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This paper was intended to efficiently extract multiclass prohibited substances in human sport drug testing by using supramolecular solvents (SUPRASs) made up of cubosomes. These SUPRASs, here first reported, are synthesized by the salt-induced coacervation of 1,2-hexanediol in urine. The formation of square and rounded cubosomes with a size range of 140-240 nm was confirmed by electron microscopy. These nanostructures consisted of 1,2-hexanediol, salt, and a high water content (36-61%, w/w). Their applicability in multiclass determinations was investigated by the extraction of 92 prohibited substances (log P from 2.4 to 9.2) belonging to the 10 categories of the World Anti-Doping Agency's (WADA) list. Variables influencing both recoveries and matrix effects were optimized. Cubosomic SUPRASs showed high extraction efficiency and interference removal capability, which was attributed to their large hydrophilicity and surface area. Both features were superior to those of the other 11 SUPRASs that were based on sponge droplets and inverted hexagonal aggregates and to those of conventional organic solvents. A sport drug-testing method based on cubosomic SUPRAS-LC-ESI-MS/MS was proposed and validated. Around 82-95% of drugs were efficiently extracted (recoveries 70-120%) in urine samples, and 81-92% did not present matrix effects. The method detection limits (0.001-4.2 ng mL

Background: The importance of artificial nutritional therapy is underrecognized, typically being considered an adjunctive rather than a primary therapy. We aimed to evaluate the influence of nutritional therapy on mortality in critically ill patients.Methods: This multicenter prospective observational study included adult patients needing artificial nutritional therapy for >48 h if they stayed in one of 38 participating intensive care units for ≥72 h between April and July 2018. Demographic data, comorbidities, diagnoses, nutritional status and therapy (type and details for ≤14 days), and outcomes were registered in a database. Confounders such as disease severity, patient type (e.g., medical, surgical or trauma), and type and duration of nutritional therapy were also included in a multivariate analysis, and hazard ratios (HRs) and 95% confidence intervals (95%CIs) were reported.Results: We included 639 patients among whom 448(70.1%) and 191(29.9%) received enteral and parenteral nutrition, respectively. Mortality was 25.6%, with non-survivors having the following characteristics: older age; more comorbidities; higher Sequential Organ Failure Assessment (SOFA) scores (6.6±3.3 vs 8.4±3.7; P); greater nutritional risk (Nutrition Risk in the Critically Ill [NUTRIC] score: 3.8±2.1 vs 5.2±1.7; P); more vasopressor requirements (70.4% vs 83.5%; P=0.001); and more renal replacement therapy (12.2% vs 23.2%; P=0.001). Multivariate analysis showed that older age (HR: 1.023; 95% CI: 1.008–1.038; P=0.003), higher SOFA score (HR: 1.096; 95% CI: 1.036–1.160; P=0.001), higher NUTRIC score (HR: 1.136; 95% CI: 1.025–1.259; P=0.015), requiring parenteral nutrition after starting enteral nutrition (HR: 2.368; 95% CI: 1.168–4.798; P=0.017), and a higher mean Kcal/Kg/day intake (HR: 1.057; 95% CI: 1.015–1.101; P=0.008) were associated with mortality. By contrast, a higher mean protein intake protected against mortality (HR: 0.507; 95% CI: 0.263–0.977; P=0.042).Conclusions: Old age, higher organ failure scores, and greater nutritional risk appear to be associated with higher mortality. Patients who need parenteral nutrition after starting enteral nutrition may represent a high-risk subgroup for mortality due to illness severity and problems receiving appropriate nutritional therapy. Mean calorie and protein delivery also appeared to influence outcomes.Trial Registration: ClinicaTrials.gov NCT: 03634943.

Anti-doping substances listed by the World Anti-Doping Agency (WADA) include hundreds of compounds of very different physico-chemical properties. Anti-doping control laboratories need to screen all these substances in the so-called Initial Testing Procedures (ITPs) what is very challenging from an analytical point of view. ITPs are mostly based on reversed-phase (RP) liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) using C18 columns, which feature poor retention and peak tailing for polar and basic compounds, respectively. While studies on this field dealing with the comparison of stationary phases are focused on certain chemical classes, this research provides a wide multi-target approach. For this purpose, a representative group of 93 anti-doping agents (log P from -2.4 to 9.2) included in ten different classes of prohibited substances was selected. A comprehensive study on the performance of six columns and four eluents on different separation parameters (retention factors, asymmetry factors, co-elutions, total run times) and matrix effects (signal enhancement or suppression) was performed for LC-MS/MS-based ITPs. Columns working in both RP [C18, C8, phenyl hexyl (PH), pentafluorophenyl (PFP) and mixed-mode hydrophilic/RP (HILIC-RP)) and hydrophilic (HILIC)] modes were investigated. Eluents contained methanol or acetonitrile as organic modifiers, with or without the addition of ammonium acetate. The best column-mobile phase binomial for ITPs was PFP using water-methanol (0.1% formic acid) as eluent, while HILIC was the best option for highly polar non-aromatic anti-doping agents, which were poorly addressed by PFP. Excellent good peak shapes and relative acceptable matrix interferences were obtained for HILIC-RP, which was tested for the first time for the analysis of anti-doping agents, although the number of compounds eluting too fast was too high. On the whole, the alkyl phase C18 showed the worst performance and although C8 and PH were better, their performance did not surpass that of PFP. Possible retention mechanisms underlying separation in the different stationary phases were discussed. This research provides valuable information to anti-doping control labs for improving LC-MS/MS-based ITPs and it proposes PFP as a suitable alternative to the already established C18.

In 2016, the WHO included haemoglobin values within normal ranges as a diagnostic criterion for Polycythaemia Vera (PV). Since then, concerns have arisen that a large number of patients are undergoing unnecessary screening for PV. To address this issue, we estimated the prevalence of JAK2 p.V617F in individuals with elevated haemoglobin or haematocrit and developed and validated a screening algorithm for PV. A total of 15,366 blood counts performed in seven non-consecutive days were reviewed, of which 1001 were selected for subsequent JAK2 p.V617F mutation screening. Eight (0.8%) new JAK2 p.V617F-mutated cases were detected. From ROC curves, a two-step algorithm was developed based on the optimal cut-off for the detection of the JAK2 p.V617F mutation. The algorithm was prospectively validated in an independent cohort of 15,298 blood counts. A total of 1595 (10.4%) cases met the criterion for haemoglobin or haematocrit, of whom 581 passed to step 2 (3.8% of the total). The JAK2 p.V617F mutation was detected in 7 of the 501 patients tested, which accounts for 0.04% of the total cohort and 0.4% of patients with erythrocytosis. In conclusion, this data show that our two-step algorithm improves the selection of candidates for JAK2 p.V617F testing.

Background Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior. Case presentation A 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum. Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident. Conclusion Inflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.

There are few publications related to postoperative morbidity in hepatic hydatidosis and these have mixed results. The aim of this study was to determine risk and protective factors of postoperative morbidity in patients operated on for hepatic hydatidosis. A comprehensive review was made of the evidence, based on systematic reviews, clinical analyses and observational studies, obtained from the Trip Database, BVS, SciELO, Cochrane Central Register of Controlled Trials, WoS, MEDLINE, EMBASE, SCOPUS, EBSCOhost, IBECS, ePORTUGUESe, LILACS and WHOLIS. 1,087 related articles were identified; 69 fulfilled the selection criteria (2 systematic reviews, 3 clinical trials and 64 observational studies). Age, history of previous surgery for hepatic hydatidosis, location in the hepatic center, existence of biliary communications and evolutionary complications of the cyst were identified as risk factors, and radical surgical techniques as protective factors. Risk and protective factors were identified; however, the studies are few and the quality moderate to low.

The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes. Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome. Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC. The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development. This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ''A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016). This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund "A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Tematica de investigacion cooperativa en cancer: RTICC (RD12/0036/0073) and La Asociacion Espanola contra el Cancer: AECC (Grupos Coordinados Estables 2016). Sí

Solitary fibrous tumors (SFTs) are a rare type of soft tissue sarcoma of unpredictable clinical behavior. Some clinicopathologic characteristics have also been related to patient outcome. This study is a retrospective review of 30 patients. We analyzed the clinical course and pathological factors to predict recurrence. The mean age was 55.9 years. Forty-five percent were located in the thoracic region. The mean tumor size was 10 cm (max24). Thirty-three percent had a relapse and 20 % have died. Median time to relapse was 7.18 (1–13) years. Median overall survival (OS) was 15.5 years (0–32). On histopathologic analysis, 6 % percent had >4 mitoses, 23 % had necroses, and 36 % had atypia/pleomorphism. Forty-three percent had tumor size >10 cm. Forty-six percent had at least one characteristic of malignancy. None of this data could predict clinical behavior by itself. SFT can be an aggressive disease and relapses can occur several years from diagnosis. We did not find any clinicopathologic factors that could predict the tumor behavior accurately. Nevertheless, it should be consider that we included different tumor locations and the sample size is small.

The perioperative nutritional status of patients undergoing cardiac surgery influences outcomes; therefore nutritional support is essential for these patients. Owing to the lack of solid evidence, no protocols have been established for the nutritional management of this specific population, and most of the recommendations are based on other critically ill populations. In this review of the main studies performed in this population, the importance of preoperative evaluation of nutritional status, the management of nutritional support immediately after cardiac surgery, the influence of nutrition on outcomes, and the importance of nutrition after hospital discharge are discussed. In addition, the possible influence of glycemic control and pharmaconutrition in the outcomes of these patients are described briefly.

BackgroundThe introduction of ‘smoke-free laws’ has reduced the population’s exposure to second-hand smoke (SHS), although SHS is still an issue in homes and other public places. Children are vulnerable to its health effects, and their greatest exposure occurs at home.ObjectivesTo assess airborne nicotine concentration of the living room and children’s bedroom of homes with children under 13 years of age, and to analyse factors associated with these levels.MethodsWe conducted a cross-sectional study in Barcelona in 2015–2016, selecting a convenience sample from families with at least one child under 13 years of age. The sample comprised 50 families with smokers and 50 without. We measured airborne nicotine concentrations in the living room and children’s bedroom, and, using a questionnaire administered to the parents, collected information about smoking habits at home.ResultsHomes without smokers showed nicotine concentrations below the limit of detection (3), while those with at least one smoker showed 0.16 µg/m3 in the living room and 0.12 µg/m3 in the bedroom. When smoking was allowed inside home, these values increased to 1.04 and 0.48 µg/m3, respectively. Moreover, nicotine concentrations in both rooms were strongly correlated (r=0.89), and higher nicotine levels were associated with the number of cigarettes smoked in the living room, smoking rules, the number of smokers living at home and tobacco smell.ConclusionsHomes with smokers present SHS in the living room and in the children’s bedroom. Therefore, programmes focused on reducing children’s SHS exposure are urgently needed.

Background: Amongst others, cocaine consumption has a detrimental effect in the vascular supply to the mesenteric area causing abdominal ischemic changes. Early recognition of these changes and adequate treatment are essential to avoid serious complications and possible death of the patient from sepsis. Case report: In this case study, the subject is a 40-years-old gentleman presenting with acute abdominal pain due to multiple ischemic changes in both small bowel and sigmoid loops. The patient required emergency surgical intervention consisting of bowel resection and anastomosis. The pathologic analysis of the segment showed transmural necrosis and necrotizing phlebitis caused by the ingestion of drugs or toxic agents. The patient later confirmed the habitual consumption of cocaine. Discussion: The increase in cocaine consumption and other recreational toxins substructed from erythroyilon coca alcaloids amongst young people have generated a large number of admissions to Hospital Accident and Emergency Departments with patients complaining of acute abdominal pain. In many of these cases, surgical intervention is required and in some cases patients will sadly die without a proper diagnosis. Some of the most common effects of cocaine and its compounds includes; hollow viscus perforation, gastro-intestinal bleed, and other vascular problems such as enteritis and ischemic colitis. It appears clear that there is a great need for an advance history taking of these patients and their habit to cocaine and other drugs together with a urine test for drug screening. These together with a suspicion of a non- occlusive ischemic bowel caused by the effects of cocaine in young adults with no cardiac risk factors will guide clinicians and establish, and plan the correct treatment for these categories of patients.

This study aimed at investigating the effects of a commercially available energy drink on shooting precision, jump performance and endurance capacity in Young basketball players. Sixteen young basketball players (first division of a junior national league; 14.9 ± 0.8 years; 73.4 ± 12.4 kg; 182.3 ± 6.5 cm) volunteered to participate in the research. They ingested either (a) an energy drink that contained 3 mg of caffeine per kg of body weight or (b) a placebo energy drink with the same appearance and taste. After 60 min for caffeine absorption, they performed free throw shooting and three-point shooting tests. After that, participants performed a maximal countermovement jump (CMJ), a repeated maximal jumps test for 15 s (RJ-15), and the Yo–Yo intermittent recovery test level 1 (Yo–Yo IR1). Urine samples were obtained before and 30 min after testing. In comparison to the placebo, the ingestion of the caffeinated energy drink did not affect precision during the free throws (Caffeine = 70.7 ± 11.8 % vs placebo = 70.3 ± 11.0 %; P = 0.45), the three-point shooting test (39.9 ± 11.8 vs 38.1 ± 12.8 %; P = 0.33) or the distance covered in the Yo–Yo IR1 (2,000 ± 706 vs 1,925 ± 702 m; P = 0.19). However, the energy drink significantly increased jump height during the CMJ (38.3 ± 4.4 vs 37.5 ± 4.4 cm; P\0.05) mean jump height during the RJ-15 (30.2 ± 3.6 vs 28.8 ± 3.4 cm; P\0.05) and the excretion of urinary caffeine (1.2 ± 0.7 vs 0.1 ± 0.1 lg/mL; P\0.05). The intake of a caffeine-containing energy drink (3 mg/kg body weight) increased jump performance although it did not affect basketball shooting precision.

The purpose of this study was to investigate the effectiveness of a caffeine-containing energy drink in enhancing rugby players' physical performance during a simulated match. A second purpose was to determine the urinary caffeine excretion derived from the energy drink intake. In a randomized and counterbalanced order, 26 elite rugby players (mean ± SD for age and body mass, 25 ± 2 y and 93 ± 15 kg) played 2 simulated rugby games (2 × 30 min) 60 min after ingesting (i) 3 mg of caffeine per kilogram of body mass in the form of an energy drink (Fure, ProEnergetics) or (ii) the same drink without caffeine (placebo). During the matches, the individual running distance and the instantaneous speed were measured, and the number of running actions above 20 km·h−1(i.e., sprints) were determined, using global positioning system devices. The number of impacts above 5 g during the matches was determined by accelerometry. The ingestion of the energy drink, compared with the placebo, increased the total distance covered during the match (4749 ± 589 vs 5139 ± 475 m, p < 0.05), the running distance covered at more than 20 km·h−1(184 ± 38 vs 208 ± 38 m, p < 0.05), and the number of sprints (10 ± 7 vs 12 ± 7, p < 0.05). The ingestion of the energy drink also resulted in a greater overall number of impacts (481 ± 352 vs 641 ± 366, p < 0.05) and a higher postexercise urine caffeine concentration (0.1 ± 0.1 vs 2.4 ± 0.9 μg·mL−1, p < 0.05). The use of an energy drink with a caffeine dose equivalent to 3 mg·kg−1considerably enhanced the movement patterns of rugby players during a simulated match.

The aim of this study was to determine the effects of a caffeine-containing energy drink on physical performance during a rugby sevens competition. A second purpose was to investigate the post-competition urinary caffeine concentration derived from the energy drink intake. On two non-consecutive days of a friendly tournament, 16 women from the Spanish National rugby sevens Team (mean age and body mass = 23 ± 2 years and 66 ± 7 kg) ingested 3 mg of caffeine per kg of body mass in the form of an energy drink (Fure®, ProEnergetics) or the same drink without caffeine (placebo). After 60 min for caffeine absorption, participants performed a 15-s maximal jump test, a 6 × 30 m sprint test, and then played three rugby sevens games against another national team. Individual running pace and instantaneous speed during the games were assessed using global positioning satellite (GPS) devices. Urine samples were obtained pre and post-competition. In comparison to the placebo, the ingestion of the energy drink increased muscle power output during the jump series (23.5 ± 10.1 vs. 25.6 ± 11.8 kW, P = 0.05), running pace during the games (87.5 ± 8.3 vs. 95.4 ± 12.7 m/min, P

A complete analytical protocol for the determination of 25 doping-related peptidic drugs and 3 metabolites in urine was developed by means of accurate-mass quadrupole time-of-flight (Q-TOF) LC-MS analysis following solid-phase extraction (SPE) on microplates and conventional SPE pre-treatment for initial testing and confirmation, respectively. These substances included growth hormone releasing factors, gonadotropin releasing factors and anti-diuretic hormones, with molecular weights ranging from 540 to 1320Da. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. Weak cation exchange SPE followed by C18 HPLC chromatography and accurate mass detection provided the required sensitivity and selectivity for all the target peptides under study. 2mg SPE on 96-well microplates can be used in combination with full scan MS detection for the initial testing, thus providing a fast, cost-effective and high-throughput protocol for the processing of a large batch of samples simultaneously. On the other hand, extraction on 30mg SPE cartridges and subsequent target MS/MS determination was the protocol of choice for confirmatory purposes. The methodology was validated in terms of selectivity, recovery, matrix effect, precision, sensitivity (limit of detection, LOD), cross contamination, carryover, robustness and stability. Recoveries ranged from 6 to 70% (microplates) and 17-95% (cartridges), with LODs from 0.1 to 1ng/mL. The suitability of the method was assessed by analyzing different spiked or excreted urines containing some of the target substances.

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumours, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole exome sequencing of the endometrioid and undifferentiated components as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: a) hypermutated tumours with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); c) high copy number alterations (copy-number high) tumours group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%) ; and d) low copy number alterations (copy-number low) tumours with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumours. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumours, which may have prognostic value.

Matrix effects (ion suppression/enhancement) are a well-observed phenomenon in analyses of biological matrices by high-performance liquid chromatography-mass spectrometry (LC-MS). However, few simple solutions for detecting and minimizing these adverse effects have been described so far in multianalyte analysis, especially in the field of doping control. This study describes an exhaustive characterization of matrix effects in one hundred urine samples fortified with 41 analytes (glucocorticoids and diuretics). It introduces a novel marker to identify samples in which the reliability of the results is compromised because of acute ion suppression. This new strategy strengthens the rigor of the analysis for screening purposes. Once the matrix effect is identified, a selective sample preparation is introduced to minimize the adverse ion suppression effect. That selective extraction together with the use of a deuterated internal standard permits enhancing the ruggedness of the estimation of glucocorticoid concentration in urine.

Laboratories devoted to the public health field have to face the analysis of a large number of organic contaminants/residues in many different types of samples. Analytical techniques applied in this field are normally focused on quantification of a limited number of analytes. At present, most of these techniques are based on gas chromatography (GC) or liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS). Using these techniques only analyte-specific information is acquired, and many other compounds that might be present in the samples would be ignored. In this paper, we explore the potential of time-of-flight (TOF) MS hyphenated to GC or LC to provide additional information, highly useful in this field. Thus, all positives reported by standard reference targeted LC-MS/MS methods were unequivocally confirmed by LC-QTOF MS. Only 61% of positives reported by targeted GC-MS/MS could be confirmed by GC-TOF MS, which was due to its lower sensitivity as nonconfirmations corresponded to analytes that were present at very low concentrations. In addition, the use of TOF MS allowed searching for additional compounds in large-scope screening methodologies. In this way, different contaminants/residues not included in either LC or GC tandem MS analyses were detected. This was the case of the insecticide thiacloprid, the plant growth regulator paclobutrazol, the fungicide prochloraz, or the UV filter benzophenone, among others. Finally, elucidation of unknowns was another of the possibilities offered by TOF MS thanks to the accurate-mass full-acquisition data available when using this technique.

