The life of the cell membrane: A paradigmatic reading from Deleuze and Guattari.

While the Fluid Mosaic model (FMM) is widely accepted as an account of the cell membrane's structure-function, its inability to explain certain phenomena has led to the lipid rafts hypothesis (nanodomains) that spontaneous spatiotemporal enriched zones of sphingolipids-cholesterol-protein exist within the membrane. In this text, we propose a novel approach that conceives the cell membrane as a living entity. The questions regarding the FMM revolve around the fact that, although these molecular components are present in many cell types, the membrane does not react in the same way to every external agent; for example, a virus evokes a particular response: why is there some marked specificity of virus (or toxin) attack on one (or some) of these cell types and not to other cell types that nevertheless have a similar membrane protein constitution? The crucial question, to explain this selectivity, would be what determines the specificity of attack on some cells and not others? While FMN assumes a dynamism between macrostates at the intramolecular, intermolecular, and/or collective levels in the membrane, the approach of the lipid raft model presupposes a much greater and more complex dynamics of microstates (even nano-states) of these molecular components. In other words, it implies higher and instantaneous mobility as assemblages ("intentional") and thus, of the membrane itself (as a collective), in response to changes in the internal and external physicochemical environment over a broad spatiotemporal scale. This suggests a mechanism of membrane adaptation in the face of evolutionary constraints. In this text, we propose a paradigmatic approach, from Deleuze-Guattari's philosophy: to conceive the cell membrane as living and not as a mere molecular conglomerate with particular functions and mechanical processes between molecules. For this, we employ the functional concepts of territory and machinic assemblage, whence the vitality of the membrane would allow us to postulate instantaneous updates, within wider spatiotemporal scales in its composition in contrast with the model that dominates as a more plausible explanation nowadays, that does not include smaller spatiotemporal events. If we resort to the concept of territory and its different media components, we could offer a more plausible explanation of the vigorous dynamism in the composition of the cell membrane since it would allow more subtle and complex differentiations between media and thus make visible the constant and instant changes. We propose that the model of nanodomains, understood as a process of dynamic territorialization, offers a more complex and subtle explanation of the instantaneous changes in the cell membrane's composition. This approach expands the explanatory framework for cellular phenomena and reveals their spatiotemporal complexity in accordance with other research.

Estimated Phytate Intake Is Associated with Bone Mineral Density in Mediterranean Postmenopausal Women.

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [ß(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm2], femoral Ward's triangle [0.033(0.013-0.054) g/cm2], total femur [0.018(0.001-0.035) g/cm2], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm2] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm2 and without type 2 diabetes (all p-for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

Implementation of Zebrafish Ontologies for Toxicology Screening.

Toxicological evaluation of chemicals using early-life stage zebrafish (Danio rerio) involves the observation and recording of altered phenotypes. Substantial variability has been observed among researchers in phenotypes reported from similar studies, as well as a lack of consistent data annotation, indicating a need for both terminological and data harmonization. When examined from a data science perspective, many of these apparent differences can be parsed into the same or similar endpoints whose measurements differ only in time, methodology, or nomenclature. Ontological knowledge structures can be leveraged to integrate diverse data sets across terminologies, scales, and modalities. Building on this premise, the National Toxicology Program's Systematic Evaluation of the Application of Zebrafish in Toxicology undertook a collaborative exercise to evaluate how the application of standardized phenotype terminology improved data consistency. To accomplish this, zebrafish researchers were asked to assess images of zebrafish larvae for morphological malformations in two surveys. In the first survey, researchers were asked to annotate observed malformations using their own terminology. In the second survey, researchers were asked to annotate the images from a list of terms and definitions from the Zebrafish Phenotype Ontology. Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, but a larger study is needed to confirm. We conclude that utilizing a common data standard will not only reduce the heterogeneity of reported terms but increases agreement and repeatability between different laboratories. Thus, we advocate for the development of a zebrafish phenotype atlas to help laboratories create interoperable, computable data.

