Physiopathological Status Research Articles

Raman spectroscopy of large extracellular vesicles derived from human microvascular endothelial cells to detect benzo[a]pyrene exposure.

Extracellular vesicles (EVs) have shown great potential as biomarkers since they reflect the physio-pathological status of the producing cell. In the context of cytotoxicity, it has been found that exposing cells to toxicants leads to changes in protein expression and the cargo of the EVs they produce. Here, we studied large extracellular vesicles (lEVs) derived from human microvascular endothelial cells (HMEC-1) to detect the modifications induced by cell exposure to benzo[a]pyrene (B[a]P). We used a custom CaF2-based biochip which allowed hyphenated techniques of investigation: surface plasmon resonance imaging (SPRi) to monitor the adsorption of objects, atomic force microscopy (AFM) to characterise EVs' size and morphology, and Raman spectroscopy to detect molecular modifications. Results obtained on EVs by Raman microscopy and tip-enhanced Raman spectroscopy (TERS) showed significant differences induced by B[a]P in the high wavenumber region of Raman spectra (2800 to 3000cm-1), corresponding mainly to lipid modifications. Two types of spectra were detected in the control sample. A support vector machine (SVM) model was trained on the pre-processed spectral data to differentiate between EVs from cells exposed or not to B[a]P at the spectrum level; this model could achieve a sensitivity of 88% and a specificity of 99.5%. Thus, this experimental setup facilitated the distinction between EVs originating from two cell culture conditions and enabled the discrimination of EV subsets within one cell culture condition.

Fractal Features of Muscle to Quantify Fatty Infiltration in Aging and Pathology

Fractal Features of Muscle to Quantify Fatty Infiltration in Aging and Pathology

Isomeric differentiation of bile acids using three‐dimensional MS2 spectrum

AbstractBile acids (BAs) currently occupy the research hotspot because of their unreplaceable physiological functions as well as their unique abilities to reflect the physiopathological status. It is always challenging to characterize BAs‐submetabolome using LC–MS/MS, primarily attributing to the high‐level structural diversity. The key obstructing confirmative identification is isomeric identification because of the inherent “isomer‐blind” disadvantage of MS/MS. The isomerism styles of BAs are broadly divided into: type‐I, 5α‐H and 5β‐H epimers; type‐II, α‐OH and β‐OH epimers; type‐III, C‐OH positional isomers; and type‐IV, hybrid isomers bearing two or more isomerism fashions. Herein, we aim to comprehensively pursue isomer‐selective clues for BAs through constructing three‐dimensional MS2 (3D‐MS2) spectrum that was accomplished by fortifying energy‐resolved MS (ER‐MS) program as the new dimension. The breakdown graphs of primary MS2 spectral signals composed of 3D‐MS2 spectrum namely full collision energy ramp (FCER)‐MS2 spectrum for each BA species after appropriate normalization, and seven isomeric BAs covering all isomerism styles were utilized as representative cases. After recording MS2 spectra with progressive CE levels, differences were observed for their FCER‐MS2 spectra. Diagnostic fragment ions (DFIs) occurred within type‐I, type‐II, type‐III or type‐IV isomers, and noteworthily, 2.02 Da neutral loss discriminated BAs containing cis‐6,7‐diol and trans‐6,7‐diol functional groups. Notably, the features such as the maximal relative ion intensity (RIImax) and optimal CE (OCE) enabled isomeric differentiation for all types, even type‐II and type‐III isomers. Above all, it is feasible to acquire in‐depth isomer‐selective MS/MS clues for BAs using FCER‐MS2 spectrum, regardless of the isomerism manner.

Glucocorticoids improve sperm performance in physiological and pathological conditions: their role in sperm fight/flight response.

Glucocorticoids play a physiologic role in the adult male reproductive functions, modulating gonadal steroid synthesis and spermatogenesis, through the glucocorticoid receptor (GR). The expression of GR has been described in several key testicular cell types, including somatic cells and early germ cell populations. Nothing is known on GR in human spermatozoa. Herein, we explored the GR expression and its possible role in normal and testicular varicocele semen samples from volunteer donors. After semen parameter evaluation by macro- and microscopic analysis, samples were centrifuged; then spermatozoa and culture media were recovered for further investigations. By western blotting and immunofluorescence analyses we evidenced for the first time in spermatozoa the presence of GR-D3 isoform which was reduced in sperm from varicocele patients. By treating sperm with the synthetic glucocorticoid dexamethasone (DEXA), we found that survival, motility, capacitation, and acrosome reaction were increased in both healthy and varicocele samples. GR involvement in mediating DEXA effects, was confirmed by using the GR inhibitor mifepristone (M2F). Worthy, we also discovered that sperm secretes different cortisol amounts depending on its physio-pathological status, suggesting a defence mechanism to escape the immune system attach in the female genital tract thus maintaining the immune-privilege as in the testis. Collectively, our data suggests a role for glucocorticoids in determining semen quality and function, as well as in participating on sperm immune defensive mechanisms. The novelty of this study may be beneficial and needs to take into account in artificial insemination/drug discovery aimed to enhancing sperm quality.

In vivo spatial-spectral photoacoustic microscopy enabled by optical evanescent wave sensing

In addition to offering morphological visualizations via capture of the spatial distributions of optical absorption, photoacoustic imaging technology can reveal abundant physical information about biological particles, including their orientation, density, and viscoelasticity, through analysis of the pressure transients in the spectral domain. However, the low-amplitude wideband photoacoustic signals of intrinsic microscopic optically-absorbing objects under the action of confined photoacoustic excitation power continue to hinder simultaneous photoacoustic structural imaging and spectroscopic analysis of the nonfluorescent chromophores in living biological tissues because of the inadequate responses to photoacoustic impulses observed in most photoacoustic imaging setups that include piezoelectric transducers. Building upon a recently-developed optical evanescent wave sensor that can respond to ultrasound with high sensitivity over a broad frequency range, we propose in vivo spatial-spectral photoacoustic microscopy for recovery of structural imaging in three dimensions and characterization of anatomical features in the acoustic frequency domain. Label-free photoacoustic images of a living zebrafish are acquired in which spectroscopically-resolved differentiation of the microarchitecture is accessed, along with isometric micrometer-scale volumetric visualizations. The proposed imaging technology could potentially provide more comprehensive evaluations of the physiopathological status of living small animals.

Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics

Cognitive deficiency is one of the fundamental characteristics of late-onset depression (LOD). Luteolin (LUT) possesses antidepressant, anti-aging, and neuroprotective properties, which can dramatically enhance cognition. The altered composition of cerebrospinal fluid (CSF), which is involved in neuronal plasticity and neurogenesis, directly reflects the physio-pathological status of the central nervous system. It is not well known whether the effect of LUT on LOD is in association with a changed CSF composition. Therefore, this study first established a rat model of LOD and then tested the therapeutic effects of LUT using several behavioral approaches. A gene set enrichment analysis (GSEA) was used to evaluate the CSF proteomics data for KEGG pathway enrichment and Gene Ontology annotation. We combined network pharmacology and differentially expressed proteins to screen for key GSEA-KEGG pathways as well as potential targets for LUT therapy for LOD. Molecular docking was adopted to verify the affinity and binding activity of LUT to these potential targets. The outcomes demonstrated that LUT improved the cognitive and depression-like behaviors in LOD rats. LUT may exert therapeutic effects on LOD through the axon guidance pathway. Five axon guidance molecules-EFNA5, EPHB4, EPHA4, SEMA7A, and NTNG-as well as UNC5B, L1CAM, and DCC, may be candidates for the LUT treatment of LOD.

The Role of Nutrition on Meta-inflammation: Insights and Potential Targets in Communicable and Chronic Disease Management.

Purpose of ReviewChronic low-grade inflammation may contribute to the onset and progression of communicable and chronic diseases. This review examined the effects and eventual mediation roles of different nutritional factors on inflammation.Recent FindingsPotential nutritional compounds influencing inflammation processes include macro and micronutrients, bioactive molecules (polyphenols), specific food components, and culinary ingredients as well as standardized dietary patterns, eating habits, and chrononutrition features. Therefore, research in this field is still required, taking into account critical aspects of heterogeneity including type of population, minimum and maximum intakes and adverse effects, cooking methods, physiopathological status, and times of intervention. Moreover, the integrative analysis of traditional variables (age, sex, metabolic profile, clinical history, body phenotype, habitual dietary intake, physical activity levels, and lifestyle) together with individualized issues (genetic background, epigenetic signatures, microbiota composition, gene expression profiles, and metabolomic fingerprints) may contribute to the knowledge and prescription of more personalized treatments aimed to improving the precision medical management of inflammation as well as the design of anti-inflammatory diets in chronic and communicable diseases.

Exploring the binding mechanism and adverse toxic effects of chiral phenothrin to human serum albumin: Based on multi-spectroscopy, biochemical and computational approach

To understand the binding mechanism of a mixture of chiral phenothrin with human serum albumin (HSA), we used multi-spectroscopy, including steady-state fluorescence spectroscopic titration, three-dimensional fluorescence spectroscopy, circular dichroism, and FTIR spectra to explore the precise interactions between the complex. Based on the modified Stern–Volmer equation, the binding constant (Ka) was calculated under three temperatures, which revealed that phenothrin interacts with HSA through a static quenching mechanism. The thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were determined by fitting the experimental data with van’t Hoff equation, which indicates that electrostatic force and hydrogen bonds dominate the interplay in the phenothrin-HSA complex. Circular dichroism and FTIR showed the addition of phenothrin changed the secondary structure of proteins, in which the α-helicity decreased from 52.37% in free HSA to 50.02%. The esterase-like activity was reduced with the increase of phenothrin concentration, which may be attributed to the perturbated senior structure of HSA. Competitive displacement experiments confirmed that phenothrin inserted into the subdomain IIA (site I) of HSA. Several computational approaches such as molecular docking, frontier molecular orbital analysis, and electrostatic potential analysis were utilized to probe into the binding mode of the phenothrin-HSA complex. The binding behaviors of the chiral phenothrin mixture differed during the complexation. In conclusion, both the experimental and theoretical investigations provide useful information for better understanding and reducing the potential deleterious effects of the chiral phenothrin mixture on human long-term physio-pathological status.

Determination of Free Amino Acids in Milk, Colostrum and Plasma of Swine via Liquid Chromatography with Fluorescence and UV Detection.

Amino acids are ubiquitous components of mammalian milk and greatly contribute to its nutritional value. The compositional analysis of free amino acids is poorly reported in the literature even though their determination in the biological fluids of livestock animals is necessary to establish possible nutritional interventions. In the present study, the free amino acid profiles in mature swine milk, colostrum and plasma were assessed using a targeted metabolomics approach. In particular, 20 amino acids were identified and quantified via two alternative and complementary reversed-phase HPLC methods, involving two stationary phases based on core-shell technology, i.e., Kinetex C18 and Kinetex F5, and two detection systems, i.e., a diode array detector (DAD) and a fluorescence detector (FLD). The sample preparation involved a de-proteinization step, followed by pre-chromatographic derivatization with 9-fluorenylmethylchloroformate (FMOC-Cl). The two optimized methods were validated for specificity, linearity, sensitivity, matrix effect, accuracy and precision and the analytical performances were compared. The analytical methods proved to be suitable for free amino acid profiling in different matrices with high sensitivity and specificity. The correlations among amino acid levels in different biological fluids can be useful for the evaluation of physio-pathological status and to monitor the effects of therapeutic or nutritional interventions in humans and animals.

Hallmarks of Testicular Aging: The Challenge of Anti-Inflammatory and Antioxidant Therapies Using Natural and/or Pharmacological Compounds to Improve the Physiopathological Status of the Aged Male Gonad.

The evolutionary theory of aging supports a trade-off relationship between reproduction and aging. Aging of the male reproductive system primarily affects the testes, leading to a decrease in the levels of sexual hormones, alterations in sperm quality and production, and a decline in fertility that does not necessarily involve a complete cessation of spermatogenesis. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases that are frequently observed in aged testes. Although the molecular mechanisms are still poorly understood, accumulating evidence points toward pro-inflammatory molecules and reactive oxygen species as primary contributing factors for testicular aging. However, the real impact of aging-related testicular alterations on fertility, reproductive health, and life span is far from being fully revealed. This work discusses the current knowledge on the impact of aging in the testis, particularly of aging-related dysregulated inflammation and oxidative damage on the functioning of its different cell populations. More interestingly, this review covers the potential benefits of anti-aging interventions and therapies using either pharmacological compounds (such as non-selective non-steroidal anti-inflammatory medication) or more natural alternatives (such as various nutraceuticals or even probiotics) that exhibit anti-inflammatory, antioxidant, and anti-apoptotic properties. Some of these are currently being investigated or are already in clinical use to delay or prevent testicular aging.

PHENSIM: Phenotype Simulator.

Despite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues' physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expensive to perform, and hard to interpret. Here we propose PHENSIM, a computational tool using a systems biology approach to simulate how cell phenotypes are affected by the activation/inhibition of one or multiple biomolecules, and it does so by exploiting signaling pathways. Our tool's applications include predicting the outcome of drug administration, knockdown experiments, gene transduction, and exposure to exosomal cargo. Importantly, PHENSIM enables the user to make inferences on well-defined cell lines and includes pathway maps from three different model organisms. To assess our approach's reliability, we built a benchmark from transcriptomics data gathered from NCBI GEO and performed four case studies on known biological experiments. Our results show high prediction accuracy, thus highlighting the capabilities of this methodology. PHENSIM standalone Java application is available at https://github.com/alaimos/phensim, along with all data and source codes for benchmarking. A web-based user interface is accessible at https://phensim.tech/.

Blood Transcriptomics of Turbot Scophthalmus maximus: A Tool for Health Monitoring and Disease Studies.

Simple SummaryThe analysis of blood gene expression is emerging as a relevant source of information about the health status of an organism. While these investigations are increasingly performed in human and terrestrial animals, their potential is still underexplored in fish pathology. The aim of this work was to analyze the blood transcriptional profile of a commercially important flatfish species, turbot (Scophthalmus maximus), in healthy and diseased specimens. The analysis of the most expressed genes in healthy fish indicated that turbot red blood cells have important immunological functions. In diseased fish, parasitized by a myxozoan, the blood analysis reflected a broad inhibition of the immune response followed by intense inflammatory activation in heavy infections. The results showed that turbot response appears delayed, dysregulated and ineffective in stopping the infection. Particularly, a proper development of the adaptive immune response was lacking. This study points out that blood gene expression profiling is a reliable tool for health monitoring, as well as to advance in the knowledge of fish immunity and diseases.Blood transcriptomics is emerging as a relevant tool to monitor the status of the immune system and assist in diagnosis, prognosis, treatment and pathogenesis studies of diseases. In fish pathology, the potential of transcriptome profiling of blood is still poorly explored. Here, RNA sequencing was applied to analyze the blood transcriptional profile of turbot (Scophthalmus maximus), the most important farmed flatfish. The study was conducted in healthy specimens and specimens parasitized by the myxozoan Enteromyxum scophthalmi, which causes one of the most devastating diseases in turbot aquaculture. The blood of healthy turbot showed a transcriptomic profile mainly related to erythrocyte gas transportation function, but also to antigen processing and presentation. In moderately infected turbot, the blood reflected a broad inhibition of the immune response. Particularly, down-regulation of the B cell receptor signaling pathway was shared with heavily parasitized fish, which showed larger transcriptomic changes, including the activation of the inflammatory response. Turbot response to enteromyxosis proved to be delayed, dysregulated and ineffective in stopping the infection. The study evinces that blood transcriptomics can contribute to a better understanding of the teleost immune system and serve as a reliable tool to investigate the physiopathological status of fish.

Palaeopathology and amino acid δ13C analysis: Investigating pre-Columbian individuals with tuberculosis at Pica 8, northern Chile (1050-500 BP)

Bulk δ15N and δ13C values of proteinaceous tissues are being increasingly used in bioarchaeological studies to elucidate the physio-pathological status of ancient individuals. This method has not always been successful.The present study aims to explore the novel use of single amino acid carbon isotope analysis in palaeopathology by investigating the effect of a serious infectious disease, tuberculosis (TB), on the isotope composition of two collagenous tissues (tendon, rib). This is achieved by comparing the bulk and amino acid stable isotope compositions of collagenous tissues collected from human remains with and without TB-like bone lesions. The sample set comprises twelve adult individuals (males = 6, females = 6), who were buried at Pica 8, an inland oasis situated on the mid-elevation plains of northern Chile (Late Intermediate Period, ~1050-500 BP). Similarity and consistency in the diet of these individuals are explored using amino acid carbon isotope analysis of 1-cm hair segments longitudinally cut along a single hair fibre.The results show that there is a difference between collagen δ13C serine values measured in the rib collagen of five individuals presenting TB-like bone lesions (3 males and 2 females) and in those five without lesions (3 males and 2 females; control individuals). The rib collagen δ13C serine values of pathological individuals are lower (more negative) than those of the control individuals. Within the group of pathological individuals, lower δ13C serine values in rib collagen are correlated with higher (more positive) δ15N values. Since only individuals (N = 10) with similar dietary intakes were included in the statistical analyses, it appears that the δ13C serine values could be linked to altered carbon metabolism, rather than induced by dietary factors. Serine accounts for less than 3% of the total carbon in bone collagen, and thus an altered serine metabolism would be masked within the averaged bulk carbon isotope value. In future studies, it is advised to undertake stable carbon isotope analysis of non-essential amino acids as a means of characterising pathologically altered body tissues.

Comparative Plasma Endocrine, Metabolic and Mineral Profile of Cyclic, Acyclic, Endometritic and Pregnant Buffaloes

Circulating concentrations of hormones, metabolites, and minerals reflect the physio-pathological status of reproduction in animals. This study was carried out on infertile (anestrus, endometritic), normal healthy cyclic and pregnant buffaloes to evaluate the comparative plasma progesterone (P4) and estrogen (E2) hormones, plasma total protein, total cholesterol, calcium, and phosphorus profile. The study showed higher mean plasma E2 and lower P4 levels in the follicular phase of estrous cycle in buffaloes. Significantly (p less than 0.05) higher mean plasma P4 level and lower E2 levels were recorded during the luteal phase and in endometritic and pregnant buffaloes. Total plasma protein concentration was non-significantly higher in normal cyclic than acyclic and endometritic buffaloes. It was also comparatively lower in buffalo with 9 months of pregnancy than 3 and 6 months of pregnancy. The mean plasma total cholesterol level was significantly (p less than 0.05) higher in pregnant than acyclic and endometritic buffaloes. Cyclic buffaloes had significantly (p less than 0.05) higher mean plasma calcium levels than acyclic buffaloes. Plasma phosphorus concentration, however, did not show any significant difference between different stages of the reproductive cycle.

Bacterial Isolates from the Genital Aspirates of Cyclic, Acyclic, Endometritic and Pregnant Buffaloes

The study was carried out on 50 vaginal secretions/aspirates/discharge samples collected aseptically using syringe and pipette method from infertile (anestrus; endometritic, n = 6 each) buffaloes of villages nearby Anand and healthy cyclic (n = 5; proestus, estrus, metestrus, diestrus) as well as 3, 6 and 9 month pregnant (n = 6 each) buffaloes of University farm to identify the vaginal microorganisms based on routine cultural examination. In all 117 bacterial isolates were recovered from all 50 vaginal samples (100 %) of 35 buffaloes during different physio-pathological status. The bacteria isolated from vaginal mucus/aspirates of buffaloes during the follicular phase comprised Corynebacterium spp. as the most predominant isolate (28.57%) followed by E. coli, Bacillus Spp., Staphylococcus spp., Streptococcus spp., Salmonella spp., Proteus spp., and vaginal yeast, whereas during the luteal phase, the most predominant bacteria were E. coli (23.33%) followed by Corynebacterium spp., Bacillus spp., Staphylococcus spp., Streptococcus spp., and Klebsiella spp. In acyclic buffaloes, the most predominant bacteria isolated were Corynebacterium spp. (21.43%) Bacillus spp., Micrococcus spp., Pseudomonas, Staphylococcus spp., Streptococcus spp., E. coli and Salmonella spp., whereas the endometritic buffaloes evinced the most predominant bacterial isolates as Corynebacterium spp. and E. coli (20.00% each) followed by Bacillus spp., Salmonella, Proteus spp., Staphylococcus spp., Streptococcus spp., and Klebsiella spp. The major bacteria isolated during the entire period of pregnancy were E. coli, Micrococcus, Corynbacterium Spp., Bacillus spp., Staphylococcus spp. and Proteus. This study concludes rich bacterial diversity in the vagina of buffaloes during different physio-pathological status.

Genetic background and immunological status influence B cell repertoire diversity in mice

The relationship between the immune repertoire and the physiopathological status of individuals is essential to apprehend the genesis and the evolution of numerous pathologies. Nevertheless, the methodological approaches to understand these complex interactions are challenging. We performed a study evaluating the diversity harbored by different immune repertoires as a function of their physiopathological status. In this study, we base our analysis on a murine scFv library previously described and representing four different immune repertoires: i) healthy and naïve, ii) healthy and immunized, iii) autoimmune prone and naïve, and iv) autoimmune prone and immunized. This library, 2.6 × 109 in size, is submitted to high throughput sequencing (Next Generation Sequencing, NGS) in order to analyze the gene subgroups encoding for immunoglobulins. A comparative study of the distribution of immunoglobulin gene subgroups present in the four libraries has revealed shifts in the B cell repertoire originating from differences in genetic background and immunological status of mice.

Monitoring Knee Biomechanics in Patients Undergoing Anterior Cruciate Ligament Reconstruction: How Joint Loading Affects Cartilage Quality

Rupture of anterior cruciate ligament (ACL) is a common injury, generally treated by reconstruction surgery. Despite good clinical outcomes, achieving a long-term success for this procedure is still a challenge: young patients could face in fact early degenerative processes, including knee osteoarthritis (OA). The altered biomechanics of the reconstructed joint could affect knee anatomical structures varying – for instance – the loads on the intra-articular cartilage, definitely inducing its degeneration. To better understand the factors that can compromise the long-term success of this procedure, this study investigated the ACL transtibial reconstruction effects on overall knee biomechanics and on articular cartilage, by integrating dynamic radiostereophotogrammetry, inferior limb multi-body modelling and MRI T2 mapping, in order to correlate knee joint loads to its physiopathological status

Cytokine secretion responsiveness of lymphomonocytes following cortisol cell exposure: Sex differences.

