How heat waves, ozone and sunlight hours affect endocrine and metabolic diseases emergency admissions? A case study in the region of Madrid (Spain).

BACKGROUND: Studies which analyse the joint effect of acoustic or chemical air pollution variables and different meteorological variables on neuroendocrine disease are practically nonexistent. This study therefore sought to analyse the impact of air pollutants and environmental meteorological variables on daily unscheduled admissions due to endocrine and metabolic diseases in the Madrid Region from January 01, 2013 to December 31, 2018. MATERIAL AND METHODS: We conducted a longitudinal, retrospective, ecological study of daily time series analysed by Poisson regression, with emergency neuroendocrine-disease admissions in the Madrid Region as the dependent variable. The independent variables were: mean daily concentrations of PM10, PM2.5, NO2 and O3; acoustic pollution; maximum and minimum daily temperatures; hours of sunlight; relative humidity; wind speed; and air pressure above sea level. Estimators of the statistically significant variables were used to calculate the relative risks (RRs). RESULTS: A statistically significant association was found between the increase in temperatures in heat waves, RR: 1.123 95% CI (1.001-1.018), and the number of emergency admissions, making it the main risk factor. An association between a decrease in sunlight and an increase in hospital admissions, RR: 1.005 95% CI (1.002 1.008), was likewise observed. Similarly, ozone, in the form of mean daily concentrations in excess of 44 µg/m3, had an impact on admissions due to neuroendocrine disease, RR: 1.010 95% CI (1.007-1.035). The breakdown by sex showed that in the case of women, NO2 was also a risk factor, RR: 1.021 95% CI (1.007-1.035). CONCLUSION: The results obtained in this study serve to identify risk factors for this disease, such as extreme temperatures in heat waves, O3 or NO2. The robust association found between the decrease in sunlight and increase in hospital admissions due to neuroendocrine disease serves to spotlight an environmental factor which has received scant attention in public health until now.

Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases.

BACKGROUND: Panniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports. OBJECTIVE: This report describes the clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis. METHODS: In each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow-up were also collected. RESULTS: Of the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late-stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T-helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD-123-positive plasmacytoid dendritic cells in the involved fat lobule. CONCLUSION: Panniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic-pathologic correlation.

Antiferromagnetic vs. non-magnetic ε phase of solid oxygen. Periodic density functional theory studies using a localized atomic basis set and the role of exact exchange.

The question of the non-magnetic (NM) vs. antiferromagnetic (AF) nature of the ε phase of solid oxygen is a matter of great interest and continuing debate. In particular, it has been proposed that the ε phase is actually composed of two phases, a low-pressure AF ε1 phase and a higher pressure NM ε0 phase [Crespo et al., Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 10427]. We address this problem through periodic spin-restricted and spin-polarized Kohn-Sham density functional theory calculations at pressures from 10 to 50 GPa using calibrated GGA and hybrid exchange-correlation functionals with Gaussian atomic basis sets. The two possible configurations for the antiferromagnetic (AF1 and AF2) coupling of the 0 ≤ S ≤ 1 O2 molecules in the (O2)4 unit cell were studied. Full enthalpy-driven geometry optimizations of the (O2)4 unit cells were done to study the pressure evolution of the enthalpy difference between the non-magnetic and both antiferromagnetic structures. We also address the evolution of structural parameters and the spin-per-molecule vs. pressure. We find that the spin-less solution becomes more stable than both AF structures above 50 GPa and, crucially, the spin-less solution yields lattice parameters in much better agreement with experimental data at all pressures than the AF structures. The optimized AF2 broken-symmetry structures lead to large errors of the a and b lattice parameters when compared with experiments. The results for the NM model are in much better agreement with the experimental data than those found for both AF models and are consistent with a completely non-magnetic (O2)4 unit cell for the low-pressure regime of the ε phase.

A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.