Characterization of γ-glutamyltransferase- and phytochelatin synthase-mediated catabolism of glutathione and glutathione S-conjugates in Arabidopsis thaliana.

Glutathione (GSH, γ-L-glutamyl-L-cysteinyl-glycine) has been implicated in a multitude of cellular functions, such as protection of cells against oxidative stress, detoxification of xenobiotics via degradation of GSH S-conjugates, and disease resistance. Glutathione also serves as a precursor of phytochelatins, and thereby plays an essential role in heavy metal detoxification. The Arabidopsis genome encodes three functional γ-glutamyltransferase genes (AtGGT1, AtGGT2, AtGGT4) and two phytochelatin synthase genes (AtPCS1, AtPCS2). The function of plant GGT has not yet been clearly defined, although it is thought to be involved in GSH and GSH S-conjugate catabolism. On the other hand, besides its role in heavy metal detoxification, PCS has also been involved in GSH S-conjugate catabolism. Herein we describe the HPLC characterization of GSH and GSH S-conjugate catabolism in Arabidopsis mutants deficient in GSH biosynthesis (pad2-1/gsh1), atggt and atpcs1 T-DNA insertion mutants, atggt pad2-1, atggt atpcs1 double mutants, and the atggt1 atggt4 atpcs1 triple mutant. The results of our HPLC analysis confirm that AtGGT and AtPCS play important roles in two different pathways related with GSH and GSH S-conjugate (GS-bimane) catabolism in Arabidopsis.

Early immunologic response to mRNA COVID-19 vaccine in patients receiving biologics and/or immunomodulators.

Patients with immune conditions and immune-modifying therapies were excluded from the Covid-19 vaccine trials. Studies have shown conflicting response to different vaccines in persons receiving immune suppressors or biologics. The aim of this study is to evaluate humoral and cellular response to Covid-19 vaccines in patients with Inflammatory Bowel Disease (IBD) using biologic and/or immunomodulatory (IMM) therapies. Methods: Participants are adults with IBD receiving biologics or IMM planning to receive a Covid 19 vaccine. Cellular immunity (CD4+ and CD8+ T cell levels) with flow cytometry are measured at baseline and 2 weeks after each vaccine dose. Humoral immunity (antibody titers and neutralizing capacity,VNT%) is analyzed by ELISA at baseline, 2 weeks after each dose, and 6 and 12 months after vaccine. We present the early results of the first 19 subjects. The study is approved by the IRB. Results: 19 subjects (18 in biologics and 1 in IMM) who received 2 doses of the Pfizer-BioNTech vaccine are included. Total IgG antibodies increased 21.13 times after the first dose and 90 times after the second dose. VTN% increased 11.92 times after the first dose and 53.79 times after the second dose. When compared with a healthy control cohort, total IgG antibodies and VTN% were lower in the subjects after the first dose. After the second dose, IgG antibodies increased but remained lower than controls, but VTN% were similar to controls. CD4 and CD8 mean levels had an upward trend after vaccination. Conclusions: Neutralizing capacity response to the vaccine in subjects was similar to a healthy cohort in spite of lower increases in total IgG antibodies. The CD4 and CD8 results observed may support the capacity to mount an effective cellular response in patients on biologics. Larger studies are needed to determine vaccine efficacy in these patients.

Association of Adherence to The Mediterranean Diet with Urinary Factors Favoring Renal Lithiasis: Cross-Sectional Study of Overweight Individuals with Metabolic Syndrome.

