Resultado funcional y mortalidad en pacientes ancianos con amputación mayor de extremidad inferior / Functional results and mortality in elderly patients with major lower limb amputation

Introducción y objetivos: los objetivos de este trabajo han sido conocer qué factores influyen en la recupera ción funcional de los pacientes ancianos que sufren una amputación mayor de una extremidad inferior (AMeI) de etiología vascular y analizar la recuperación de la marcha y de la mortalidad al año de la amputación. Material y métodos: estudio longitudinal observacional de los pacientes mayores de 70 años valorados por el servicio de rehabilitación tras una AMeI desde el 1 enero de 2019 hasta el 1 enero de 2021. Se recogieron las siguientes variables: edad, sexo, etiología, índice de masa corporal, comorbilidad (escala de Charlson), independencia en las AVd básicas (índice de Barthel) y capacidad de marcha (FAC) previas. Al año se analizaron la capacidad de marcha y la mortalidad. Resultados: el estudio se realizó en 45 pacientes con una edad media de 80,3 años (el 64,3 % varones). Todos fueron de etiología vascular. el nivel de amputación fue supracondíleo en 31 pacientes e infracondíleo en 14. Se protetizaron 13. Al año solo caminaban 5 pacientes y habían fallecido 21. Las variables relacionadas con la posibilidad de rehabilitación-protetización fueron: presentar menos comorbilidad (p = 0,004) y tener una mayor independencia funcional y de marcha previa a la amputación (p = 0,000), al igual que las relacionadas con la no mortalidad, con p = 0,005 y p = 0,017 (p = 0,013), respectivamente. Conclusión: la mejor situación funcional y clínica previa a la amputación son los factores más importantes tanto para la posibilidad de rehabilitación protésica como para la supervivencia de nuestros ancianos amputados.(AU)

Introduction and objectives: the objectives of this work have been to know what factors influence in thefunctional recovery of elderly patients who suffer a major lower limb amputation (SMA) of vascular etiology andto analyze the recovery of gait and mortality one year after the amputation. Material and methods: longitudinal observational study of patients older than 70 years assessed by the Reha-bilitation Service after SMA from January 1, 2019 to January 1, 2021. The following variables were collected: Age, sex, etiology, body mass index, comorbidity (Charlson scale), independence in basic ADL (Barthel index) and previous walking capacity (FAC). One year later, walking ability and mortality. Results: the study was conducted in 45 patients with a mean age of 80.3 years, 64.3 % male. All were of vascularetiology. The level of amputation was: supracondylar 31 and infracondylar 14. After a year, only 5 patients werewalking and 21 had died. The variables related to the possibility of rehabilitation-fitting were: having less comorbidity (p = 0.004) as well as having greater functional and gait independence prior to amputation (p = 0.000), as well as those related to nomortality, with a (p = 0.005) and (p = 0.017) (p = 0.013) respectively. Conclusion: the best functional and clinical situation prior to amputation are the most important factors both forthe possibility of prosthetic rehabilitation and for the survival of our elderly amputees.(AU)

Competition among public good providers for donor rewards.

We present experimental evidence for decision settings where public good providers compete for endogenous rewards which are donations (transfers) offered by outside donors. Donors receive benefits from public good provision but cannot provide the good themselves. The performance of three competition mechanisms is examined in relation to the level of public good provision and transfers offered by donors. In addition to a contest where transfers received by public good providers are proportional to effort, we study two contests with exclusion from transfers, namely a winner-takes-all and a loser-gets-nothing. We compare behavior in these three decision settings to the default setting of no-contest (no-transfers). Results for this novel decision environment with endogenous transfers show that donors offer transfers (contest prizes) at similar levels across contests and contributions to the public good are not significantly different in the three contests settings, but are consistently and significantly higher in all contests compared to the setting with no-transfers. Initially, the winner-takes-all setting leads to a significantly higher increase in public good contributions compared to the other two contests; but this difference diminishes across decision rounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-022-09766-7.

Multi-event capture-recapture models estimate the diagnostic performance of serological tests for myxoma and rabbit haemorrhagic disease viruses in the absence of reference samples.

Estimation of the diagnostic performance of serological tests often relies on another test assumed as a reference or on samples of known infection status, yet both are seldom available for emerging pathogens in wildlife. Longitudinal disease serological data can be analysed through multi-event capture-mark-recapture (MECMR) models accounting for the uncertainty in state assignment, allowing us to estimate epidemiological parameters such as incidence and mortality. We hypothesized that by estimating the uncertainty in state assignment, MECMR models estimate the diagnostic performance of serological tests for rabbit haemorrhagic disease virus (RHDV) and myxoma virus (MYXV). We evaluated this hypothesis on longitudinal serological data of three tests of RHDV and one test of MYXV in two populations of the European rabbit (Oryctolagus cuniculus algirus). First, we selected the optimal cut-off threshold for each test using finite mixture models, a reference method not relying on reference tests or samples. Second, we used MECMR models to compare the diagnostic sensitivity (Se) and specificity (Sp) of the three tests for RHDV. Third, we compared the estimates of diagnostic performance by MECMR and finite mixture models across a range of cut-off values. The MECMR models showed that the RHDV test employing GI.2 antigens (Se: 100%) outperformed two tests employing GI.1 antigens (Se: 21.7% ± 8.6% and 8.7% ± 5.9%). At their selected cut-offs (2.0 for RHDV GI.2 and 2.4 for MYXV), the estimates of Se and Sp were concordant between the MECMR and finite mixture models. Over the duration of the study (May 2018 to September 2020), the monthly survival of European rabbits seropositive for MYXV was significantly higher than that of seronegative rabbits (82.7% ± 4.9% versus 61.5% ± 12.7%) at the non-fenced site. We conclude that MECMR models can reliably estimate the diagnostic performance of serological tests for RHDV and MYXV in European rabbits. This conclusion could extend to other diagnostic tests and host-pathogen systems. Longitudinal disease surveillance data analysed through MECMR models allow the validation of diagnostic tests for emerging pathogens in novel host species while simultaneously estimating epidemiological parameters.

Comparison of Biological Features of Wild European Rabbit Mesenchymal Stem Cells Derived from Different Tissues.

Although the European rabbit is an "endangered" species and a notorious biological model, the analysis and comparative characterization of new tissue sources of rabbit mesenchymal stem cells (rMSCs) have not been well addressed. Here, we report for the first time the isolation and characterization of rMSCs derived from an animal belonging to a natural rabbit population within the native region of the species. New rMSC lines were isolated from different tissues: oral mucosa (rOM-MSC), dermal skin (rDS-MSC), subcutaneous adipose tissue (rSCA-MSC), ovarian adipose tissue (rOA-MSC), oviduct (rO-MSC), and mammary gland (rMG-MSC). The six rMSC lines showed plastic adhesion with fibroblast-like morphology and were all shown to be positive for CD44 and CD29 expression (characteristic markers of MSCs), and negative for CD34 or CD45 expression. In terms of pluripotency features, all rMSC lines expressed NANOG, OCT4, and SOX2. Furthermore, all rMSC lines cultured under osteogenic, chondrogenic, and adipogenic conditions showed differentiation capacity. In conclusion, this study describes the isolation and characterization of new rabbit cell lines from different tissue origins, with a clear mesenchymal pattern. We show that rMSC do not exhibit differences in terms of morphological features, expression of the cell surface, and intracellular markers of pluripotency and in vitro differentiation capacities, attributable to their tissue of origin.

Development and Evaluation of a Duplex Lateral Flow Assay for the Detection and Differentiation between Rabbit Haemorrhagic Disease Virus Lagovirus europaeus/GI.1 and /GI.2.

Rabbit Haemorrhagic Disease Virus 2 (RHDV2, recently named Lagovirus europaeus/GI.2) was first reported in France in 2010 and has spread globally since then, replacing most of the circulating former RHDV (genotype GI.1) in many countries. The detection and differentiation of both genotypes is of crucial importance for the surveillance of the disease. In this article, a duplex lateral flow assay (LFA) for antigen detection is described and evaluated, providing the first description of a quick and easy-to-use test that allows for the simultaneous detection and differentiation of RHDV genotypes GI.1 and GI.2. A panel of GI.1- or GI.2-infected and non-infected rabbit liver samples and liver exudates (136 samples) was analysed, obtaining a total sensitivity of 94.4% and specificity of 100%. These data confirm that the developed duplex LFA can be used as a reliable diagnostic test for RHD surveillance, especially in farms and the field.

Immunogenicity of Multi-Target Chimeric RHDV Virus-Like Particles Delivering Foreign B-Cell Epitopes.

The rabbit hemorrhagic disease virus (RHDV) vaccine platform is a nanoparticle composed of 180 copies of the viral capsid protein, VP60, self-assembled into virus-like particles (VLPs). RHDV VLPs are able to accept the simultaneous incorporation of target epitopes at different insertion sites. The resulting chimeric RHDV VLPs displaying immunogenic foreign antigens have been shown to induce specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes in the mouse and pig models. In this study, we explored whether RHDV-based engineered VLPs can be developed as efficient multivalent vaccines co-delivering different foreign B-cell antigens. We generated bivalent chimeric RHDV VLPs displaying two model B-cell epitopes at different surface-exposed insertion sites, as well as the corresponding monovalent chimeric VLPs. The immunogenic potential of the bivalent chimeric VLPs versus the monovalent constructs was assessed in the mouse model. We found that the bivalent chimeric VLPs elicited a strong and balanced antibody response towards the two target epitopes tested, although slight reductions were observed in the levels of specific serum antibody titers induced by bivalent chimeric VLPs as compared with the corresponding monovalent constructs. These results suggest that RHDV VLPs could represent a promising platform for the development of efficient multivalent vaccines.

Substitution of social sustainability concerns under the Covid-19 pandemic.

Think tanks and political leaders have raised concerns about the implications that the Covid-19 response and reconstruction might have on other social objectives that were setting the international agenda before the Covid-19 pandemic. We present evidence for eight consecutive weeks during April-May 2020 for Austria, testing the extent to which Covid-19 concerns substitute other social concerns such as the climate crisis or the protection of vulnerable sectors of the society. We measure behavior in a simple donation task where participants receive €3 that they can distribute between themselves and a list of charitable organizations, which vary between treatments. We consider initially a list of eight charities, including a broad set of social concerns. Results show that introducing the WHO Covid-19 Solidarity Response Fund significantly reduces the sum of donations to the original eight charities. This derives from two effects: First, introducing the Covid-19 Solidarity Response Fund does not significantly change aggregate donations. Second, results point to a high support to the WHO Covid-19 Fund. Overall, our results indicate that donations to diverse social concerns are partially substituted by donations to the Covid-19 fund; yet, this substitution does not fully replace all other social concerns. Results are robust to a 10-fold increase in endowment, with decisions made over €30.

Long Term Effects of the COVID-19 Pandemic on Social Concerns.

While some local, temporary past crises have boosted overall charitable donations, there have been concerns about potential substitution effects that the Covid-19 pandemic might have on other social objectives, such as tackling climate change and reducing inequality. We present results from a donation experiment (n = 1, 762), with data collected between April 2020 and January 2021. We combine data from (i) an online donation experiment, (ii) an extended questionnaire including perceptions, actions, and motives on the Covid-19 pandemic, the climate crisis, and poverty, as well as charitable behavior and (iii) epidemiological data. The experimental results show that donations to diverse social concerns are partially substituted by donations to the Covid-19 fund; yet, this substitution does not fully replace all other social concerns. Over time we observe no systematic trend in charitable donations. In regards to the determinants of individual donations, we observe that women donate more, people taking actions against Covid-19 and against poverty donate more, while those fearing risks from poverty donate less. In addition, we observe that the population under consideration is sensitive to the needs of others, enhancing total donations for higher Covid-19 incidence. For donations to each charity, we find that trusting a given charitable organization is the strongest explanatory factor of donations. JEL: L3, D64, Q54, I3, D9.

An Adenovirus Vector Expressing FMDV RNA Polymerase Combined with a Chimeric VLP Harboring a Neutralizing Epitope as a Prime Boost Strategy to Induce FMDV-Specific Humoral and Cellular Responses.

Foot and mouth disease is a highly contagious disease affecting cattle, sheep, and swine among other cloven-hoofed animals that imposes serious economic burden by its direct effects on farm productivity as well as on commerce of farmed produce. Vaccination using inactivated viral strains of the different serotypes is an effective protective measure, but has several drawbacks including a lack of cross protection and the perils associated with the large-scale growth of infectious virus. We have previously developed chimeric virus-like particles (VLPs) bearing an FMDV epitope which induced strong specific humoral responses in vaccinated pigs but conferred only partial protection against homologous challenge. While this and other FMD vaccines under development mostly rely on the induction of neutralizing responses, it is thought that induction of specific T-cell responses might improve both cross protective efficacy as well as duration of immunity. Therefore, we here describe the development of a recombinant adenovirus expressing the highly conserved nonstructural FMDV 3D protein as well as its capacity to induce specific T-cell responses in a murine model. We further describe the generation of an FMDV serotype C-specific chimeric VLP and analyze the immunogenicity of two different prime-boost strategies combining both elements in mice. This combination can effectively induce both humoral and cellular FMDV-specific responses eliciting high titers of ELISA and neutralizing antibodies anti-FMDV as well as a high frequency of IFNγ-secreting cells. These results provide the basis for further testing of this anti FMD vaccination strategy in cattle or pig, two of the most relevant natural host of this pathogen.

