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BACKGROUND: Differentiation between subtle changes in low serum testosterone concentrations, common in women and children, is not possible with current commercially available assays. The objectives of the study were to develop a method based on stable isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with adequate sensitivity and specificity and to investigate the applicability of this assay in serum samples from pre- and postmenopausal women. METHODS: For 16 women, testosterone levels were measured in blood samples drawn two years before and after physiological menopause, and for eight women in samples drawn before and after bilateral oophorectomy. Testosterone was extracted from serum, derivatized and analysed on an LC-MS/MS. RESULTS: The developed ID-LC-MS/MS method allowed for specific and reproducible measurement of testosterone. Comparison with stable isotope dilution-gas chromatography coupled to mass spectrometry detection by Deming regression analysis gave a slope of 1.025 and an intercept of 0.055 nmol/L (r = 0.9998). A significant decrease was found in testosterone concentrations before and after bilateral oophorectomy (P = 0.02), whereas no significant difference was found before and after natural menopause (P = 0.4). CONCLUSIONS: The ID-LC-MS/MS assay measures serum testosterone with acceptable accuracy and is useful in female samples, supporting the conclusion that the postmenopausal ovary contributes to circulating testosterone. To our knowledge, our analytical method compares favourably to similar published methods in terms of sensitivity. The sensitivity and specificity of this method comply with the reference method for measurement of testosterone in serum samples of women, children and men suffering from hypogonadism and can also be used for men with testosterone in the reference range. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this study was to confirm the ability of the airway occlusion pressure after 0.1 second (P0.1) recorded after extubation to define chronic obstructive pulmonary disease (COPD) patients with a high risk of postextubation respiratory failure and to evaluate the role of the expiratory flow limitation (EFL) in these patients. MATERIALS AND METHODS: Thirty 5 COPD patients who had been weaned from mechanical ventilation and extubated were included in the study. Expiratory flow limitation by the negative expiratory pressure method and P0.1 were recorded at the first hour of postextubation. We determined whether those patients who developed postextubation respiratory failure (failed extubation group) differed from those who did not (successful extubation group). RESULTS: Fourteen patients presented a postextubation respiratory failure. Expiratory flow limitation and P0.1 values in the failed extubation group, respectively (61.6% +/- 34.0%; 4.3 +/- 1.7 cm H(2)0) were significantly different (P < .05) from those observed in the successful extubation group, respectively (20.3% +/- 24.6%; 1.8 +/- 0.8 cm H(2)0). P0.1 and EFL would seem to be of use in predicting extubation outcome, respectively (OR 3.66, 95% confidence interval 1.68-7.94; OR 1.04, 95% confidence interval 1.01-1.07). The area under the receiver operating characteristic curve for diagnosing postextubation respiratory failure was 0.84 for EFL and 0.87 for P0.1. CONCLUSION: Bedside evaluation of EFL and P0.1 helps to define COPD patients at high risk for postextubation respiratory failure. Extubation failure in COPD was associated with higher EFL. © 2008 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

The present study examines help-seeking behavior among abused Vietnamese American women to understand factors associated with their decisions to seek help. Using a qualitative method and data obtained from in-depth interviews with 34 abused Vietnamese American women selected from four different Vietnamese communities in the United States (Orange County, CA; Houston, TX; Boston, MA; and Lansing, MI) and 11 Vietnamese Americans who had contacts with Vietnamese American victims of domestic violence through their jobs, the study found that abused Vietnamese American women have sought help from their personal networks, the criminal justice system, and various victim service agencies. Data analyses suggest that the decisions of Vietnamese American women to reach out are complex and diverse and are shaped by various structural, cultural, and organizational factors. Acculturation on the part of abused women as well as victim services can facilitate the women's efforts to seek help outside their personal networks. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) is a powerful, highly efficient analytical technique capable of providing label-free, non-invasive, rapid, and ultrasensitive molecular detection down to the single-molecule level. Despite its advantages, SERS remains largely confined to laboratory settings due to the complexities of substrate fabrication and challenges in analyzing real-world samples. Developing flexible SERS substrates that achieve both high fabrication efficiency and high sensing performance, while being practical for field applications, is critical for advancing SERS toward broader, real-world use. In this study, we present a novel paper-based Ag dendritic SERS chip, fabricated via a simple chemical reduction process that directly forms Ag dendritic nanostructures on cellulose fibers. This chip substrate demonstrates exceptional sensitivity for the detection of thiram pesticide, with a detection limit as low as 7.76 × 10 -11 M. The chip substrate also exhibits outstanding reliability, with reproducibility and repeatability both less than 5%. Furthermore, the flexible nature of the paper substrate enables it to conform to curved surfaces and be in direct contact with analytes, exemplified by its ability to adhere to and retrieve thiram from pear skin using a novel "paste-and-peel-off" technique. The substrate shows remarkable performance for thiram detection on pear skin, with sharp recovery rates ranging from 90% to 105%. With its facile fabrication, excellent sensitivity, high reliability, and practical applicability in non-invasive sampling, the paper-based Ag dendritic SERS substrate offers significant potential as an advanced substrate to bring SERS out of the laboratory and closer to real-world applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Notch plays critical roles in developmental processes and disease pathogenesis, which has led to numerous efforts to modulate its function with small molecules and antibodies. Here we present a nanobody inhibitor of Notch signaling, derived from a synthetic phage-display library targeting the notch Negative Regulatory Region (NRR). The nanobody inhibits Notch signaling in a luciferase reporter assay and in Notch-dependent hematopoietic progenitor cell differentiation assay, despite a modest 19uM affinity for Notch. We addressed the low affinity by fusion to a membrane-associating domain derived from the β-Pore forming toxin Aerolysin, resulting in a significantly improved IC50 for Notch inhibition. The nanobody-aerolysin fusion inhibits proliferation of T-ALL cell lines with similar efficacy to other Notch pathway inhibitors. Overall, this study reports the development of a Notch inhibitory antibody, and demonstrates a proof-of-concept for a generalizable strategy to increase the efficacy and potency of low-affinity antibody binders., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest in this work.

