the subject of only a limited number of studies to elucidate their pathobiology and identify novel pharmacological approaches. Herewith, the authors revise the most recent contributions on the subject based on the experience they have gained in the extensive application of microarray technologies. PTCL/NOS are characterised by erratic expression of T cell associated antigens, including CD4 and CD52, which have recently been proposed as targets for ad hoc immunotherapies. PTCL/NOS also show variable Ki-67 marking, with rates >80% heralding a worse prognosis. Gene expression profiling studies have revealed that PTCL/NOS derive from activated T lymphocytes, more often of the CD4+ type, and bear a signature composed of 155 genes and related products that play a pivotal role in cell signalling transduction, proliferation, apoptosis and matrix remodelling. This observation seems to pave the way for the use of innovative drugs such as tyrosine kinase and histone deacetylase inhibitors whose efficacy has been proven in PTCL primary cell cultures. Gene expression profiling also allows better distinction of PTCL/NOS from angioimmunoblastic T cell lymphoma, the latter being characterised by follicular T helper lymphocyte derivation and CXCL13, PD1 and vascular endothelial growth factor expression.
The effect of an atmospheric pressure non-equilibrium plasma on human mesenchymal stem cells was investigated. A dielectric barrier discharge non-equilibrium plasma source driven by two different ...high-voltage pulsed generators was used and cell survival, senescence, proliferation, and differentiation were evaluated. Cells deprived of the culture medium and treated with nanosecond pulsed plasma showed a higher mortality rate, while higher survival and retention of proliferation were observed in cells treated with microsecond pulsed plasma in the presence of the culture medium. While a few treated cells showed the hallmarks of senescence, unexpected delayed apoptosis ensued in cells exposed to plasma-treated medium. The plasma treatment did not change the expression of OCT4, a marker of mesenchymal stem cell differentiation.
The miniature tomato (Solanum lycopersicum) cultivar Micro‐Tom (MT) has become an important platform to investigate plant–pathogen interactions. In the case of the witches' broom disease of Theobroma ...cacao (cacao), the existence of Moniliophthora perniciosa isolates pathogenic to Solanaceae (S‐biotype) may enable the use of MT to circumvent limitations of the cacao host, whereas the availability of a non‐infective cacao C‐biotype allows the evaluation of contrasting responses of MT. Infection of MT by the S‐biotype led to stem swelling and axillary shoot growth to form broom‐like symptoms similar to the biotrophic phase in cacao, but the infected tissues did not progress to necrosis. Conversely, inoculation with the C‐biotype did not cause typical symptoms, but reduced plant height, appearing as a non‐host interaction. Histopathological characterization of the S‐biotype infection of MT by light and electron microscopy indicated limited germ tube penetration, preferentially through wounds at the base of trichomes or actively through the epidermis. No intracellular mycelium was observed, corroborating the lack of the necrotrophic stage of the pathogen. The analysis of gene expression during the interaction between the S‐ or C‐biotype with MT indicated that expression of plant defence‐associated genes differs for kinetics and intensity between a compatible or incompatible M. perniciosa–MT interaction. The pattern of spore germination and low rate of mycelia penetration suggests that the S‐biotype is not a fully adapted tomato pathogen, but possibly a case of broken non‐host resistance, and evidence suggests the occurrence of a non‐host MT response against the C‐biotype.
The main goal of the FAMU experiment is the measurement of the hyperfine splitting (hfs) in the 1S state of muonic hydrogen ΔEhfs (μ - p)1S. The physical process behind this experiment is the ...following: μp are formed in a mixture of hydrogen and a higher-Z gas. When absorbing a photon at resonance-energy ΔEhfs ≈ 0.182 eV, in subsequent collisions with the surrounding H 2 molecules, the μp is quickly de-excited and accelerated by ∼ 2/3 of the excitation energy. The observable is the time distribution of the K-lines X-rays emitted from the μZ formed by muon transfer (μp) + Z → (μZ)* + p, a reaction whose rate depends on the μp kinetic energy. The maximal response, to the tuned laser wavelength, of the time distribution of X-ray from K-lines of the (μZ)* cascade indicate the resonance. During the preparatory phase of the FAMU experiment, several measurements have been performed both to validate the methodology and to prepare the best configuration of target and detectors for the spectroscopic measurement. We present here the crucial study of the energy dependence of the transfer rate from muonic hydrogen to oxygen (Λ μp → μ0 ), precisely measured for the first time.
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