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1.
Phys Chem Chem Phys ; 19(33): 22555-22563, 2017 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-28809977

RESUMEN

UV Raman and Brillouin light scattering (BLS) experiments have been used in this study to explore the complex phase change behavior occurring in pH-responsive polysaccharide hydrogels as a function of temperature. Due to the different physical quantities measured by the two techniques, the joint analysis of Raman and BLS spectra has provided an unprecedented large-scale characterization of the molecular rearrangements and of the different kinds of hydrophilic and hydrophobic interactions that cooperate to determine the phase transformation observed in these hydrogels during the heating of the gel. As the main result, the analysis of the Raman and BLS spectra showed the existence of a correlation between the local (molecular) and collective properties of the gels during the phase transformation undergone by the system, which is markedly triggered by pH. The joint set of experimental results suggests a model according to which the mechanism of pH dependence in the hydrogels under investigation is dominated by the interactions involving the hydrophobic parts of the polymer skeleton, whereas the solvation process observed under heating of the gels is driven by the progressive distancing of the polymer domains among them, as monitored by the Brillouin sound velocity.

2.
Eur Ann Allergy Clin Immunol ; 49(6): 270-275, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29249135

RESUMEN

SUMMARY: Prevalence of the Anisakis Simplex's (AS) sensitization in children sensitized to Dermatophagoides pteronissynus (DP) is not known, neither it is to which percentage it might be due to cross-reactivity. The primary objective of the present retrospective cross-sectional study is to evaluate the prevalence of sensitization to AS in children sensitized or allergic to DP. Secondary outcomes were the prevalence of cross-reactivity and clinical relevance of the condition. The prevalence of sensitization to AS differs significantly among patients sensitized and not to DP (13.43% vs. 3.80%; p=0.019). The higher prevalence is mainly due to cross-reactivity with Der p10 (OR=8.86; 95% CI=4.33-40.74; p=0.0001). Currently, the sensitization to AS seems to have no clinical relevance in the pediatric population.


Asunto(s)
Anisakiasis/inmunología , Anisakis/inmunología , Antígenos Dermatofagoides/inmunología , Antígenos Helmínticos/inmunología , Proteínas de Artrópodos/inmunología , Reacciones Cruzadas , Dermatophagoides pteronyssinus/inmunología , Hipersensibilidad/inmunología , Tropomiosina/inmunología , Adolescente , Animales , Anisakiasis/diagnóstico , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/epidemiología , Lactante , Italia/epidemiología , Masculino , Prevalencia , Estudios Retrospectivos
3.
Am J Transplant ; 16(1): 235-45, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26317167

RESUMEN

Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas-kidney allografts for T1D recurrence and its risk factors. With long-term follow-up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D-associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor-recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor-recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.


Asunto(s)
Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Rechazo de Injerto/etiología , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias , Adolescente , Adulto , Autoanticuerpos/sangre , Niño , Preescolar , Diabetes Mellitus Tipo 1/cirugía , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Lactante , Pruebas de Función Renal , Masculino , Pronóstico , Recurrencia , Factores de Riesgo , Receptores de Trasplantes , Adulto Joven
4.
Clin Exp Immunol ; 185(1): 33-41, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27029857

RESUMEN

The Network for Pancreatic Organ donors with Diabetes (nPOD) programme was developed in response to an unmet research need for human pancreatic tissue obtained from individuals with type 1 diabetes mellitus and people at increased risk [i.e. autoantibody (AAb)-positive] for the disease. This necessitated the establishment of a type 1 diabetes-specific AAb screening platform for organ procurement organizations (OPOs). Assay protocols for commercially available enzyme-linked immunosorbent assays (elisas) determining AAb against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A) and zinc transporter-8 (ZnT8A) were modified to identify AAb-positive donors within strict time requirements associated with organ donation programmes. These rapid elisas were evaluated by the international islet AAb standardization programme (IASP) and used by OPO laboratories as an adjunct to routine serological tests evaluating donors for organ transplantation. The rapid elisas performed well in three IASPs (2011, 2013, 2015) with 98-100% specificity for all three assays, including sensitivities of 64-82% (GADA), 60-64% (IA-2A) and 62-68% (ZnT8A). Since 2009, nPOD has screened 4442 organ donors by rapid elisa; 250 (5·6%) were identified as positive for one AAb and 14 (0.3%) for multiple AAb with 20 of these cases received by nPOD for follow-up studies (14 GADA+, two IA-2A(+) , four multiple AAb-positive). Rapid screening for type 1 diabetes-associated AAb in organ donors is feasible, allowing for identification of non-diabetic, high-risk individuals and procurement of valuable tissues for natural history studies of this disease.