STUDY QUESTION: Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress? SUMMARY ANSWER: Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress. WHAT IS KNOWN ALREADY: Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive. STUDY DESIGN, SIZE, DURATION: The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded. MAIN RESULTS AND ROLE OF CHANCE: Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the antioxidant enzyme, GPX5. Our results indicate that an 8 week pretreatment of Gpx5 KO mice with the antioxidant formulation provided complete protection of sperm DNA against oxidative damage. In mouse models of scrotal heat stress, only 35% (19/54) of female mice became pregnant resulting in 169 fetuses with 18% fetal resorption (30/169). This is in contrast to the antioxidant pretreated group where 74% (42/57) of female mice became pregnant, resulting in 427 fetuses with 9% fetal resorption (38/427). In both animal models the protection provided by the novel antioxidant was statistically significant (P < 0.01 for the reduction of 8OHdG in the spermatozoa of Gpx5 KO mice and P < 0.05 for increase in fertility in the scrotal heat stress model). LIMITATIONS, REASONS FOR CAUTION: It was not possible to determine the exact level of antioxidant consumption for each mouse during the treatment period. WIDER IMPLICATIONS OF THE FINDINGS: Recent clinical studies confirm moderate to severe sperm DNA damage in about 60% of all men visiting IVF centers and in about 80% of men diagnosed with idiopathic male infertility. Our results, if confirmed in humans, will impact clinical fertility practice because they support the concept of using an efficacious antioxidant supplementation as a preconception therapy, in order to optimize fertilization rates, help to maintain a healthy pregnancy and limit the mutational load carried by children. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Clermont Université and the University of Madrid. P.G. is the Managing Director of CellOxess LLC, which has a commercial interest in the detection and resolution of oxidative stress. A.M. and A.P. are employees of CellOxess, LLC. J.R.D., A.G.-A. and R.J.A. are honorary members of the CellOxess advisory board.

Does the menopausal status of female gynecologists affect their prescription of menopausal hormone therapy?

OBJECTIVE: To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT). METHODS: Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use. RESULTS: A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%). CONCLUSION: Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.

Yeasts isolated from figs (Ficus carica L.) as biocontrol agents of postharvest fruit diseases.

Fresh fruit is highly perishable during postharvest life, mainly due to fungal growth. Thus, fungal control is an important goal for the fruit industry. In this work, a selection of antagonistic yeasts isolated from fig and breba crops were screened in vitro. The isolated yeasts were challenged with three moulds isolated from decayed figs and breba crops, identified as Penicillium expansum M639 and Cladosporium cladosporioides M310 and M624, and pathogenic moulds Botrytis cinerea CECT20518 and Monilia laxa CA1 from culture collections. Two yeast isolates, Hanseniaspora opuntiae L479 and Metschnikowia pulcherrima L672, were selected for their ability to inhibit the growth of aforementioned moulds. These yeasts reduced the radial growth of moulds on PDA by between 45.23% and 66.09%. Antagonistic activity was associated with the interaction of live yeast cells with moulds. M. pulcherrima L672 apparently parasitised C. cladosporioides isolates. In addition, challenges were assayed using wounded apples and nectarines, with significant reductions in percent infection and lesion size for all moulds tested. To our knowledge, this is the first report identifying H. opuntiae as an antagonist against different pathogenic moulds.

Band separation and electric field prediction in square Bravais-Moiré photonic crystals.

In this study, we address three key challenges in photonic crystals: modeling of isolated flat bands, electric field prediction, and band separation in dispersion relations. Using twisted square Bravais lattices at specific angles, we create Bravais-Moiré photonic crystals exhibiting unique characteristics. These include band pairing and parallelism in certain Brillouin zones, enabling predictable electric field behavior and identification of isolated, flat band pairs within extensive band gaps. We apply advanced Shape theory-based classification methods for precise band separation, offering significant contributions to photonics research and light manipulation applications.

On the stability of the cuboid singlet (S2)4 supermolecule: benchmark ab initio studies.

We report high level ab initio supermolecular calculations for the cuboid structure of the disulfur tetramer, (S2)4. Accurate geometries and interaction energies with respect to 4S2 ((3)Σg (-)) were obtained using four different methods, Möller-Plesset perturbation theory (MP2), complete-active-space SCF (CASSCF) + complete active space second-order perturbation (CASPT2), RCCSD(T), and a hybrid CASPT2(singlet-nonet)∕RCCSD(T)-nonet approach with systematic sequences of augmented correlation-consistent basis sets extrapolated to the complete basis set limit. Unlike the van der Waals-like (O2)4 cluster, (S2)4 is found to be much more chemically bound. Our best estimate of the dissociation energy to four S2 molecules is 65 kcal∕mol including the counterpoise correction and an intermolecular distance of 2.74 Å. The singlet ground state of (S2)4 is much less multiconfigurational than that of (O2)4 van der Waals complex, which allows a reliable CCSD(T) description of the singlet potential energy surface of the supermolecule around its equilibrium geometry. The electron pair localization function clearly reveals electron pairing between the S2 units in the complex at the ROHF and the CASSCF∕aug-cc-pVTZ levels. Vibrational analysis at the MP2∕cc-pV(D,T,Q)Z,aug-cc-pVTZ levels yield stable cuboid structures; however, at the CCSD∕aug-cc-pV(D,T)Z levels this analysis reveals a transition state with one imaginary frequency. Thus, further multireference-based studies with large basis sets are required to reliably settle the stability issue for this supermolecular sulfur species.

Type II diabetes mellitus and menopause: a multinational study.

BACKGROUND: Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. OBJECTIVES: To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. METHODS: A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. RESULTS: The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confidence interval (CI) 3.47-5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22-1.94), hormonal therapy (OR 1.46; 95% CI 1.11-1.92), ≥ 50 years of age (OR 1.48; 95% CI 1.17-1.86), overweight or obese (OR 1.47; 95% CI 1.15-1.89), and waist circumference ≥ 88 cm (OR 1.32; 95% CI 1.06-1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35-0.87), alcohol (OR 0.73; 95% CI 0.54-0.98) and living in cities > 2500 meters above sea level (OR 0.70; 95% CI 0.53-0.91) or with high temperatures (OR 0.67; 95% CI 0.51-0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. CONCLUSION: Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.

Sex-specific embryonic origin of postnatal phenotypic variability.

Preimplantation developmental plasticity has evolved in order to offer the best chances of survival under changing environments. Conversely, environmental conditions experienced in early life can dramatically influence neonatal and adult biology, which may result in detrimental long-term effects. Several studies have shown that small size at birth, which is associated with a greater risk of metabolic syndrome, is largely determined before the formation of the blastocysts because 70%-80% of variation in bodyweight at birth has neither a genetic nor environmental component. In addition, it has been reported that adult bodyweight is programmed by energy-dependent process during the pronuclear stage in the mouse. Although the early embryo has a high developmental plasticity and adapts and survives to adverse environmental conditions, this adaptation may have adverse consequences and there is strong evidence that in vitro culture can be a risk factor for abnormal fetal outcomes in animals systems, with growing data suggesting that a similar link may be apparent for humans. In this context, male and female preimplantation embryos display sex-specific transcriptional and epigenetic regulation, which, in the case of bovine blastocysts, expands to one-third of the transcripts detected through microarray analysis. This sex-specific bias may convert the otherwise buffered stochastic variability in developmental networks in a sex-determined response to the environmental hazard. It has been widely reported that environment can affect preimplantation development in a sex-specific manner, resulting in either a short-term sex ratio adjustment or in long-term sex-specific effects on adult health. The present article reviews current knowledge about the natural phenotypic variation caused by epigenetic mechanisms and the mechanisms modulating sex-specific changes in phenotype during early embryo development resulting in sex ratio adjustments or detrimental sex-specific consequences for adult health. Understanding the natural embryo sexual dimorphism for programming trajectories will help understand the early mechanisms of response to environmental insults.

Menopausal symptoms appear before the menopause and persist 5 years beyond: a detailed analysis of a multinational study.

