Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors. This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021. Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%). We pre­sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population

Ellipsoidal analysis of coordination polyhedra

The idea of the coordination polyhedron is essential to understanding chemical structure. Simple polyhedra in crystalline compounds are often deformed due to structural complexity or electronic instabilities so distortion analysis methods are useful. Here we demonstrate that analysis of the minimum bounding ellipsoid of a coordination polyhedron provides a general method for studying distortion, yielding parameters that are sensitive to various orders in metal oxide examples. Ellipsoidal analysis leads to discovery of a general switching of polyhedral distortions at symmetry-disallowed transitions in perovskites that may evidence underlying coordination bistability, and reveals a weak off-centre ‘d(5) effect' for Fe(3+) ions that could be exploited in multiferroics. Separating electronic distortions from intrinsic deformations within the low temperature superstructure of magnetite provides new insights into the charge and trimeron orders. Ellipsoidal analysis can be useful for exploring local structure in many materials such as coordination complexes and frameworks, organometallics and organic molecules

Beef quality differentiation in the framework of the Serrana de Teruel endangered breed conservation programme

La Serrana de Teruel es una raza bovina en peligro de extinción, criada tradicionalmente en áreas montañosas del Sur de Aragón (España). Con objeto de recuperar la raza, se realizó la caracterización morfológica, zootécnica y genética de la población existente. La raza presentó un grado medio-alto de armonía y homogeneidad, siendo la mayoría de individuos de perfil recto, eumétricos y sublongilíneos, aunque de menor tamaño al observado en otras razas filogenéticamente próximas. Los estudios de biodiversidad mostraron niveles altos de variabilidad genética y bajos de consanguinidad, a pesar del censo reducido (240 individuos en 2010), y proporcionaron las bases para llevar a cabo un programa sostenible de conservación. Para garantizar su mantenimiento a largo plazo, los bancos de germoplasma mantienen 6400 dosis de semen y 74 embriones. Paralelamente, se analizó la viabilidad comercial de la raza, a través del estudio de la calidad de canal y carne de las categorías comerciales de ternero, añojo y cebón (castrados con 9 meses), con edades a sacrificio de 12, 22 y 22 meses y pesos vivos de 470, 720 y 660 kg, respectivamente. Finalmente, se realizó un análisis prospectivo, según la opinión de expertos, de una nueva carne de vacuno con denominación de calidad, llamada ‘Serrana de Teruel’. Estos trabajos muestran la posibilidad de realizar una producción alternativa, tipo cebón, susceptible de acogerse a distintivos de calidad diferenciada, que podrían suponer un incentivo para la explotación de la Serrana de Teruel frente a otras razas, lo que favorecería su conservación a medio plazo.Serrana de Teruel is an endangered cattle breed raised traditionally in the mountainous areas of Southern Aragon (Spain). With the aim of recovering the breed, a characterization was carried out to determine the morphology, husbandry and genetic values of the Serrana de Teruel breed. Individuals showed a medium to high degree of homogeneity and harmony, most of the animals being of straight profile, and eumetrical and sublongilineal individuals, although smaller in size than other phylogenetically proximate breeds. Biodiversity studies showed good diversity values despite the breed’s low effective population size (240 individuals in 2010). These studies provided the basis for a sustainable programme of genetic conservation. In order to guarantee long-term maintenance, germplasm banks contain 6400 doses of semen and 74 embryos. Concurrently, the commercial viability of the breed was studied by means of an analysis of carcass and meat quality from three commercial categories – yearling, bull and steer (castrated at 9 months old) – with ages at slaughter of 12, 22 and 22 months and live weights of 470, 720 and 660 kg,, respectively. Good performances and high-quality products with no commercial constraints in the beef market were obtained. Finally, a prospective study for a new beef quality product labelled ‘Serrana de Teruel’ was performed, according to the opinions of experts. These studies provide the standard requirements for the alternative production of a labelled beef product that might create an incentive for the production of the Serrana de Teruel breed among other breeds, and thus favour the conservation of the breed in the medium termLa Serrana de Teruel est une race bovine rustique élevée dans les régions montagneuses du sud de l’Aragon (Espagne) qui est en danger d’extinction. Afin de récupérer cette race on a réalisé la caractérisation morphologique, génétique et zootechnique de la population existante. La race présente un degré moyen-élevé d’harmonie et d’uniformité, la plupart des animaux étant de profil droit, eumétrique et sublongiligne, bien que plus petit en taille que les autres races proches. Des études sur la biodiversité ont montré des niveaux élevés de diversité génétique et un faible niveau de consanguinité, malgré les effectifs limités d’animaux (240 individus en 2010), en fournissant les bases du programme de conservation. Afin de garantir le maintien à long terme, a été créée une banque de matériel génétique contenant 6400 doses de semence et 74 embryons. En parallèle, on a confirmé la viabilité commerciale de la race à travers l’étude de la qualité de la carcasse et de la viande pour les catégories commerciales de veau, taurillon et bouvillons (castrés à 9 mois), avec des âges à l’abattage de 12, 22 et 22 mois, et 470, 720 et 660 kg de poids vif, respectivement. Enfin, nous avons mené une analyse prospective, à dires d’experts, pour un nouveau label de qualité du boeuf appelé ‘Serrana de Teruel’. Ces travaux montrent la possibilité d’une production alternative, comme boeuf, susceptible de bénéficier d’une certification de qualité, ce qui pourrait créer une incitation pour l’exploitation de la Serrana de Teruel parmi les autres races, et ainsi favoriser sa préservation à long termePublishe

Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes. alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients

A qualitative investigation of the impact of peer to peer online support for women living with Polycystic Ovary Syndrome

Background: Polycystic Ovary Syndrome is a common, chronic condition which affects women living with the condition both physically and psychologically. Social support may be beneficial to sufferers in coping with chronic conditions and the Internet is becoming a common place for accessing social support and information. The aim of this study was to consider the experiences of women living with Polycystic Ovary Syndrome who access and participate in an online support group discussion forum dedicated to issues surrounding this condition. Methods: Fifty participants responded to a series of open-ended questions via an online survey. Results: Thematic analysis revealed a number of empowering and disempowering experiences associated with online support group participation. The empowering processes reported by members of the group included: Connecting with others who understand; Access to information and advice; Interaction with healthcare professionals; Treatment-related decision making; Improved adjustment and management. In terms disempowering processes, only two were described by group participants: Reading about the negative experiences of others and Feeling like an outsider. Conclusions: For women living with Polycystic Ovary Syndrome, participation within an online support group may help to empower them in a range of important ways however, there may be some disempowering consequences

Ibero-American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages

International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2-4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(&gt; MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of &gt;= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3&nbsp;days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3&nbsp;days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely