The association between vitamin D binding protein levels and periodontal status: A systematic review.

BACKGROUND AND OBJECTIVES: Vitamin D binding protein (DBP) is biosynthesised in the liver and is predominantly expressed in serum. Its primary role centres on facilitating the systemic transportation of vitamin D and its metabolites, notably 25-hydroxyvitamin D, to specific target tissues where vitamin D exerts its biological functions. Due to the paucity of studies, it is unclear whether there is an association between DBP and periodontal status and thus its potential use as a diagnostic biomarker. Therefore, the aim of the systematic review is to investigate the association between DBP in periodontal disease. METHODS: Two independent reviewers (YD and RG) performed a systematic literature search of English publications using several databases including MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1974 onwards), and Global Health (OVID interface, 1973 onwards). This search strategy enabled the identification of relevant publications and the development of a comprehensive library of studies. Studies were included based on previously agreed eligibility criteria. Of the eight studies included as part of this systematic review, seven were case-control studies and one was a cross-sectional study. The quality assessment was based on the Newcastle-Ottawa Scale (NOS) for case-control studies and the modified NOS for the cross-sectional study. RESULTS: The NOS quality assessment was 'favorable' for 6 included case control studies; and 'fair' for one study. The modified NOS quality assessment for the single cross-sectional study demonstrated a medium risk of bias. The results of the majority of the included studies indicated a statistically significant higher concentration of DBP levels in individuals with periodontitis in comparison to those who were periodontally healthy. This trend held true irrespective of the sampling method employed for the assessment of DBP concentration. CONCLUSION: The results summarised in this systematic review indicate a positive association between DBP and periodontitis. Nonetheless, there is a need for longitudinal, prospective trials, to confirm the use of DBP as a potential biomarker for the diagnosis of periodontitis.

¿Es posible mezclar insulinas en una misma jeringa? / It is possible to mix insulins in the same syringe?

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Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.

AIMS: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS: Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.

Estudio genético preimplantación para aneuploidias: resultados de la transición entre diferentes tecnologías / Preimplantation genetic testing for aneuploidies PGT-A: Results of the transition between different technologies

Resumen OBJETIVO Comunicar los resultados obtenidos del análisis del estudio genético preimplantación para aneuploidias en dos centros de reproducción asistida de México en un periodo de tres años, utilizando dos diferentes técnicas moleculares. MATERIALES Y MÉTODOS Estudio observacional, retrospectivo, en donde se reporta el resultado de blastocistos sometidos a preimplantación para aneuploidias durante 2014-2017, en dos centros de reproducción asistida (Ciudad de México y Guadalajara). RESULTADOS Se analizaron 404 blastocistos de 129 pacientes (edad promedio 39 ± 4 años). Los embriones se dividieron en dos grupos según la técnica aplicada: 76 por a-CGH y 328 por secuenciación de nueva generación. El porcentaje de embriones euploides fue de 33%. Las aneuploidias numéricas fueron las más frecuentes. Hasta la terminación del estudio se habían transferido 69 embriones euploides con tasas de implantación de 78% para secuenciación de nueva generación y de 57% para a-CGH. CONCLUSIONES La tasa de implantación reportada en este estudio fue mayor con el análisis de preimplantación para aneuploidias por secuenciación de nueva generación. Los resultados reportados en nuestra experiencia soportan la necesidad de favorecer una opción de transferencia de embrión único. Es importante reconocer los retos de las nuevas tecnologías y la necesidad de técnicas moleculares más sensibles.

Abstract OBJECTIVE Communicate the results obtained from the analysis of the preimplantation genetic study for aneuploidy in two centers of assisted reproduction in Mexico in a period of three years, using two differentmolecular techniques. MATERIALS AND METHODS Descriptive, retrospective study, which reports the blastocysts PGT-A results, over 2014-2017, in two Fertility Centers (Ciudad de México and Guadalajara). The embryos where divided in two groups by their molecular techniques studied: 76 by a-CGH and 328 by NGS RESULTS We analyzed a total of 404 blastocysts from 129 patients (mean age 39 ± 4 years), with two different molecular techniques: a-CGH and NGS. The euploid embryos percentage was 33%. The numerical aneuploidies were the most frequent. Up to the ending of the study, 69% of the euploid embryos had been transferred. The implantation rates were 78% for those analyzed by NGS and 57% with a-CGH. CONCLUSIONS The implantation rate was bigger with the PGT-A by NGS. Our results reported, supports a single embryo transfer policy. It is important to recognize the challenges of new technologies and the need for more sensitive molecular techniques.

Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.