Our purpose was to study the relationship of adherence to the Mediterranean diet (MedDiet) with urinary factors that favor the formation of renal calcium and uric acid stones in overweight and obese participants who had metabolic syndrome. This cross-sectional study examined 267 participants. A well-known MedDiet score (range 0-9) was calculated for each patient, and patients were then categorized has having low (≤3), medium (4-5), or high (≥6) adherence to the MedDiet. Baseline characteristics and urinary parameters were also analyzed. High calcium salt urinary crystallization risk (CaUCR) and high uric acid urinary crystallization risk (UrUCR) were calculated from urinary parameters using pre-defined criteria. More than half of patients with MedDiet scores ≤3 had high UrUCR (55.4%) and high CaUCR (53.8%). In contrast, fewer patients with high adherence (≥6) to the MedDiet had high UrUCR (41.2%) and high CaUCR (29.4%). Relative to those with low adherence, individuals with high adherence had a prevalence ratio (PR) of 0.77 for a high UrUCR (95% CI: 0.46-1.12; p for trend: 0.069) and a PR of 0.51 for a high CaUCR (95% CI: 0.26-0.87; p for trend: 0.012) after adjusting for age, sex, body mass index, type 2 diabetes, and total energy intake. Our findings indicate that greater adherence to the MedDiet was associated with a reduced CaUCR and a reduced UrUCR. This suggests that adequate dietary management using the MedDiet patterns may prevent or reduce the incidence and recurrence of calcium salt and uric acid renal stones.

Impaired Liver Size and Compromised Neurobehavioral Activity are Elicited by Chitosan Nanoparticles in the Zebrafish Embryo Model.

The use of chitosan nanoparticles (ChNPs) in various biological and environmental applications is attracting great interest. However, potential side effects related to ChNP toxicity remain the major limitation hampering their wide application. For the first time, we investigate the potential organ-specific (cardiac, hepatic, and neuromuscular) toxicity of ChNPs (size 100⁻150 nm) using the zebrafish embryo model. Our data highlight the absence of both acute and teratogenic toxic effects of ChNPs (~100% survival rate) even at the higher concentration employed (200 mg/L). Although no single sign of cardiotoxicity was observed upon exposure to 200 mg/L of ChNPs, as judged by heartbeat rate, the corrected QT interval (QTc, which measures the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle), maximum cardiac arrest, and ejection fraction assays, the same dosage elicited the impairment of both liver size (decreased liver size, but without steatosis and lipid yolk retention) and neurobehavioral activity (increased movement under different light conditions). Although the observed toxic effect failed to affect embryo survival, whether a prolonged ChNP treatment may induce other potentially harmful effects remains to be elucidated. By reporting new insights on their organ-specific toxicity, our results add novel and useful information into the available data concerning the in vivo effect of ChNPs.

Effect of Consumption of Cocoa-Derived Products on Uric Acid Crystallization in Urine of Healthy Volunteers.

The purpose of this study was to determine the effects of consumption of different cocoa-derived products on uric acid crystallization in urine of 20 healthy volunteers. Participants were requested to select the specific diet that they wished to follow during the 12 h prior to collection of urine. The only restriction was that the diet could not include any product with cocoa, coffee, or caffeine. On the first day, each volunteer followed their selected diet, and an overnight 12 h urine sample was collected as the baseline urine. After seven days on an unrestricted diet, each volunteer repeated the same diet with 20 g of milk chocolate, chocolate powder, or dark chocolate during breakfast and another 20 g during dinner. Overnight 12 h urine samples were then collected. Urine volume, pH, oxalate, creatinine, uric acid, theobromine, and a uric acid crystallization test were determined for each sample. The results for all 20 patients show that uric acid crystallization was significantly lower following the consumption of chocolate powder or dark chocolate relative to baseline or following the consumption of milk chocolate. The results indicated that increased concentrations of urinary theobromine reduced the risk of uric acid crystallization.

[Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities]. / Uso continuado de inhibidores de la PDE5 en el tratamiento de la disfunción eréctil: nuevas perspectivas y oportunidades.