Asunto(s)
Autoanticuerpos/sangre , Selección de Donante/normas , Ensayo de Inmunoadsorción Enzimática/normas , Donantes de Tejidos/provisión & distribución , Adolescente , Adulto , Área Bajo la Curva , Proteínas de Transporte de Catión/antagonistas & inhibidores , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/inmunología , Niño , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/cirugía , Femenino , Glutamato Descarboxilasa/antagonistas & inhibidores , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/inmunología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/genética , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/inmunología , Riesgo , Sensibilidad y Especificidad , Transportador 8 de Zinc
5.
J Theor Biol ; 377: 25-35, 2015 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-25886821

RESUMEN

Heterogeneity in transmission and stochastic events can play a significant role in shaping the epidemic dynamics of vector-borne infections, especially in the initial phase of an outbreak. In this work, by using multi-type branching process methodologies, we assess how heterogeneities in transmission among a large number of host groups can affect the invasion probabilities of a mosquito-borne disease. We show with both analytical and numerical methods that heterogeneities in transmission can shape the invasion probabilities differently from how they affect the basic reproduction number (R0). In particular, we find that, while R0 always increases with the heterogeneity, the invasion probability after the introduction of infected hosts can decrease with the increase of transmission heterogeneity, even approaching zero when the number of host groups is very large. In addition, we show that the invasion probability via infected vectors is always larger than via infected hosts when heterogeneous transmission is sufficiently high. Our findings suggest that, for multi-species infections (e.g. West Nile fever and Rift Valley fever) or for single-species infections with patchy host distribution, the introduction of primary infected vectors may represent a higher risk for major outbreaks occurrence than introductions of infected hosts.


Asunto(s)
Culicidae/microbiología , Transmisión de Enfermedad Infecciosa , Insectos Vectores/microbiología , Modelos Biológicos , Algoritmos , Animales , Número Básico de Reproducción , Brotes de Enfermedades , Interacciones Huésped-Patógeno , Procesos Estocásticos
6.
Tissue Antigens ; 84(4): 361-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25040682

RESUMEN

Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology.


Asunto(s)
Enfermedad de Addison/genética , Autoanticuerpos/inmunología , Antígeno HLA-A2/genética , Esteroide 21-Hidroxilasa/inmunología , Enfermedad de Addison/inmunología , Adolescente , Adulto , Femenino , Antígeno HLA-A2/inmunología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sudáfrica , Estados Unidos
7.
Neurol Sci ; 35 Suppl 1: 189-93, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24867864

RESUMEN

In recent years research explored different acupuncture stimulation techniques but interest has focused primarily on somatic acupuncture and on a limited number of acupoints. As regards ear Acupuncture (EA) there is still some criticism about the clinical specificity of auricular points/areas representing organs or structures of the body. The aim of this study was to verify through (Functional magnetic resonance imaging) fMRI the hypothesis of EA point specificity using two auricular points having different topographical locations and clinical significance. Six healthy volunteers underwent two experimental fMRI sessions: the first was dedicated to the stimulation of Thumb Auricular Acupoint (TAA) and the second to the stimulation of Brain Stem Auricular Acupoint (BSAA). The stimulation of the needle placed in the TAA of the left ear produced an increase in activation bilaterally in the parietal operculum, region of the secondary somatosensory area SII. Stimulation of the needle placed in the BSAA of the left ear showed a pattern that largely overlapped regions belonging to the pain matrix, as shown to be involved in previous somatic acupuncture studies but with local differences in the left amygdala, anterior cingulate cortex, and cerebellum. The differences in activation patterns between TAA and BSAA stimulation support the specificity of the two acupoints. Moreover, the peculiarity of the regions involved in BSAA stimulation compared to those involved in the pain matrix, is in accordance with the therapeutic indications of this acupoint that include head pain, dizziness and vertigo. Our results provide preliminary evidence on the specificity of two auricular acupoints; further research is warranted by means of fMRI both in healthy volunteers and in patients carrying neurological/psychiatric syndromes.


Asunto(s)
Puntos de Acupuntura , Acupuntura Auricular , Encéfalo/fisiología , Adulto , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Actividad Motora/fisiología , Dimensión del Dolor , Estimulación Física , Proyectos Piloto , Pulgar/fisiología , Percepción del Tacto/fisiología
8.
Diabet Med ; 30(2): 135-46, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23181718

RESUMEN

It is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic ß-cells, eventually leading to ß-cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune-mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen-specific responses in patients with recent onset diabetes and subjects with pre-diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new-onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and ß-cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re-evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of ß-cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms.


Asunto(s)
Autoinmunidad , Diabetes Mellitus Tipo 1/etiología , Hiperglucemia/etiología , Células Secretoras de Insulina/inmunología , Estado Prediabético/etiología , Autoantígenos/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Dieta/efectos adversos , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hiperglucemia/genética , Hiperglucemia/inmunología , Intestinos/microbiología , Masculino , Metagenoma , Estado Prediabético/genética , Estado Prediabético/inmunología , Factores de Riesgo
9.
Nat Genet ; 15(3): 293-7, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9054945

RESUMEN

Type 1, or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease associated with loss of tolerance to several pancreatic islet cell molecules, including insulin, glutamic acid decarboxylase (GAD), ICA69 and the tyrosine phosphatase IA-2 (refs 1-3). Among several predisposing loci, IDDM2 maps to the insulin gene (INS) VNTR (variable number of tandem repeats) minisatellite on chromosome 11p15 (refs 4-9). Allelic variation at this VNTR locus correlates with steady-state levels of INS mRNA in pancreas and transfected rodent cell lines, but it is difficult to reconcile the association of lower INS mRNA levels in the pancreas with class III VNTRs that are dominantly protective from IDDM. We show that during fetal development and childhood, mRNAs for insulin and other islet cell autoantigens (GAD, ICA69, IA-2) are expressed at low levels in the human thymus. Critically, we also detect proinsulin and insulin protein. VNTR alleles correlate with differential INS mRNA expression in the thymus where, in contrast to the pancreas, protective class III VNTRs are associated with higher steady-state levels of INS mRNA expression. This finding provides a plausible explanation for the dominant protective effect of class III VNTRs, and suggests that diabetes susceptibility and resistance associated with IDDM2 may derive from the VNTR influence on INS transcription in the thymus. Higher levels of (pro)insulin in the thymus may promote negative selection (deletion) of insulin-specific T-lymphocytes which play a critical role in the pathogenesis of type-1 diabetes.


Asunto(s)
Cromosomas Humanos Par 11 , Diabetes Mellitus Tipo 1/genética , Regulación del Desarrollo de la Expresión Génica , Insulina/biosíntesis , Insulina/genética , Repeticiones de Minisatélite , Timo/metabolismo , Transcripción Genética , Envejecimiento , Alelos , Niño , Preescolar , Mapeo Cromosómico , Cartilla de ADN , Susceptibilidad a Enfermedades , Desarrollo Embrionario y Fetal , Variación Genética , Humanos , Lactante , Recién Nacido , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , Proinsulina/biosíntesis , ARN Mensajero/biosíntesis , Timo/embriología , Timo/crecimiento & desarrollo
10.
Nat Genet ; 17(3): 350-2, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9354805

RESUMEN

The IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis. The mode of action of IDDM2 is complicated, however, by parent-of-origin effects and possible allelic heterogeneity within the two defined allele classes. We have now analysed transmission of specific VNTR alleles in 1,316 families and demonstrate that a particular class I allele does not predispose to disease when paternally inherited, suggestive of polymorphic imprinting. But this paternal effect is observed only when the father's untransmitted allele is a class III. This allelic interaction is reminiscent of epigenetic phenomena observed in plants (for example, paramutation; ref. 17) and in yeast (for example, trans-inactivation; ref. 18). If untransmitted chromosomes can have functional effects on the biological properties of transmitted chromosomes, the implications for human genetics and disease are potentially considerable.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Insulina/genética , Alelos , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Variación Genética , Genética de Población , Homocigoto , Humanos , Masculino
11.
Neuromuscul Disord ; 33(2): 145-147, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36628839

RESUMEN

AChR and MuSK double positive myasthenia gravis has been rarely reported. Generally, it occurs in children and adults after thymectomy or immunotherapy. Furthermore, in a few patients with bulbar or respiratory involvement, MuSK antibodies might be detected after clinical deterioration. We report a man with a very late onset myasthenia gravis (86-year-old) and the coexistence of both antibodies at the time of the diagnosis. Despite the presence of MuSK antibodies, he manifested no bulbar symptoms and had a favorable clinical outcome. However, side effects related to low dose pyridostigmine were evident. Hence, double positivity can also occur in elderly and in more benign forms of myasthenia gravis. Other cases of AChR and MuSK double positive myasthenia gravis could allow a better definition of this condition.


Asunto(s)
Miastenia Gravis , Receptores Colinérgicos , Adulto , Masculino , Niño , Humanos , Anciano , Anciano de 80 o más Años , Proteínas Tirosina Quinasas Receptoras , Autoanticuerpos , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Timectomía
13.
Am J Transplant ; 12(12): 3363-76, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22946986

RESUMEN

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.


Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Trasplante de Páncreas , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Femenino , Supervivencia de Injerto/efectos de los fármacos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Trasplante Homólogo , Adulto Joven
14.
Epidemiol Infect ; 139(1): 68-79, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20546633

RESUMEN

We describe the real-time modelling analysis conducted in Italy during the early phases of the 2009 A/H1N1v influenza pandemic in order to estimate the impact of the pandemic and of the related mitigation measures implemented. Results are presented along with a comparison with epidemiological surveillance data which subsequently became available. Simulated epidemics were fitted to the estimated number of influenza-like syndromes collected within the Italian sentinel surveillance systems and showed good agreement with the timing of the observed epidemic. On the basis of the model predictions, we estimated the underreporting factor of the influenza surveillance system to be in the range 3·3-3·7 depending on the scenario considered. Model prediction suggested that the epidemic would peak in early November. These predictions have proved to be a valuable support for public health policy-makers in planning interventions for mitigating the spread of the pandemic.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/prevención & control , Pandemias/prevención & control , Humanos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Italia/epidemiología , Modelos Biológicos
15.
Proc Math Phys Eng Sci ; 477(2253): 20210027, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35153578

RESUMEN

The COVID-19 epidemic is the latest in a long list of pandemics that have affected humankind in the last century. In this paper, we propose a novel mathematical epidemiological model named SUIHTER from the names of the seven compartments that it comprises: susceptible uninfected individuals (S), undetected (both asymptomatic and symptomatic) infected (U), isolated infected (I), hospitalized (H), threatened (T), extinct (E) and recovered (R). A suitable parameter calibration that is based on the combined use of the least-squares method and the Markov chain Monte Carlo method is proposed with the aim of reproducing the past history of the epidemic in Italy, which surfaced in late February and is still ongoing to date, and of validating SUIHTER in terms of its predicting capabilities. A distinctive feature of the new model is that it allows a one-to-one calibration strategy between the model compartments and the data that are made available daily by the Italian Civil Protection Department. The new model is then applied to the analysis of the Italian epidemic with emphasis on the second outbreak, which emerged in autumn 2020. In particular, we show that the epidemiological model SUIHTER can be suitably used in a predictive manner to perform scenario analysis at a national level.

16.
Diabetologia ; 53(4): 690-8, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20062967

RESUMEN

AIMS/HYPOTHESIS: Childhood diabetes is thought to usually result from autoimmune beta cell destruction (type 1A) with eventual total loss of beta cells. Analysis of C-peptide in children characterised at diabetes onset for autoantibodies shows heterogeneous preservation of insulin secretion in long-standing diabetes. The aim of this study was to characterise the pancreases of childhood-onset diabetes in order to define the pathological basis of this heterogeneity. METHODS: We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements. RESULTS: Pancreases from the majority of cadaveric donors contained only insulin-deficient islets (14 of 20). The remaining six patients (30%) had numerous insulin-positive cells within at least some islets, with two different histological patterns. Pattern A (which we would associate with type 1A diabetes) had lobular retention of areas with 'abnormal' beta cells producing the apoptosis inhibitor survivin and HLA class I. In pattern B, 100% of all islets contained normal-appearing but quantitatively reduced beta cells without survivin or HLA class I. CONCLUSIONS/INTERPRETATION: Our data demonstrate that C-peptide secretion in long-standing diabetic patients can be explained by two different patterns of beta cell survival,possibly reflecting different subsets of type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/patología , Células Secretoras de Insulina/patología , Páncreas/patología , Caracteres Sexuales , Adolescente , Adulto , Edad de Inicio , Autoanticuerpos/sangre , Péptido C/sangre , Niño , Preescolar , Diabetes Mellitus Tipo 1/inmunología , Femenino , Antígenos HLA-DR , Prueba de Histocompatibilidad , Humanos , Hiperinsulinismo/patología , Masculino , Persona de Mediana Edad , Donantes de Tejidos
17.
Genes Immun ; 10 Suppl 1: S121-7, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19956109