A flexible, ultrasensitive, and practical SERS chip is presented based on a paper/f-TiO 2 /Ag structure. The chip enhances the self-assembly of Ag nanoparticles on a cellulose fiber matrix, facilitated by smart functionalized TiO 2 nanomaterials (f-TiO 2 ). This design enables superior detection of the hazardous pesticide tricyclazole (TCZ) on crops using an advanced, simple, and efficient analytical method. Despite its straightforward fabrication process via a solvent immersion method, the intrinsic smart surface properties of the TiO 2 bridging material - both hydrophilic and hydrophobic - enable the uniform and dense self-assembly of hydrophilic Ag nanoparticles (NPs) on the cellulose fiber paper substrate. This innovative design provides superior sensing efficiency for TCZ molecules with a detection limit reaching 2.1 × 10 -9  M, a remarkable improvement compared to Paper/Ag substrates lacking f-TiO 2 nanomaterials, which register at 10 -5  M. This flexible SERS substrate also exhibits very high reliability as indicated by its excellent reproducibility and repeatability with relative standard deviations (RSD) of only 5.93% and 4.73%, respectively. Characterized by flexibility and a water-attractive yet non-soluble surface, the flexible Paper/f-TiO 2 /Ag chips offer the convenience of direct immersion into the analytical sample, facilitating seamless target molecule collection while circumventing interference signals. Termed the "dip and dry" technique, its advantages in field analysis are indisputable, boasting in situ deployment, simplicity, and high efficiency, while minimizing interference signals to negligible levels. Through the application of this advanced technique, we have successfully detected TCZ in two high-value crops, ST25 rice and dragon fruit, achieving excellent recovery values ranging from 90 to 128%. This underscores its immense potential in ensuring food quality and safety. As a proof of concept, flexible Paper/f-TiO 2 /Ag SERS chips, with a simple fabrication process, advanced analytical technique, and superior sensing efficiency, bring SERS one step closer to field applications beyond the laboratory., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience., Methods: This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ)., Results: Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience (p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008-1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950-0.996; p = 0.02)., Conclusions: Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes., (© 2024. The Author(s).)

Flexible surface-enhanced Raman scattering (SERS) sensors have gained significant attention for their practical applications in detecting chemical and biological molecules. However, the fabrication of flexible SERS chips is often complex and requires advanced techniques. In this study, we present a simple and rapid method to design a flexible SERS chip based on polyvinyl alcohol (PVA), cellulose, and silver nanoparticles (AgNPs) using mechanical stirring and drying methods. Benefiting from the abundant hydroxide groups on cellulose, AgNPs easily adhere and distribute evenly on the cellulose surface. The combination of PVA and cellulose forms a bendable film-like SERS chip. This chip allows convenient immersion in liquid analyte samples. We demonstrate its effectiveness by using it to detect the thiram pesticide in apple juice using the "dip and dry" method, achieving an outstanding detection limit of 1.01 × 10 -8  M. The Raman signals on the SERS chips exhibit high repeatability and reproducibility, with relative standard deviation values below 10%. These findings show that the flexible PVA/cellulose/Ag SERS chips is a strong candidate for real-world analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Anh-Tuan Le reports administrative support and equipment, drugs, or supplies were provided by Phenikaa University., (© 2023 The Authors.)

Background: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets., Methods: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed., Findings: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032)., Interpretation: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications., Funding: French Ministry of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