At present, there is debate regarding the continuous use of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Cumulative evidence supports the benefit, even at low doses, thatcontinuous treatment has on erectile function -even in difficult-to-treat patients-, and on the spontaneity and naturalness of sexual relationships. Safety and tolerability have also proven to be good. Beyond phosphodiesterase 5 inhibition, the effect of continuous treatment of erectile function appears to be based on improvement of endothelial function and oxygenation of the penile vascular bed as a result of the increased number of erections, hence playing down the importance of pharmacokinetics. Although evidence is still limited, this new scenario opens new paths for the treatment of erectile dysfunction patients in whom on-demand treatments are not effective or deemed appropriate, and would benefit the spontaneity of sexual life.

Relationship Between Erectile Dysfunction, Diabetes and Dyslipidemia in Hypertensive-Treated Men.

PURPOSE: PRESIDEN study is a large study to analyze the erectile dysfunction (ED) incidence in Spanish population. The present study is a pilot sub-analysis from PRESIDEN to determine if ED or plasma testosterone (TST) level in controlled hypertensive patients may be associated with comorbidities and/or plasma nitrite+nitrate and antioxidant capacity. MATERIALS AND METHODS: Forty-four hypertensive individuals were aleatory selected from PRESIDEN study, matching by age (28 showing ED and 16 without ED). RESULT: Diabetes was present in 28.57% of ED patients and in 18.75% of patients without ED. In patients with and without ED, increasing age showed tendency of higher frequency of an additional comorbidity (diabetes or dyslipemia) (P = .09). Apparently, plasma TST levels were lower in older ED patients compared to younger patients with and without ED, although it did not reach statistical significance (P = .69). Older ED patients also showed lower TST levels than older patients without ED, although it was not statistical significant (16.15 ± 2.84 vs 13.91± 2.77; P = .69). Dyslipidemia was showed by 52.17% with lower TST (? nmol/L) while 23.80% of patients with plasma TST levels > 15 nmol/L had dyslipidemia. The percentage of ED patients was similar between patients with low and high TST levels. CONCLUSION: More ED hypertensive patients seem to show two comorbidities (diabetes and dyslipidemia) than hypertensivepatients without ED. Younger patients with ED tended to show more commonly diabetes than older ED patients. Plasma TST levels were not associated with more prevalence of ED but lower plasma TST levels showed tendency to higher prevalence of dyslipidemia.

Uso continuado de inhibidores de la PDE5 en el tratamiento de la disfunción eréctil: nuevas perspectivas y oportunidades / Continuous use of PDE5 inhibitors in the treatment of erectile dysfunction: New insights and opportunities

Actualmente existe un debate acerca del uso continuado de los inhibidores de la fosfodiesterasa 5 en el tratamiento de la disfunción eréctil. Varios estudios apoyan el beneficio que, incluso a bajas dosis, esta estrategia terapéutica tiene sobre la función eréctil -incluso en pacientes considerados difíciles de tratar-, y sobre la espontaneidad y naturalidad de las relaciones sexuales. También ha demostrado además ser bien tolerados y seguros. Más allá de la inhibición de la fosfodiesterasa 5, el efecto sobre la función eréctil parece basarse en la mejora de la función endotelial y de la oxigenación del área vascular peneana resultado del incremento del número de erecciones, restando así importancia a la farmacocinética. Aunque la evidencia es limitada, este nuevo escenario abre nuevas oportunidades en el tratamiento de pacientes para los que el tratamiento a demanda no es efectivo o apropiado, y podría favorecer la espontaneidad de la vida sexual (AU)

At present, there is debate regarding the continuous use of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Cumulative evidence supports the benefit, even at low doses, thatcontinuous treatment has on erectile function -even in difficult-to-treat patients-, and on the spontaneity and naturalness of sexual relationships. Safety and tolerability have also proven to be good. Beyond phosphodiesterase 5 inhibition, the effect of continuous treatment of erectile function appears to be based on improvement of endothelial function and oxygenation of the penile vascular bed as a result of the increased number of erections, hence playing down the importance of pharmacokinetics. Although evidence is still limited, this new scenario opens new paths for the treatment of erectile dysfunction patients in whom on-demand treatments are not effective or deemed appropriate, and would benefit the spontaneity of sexual life (AU)

Disfunción eréctil, litiasis renal y test de ADAM: estudio observacional mediante encuesta telefónica / Renal lithiasis, erectile dysfunction and ADAM test: observational study using telephone survey

Objetivo. La litiasis renal se asocia con trastornos hormonales y metabólicos, factores comunes a la disfunción eréctil. Algunos trabajos han estudiado la asociación entre la disfunción eréctil y la urolitiasis; sin embargo, los datos son todavía escasos. El objetivo del presente estudio fue estudiar la asociación entre la disfunción eréctil y la litiasis renal, así como las relaciones entre disfunción eréctil y síntomas asociados con el envejecimiento sugestivos de síndrome de déficit de testosterona con factores de riesgo cardiovascular. Material y métodos. Se realizó un estudio observacional transversal mediante encuesta telefónica. Por muestreo polietápico aleatorio, se seleccionó una muestra de 1.193 varones de edades comprendidas de 40 a 65años residentes en España. Se recogieron variables sociodemográficas y clínicas. Se usó el cuestionario del ADAM para evaluar los síntomas sugestivos de síndrome de deficiencia de testosterona. Resultados. La litiasis renal fue más frecuente en los pacientes con disfunción eréctil. La hipertensión arterial, la diabetes y la hipercolesterolemia se asociaron significativamente con la disfunción eréctil. La diabetes, la edad, la clase social media-alta basada en la ocupación laboral (claseii), la hipertensión arterial y la hipercolesterolemia fueron factores predictores independientes de un cuestionario ADAM positivo. Conclusiones. Nuestros datos indican una posible relación entre la disfunción eréctil y la litiasis renal. La relación entre la disfunción eréctil y un cuestionario de ADAM positivo con los factores de riesgo cardiovascular ponen de manifiesto la importancia de evaluar el riesgo cardiovascular de los pacientes que presentan dichas condiciones (AU)

Objective. Renal lithiasis is associated with hormonal and metabolic disorders, common factors to erectile dysfunction. A number of studies have analyzed the association between erectile dysfunction and urolithiasis, however data are still scarce. We aimed to study the association between erectile dysfunction and renal lithiasis, as well as the relations between erectile dysfunction and symptoms associated with aging suggestive of testosterone deficiency syndrome, and cardiovascular risk factors. Material and methods. A cross-sectional observational study of population level by telephone survey was conducted. By sampling random multistage, we selected a sample of 1,193 males aged 40 to 65 living in Spain. Socio-demographic and clinical variables were recorded. Suggestive symptoms of testosterone deficiency syndrome were screened by the ADAM questionnaire. Results. Renal lithiasis was more frequent in patients with erectile dysfunction. High blood pressure, diabetes and hypercholesterolemia were significantly associated with erectile dysfunction. Age, upper middle based on occupation (social classii), high blood pressure, diabetes and hypercholesterolemia were independent predictors of a positive ADAM questionnaire. Conclusions. Our results point out a possible relationship between erectile dysfunction and renal lithiasis. The connection between erectile dysfunction, symptoms associated with aging suggestive of testosterone deficiency syndrome, and cardiovascular risk factors remarks the importance of assessing the cardiovascular risk of patients presenting these conditions (AU)

Diagnóstico, tratamiento y seguimiento de la eyaculación precoz: recomendaciones de experto / Diagnosis, treatment and follow-up of premature ejaculation: expert's recommendations

