Effect of short-term creatine supplementation on renal responses in men.

There is an increasing utilisation of oral creatine (Cr) supplementation among athletes who hope to enhance their performance but it is not known if this ingestion has any detrimental effect on the kidney. Five healthy men ingested either a placebo or 20 g of creatine monohydrate per day for 5 consecutive days. Blood samples and urine collections were analysed for Cr and creatinine (Crn) determination after each experimental session. Total protein and albumin urine excretion rates were also determined. Oral Cr supplementation had a significant incremental impact on arterial content (3.7 fold) and urine excretion rate (90 fold) of this compound. In contrast, arterial and urine Crn values were not affected by the Cr ingestion. The glomerular filtration rate (Crn clearance) and the total protein and albumin excretion rates remained within the normal range. In conclusion, this investigation showed that short-term oral Cr supplementation does not appear to have any detrimental effect on the renal responses of healthy men.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPANTS: A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). RESULTS: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Land plants and DNA barcodes: short-term and long-term goals.

Land plants have had the reputation of being problematic for DNA barcoding for two general reasons: (i) the standard DNA regions used in algae, animals and fungi have exceedingly low levels of variability and (ii) the typically used land plant plastid phylogenetic markers (e.g. rbcL, trnL-F, etc.) appear to have too little variation. However, no one has assessed how well current phylogenetic resources might work in the context of identification (versus phylogeny reconstruction). In this paper, we make such an assessment, particularly with two of the markers commonly sequenced in land plant phylogenetic studies, plastid rbcL and internal transcribed spacers of the large subunits of nuclear ribosomal DNA (ITS), and find that both of these DNA regions perform well even though the data currently available in GenBank/EBI were not produced to be used as barcodes and BLAST searches are not an ideal tool for this purpose. These results bode well for the use of even more variable regions of plastid DNA (such as, for example, psbA-trnH) as barcodes, once they have been widely sequenced. In the short term, efforts to bring land plant barcoding up to the standards being used now in other organisms should make swift progress. There are two categories of DNA barcode users, scientists in fields other than taxonomy and taxonomists. For the former, the use of mitochondrial and plastid DNA, the two most easily assessed genomes, is at least in the short term a useful tool that permits them to get on with their studies, which depend on knowing roughly which species or species groups they are dealing with, but these same DNA regions have important drawbacks for use in taxonomic studies (i.e. studies designed to elucidate species limits). For these purposes, DNA markers from uniparentally (usually maternally) inherited genomes can only provide half of the story required to improve taxonomic standards being used in DNA barcoding. In the long term, we will need to develop more sophisticated barcoding tools, which would be multiple, low-copy nuclear markers with sufficient genetic variability and PCR-reliability; these would permit the detection of hybrids and permit researchers to identify the 'genetic gaps' that are useful in assessing species limits.

Impact of 3 different short-term chemotherapy regimens on lymphocyte-depletion and reconstitution in melanoma patients.

Recent immunotherapy trials have shown that lymphodepletion induced by short-term chemotherapy favors subsequent expansion of adoptively transferred T cells, by homeostatic mechanisms. To take advantage of this effect, novel regimens are being developed with the aim to enhance tumor immunity and reduce treatment toxicity. We have designed a clinical phase I trial combining chemotherapy, reinfusion of PBMC containing Melan-A(MART-1)-specific T cells, and vaccination with Melan-A peptide in Incomplete Freund's Adjuvant. Treatment with Busulfan plus Fludarabine depleted lymphocytes only weakly. Cyclophosphamide (CTX) plus Fludarabine depleted lymphocytes more profoundly, with a maximal effect using high doses of CTX. It is interesting to note that, the degree of homeostatic T-cell proliferation correlated tightly with the extent of lymphodepletion. As compared with CD4 T cells, CD8 T cells showed higher susceptibility to chemotherapy, followed by more rapid homeostatic proliferation and recovery, resulting in strong inversions of CD4/CD8 ratios. Despite efficient homeostatic proliferation of total CD4 and CD8 T cells, the frequency of CD8 T cells specific for Melan-A and cancer-testis antigens remained relatively low. In contrast, EBV-specific T cells expanded and reached high numbers. We conclude that short-term chemotherapy promoted homeostatic lymphocyte proliferation depending on the intensity of lymphocyte depletion, however without preferential expansion of tumor antigen-specific T cells.

Short-term increase in particulate matter blunts nocturnal blood pressure dipping and daytime urinary sodium excretion

Short-term exposure to ambient particulate matter with aerodynamic diameters<10 µm were found to be positively associated with blood pressure. Yet, little information exists regarding the association between particles and circadian rhythm of blood pressure. Hence, we analyzed the association of exposure to particulate matter with aerodynamic diameters<10 µm on the day of examination and ≤7 days before with ambulatory blood pressure and with sodium excretion in 359 adults from the general population using multiple linear regression. After controlling for potential confounders, a 10-µg/m3 increase in particulate matter with aerodynamic diameters<10 µm levels was associated with nighttime systolic blood pressure (β=1.32 mm Hg 95% CI, 0.06-2.58 mm Hg at lag 0; P=0.04), nighttime diastolic blood pressure (0.72 mm Hg 95% CI, 0.03-1.42 mm Hg at lag 2; P=0.04), nocturnal systolic blood pressure dipping (-0.96 mm Hg 95% CI, -1.89 to -0.03 mm Hg at lag 0; P=0.044), and daytime urinary sodium excretion (-0.05 log-mmol/min 95% CI, -0.10 to -0.01 log-mmol/min at lag 0; P=0.027) but not with nighttime sodium excretion. The associations with blood pressure rapidly diminished with increasing lag days, and the associations with daytime sodium excretion were maximal with particulate matter with aerodynamic diameters<10 µm in exposures 2 to 5 days before. The associations of short-term increases in particulate matter with aerodynamic diameters<10 µm with higher nighttime blood pressure and blunted systolic blood pressure dipping were preceded by associations with reduced ability of the kidney to excrete sodium during daytime. The underlying mechanism linking air pollution to increased cardiovascular risk may include disturbed circadian rhythms of renal sodium handling and blood pressure.

Three essays on short-term macroeconomics : business fluctuations, large devaluations and inflation dynamics

Résumé: At least since the Great Depression, explaining why there are business fluctuations has been one of the biggest challenges that the science of economics has had to face. The hope is that if we could better understand recessions, then we could also be more successful in overcoming them. This dissertation consists of three papers that are part of the general endeavor of economists to understand these fluctuations. The first paper discusses, for a particular model, whether a result related to fluctuations would still hold if time were modeled as continuous rather than discrete. The two other papers focus on price stickiness. The second paper discusses why, after a large devaluation, prices of non-tradables may change by only a small amount in comparison to the magnitude of the devaluation. The third paper examines price adjustment in a model in which information is imperfect and it is costly to change prices.

Short-term effects of particulate matters on pulse pressure in two general population studies.

OBJECTIVES: To explore the association of short-term exposure to particulate matter with aerodynamic diameters less than 10 μm (PM10) with pulse pressure, SBP, and DBP taking outdoor temperature into account in two large population-based studies in Switzerland. METHODS: We used data from the Bus Santé study including 5605 adults in Geneva and the CoLaus study including 6183 adults in Lausanne. PM10 and meteorological data were measured from fixed monitoring stations. We analyzed the association of short-term exposure to PM10 (on the day of examination visit and up to 7 days before) with pulse pressure, SBP, and DBP by linear regression, controlling for potential confounders and effect modifiers. RESULTS: Average PM10 levels were 22.4 μg/m in Geneva and 31.7 μg/m in Lausanne. In adjusted models, for each 10 μg/m increase in 7-day PM10 average, pulse pressure and SBP increased by 0.583 (95% confidence interval, 0.296-0.870) mmHg and 0.490 (0.056-0.925) mmHg in Geneva, and 0.183 (0.017-0.348) mmHg and 0.036 (0.042-0.561) mmHg in Lausanne, respectively. Stronger associations of pulse pressure and SBP with PM10 were observed when outdoor temperature was above 5°C. CONCLUSION: Positive associations of pulse pressure and SBP with short-term exposure to PM10 were found and replicated in the Swiss adult population. Our results suggest that even low levels of air pollution may substantially impact cardiovascular risk in the general population.

Cognitive Predictors and Risk Factors of PTSD Following Stillbirth: A Short-Term Longitudinal Study.

This short-term longitudinal study investigated cognitive predictors and risk factors of posttraumatic stress disorder (PTSD) in mothers following stillbirth. After a stillbirth at ≥ 24 weeks gestational age, 65 women completed structured clinical interviews and questionnaires assessing PTSD symptoms, cognitive predictors (appraisals, dysfunctional strategies), and risk factors (perceived social support, trauma history, obstetric history) at 3 and 6 months. PTSD symptoms decreased between 3 and 6 months (Cohen's d ranged .34-.52). Regression analyses also revealed a specific positive relationship between Rumination and concurrent frequency of PTSD symptoms (β = .45). Negative Self-View and Negative World-View related positively and Self-Blame related negatively to concurrent number of PTSD symptoms (β = .48, .44, -.45, respectively). Suppression and Distraction predicted a decrease and Numbing predicted an increase in time-lagged number of PTSD symptoms (β = -.33, -.28, .30, respectively). Risk factors for PTSD symptoms were younger age (β = -.25), lower income (β = -.29), fewer previous pregnancies (β = -.31), and poorer perceived social support (β = -.26). Interventions addressing negative appraisals, dysfunctional strategies, and social support are recommended for mothers with PTSD following stillbirth. Knowledge of cognitive predictors and risk factors of PTSD may inform the development of a screening instrument.

Learning-induced gene expression in the heads of two Nasonia species that differ in long-term memory formation.

BACKGROUND: Cellular processes underlying memory formation are evolutionary conserved, but natural variation in memory dynamics between animal species or populations is common. The genetic basis of this fascinating phenomenon is poorly understood. Closely related species of Nasonia parasitic wasps differ in long-term memory (LTM) formation: N. vitripennis will form transcription-dependent LTM after a single conditioning trial, whereas the closely-related species N. giraulti will not. Genes that were differentially expressed (DE) after conditioning in N. vitripennis, but not in N. giraulti, were identified as candidate genes that may regulate LTM formation. RESULTS: RNA was collected from heads of both species before and immediately, 4 or 24 hours after conditioning, with 3 replicates per time point. It was sequenced strand-specifically, which allows distinguishing sense from antisense transcripts and improves the quality of expression analyses. We determined conditioning-induced DE compared to naïve controls for both species. These expression patterns were then analysed with GO enrichment analyses for each species and time point, which demonstrated an enrichment of signalling-related genes immediately after conditioning in N. vitripennis only. Analyses of known LTM genes and genes with an opposing expression pattern between the two species revealed additional candidate genes for the difference in LTM formation. These include genes from various signalling cascades, including several members of the Ras and PI3 kinase signalling pathways, and glutamate receptors. Interestingly, several other known LTM genes were exclusively differentially expressed in N. giraulti, which may indicate an LTM-inhibitory mechanism. Among the DE transcripts were also antisense transcripts. Furthermore, antisense transcripts aligning to a number of known memory genes were detected, which may have a role in regulating these genes. CONCLUSION: This study is the first to describe and compare expression patterns of both protein-coding and antisense transcripts, at different time points after conditioning, of two closely related animal species that differ in LTM formation. Several candidate genes that may regulate differences in LTM have been identified. This transcriptome analysis is a valuable resource for future in-depth studies to elucidate the role of candidate genes and antisense transcription in natural variation in LTM formation.

Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. METHODS AND RESULTS: A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. CONCLUSIONS: In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation.

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry.

BACKGROUND: Recently, it has been suggested that the type of stent used in primary percutaneous coronary interventions (pPCI) might impact upon the outcomes of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS). Moreover, the later generation DES, due to its biocompatible polymer coatings and stent design, allows for greater deliverability, improved endothelial healing and therefore less restenosis and thrombus generation. However, data on the safety and performance of DES in large cohorts of AMI is still limited. AIM: To compare the early outcome of DES vs. BMS in AMI patients. METHODS: This was a prospective, multicentre analysis containing patients from 64 hospitals in Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint was in-hospital all-cause death, whereas the secondary endpoint included a composite measure of major adverse cardiac and cerebrovascular events (MACCE) of death, reinfarction, and cerebrovascular event. RESULTS: Of 20,464 patients with a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were referred for pPCI and 13,442 received stent implantation. 10,094 patients were implanted with DES and 2,260 with BMS. The overall in-hospital mortality was significantly lower in patients with DES compared to those with BMS implantation (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all confounding covariables, DES remained an independent predictor for lower in-hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed as regards to baseline characteristics and pharmacological treatment, we performed a propensity score matching (PSM) to limit potential biases. Even after the PSM, DES implantation remained independently associated with a reduced risk of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001). CONCLUSIONS: In unselected patients from a nationwide, real-world cohort, we found DES, compared to BMS, was associated with lower in-hospital mortality and MACCE. The identification of optimal treatment strategies of patients with AMI needs further randomised evaluation; however, our findings suggest a potential benefit with DES.

Short-term HIIT and Fatmax training increase aerobic and metabolic fitness in men with class II and III obesity.

OBJECTIVE: To compare the effects of two different 2-week-long training modalities [continuous at the intensity eliciting the maximal fat oxidation (Fatmax ) versus high-intensity interval training (HIIT)] in men with class II and III obesity. METHODS: Nineteen men with obesity (BMI ≥ 35 kg(.) m(-2) ) were assigned to Fatmax group (GFatmax ) or to HIIT group (GHIIT ). Both groups performed eight cycling sessions matched for mechanical work. Aerobic fitness and fat oxidation rates (FORs) during exercise were assessed prior and following the training. Blood samples were drawn to determine hormones and plasma metabolites levels. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA2-IR). RESULTS: Aerobic fitness and FORs during exercise were significantly increased in both groups after training (P ≤ 0.001). HOMA2-IR was significantly reduced only for GFatmax (P ≤ 0.001). Resting non-esterified fatty acids (NEFA) and insulin decreased significantly only in GFatmax (P ≤ 0.002). CONCLUSIONS: Two weeks of HIIT and Fatmax training are effective for the improvement of aerobic fitness and FORs during exercise in these classes of obesity. The decreased levels of resting NEFA only in GFatmax may be involved in the decreased insulin resistance only in this group.

Short-term heparin kinetics during catheter ablation of atrial fibrillation

CONTEXTE: L'ablation percutanée par cathéter de la fibrillation auriculaire (AC-FA) est une option de traitement pour les patients souffrant de fibrillation auriculaire (FA) symptomatique réfractaire au traitement médicamenteux. L'AC-FA comporte un risque de complications thromboemboliques qui a été réduit par l'utilisation de l'héparine non fractionnée (HNF) intraveineuse durant la procédure. L'administration optimale de l'HNF ainsi que sa cinétique ne sont pas bien établies et nécessitent d'être déterminées avec précision. MÉTHODES ET RÉSULTATS: Cette étude a inclus 102 patients consécutifs atteints de FA symptomatique, réfractaire au traitement médicamenteux, référés pour une AC-FA. L'âge moyen était de 61 ± 10 ans. Après une ponction transseptale de la fosse ovale, une injection intraveineuse de HNF ajustée au poids (100 U / kg) a été administré. Une augmentation significative du temps de coagulation activé (ACT) a été observée passant d'une valeur de base moyenne de 100 ± 27 secondes, à 355 ± 94 secondes à 10 minutes (T10) et à 375 ± 90 secondes à 20 minutes (T20). 24 patients n'ont pas atteint la valeur visée d'ACT > 300 secondes à T10 et plus de la moitié de ce collectif est resté avec les valeurs d'ACT infrathérapeutiques à T20. Ce sous-ensemble de patients avait des caractéristiques cliniques similaires et avait reçu des doses similaires d'HNF, mais s'était plus fréquemment fait prescrire de la vitamine Kl pré-procédurale que le reste de la population de l'étude. CONCLUSION: Au cours d'une intervention standard, l'HNF montre, de manière inattendue, une cinétique d'anticoagulation lente dans une proportion significative des procédures et ceci jusqu'à 20 minutes après l'administration. Ces résultats soutiennent l'importance d'une administration d'HNF avant la ponction transseptale ou tout cathétérisme gauche avec des mesures précoces et répétées d'ACT afin d'identifier les patients avec une cinétique retardée. Ils sont en ligne avec les directives récentes proposant d'effectuer l'AC-FA sous anticoagulation thérapeutique.