RESUMEN

Candidate gene studies have long been the principal method for identification of susceptibility genes for type I diabetes (T1D), resulting in the discovery of HLA, INS, PTPN22, CTLA4, and IL2RA. However, many of the initial studies that relied on this strategy were largely underpowered, because of the limitations in genomic information and genotyping technology, as well as the limited size of available cohorts. The Type I Diabetes Genetic Consortium (T1DGC) has established resources to re-evaluate earlier reported genes associated with T1D, using its collection of 2298 Caucasian affected sib-pair families (with 11 159 individuals). A total of 382 single-nucleotide polymorphisms (SNPs) located in 21 T1D candidate genes were selected for this study and genotyped in duplicate on two platforms, Illumina and Sequenom. The genes were chosen based on published literature as having been either 'confirmed' (replicated) or not (candidates). This study showed several important features of genetic association studies. First, it showed the major impact of small rates of genotyping errors on association statistics. Second, it confirmed associations at INS, PTPN22, IL2RA, IFIH1 (earlier confirmed genes), and CTLA4 (earlier confirmed, with distinct SNPs) loci. Third, it did not find evidence for an association with T1D at SUMO4, despite confirmed association in Asian populations, suggesting the potential for population-specific gene effects. Fourth, at PTPN22, there was evidence for a novel contribution to T1D risk, independent of the replicated effect of the R620W variant. Fifth, among the candidate genes selected for replication, the association of TCF7-P19T with T1D was newly replicated in this study. In summary, this study was able to replicate some genetic effects, reject others, and provide suggestions of association with several of the other candidate genes in stratified analyses (age at onset, HLA status, population of origin). These results have generated additional interesting functional hypotheses that will require further replication in independent cohorts.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Selección Genética , Población Blanca/genética , Familia , Genotipo , Humanos
18.
Scand J Immunol ; 70(5): 439-46, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19874548

RESUMEN

Insulin is a critical autoantigen for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. About 80% of NOD females and 30-40% of NOD males develop diabetes. However, Insulin2 (Ins2) knockout NOD mice develop autoimmune diabetes with complete penetrance in both sexes, at an earlier age, and have stronger autoimmune responses to insulin. The severe diabetes phenotype observed in NOD-Ins2-/- mice suggests that lack of Ins2 expression in the thymus may compromise immunological tolerance to insulin. Insulin is a prototypical tissue specific antigen (TSA) for which tolerance is dependent on expression in thymus and peripheral lymphoid tissues. TSA are naturally expressed by medullary thymic epithelial cells (mTEC), stromal cells in peripheral lymphoid tissues and bone marrow (BM)-derived cells, mainly CD11c(+) dendritic cells. The natural expression of TSA by mTEC and stromal cells has been shown to contribute to self-tolerance. However, it is unclear whether this also applies to BM-derived cells naturally expressing TSA. To address this question, we created BM chimeras and investigated whether reintroducing Ins2 expression solely by NOD BM-derived cells delays diabetes development in NOD-Ins2-/- mice. On follow-up, NOD-Ins2-/- mice receiving Ins2-expressing NOD BM cells developed diabetes at similar rates of those receiving NOD-Ins2-/- BM cells. Diabetes developed in 64% of NOD recipients transplanted with NOD BM and in 47% of NOD mice transplanted with NOD-Ins2-/- BM (P = ns). Thus, NOD-Ins2-/- BM did not worsen diabetes in NOD recipients and Ins2 expression by NOD BM-derived cells did not delay diabetes development in NOD-Ins2-/- mice.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Tolerancia Inmunológica , Insulina/genética , Insulina/inmunología , Animales , Células de la Médula Ósea/inmunología , Femenino , Masculino , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética
20.
Am J Transplant ; 8(6): 1262-74, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18444924

RESUMEN

To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 +/- 2113 IEQ/kg) followed by high doses of donor HSC (4.3 +/- 1.9 x 10(6) HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFalpha antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 +/- 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 +/- 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 +/- 0.48%), highly reduced at 1-year (0.20 +/- 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.


Asunto(s)
Quimerismo , Diabetes Mellitus Tipo 1/cirugía , Trasplante de Células Madre Hematopoyéticas , Trasplante de Islotes Pancreáticos/inmunología , Tolerancia al Trasplante/inmunología , Adulto , Antígenos CD34/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Trasplante Homólogo
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