Objetivos. Elaborar recomendaciones sobre el diagnóstico, tratamiento y seguimiento de la eyaculación precoz (EP). Material y método. Un grupo multidisciplinar de expertos planteó las preguntas clínicas. En base a una revisión sistemática no exhaustiva y la experiencia clínica, se elaboraron recomendaciones que fueron validadas en una ronda Delphi y, posteriormente, en una reunión presencial. Resultados. El interrogatorio es básico para el diagnóstico de la EP, que se complementará con una exploración física y con el uso de cuestionarios específicos. El tratamiento psicológico de la EP con terapia sexual y técnicas conductuales es eficaz, siendo más eficaz combinado con tratamiento farmacológico. No se recomienda el uso de agentes anestésicos ni las intervenciones quirúrgicas. Los inhibidores selectivos de la recaptación de serotonina (ISRS) son eficaces y seguros, siendo la dapoxetina el único fármaco con indicación. Los inhibidores de la fosfodiesterasa tipo5 no tienen suficiente evidencia que avale su uso. No existen estrategias estandarizadas de seguimiento de esta patología, si bien se pueden utilizar herramientas como escalas, cuestionarios o la autoestimación del tiempo de latencia intravaginal para la evaluación de la respuesta, y un seguimiento específico de visitas en caso de la toma de ISRS. Conclusiones. El presente consenso propone diversas recomendaciones referidas al manejo de la EP fundamentadas en la evidencia y en la experiencia clínica y que pretende ser un instrumento útil al clínico implicado en el manejo de estos pacientes (AU)

Objectives. To develop recommendations on the diagnosis, treatment and monitoring of premature ejaculation (PE). Material and method. A multidisciplinary group of experts created clinical questions. Based on a non-exhaustive systematic review and their clinical experience, recommendations were developed and validated in a Delphi round and, after that, in a meeting. Results. Interviews are essential for the diagnosis of PE, which has to be complemented with a physical examination and the use of specific questionnaires. Psychological treatment of PE with sex therapy and behavioral techniques is effective, and it is more effective when combined with drug treatment. The use of anesthetic agents or surgical interventions is not recommended. Selective serotonin reuptake inhibitors (SSRIs) are effective and safe, being dapoxetine the only drug with specific indication for PE. Inhibitors of phosphodiesterase type5 have not enough evidence to support their use. There are no standardized monitoring strategies for this disease, although tools such as scales, questionnaires or self-esteem intravaginal latency time for response assessment can be used, in addition to specific follow-up visits if the patient is taking SSRIs. Conclusions. This consensus proposes several recommendations regarding the management of PE according to evidence and clinical experience and aims at being a useful clinical instrument for the management of these patients (AU)

ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish.

Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs principles. It Reduces, by up to a third, the number of animals required to assess toxicity in those organs. It Refines the drug toxicity evaluation through novel physiological parameters. Finally, it might allow the Replacement of classical species, such as rodents and larger mammals, thanks to its high predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).

[May renal lithiasis be really prevented? New trends and therapeutic tools.] / Se puede realmente prevenir la litiasis renal? Nuevas tendencias y herramientas terapéuticas.

Renal calculi are generally formed as a result of the combination of certain factors, some related to urine composition (concentration of lithogenic substances, deficiency of crystallization inhibitors, presence of heterogeneous nucleants) and others with renal morphology and anatomy (urinary tract stasis, low urodynamic efficiency cavities, morpho-anatomic deformations, renal papillary tissue lesions). In fact, the composition, macrostructure and microstructure of the calculus will clearly depend on the factors that have induced it. For this reason, the appropriate study and classification of the renal calculi simplifies the diagnosis and allows a more effective therapeutic approach since it can be oriented to directly correct the etiological factors responsible for stone formation. In this article, we review the main etiological factors involved in the formation of each type of calculus and the prophylactic measures that can be adopted for proper correction. The most frequent kidney stones have been classified into the following types: calcium oxalate monohydrate papillary calculi, calcium oxalate monohydrate non-papillary calculi, calcium oxalate dihydrate calculi, mixed hydroxyapatite/ calcium oxalate calculi, carboxyapatite/hydroxyapatite calculi, brushite calculi, struvite/carboxyapatite calculi, uric acid calculi, uric acid/calcium oxalate monohydrate calculi, and cystine calculi. Occasionally, however, the calculus is not available for study, in which case the only way forward is to use all available information (clinical history, life habits, radiological data), together with basic biochemical information, to identify and correct all etiological factors related to renal lithiasis that have been identified.

