Hyper-IgD and Periodic Fever Syndrome: a New MVK Mutation (p.R277G) Associated with a Severe Phenotype

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM#260920) is a rare recessively-inherited autoinflammatory condition caused bymutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Herewe report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, where as anakinra showed positive responses only at high doses. The p.R277Gmutation here described is a novel missense MVK mutation, and it has been detected in this casewith a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies

A 3D geological model of Campo de Cartagena, SE Spain : Hydrogeological implications

Knowledge and understanding of geologic basins for hydrogeologic purposes requires an accurate 3D geological architecture representation. For model building, surface and subsurface data integration with the interpretation of geophysical survey and lithologic logs is needed. A methodology to reconstruct the geometric architecture of the sedimentary basin and relationships among stratigraphic formations, as well as to define hydrostratigraphic units, has been applied to the Campo de Cartagena Neogene formations. Data analysis included seismic reflection profiles and gravimetric data from oil exploration, electric resistivity surveys and 491 lithologic logs. The 3D model obtained from a close integration of stratigraphic and geophysical data was generated through a computerbased tool. It presents a common framework and a good starting point for hydrogeologic applications

Towed sensors and hydrodynamic model evidence the need to include submarine in coastal lagoons water balance, the Mar Menor example (SE Spain).

The use of radionuclide tracers to determine the submarine groundwater discharges has been used widely but in areas highly anthropized as the Mar Menor surface water tributaries can carry high concentration of Radon, making very difficult to distinguish the radionuclide origin. In this paper a combined approach was applied in the Mar Menor, a towed system was designed to enable the continuous measurement of Radon and Nitrate and a hydrodynamic model was used to establish the influence areas of the surface discharge to the lagoon. The areas were Radon was detected and was out from the area located with the model could be establish as a submarine groundwater discharge point.Peer Reviewe

Development of appropriateness explicit criteria for cataract extraction by phacoemulsification

BACKGROUND: Consensus development techniques were used in the late 1980s to create explicit criteria for the appropriateness of cataract extraction. We developed a new appropriateness of indications tool for cataract following the RAND method. We tested the validity of our panel results. METHODS: Criteria were developed using a modified Delphi panel judgment process. A panel of 12 ophthalmologists was assembled. Ratings were analyzed regarding the level of agreement among panelists. We studied the influence of all variables on the final panel score using linear and logistic regression models. The explicit criteria developed were summarized by classification and regression tree analysis. RESULTS: Of the 765 indications evaluated by the main panel in the second round, 32.9% were found appropriate, 30.1% uncertain, and 37% inappropriate. Agreement was found in 53% of the indications and disagreement in 0.9%. Seven variables were considered to create the indications and divided into three groups: simple cataract, with diabetic retinopathy, or with other ocular pathologies. The preoperative visual acuity in the cataractous eye and visual function were the variables that best explained the panel scoring. The panel results were synthesized and presented in three decision trees. Misclassification error in the decision trees, as compared with the panel original criteria, was 5.3%. CONCLUSION: The parameters tested showed acceptable validity for an evaluation tool. These results support the use of this indication algorithm as a screening tool for assessing the appropriateness of cataract extraction in field studies and for the development of practice guidelines

Long-term Responders after autologous stem cell transplantation in multiple myeloma

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT. Methods: We retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as 'long-term responders' (LTRs). In the non-LTR group, a cohort referred to as 'prolonged responders' (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data. Results: Two hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up

The BRICS in the Global Order: A New Political Agenda?

Regarding the BRICS (Brazil, Russia, India, China and South Africa) it’s important to analyze comparatively the new power cycle in order to understand not only the impact of the world crisis as well as the relationship between the official political discourses and the economic instability. Actually, the trade liberalization and economic interdependence accompanied with an uncertain international system are putting pressure to the BRICS with their own agendas for global order in seeking for a balance and also to regain a new political and economical dynamic for the promotion of new strategies

Granulomas in Dermatopathology: Principal Diagnoses — Part 2

Esta es la segunda parte de una serie dedicada a la patología granulomatosa en la biopsia cutánea. Mientras que en la primera parte hablamos, entre otras, de algunas condiciones metabólicas y tumorales, esta segunda parte abordará fundamentalmente patología infecciosa de diversos tipos, junto con otras condiciones relativamente frecuentes en las consultas de dermatología.Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists

Integrating stakeholders' inputs to co-design climate resilience adaptation measures in Mediterranean areas with conflicts between wetland conservation and intensive agriculture

[EN] Designing sustainable management strategies in groundwater-dependent socio-economic systems in areas with scarce water resources and protected wetlands is a challenging issue. The high vulnerability of these systems to droughts will be exacerbated even further under future climate change (CC) and socio-economic scenarios. A novel integrated bottom-up/top-down approach is used to identify “climate resilient pathways”, from which to co-design adaptation strategies to reduce the impact of potential future CC and socio-economic scenarios. The approach followed two steps (1) the generation of local CC and socio-economic scenarios by downscaling global/regional climate models and (2) the identification and assessment of potential adaptation strategies through an iterative bottom-up/top-down approach. Top-down assessments of the impact of CC have been undertaken by propagating local scenarios within a chain of mathematical models based on expert criteria/assumptions. This allowed us to analyse of the physical vulnerability of the system under different potential CC and socio-economic scenarios by simulating them with a sequential modelling of rainfall–recharge, agriculture, and hydrological processes through a distributed groundwater finite difference model. These model results were discussed with the stakeholders at a first workshop, which aimed to identify potential adaptation strategies. The influence of the adaptation strategies on the future hydrological status was assessed by simulating them through the chain of models. These results were the inputs into the discussions at a second workshop, which aimed to validate and/or improve the results of the first workshop. The methodology was applied in the Upper Guadiana River Basin, where there is a long-standing conflict between wetland conservation and groundwater overexploitation for intensive agriculture. The future horizon 2016–2045 is analysed with the scenarios compatible with the emission scenario RCP4.5. The research has allowed us to conclude that groundwater pumping reduction would be the most robust and effective measure to reduce the impact of CC in the area.This research was partially supported by the research projects SIGLO-AN (RTI2018-101397-B-I00) and SIGLO-PRO (PID2021-128021OB-I00) from the Spanish Ministry of Science, Innovation and Universities (Programa Estatal de ICDCI orientado a los Retos de la Sociedad), the GeoE.171.008-TACTIC Project funded by European Union's Horizon 2020 - Research and Innovation Framework Programme, and the NextGenerationEU Fund through the programme “Fondos de Recuperación”.Peer reviewe