Importance of total and measured free testosterone in diagnosis of male hypogonadism: immunoassay versus mass spectrometry in a population of healthy young/middle-aged blood donors.

PURPOSE: To meet clinicians' request for adequate results and reliable reference ranges for testosterone, this study was planned with the aims (i) to verify the reliability of the reference interval for total testosterone (TT) declared by immunoassay manufacturer and adopted by laboratory, (ii) to compare results for serum TT obtained by immunoassay and LC-MS/MS and (iii) to verify if the cutoff values for low TT and measured free testosterone (FT), defined by Endocrine Society Guidelines for diagnosis of hypogonadism, are applicable to our study group. METHODS: Sera from anonymous young/middle-aged male blood donors were selected for the study. TT was measured by immunoassay and LC-MS/MS. SHBG was measured by immunoassay and used with albumin concentration to calculate FT according to Vermeulen's formula. RESULTS: The reference interval declared by the manufacturer and adopted by the lab was validated. The two methods for TT evaluation correlated very well. TT and FT lower limits at 5th and 2.5th percentile are below the cutoffs reported in the literature for the diagnosis of hypogonadism. CONCLUSIONS: The immunoassay currently used in our lab can be considered an adequate tool for TT, but it's essential that clinical data agree with the biochemical ones, particularly in the presence of TT values between the lower limit of reference range and the cutoff values recommended by scientific societies.

Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF).

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

Unconstrained mining of transcript data reveals increased alternative splicing complexity in the human transcriptome.

Mining massive amounts of transcript data for alternative splicing information is paramount to help understand how the maturation of RNA regulates gene expression. We developed an algorithm to cluster transcript data to annotated genes to detect unannotated splice variants. A higher number of alternatively spliced genes and isoforms were found compared to other alternative splicing databases. Comparison of human and mouse data revealed a marked increase, in human, of splice variants incorporating novel exons and retained introns. Previously unannotated exons were validated by tiling array expression data and shown to correspond preferentially to novel first exons. Retained introns were validated by tiling array and deep sequencing data. The majority of retained introns were shorter than 500 nt and had weak polypyrimidine tracts. A subset of retained introns matching small RNAs and displaying a high GC content suggests a possible coordination between splicing regulation and production of noncoding RNAs. Conservation of unannotated exons and retained introns was higher in horse, dog and cow than in rodents, and 64% of exon sequences were only found in primates. This analysis highlights previously bypassed alternative splice variants, which may be crucial to deciphering more complex pathways of gene regulation in human.

Comparative clinical- and cost-effectiveness of candesartan and losartan in the management of hypertension and heart failure: a systematic review, meta- and cost-utility analysis.

The UK National Health Service (NHS) currently spends in excess of £250 million per annum on angiotensin II receptor blockers (ARBs) for the treatment of hypertension and heart failure; with candesartan currently dominating the market. With the recent introduction of generic losartan, we set out to directly compare the branded market leader to its now cheaper alternative. The primary objectives were to compare the blood pressure (BP) lowering efficacy and cardiovascular outcomes of candesartan and losartan in the treatment of essential hypertension and chronic heart failure, respectively. The secondary objective was to model their comparative incremental cost-effectiveness in a UK NHS setting. The Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2), which contains the Hypertension and Heart Group's specialist register, Medline (1950-February 2010), and Embase (1980-February 2010) were included in the search strategy. Selection criteria were randomised studies of candesartan versus losartan in adults (> 18 years). The main outcome measures were as follows: Hypertension: mean change from baseline in trough (24 h postdose) systolic and diastolic BP. Heart failure: composite of cardiovascular death and hospital admission for management of heart failure. Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Eight (three of which met inclusion criteria) and zero trials compared candesartan directly with losartan in the treatment of hypertension and heart failure, respectively. A between-treatment difference of -1.96 mmHg [95% confidence interval (CI) -2.40 to -1.51] for trough diastolic BP and -3.00 mmHg (95% CI -3.79 to -2.22) for trough systolic BP in favour of candesartan was observed. Based on this differential, a 10-year Markov model estimates the cost per quality-adjusted life-year gained to exceed £40,000 for using candesartan in place of generic losartan. Candesartan reduces BP to a slightly greater extent when compared with losartan, however, such difference is unlikely to be cost-effective based on current acquisition costs, perceived NHS affordability thresholds and use of combination regimens. We could find no robust evidence supporting the superiority of candesartan over losartan in the treatment of heart failure. We therefore recommend using generic losartan as the ARB of choice which could save the UK NHS approximately £200 million per annum in drug costs.

[Perilunares dislocations of minor arch what is the best therapeutic method?] / Luxaciones perilunares de arco menor ¿cuál es el mejor método terapéutico?