Testing a Deep Learning Algorithm for Detection of Diabetic Retinopathy in a Spanish Diabetic Population and with MESSIDOR Database.

BACKGROUND: The aim of the present study was to test our deep learning algorithm (DLA) by reading the retinographies. METHODS: We tested our DLA built on convolutional neural networks in 14,186 retinographies from our population and 1200 images extracted from MESSIDOR. The retinal images were graded both by the DLA and independently by four retina specialists. Results of the DLA were compared according to accuracy (ACC), sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC), distinguishing between identification of any type of DR (any DR) and referable DR (RDR). RESULTS: The results of testing the DLA for identifying any DR in our population were: ACC = 99.75, S = 97.92, SP = 99.91, PPV = 98.92, NPV = 99.82, and AUC = 0.983. When detecting RDR, the results were: ACC = 99.66, S = 96.7, SP = 99.92, PPV = 99.07, NPV = 99.71, and AUC = 0.988. The results of testing the DLA for identifying any DR with MESSIDOR were: ACC = 94.79, S = 97.32, SP = 94.57, PPV = 60.93, NPV = 99.75, and AUC = 0.959. When detecting RDR, the results were: ACC = 98.78, S = 94.64, SP = 99.14, PPV = 90.54, NPV = 99.53, and AUC = 0.968. CONCLUSIONS: Our DLA performed well, both in detecting any DR and in classifying those eyes with RDR in a sample of retinographies of type 2 DM patients in our population and the MESSIDOR database.

Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses.

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140-158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21-35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.

Rendimiento de las pruebas complementarias en el estudio de pacientes con dolor abdominal crónico / Usefulness of complementary test in the study of patients with chronic abdominal pain

Introducción: El dolor abdominal crónico (DAC) en la infancia es un motivo de consulta frecuente que afecta a la vida familiar, y en ocasiones precisa realización de pruebas complementarias. El objetivo fue realizar el análisis cualitativo, cuantitativo y económico de las pruebas que se solicitan.Pacientes y métodos: Estudio observacional, prospectivo y multicéntrico, incluyendo pacientes entre 4-15 años con DAC. Se diferenciaron 2 grupos: orgánico y funcional. Se recogieron las siguientes variables: clínicas, pruebas complementarias y su coste.Resultados: Se incluyeron 235 niños con DAC (edad media 9,7±2,7 años). Un 79% resultaron trastornos funcionales y un 21% orgánicos. Casi la mitad de los pacientes presentaba algún tipo de síntoma o signo de alarma, pero solo la clínica miccional se asoció con organicidad. La ecografía abdominal, estudio de parásitos en heces, test de hidrógeno espirado y gastroscopia son las que más se asociaron con enfermedad orgánica. Existía una diferencia apreciable entre el coste de las pruebas según cada centro. El gasto económico total fue de 52.490,8euros, siendo 195euros por paciente para los funcionales y 306euros para los orgánicos.Conclusiones: Los síntomas y signos de alarma en el DAC son frecuentes, pero poco específicos. La ecografía abdominal y el estudio de parásitos podrían ser pruebas útiles de primer nivel por su inocuidad para diferenciar TO de TDAF. La gastroscopia y el test de hidrógeno espirado fueron las pruebas más discriminativas de organicidad. El coste económico invertido en pruebas para la orientación diagnóstica del DAC de origen funcional es elevado. (AU)