We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open-label metformin and saxagliptin 5 mg/day for 8-16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open-label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (-0.74% vs. 0.07%), FPG (-27 vs. 10 mg/dL) and BW (-2.1 vs. -0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (≤2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin is a durable, effective and well-tolerated intervention for the treatment of T2D.

Impact of the ENDORSE study results on thromboprophylaxis prescribing patterns in medical patients attending the emergency department.

AIMS: The aim of the study was to evaluate the impact of the ENDORSE study results on thromboprophylaxis prescribing patterns in medical patients attending the Emergency Department (ED) by assessing prescribing appropriateness at admission. METHODS: A cross-sectional, observational, descriptive study was designed and included all adult medical patients admitted from an ED between 20 November 2012 and 26 November 2012 at a large tertiary hospital. Patients to whom anticoagulants were prescribed for therapeutic purposes, patients admitted to Intensive Care Unit or maternity wards were excluded. Prescribing appropriateness was assessed using the Padua Prediction Score (ACCP 2012 guideline) for thromboembolic risk assessment and the NICE model to determine risk of bleeding. The primary end-point was the adequacy of thromboprophylaxis prescribed at the ED according to the ACCP 2012 guideline. RESULTS: A total of 393 patients were examined and 207 patients were included in the study (53.1% were male) with a median age of 75.3 years. The most common diagnosis at admission was related to a respiratory disease (41.1%). In 34.8% of the patients (72 patients), the recommendation of prophylaxis according to ACCP 2012 guideline did not match with the prophylaxis prescribed at admission. Reasons for non-concordance were undertreatment (14.5%) and overtreatment (20.3%). CONCLUSIONS: The adequacy of thromboprophylaxis in high risk patients for VTE has improved compared with the ENDORSE study. However, the percentage of patients with discordant prescriptions remains high. Despite the existence of treatment omissions, this percentage has been overcome by patients overtreated.

Papel y uso de los probióticos en el niño pretérmino y en el lactante / Role and use of probiotics in the pre-term and infant child

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Hospitalizaciones por hipoglucemia grave en pacientes con diabetes mellitus en España / Hospitalizations due to severe hypoglycemia in patients with diabetes mellitus in Spain

Antecedentes y objetivo. Una de las complicaciones terapéuticas más importantes en los pacientes con diabetes mellitus (DM) es la hipoglucemia. Hemos estimado el número de hospitalizaciones por hipoglucemia grave en los pacientes con DM tipo 1 (DM1) y tipo 2 (DM2). Pacientes y métodos. El universo hospitalario se definió a partir del Catálogo Nacional de Hospitales (CNH) de 2007 (últimos datos disponibles), y se incluyeron 260 hospitales generales del Sistema Nacional de Salud. El número de hospitalizaciones por hipoglucemia grave fue extraído del Conjunto Mínimo Básico de Datos (CMBD) para 183 hospitales. Para los 77 restantes se estimó a partir de la información disponible. Resultados. En el año 2007 se produjeron un total de 26.701 (0,82%) hospitalizaciones con hipoglucemia. En los enfermos con DM2 se reportaron 8.242 (0,25%) ingresos como diagnóstico principal y 16.649 (0,51%) como secundario. En los pacientes con DM1 se reportaron 1.157 (0,04%) y 653 (0,02%) ingresos como diagnóstico principal y secundario, respectivamente. La incidencia global en DM2 fue de 1,82 episodios/10.000 habitantes/año, y osciló entre los 1,10 episodios/10.000 habitantes/año en Canarias y los 3,37 episodios en Castilla y León. Conclusiones. La hipoglucemia grave es una causa importante de hospitalización en los pacientes con DM en España, con una gran variabilidad entre CCAA (AU)

Background and objectives One of the most important therapeutic complications in patients with diabetes mellitus (DM) is hypoglycemia. This study has estimated the number of hospitalizations due to severe hypoglycemia in patients with type DM1 and DM2. Patients and methods. The study hospital population was defined using the National Catalogue of Hospitals (CNH) 2007 (last available data), and has included 260 general hospitals of the National Health System. The number of hospitalizations due to severe hypoglycemia was obtained from the Basic Minimum Data Set (BMDS) for the 183 hospitals. For the remaining 77 hospitals, this number was estimated based on the available information. Results. In 2007, there were 26,701 (0.82%) hospitalizations with hypoglycemia. In DM2 patients, 8,242 (0.25%) episodes were reported as primary diagnosis and 16,649 (0.51%) as secondary. In DM1 patients, 1,157 (0.04%) and 653 (0.02%) episodes were reported as primary and secondary diagnosis, respectively. Overall incidence in DM2 was 1.82 episodes/10,000 inhabitants-year, this ranging between 1.10 episodes/10,000 inhabitants-year in the Islas Canarias to 3.37 in Castilla y León. Conclusions. Severe hypoglycemia is an important reason for hospitalization of patients with DM in Spain, there being great variability according to the Autonomous Regions (AU)

Hospitalizations due to severe hypoglycemia in patients with diabetes mellitus in Spain.

BACKGROUND AND OBJECTIVES: One of the most important therapeutic complications in patients with diabetes mellitus (DM) is hypoglycemia. This study has estimated the number of hospitalizations due to severe hypoglycemia in patients with type DM1 and DM2. PATIENTS AND METHODS: The study hospital population was defined using the National Catalogue of Hospitals (CNH) 2007 (last available data), and has included 260 general hospitals of the National Health System. The number of hospitalizations due to severe hypoglycemia was obtained from the Basic Minimum Data Set (BMDS) for the 183 hospitals. For the remaining 77 hospitals, this number was estimated based on the available information. RESULTS: In 2007, there were 26,701 (0.82%) hospitalizations with hypoglycemia. In DM2 patients, 8,242 (0.25%) episodes were reported as primary diagnosis and 16,649 (0.51%) as secondary. In DM1 patients, 1,157 (0.04%) and 653 (0.02%) episodes were reported as primary and secondary diagnosis, respectively. Overall incidence in DM2 was 1.82 episodes/10,000 inhabitants-year, this ranging between 1.10 episodes/10,000 inhabitants-year in the Islas Canarias to 3.37 in Castilla y León. CONCLUSIONS: Severe hypoglycemia is an important reason for hospitalization of patients with DM in Spain, there being great variability according to the Autonomous Regions.

Newly diagnosed adult AML and MPAL patients frequently show clonal residual hematopoiesis.

Adult acute myeloid leukemia (AML) is a highly heterogeneous stem cell malignancy characterized by the clonal expansion of immature myeloid precursors. AML may emerge de novo, following other hematopoietic malignancies or after cytotoxic therapy for other disorders. Here, we investigated the clonal vs reactive nature of residual maturing bone marrow cells in 59 newly diagnosed adult AML and mixed phenotype acute leukemia (MPAL) patients as assessed by interphase fluorescence in situ hybridization analysis of AML and myelodysplastic syndrome-associated cytogenetic alterations and/or the pattern of chromosome X inactivation, in females. In addition, we investigated the potential association between the degree of molecular/genetic involvement of hematopoiesis and coexistence of altered immunophenotypes by flow cytometry. Our results indicate that residual maturing neutrophils, monocytes and nucleated red cell precursors from the great majority of newly diagnosed AML and MPAL cases show a clonal pattern of involvement of residual maturing hematopoietic cells, in association with a greater number of altered immunophenotypes. These findings are consistent with the replacement of normal/reactive hematopoiesis by clonal myelopoiesis and/or erythropoiesis in most newly diagnosed AML and MPAL cases, supporting the notion that in most adults presenting with de novo AML, accumulation of blast cells could occur over a pre-existing clonal hematopoiesis.

Línea estratégica 4: Optimización del tratamiento individualizado / No disponible

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Trichinellosis survey in the wild boar from the Toledo mountains in south-western Spain (2007-2008): molecular characterization of Trichinella isolates by ISSR-PCR.

In Spain, trichinellosis represents a public health problem, with an average of five outbreaks per year, wild boar meat being the main source of infection. A trichinellosis survey (2007-2008 hunting campaign) was carried out on wild boars in the Toledo Mountains (south-western Spain, EU) in the context of a surveillance programme on wildlife diseases. A total of 2216 wild boars from different locations of the region were examined. The examination was carried out by veterinarians in the local abattoir (Matadero Municipal de Toledo). The positive samples were sent to the Department of Parasitology (Facultad de Farmacia, UCM) for experimental isolation and specific identification by inter-simple sequence repeat-polymerase chain reaction (ISSR-PCR). Using this technique we identified 17 isolates as Trichinella spiralis with an electrophoretic profile indistinguishable from the T. spiralis reference strain (ISS48). We confirmed that ISSR-PCR is a robust technique for the molecular identification of Trichinella isolates. According to our results, the prevalence of T. spiralis in wild boars from the Toledo Mountains (>800 m above sea level) during the hunting season was approximately 0.77%. The prevalence of T. spiralis (100% of our observations) is a good example of the persistence of this species in sylvatic conditions (coming from the domestic cycle), if a good wild host is abundant. Our observations confirm the major prevalence of T. spiralis over T. britovi in this region, as well as the risk to human health represented by the consumption of uninspected wild boar meat.

Identification of Spanish Trichinella isolates by ISSR-PCR: intra-specific variability of Trichinella britovi.

In the present work, we investigated genetic variability of the Spanish Trichinella isolates by ISSR-PCR (inter-simple sequence repeat polymerase chain reaction), a technique that is being successfully used to study diversity among related populations. We recovered a total of 43 isolates from different host and geographic localization and identified them by molecular techniques (RAPD and multiplex-PCR) and by Western blot with monoclonal antibodies US5 and US9. Nineteen (44.2%) out of 43 were identified as Trichinella spiralis and 24 (55.8%) as Trichinella britovi. When these samples were analysed by the ISSR technique, all the T. spiralis isolates presented a pattern similar to the T. spiralis ISS116. By contrast, the ISSR-PCR analysis of the isolates identified as T. britovi, showed two different banding profiles compatible with the European T. britovi isolate pattern (ISS2), and the autochthonous Spanish T. britovi isolate (ISS11). Three of these 43 isolates were involved in human outbreaks; the three were identified as T. britovi and showed a pattern similar to the European isolate ISS2. As conclusion, we highlight that an intra-species variability within the Spanish T. britovi isolates analysed was observed, with a predominant group similar to T. britovi ISS2, while T. spiralis group isolates were more homogeneous. No correlations were found between the different ISSR-PCR T. britovi types and the host/geographical origin of the isolates.

Prevalence of Trichinella spp. in North Spain wild fauna and new variety of Trichinella britovi identification.

Trichinella spiralis and Trichinella britovi live in apparent sympatry among wild fauna of the Iberian Peninsula. In the present study 105 Trichinella isolates from wild mammals were typed by inter-sequence simple repeat PCR (ISSR-PCR). All isolates identified as T. spiralis were indistinguishable from the ISS48 reference strain. Among those belonging to T. britovi, four variations were clearly distinguishable; two of them, ISS11 C-76 and ISS86 MON, had been previously detected while the ISS2 reference strain and Trichinella Rioja 3, (MVUL/SP/02/R3) had not been reported before. The newly distinguished genotype of T. britovi was analyzed by ISSR-PCR, multiplex-PCR, UARR sequencing, and single larva cross-breeding with the other T. britovi genotypes including Trichinella T8 (ISS49). Among all of them, the ISS11 and ISS2 isolates were found to be the most frequent. The uniformity found within T. spiralis isolates is consistent with its recent introduction in Iberian Peninsula, whereas the presence of four variations within T. britovi suggests that this species is an endemic species. Orographical diversity of the West-End of Eurasian Region could act to preserve population diversity observed within T. britovi.

A rapid and reliable method for Pb isotopic analysis of peat and lichens by laser ablation-quadrupole-inductively coupled plasma-mass spectrometry for biomonitoring and sample screening.

An analytical protocol for rapid and reliable laser ablation-quadrupole (LA-Q)- and multi-collector (MC-) inductively coupled plasma-mass spectrometry (ICP-MS) analysis of Pb isotope ratios ((207)Pb/(206)Pb and (208)Pb/(206)Pb) in peats and lichens is developed. This technique is applicable to source tracing atmospheric Pb deposition in biomonitoring studies and sample screening. Reference materials and environmental samples were dry ashed and pressed into pellets for introduction by laser ablation. No binder was used to reduce contamination. LA-MC-ICP-MS internal and external precisions were <1.1% and <0.3%, respectively, on both (207)Pb/(206)Pb and (208)Pb/(206)Pb ratios. LA-Q-ICP-MS internal precisions on (207)Pb/(206)Pb and (208)Pb/(206)Pb ratios were lower with values for the different sample sets <14.3% while external precisions were <2.9%. The level of external precision acquired in this study is high enough to distinguish between most modern Pb sources. LA-MC-ICP-MS measurements differed from thermal ionisation mass spectrometry (TIMS) values by 1% or less while the accuracy obtained using LA-Q-ICP-MS compared to solution MC-ICP-MS was 3.1% or better using a run bracketing (RB) mass bias correction method. Sample heterogeneity and detector switching when measuring (208)Pb by Q-ICP-MS are identified as sources of reduced analytical performance.

Removal of interfering elements in ICP-QMS for the determination of Pt, Rh, and Pd by chemically modified sample introduction capillaries.

New on-line methods developed for the determination of Pt, Rh, and Pd by inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS) include separation of elements which might lead to spectral interference in the quadrupole instrument. The fused-silica capillaries generally used for transport of the sample to mu-flow nebulizers have been chemically modified with ion-exchanger compounds to remove interfering elements such as Cu, Pb, or Hf. Characterization of the modification procedures by atomic-force microscopy showed that the quality of the quartz material and the kind of modification had a decisive influence on the yield of surface modification, and thus the exchange capacity of the capillaries.