¿Se puede realmente prevenir la litiasis renal? Nuevas tendencias y Herramientas terapéuticas / May renal lithiasis be really prevented? New trends and therapeutic tools

Los cálculos renales se forman en general como consecuencia de la combinación de determinados factores, algunos relacionados con la composición de la orina (concentración de sustancias litógenas, déficit de inhibidores de la cristalización, presencia de nucleantes heterogéneos) y otros con la morfoanatomía renal (estasis urinaria, cavidades de baja eficacia urodinámica, deformaciones morfoanatómicas, lesiones del tejido papilar renal). De hecho, la composición, macroestructura y microestructura del cálculo dependerán claramente de los factores que lo han inducido. Por esta razón, disponer del cálculo renal convenientemente estudiado y clasificado simplifica el diagnóstico y posibilita un enfoque terapéutico más eficaz ya que se dirige directamente a corregir los factores etiológicos responsables de la litiasis. En esta publicación revisamos los principales factores etiológicos implicados en la formación de cada tipo de cálculo y las medidas profilácticas que pueden adoptarse para su adecuada corrección. Los cálculos renales más frecuentes se han clasificado en los siguientes tipos: cálculos de oxalato cálcico monohidrato papilares, cálculos de oxalato cálcico monohidrato de cavidad, cálculos de oxalato cálcico dihidrato, cálculos mixtos de hidroxiapatita/oxalato cálcico, cálculos de carboxiapatita/hidroxiapatita, cálculos de brushita, cálculos de estruvita/carboxiapatita, cálculos de ácido úrico, cálculos de ácido úrico/oxalato cálcico monohidrato y cálculos de cistina. En ocasiones, sin embargo, no se dispone del cálculo para su estudio, en cuyo caso el único camino a seguir consiste en utilizar toda la información disponible (historial clínico, hábitos de vida, datos radiológicos), junto con la información bioquímica urinaria básica, para identificar y corregir cuantos factores etiológicos relacionados con la litiasis renal se hayan identificado

Renal calculi are generally formed as a result of the combination of certain factors, some related to urine composition (concentration of lithogenic substances, deficiency of crystallization inhibitors, presence of heterogeneous nucleants) and others with renal morphology and anatomy (urinary tract stasis, low urodynamic efficiency cavities, morpho-anatomic deformations, renal papillary tissue lesions). In fact, the composition, macrostructure and microstructure of the calculus will clearly depend on the factors that have induced it. For this reason, the appropriate study and classification of the renal calculi simplifies the diagnosis and allows a more effective therapeutic approach since it can be oriented to directly correct the etiological factors responsible for stone formation. In this article, we review the main etiological factors involved in the formation of each type of calculus and the prophylactic measures that can be adopted for proper correction. The most frequent kidney stones have been classified into the following types: calcium oxalate monohydrate papillary calculi, calcium oxalate monohydrate non-papillary calculi, calcium oxalate dihydrate calculi, mixed hydroxyapatite/ calcium oxalate calculi, carboxyapatite/hydroxyapatite calculi, brushite calculi, struvite/carboxyapatite calculi, uric acid calculi, uric acid/calcium oxalate monohydrate calculi, and cystine calculi. Occasionally, however, the calculus is not available for study, in which case the only way forward is to use all available information (clinical history, life habits, radiological data), together with basic biochemical information, to identify and correct all etiological factors related to renal lithiasis that have been identified

Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. FROM THE CLINICAL EDITOR: Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase.

Factors influencing dry mouth in patients with primary Sjögren syndrome: usefulness of the ESSPRI index.