OBJECTIVE: Few Latin American studies have described menopausal symptoms in detail by means of a standardized assessment tool. The objective of this study was to assess the prevalence and severity of menopausal symptoms and their impact over quality of life among mid-aged Latin American women. METHOD: In this cross-sectional study, 8373 otherwise healthy women aged 40-59 years from 12 Latin American countries were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. Menopause status (pre-, peri- and postmenopausal) was defined according to the criteria of the Stages of Reproductive Aging Workshop. RESULTS: Of all the studied women, 90.9% had at least one menopausal symptom (complaint) that they rated. Muscle and joint discomfort, physical and mental exhaustion and depressive mood were highly prevalent and rated as severe-very severe (scores of 3 and 4), at a higher rate than vasomotor symptoms (15.6%, 13.8% and 13.7% vs. 9.6%, respectively). Of premenopausal women (40-44 years), 77.0% reported at least one rated complaint, with 12.9% displaying MRS scores defined as severe (> 16). The latter rate increased to 26.4% in perimenopausal, 31.6% in early postmenopausal and 29.9% among late postmenopausal women. As measured with the MRS, the presence of hot flushes increased the risk of impairment of overall quality of life in both premenopausal (odds ratio 12.67; 95% confidence interval 9.53-16.83) and peri/postmenopausal women (odds ratio 9.37; 95% confidence interval 7.85-11.19). CONCLUSION: In this large, mid-aged, female Latin American series, muscle/joint discomfort and psychological symptoms were the most prevalent and severely rated menopausal symptoms. The symptoms appear early in the premenopause, significantly impair quality of life and persist 5 years beyond the menopause.

Simultaneous electrochemical immunosensing of relevant cytokines to diagnose and track cancer and autoimmune diseases.

This work reports the first dual magnetic beads (MBs) assisted immunoplatform for the simultaneous determination of BAFF (B cell activation factor) and APRIL (a proliferation-induced ligand), two cytokines related to immunity and tumour invasion, growth and metastasis. The electrochemical immunoplatform involves sandwich-type immunoassays implemented on magnetic microparticles functionalized with neutravidin (NA-MBs) or carboxylic groups (HOOC-MBs), and amperometric detection (Eapp =  - 0.20 V vs. Ag pseudo-reference electrode) at screen-printed dual carbon electrodes (SPdCE) using the H2O2/hydroquinone (HQ) system. The developed immunosensors provide improved sensitivity, with LOD values of 0.33 and 16.4 pg mL-1 for BAFF and APRIL, respectively, and much shorter assay time that those claimed for ELISA kits and allow their simultaneous determination. The dual immunosensor permits discrimination between healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) or colorectal cancer (CRC) through the determination of both cytokines in 100-times diluted human sera with results in agreement with those provided by the individual ELISA methodologies.

Blood glucose control and quality of health care in non-insulin-treated patients with Type 2 diabetes in Spain: a retrospective and cross-sectional observational study.

AIMS: To assess blood glucose control and quality of health care provided to non-insulin-treated patients with Type 2 diabetes mellitus in routine clinical practice in Spain. METHODS: In this observational, retrospective, cross-sectional study, patients were grouped as either having good or suboptimal blood glucose control according to International Diabetes Federation or American Diabetes Association HbA(1c) goals. Clinical and socio-demographic data and compliance with the main standard level of care recommendations of the International Diabetes Federation were recorded during a routine visit. Correlates of glucose control were analysed by logistic regression. RESULTS: Many patients were grouped as having suboptimal control under International Diabetes Federation (61.9%) or American Diabetes Association (45.0%) criteria. The mean number of accomplished International Diabetes Federation recommendations (7.3 out of 11) was higher for endocrinologists (than for internists or primary care physicians), and significantly more patients under their care were in the good glucose control group (than with primary care physicians). More recommendations were associated with blood glucose control using International Diabetes Federation than American Diabetes Association criteria, demanding higher quality of health care for achieving stricter goals. Some recommendations were poorly observed, particularly those concerning patients' education on diabetes, the prompt prescription of effective treatments and monitoring of complications. Diabetes complications were associated with being in the suboptimal control group. Patients' education on diabetes and HbA(1c) monitoring were associated with being in the good control group. CONCLUSIONS: These results demonstrate the need for improvement in the management of patients with non-insulin-treated Type 2 diabetes in actual clinical practice in Spain. Such improvement would entail a stricter adherence to International Diabetes Federation recommendations.

Precursors of Reading Performance and Double- and Triple-Deficit Risks in Spanish.