The stress hormone cortisol has been recognized as a coordinator of immune response. However, its different ability to modulate the release of inflammatory mediators in males and females has not been clarified yet. Indeed, the dissection of cortisol specific actions may be difficult due to the complex hormonal and physio-pathological individual status. Herein, the release of inflammatory mediators following increasing cortisol concentrations was investigated in an in vitro model of primary human male and female lymphomonocytes. The use of a defined cellular model to assess sex differences in inflammatory cytokine secretion could be useful to exclude the effects of divergent and fluctuating sex hormone levels occurring in vivo. Herein, the cells were challenged with cortisol concentrations resembling the plasma levels achieving in physiological and stressful conditions. The production of cytokines and other molecules involved in inflammatory process was determined. In basal conditions, male cells presented higher levels of some pro-inflammatory molecules (NF-kB and IDO-1 mRNAs, IL-6 and kynurenine) than female cells. Following cortisol exposure, the levels of the pro-inflammatory cytokines, IL-6 and IL-8, were increased in male cells. Conversely, in female cells IL-6 release was unchanged and IL-8 levels were decreased. Anti-inflammatory cytokines, IL-4 and IL-10, did not change in male cells and increased in female cells. Interestingly, kynurenine levels were higher in female cells than in male cells following cortisol stimulus. These results highlighted that cortisol differently affects male and female lymphomonocytes, shifting the cytokine release in favour of a pro-inflammatory pattern in male cells and an anti-inflammatory secretion profile in female cells, opening the way to study the influences of other stressful factors involved in the neurohumoral changes occurring in the response to stress conditions.

Potentially inappropriate prescriptions in elderly outpatiens. Results of implicit criteria applied by clinical pharmacists.

Management of therapy in elderly patients is a critical issue in primary care. The physiopathological status is usually complex, and the prescription of multiple drugs is typically required, with a consequent higher risk of adverse effects. Many tools have been developed to cope with this problem, and identify drugs that are inappropriate in the elderly. The objective of the study was to evaluate the appropriateness of therapies in the elderly according to implicit criteria. A prospective study of outpatients aged ≥65 years who visited our outpatient clinic on even calendar dates of the week, from Monday to Friday, from September 1, 2013 to March 31, 2014 was performed. Appropriateness of therapy was evaluated by applying three sets of implicit tools: Lipton Criteria, MAI and POM. A questionnaire was used assess information given to patients by physicians, and adherence to therapy. Information about clinical history and therapy was obtained from electronic medical records. Patient diagnosis and allergies, drugs, dosages, pharmacological indications, and questionnaire results, were entered into a database. The results were expressed in percentage. A total of 265 patients aged ≥65 years were included. Of these, 83% (220/265) had 2 to 6 comorbidities. According to the Lipton, MAI and POM criteria, the prescriptions were appropriate for 97% (1289/1327), 96% (1274/1327), and 94% (1251/1327) respectively. Only 33% (87/265) of the patients reported being thoroughly informed about the prescribed therapy and main side effects, and 67% (178/265) reported full compliance with the dosing schedule. The overall assessment of the elderly patient, with particular reference to comorbidity, is essential in choosing the best tailored-therapy. For this reason, the support of tools that can make safer therapeutic choices is important. The implicit indicators used allow for a reduction of number of the medications, and inappropriate prescriptions, avoiding drugs with greater potential for interactions, and promoting adherence by patients.

Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents

ContextIrisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism. ObjectiveWe studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels. Materials and MethodsData were obtained from the Korean Children–Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12–15years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit. ResultsMean body mass index (BMI) was 19.4kg/m2 in normal-weight adolescents and 31.4kg/m2 in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p≤0.006). Of these, increased body fat mass [standardized (Std) ß, 0.23; p<0.0001], LDL-C (Std ß, 0.14; p=0.0005) and fasting glucose (Std ß, 0.08; p=0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19–3.87] and MetS (OR, 2.0; CI, 1.15–3.47). Furthermore, irisin and branched-chain amino acids were positively associated (p<4×10−4 for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys (p=0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents (p=0.0388). The relationship between physical activity and irisin levels was not observed in obese adolescents. ConclusionsElevated serum irisin was independently associated with the risk of obesity and positively correlated with unhealthy metabolic parameters and metabolites. Moreover, irisin levels were higher in active versus sedentary adolescents in the normal-weight group, but not in the obese group. Our findings suggest that irisin plays an important role in metabolic disorders and may be affected by physiopathological status.