The ergogenic effect of caffeine is well-established, but the extent of its consumption in sport is unknown at the present. The use of caffeine was considered &ldquo, prohibited&rdquo, until 2004, but this stimulant was moved from the List of Prohibited Substances to the Monitoring Program of the World Anti-Doping Agency to control its use by monitoring urinary caffeine concentration after competition. However, there is no updated information about the change in the use of caffeine as the result of its inclusion in the Monitoring Program. The aim of this study was to describe the changes in urine caffeine concentration from 2004 to 2015. A total of 7488 urine samples obtained in official competitions held in Spain and corresponding to athletes competing in Olympic sports (2788 in 2004, 2543 in 2008, and 2157 in 2015) were analyzed for urine caffeine concentration. The percentage of samples with detectable caffeine (i.e., &gt, 0.1 &mu, g/mL) increased from ~70.1%, in 2004&ndash, 2008 to 75.7% in 2015. The median urine caffeine concentration in 2015 (0.85 &mu, g/mL) was higher when compared to the median value obtained in 2004 (0.70 &mu, g/mL, p &lt, 0.05) and in 2008 (0.70 &mu, 0.05). The urine caffeine concentration significantly increased from 2004 to 2015 in aquatics, athletics, boxing, judo, football, weightlifting, and rowing (p &lt, 0.05). However, the sports with the highest urine caffeine concentration in 2015 were cycling, athletics, and rowing. In summary, the concentration of caffeine in the urine samples obtained after competition in Olympic sports in Spain increased from 2004 to 2015, particularly in some disciplines. These data indicate that the use of caffeine has slightly increased since its removal from the list of banned substances, but urine caffeine concentrations suggest that the use of caffeine is moderate in most sport specialties. Athletes of individual sports or athletes of sports with an aerobic-like nature are more prone to using caffeine in competition.

Smoke-free legislation in indoor public places has concentrated smokers in the areas outside building entrances or other outdoor areas. This study assessed the drift of second-hand smoke between outdoor and indoor areas of cafes and restaurants in Barcelona, Spain, and characterized the exposure on outdoor terraces. Using a cross-sectional design, we monitored vapor-phase nicotine in indoor areas and outside entrances simultaneously (n=47), and on some outdoor terraces (n=51). We computed the median nicotine concentration and inter quartile range (IQR) to describe the data and performed multivariate analysis to describe nicotine concentration and its determinants. The overall median nicotine concentration indoors was 0.65 mu g/m(3) (IQR: 029-1.17 mu g/m(3)), with significant differences based on the number of smokers at the entrance (p=0.039). At outside entrances, the overall median nicotine concentration was 0.41 mu g/m(3) (IQR: 0.21-1.17 mu g/m(3)). The nicotine concentrations indoors and at the corresponding outside entrances were not significantly different, and the multivariate analysis confirmed the relationship between these variables. On terraces, the overall median nicotine concentration was 0.54 mu g/m(3) (IQR: 025-1.14 mu g/m(3)), but it increased to 0.60 mu g/m(3) when a tobacco smell was perceived, 0.72 mu g/m(3) on closed terraces, 124 mu g/m(3) when there were > 6 smokers, and 1.24 mu g/m(3) when someone smoked > 20 min. Multivariate analysis confirmed the outdoor terrace area, the season, the type of enclosure, and the number of smokers as the most relevant variables explaining nicotine concentration (R-2=0.396). These findings show that second-hand smoke exposure exists in indoor areas due to smokers smoking at the outside entrances. In addition, exposure may occur on outdoor terraces when smokers are present and the terrace is enclosed to some extent. Thus, the current Spanish law does not fully protect nonsmokers from second-hand smoke and supports extending regulation to some outdoor areas. (C) 2016 Elsevier Inc All rights reserved.

Caffeine is an ergogenic aid widely used before and during prolonged exercise. Due to its prolonged biological half-life caffeine effects could remain after exercise. We aimed to investigate the metabolic, respiratory, and cardiovascular postexercise responses to preexercise graded caffeine ingestion. Twelve aerobically trained subjects (mean VO2max = 54 ± 7 ml · min−1 · kg−1) cycled for 60-min at 75% VO2max after ingesting placebo (0 mg of caffeine per kg of body weight) or 0.5, 1.5, 3.0 and 4.5 mg · kg−1 on five occasions. During the 3 hr postexercise, heart rate, blood pressure, glucose, lactate, and fatty acids were analyzed. None of these variables were statistically affected by preexercise caffeine ingestion between 0.5 and 4.5 mg · kg−1. However, ingestion of 4.5 mg · kg−1 of caffeine raised postexercise energy expenditure 15% above placebo (233 ± 58 vs. 202 ± 49 kcal/3 hr; p < .05). Ventilation and tidal volume were elevated after the 4.5 mg·kg−1 caffeine dose above placebo (9.2 ± 2.5 L · min−1 and 0.67 ± 0.29 L · breath−1 vs. 7.8 ± 1.5 L · min−1 and 0.56 ± 0.20 L · breath−1, respectively; p < .05). Ventilation correlated with tidal volume (r = .45; p < .05) and energy expenditure (r = .72; p < .05). In summary, preexercise ingestion of ergogenic caffeine doses do not alter postexercise cardiovascular responses. However, ingestion of 4.5 mg · kg−1 of caffeine raises 3-hr postexercise energy expenditure (i.e., 31 kcal) likely through increased energy cost of ventilation.

PALLARES, J. G., V. E. FERNANDEZ-ELIAS, J. F. ORTEGA, G. MUNOZ, J. MUNOZ-GUERRA, and R. MORA-RODRIGUEZ. Neuromuscular Responses to Incremental Caffeine Doses: Performance and Side Effects. Med. Sci. Sports Exerc., Vol. 45, No. 11, pp. 2184-2192, 2013. Purpose: The purpose of this study was to determine the oral dose of caffeine needed to increase muscle force and power output during all-out single multijoint movements. Methods: Thirteen resistance-trained men underwent a battery of muscle strength and power tests in a randomized, double-blind, crossover design, under four different conditions: (a) placebo ingestion (PLAC) or with caffeine ingestion at doses of (b) 3 mgIkg j1 body weight (CAFF3mg), (c) 6 mgIkg j1 (CAFF6mg), and (d) 9 mgIkg j1 (CAFF9mg). The muscle strength and power tests consisted in the measurement of bar displacement velocity and muscle power output during free- weight full-squat (SQ) and bench press (BP) exercises against four incremental loads (25%, 50%, 75%, and 90% one-repetition maxi- mum (1RM)). Cycling peak power output was measured using a 4-s inertial load test. Caffeine side effects were evaluated at the end of each trial and 24 h later. Results: Mean propulsive velocity at light loads (25%-50% 1RM) increased significantly above PLAC for all caffeine doses (5.4%-8.5%, P = 0.039-0.003). At the medium load (75% 1RM), CAFF3mg did not improve SQ or BP muscle power or BP velocity. CAFF9mg was needed to enhance BP velocity and SQ power at the heaviest load (90% 1RM) and cycling peak power output (6.8%-11.7%, P = 0.03-0.05). The CAFF9mg trial drastically increased the frequency of the adverse side effects (15%-62%). Conclusions: The ergogenic dose of caffeine required to enhance neuromuscular performance during a single all-out contraction depends on the magnitude of load used. A dose of 3 mgIkg j1 is enough to improve high-velocity muscle actions against low loads, whereas a higher

[Background] To investigate the effects of a caffeine-containing energy drink on soccer performance during a simulated game. A second purpose was to assess the post-exercise urine caffeine concentration derived from the energy drink intake. [Methodology/Principal Findings] Nineteen semiprofessional soccer players ingested 630±52 mL of a commercially available energy drink (sugar-free Red Bull®) to provide 3 mg of caffeine per kg of body mass, or a decaffeinated control drink (0 mg/kg). After sixty minutes they performed a 15-s maximal jump test, a repeated sprint test (7×30 m; 30 s of active recovery) and played a simulated soccer game. Individual running distance and speed during the game were measured using global positioning satellite (GPS) devices. In comparison to the control drink, the ingestion of the energy drink increased mean jump height in the jump test (34.7±4.7 v 35.8±5.5 cm; P

Objective Studies evaluating the long-term impact of smoking laws on secondhand smoke (SHS) exposure using airborne markers are scarce. This study aimed to assess the long-term impact of the Spanish smoking law on SHS levels, using a specific and objective marker. Methods Follow-up study, measuring vapour-phase nicotine levels before the implementation of the law and 6, 12 and 24 months after the initial assessment. A total of 443 samples were taken at baseline in eight different regions in offices in the public administration, private sector, universities and hospitality venues. Results Two years after the law was implemented, the nicotine concentration decreased by a minimum of 60% in public administration, university and private sector offices, as well as in venues where smoking was totally banned. However, nicotine levels significantly increased by 40% in hospitality venues allowing smoking. No significant differences were found in hospitality venues with areas for smokers and non-smokers or in pubs and discotheques. Conclusions Two years after the smoking law came into force, levels of SHS exposure in the workplace were significantly lower than before the law was implemented. Importantly, however, SHS levels were even higher than before the law was implemented in venues still allowing smoking. The data obtained in this study clearly show that the 'Spanish model' is not protecting the health of hospitality workers and that a complete ban is required. Furthermore, this study highlights the importance of long-term monitoring of compliance with smoking laws over time.

Objective To assess changes in secondhand smoke exposure by means of airborne nicotine concentrations in public hospitals of Catalonia (Spain) before and after a comprehensive national smoking ban. Methods We monitored vapor-phase nicotine concentrations in 44 public hospitals in Catalonia (Spain) before the smoking ban (September–December 2005) and one year after (September–December 2006). We installed 5–7 sampling devices per hospital for 7 days in different places (228 pairs of samples), and 198 pairs of samples were available for the final analysis. Results The median nicotine concentration declined from 0.23 μg/m3 (interquartile range: 0.13–0.63) before the law to 0.10 μg/m3 (interquartile range: 0.02–0.19) after the law (% decline = 56.5, p

Background: Outdoor secondhand smoke (SHS) concentrations are usually lower than indoor concentrations, yet some studies have shown that outdoor SHS levels could be comparable to indoor levels under specific conditions. The main objectives of this study were to assess levels of SHS exposure in terraces and other outdoor areas of hospitality venues and to evaluate their potential displacement to adjacent indoor areas. Methods: Nicotine and respirable particles (PM2.5) were measured in outdoor and indoor areas of hospitality venues of 8 European countries. Hospitality venues of the study included night bars, restaurants and bars. The fieldwork was carried out between March 2009 and March 2011. Results: We gathered 170 nicotine and 142 PM2.5 measurements during the study. The median indoor SHS concentration was significantly higher in venues where smoking was allowed (nicotine 3.69 mg/m3, PM2.5: 120.51 mg/m3) than in those where smoking was banned (nicotine: 0.48 mg/m3, PM2.5: 36.90 mg/m3). The median outdoor nicotine concentration was higher in places where indoor smoking was banned (1.56 mg/m3) than in venues where smoking was allowed (0.31 mg/m3). Among the different types of outdoor areas, the highest median outdoor SHS levels (nicotine: 4.23 mg/m3, PM2.5: 43.64 mg/ m3) were found in the semi-closed outdoor areas of venues where indoor smoking was banned. Conclusions: Banning indoor smoking seems to displace SHS exposure to adjacent outdoor areas. Furthermore, indoor settings where smoking is banned but which have a semi-closed outdoor area have higher levels of SHS than those with open outdoor areas, possibly indicating that SHS also drifts from outdoors to indoors. Current legislation restricting indoor SHS levels seems to be insufficient to protect hospitality workers – and patrons – from SHS exposure. Tobacco-free legislation should take these results into account and consider restrictions in the terraces of some hospitality venues to ensure effective protection, This work was supported by the Executive Agency for Health and Consumers, DG SANCO, European Commission, grant number 2007313. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The effect upon lactation of two methods of post-partum contraception was evaluated. An experimental group of 100 healthy young mothers, positively oriented towards breast-feeding, received Chlormadinone diacetate (Clogestone), a C 21 progestogen, 0.6 mg daily in a continuous oral regimen. This group was observed for a total of 1,300 months. A similar group of 173 young women, who received an inert I.U.D. (Lippes' D) was used as control. In this latter group, 100 women were strongly motivated to breast-feed and were encouraged about proper procedures. The remaining 73 were not comparably motivated. Lactation was maintained for the longest period, in the greatest number of mothers in the Clogestone series. The overall lactation performance of women in the I.U.D. series was markedly lower; motivated mothers were able to breast-feed their infants for longer periods than the disinterested mothers, in whom milk secretion declined rapidly. The C 21 progestogen did not interfere with lactation; more than 40% of mothers in this series were able to nurse their children for periods over 12 months. Some factors involved in lactation are discussed.