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In order to confirm the genetic character of porphyria cutanea tarda (PCT), the quantitative and qualitative porphyrin excretion from 56 unrelated PCT patients and 259 relatives was analyzed by a sensitive fluorimetric thin-layer chromatographic technique. Porphyrin excretion abnormalities were observed in 111 (35.24%) of the 315 subjects studied. Of the 259 relatives, 55 (21.24%) suffered from manifest (24 cases) or subclinical (31 cases) PCT. The relatives from the older generation or a generation similar to the propositi were more frequently affected than those from a younger generation. A clear family incidence was observed in 32 families, while PCT was apparently limited to the propositi in the remaining 24. It is discussed whether these latter families correspond to the so-called 'sporadic' type of PCT or include porphyric gene carriers lacking biochemical expression of the disease. While the measurements of the activity of the defective enzyme (uroporphyrinogen decarboxylase) for the genetic research of PCT turned out to be impracticable in hepatic tissue and contradictory in erythrocytes, our study confirms that the familial character of this disease may be revealed by the chromatographic analysis of the porphyrin excretion pattern. [ABSTRACT FROM AUTHOR]

The quantum dimer magnet (QDM) is the canonical example of quantum magnetism. The QDM state consists of entangled nearest-neighbor spin dimers and often exhibits a field-induced triplon Bose-Einstein condensate (BEC) phase. We report on a new QDM in the strongly spin-orbit coupled, distorted honeycomb-lattice material Yb2Si2O7. Our single crystal neutron scattering, specific heat, and ultrasound velocity measurements reveal a gapped singlet ground state at zero field with sharp, dispersive excitations. We find a field-induced magnetically ordered phase reminiscent of a BEC phase, with exceptionally low critical fields of Hc1∼0.4 and Hc2∼1.4 T. Using inelastic neutron scattering in an applied magnetic field we observe a Goldstone mode (gapless to within δE=0.037 meV) that persists throughout the entire field-induced magnetically ordered phase, suggestive of the spontaneous breaking of U(1) symmetry expected for a triplon BEC. However, in contrast to other well-known cases of this phase, the high-field (μ0H≥1.2 T) part of the phase diagram in Yb2Si2O7 is interrupted by an unusual regime signaled by a change in the field dependence of the ultrasound velocity and magnetization, as well as the disappearance of a sharp anomaly in the specific heat. These measurements raise the question of how anisotropy in strongly spin-orbit coupled materials modifies the field induced phases of QDMs. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the nutritional status in older adults in the community, to determine malnutrition, obesity and their risks and to identify determinants related to both clinical situations., Design: Cross-sectional study. SITE: 3 Primary care health centers in La Rioja in urban, semiurban and rural areas., Participants: 409 people ≥ 65 years old who came to receive consultation, with 3 abandonments., Interventions: Nutritional assessment by tools screening and anthropometric measurements., Main Measurement: The MNA SF® was used to determine the prevalence of malnutrition and the BMI for obesity. Sociodemographic, socioeconomic, health-disease variables, lifestyle habits, metabolic status, and anthropometric measurements were included. Binary logistic regression was performed to predict dichotomous dependent variables., Results: The prevalence of malnutrition and its risk (DR) were 18.7% and obesity and its risk were 66,5%. The multivariate model for malnutrition and DR includes polypharmacy, dyslipidemia, sedentary lifestyle, and having mental pathology (OR=3.09, 2.01, 2.12, 1.72, respectively). On the other hand, the probability of presenting obesity is associated with cardiovascular risk, age, excessive-moderate alcohol consumption, hypertension and low adherence to the Mediterranean diet (OR=2.73, 4.27, 2.03, 1.97, 1.81 respectively)., Conclusion: This results stand out that the study population has a poor nutritional status, detecting a risk of malnutrition, obesity and overweight. The identified predictors related to lifestyle habits, presence of diseases, psychosocial problems, metabolic alterations, etc. They can guide the selection of those people who would benefit from screening to detect and approach the risk of malnutrition early., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Objective: Sentinel surveillance is used to monitor health problems. The COVID detection strategy conducts universal surveillance of SARS-CoV-2 infection, which can be monitored by sentinel systems, through surveillance of mild acute respiratory infection (IRA) or severe respiratory infection (IRAG). The objective of this study was to compare incidence data obtained through sentinel surveillance against versus universal surveillance in acute respiratory infections., Methods: A descriptive study of the incidences (cases/100,000 inhabitants) of acute respiratory infection (sudden onset of cough, sore throat, dyspnea or runny nose and clinical judgment of infection) was carried out in the entire population of La Rioja recorded in the primary care medical record, and in a sentinel cohort, by age and sex during the period from weeks 40-2021 to 06-2022. For SARI, the total number of hospitalized cases per 100,000 inhabitants with onset of symptoms in the previous ten days was calculated, as well as the incidence in a systematic selection of all SARI hospitalized one day a week. Weekly incidence rates were calculated in each cohort from week forty of 2021 to week six of 2022 by sex and age group. The characteristics of the population were expressed in their distribution by number and percentage., Results: The data observed for ARI were similar in both systems by sex and age, except for the zero to four-year-old group and the group over seventy-nine years of age, where differences were observed, with the highest ARI figures in the first age group in sentinel surveillance, while in the older group they were superior in universal surveillance. SARIs showed a similar incidence, except in the fifteen/fourty-four age groups, which was higher in universal surveillance than in sentinel surveillance., Conclusions: There are no significant differences. Sentinel surveillance allows optimization of resources, being the most efficient methods for surveillance of high-incidence diseases.

[ GAR + ] prion-like elements partially relieve carbon catabolite repression in Saccharomyces cerevisiae . They have been hypothesized to contribute to wine yeast survival and alcohol level reduction, as well as communication with bacteria and stuck fermentation. In this work, we selected [ GAR + ] derivatives from several genetic backgrounds. They were characterized for phenotypic penetrance, heritability and confirmed as prion-like through curing by desiccation. In terms of fermentation kinetics, the impact of the prion on anaerobic wine fermentation (natural grape juice) was either neutral or negative, depending on the genetic background. Likewise, residual sugars were higher or similar for [ GAR + ] as compared to the cognate [ gar - ] strains. The prions had little or no impact on glycerol and ethanol yields; while acetic acid yields experienced the highest variations between [ GAR + ] and [ gar - ] strains. Strains analyzed under aerobic conditions followed the same pattern, with either little or no impact on fermentation kinetics, ethanol or glycerol yield; and a clearer influence on volatile acidity. Although no clear winemaking advantages were found for [ GAR + ] strains in this work, they might eventually show interest for some combinations of genetic background or winemaking conditions, e.g., for reducing acetic acid yield under aerated fermentation.

Polycystic ovary syndrome (PCOS) is the most common cause of female infertility worldwide. Although the related research output is constantly growing, no detailed global map of the scientific architecture has so far been created encompassing quantitative, qualitative, socioeconomic and gender aspects. We used the NewQIS platform to assess all PCOS-related publications indexed between 1900 and 2014 in the Web of Science, and applied density equalizing mapping projections, scientometric techniques and economic benchmarking procedures. A total of 6261 PCOS-specific publications and 703 international research collaborations were found. The USA was identified as the most active country in total and collaborative research activity. In the socioeconomic analysis, the USA was also ranked first (25.49 PCOS-related publications per gross domestic product [GDP]/capita), followed by the UK, Italy and Greece. When research activity was related to population size, Scandinavian countries and Greece were leading the field. For many highly productive countries, gender analysis revealed a high ratio of female scientists working on PCOS with the exception of Japan. In this study, we have created the first picture of global PCOS research, which largely differs from other gynaecologic conditions and indicates that most related research and collaborations originate from high-income countries., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The efficiency of the complement system as an innate immune defense mechanism depends on a fine control that restricts its action to pathogens and prevents non-specific damage to host tissues. Genetic and functional analyses have shown that this critical control of complement activation may be impaired in atypical hemolytic uremic syndrome (aHUS) patients. Mutations in HF1, MCP or FI have been found in aHUS patients, but incomplete penetrance of the disease in individuals carrying these mutations is relatively frequent and no genetic defect has yet been found in a majority of aHUS patients. We report here the identification of a specific SNP haplotype block, spanning the MCP gene in the regulators of complement activation gene cluster, which is over-represented in aHUS patients and strongly associates with the severity of the disease. Linkage disequilibrium analyses suggest that this SNP haplotype also includes the CR1, DAF and C4BP genes. Initial studies identified two SNPs in the haplotype that influence the transcription activity of the MCP promoter in transient transfection experiments. Notably, the SNP haplotype block was found to be particularly frequent among patients who carry mutations in HF1, MCP or FI. These findings and the identification of aHUS patients carrying mutations in two complement regulatory genes provide an important insight into the etiology of aHUS. Together, they suggest that complement regulatory molecules act as a protein network and that multiple hits, involving plasma- and membrane-associated complement regulatory proteins, are necessary to impair protection to host tissues and to confer significant predisposition to aHUS.

Objective: To study the risk factors for HIV-1 in semen according to the localization of HIV-1 in sperm cell fractions and to assess the efficiency of sperm processing in obtaining spermatozoa without HIV-1 genomes., Methods: Ninety-four HIV-infected patients provided 281 paired blood and semen samples. Sperm cell separation was performed using two successive methods. HIV-1 RNA was quantified in blood and seminal plasma. HIV-1 RNA and DNA were detected in cell fractions., Results: HIV-1 RNA was found in 14% of seminal plasma samples and up to 8.7% of native semen cells were positive for HIV-1 RNA and DNA. Ten seminal plasma samples had detectable RNA although blood viral load was undetectable. Antiretroviral treatment reduced the likelihood of RNA detection in seminal plasma. For semen with polynuclear cells and HIV-1 RNA in seminal plasma, the likelihood of detecting HIV-1 genomes in semen cells was increased fourfold and sixfold, respectively. In 25% of patients, HIV-1 excretion was intermittent. In the group of patients with systematic negative seminal plasma, HIV-1 genomes were detected in up to 10% of sperm cell samples. Our method of sperm processing always enabled us to obtain spermatozoa without detectable HIV-1 genomes., Conclusions: Polynuclear cells in semen are a risk factor for seminal HIV-1 excretion. Blood viral load was the only predictive factor for the intermittence of HIV-1 excretion in semen over time. Sperm processing using two successive methods was effective in obtaining spermatozoa without detectable HIV-1 genomes regardless of the viral load level in native semen.

HCV is usually transmitted via the blood, but HCV RNA has been detected recently in seminal fluid. This study was done to study HCV seminal shedding and factors that could influence the presence of HCV in the seminal fluid of men coinfected with HCV and HIV-1. HCV and HIV-1 genomes were assayed in multiple paired blood and semen samples obtained from 35 men enrolled in an assisted medical procreation protocol. HCV RNA was found intermittently in semen samples from 9 patients (25.7%). Samples from 9 men with HCV RNA in their semen and 26 men without were compared to further analyze these parameters. No correlation was found between HCV RNA in the seminal fluid and age, HCV virus load, the duration of HIV-1 infection, HIV treatment, the CD4(+) cell count, HIV-1 virus load or HIV-1 detection in the semen. The intermittent detection of HCV RNA in semen samples support the systematic search for HCV RNA in semen and the use of processed spermatozoa in assisted medical procreation of infertile HCV serodiscordant couples., (Copyright 2003 Wiley-Liss, Inc.)

Human cytomegalovirus (HCMV) infections and anti-HCMV treatment are usually monitored by measuring pp65 antigenemia. This method is time-consuming, labour-intensive and requires skilled operators. We have compared results obtained using real-time Light Cycler quantitative PCR (QPCR) and the pp65 antigen assay on serial samples collected from recipients of solid organ transplants. We collected 198 blood samples from 14 solid organ transplant recipients and assayed them for pp65 antigen and with Light Cycler PCR. HCMV DNA was extracted from leukocytes and measured using primers and probe located in the UL83 region. The quantity of HCMV DNA was calculated using a standard curve prepared from a plasmid containing the target sequence. There was a good correlation between the number of pp65-positive cells and the DNA copy number (r = 0.57, P < 0.0001). A clinical threshold of 50 positive polymorphonuclear leukocytes/200,000 cells was equivalent to two log10 genome copies per capillary by Light Cycler PCR. HCMV DNA was detected before pp65 antigen in three patients at a mean time of 10 days, whereas the two tests were positive simultaneously for eight patients. Both the pp65 antigen data and DNA copy number decreased over time during antiviral treatment, although the QPCR was positive 28.2 days after the pp65 antigen assay had become negative. The real-time Light Cycler quantitative PCR assay is a rapid and labour-saving technique. This molecular method could be useful for monitoring infections and antiviral treatment in recipients of solid organ transplants.

Background: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected., Patients: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV., Methods: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation., Results: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions., Conclusions: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.

The aim was to evaluate the long-term stability of cyclosporin A-loaded nanoparticle suspensions, stored at 8 and 25 degrees C. The stability of freeze-dried samples was also investigated. Nanoparticles (NP) of poly-sigma-caprolactone (P sigma CL), a biodegradable polymer, were obtained by a modified nanoprecipitation method. A central composite experimental design was used to investigate the simultaneous effect of technological factors (temperature of the aqueous phase and needle gauge) and formulation variables (volume of acetone and the amount of polymer and surfactant). The effect of these variables on the stability of the 100-220 nm particles obtained was evaluated. The percentage of cyclosporin A (CyA) encapsulated in the NP suspensions stored at 8 and 25 degrees C for at least 3 months remained unaltered. Moreover, there was no change in the size of NP. After 4 months storage, the physical stability of the preparation was affected. NP aggregates could be observed by light microscopy. Reconstituted freeze-dried preparations showed a mean increase of 1% in the incorporated drug and also a considerable increase in mean size and size distribution. Additional experiments investigated the effect of freezing temperature (-70 and -196 degrees C) and of 5, 10 and 20% (w/v) cryoprotector (mannitol, sorbitol, glucose and threalose) on 100 nm particles. The addition of glucose and threalose at concentrations > 10% permitted adequate reconstitution of the freeze-dried product with conservation of the encapsulated CyA.

Cyclosporin A (CyA) is a good candidate for incorporation in colloidal carriers such as nanoparticles (NP) that would diminish the adverse effects associated with its use under conventional pharmaceutical dosage forms and improve bioavailability after oral administration. In this study a composite rotational experimental design was used to evaluate the joint influence of five formulation variables: temperature of the aqueous phase, needle gauge, volume of the organic phase, and the amounts of polymer and surfactant on the micromeritic characteristics of the CyA-loaded NP obtained by the method of Fessi et al. The percentage of drug encapsulated in the NP was also evaluated for each formulation, and the yield, which was expressed as the ratio between the experimentally measured quantity of drug in the formulation and the theoretical content, was determined because CyA undergoes surface absorption. Potential variables such as stirring speed (500 rpm), final drug concentration (100 micrograms/mL), or injection rates (GRi = 0.379 mL/s) were maintained constant. The ANOVA corresponding to the experimental design showed that the amounts of polymer and surfactant, and the diameter of the needle used in the preparation of NP, significantly affected the percentage of entrapped drug (I2 = 0.8916). The mean particle size was significantly affected by all the formulation variables tested except for the amount of surfactant dissolved in the external aqueous phase (r2 = 0.9518). Neither the yield (mean value of 99.61%) nor the size distribution parameters (polydispersity and coefficient of variation) presented good correlation coefficients for the equations obtained, although some variables showed statistical significance. A second study was carried out to investigate the effects on the drug-loaded NP characteristics of varying the global injection rates (GRi) for the organic phase into the aqueous medium. The results showed a dramatic decrease in both particle size and drug incorporation in the carrier as the rate of mixing increased. From the results of both the experimental design and the second study, a theoretical model for nanoparticle formation is proposed that considers the most significant variables, and an empirical relationship to predict mean particle size is presented. Thus, particle size can be controlled by the injection rates (GRi), the needle gauge, and the polymer concentration.