INTRODUCTION: Carpal dislocations and fracture-dislocations are uncommon injuries and represent approximately 5-7% of all wrist injuries, or about 10% of all carpal injuries. Multiple treatments are proposed to treat these injuries. The aim of our paper is to review the evidence about the treatment of lesser arc perilunate dislocations and to assess the results of the different therapeutic methods. MATERIAL AND METHODS: A systematic review was carried out through the electronic search engines PubMed, Bireme and Timbó. The search reached a total of 898 articles, according to the inclusion and exclusion criteria, 16 works were selected to carry out our systematic bibliographic review. RESULTS: The majority of the studies analyzed are retrospective case series studies, level of evidence IV. Our results are based on the extraction of data only from minor arc lesions of said works. Five subgroups were performed according to the type of treatment to analyze the results. DISCUSSION: The different therapeutic methods were analyzed and clinical, functional and radiographic parameters were compared during follow-up. CONCLUSION: There are no significant differences, in terms of the scores used, between closed reduction and percutaneous fixation or open reduction and ligament repair.

INTRODUCCIÓN: Las luxaciones y luxo-fracturas del carpo son lesiones de baja incidencia, constituyendo aproximadamente 5-7% de todas las lesiones de la muñeca o alrededor de 10% de todas las lesiones del carpo. Los tratamientos propuestos para tratar dichas lesiones son múltiples. El objetivo de nuestro trabajo es revisar la evidencia acerca del tratamiento de las luxaciones perilunares de arco menor y valorar resultados de los diferentes métodos terapéuticos. MATERIAL Y MÉTODOS: Se realizó una búsqueda sistematizada a través de los buscadores electrónicos PubMed, Bireme y Timbó. La búsqueda alcanzó un total de 898 artículos, de acuerdo con los criterios de inclusión y exclusión se seleccionaron 16 trabajos para realizar nuestra revisión bibliográfica. RESULTADOS: La mayoría de los estudios analizados son estudios tipo serie de casos retrospectivos, nivel de evidencia IV. Nuestros resultados se basan en la extracción de datos únicamente de las lesiones de arco menor de dichos trabajos. Se realizaron cinco subgrupos según tipo de tratamiento para analizar los resultados. DISCUSIÓN: Se analizaron los diferentes métodos terapéuticos y se compararon parámetros clínicos, funcionales y radiográficos en el seguimiento. CONCLUSIÓN: No existen diferencias en cuanto a los puntajes utilizados entre la reducción cerrada y fijación percutánea o reducción abierta y reparación ligamentaria.

What defines airflow obstruction in asthma?

Asthma guidelines from the Global Initiative for Asthma (GINA) and from the National Heart, Lung, and Blood Institute provide conflicting definitions of airflow obstruction, suggesting a fixed forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) cut-off point and the lower limit of normality (LLN), respectively. The LLN was recommended by the recent American Thoracic Society/European Respiratory Society guidelines on lung function testing. The problem in using fixed cut-off points is that they are set regardless of age and sex in an attempt to simplify diagnosis at the expense of misclassification. The sensitivity and specificity of fixed FEV(1)/FVC ratios of 0.70, 0.75 and 0.80 versus the LLN were evaluated in 815 subjects (aged 20-44 yrs) with a diagnosis of asthma within the framework of the European Community Respiratory Health Survey. In males, the 0.70 ratio showed 76.5% sensitivity and 100.0% specificity, the 0.75 ratio 100.0% sensitivity and 92.4% specificity, and the 0.80 ratio 100.0% sensitivity but 58.1% specificity. In females, the 0.70 ratio showed 57.3% sensitivity and 100.0% specificity, the 0.75 ratio 91.5% sensitivity and 95.9% specificity, and the 0.80 ratio 100.0% sensitivity but 72.9% specificity. The fixed cut-off points cause a lot of misidentification of airflow obstruction in young adults, with overestimation with the 0.80 ratio and underestimation with the 0.70 ratio. In conclusion, the GINA guidelines should change their criteria for defining airflow obstruction.

Mytilus galloprovincialis CYP1A-like mRNAs reveal closer proximity of mytilid CYP1A to the eumetazoan CYP2 family.

Due to the role of Cytochrome P450, Family 1, Subfamily A (CYP1A) in the detoxification of many polycyclic aromatic hydrocarbons (PAHs), there has been an effort to characterise the gene and the products from its expression in organisms that are relevant for biomonitoring and toxicity testing procedures. Nonetheless, the existence of functional homologues in aquatic invertebrates is not entirely consensual, especially in bivalve molluscs, which pose as one of the most important models for aquatic toxicologists, especially mytilids. After isolation and sequencing of CYP1A-like mRNA from the Mediterranean mussel, Mytilus galloprovincialis, phylogenetics incorporating homologues from molluscs and other eumetazoans, vertebrates included, yielded notorious similarity to sequences belonging to the CYP2 Family. Altogether, the findings further indicate that CYP1A-like CYPs may be absent in bivalves, in lieu of Families CYP2, 3 and 4, suggesting caution when interpreting data from common biomarkers of exposure to aromatic hydrocarbons that have been developed for CYP1A activity and expression in higher deuterostomes.

Runaway electron imaging spectrometry (REIS) system.

A portable Runaway Electron Imaging and Spectrometry System (REIS) was developed in ENEA-Frascati to measure synchrotron radiation spectra from in-flight runaway electrons in tokamaks. The REIS is a wide-angle optical system collecting simultaneously visible and infrared emission spectra using an incoherent bundle of fibers, in a spectral range that spans from 500 nm to 2500 nm, and visible images using a CCD color microcamera at a rate of 25 frames/s. The REIS system is supervised and managed using a dedicated LabVIEW program to acquire data simultaneously from three spectrometers every 20 ms (configurable down to 10 ms). An overview of the REIS architecture and acquisition system and resulting experimental data obtained in FTU are presented and discussed in this paper.

A histochemical approach to the evaluation of the in vivo cytotoxicity of the nitrobutadienes (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate in mice liver and kidney.

Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.

The course of asthma during pregnancy in a recent, multicase-control study on respiratory health.

BACKGROUND: Over the years it has been widely stated that approximately one-third of asthmatic women experience worsening of the disease during pregnancy. However, the literature has not been reviewed systematically and the meta-analytic reviews include old studies. This study aimed to examine whether the prevalence of worsening asthma during pregnancy is still consistent with prior estimate or it has been reduced. METHODS: A detailed Clinical Questionnaire on respiratory symptoms, medical history, medication, use of services, occupation, social status, home environment and lifestyle was administered to random samples of the Italian population in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Only clinical data belong to 2.606 subjects that completed the clinical stage of the GEIRD study, were used for the present study. RESULTS: Out of 1.351 women, 284 self-reported asthma and 92 of them had at least one pregnancy. When we considered the asthma course during pregnancy, we found that 16 women worsened, 31 remained unchanged, 25 improved. Seven women had not the same course in the different pregnancies and 13 did not know. The starting age of ICS use almost overlaps with that of asthma onset in women with worsening asthma during pregnancy (19 years ± 1.4), unlike the other women who started to use ICS much later (30.3 years ± 12). In addition, the worsening of asthma was more frequent in women with an older age of onset of asthma (18 years ± 9 vs 13 years ± 10). Among women who completed the ACT during the clinical interview, the 50% of women who experienced worsening asthma during pregnancy (6/12) had an ACT score below 20. CONCLUSION: Asthma was observed to worsen during pregnancy in a percentage much lower to that generally reported in all the previous studies. There is still room in clinical practice to further reduce worsening of asthma during pregnancy by improving asthma control, with a more structured approach to asthma education and management prepregnancy.

Luxaciones perilunares de arco menor ¿cuál es el mejor método terapéutico? / Perilunares dislocations of minor arch what is the best therapeutic method?

Resumen: Introducción: Las luxaciones y luxo-fracturas del carpo son lesiones de baja incidencia, constituyendo aproximadamente 5-7% de todas las lesiones de la muñeca o alrededor de 10% de todas las lesiones del carpo. Los tratamientos propuestos para tratar dichas lesiones son múltiples. El objetivo de nuestro trabajo es revisar la evidencia acerca del tratamiento de las luxaciones perilunares de arco menor y valorar resultados de los diferentes métodos terapéuticos. Material y métodos: Se realizó una búsqueda sistematizada a través de los buscadores electrónicos PubMed, Bireme y Timbó. La búsqueda alcanzó un total de 898 artículos, de acuerdo con los criterios de inclusión y exclusión se seleccionaron 16 trabajos para realizar nuestra revisión bibliográfica. Resultados: La mayoría de los estudios analizados son estudios tipo serie de casos retrospectivos, nivel de evidencia IV. Nuestros resultados se basan en la extracción de datos únicamente de las lesiones de arco menor de dichos trabajos. Se realizaron cinco subgrupos según tipo de tratamiento para analizar los resultados. Discusión: Se analizaron los diferentes métodos terapéuticos y se compararon parámetros clínicos, funcionales y radiográficos en el seguimiento. Conclusión: No existen diferencias en cuanto a los puntajes utilizados entre la reducción cerrada y fijación percutánea o reducción abierta y reparación ligamentaria.