Introduction: Chronic abdominal pain (CAP) in children is a symptom that frequently leads to a visit to the paediatrician, which affects family life and occasionally requires the need to perform diagnostic studies (DS). The objective was to carry out a qualitative, quantitative, and economic analysis on the tests requested.Patients and methods: An observational, prospective and multicentre study was conducted that included children between 4-15 years old affected by CAP. The difference between organic and functional disorders was taken into account. The following variables were collected: history, warning signs and symptoms, DS, and the cost of these.Results: The study included 235 children with CAP (Age; mean 9.7±2.7 SD). The large majority (79%) were functional disorders and 21% organic disorders. Almost half of the patients had some warning sign or symptom, but urinary symptoms were only associated with organic disorders. The abdominal ultrasound, faecal parasites, breath test, and endoscopy were the most associated with organic disorders. There was a difference between the costs of the DS according to each centre. The total economic cost was 52,490.80 euros, with 195 euros per patient for functional disorders and 306 euros for organic disorders.Conclusion: Signs and symptoms of alarm in CAP were very frequent, but had low discriminative capacity. The abdominal ultrasound and faecal parasites are innocuous DS, and could be useful as a first level study. The endoscopy and the breath test were the most discriminative of organic disease. The economic cost of DS arising from the diagnosis of exclusion in CAP was high. (AU)

Continuous intravenous anakinra for treating severe secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome in critically ill children.

The cytokine storm of secondary haemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) can cause life-threatening multiorgan failure. Interleukin-1 (IL-1) receptor blockade with anakinra can be effective in the management of sHLH/MAS. Subcutaneous (SC) dosing regimens are widely described; however, intravenous (IV) dosing is advantageous where time-critical intervention is vital and where SC oedema and/or hypoperfusion limits absorption. We review three critically ill children (aged 9, 11 and 17) with sHLH and rapidly progressive multiorgan dysfunction, successfully treated with continuous IV anakinra infusion. This case series significantly enhances the incipient knowledge regarding the safety and efficacy of IV anakinra for life-threatening sHLH.

Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health.

Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, e.g., to cold chain transport, handling and storage. In this context, subunit vaccines where the essential antigenic traits (but not the entire pathogen) are presented in rationally designed fashion have emerged as an attractive alternative to conventional ones. In particular, this includes the option of fully synthetic peptide vaccines able to mimic well-defined B- and T-cell epitopes from the infectious agent and to induce protection against it. Although, in general, linear peptides have been associated to low immunogenicity and partial protection, there are several strategies to address such issues. In this review, we report the progress towards the development of peptide-based vaccines against foot-and-mouth disease (FMD) a highly transmissible, economically devastating animal disease. Starting from preliminary experiments using single linear B-cell epitopes, recent research has led to more complex and successful second-generation vaccines featuring peptide dendrimers containing multiple copies of B- and T-cell epitopes against FMD virus or classical swine fever virus (CSFV). The usefulness of this strategy to prevent other animal and human diseases is discussed.

Chimeric RHDV Virus-Like Particles Displaying Foot-and-Mouth Disease Virus Epitopes Elicit Neutralizing Antibodies and Confer Partial Protection in Pigs.

Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.

Usefulness of complementary test in the study of patients with chronic abdominal pain.

INTRODUCTION: Chronic abdominal pain (CAP) in children is a symptom that frequently leads to a visit to the paediatrician, which affects family life and occasionally requires the need to perform diagnostic studies (DS). The objective was to carry out a qualitative, quantitative, and economic analysis on the tests requested. MATERIAL AND METHODS: An observational, prospective and multicentre study was conducted that included children between 4-15 years old affected by CAP. The difference between organic and functional disorders was taken into account. The following variables were collected: history, warning signs and symptoms, DS, and the cost of these. RESULTS: The study included 235 children with CAP (Age; mean 9.7 ± 2.7 SD). The large majority (79%) were functional disorders and 21% organic disorders. Almost half of the patients had some warning sign or symptom, but urinary symptoms were only associated with organic disorders. The abdominal ultrasound, faecal parasites, breath test, and endoscopy were the most associated with organic disorders. There was a difference between the costs of the DS according to each centre. The total economic cost was 52,490.80 euros, with 195 euros per patient for functional disorders and 306 euros for organic disorders. CONCLUSION: Signs and symptoms of alarm in CAP were very frequent, but had low discriminative capacity. The abdominal ultrasound and faecal parasites are innocuous DS, and could be useful as a first level study. The endoscopy and the breath test were the most discriminative of organic disease. The economic cost of DS arising from the diagnosis of exclusion in CAP was high.

Validation of a Diagnostic Support System for Diabetic Retinopathy Based on Clinical Parameters.