OBJECTIVE: To evaluate health-related quality of life in a large series of primary SS patients using the recently-proposed ESSPRI questionnaire and to evaluate the relationship between the intensity of oral dryness and other signs and symptoms frequently found in these patients. METHODS: We evaluated 90 primary SS patients seen consecutively; all fulfilled the current classification criteria. All patients completed the ESSPRI questionnaire. We compared the mean values of the ESSPRI-dry mouth item with other ESSPRI items related to sicca features, general symptoms, quality of life, quality of sleep, psychological and psychiatric features, extraglandular involvement, laboratory features and immunological markers and cardiovascular risk factors. Multivariate regression analysis with a backwards stepwise selection method was performed to identify those variables that were independently associated with dry mouth. RESULTS: Mean intensity of oral dryness measured by the corresponding ESSPRI item was 7.17±0.23. Oral dryness correlated with age both at diagnosis and at study inclusion (p=0.013), but not with gender or with time of disease evolution. No significant correlation was found with the SF-36, HAQ and FIQ questionnaires. We found a significant correlation between the intensity of oral dryness and the quality of sleep (p=0.001), anxiety and depression measured by the GH28 (p=0.004 and 0.024, respectively), and a statistically-significant trend for anxiety and depression measured by the HADS (p=0.08 and 0.07, respectively). No significant correlation was found with the main extraglandular and immunological features; however, a significant correlation between oral dryness and hypertension (p=0.019), type II diabetes mellitus (p=0.005) and hypercholesterolemia (p=0.011) was found. Multivariate regression analysis shows that fatigue measured by ESSPRI (p=0.049), sleep quality (p=0.008) and hypercholesterolemia (p=0.008) were independently associated with dry mouth. CONCLUSION: We report on the usefulness of the ESSPRI index in evaluating HRQOL associated with oral dryness in primary SS patients. Oral dryness correlated with age and the other sicca symptoms measured by ESSPRI, but not with the main systemic and immunological SS features. In contrast, oral dryness was strongly correlated with fatigue, pain, psychological distress, poor sleep and vascular risk factors. A multidisciplinary therapeutic approach may be the best way of minimizing oral dryness and its consequences in primary SS patients.

A new device for simple and accurate urinary pH testing by the Stone-former patient.

PURPOSE: Urinary pH is an important factor linked to renal stone disease and a useful marker in the treatment of urolithiasis. Although the gold standard for measuring urinary pH utilizes a glass electrode and a pH meter, at present dipstick testing is largely used to estimate urinary pH. However, the accuracy and precision of this method may be insufficient for making clinical decisions in patients with lithiasis. The aim of this study is to describe a new device for urinary pH testing. METHODS: The device includes a pH sensor based on differential measurement of an ISFET-REFET pair. The drawbacks associated with this type of configuration, namely short lifetime and manual fabrication, have been overcome in the prototype. An automatic one point calibration is performed when turning on the system. Two buffer solutions were utilized to determine the intra- and inter-day precision of the device. The pH of 30 fresh human urine samples was measured using a pH-meter, a dipstick and the new electronic device. RESULTS: In some cases, dipstick measurements differed from those of the pH meter by more than 0.40 units, a clinically relevant discrepancy, whereas none of the measurements made with the new electronic device differed from the results of the pH-meter by more than 0.1 pH units. CONCLUSIONS: This new electronic device has the possibility to be used by stone-formers to control their urinary pH at home, increasing the tools available for stone prevention and prophylaxis.

Spanish consensus on sexual health in men and women over 50.

Sexual health has been defined as "the state of physical, emotional and social wellbeing related to sexuality. However, there are medical, psychological and social reasons that complicate full sexual health that are frequently not attended to sufficiently. The objective of this guide will be to analyze the factors that impact the sexual health of men and women over 50 and to provide recommendations for the most appropriate diagnostic and therapeutic measures for this age group. A panel of experts from various Spanish scientific societies related to sexual health (Spanish Menopause Society, SMS; Asociación Española de Andrología, Medicina Sexual y Reproductiva, ASESA; Federación Española de Sociedades de Sexología, FESS; and Sociedad Española de Médicos de Atención Primaria SEMERGEN) met to reach a consensus on these issues and to decide the optimal timing and methods based on the best evidence available.