Abstract: Introduction: Carpal dislocations and fracture-dislocations are uncommon injuries and represent approximately 5-7% of all wrist injuries, or about 10% of all carpal injuries. Multiple treatments are proposed to treat these injuries. The aim of our paper is to review the evidence about the treatment of lesser arc perilunate dislocations and to assess the results of the different therapeutic methods. Material and methods: A systematic review was carried out through the electronic search engines PubMed, Bireme and Timbó. The search reached a total of 898 articles, according to the inclusion and exclusion criteria, 16 works were selected to carry out our systematic bibliographic review. Results: The majority of the studies analyzed are retrospective case series studies, level of evidence IV. Our results are based on the extraction of data only from minor arc lesions of said works. Five subgroups were performed according to the type of treatment to analyze the results. Discussion: The different therapeutic methods were analyzed and clinical, functional and radiographic parameters were compared during follow-up. Conclusion: There are no significant differences, in terms of the scores used, between closed reduction and percutaneous fixation or open reduction and ligament repair.

Isoproterenol-induced intramembrane particle aggregation and water flux in toad epidermis.

Stimulation of toad skin with isproterenol resulted in a dramatic increase in water flow, and in the appearance of aggregates of intramembrane particles in the apical membrane of granular cells of the replacement layer, just beneath the stratum corneum. This membrane structural modification appears to be a general prerequisite for the change in water permeability of vasopressin-sensitive epithelia.

Increased dose-intensity of gemcitabine in advanced non small cell lung cancer (NSCLC): a multicenter phase II study in elderly patients from the "polmone toscano group" (POLTO).

Gemcitabine is usually administered at a planned dose-intensity (DI) from 750 to 800 mg/m2/week. Preclinical data have suggested a possible dose-response relationship of gemcitabine. A multicenter phase II study was conducted to evaluate the activity in terms of no progression rate (complete responses+partial responses+stable diseases) of gemcitabine administered at an increased DI (1000 mg/m2/week) in elderly advanced non-small-cell lung cancer (NSCLC) patients. Secondary endpoints were to evaluate tolerability, progression free survival and overall survival. Elderly (age>or=70 years) chemo-naive advanced NSCLC patients, ECOG PS 0-2, were treated with intravenous gemcitabine 1500 mg/m2 intravenous (30 min infusion) on days 1 and 8 every 21 days for four courses. One hundred and twenty-two patients with a median age of 75 years (range 70-84) entered the study. The following grade 3 (NCI-CTC) haematological toxicities were reported (percent of patients): neutropenia 2.4%, thrombocytopenia 1.6%, anaemia 2.4%. No grades 3-4 non-haematological toxicities were observed. Among 111 evaluable patients 52 (46.8%) no progressions, 17 (15.3%) partial responses (WHO criteria), 35 (31.5%) stable diseases and 59 (53.2%) progressions were observed. Median time to progression was 3.2 months and median duration of survival was 5.4 months. The overall 1-year survival rate was 27%. Although increased dose-intensity of gemcitabine in elderly NSCLC patients is feasible without severe toxicities, this does not seem to be associated with an increased activity and efficacy in comparison to standard gemcitabine regimens with lower dose-intensities.

Hypertensive retinopathy revisited: some answers, more questions.

Hypertension is associated with cardiovascular risk and systemic target organ damage. Retinopathy is considered one of the indicators of target organ damage. This review focuses on recent studies on hypertensive retinopathy and their implications for clinical care. Early recognition of hypertensive retinopathy signs remains an important step in the risk stratification of hypertensive patients.

Auditory cortex involvement in emotional learning and memory.

Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged.

Perspectiva de los pacientes sobre el uso de la telemedicina en las consultas urológicas ambulatorias: aprendiendo de la pandemia del COVID-19 / Patients' perspective on the use of telemedicine for outpatient urological visits: Learning from the COVID-19 outbreak

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Cyclic AMP levels in isolated frog skin epithelium: effects of phosphodiesterase inhibitors, oxytocin and catecholamines.

Direct measurements of cyclic AMP were performed in the isolated epithelium of frog skin. Phosphodiesterase inhibitors (methylxanthines, papaverine) and activators of adenylyl cyclase (oxytocin, catecholamines) significantly increased the cyclic AMP content. Propranolol completely blocked the generation of cAMP induced by beta-adrenergic agonists but had little or no effect on that induced by oxytocin. Phentolamine enhanced the cAMP production by adrenalin and noradrenalin. At supramaximal concentrations, oxytocin and isoproterenol produced similar increments in cAMP, while exposure to both agents roughly doubled the increase in cAMP. The results suggest the presence of independent receptors for oxytocin and catecholamines in frog skin, with additive effects on cAMP generation.