Early literacy skills serve as the best precursors of reading success and risk indicators of the double deficit and triple deficit hypotheses according to the spelling consistency of languages. Our study analyzes the predictive value of phonological awareness, naming speed, and orthographic skills for early reading in Spanish. Participants included 362 Spanish children aged 4 to 5 years. We used data analysis to examine the relationships between these precursors and fluency through a structural equation model and investigated the risk indicators of poor reading performance according to the double deficit and triple deficit hypotheses using binary logistic analysis. Our research delimits a model for the Spanish language that emphasizes the predictive value of phonological awareness, letter-naming fluency, and knowledge of graphemes in early reading. Letter-naming fluency is the best precursor to early reading experiences, and poor early reading performance in children is explained by deficits in phonological awareness, naming speed, and visual orientation. Our findings confirm the risk indicators of the triple deficit hypothesis in the early learning of reading in Spanish.

Dicke and Fano-Andreev reflections in a triple quantum-dot system.

This article studies quantum interference effects and their influence on the electronic transport through a parallel triple quantum-dot system coupled to normal and superconducting leads in the linear response and non-equilibrium regime. We model the system by a triple impurity Anderson Hamiltonian including the Coulomb intra-dot correlations in all quantum-dots. Using the non-equilibrium Green's function formalism, we calculate the Andreev conductance and the transmittance for energies within the superconductor gap. Our results show that the Andreev reflection spectra, both in the presence and absence of Coulomb interaction, reveal Fano and Dicke-like resonances in analogy to the Fano and Dicke effects in atomic physics. As one of the main results, we obtain that the charge shows abrupt changes due to the Dicke effect.

Diagnosis and management of immunodeficiencies in adults by allergologists.

Primary immunodeficiencies (PIDs) are genetic diseases that cause alterations in the immune response and occur with an increased rate of infection, allergy, autoimmune disorders, and cancer. They affect adults and children, and the diagnostic delay, morbidity, effect on quality of life, and socioeconomic impact are important. Therapy (gamma-globulin substitution in most cases) is highly effective. We examine adult PIDs and their clinical presentation and provide a sequential and directed framework for their diagnosis. Finally, we present a brief review of the most important adult PIDs, common variable immunodeficiency, including diagnosis, pathogenesis, clinical signs, and disease management.

Enlightening the advancements in electrochemical bioanalysis for the diagnosis of Alzheimer's disease and other neurodegenerative disorders.

Neurodegenerative disorders (NDD), and particularly Alzheimer's disease (AD), are one of the greatest challenges facing our current medicine and society because of its increasing incidence and the high burden imposed both on patients' families and health systems. Despite this, their accurate diagnosis, mostly conducted by cerebrospinal fluid (CSF) analysis or neuroimaging techniques, costly, time-consuming, and unaffordable for most of the population, remains a complex task. In this situation, electrochemical biosensors are flourishing as promising alternative tools for the simple, fast, and low-cost diagnosis of NDD/AD. This review article provides the relevant clinical details of NDD/AD along with the closely related genetic (genetic mutations, polymorphisms of ApoE and specific miRNAs) and proteomic (amyloid-ß peptides, total and phosphorylated tau protein) biomarkers circulating mostly in CSF. In addition, the article systematically enlightens a general view of the electrochemical affinity biosensors (mostly aptasensors and immunosensors) reported in the past two years for the determination of such biomarkers. The different developed strategies, analytical performances and applications are comprehensively discussed. Recent advancements in signal amplification methodologies involving smart designs and the use of nanomaterials and rational surface chemistries, as well as the challenges that must be struggled and the prospects in electrochemical affinity biosensing to bring more accessibility to NDD/AD diagnosis, prognosis, and follow-up, are also pointed out.

Label-free detection of DNA mutations by SPR: application to the early detection of inherited breast cancer.

A screening analysis of DNA hybridization and the presence of DNA mutations using an surface plasmon resonance (SPR) biosensor is shown. The influence of lateral and vertical spacers, as well as several hybridization conditions, was studied to optimize the differentiation between fully complementary and mismatched DNA strands. Our results demonstrated that SPR biosensors were able to detect mismatch sequences related to inherited breast cancer, with high specificity and sensitivity. Using PCR synthetic sequences as targets, mutant sequences were clearly discriminated from fully complementary ones, and detection limits below 50 nM were achieved.

[Results of applying the Scientific Technical Quality Programme and Constant Quality Improvement for peritoneal dialysis]. / Resultados de la aplicación del plan de calidad científico-técnica y de mejora continua de calidad en diálisis peritoneal.

INTRODUCTION: In last time it was tried to homogenize the clinical activity and to make the decisions easier. In the field of Nephrology, the Spanish Society of Nephrology has developed different guidelines that have managed an improvement in patient s monitoring. That is the reason why the Quality Working Group in Nephrology was created, whose basic working field was haemodialysis, although its collaboration with an expert group in peritoneal dialysis (PD) has allowed the developement of a Scientific Technical Quality Programme and Constant Quality Improvement in PD. MATERIAL AND METHODS: We checked the clinical histories of all the patients in PD in the course of 2008 in the Peritoneal Dialysis Unit at our institution and we evaluated all the quality indicators that were described in the Scientific Technical Quality Programme and of Constant Quality Improvement in PD. RESULTS: During 2008 a total of 41 patients were treated in the Peritoneal Dialysis Unit at our institution, 43.9% women. Incidence was 14 (51.8%) and 21.4% were diabetics. No patients cames from transplant unit and 2 came from haemodilalysis unit (7.1%). Mean age in incident population was 60 +/- 13 years and in prevalent population was 53.9 +/- 14.4 years. Mean follow-up in PD was 25.9 +/- 19.9 months. Modified Charlson comorbility index average in incident patients was 6 and in prevalent patients was 5. 70.7% were included in transplant programme and 3 were transplanted in the year s course (10.3%). There were 19 hospital admissions (rate: 0.46 admission per patient/year in risk) with a mean stay of 7.3 days (rate: 3.4 days per patient/year in risk). During 2008 6 patients leaved PD (2 transfers to haemodialysis, 3 transplants and 1 death). 16 infective peritonitis (overall rate: 1 episode every 24 months) and 23 exit side infections were reported (rate: 1 episode every 18 months). Mean Kt/V was 2,4 +/- 0.06 (92.7% of patients achieved the stablished standards). All non-anuric patients had measured residual renal function and only 1 patient did not achieve the goal of fluid output > 1000 ml/day. No patient used 3.86-4.25% bags. Stablished standards were achieve by analitic indicators with regard to epoetin resistence index, LDL- cholesterol, phosphate, calcium-phosphate product and PTH. CONCLUSIONS: The application of the Scientific Technical Quality Programme and of Constant Quality Improvement in PD has made possible to know the current situation of our unit and to raise some matters when it is necessary to insist to get a better quality in our assistance.

Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably representing a compensatory up-regulation to counteract the cocaine-induced increases in dopamine D(2) and D(3) signaling. Therefore, A(2A) agonists, through antagonizing D(2) and D(3) signaling within A(2A)/D(2) and A(2A)/D(3) RM heteromers in the nucleus accumbens, may be found useful as a treatment for cocaine dependence. Furthermore, antagonistic cannabinoid CB(1)/D(2) interactions requiring A(2A) receptors have also been discovered and possibly operate in CB(1)/D(2)/A(2A) RM located principally on striatal glutamate terminals but also on some ventral striato-pallidal GABA neurons, thereby opening up a new mechanism for the integration of endocannabinoid, DA and adenosine mediated signals. Thus, A(2A), mGluR5 and/or CB(1) receptors can form integrative units with D(2) receptors within RM displaying different compositions, topography and localization. Also galaninR/5-HT(1A) RM probably participates in the transmission of the ascending 5-hydroxytryptamine neurons, where galanin receptors antagonize 5-HT(1A) recognition and signaling. Subtype specific galanin receptor antagonists may therefore represent novel antidepressant drugs. These results suggest the importance of a complete understanding of the function of these RM with regard to disease. Ultimately receptor-receptor interactions within RM that modify dopaminergic and serotonergic signaling may give new strategies for treatment of a wide range of diseases associated with altered dopaminergic and serotonergic signaling.