A model of maxilla resection to test new hybrid implants:macroporous titanium and tissue engineering elements

Maxillary bone loss in commonly found in humans, due to bone ageing, tooth loos, periodontal disease and, more severely, to trauma, radiotherapy and tumor resection. Masillofacial reconstructive surgery is a still unmet clinical demand, available therapies include grafting of autologous or heterologous bone tissue and/or the implantation of metallic plates, buy these treatments are still unable to resume form and function. The emrgence of 3D-printing technology applied to metal alloys now allows the manufacturing of customized, patient-tailored prosthetic implants. However, poor bone quiality at the implant site due to ageing or disease still hamper proper osseointegration. By combining Electron Beam Melting metal sintering and tissue engineering, we are developing hybrid maxillofacial implants, wher a metal framework of Ti6Al4V alloy confers both and appropiaate shape and mechanical stabilty, while stem cells and osteogenic molecules stimulate bone growth into the metal framework, thus pormoting osseointegration. We hereby present the in vitro work driving to the development of our hybrid maxillofacial prostheses, as well as the setting up of an in vivo model of complete maxilla full resection, created in order to test the prostheses in a preclinical studyUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Metabolic rate and hypoxia tolerance in Girardinichthys multiradiatus (Pisces: Goodeidae), an endemic fish at high altitude in tropical Mexico

Artículo científico JCR Q1The darkedged splitfin (Amarillo fish), Girardinichthys multiradiatus is a vulnerable endemic fish species inhabiting central Mexico's high altitude Upper Lerma Basin, where aquatic hypoxia is exacerbated by low barometric pressures (lower PO2s), large aquatic oxygen changes, poor aquatic systems management and urban, agricultural and industrial pollution. The respiratory physiology of G. multiradiatus under such challenging conditions is unknown - therefore the main goal of the present study was to determine metabolic rates and hypoxia tolerance to elucidate possible physiological adaptations allowing this fish to survive high altitude and increasingly eutrophic conditions. Fish came from two artificial reservoirs – San Elías and Ex Hacienda - considered refuges for this species. Both reservoirs showed high dial PO2 variation, with hypoxic conditions before midday and after 20:00 h, ~4 h of normoxia (15 kPa) from 16:00–20:00, and ~4 h of hyperoxia (16–33 kPa) from 12:00–16:00. Standard metabolic rate at 20 ± 0.5 °C of larvae from Ex Hacienda was significantly higher than those from San Elías, but these differences disappeared in juveniles and adults. Metabolic rate at 20 ± 0.5 °C for adults was 9.8 ± 0.1 SEM μmol O2/g/h. The metabolic scaling exponent for adults was 0.58 for San Elías fish and 0.83 for Ex Hacienda fish, indicating possible ecological effects on this variable. Post-larval fish in Ex Hacienda and all stages in San Elias site showed considerable hypoxia tolerance, with PCrit mean values ranging from 1.9–3.1 kPa, lower than those of many tropical fish at comparable temperatures. Collectively, these data indicate that G. multiradiatus is well adapted for the hypoxia associated with their high-altitude habitat.CONACyT PRODEP-SEP UAEMé

Effect of the topical administration of corticosteroids and tuberculin pre-sensitisation on the diagnosis of tuberculosis in goats

Background: Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals. In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed. Methods: The animals (n = 151) were distributed into three groups: (1) a group topically treated with corticosteroids 48 h after intradermal tuberculin tests (n = 53); (2) a group pre-sensitised with bovine and avian purified protein derivatives (PPDs) 3 days before the intradermal tuberculin test used for TB diagnosis (n = 48); and (3) a control group (n = 50). All the animals were tested using single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, an interferon-gamma release assay (IGRA) and a P22 ELISA. Results: The number of SIT test reactors was significantly lower in the group treated with corticosteroids when compared to the pre-sensitised (p 0.05). No significant effect was observed on IGRA and P22 ELISA due to corticosteroids administration. Nevertheless, a previous PPD injection affected the IGRA performance in some groups. Conclusions: The application of topical corticosteroid 24 h before reading the SIT and CIT tests can reduce the increase in skin fold thickness and subsequently significantly decrease the number of positive reactors. Corticosteroids used can be detected in hair samples. A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs.This study was funded by the “Analysis of the long-term caprine tuberculosis eradication process and development of diagnostic tests and control measures for its improvement (GoaTBfree-UCM)” Project (PID2019-105155RB-C31, Ministry of Science and Innovation of Spain) and the Ministry of Agriculture, Fisheries and Food of Spain. JO was supported by an FPU contract-fellowship (Formación de Profesorado Universitario) from the Spanish Ministerio de Ciencia, Innovación y Universidades (FPU18/05197).S

Evaluation and use of surveillance system data toward the identification of high-risk areas for potential cholera vaccination: a case study from Niger.

In 2008, Africa accounted for 94% of the cholera cases reported worldwide. Although the World Health Organization currently recommends the oral cholera vaccine in endemic areas for high-risk populations, its use in Sub-Saharan Africa has been limited. Here, we provide the principal results of an evaluation of the cholera surveillance system in the region of Maradi in Niger and an analysis of its data towards identifying high-risk areas for cholera

The Role of Expert Opinion in Projecting Long-Term Survival Outcomes Beyond the Horizon of a Clinical Trial

INTRODUCTION: Clinical trials often have short follow-ups, and long-term outcomes such as survival must be extrapolated. Current extrapolation methods often produce a wide range of survival values. To minimize uncertainty in projections, we developed a novel method that incorporates formally elicited expert opinion in a Bayesian analysis and used it to extrapolate survival in the placebo arm of DAPA-CKD, a phase 3 trial of dapagliflozin in patients with chronic kidney disease (NCT03036150). METHODS: A summary of mortality data from 13 studies that included DAPA-CKD-like populations and training on elicitation were provided to six experts. An elicitation survey was used to gather the experts' 10- and 20-year survival estimates for patients in the placebo arm of DAPA-CKD. These estimates were combined with DAPA-CKD mortality and general population mortality (GPM) data in a Bayesian analysis to extrapolate long-term survival using seven parametric distributions. Results were compared with those from standard frequentist approaches (with and without GPM data) that do not incorporate expert opinion. RESULTS: The group expert-elicited estimate for 20-year survival was 31% (lower estimate, 10%; upper estimate, 40%). In the Bayesian analysis, the 20-year extrapolated survival across the seven distributions was 14.9-39.1%, a range that was 2.4- and 1.6-fold smaller than those produced by the frequentist methods (0.0-56.9% without and 0.0-39.2% with GPM data). CONCLUSIONS: Using expert opinion in a Bayesian analysis provided a robust method for extrapolating long-term survival in the placebo arm of DAPA-CKD. The method could be applied to other populations with limited survival data

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

Differences in cognitive, motivational and contextual variables among under-achieving, normally-achieving, and over-achieving students:a mixed-effects analysis

There are few studies in Spain which analyze the influence of individual, motivational and contextual variables, which might be different between underachieving, normally achieving and overachieving students. Method: A total of 1,398 Spanish high school students participated. Mixed-effects models were used to analyze data. Results: The results showed some evidence of: (a) Partial mediational effect of self-concept on the association between cognitive ability and academic achievement. (b) Higher levels of learning goals in the overachieving group than in the underachieving group, but no differences in achievement and reinforcement goals between groups. (c) Positive effect of learning strategies on attainment, both in the underachieving and the non-underachieving students. (d) Little effect of context variables on academic achievement, both in the underachieving and non-underachieving students. Conclusions: Underachieving students seem to employ all the learning strategies considered to a lesser extent than normally and overachieving students. They also have a lower level of learning goals. On the contrary, overachieving students score more highly than under and normally achieving students in almost all of the above factors.Antecedentes: apenas existen estudios en España que analicen la influencia de variables cognitivas, motivacionales y contextuales capaces de establecer diferencias entre los estudiantes con rendimiento menor, igual y mayor al esperado. Método: participaron 1.398 estudiantes españoles de Educación Secundaria Obligatoria. Se emplearon modelos de efectos mixtos para el análisis de datos. Resultados: los resultados mostraron evidencia de: (a) efecto mediacional parcial del auto-concepto en la asociación de la habilidad cognitiva y el rendimiento académico; (b) mayores niveles de metas de aprendizaje en el grupo de estudiantes con rendimiento mayor al esperado; (c) efecto positivo de las estrategias de aprendizaje sobre el rendimiento en todos los grupos; (d) efecto pequeño de las variables contextuales sobre el rendimiento en todos los grupos. Conclusiones: los estudiantes con rendimiento menor al esperado emplean en menor medida las estrategias de aprendizaje y las metas orientadas al aprendizaje. Por el contrario, los estudiantes con rendimiento mayor al esperado muestran niveles superiores que el resto de grupos en la mayor parte de variables.The present work was supported by the Spanish Ministry of Economy and Competitiveness (Award number: EDU2012-32156) and the Vice Chancellor for Research of the University of Alicante (Award number: GRE11-15). This work has also been developed thanks to an academic stay of the corresponding author at the University of Bristol (Reference of the grant: EEBB-I-15_09943)

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Prevalence of Cryptosporidium oocysts and Giardia cysts in raw and treated sewage sludges

Treated sludge from wastewater treatment plants (WWTPs) is commonly used in agriculture as fertilizers and to amend soils. The most significant health hazard for sewage sludge relates to the wide range of pathogenic microorganisms such as protozoa parasites.The objective of this study was to collect quantitative data on Cryptosporidium oocysts and Giardia cysts in the treated sludge in wastewater treatment facilities in Spain. Sludge from five WWTPs with different stabilization processes has been analysed for the presence of Cryptosporidium and Giardia in the raw sludge and after the sludge treatment. A composting plant (CP) has also been assessed. After a sedimentation step, sludge samples were processed and (oo)cysts were isolated by immunomagnetic separation (IMS) and detected by immunofluorescence assay (IFA). Results obtained in this study showed that Cryptosporidium oocysts and Giardia cysts were present in 26 of the 30 samples (86.6%) of raw sludge samples. In treated sludge samples, (oo)cysts have been observed in all WWTP's analysed (25 samples) with different stabilization treatment (83.3%). Only in samples from the CP no (oo)cysts were detected. This study provides evidence that (oo)cysts are present in sewage sludge-end products from wastewater treatment processes with the negative consequences for public health.We appreciate the financial support provided by Entidad Publica Saneamiento Aguas (EPSAR).Amoros Muñoz, I.; Moreno Trigos, MY.; Reyes-Sosa, MB.; Moreno-Mesonero, L.; Alonso Molina, JL. (2016). Prevalence of Cryptosporidium oocysts and Giardia cysts in raw and treated sewage sludges. Environmental Technology. 37(22):2898-2904. doi:10.1080/09593330.2016.1168486S28982904372

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline