Coulometer from a Digitally Controlled Galvanostat with Photometric Endpoint Detection.

In this work, a coulometer was developed from a digitally controlled galvanostat. A simple colorimeter based on a RGB LED was used as a light emitter coupled to light detectors, while light dependent resistance (LDR) and photodiodes have been developed as endpoint detectors. Both hardware and software have been adapted from the original galvanostat design. Regarding the hardware, new electrical signal conditioners (filters and voltage dividers) were included to optimize the working system. The software was developed based on an open source Arduino UNO microcontroller. The different variables that control the titration process are managed by an add-in module for Excel data acquisition software that is freely available. A study of the possible variables that influence the titration process has been carried out. The system was tested with two classical coulometric titrations such as iodometry (thiosulfate, ascorbic acid) and acid/base (potassium acid phthalate as standard). The developed system is versatile as different endpoint color indicators can be employed (starch and phenolphthalein for the investigated reactions). Different experimental arrangements have been studied: the nature of the electrodes (Pt, Ag), type of cells (two separate compartments or a single compartment), and light detectors (LDR, photodiode). The influence of several experimental parameters (both electrical, light, and integration time) was studied and chosen to obtain the best performance of the complete system. Reproducibility results below 1% can be obtained under controlled conditions. In the case of acid/base titrations, the presence of atmospheric carbon dioxide was detected, whose interference was mainly affected by the stirring rate and the titration time.

Long-term clinical, angiographic, and optical coherence tomography findings of Mg-based bioresorbable scaffold in patients with acute coronary syndrome.

BACKGROUND: This study sought to evaluate the clinical outcomes of patients treated with magnesium-based bioresorbable scaffolds (MgBRS) in the context of acute coronary syndromes (ACS) at long-term follow-up (24 months). The study also aims to investigate the MgBRS performance by angiography and the healing and bioresorption pattern by optical coherence tomography (OCT) at 18 months. METHODS: Between December 2016 and December 2018, a total of 90 patients admitted for ACS and treated with MgBRS (Magmaris, Biotronik AG, Bülach, Switzerland) were enrolled in a multicenter prospective study. Clinical follow-up was performed in all patients at 24 months and angiographic and OCT follow-up in 51.5% of patients at 18 months. Serial OCT was available in 33 patients (36.7%). RESULTS: At a 2-year follow-up, 88.8% were free of symptoms, no cardiac death was reported, and the device-oriented composite event (DOCE): consisting of cardiac death, target vessel myocardial infarction, and target lesion revascularization (TLR) was 13.3%. Stent thrombosis and TLR were observed in 2.2 and 11.1%, respectively. Binary restenosis was observed in 21.7% of cases and in-stent late lumen loss was 0.61 ± 0.75 mm. By serial OCT imaging, the minimal lumen area was significantly reduced greater than 40% (from 6.12 ± 1.59 to 3.5 ± 1.55 mm2, p < .001). At follow-up, area stenosis was 44.33 ± 23.07% and half of the patients presented indiscernible struts. The principal observed mechanism of restenosis was scaffold collapse. CONCLUSIONS: At long-term follow-up, MgBRS implantation in ACS patients showed a high rate of DOCE, mainly caused by clinically driven TLR. MgBRS restenosis was caused by scaffold collapse in most of the cases.

The radioprotective effect of the Cathpax® AIR cabin during interventional cardiology procedures.

BACKGROUND: The use of ionizing radiation during cardiac catheterization interventions adversely impacts the medical staff. Traditional radiation protection equipment is only partially effective. The Cathpax® radiation protection cabin (RPC) has proven to significantly reduce radiation exposure in electrophysiological and neuroradiology interventions. Our objective was to analyze whether the Cathpax® RPC reduces radiation dose in coronary and cardiac structural interventions in unselected real-world procedures. METHODS AND RESULTS: In this nonrandomized all-comers prospective study, 119 consecutive cardiac interventional procedures were alternatively divided into two groups: the RPC group (n = 59) and the non-RPC group (n = 60). No significant changes in the characteristics of patients and procedures, average contrast volume, air kerma (AK), dose area-product (DAP) and fluoroscopy time between both groups were apparent. In the RPC group, the first-operator relative radiation exposure was reduced by 78% at the chest and by 70% at the wrist. This effect was consistent during different types of procedures including complex percutaneous interventions and structural procedures. CONCLUSIONS: Our study demonstrates, for the first time, that the Cathpax® cabin significantly and efficiently reduces relative operator radiation exposure during different types of interventional procedures, confirming its feasibility in a real-world setting.

Design, synthesis, and biological evaluation of 1,9-diheteroarylnona-1,3,6,8-tetraen-5-ones as a new class of anti-prostate cancer agents.

In search of more effective chemotherapeutics for the treatment of castration-resistant prostate cancer and inspired by curcumin analogues, twenty five (1E,3E,6E,8E)-1,9-diarylnona-1,3,6,8-tetraen-5-ones bearing two identical terminal heteroaromatic rings have been successfully synthesized through Wittig reaction followed by Horner-Wadsworth-Emmons reaction. Twenty-three of them are new compounds. The WST-1 cell proliferation assay was employed to assess their anti-proliferative effects toward both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Eighteen out of twenty-five synthesized compounds possess significantly improved potency as compared with curcumin. The optimal compound, 78, is 14- to 23-fold more potent than curcumin in inhibiting prostate cancer cell proliferation. It can be concluded from our data that 1,9-diarylnona-1,3,6,8-tetraen-5-one can serve as a new potential scaffold for the development of anti-prostate cancer agents and that pyridine-4-yls and quinolin-4-yl act as optimal heteroaromatic rings for the enhanced potency of this scaffold. Two of the most potent compounds, 68 and 75, effectively suppress PC-3 cell proliferation by activating cell apoptosis and by arresting cell cycle in the G0/G1 phase.

HB Puerta del Sol [HBA1:c.148A>C], HB Valdecilla [HBA2:c.3G>T], HB Gran Vía [HBA2:c.98T>G], HB Macarena [HBA2:c.358C>T] and HB El Retiro [HBA2:c.364_366dupGTG]: description of five new hemoglobinopathies.

BACKGROUND: Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. METHODS: We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. RESULTS: The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. CONCLUSIONS: Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.

Integrating sampling techniques and inverse virtual screening: toward the discovery of artificial peptide-based receptors for ligands.

A novel heuristic using an iterative select-and-purge strategy is proposed. It combines statistical techniques for sampling and classification by rigid molecular docking through an inverse virtual screening scheme. This approach aims to the de novo discovery of short peptides that may act as docking receptors for small target molecules when there are no data available about known association complexes between them. The algorithm performs an unbiased stochastic exploration of the sample space, acting as a binary classifier when analyzing the entire peptides population. It uses a novel and effective criterion for weighting the likelihood of a given peptide to form an association complex with a particular ligand molecule based on amino acid sequences. The exploratory analysis relies on chemical information of peptides composition, sequence patterns, and association free energies (docking scores) in order to converge to those peptides forming the association complexes with higher affinities. Statistical estimations support these results providing an association probability by improving predictions accuracy even in cases where only a fraction of all possible combinations are sampled. False positives/false negatives ratio was also improved with this method. A simple rigid-body docking approach together with the proper information about amino acid sequences was used. The methodology was applied in a retrospective docking study to all 8000 possible tripeptide combinations using the 20 natural amino acids, screened against a training set of 77 different ligands with diverse functional groups. Afterward, all tripeptides were screened against a test set of 82 ligands, also containing different functional groups. Results show that our integrated methodology is capable of finding a representative group of the top-scoring tripeptides. The associated probability of identifying the best receptor or a group of the top-ranked receptors is more than double and about 10 times higher, respectively, when compared to classical random sampling methods.

Evidence for homologous recombination in Chikungunya Virus.

Chikungunya Virus (CHIKV), a mosquito-transmitted alphavirus, causes acute fever and joint pain in humans. Recently, endemic CHIKV infection outbreaks have jeopardized public health in wider geographical regions. Here, we analyze the phylogenetic associations of CHIKV and explore the potential recombination events on 152 genomic isolates deposited in GenBank database. The CHIKV genotypes [West African, Asian, East/Central/South African (ECSA)], and a clear division of ECSA clade into three sub-groups (I-II-III), were defined by Bayesian analysis; similar results were obtained using E1 gene sequences. A nucleotide identity-based approach is provided to facilitate CHIKV classification within ECSA clade. Using seven methods to detect recombination, we found a statistically significant event (p-values range: 1.14×10(-7)-4.45×10(-24)) located within the nsP3 coding region. This finding was further confirmed by phylogenetic networks (PHI Test, p=0.004) and phylogenetic tree incongruence analysis. The recombinant strain, KJ679578/India/2011 (ECSA III), derives from viruses of ECSA III and ECSA I. Our study demonstrates that recombination is an additional mechanism of genetic diversity in CHIKV that might assist in the cross-species transmission process.

Comparative serology techniques for the diagnosis of Trypanosoma cruzi infection in a rural population from the state of Querétaro, Mexico.

Immunological diagnostic methods for Trypanosoma cruzi depend specifically on the presence of antibodies and parasitological methods lack sensitivity during the chronic and "indeterminate" stages of the disease. This study performed a serological survey of 1,033 subjects from 52 rural communities in 12 of the 18 municipalities in the state of Querétaro, Mexico. We detected anti-T. cruzi antibodies using the following tests: indirect haemagglutination assay (IHA), indirect immunofluorescence assay (IFA), ELISA and recombinant ELISA (rELISA). We also performed Western blot (WB) analysis using iron superoxide dismutase (FeSOD), a detoxifying enzyme excreted by the parasite, as the antigen. Positive test results were distributed as follows: ELISA 8%, rELISA 6.2%, IFA and IHA 5.4% in both cases and FeSOD 8%. A comparative study of the five tests was undertaken. Sensitivity levels, specificity, positive and negative predictive values, concordance percentage and kappa index were considered. Living with animals, trips to other communities, gender, age, type of housing and symptomatology at the time of the survey were statistically analysed using SPSS software v.11.5. Detection of the FeSOD enzyme that was secreted by the parasite and used as an antigenic fraction in WBs showed a 100% correlation with traditional ELISA tests.

Chemical nature evolution of solid supports used in electromembrane extraction procedures: A comparative analysis based on metric tools.

BACKGROUND: In recent decades, green chemistry has been focusing on the adaptation of different chemical methods towards environmental friendliness. Sample preparation procedures, which constitute a fundamental step in analytical methodology, have also been modified and implemented in this direction. In particular, electromembrane extraction (EME) procedures, which have traditionally used plastic supports, have been optimized towards greener approaches through the emergence of alternative materials. In this regard, biopolymer-based membranes (such as agarose or chitosan) have become versatile and very promising substitutes to perform these processes. RESULTS: Different green metric tools (Analytical Eco-Scale, ComplexGAPI and AGREEprep have been applied to study the evolution of solid supports used in EME from nanostructured tissues and polymer inclusion membranes to agar films and chitosan flat membranes. The main goal is to evaluate the usage of these new biomaterials in the analytical procedure to quantify their environmental impact in the frame of Green Analytical Chemistry (GAC). In addition, both RGB model and BAGI metrics have been employed to study the sustainability of the whole procedure, including not only greenness, but also analytical performance and feasibility aspects. Results obtained after the performance of the mentioned metrics have demonstrated that the most efficient and environmentally friendly analytical methods are based on the use of chitosan supports. This improvement is mainly due to the chemical nature of this biopolymer as well as to the removal of organic solvents. SIGNIFICANCE: This work highlights the advantages of biodegradable materials employment in EME procedures to achieve green analytical methodologies. These materials also contribute to raise the figure of merits regarding to the quantification parameters in a wide range of applications compared to classical supports employed in EME, thus enhancing sustainability of procedures.

Impact of mHealth application on adherence to cardiac rehabilitation guidelines after a coronary event: Randomised controlled clinical trial protocol.

Background: Coronary disease is the main cause of death around the world. mHealth technology is considered attractive and promising to promote behavioural changes aimed at healthy lifestyle habits among coronary patients. The purpose of this study is to evaluate the efficacy of an mHealth intervention regarding improved results in secondary prevention in patients after an acute myocardial infarction (AMI) or angina in terms of lifestyle, clinical variables and therapeutic compliance. Methods: Randomised clinical trial with 300 patients who underwent a percutaneous coronary intervention (PCI) with stent implant. They will be assigned to either the mHealth group, subject to a self-monitored educational intervention involving an internet application installed on their mobile phone or tablet, or to a control group receiving standard healthcare (150 patients in each arm). The primary outcome variables will be adherence to the Mediterranean diet, physical activity, smoking, therapeutic compliance, knowledge acquired, user-friendliness and satisfaction with the application. Measurements of blood pressure, heart rate, body weight, waist circumference (WC) and the 6-min walk test will be taken. Furthermore, the blood lipid profile, glucose and HbA1c will be evaluated. Clinical interview will be conducted, and validated questionnaires completed. The primary quantitative results will be compared using an analysis of covariance adjusted for age and sex. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of cardiovascular risk factors (CDRFs) and the results after the hospital discharge (major adverse events, treatment compliance and lifestyle). Conclusions: The study will provide evidence about the effectiveness of an mHealth intervention at improving the lifestyle of the participants and could be offered to patients with coronary disease to complement existing services. Trial registration: NCT05247606. [https://ClinicalTrials.gov]. 21/02/2022.

Coronary Flow Reserve and Myocardial Resistance Reserve Changes After Transcatheter Aortic Valve Implantation in Aortic Stenosis.

Aortic valve stenosis (AS) induces an alteration in hemodynamic conditions that are responsible for coronary microvasculature impairment. Relief of AS by transcatheter aortic valve implantation (TAVI) is expected to improve the coronary artery hemodynamic. We aimed to assess the midterm effects of TAVI in coronary flow reserve (CFR) and myocardial resistance reserve (MRR) by a continuous intracoronary thermodilution technique. At-rest and hyperemic coronary flow was measured by a continuous thermodilution technique in 23 patients with AS and compared with that in 17 matched controls, and repeated 6 ± 3 months after TAVI in 11 of the patients with AS. In patients with AS, absolute coronary flow at rest was significantly greater, and absolute resistance at rest was significantly less, than in controls (p <0.01 for both), causing less CFR and MRR (1.73 ± 0.4 vs 2.85 ± 1.1, p <0.01 and 1.95 ± 0.4 vs 3.22 ± 1.4, p <0.01, respectively). TAVI implantation yielded a significant 35% increase in CFR (p >0.01) and a 39% increase in MRR (p <0.01) driven by absolute coronary flow at rest reduction (p = 0.03). In patients with AS, CFR and MRR determined by continuous thermodilution are significantly impaired. At 6-month follow-up, TAVI improves these indexes and partially relieves the pathophysiologic alterations, leading to a partial restoration of CFR and MRR.

Analysis of the genetic diversity and phylogenetic relationships of putative human papillomavirus types.

More than 170 human papillomavirus (HPV) types have been completely sequenced, curated and divided into five genera: Alphapapillomavirus, Betapapillomavirus, Gammapapillomavirus, Mupapillomavirus and Nupapillomavirus. With the application of PCR methods, hundreds of putative novel HPV types have been identified as PCR amplicons in mucosa and skin. However, at present there are no studies reporting a systematic search of the currently known L1 amplicons and their phylogenetic relationships. This survey revealed the existence of at least 202 different putative HPV types that are pending for full-genome characterization: five alphapapillomaviruses, 37 betapapillomaviruses, 159 gammapapillomaviruses and one mupapillomavirus. All potential viruses of the genera Alphapapillomavirus and Betapapillomavirus were grouped in the defined species, while 59 putative gammapapillomaviruses types were segregated in 21 unidentified putative species. These data highlight the need for progress in the identification of additional taxa of the family Papillomaviridae in order to elucidate the diversity, evolution and medical implications of these viruses.

MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS): a global mechanism for the regulation of alternative splicing.

While RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation of Nmnat pre-mRNA to regulate the outcomes of alternative splicing. However, the fundamental question remains whether such microRNA-mediated interference with RNA secondary structures is a global molecular mechanism for regulating mRNA splicing. We designed and refined a bioinformatic pipeline to predict candidate microRNAs that potentially interfere with pre-mRNA stem-loop structures, and experimentally verified splicing predictions of three different long-range pre-mRNAs in the Drosophila model system. Specifically, we observed that microRNAs can either disrupt or stabilize stem-loop structures to influence splicing outcomes. Our study suggests that MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing, increases the repertoire of microRNA function and further indicates cellular complexity of post-transcriptional regulation. One-Sentence Summary: MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing.

MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS): a global mechanism for the regulation of alternative splicing.

While RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation of Nmnat pre-mRNA to regulate the outcomes of alternative splicing. However, the fundamental question remains whether such microRNA-mediated interference with RNA secondary structures is a global molecular mechanism for regulating mRNA splicing. We designed and refined a bioinformatic pipeline to predict candidate microRNAs that potentially interfere with pre-mRNA stem-loop structures, and experimentally verified splicing predictions of three different long-range pre-mRNAs in the Drosophila model system. Specifically, we observed that microRNAs can either disrupt or stabilize stem-loop structures to influence splicing outcomes. Our study suggests that MicroRNA-Mediated Obstruction of Stem-loop Alternative Splicing (MIMOSAS) is a novel regulatory mechanism for the transcriptome-wide regulation of alternative splicing, increases the repertoire of microRNA function and further indicates cellular complexity of post-transcriptional regulation.

Interactions between Cyanobacteria and Methane Processing Microbes Mitigate Methane Emissions from Rice Soils.

Cyanobacteria play a relevant role in rice soils due to their contribution to soil fertility through nitrogen (N2) fixation and as a promising strategy to mitigate methane (CH4) emissions from these systems. However, information is still limited regarding the mechanisms of cyanobacterial modulation of CH4 cycling in rice soils. Here, we focused on the response of methane cycling microbial communities to inoculation with cyanobacteria in rice soils. We performed a microcosm study comprising rice soil inoculated with either of two cyanobacterial isolates (Calothrix sp. and Nostoc sp.) obtained from a rice paddy. Our results demonstrate that cyanobacterial inoculation reduced CH4 emissions by 20 times. Yet, the effect on CH4 cycling microbes differed for the cyanobacterial strains. Type Ia methanotrophs were stimulated by Calothrix sp. in the surface layer, while Nostoc sp. had the opposite effect. The overall pmoA transcripts of Type Ib methanotrophs were stimulated by Nostoc. Methanogens were not affected in the surface layer, while their abundance was reduced in the sub surface layer by the presence of Nostoc sp. Our results indicate that mitigation of methane emission from rice soils based on cyanobacterial inoculants depends on the proper pairing of cyanobacteria-methanotrophs and their respective traits.

Uncertain project network analysis with fuzzy-PERT and Interval Type-2 fuzzy activity durations.

Project network analysis is often subject to different uncertainties that can occur in real world scenarios. These uncertainties are not always measurable which makes its statistical estimation hard, so the use of third party information coming from experts is useful to provide an estimation of activity durations of the project. Projects usually have multiple experts who provide different estimates of their perceptions about activity durations which can be represented as Type-2 fuzzy sets in cases where experts do not agree on their estimates. Such disagreement/ambiguitites can be either expressed with Interval Type-2 fuzzy numbers or the proposed fuzzy-PERT set which is an extension of the classical PERT distribution to a fuzzy environment. To do so, a mathematical formulation of the fuzzy problem is presented, two solution methods are described and two illustrative examples are solved.

Green Method for the Selective Electromembrane Extraction of Parabens and Fluoroquinolones in the Presence of NSAIDs by Using Biopolymeric Chitosan Films.

A chitosan biopolymeric membrane was successfully used as a support in a green electromembrane extraction procedure for the simultaneous and selective extraction of seven parabens and three fluoroquinolones in the presence of three non-steroidal anti-inflammatory drugs. The optimal experimental conditions (10 mL donor phase and 50 µL acceptor phase, pH 10 in both phases; 80 V of applied voltage during 15 min of extraction time) were determined, providing high enrichment factors for six of the studied parabens (EF ≥ 90) and the three fluoroquinolones (EF ≥ 50). Wide linear concentration ranges (0.5-500 µg L-1), good linearity (>97%), low limits of detection (0.2-1.1 µg L-1), and good repeatability (relative standard deviation values 4-10%) were achieved. The proposed method was successfully applied for the extraction of the target analytes from different kinds of water samples (river, lake, and swimming pool). The usage of a chitosan membrane in the extraction process presents many advantages, as it is a biodegradable and versatile support, offering a good alternative to commercial plastic materials commonly used in this methodology and these procedures.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Diffusional surface voltammetry as a probe of adsorption energetics.

Direct determination of the adsorption free energy for extremely low surface coverages (Henry limit) requires the use of a technique that must be highly sensitive to both the amount and the energetics of adsorbed molecules. Herein, we demonstrate that diffusional surface voltammetry (DSV), which embodies film and stripping voltammetries as two limiting cases, can be used to achieve this goal for electroactive adsorbates. To this end, a general analytical expression for the surface voltammetric peak potential of DSV is derived, which covers the full range of scan rates, bulk concentrations, and adsorptivity of the freely diffusing form of the redox couple, so that the surface redox conversion can be either equilibrated with or transport-isolated from the solution bulk. Strategies to get a quantitative insight into the energetics of electrosorption are outlined, and diagnostic criteria for their application are developed. In particular, it is demonstrated that DSV can be used in its stripping mode to determine group contributions to the adsorption free energy, avoiding possible interferences from intermolecular interactions or formation of oligomeric species. Application of this protocol to the reductive desorption of distinct homologous series of alkylthiolates adsorbed at mercury electrodes has allowed us to determine the contributions of the CH(n) groups (n = 0-3) to the free energy of adsorption of these molecules. These estimates are shown to correlate linearly with the corresponding group contributions to the octanol-water partition coefficient, revealing that adsorption of individual hydrocarbon groups at the mercury/solution interface scales with their hydrophobicity. Overall, the present work enlarges the capability of surface voltammetry to probe adsorption energetics down to the micromolar level, and it represents a first step toward the development of a unified treatment of stripping and film voltammetries.

Renin-angiotensin system blockade and kidney transplantation: a longitudinal cohort study.

BACKGROUND: The beneficial effect of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in kidney transplant recipients on modern immunosuppression is not yet well established. Our objective was to investigate the impact of the use of ACEI/ARB on patient and graft survival in a cohort of kidney transplant recipients. METHODS: A total of 990 patients, who received a single deceased donor kidney at our institution between 1996 and 2005, were included in this longitudinal cohort study. All-cause mortality and death-censored graft loss were the primary outcomes. We used traditional time-dependent Cox model (unweighted) and inverse-probability-of-treatment weighting of marginal structural models (weighted Cox model), controlling for time-dependent confounding by indication. RESULTS: A total of 414 patients (42%) received ACEI/ARB through the study period (median duration 14 months, interquartile range 6-40 months). ACEI/ARB use was associated with reduction of risk for mortality in the crude [hazard ratio (HR) 0.627, 95% confidence interval (CI) 0.412-0.953] and adjusted Cox analysis (HR 0.626, 95% CI 0.407-0.963). Similar results were observed after adjusting for confounding by indication (HR 0.629, 95% CI 0.407-0.973). By contrast, ACEI/ARB use was not associated with significant improvement of graft survival after kidney transplantation. CONCLUSION: ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.