Search

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus. We restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. Unlike the liver and eWAT, rhythmic clock genes in the BAT remained insensitive to feeding time, similar to the hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating tissue-specific responses on circadian transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at unusual times., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the particular use of smartphones among Primary Care Health professionals during the care act and its consequences., Design: Multicenter, cross-sectional study in a primary care setting, carried out in 3phases: survey of professionals, checklist of professionals and survey of patients., Participants: Primary Care Health professionals from the Territorial Primary Care Management of Barcelona (online survey) and health professionals (checklist) and patients (patient survey) from 2primary care teams in Barcelona city., Main Measurements: Bivariate descriptive analysis of the variables from the different surveys. Use of the mobile phone in the consultation, time, reason, type of use and perception of appropriateness. Characteristics of interruptions., Results: In relation to patients, 31% consider that the health professional should only consult the mobile phone if it is to resolve some aspect of their reason for consultation and 10% consider it a lack of respect. Eighteen percent of patients describe interruptions, the majority lasting between 10 and 30s and considering them mostly avoidable. In relation to professionals, the majority (96%) claim to have their mobile phone in the consultation and on mute (77%), with only 2% recognizing its use in the presence of the patient, which is in line with what the patients describe. Furthermore, 80% of professionals say they ask permission to use it, contrasting with what patients report (50%). Eighty-five percent of professionals consider its use appropriate., Conclusions: The use of mobile phones is perceived by patients as an interruption that can affect the care act, generating dissatisfaction, which must be taken into account by health professionals. Healthcare organizations should establish recommendations regarding the use of mobile phones in consultations., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology., (© 2024. The Author(s).)

Lathyrane-type diterpenes have a wide range of biological activities. Among them, euphoboetirane A ( 1 ) exerts neurogenesis-promoting activity. In order to increase the structural diversity of this type of lathyrane and explore its potential use in neurodegenerative disorders, the biotransformation of 1 by Streptomyces puniceus BC-5GB.11 has been investigated. The strain BC-5GB.11, isolated from surface sediments collected from the intertidal zone of the inner Bay of Cadiz, was identified as Streptomyces puniceus , as determined by phylogenetic analysis using 16S rRNA gene sequence. Biotransformation of 1 by BC-5GB.11 afforded five products ( 3 - 7 ), all of which were reported here for the first time. The main biotransformation pathways involved regioselective oxidation at non-activated carbons ( 3 - 5 ) and isomerization of the ∆ 12,13 double bond ( 6 ). In addition, a cyclopropane-rearranged compound was found ( 7 ). The structures of all compounds were elucidated on the basis of extensive NMR and HRESIMS spectroscopic studies.

The microbiota is attributed to be important for initial soil formation under extreme climate conditions, but experimental evidence for its relevance is scarce. To fill this gap, we investigated the impact of in situ microbial communities and their interrelationship with biocrust and plants compared to abiotic controls on soil formation in initial arid and semiarid soils. Additionally, we assessed the response of bacterial communities to climate change. Topsoil and subsoil samples from arid and semiarid sites in the Chilean Coastal Cordillera were incubated for 16 weeks under diurnal temperature and moisture variations to simulate humid climate conditions as part of a climate change scenario. Our findings indicate that microorganism-plant interaction intensified aggregate formation and stabilized soil structure, facilitating initial soil formation. Interestingly, microorganisms alone or in conjunction with biocrust showed no discernible patterns compared to abiotic controls, potentially due to water-masking effects. Arid soils displayed reduced bacterial diversity and developed a new community structure dominated by Proteobacteria , Actinobacteriota , and Planctomycetota , while semiarid soils maintained a consistently dominant community of Acidobacteriota and Proteobacteria . This highlighted a sensitive and specialized bacterial community in arid soils, while semiarid soils exhibited a more complex and stable community. We conclude that microorganism-plant interaction has measurable impacts on initial soil formation in arid and semiarid regions on short time scales under climate change. Additionally, we propose that soil and climate legacies are decisive for the present soil microbial community structure and interactions, future soil development, and microbial responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rodríguez, Bartholomäus, Witzgall, Riveras-Muñoz, Oses, Liebner, Kallmeyer, Rach, Mueller, Seguel, Scholten and Wagner.)

Plant pathogenic infections causing substantial global food losses are a persistent challenge. This study investigates a potential biocontrol strategy against the necrotrophic fungus Botrytis cinerea using the endophytic fungus Sordaria tomento-alba isolated from Gliricidia sepium in Colombia. Today, synthetic fungicides dominate B. cinerea control, raising environmental and health concerns. S. tomento-alba exhibits notable in vitro effects, inhibiting B. cinerea growth by approximately 60% during co-culture and 50% in double disc co-culture. Additionally, it suppresses botryanes production and produces the compound heptacyclosordariolone, which has proven effective in inhibiting B. cinerea mycelial growth and spore germination in vitro. This biocontrol agent could be a potential eco-friendly alternative to replace synthetic fungicides. Our study provides insights into the chemical and biological mechanisms underpinning the antagonistic activity of S. tomento-alba , emphasizing the need for further research to understand its biosynthesis pathways and optimize its biocontrol potential. It also contributes molecular evidence of fungal interactions with implications for advanced forums in molecular studies in biology and chemistry, particularly in addressing plant pathogenic infections and promoting sustainable agriculture.

Neurocognitive deficits are a core feature of psychotic disorders, but it is unclear whether they affect all individuals uniformly. The aim of this systematic review and meta-analysis was to synthesize the evidence on the magnitude, progression, and variability of neurocognitive functioning in individuals with first-episode psychosis (FEP). A multistep literature search was conducted in several databases up to November 1, 2022. Original studies reporting on neurocognitive functioning in FEP were included. The researchers extracted the data and clustered the neurocognitive tasks according to the seven Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and six additional domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. The primary effect size reported was Hedges g of (1) neurocognitive functioning in individuals at FEP measuring differences with healthy control (HC) individuals or (2) evolution of neurocognitive impairment across study follow-up intervals. Of 30,384 studies screened, 54 were included, comprising 3,925 FEP individuals and 1,285 HC individuals. Variability analyses indicated greater variability in FEP compared to HC at baseline and follow-up. We found better neurocognitive performance in the HC group at baseline and follow-up but no differences in longitudinal neurocognitive changes between groups. Across the 13 domains, individuals with FEP showed improvement from baseline in all studied domains, except for visual memory. Metaregressions showed some differences in several of the studied domains. The findings suggest that individuals with FEP have marked cognitive impairment, but there is greater variability in cognitive functioning in patients than in HC. This suggests that subgroups of individuals suffer severe disease-related cognitive impairments, whereas others may be much less affected. While these impairments seem stable in the medium term, certain indicators may suggest potential further decline in the long term for a specific subgroup of individuals, although more research is needed to clarify this. Overall, this study highlights the need for tailored neurocognitive interventions for individuals with FEP based on their specific deficits and progression., (© 2024. The Author(s).)

Background and Objectives: The efficacy of COVID-19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas-19 clinical trial showed that CP reduces the risk of progression to severe COVID-19 at 28 days. Here, we aim to study ConPlas-19 donors and characteristics that associate with high anti-SARS-CoV-2 antibody levels., Materials and Methods: Four-hundred donors were enrolled in ConPlas-19. The presence and titres of anti-SARS-CoV-2 antibodies were evaluated by EUROIMMUN anti-SARS-CoV-2 S1 IgG ELISA., Results: A majority of 80.3% of ConPlas-19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti-SARS-CoV-2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24-3.42), with more than 7 days of COVID-19 symptoms (RR 1.89; 95% CI 1.05-3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16-5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91-3.06)., Conclusion: SARS-CoV-2 CP candidate donors' age, duration of COVID-19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID-19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks., (© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as Emericellopsis maritima . On the basis of the one strain-many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes ( 1 - 4 ), together with thirteen known derivatives ( 5 - 17 ) and two reported diketopiperazines ( 18 , 19 ), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation. Thirteen of the isolated eremophilanes were examined for cytotoxic and antimicrobial activities. PR toxin ( 16 ) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058, and Mia PaCa-2 human cancer cell lines with IC 50 values ranging from 3.75 to 33.44 µM. (+)-Aristolochene ( 10 ) exhibited selective activity against the fungal strains Aspergillus fumigatus ATCC46645 and Candida albicans ATCC64124 at 471 µM.

Agriculture currently confronts a multitude of challenges arising from the excessive utilization of chemical pesticides and the proliferation of phytopathogenic fungi strains that exhibit resistance to commonly employed active compounds in the field. Botrytis cinerea and Colletotrichum acutatum are phytopathogenic fungi that inflict substantial economic losses within agriculture and food due to their high impacts on crops both pre- and post-harvest. Furthermore, the emergence of fungal strains that are resistant to commercial fungicides has exacerbated this problem. To explore more environmentally sustainable alternatives for the control of these pathogens, an investigation into the endophytic bacteria associated with ginger ( Zingiber officinale Rosc.) was conducted. The primary focus of this study involved evaluating their inhibitory efficacy against the fungi and assessing their potential for promoting plant growth. The endophytic bacteria genera Lelliottia , Lysinibacillus , Kocuria , Agrococcus , Acinetobacter , Agrobacterium , Zymobacter , and Mycolicibacterium were identified. All isolates showed remarkable in vitro antagonistic ability against B. cinerea (>94%) and C. acutatum (>74%). Notably, the Lelliottia amnigena J29 strain exhibited a notable proficiency in producing extracellular enzymes and indole compounds (IAA), solubilizing phosphate and potassium, and forming biofilm. Furthermore, the Lysinibacillus capsici J26, Agrococcus citreus J28, and Mycolicibacterium sp. J5 strains displayed the capacity for atmospheric nitrogen fixation and siderophore production. These findings underscore the agricultural and biotechnological potential of endophytic bacteria derived from ginger plants and suggest the feasibility of developing alternative approaches to manage these two phytopathogenic fungi.

Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

The COVID-19 pandemic has impacted the mental health of the youngest, worsening their emotional well-being. The demand for care in psychiatric emergencies may indirectly reflect the mental health state of children and adolescents and the emotional consequences of the pandemic. Moreover, suicidality can be considered a marker of severity in this population group. Therefore, we have aimed to longitudinally describe the number of children and adolescents attended in the psychiatry emergency department due to suicidal ideation or attempts and, to explore differences in suicidality according to gender and age. A retrospective study was carried out in the University Hospital of San Juan, Alicante, Spain, from January 01, 2018 to December 31, 2021. A total of 138 participants under 18 years requesting psychiatric care due to suicidal ideation or attempts were included. The sample was composed by 35% of males and the mean age was 14.8 years old (SD = 2.2). The number of cases per year range from 10 in 2018 to 88 in 2021. Attendances were significantly higher between 2021 and the three previous years. Besides, the number of attentions registered in the last 9 months of 2021 equals those that occurred in the entire previous period. Most of the cases were girls and middle adolescents. Suicide ideation or attempts have skyrocketed in children and adolescents. This alarming increase presents a one-year lag peak from the COVID-19 outbreak and continues until the end of 2021. Girls and those over 12 years have been identified as risk groups to present suicidal ideation or attempts., Competing Interests: Declaration of competing interest Dr. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini. Dr. G. Lahera has been a consultant to or has received honoraria or grants from Janssen-Cilag, Otsuka-Lundbeck, Lilly, Astra-Zeneca, CIBERSAM and Instituto de Salud Carlos III. All other authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

A series of new D-ring ethisterones substituted with 1,4-1,2,3-triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, IR and unequivocally by single crystal X-ray diffraction studies for compound 1. The cytotoxic activity of these derivatives was tested against a series of human cancer cell lines including human glioblastoma (U-251), human prostatic adenocarcinoma (PC-3), human colorectal adenocarcinoma (HCT-15), human mammary adenocarcinoma (MCF-7), human chronic myelogenous leukemia (K562), and human lung adenocarcinoma (SKLU-1). Derivatives (3, X=Cl) and (5, X=I) showed promising cytotoxicity activities for leukemia adenocarcinoma (K562) and lung adenocarcinoma (SKLU). CI 50% of K562: 11.72±0.9 μM (3) and 24.50±1.0 μM (5). CI 50% of SKLU: 14.9±0.8 μM (3) and 46.0±2.8 μM (5). In addition, DNA docking simulations showed that all compounds interact with DNA through crosslink instrastrand p-alkyl-like interactions., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Introduction: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC., Objective: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC., Methods: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT., Results and Limitations: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients., Conclusions: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile., Competing Interests: Daniel A. González-Padilla has received payment for trial collaboration from Combat Medical. Félix Guerrero Ramos is a consultant and speaker for Combat Medical. Wei Shen Tan is a consultant to Combat Medical. Joan Palou Redorta is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. Wei Phin Tan, Ana Plata Bello, Carlos Garcia Alvarez, Cajetan Nzeh, Jose Manuel de la Morena, Ignacio Gonzalez Valcarcel de Torres, Kees Hendricksen, Francisco Javier Díaz Goizueta, Fernandez J. Del Alamo, Francesco Chiancone, Paolo Fedelini, Massimiliano Poggio, Francesco Porpiglia, Victoria C. Gonzalo Rodríguez, Javier Montero Torres, Daniel Wilby, Richard Robinson, Alejandro Sousa-Escandón, Juan León Mata, Jose L. Pontones Moreno, Francisco Delgado Molina, Miguel A. Adriazola Semino, Andrew Townsley Stemberger and Jesús Calleja-Escudero declare no conflicts of interest., (© 2022 – The authors. Published by IOS Press.)

Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38 + bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8 + T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

A psychiatric epidemic has accompanied the COVID-19 pandemic and specific vulnerable populations have been identified. We aimed to explore the presence of anxiety, acute stress and depression among these vulnerable groups after a year of pandemic and relate them to our previous results obtained with the same methodology during the initial peak of the pandemic in Spain. A total of 2182 participants conducted a national survey, starting on March 2021. Sociodemographic information and clinical symptoms were assessed. The sample was divided into four groups in order to develop four substudies with these results: 1) Healthcare workers presented lower anxiety, acute stress, and depression than non-Healthcare workers (p < 0.001), being nurses the most affected. 2) People with mental disorders experienced higher anxiety, acute stress, and depression than people without (p < 0.001), as well as a higher rate of COVID cases (14% vs. 9.3%, p = 0.041). 3) People ≥60 years old presented lower anxiety and acute stress than people <60, (p < 0.05) and a weaker depressive syndrome (p = 0.003). 4) Males presented lower anxiety, acute stress and depression than females (p < 0.001). According to the results obtained during the initial peak, Healthcare workers have developed efficient coping strategies, while elders have managed to maintain their previously emotional balance. Notwithstanding, women and people with mental disorders continue to be vulnerable to emotional distress after a year of pandemic. Women and people with mental disorders continue to be especially vulnerable to emotional distress after a year of pandemic., (Copyright © 2022. Published by Elsevier Ltd.)

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum-fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.

Objective: 24.1% of COVID-19 cases reported in Spain from the start of the COVID-19 alert until 29 May 2020 were in healthcare workers. The aim was to describe the demographic, clinical and epidemiological characteristics of Primary Care professionals notified for suspected or contact COVID-19 and to know the factors associated with the severity of the disease. This will allow the development of risk prevention strategies in Primary Care professionals., Methods: We included all Primary Care professionals of the Territorial Management of Barcelona (GTBCN) notified as suspicion or contact with COVID-19 between March 15 and June 15, 2020. Demographic, clinical and epidemiological variables of the professionals and episodes reported were collected, as well as possible risk factors associated with severity. Descriptive and logistic regression analysis were performed., Results: 1,511 episodes corresponding to 1,427 professionals (31.3% of the GTBCN staff) were reported. 76.4% were women, with a mean age of 45.32 years. Of the professionals reported, 28.5% presented COVID-19 in some episode, and of these 18.2% presented severe symptomatology. Risk factors associated with severity were: respiratory pathology (OR: 2.54, 95%CI: 1.16-5.56) and neoplasia (OR: 4.48, 95%CI: 1.38-14.55)., Conclusions: The proportion of professionals notified due to suspicion or contact with COVID-19 is similar to that observed in other studies, being mostly concentrated in the care categories of primary care teams. The factors associated with symptom severity were previous respiratory disease and neoplasia.

The manufacturing process of the aircraft cabin interior panels is expensive and time-consuming, and the resulting panel requires rework due to damages that occurred during their fabrication. The aircraft interior panels must meet structural requirements; hence sandwich composites of a honeycomb core covered with two layers of pre-impregnated fiberglass skin are used. Flat sandwich composites are transformed into panels with complex shapes or geometries using the compression molding process, leading to advanced manufacturing challenges. Some aircraft interior panels are required for non-structural applications; hence sandwich composites can be substituted by cheaper alternative materials and transformed using disruptive manufacturing techniques. This paper evaluates the feasibility of replacing the honeycomb and fiberglass skin layers core with rigid polyurethane foams and thermoplastic polymers. The results show that the structural composites have higher mechanical performances than the proposed sandwich composites, but they are compatible with non-structural applications. Sandwich composite fabrication using the vacuum forming process is feasible for developing non-structural panels. This manufacturing technique is fast, easy, economical, and ecological as it uses recyclable materials. The vacuum forming also covers the entire panel, thus eliminating tapestries, paints, or finishes to the aircraft interior panels. The conclusion of the article describes the focus of future research.

Sandwich composites are widely used in the manufacture of aircraft cabin interior panels for commercial aircraft, mainly due to the light weight of the composites and their high strength-to-weight ratio. Panels are used for floors, ceilings, kitchen walls, cabinets, seats, and cabin dividers. The honeycomb core of the panels is a very light structure that provides high rigidity, which is considerably increased with fiberglass face sheets. The panels are manufactured using the compression molding process, where the honeycomb core is crushed up to the desired thickness. The crushed core breaks fiberglass face sheets and causes other damage, so the panel must be reworked. Some damage is associated with excessive build-up of resin in localized areas, incomplete curing of the pre-impregnated fiberglass during the manufacturing process, and excessive temperature or residence time during the compression molding. This work evaluates the feasibility of using rigid polyurethane foams as a substitute for the honeycomb core. The thermal and viscoelastic behavior of the cured prepreg fiberglass under different manufacturing conditions is studied. The first part of this work presents the influence of the manufacturing parameters and the feasibility of using rigid foams in manufacturing flat panels oriented to non-structural applications. The conclusion of the article describes the focus of future research.

During the infection of grapevine ( Vitis vinifera ) by the fungus Botrytis cinerea , the concentration of polyamines, which are toxic substances for the phytopathogen, increases in the grape. Nine NRPS genes have been identified in the genome of B. cinerea , yet the function of five of them remains unknown. For this reason, we have studied the expression of the 9 NRPS genes by RT-qPCR in a medium supplemented with sublethal concentrations of three polyamines (1,3-diaminopropane (1,3-DAP), spermidine (SPD), and spermine (SPM)). Our results show that the presence of polyamines in the culture medium triggered the overexpression of the Bcnrps 1 gene in the pathogen. Deleting Bcnrps 1 did not affect mycelial growth or adaptation to osmotic stress, and we show that its expression is not essential for the cycle of infection of the B. cinerea . However, mutating the Bcnrps 1 gene resulted in overexpression of the Bcnrps 6 gene, which encodes for the excretion of siderophores of the coprogen family. Moreover, gene deletion has reduced the tolerance of B. cinerea B05.10 to toxic substances such as the polyamine SPD and the fungicide pyrimethanil, and its virulence has increased. Our findings provide new insights into the function of the Bcnrps 1 gene and its involvement in the tolerance of B. cinerea against exogenous toxic compounds.

Plant diseases are one of the main factors responsible for food loss in the world, and 20-40% of such loss is caused by pathogenic infections. Botrytis cinerea is the most widely studied necrotrophic phytopathogenic fungus. It is responsible for incalculable economic losses due to the large number of host plants affected. Today, B. cinerea is controlled mainly by synthetic fungicides whose frequent application increases risk of resistance, thus making them unsustainable in terms of the environment and human health. In the search for new alternatives for the biocontrol of this pathogen, the use of endophytic microorganisms and their metabolites has gained momentum in recent years. In this work, we isolated endophytic bacteria from Zea mays cultivated in Colombia. Several strains of Bacillus subtilis , isolated and characterized in this work, exhibited growth inhibition against B. cinerea of more than 40% in in vitro cultures. These strains were characterized by studying several of their biochemical properties, such as production of lipopeptides, potassium solubilization, proteolytic and amylolytic capacity, production of siderophores, biofilm assays, and so on. We also analyzed: (i) its capacity to promote maize growth ( Zea mays ) in vivo, and (ii) its capacity to biocontrol B. cinerea during in vivo infection in plants ( Phaseolus vulgaris ).

Dietary restriction (DR) decreases body weight, improves health, and extends lifespan. DR can be achieved by controlling how much and/or when food is provided, as well as by adjusting nutritional composition. Because these factors are often combined during DR, it is unclear which are necessary for beneficial effects. Several drugs have been utilized that target nutrient-sensing gene pathways, many of which change expression throughout the day, suggesting that the timing of drug administration is critical. Here, we discuss how dietary and pharmacological interventions promote a healthy lifespan by influencing energy intake and circadian rhythms.

Low birth weight (LBW) is a global problem that annually affects nearly 20 million children, 96% of these in developing countries. According to the WHO, the poorest and the ethnic minorities are the groups most affected by this indicator. A cross-sectional study of the database of all newborns officially registered in Colombia in 2008-2014 was done. While dichotomizing the mestizo population and ethnic minorities (Afro-descendants, indigenous, ROM), normal and low birth weight was used as the dependent variable and ethnicity as the explanatory variable. Other variables of the parents and the newborns were used as covariates. To assess associations, bivariate and multivariate logistic regression analyses were performed. The incidence of LBW among newborns registered in Colombia fluctuated at around 9%. Among the ethnic minorities, the probability of LBW, adjusted for other variables, was significantly higher (OR 1.07, 95% CI 1.05-1.08) than among mestizos. A significantly higher risk of LBW to newborns in the ethnic minorities' group, and those with unfavorable socioeconomic conditions, was found.

This work deals with the manufacture and mechanical characterization of natural-fiber-reinforced biobased epoxy resins. Biolaminates are attractive to various industries because they are low-density, biodegradable, and lightweight materials. Natural fibers such as Ixtle, Henequen, and Jute were used as reinforcing fabrics for two biobased epoxy resins from Sicomin ® . The manufacture of the biolaminates was carried out through the vacuum-assisted resin infusion process. The mechanical characterization revealed the Jute biolaminates present the highest stiffness and strength, whereas the Henequen biolaminates show high strain values. The rigid and semirigid biolaminates obtained in this work could drive new applications targeting industries that require lightweight and low-cost sustainable composites.

Cultivation of the phytopathogenic fungus Botrytis cinerea using sublethal amounts of copper sulfate yielded a cryptic sesquiterpenoids family, which displayed the basic chemical structure of (+)-4-epi-eremophil-9-ene. The biosynthesis pathway was established, and the route involved the likely transformation of the diphosphate of farnesyl (FDP), to give a cis -fused eudesmane cation, through ( S )-hedycaryol, finally yielding the (+)-4-epi-eremophil-9-enol derivatives. An expression study of genes that code for the sesquiterpene cyclases (STC), including the recently reported gene Bcstc7 present in the B. cinerea genome, was performed in order to establish the STC involved in this biosynthesis. The results showed a higher expression level for the Bcstc7 gene with respect to the other stc1-5 genes in both wild-type strains, B05.10 and Botrytis cinerea UCA992. Deletion of the Bcstc7 gene eliminated (+)-4-epi-eremophilenol biosynthesis, which could be re-established by complementing the null mutant with the Bcstc7 gene. Chemical analysis suggested that STC7 is the principal enzyme responsible for the key step of cyclization of FDP to eremophil-9-en-11-ols. Furthermore, a thorough study of the two wild-types and the complemented mutant revealed four new eremophilenol derivatives whose structures are reported here.

Introduction: Leishmaniasis is a zoonotic disease which is caused by protozoan parasites of the genus Leishmania . Canids are the most important reservoir of the parasites; however, limited data are available on the species of Leishmania prevalent in these animals and their impact on human health. The objective of this study was to estimate the seroprevalence of leishmaniasis in dogs from an inter-Andean region of Colombia during July 2016-July 2017, and to describe the clinical and histopathological features of the disease., Material and Methods: A total of 155 dogs were subjected to clinical examination and a serological test for detection of antibodies against Leishmania . Necropsy was carried out on positive animals and tissue samples were processed by routine histopathology., Results: Altogether 19 dogs were positive in the serological test, establishing a 12% seroprevalence of Leishmania . Clinical examination and necropsy revealed exfoliative and ulcerative dermatitis with haemorrhagic borders on the ears, head, nose, and legs. Histopathology revealed severe multifocal dermatitis with abundant Leishmania amastigotes within the cytoplasm of phagocytic cells, depletion of lymphocytes in lymphoid tissues, interstitial pneumonia, and interstitial nephritis. Tissue samples were positive for Leishmania by PCR., Conclusion: The macro- and microscopic changes correlated with the presence of Leishmania as established by serological test and PCR., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2020 Y. Picón et al. published by Sciendo.)

Severe (grades IV and V) vesicoureteral reflux (VUR) is a risk factor for acute pyelonephritis, renal scars, and renal failure. This study evaluates albumin and N-acetylglucosaminidase (NAG) urinary excretion, and renal concentrating ability as screening tools to select patients for voiding cystourethrogram (VCUG). Children (111 M, 52 F) aged 10.97 ± 21.17 months (mean + SD), diagnosed with UTI, and who had undergone renal ultrasound and a VCUG, underwent a desmopressin test and had albumin/creatinine and NAG/creatinine urinary excretion measured. Urine osmolality was significantly lower in 27 children with severe VUR (375.3 ± 171.8 mOsm/kg; mean + SD) compared to 100 patients with normal VCUG (611.5 ± 175.8 mOsm/kg), p < 0.001, and to 36 patients with VUR grades I to III (636.2 ± 180.2 mOsm/kg), p < 0.001. NAG/creatinine ratio was significantly elevated in 20 children with severe VUR (26.4 (28.3) U/g); median and interquartile range compared to 67 children with normal VCUG (10.8 (17.9) U/g), p = 0.003, and to 20 patients with VUR grades I to III (7.6 (21.1) U/g), p = 0.009.Conclusions: Urinary osmolality is significantly decreased and urinary excretion of NAG is significantly increased in patients with severe VUR. These tests could select patients for VCUG to assess for severe VUR. What is Known: • Severe vesicoureteral reflux (SVUR) may contribute to renal damage. Severe vesicoureteral reflux is diagnosed by voiding cystourethrogram and represents about 10% of all patients with VUR. Currently, there are no reliable tests used prior to VCUG to help on the decision of obtaining a VCUG to diagnose SVUR. What is New: • This study shows that renal tubular markers (concentrating ability and N-acetylglucosaminidase (NAG) excretion) are useful tests prior to voiding cystourethrogram to screen for severe vesicoureteral reflux. • This study suggests the use of renal concentrating ability and urinary N-acetylglucosaminidase (NAG) excretion to screen for severe vesicoureteral reflux before requesting a voiding cystourethrogram.

Age-related reference intervals (RIs) of aortic pulse wave velocity (Ao-PWV) obtained from a large healthy population are lacking in South America. The aims of this study were to determine Ao-PWV RIs in a cohort of healthy children and adolescents from Argentina and to generate year-to-year percentile curves. Ao-PWV was measured in 1000 healthy subjects non-exposed to traditional cardiovascular risk factors (Age: 10-22 y. o., 56% males). First, we evaluated if RIs for males and females were necessaries (correlation and covariate analysis). Second, mean (M) and standard deviation (SD) age-related equations were obtained for cf-PWV, using parametric regression methods based on fractional polynomials. Third, age-specific (year to year) percentiles curves (for all, males and females children and adolescents) were generated using the standard normal distribution. They were, age-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th and 99th percentile curves and values. After covariate analysis (i.e., adjusting by age, jugulum-symphysis distance, body weight and height), specific RIs for males and females of children and adolescents were evidenced as necessaries. The equations were For all subjects: Ao-PWV&#95;Mean = 4.98 + 12.86x10 -5 Age 3 . Ao-PWV&#95;SD = 0.47 + 21.00x10 -6 Age 3 . For girls: Ao-PWV&#95;Mean = 5.07 + 10.23x10 -5 Age 3 . Ao-PWV&#95;SD = 0.50 + 10.00x10 -6 Age 3 . For boys: Ao-PWV&#95;Mean = 4.87 + 15.81x10 -5 Age 3 . Ao-PWV&#95;SD = 0.46 + 22.34x10 -6 Age 3 . Our study provides the largest database to-date concerning Ao-PWV in healthy children and adolescents in Argentina. Age-related equations (M and SD values) for Ao-PWV are reported by the first time. Specific RIs and percentiles of Ao-PWV are now available according to age and sex for an Argentinian population.

While abscisic acid (ABA) is known as a hormone produced by plants through the carotenoid pathway, a small number of phytopathogenic fungi are also able to produce this sesquiterpene but they use a distinct pathway that starts with the cyclization of farnesyl diphosphate (FPP) into 2Z,4E-α-ionylideneethane which is then subjected to several oxidation steps. To identify the sesquiterpene cyclase (STC) responsible for the biosynthesis of ABA in fungi, we conducted a genomic approach in Botrytis cinerea. The genome of the ABA-overproducing strain ATCC58025 was fully sequenced and five STC-coding genes were identified. Among them, Bcstc5 exhibits an expression profile concomitant with ABA production. Gene inactivation, complementation and chemical analysis demonstrated that BcStc5/BcAba5 is the key enzyme responsible for the key step of ABA biosynthesis in fungi. Unlike what is observed for most of the fungal secondary metabolism genes, the key enzyme-coding gene Bcstc5/Bcaba5 is not clustered with the other biosynthetic genes, i.e., Bcaba1 to Bcaba4 that are responsible for the oxidative transformation of 2Z,4E-α-ionylideneethane. Finally, our study revealed that the presence of the Bcaba genes among Botrytis species is rare and that the majority of them do not possess the ability to produce ABA., (© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Various genetic and environmental factors are involved in urolithiasis. The 2 most common metabolic abnormalities are the increase in urinary calcium and low urinary citrate excretion. The ratio calculated between the concentrations of both substances is a good risk marker for the formation of calcium stones., Objectives: To determine whether the risk of urinary calcium stone formation changes throughout the day in the same patient., Methods: We studied 56 children (23V, 33M) to check if they had prelithiasis. Calcium, citrate, and creatinine concentrations were determined in two urine samples collected one before dinner and the other in the morning. It was collected if they had ultrasound stones and if there was a history of urolithiasis in first and/or second degree relatives., Results: In 25 patients (44.6%), renal ultrasound was positive for lithiasis (stones [n=9] and microlithiasis [n=16]). Forty of the 56 families (71.4%) had a history of urolithiasis. The percentage of abnormal urinary calcium (28.6%) concentrations and an abnormal calcium/citrate ratio (69.6%) was higher in the first urine of the day. The calcium/citrate ratio was the only studied parameter that was related to a family history of urolithiasis. There were no differences in urinary parameters between patients with and without ultrasound-confirmed kidney stones., Conclusions: Urinary concentrations of calcium and the calcium/citrate ratio vary throughout the day. Urine produced at night has a higher risk of urinary calcium stone formation., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Caloric restriction (CR) extends lifespan in mammals, yet the mechanisms underlying its beneficial effects remain unknown. The manner in which CR has been implemented in longevity experiments is variable, with both timing and frequency of meals constrained by work schedules. It is commonplace to find that nocturnal rodents are fed during the daytime and meals are spaced out, introducing prolonged fasting intervals. Since implementation of feeding paradigms over the lifetime is logistically difficult, automation is critical, but existing systems are expensive and not amenable to scale. We have developed a system that controls duration, amount, and timing of food availability and records feeding and voluntary wheel-running activity in mice. Using this system, mice were exposed to temporal or caloric restriction protocols. Mice under CR self-imposed a temporal component by consolidating food intake and unexpectedly increasing wheel-running activity during the rest phase, revealing previously unrecognized relationships among feeding, metabolism, and behavior., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Filamentous (F-) actin is an integral part of the cytoskeleton allowing for cell growth, intracellular motility, and cytokinesis of eukaryotic cells. Its assembly from G-actin monomers and its disassembly are tightly regulated processes involving a number of actin-binding proteins (ABPs) such as F-actin nucleators and cross-linking proteins. F-actin capping protein (CP) is an alpha/beta heterodimer known from yeast and higher eukaryotes to bind to the fast growing ends of the actin filaments stabilizing them. In this study, we identified the orthologs of the two CP subunits, named BcCPA1 and BcCPB1, in the plant pathogenic fungus Botrytis cinerea and showed that the two proteins physically interact in a yeast two-hybrid approach. GFP-BcCPA1 fusion proteins were functional and localized to the assumed sites of F-actin accumulation, i.e. to the hyphal tips and the sites of actin ring formation. Deletion of bccpa1 had a profound effect on hyphal growth, morphogenesis, and virulence indicating the importance of F-actin capping for an intact actin cytoskeleton. As polarized growth - unlike septum formation - is impaired in the mutants, it can be concluded that the organization and/or localization of actin patches and cables are disturbed rather than the functionality of the actin rings., (Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The sequencing of the genomes of the B05.10 and T4 strains of the fungus Botrytis cinerea revealed an abundance of novel biosynthetic gene clusters, the majority of which were unexpected on the basis of the previous analyses of the fermentation of these and closely related species. By systematic alteration of easy accessible cultivation parameters, using chemical induction with copper sulfate, we have found a cryptic sesquiterpenoid family with new structures related to eremophil-9-ene, which had the basic structure of the sesquiterpene (+)-5-epiaristolochene ((+)-4-epieremophil-9-ene). An expression study of the sesquiterpene cyclase genes present in the Botrytis cinerea genome, under culture conditions, is reported. In general, a 3 day delay and a higher BcSTC genes expression were observed when copper (5 ppm) was fed to the fermentation broth. In addition, to the observed effect on the BcBOT2 (BcSTC1) gene, involved in the biosynthesis of the botrydial toxin, a higher expression level for BcSTC3 and BcSTC4 was observed with respect to the control in the strain B05.10. Interestingly, under copper conditions, the BcSTC4 gene was the most expressed gene in the Botrytis cinerea UCA992 strain. In vitro evaluation of the biological role of these metabolites indicates that they contributed to the conidial development in B. cinerea and appear to be involved in self-regulation of the production of asexual spores. Furthermore, they promoted the formation of complex appressoria or infection cushions.

Unlabelled: Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans., Methods: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model., Results: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively., Conclusion: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVβ3 expression., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Wines can be modified by microorganisms during the ageing process, by producing off-flavours like volatile phenols (VP), leading to their deterioration, with great economic losses. The development of methods to recover wines affected by unwanted VP became an important target. Molecular imprinted polymers (MIPs) are synthetic materials with artificially-generated recognition sites for selective extraction of organic compounds from different matrices. In this work, two MIPs to remove unwanted VP from wines were developed and their effects were evaluated. Volatile compounds were determined by GC-FID and GC-IT/MS and phenolic compounds (non-coloured and anthocyanins) by HPLC-DAD. The treatment with MIP-4EG and MIP-4EP significantly reduced the content of 4-ethylguaiacol and 4-ethylphenol, respectively. Nevertheless, the changes observed in wine non-coloured and coloured phenolics and sensorial analysis indicate that their specificity and selectivity regarding off-flavours still needs to be improved.

Botrytis cinerea is one of the most relevant plant pathogenic fungi. The first step during its infection process is the germination of the conidia. Here, we report on the first proteome analysis during the germination of B. cinerea conidia, where 204 spots showed significant differences in their accumulation between ungerminated and germinated conidia by two-dimensional polyacrylamide gel electrophoresis and qPCR. The identified proteins were grouped by gene ontology revealing that the infective tools are mainly preformed inside the ungerminated conidia allowing a quick fungal development at the early stages of conidial germination. From 118 identified spots, several virulence factors have been identified while proteins, such as mannitol-1-phosphate dehydrogenase, 6,7-dimethyl-8-ribityllumazine synthase or uracil phosphoribosyltransferase, have been disclosed as a new potential virulence factors in botrytis whose role in pathogenicity needs to be studied to gain new insights about the role of these proteins as therapeutic targets and virulence factors.

The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

Introduction: Eight Giardia duodenalis genotypes (A-H) have been described to date. Genotypes A and B have been isolated from humans and a wide range of mammals; however, genotypes C-H have shown greater host specificity., Objective: Identifying G. duodenalis genotypes from cysts in faeces obtained from children attending the Instituto Colombiano de Bienestar Familiar (ICBF) day care centres and from dogs in Ibagué by PCR-RFLP targeting both the b -giardin and glutamate dehydrogenase genes., Materials and Methods: Cysts from G. duodenalis positive samples were concentrated, DNA was extracted and the b -giardin and glutamate dehydrogenase genes were analysed by PCR-RFLP. The MHOM/CO/04/G40 strain was used as positive control (this was obtained from the Grupo de Parasitología at the Instituto Nacional de Salud )., Results: Of the total human samples, 11/23 (48%) were genotyped as A and 12/23 (52%) as B; PCR-RFLP revealed that four canine samples were genotypes C and D, these being host-specific., Conclusions: Only genotypes associated with human infection (AII, BIII and BIV) were found in the children and host-specific genotypes were observed in canines (C and D). No interaction could be established between animal and human transmission cycles due to the small canine sample size and as the former did not come into contact with children attending ICBF day-care centres.

Circadian clocks regulate the temporal organization of several biochemical processes, including lipid metabolism, and their disruption leads to severe metabolic disorders. Immortalized cell lines acting as circadian clocks display daily variations in [(32)P]phospholipid labeling; however, the regulation of glycerophospholipid (GPL) synthesis by internal clocks remains unknown. Here we found that arrested NIH 3T3 cells synchronized with a 2 h-serum shock exhibited temporal oscillations in a) the labeling of total [(3)H] GPLs, with lowest levels around 28 and 56 h, and b) the activity of GPL-synthesizing and GPL-remodeling enzymes, such as phosphatidate phosphohydrolase 1 (PAP-1) and lysophospholipid acyltransferases (LPLAT), respectively, with antiphase profiles. In addition, we investigated the temporal regulation of phosphatidylcholine (PC) biosynthesis. PC is mainly synthesized through the Kennedy pathway with choline kinase (ChoK) and CTP:phosphocholine cytidylyltranferase (CCT) as key regulatory enzymes. We observed that the PC labeling exhibited daily changes, with the lowest levels every ~28 h, that were accompanied by brief increases in CCT activity and the oscillation in ChoK mRNA expression and activity. Results demonstrate that the metabolisms of GPLs and particularly of PC in synchronized fibroblasts are subject to a complex temporal control involving concerted changes in the expression and/or activities of specific synthesizing enzymes.

Introduction: We analysed a large sample of children diagnosed with urinary tract malformations and/or infections and calculated diagnostic efficiency and quality indexes for five different functional markers, with the goal of testing which is the most sensitive for detecting a loss of renal parenchyma., Patients and Method: Ours was a cross-sectional retrospective study in which the clinical histories of 179 paediatric patients (91 male and 88 female) were evaluated. In 102 of these patients (57%), a scintigraphy revealed loss of parenchyma. The most commonly observed morphological type of damage was renal scarring. All patients had undergone at least one desmopressin urine concentration test. We also analysed albumin/creatinine and N-acetyl-glucosaminidase (NAG)/creatinine ratios, glomerular filtration rate (GFR), and urine volume., Results: By distributing patients according to normal/abnormal scintigraphy, we observed statistically significant differences between the two groups in maximum urine osmolality and GFR. Urine volume was elevated in 31.3% of cases (sensitivity: 37.9%; specificity: 81.8%) and 24% had a defect in renal concentrating ability (sensitivity: 30.4%; specificity: 84.8%). Urinary albumin excretion was high in 12.2% of patients, and 7.2% had a high NAG/creatinine ratio. GFR was low in only 5.7% of patients. These last two markers were the least sensitive but most specific for detecting a loss of renal parenchyma (100%)., Conclusions: In our study, the most sensitive functional tests for detecting the loss of renal parenchyma were the two that take into account the ability of the kidney to manage water, i.e. urine volume and maximum urine osmolality. These two tests had specificity >80%. However, the maximum specificity was obtained by the NAG/creatinine ratio and GFR, which were, conversely, the least sensitive tests. A normal GFR does not necessarily show normal renal function.

Seventeenth-century English closets were books containing a wide repertoire of household supplies targeted at female readers. Such volumes typically included medical recipes, as early modern women also used to be responsible for preserving and restoring the health of relatives and close neighbors. A Closet for Ladies and Gentlewomen (Sir Hugh Platt, 1608), in particular, incorporates 13 medicinal remedies devised for the therapeutic management of 3 different types of headaches: head-ache, migraine and pain in the head. This article historically contextualizes the text, offers a valid classification of headaches in 17th-century England, and describes the composition of the homemade pharmaceutical forms recommended to female caregivers, the guidelines for administration and its potential pain-relieving effects., (© 2010 American Headache Society.)

Proteomics has become one of the most relevant high-throughput technologies. Several approaches have been used for studying, for example, tumor development, biomarker discovery, or microbiology. In this "post-genomic" era, the relevance of these studies has been highlighted as the phenotypes determined by the proteins and not by the genotypes encoding them that is responsible for the final phenotypes. One of the most interesting outcomes of these technologies is the design of new drugs, due to the discovery of new disease factors that may be candidates for new therapeutic targets. To our knowledge, no commercial fungicides have been developed from targeted molecular research, this review will shed some light on future prospects. We will summarize previous research efforts and discuss future innovations, focused on the fight against one of the main agents causing a devastating crops disease, fungal phytopathogens.

The vertebrate retina is known to contain three classes of photoreceptor cells: cones and rods responsible for vision, and intrinsically photoresponsive retinal ganglion cells (RGCs) involved in diverse non-visual functions such as photic entrainment of daily rhythms and pupillary light responses. In this paper we investigated the potential intrinsic photoresponsiveness of the rat RGC line, RGC-5, by testing for the presence of visual and non-visual opsins and assessing expression of the immediate-early gene protein c-Fos and changes in intracellular Ca(2+) mobilization in response to brief light pulses. Cultured RGC-5 cells express a number of photopigment mRNAs such as retinal G protein coupled receptor (RGR), encephalopsin/panopsin (Opn3), neuropsin (Opn5) and cone opsin (Opn1mw) but not melanopsin (Opn4) or rhodopsin. Opn5 immunoreactivity was observed in RGC-5 cells and in the inner retina of rat, mainly localized in the ganglion cell layer (GCL). Furthermore, white light pulses of different intensities and durations elicited changes both in intracellular Ca(2+) levels and in the induction of c-Fos protein in RGC-5 cell cultures. The results demonstrate that RGC-5 cells expressing diverse putative functional photopigments display intrinsic photosensitivity which accounts for the photic induction of c-Fos protein and changes in intracellular Ca(2+) mobilization. The presence of Opn5 in the GCL of the rat retina suggests the existence of a novel type of photoreceptor cell.

The rat retinal ganglion cell (RGC) line RGC-5 constitutes a widely used model for studying physiological processes in retinal cells. In this paper we investigated the expression of clock and immediately early genes, and calcium mediated responses to physiological stimuli in differentiated and mitotically active RGC-5 cells. To this end, we attempted to differentiate the RGC-5 cells with a variety of effectors classically used to induce morphological differentiation. No sign of morphological differentiation was observed after 24 h of treatment with BDNF (80 ng/mL), NGF (100 ng/mL) and retinoic acid (20 ng/mL), among others. Only staurosporine (SSP) was able to promote neurite outgrowth at concentrations ranging from 53.5 to 214 nM. However, apoptotic nuclei were seen at 24 h of treatment using DNA staining, and a few cells remained at 72 h post-treatment. Concentrations of SSP lower than 214 nM were partially effective in inducing cell differentiation. Dividing RGC-5 cells express the RGC marker Thy-1 and different clock genes such as Per1, Clock and Bmal1. When characterizing the responsiveness of proliferative RGC-5 cells we found that in most of them, brief pulses of 50% FBS induced c-Fos and PER1 expression. Subsets of RGC-5 cells displayed significant changes in intracellular Ca2+ levels by ATP (100 microM) but not by glutamate (100-200 microM) stimulation. On the basis of cell morphology, size and complexity and effector responsiveness it was possible to distinguish different subpopulations within the cell line. The results demonstrate that only SSP is effective in promoting RGC-5 morphological differentiation, though the treatment provoked cell death. Proliferative cells expressing the RGC marker Thy-1 and a number of clock genes, responded differentially to diverse physiological stimuli showing a rapid c-Fos and PER1 induction by FBS stimulation, and an increase in intracellular Ca2+ by ATP., ((c) 2010 Elsevier Ltd. All rights reserved.)

Objectives: In this paper we describe the history of lithiasis and the development of its treatment. We discuss the steps that led to the birth of endoscopic surgery and extracorporeal shockwave lithotripsy., Methods: We reviewed books and writings of History of Urology and Endourology., Results/conclusions: To know a little of the history and treatment of lithiasis, the contributions of Spanish urologists, as well as the instruments that made it possible.

Objectives: The objective of this work is to analyze the treatment of staghorn calculi at our Department of Urology. We have to know the recent development of endoscopic surgery (percutaneous renal surgery) and external shock wave lithotripsy., Methods: We reviewed the surgical management of staghorn calculi during the period between 1987 and 2004., Results: Percutaneous renal surgery was performed successfully in 24.1% of the cases. Persisting residual fragments appeared in 75.9% and were treated by ESWL or second endoscopic surgery., Conclusions: Percutaneous renal surgery may be considered the technique of choice to treat staghorn calculi. Endoscopic surgery has good results and little complications with low morbidity. In other cases the treatment is combined therapy, percutaneous renal surgery and ESWL.