Purpose: To validate a clinical decision support system (CDSS) that estimates risk of diabetic retinopathy (DR) and to personalize screening protocols in type 2 diabetes mellitus (T2DM) patients. Methods: We utilized a CDSS based on a fuzzy random forest, integrated by fuzzy decision trees with the following variables: current age, sex, arterial hypertension, diabetes duration and treatment, HbA1c, glomerular filtration rate, microalbuminuria, and body mass index. Validation was made using the electronic health records of a sample of 101,802 T2DM patients. Diagnosis was made by retinal photographs, according to EURODIAB guidelines and the International Diabetic Retinopathy Classification. Results: The prevalence of DR was 19,759 patients (19.98%). Results yielded 16,593 (16.31%) true positives, 72,617 (71.33%) true negatives, 3165 (3.1%) false positives, and 9427 (9.26%) false negatives, with an accuracy of 0.876 (95% confidence interval [CI], 0.858-0.886), sensitivity of 84% (95% CI, 83.46-84.49), specificity of 88.5% (95% CI, 88.29-88.72), positive predictive value of 63.8% (95% CI, 63.18-64.35), negative predictive value of 95.8% (95% CI, 95.68-95.96), positive likelihood ratio of 7.30, and negative likelihood ratio of 0.18. The type 1 error was 0.115, and the type 2 error was 0.16. Conclusions: We confirmed a good prediction rate for DR from a representative sample of T2DM in our population. Furthermore, the CDSS was able to offer an individualized screening protocol for each patient according to the calculated risk confidence value. Translational Relevance: Results from this study will help to establish a novel strategy for personalizing screening for DR according to patient risk factors.

Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides.

Dendrimer peptides are promising vaccine candidates against the foot-and-mouth disease virus (FMDV). Several B-cell epitope (B2T) dendrimers, harboring a major FMDV antigenic B-cell site in VP1 protein, are covalently linked to heterotypic T-cell epitopes from 3A and/or 3D proteins, and elicited consistent levels of neutralizing antibodies and IFN-γ-producing cells in pigs. To address the contribution of the highly polymorphic nature of the porcine MHC (SLA, swine leukocyte antigen) on the immunogenicity of B2T dendrimers, low-resolution (Lr) haplotyping was performed. We looked for possible correlations between particular Lr haplotypes with neutralizing antibody and T-cell responses induced by B2T peptides. In this study, 63 pigs immunized with B2T dendrimers and 10 non-immunized (control) animals are analyzed. The results reveal a robust significant correlation between SLA class-II Lr haplotypes and the T-cell response. Similar correlations of T-cell response with SLA class-I Lr haplotypes, and between B-cell antibody response and SLA class-I and SLA class-II Lr haplotypes, were only found when the sample was reduced to animals with Lr haplotypes represented more than once. These results support the contribution of SLA class-II restricted T-cells to the magnitude of the T-cell response and to the antibody response evoked by the B2T dendrimers, being of potential value for peptide vaccine design against FMDV.

Immunogenicity of a Dendrimer B2T Peptide Harboring a T-Cell Epitope From FMDV Non-structural Protein 3D.

Synthetic dendrimer peptides are a promising strategy to develop new FMD vaccines. A dendrimer peptide, termed B2T-3A, which harbors two copies of the major FMDV antigenic B-cell site [VP1 (140-158)], covalently linked to a heterotypic T-cell from the non-structural protein 3A [3A (21-35)], has been shown to protect pigs against viral challenge. Interestingly, the modular design of this dendrimer peptide allows modifications aimed at improving its immunogenicity, such as the replacement of the T-cell epitope moiety. Here, we report that a dendrimer peptide, B2T-3D, harboring a T-cell epitope from FMDV 3D protein [3D (56-70)], when inoculated in pigs, elicited consistent levels of neutralizing antibodies and high frequencies of IFN-γ-producing cells upon in vitro recall with the homologous dendrimers, both responses being similar to those evoked by B2T-3A. Lymphocytes from B2T-3A-immunized pigs were in vitro-stimulated by T-3A peptide and to a lesser extent by B-peptide, while those from B2T-3D- immunized animals preferentially recognized the T-3D peptide, suggesting that this epitope is a potent inducer of IFN-γ producing-cells. These results extend the repertoire of T-cell epitopes efficiently recognized by swine lymphocytes and open the possibility of using T-3D to enhance the immunogenicity and the protection conferred by B2T-dendrimers.