It is essential to achieve herd immunity in order to control the COVID-19 pandemic, and this requires a high level of vaccination rate. Despite the importance of vaccination, hesitancy and unwillingness in receiving the COVID-19 vaccine still exists. It is therefore crucial to comprehend the intentions of adults regarding COVID-19 vaccination, which is beneficial for establishing community immunity and an efficient future pandemic response. An online survey was administered to 2722 adults in Vietnam. Cronbach's alpha, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) were used to test the reliability and validity of the developed scales. Then, structural equational modeling (SEM) was employed to test correlations. This study found that favorable attitudes toward COVID-19 vaccines played the most important role in shaping adults' intention to receive these vaccines, followed by perceived behavioral control, perceived benefits of COVID-19 vaccines, and subjective norms. Concurrently, all three core dimensions of the theory of planned behavior mediated the link between the perceived benefits of COVID-19 vaccines and the intention to receive them. Also, there were significant differences between males and females in the way they formed this intention. The findings of this study offer valuable guidance for practitioners on how to encourage adults to receive COVID-19 vaccinations, as well as how to limit the transmission of the COVID-19 virus., Competing Interests: The authors declare no conflict of interest.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Over the past decade the use of LC-MS/MS has increased significantly in the hospital laboratories. Clinical laboratories have switched from immunoassays to LC-MS/MS methods due to the promise of improvements in sensitivity and specificity, better standardization with often non-commutable international standards, and better between-laboratory comparison. However, it remains unclear whether routine performance of the LC-MS/MS methods have met these expectations., Method: This study examined the EQAS results, from the Dutch SKML, of serum cortisol, testosterone, 25OH-vitaminD and cortisol in urine and saliva over 9 surveys (2020 to first half of 2021)., Results: The study found a significant increase in the number of compounds and in the number of results measured in the different matrices, with LC-MS/MS over a period of eleven years. In 2021, approximately 4000 LC-MS/MS results were submitted (serum: urine: saliva = 58:31:11%) compared to only 34 in 2010. When compared to the individual immunoassays, the LC-MS/MS based methods for serum cortisol, testosterone and 25OH-vitaminD showed comparable but also higher between-laboratory CVs in different samples of the surveys. For cortisol, testosterone and 25OH-vitaminD the median CV was 6.8%, 6.1% and 4.7% respectively for the LC-MS/MS compared to 3.9-8.0%,4.5-6.7%, and 7.5-18.3% for immunoassays. However, the bias and imprecision of the LC-MS/MS was better than that of the immunoassays., Conclusion: Despite the expectation that LC-MS/MS methods would result in smaller between-laboratory differences, as they are relatively matrix independent and better to standardize, the results of the SKML round robins do not reflect this for some analytes and may be in part explained by the fact that in most cases laboratory developed tests were used., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide. The chronic course of COPD is frequently worsened by acute exacerbations (AECOPD). Mortality in patients hospitalized for severe AECOPD remains dramatically high, and the underlying mechanisms are poorly understood. Lung microbiota is associated with COPD outcomes in nonsevere AECOPD, but no study specifically investigated severe AECOPD patients. The aim of this study is thus to compare lung microbiota composition between severe AECOPD survivors and nonsurvivors. Induced sputum or endotracheal aspirate was collected at admission from every consecutive severe AECOPD patient. After DNA extraction, the V3-V4 and ITS2 regions were amplified by PCR. Deep-sequencing was performed on a MiSeq sequencer (Illumina); the data were analyzed using DADA2 pipeline. Among 47 patients admitted for severe AECOPD, 25 (53%) with samples of sufficient quality were included: 21 of 25 (84%) survivors and 4 of 25 (16%) nonsurvivors. AECOPD nonsurvivors had lower α-diversities indices than survivors for lung mycobiota but not for lung bacteriobiota. Similar results were demonstrated comparing patients receiving invasive mechanical ventilation ( n = 13 [52%]) with those receiving only noninvasive ventilation ( n = 12 [48%]). Previous systemic antimicrobial therapy and long-term inhaled corticosteroid therapy could alter the lung microbiota composition in severe AECOPD patients. In acidemic AECOPD, lower lung mycobiota α-diversity is linked to the severity of the exacerbation, assessed by mortality and the requirement for invasive mechanical ventilation, whereas lung bacteriobiota α-diversity is not. This study encourages a multicenter cohort study investigating the role of lung microbiota, especially fungal kingdom, in severe AECOPD. IMPORTANCE In AECOPD with acidemia, more severe patients- i.e. , nonsurvivors and patients requiring invasive mechanical ventilation-have lower lung mycobiota α-diversity than survivors and patients receiving only noninvasive ventilation, respectively. This study encourages a large multicenter cohort study investigating the role of lung microbiota in severe AECOPD and urges investigation of the role of the fungal kingdom in severe AECOPD.

Objectives: To compare the accuracy of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) Scores in predicting mortality among intensive care unit (ICU) patients with sepsis in a low-income and middle-income country., Design: A multicentre, cross-sectional study., Setting: A total of 15 adult ICUs throughout Vietnam., Participants: We included all patients aged ≥18 years who were admitted to ICUs for sepsis and who were still in ICUs from 00:00 to 23:59 of the specified study days (ie, 9 January, 3 April, 3 July and 9 October of the year 2019)., Primary and Secondary Outcome Measures: The primary outcome was hospital all-cause mortality (hospital mortality). We also defined the secondary outcome as all-cause deaths in the ICU (ICU mortality)., Results: Of 252 patients, 40.1% died in hospitals, and 33.3% died in ICUs. SOFA Score (areas under the receiver operating characteristic curve (AUROC): 0.688 (95% CI 0.618 to 0.758); cut-off value≥7.5; P AUROC <0.001) and APACHE II Score (AUROC: 0.689 (95% CI 0.622 to 0.756); cut-off value ≥20.5; P AUROC <0.001) both had a poor discriminatory ability for predicting hospital mortality. However, the discriminatory ability for predicting ICU mortality of SOFA (AUROC: 0.713 (95% CI 0.643 to 0.783); cut-off value≥9.5; P AUROC <0.001) was fair and was better than that of APACHE II Score (AUROC: 0.672 (95% CI 0.603 to 0.742); cut-off value≥18.5; P AUROC <0.001). A SOFA Score≥8 (adjusted OR (AOR): 2.717; 95% CI 1.371 to 5.382) and an APACHE II Score≥21 (AOR: 2.668; 95% CI 1.338 to 5.321) were independently associated with an increased risk of hospital mortality. Additionally, a SOFA Score≥10 (AOR: 2.194; 95% CI 1.017 to 4.735) was an independent predictor of ICU mortality, in contrast to an APACHE II Score≥19, for which this role did not., Conclusions: In this study, SOFA and APACHE II Scores were worthwhile in predicting mortality among ICU patients with sepsis. However, due to better discrimination for predicting ICU mortality, the SOFA Score was preferable to the APACHE II Score in predicting mortality.Clinical trials registry - India: CTRI/2019/01/016898., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The simple scoring systems for predicting the outcome of sepsis in intensive care units (ICUs) are few, especially for limited-resource settings. Therefore, this study aimed to evaluate the accuracy of the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score in predicting the mortality of ICU patients with sepsis in Vietnam., Methods: We did a multicenter cross-sectional study of patients with sepsis (≥18 years old) presenting to 15 adult ICUs throughout Vietnam on the specified days (i.e., 9th January, 3rd April, 3rd July, and 9th October) representing the different seasons of 2019. The primary and secondary outcomes were the hospital and ICU all-cause mortalities, respectively. The area under the receiver operating characteristic curve (AUROC) was calculated to determine the discriminatory ability of the qSOFA score for deaths in the hospital and ICU. The cut-off value of the qSOFA scores was determined by the receiver operating characteristic curve analysis. Upon ICU admission, factors associated with the hospital and ICU mortalities were assessed in univariable and multivariable logistic models., Results: Of 252 patients, 40.1% died in the hospital, and 33.3% died in the ICU. The qSOFA score had a poor discriminatory ability for both the hospital (AUROC: 0.610 [95% CI: 0.538 to 0.681]; cut-off value: ≥2.5; sensitivity: 34.7%; specificity: 84.1%; PAUROC = 0.003) and ICU (AUROC: 0.619 [95% CI: 0.544 to 0.694]; cutoff value: ≥2.5; sensitivity: 36.9%; specificity: 83.3%; PAUROC = 0.002) mortalities. However, multivariable logistic regression analyses show that the qSOFA score of 3 was independently associated with the increased risk of deaths in both the hospital (adjusted odds ratio, AOR: 3.358; 95% confidence interval, CI: 1.756 to 6.422) and the ICU (AOR: 3.060; 95% CI: 1.651 to 5.671)., Conclusion: In our study, despite having a poor discriminatory value, the qSOFA score seems worthwhile in predicting mortality in ICU patients with sepsis in limited-resource settings., Clinical Trial Registration: Clinical trials registry-India: CTRI/2019/01/016898., Competing Interests: The authors have declared that no competing interests exist.

Lorentz reciprocity is a fundamental physical property limiting advanced wave propagation control. Previously, special materials and magnetic bias were used to break the reciprocity; however, the approaches are limited by the bulky and costly implementation. To achieve nonreciprocity without magnetic bias, space-time-modulated metamaterials have been investigated for far-field wave propagation control. The metamaterial can also support wave propagation based on near-field coupling between the periodically arranged unit cells, i.e., magneto-inductive waves (MIWs). Near-field wave propagation control via the metamaterial has various significant applications; nevertheless, the potential for near-field wave propagation control has not been fully explored. Therefore, it is necessary to investigate the potential of the space-time-modulated near-field metamaterial. This paper demonstrates nonreciprocal MIW propagation control using a space-time-modulated metamaterial. To achieve field manipulation, we propose a tunable unit cell suitable for creating a cavity mode at a deep subwavelength scale (∼λ/10 3 ). Spatial field modulation, achieved by breaking the translational symmetry of the unit cells, allows for the creation of reconfigurable waveguides on the metamaterial. Temporal field modulation, achieved by breaking the capacitive symmetry of the varactor, allows for direction-dependent transmission in the waveguide. This spatiotemporal modulation successfully achieves nonreciprocal wave propagation and frequency conversion, investigated under various conditions. The proposed space-time-modulated metamaterial may provide significant advances for a wide range of systems that require dynamic, nonreciprocal, near-field wave propagation control.

Purpose: Acute mesenteric ischemia (AMI) is a rare, but life-threatening condition occurring among critically ill patients. Several factors have been associated with AMI, but the causal link is debated, most studies being retrospective. Among these factors, enteral nutrition (EN) could be associated with AMI, in particular among patients with shock. We aimed to study the factors independently associated with AMI in a post hoc analysis of the NUTRIREA-2 trial including 2410 critically ill ventilated patients with shock, randomly assigned to receive EN or parenteral nutrition (PN)., Methods: Post hoc analysis of the NUTRIREA-2 trial was conducted. Ventilated adults with shock were randomly assigned to receive EN or PN. AMI was assessed by computed tomography, endoscopy, or laparotomy. Factors associated with AMI were studied by univariate and multivariate analysis., Results: 2410 patients from 44 French intensive care units (ICUs) were included in the study: 1202 patients in the enteral group and 1208 patients in the parenteral group. The median age was 67 [58-76] years, with 67% men, a SAPS II score of 59 [46-74], and a medical cause for ICU admission in 92.7%. AMI was diagnosed among 24 (1%) patients, mainly by computed tomography (79%) or endoscopy (38%). The mechanism of AMI was non-occlusive mesenteric ischemia (n = 12), occlusive (n = 4), and indeterminate (n = 8). The median duration between inclusion in the trial and AMI diagnosis was 4 [1-11] days. Patients with AMI were older, had a higher SAPS II score at ICU admission, had higher plasma lactate, creatinine, and ASAT concentrations and lower hemoglobin concentration, had more frequently EN, dobutamine, and CVVHDF at inclusion, developed more frequently bacteremia during ICU stay, and had higher 28-day and 90-day mortality rates compared with patients without AMI. By multivariate analysis, AMI was independently associated with EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin concentration ≤ 10.9 g/dL., Conclusion: Among critically ill ventilated patients with shock, EN, dobutamine use, SAPS II score ≥ 62 and hemoglobin ≤ 10.9 g/dL were independently associated with AMI. Among critically ill ventilated patients requiring vasopressors, EN should be delayed or introduced cautiously in case of low cardiac output requiring dobutamine and/or in case of multiple organ failure with high SAPS II score., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Although in a critical position in the economy, the paper industry releases a lot of wastewater that requires adequate treatment for sustainable development. This study presents an application of Life cycle assessment (LCA) with the ReCiPe tool on the wastewater treatment plant (WWTP) of a paper factory in Vietnam to evaluate the environmental effect of the individual techniques in WWTP, especially the internal circulation (IC) reactor, a pioneer and practical anaerobic technology. Both Midpoint and Endpoint categories results demonstrated that chemical use and electricity consumption mainly contributed to the environmental impact in the WWTP. The Dissolved air flotation (DAF) and Moving bed biofilm reactor (MBBR) are classified as effective techniques to reduce the impacts on the environment. Moreover, the comparison of LCA between IC and up-flow anaerobic sludge bed (UASB) shows that IC is the better practically green technique for the environment.

In this study, the electro-Fenton (EF) method was applied to remove total organic carbon (TOC) from the pesticide production wastewater containing tricyclazole (TC). Statistical Taguchi method was used to optimize the treatment performance. Analysis of variance (ANOVA) indicated that the polynomial regression model fitted experimental data with R 2 of 0.969. The optimal conditions for eliminating 75.4% TOC and 93.7% TC were 0.2 mM of Fe 2+ , 990 mg/L of Na 2 SO 4 , 180 min of reaction time at pH 3 with 2.22 mA/cm 2 of current density. The removal of TC present in the wastewater followed the first-order reaction kinetic model (R 2 = 0.993); while that was the second-order kinetic model in the case of the TOC removal (R 2 = 0.903). In addition, the experimental results and theory approaches (density functional theory and natural bond orbital calculations) also showed the C-N bond breaking and nitrate ions cleavage to ammonia. Acute toxicity of the pesticide wastewater after treatment (PWAT) on microcrustaceans showed that the treated wastewater still exhibited high toxicity against D. magna, with LC 50 values of 3.84%, 2.68%, 2.05%, and 1.78% at 24 h, 48 h, 72 h, and 96 h, respectively.

Sepsis is the most common cause of in-hospital deaths, especially from low-income and lower-middle-income countries (LMICs). This study aimed to investigate the mortality rate and associated factors from sepsis in intensive care units (ICUs) in an LMIC. We did a multicenter cross-sectional study of septic patients presenting to 15 adult ICUs throughout Vietnam on the 4 days representing the different seasons of 2019. Of 252 patients, 40.1% died in hospital and 33.3% died in ICU. ICUs with accredited training programs (odds ratio, OR: 0.309; 95% confidence interval, CI 0.122-0.783) and completion of the 3-h sepsis bundle (OR: 0.294; 95% CI 0.083-1.048) were associated with decreased hospital mortality. ICUs with intensivist-to-patient ratio of 1:6 to 8 (OR: 4.533; 95% CI 1.621-12.677), mechanical ventilation (OR: 3.890; 95% CI 1.445-10.474) and renal replacement therapy (OR: 2.816; 95% CI 1.318-6.016) were associated with increased ICU mortality, in contrast to non-surgical source control (OR: 0.292; 95% CI 0.126-0.678) which was associated with decreased ICU mortality. Improvements are needed in the management of sepsis in Vietnam such as increasing resources in critical care settings, making accredited training programs more available, improving compliance with sepsis bundles of care, and treating underlying illness and shock optimally in septic patients., (© 2021. The Author(s).)

This study investigates distribution, pollution indices, and potential risk assessment for human health and ecology of eight heavy metals in twenty-five street dust samples collected from metropolitan area-Ho Chi Minh City, Vietnam. Results showed that Zn was of the highest concentration (466.4 ± 236.5 mg/kg), followed by Mn (393.9 ± 93.2 mg/kg), Cu (153.7 ± 64.7 mg/kg), Cr (102.4 ± 50.5 mg/kg), Pb (49.6 ± 21.4 mg/kg), Ni (36.2 ± 15.4 mg/kg), Co (7.9 ± 1.9 mg/kg), and Cd (0.5 ± 0.5 mg/kg). The principal component analysis revealed that three sources of heavy metals measured in street dust include vehicular activities (32.38%), mixed source of vehicular and residential activities (26.72%), and mixture of industrial and natural sources (20.23%). The geo-accumulation index values showed levels of non-pollution to moderately pollution for Mn and Co; moderately pollution for Ni; moderately to strongly pollution for Cd, Cr, and Pb; and strongly pollution for Cu and Zn. The potential ecological risk values of all sampling sites were close to the high-risk category. Zn (28.9%), Cu (25.4%), and Mn (24.4%) dominantly contributed to the ecological risk. For non-carcinogenic risk, the hazard quotient values for both children and adults were within a safety level. For carcinogenic risk, the TCR Children was about 3 times higher than TCR Adults , but still within a tolerable limit (1 × 10 -6 to 1 × 10 -4 ) of cancer risk. Cr was a major contribution to potential risks in humans. Such studies on heavy metal in street dust are crucial but are still limited in Vietnam/or metropolitan area in Southeast Asia. Therefore, this study can fill the information gap about heavy metal contaminated street dust in a metropolitan area of Vietnam., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets., Methods and Analysis: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes., Ethics and Dissemination: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT03573739., Competing Interests: Competing interests: JR had travel and accommodation expenses to attend scientific meetings covered by Baxter and Fresenius., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported., Methods: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated., Results: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively., Conclusion: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Wireless power transfer (WPT) provides a convenient method of delivering energy to multiple devices. With the increasing use of WPT, safety concerns inevitably create the need for a reliable control mechanism. Previous approaches in advanced WPT or metamaterial-enhanced WPT, however, have the limitation that neither the intensity nor the shape of the field-localizing area can be dynamically controlled. To address this limitation, we introduce the novel concept of a hotspot or power-focused region using field-localizing WPT. Using the proposed method, we provide experimental evidence demonstrating that the location, shape, and intensity of the hotspot can be manipulated as desired. The hotspot effectively enhances power delivery to the intended device while reducing leakage to unwanted areas. To dynamically reconfigure the hotspots, we propose an active metasurface with multi-functionality due to its frequency switching and tuning capability. The dynamic reconfiguring capability provides a wide range of versatile practical applications, overcoming the limitations associated with passive metamaterials. Because the location, shape, and intensity of hotspots can readily be controlled, the proposed method is not limited to WPT applications. It can also be used for a broad range of applications that require precise control of power delivery.

Background: Whether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition., Methods: In this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20-25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate <2 mmol/L). The primary endpoint was mortality on day 28 after randomisation in the intention-to-treat-population. This study is registered with ClinicalTrials.gov, number NCT01802099., Findings: After the second interim analysis, the independent Data Safety and Monitoring Board deemed that completing patient enrolment was unlikely to significantly change the results of the trial and recommended stopping patient recruitment. Between March 22, 2013, and June 30, 2015, 2410 patients were enrolled and randomly assigned; 1202 to the enteral group and 1208 to the parenteral group. By day 28, 443 (37%) of 1202 patients in the enteral group and 422 (35%) of 1208 patients in the parenteral group had died (absolute difference estimate 2·0%; [95% CI -1·9 to 5·8]; p=0·33). Cumulative incidence of patients with ICU-acquired infections did not differ between the enteral group (173 [14%]) and the parenteral group (194 [16%]; hazard ratio [HR] 0·89 [95% CI 0·72-1·09]; p=0·25). Compared with the parenteral group, the enteral group had higher cumulative incidences of patients with vomiting (406 [34%] vs 246 [20%]; HR 1·89 [1·62-2·20]; p<0·0001), diarrhoea (432 [36%] vs 393 [33%]; 1·20 [1·05-1·37]; p=0·009), bowel ischaemia (19 [2%] vs five [<1%]; 3·84 [1·43-10·3]; p=0·007), and acute colonic pseudo-obstruction (11 [1%] vs three [<1%]; 3·7 [1·03-13·2; p=0·04)., Interpretation: In critically ill adults with shock, early isocaloric enteral nutrition did not reduce mortality or the risk of secondary infections but was associated with a greater risk of digestive complications compared with early isocaloric parenteral nutrition., Funding: La Roche-sur-Yon Departmental Hospital and French Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders., Methods: A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852)., Results: Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2-6) versus 4 days (IQR 2-7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59-14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07-13.31); p = 0.04]., Conclusions: Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.

Introduction: We evaluated the performance of the HemoCue WBC DIFF, a point-of-care device for total and differential white cell count, primarily to test its suitability for the mandatory white blood cell monitoring in clozapine use., Method: Leukocyte count and 5-part differentiation was performed by the point-of-care device and by routine laboratory method in venous EDTA-blood samples from 20 clozapine users, 20 neutropenic patients, and 20 healthy volunteers. From the volunteers, also a capillary sample was drawn. Intra-assay reproducibility and drop-to-drop variation were tested., Results: The correlation between both methods in venous samples was r > 0.95 for leukocyte, neutrophil, and lymphocyte counts. The correlation between point-of-care (capillary sample) and routine (venous sample) methods for these cells was 0.772; 0.817 and 0.798, respectively. Only for leukocyte and neutrophil counts, the intra-assay reproducibility was sufficient., Conclusion: The point-of-care device can be used to screen for leukocyte and neutrophil counts. Because of the relatively high measurement uncertainty and poor correlation with venous samples, we recommend to repeat the measurement with a venous sample if cell counts are in the lower reference range. In case of clozapine therapy, neutropenia can probably be excluded if high neutrophil counts are found and patients can continue their therapy., (© 2016 John Wiley & Sons Ltd.)

The present study examines intimate partner violence (IPV) reported by a sample of women in Zimbabwe to explore factors associated with the problem. Findings from the study indicate an important role of gender relationships in violence against women. The effects of gender inequalities on the likelihood of IPV vary with types of violence, but husband's patriarchal behaviors increase the likelihood of all forms of violence. The study suggests the importance of improving gender equality through public education on gender relationships, increasing women's education and economic opportunities, and eliminating customary laws that sustain gender inequality as necessary steps to combat IPV against women in Zimbabwe., (© The Author(s) 2015.)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations., Objective: The aim of the study was to evaluate the recruitment of blood fibrocytes in patients with COPD during exacerbations and, subsequently, to identify potential mechanisms implicated in such recruitment., Methods: Using flow cytometry, we quantified circulating fibrocytes and characterized their chemokine receptor expression in 54 patients with COPD examined during an acute exacerbation (V1) and 2 months afterward (V2) and in 40 control subjects. The role of the chemokines CXCL12 and CCL11 in fibrocyte migration was investigated by using a chemotaxis assay. Patients were followed for up to 3 years after V1., Results: We demonstrated a significantly increased number of circulating fibrocytes at V1 compared with control subjects. The number of circulating fibrocytes decreased at V2. A high percentage of circulating fibrocytes during exacerbation was associated with increased risk of death. The percentage of fibrocytes at V2 was negatively correlated with FEV1, forced vital capacity, FEV1/forced vital capacity ratio, transfer lung capacity of carbon monoxide, and Pao2. Fibrocytes highly expressed CXCR4 and CCR3, the chemokine receptors for CXCL12 and CCL11, respectively. Fibrocytes collected from patients with COPD at V1 had increased chemotactic migration in response to CXCL12 but not to CCL11 compared with those from control subjects. Plerixafor, a CXCR4 antagonist, decreased fibrocyte migration to plasma from patients with exacerbating COPD., Conclusion: Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in such fibrocyte recruitment (Firebrob study; ClinicalTrials NCT01196832)., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of our study was to determine reference intervals and biologic variation for testosterone (T), free testosterone (fT), and free androgen index (FAI) in women with accurate methods and to test the discriminative value of these parameters in a polycystic ovary syndrome (PCOS)-population., Methods: Serum was obtained daily during a normal menstrual cycle from 25 healthy women (677 data-points). A single serum sample was obtained from 44 PCOS-patients. T was measured by LC–MS/MS and by Architect® 2nd generation T Immunoassay. Sex hormone-binding globulin was measured to calculate fT and FAI. Results: Reference intervals which were established in healthy women with an ovulatory menstrual cycle were T = 0.3-1.6 nmol/L and 0.5-2.0 nmol/L, fT = 5.2-26 pmol/L and 7.2-33 pmol/L, and FAI = 0.4-2.9 and 0.6-4.4, by LC-MS/MS and immunoassay, respectively. T, fT and FAI were higher in PCOS patients than in controls (p b 0.0001). The areas under the curve of receiver operator characteristic (ROC) plots were not different for T, fT, or FAI when T was measured by LC–MS/MS versus immunoassay based on prediction of PCOS. FAI and fT were the strongest predictors of PCOS., Conclusions: When based upon the appropriate reference intervals and ROC analysis, LC-MS/MS and second generation immunoassay have equivalent clinical utility for the diagnosis of PCOS.

Background: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock., Methods/design: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs., Discussion: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015., Trial Registration: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).

To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab., Methods: The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab., Results: Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3-12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L; creatinine 152 (range 48-797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0-4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab., Conclusions: Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

Using data from the National Longitudinal Studies of Adolescent Health, the present study examines self-reported substance use (cigarettes, tobacco, and marijuana) among youth from different immigration generations to determine the immigrant paradox in substance use for different racial and ethnic groups as well as factors contributing to the relationship between immigration and substance use. Results of data analysis indicate the immigrant paradox in substance use among non-Hispanic Whites, Asians, and Hispanics, but not among non-Hispanic Blacks. The study also shows that factors explaining the immigrant paradox in substance use vary with racial and ethnic groups, but English use at home, friends' cigarette and marijuana use appear to be the most important mediating factors. Findings from the study suggest that effective interventions in youth substance use require an understanding of adaptation patterns in different racial and ethnic groups, so that factors associated with adaptation problems experienced by particular groups will be appropriately addressed.

Objective: To evaluate the relationship between the body mass index (BMI) and serum testosterone concentrations in men receiving luteinizing hormone-releasing hormone (LHRH) agonist therapy for prostate cancer., Materials and Methods: A total of 66 white men were included in the present study. All subjects had received LHRH agonist therapy for ≥ 3 months. The BMI was calculated, and the subjects were classified as normal weight (i.e. BMI <25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI >30 kg/m(2)). The serum testosterone concentration was determined using the highly sensitive isotope dilution-liquid chromatography-tandem mass spectrometry technique. The sex hormone-binding globulin level was determined using an immunometric assay, and the free serum testosterone concentration was calculated., Results: The median serum testosterone concentration of the patients with a BMI <25 kg/m(2) was 5.5 ng/dL. The patients with a BMI of 25-30 kg/m(2) had a median serum testosterone concentration of 3.8 ng/dL. Those patients with a BMI >30 kg/m(2) had a median concentration of 5.7 ng/dL. No significant difference in the serum testosterone concentrations among the 3 groups was found. The sex hormone-binding globulin levels declined with an increasing BMI. The concentration of free testosterone was significantly greater in the obese men., Conclusion: Using an ultrasensitive technique of serum testosterone measurement, the present data have shown that no difference exists in the serum testosterone concentration in the castrate range among normal weight, overweight, and obese patients receiving LHRH agonist therapy for prostate cancer. From our findings and current knowledge, more stringent follow-up or changes in dosage or dosage intervals of LHRH agonist therapy in those with a greater or high BMI is not warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: In our hospital, female-to-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the end of the inter-injection period, which calls for an evaluation of the time-course of testosterone levels between injections. Evaluation of salivary testosterone is a practical approach for sequential measurements. Since only ∼2% of total serum testosterone is present in saliva, a sensitive assay is necessary. The objective was to develop an isotope dilution-liquid chromatography-tandem mass spectrometry method (ID-LC-MS/MS) for salivary testosterone measurements and to evaluate the testosterone profiles after testosterone-ester mixture injections in FtM-adolescents., Experimental: FtM treated with 125 mg/2 weeks or with 250 mg/4 weeks depots of testosterone-ester mixture collected saliva at different time intervals. Salivary testosterone was measured by a thoroughly validated ID-LC-MS/MS assay., Results: An ID-LC-MS/MS method for measuring salivary testosterone was developed with adequate accuracy and specificity. The reference range was established at 135-400 pmol/L. Testosterone levels peaked supra-physiologically immediately post-injection, and decreased to levels within the male reference range after nine days in all patients. 250 mg/4 weeks depots resulted in values below the reference range at the end of the 4 weeks., Discussion: The development of an adequate ID-LC-MS/MS method for measuring salivary testosterone allowed us to investigate the testosterone profile in FtM-adolescents after testosterone-esters mixture injections. These injections lead to extreme concentrations which may affect the wellbeing of the patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The safety of fiberoptic bronchoscopy (FOB) in nonintubated critically ill patients with acute respiratory failure has not been extensively evaluated. We aimed to measure the incidence of intubation and the need to increase ventilatory support following FOB and to identify predictive factors for this event., Methods: A prospective multicenter observational study was carried out in eight French adult intensive care units. The study included 169 FOB performed in patients with a PaO(2)/FiO(2) ratio ≤ 300. The main end-point was intubation rate. The secondary end-point was rate of increased ventilatory support defined as an increase in oxygen requirement >50 %, the need to start noninvasive positive pressure ventilation (NI-PPV) or increase NI-PPV support., Results: Within 24 h, an increase in ventilatory support was required following 59 bronchoscopies (35 %), of which 25 (15 %) led to endotracheal intubation. The existence of chronic obstructive pulmonary disease (COPD; OR 5.2, 95 % CI 1.6-17.8; p = 0.007) or immunosuppression (OR 5.4, 95 % CI 1.7-17.2; p = 0.004] were significantly associated with the need for intubation in the multivariable analysis. None of the baseline physiological parameters including the PaO(2)/FiO(2) ratio was associated with intubation., Conclusions: Bronchoscopy is often followed by an increase in ventilatory support in hypoxemic critically ill patients, but less frequently by the need for intubation. COPD and immunosuppression are associated with the need for invasive ventilation in the 24 h following bronchoscopy.

Background: Testosterone concentrations in normally cycling women are assumed to be elevated around the time of ovulation. The clinical relevance of changing testosterone concentrations during the menstrual cycle, however, is unclear. Poor performance of current direct immunoassays for testosterone at low concentrations confounds this issue. Therefore, our objective was to assess daily testosterone fluctuation during the menstrual cycle by a thoroughly validated isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method and to evaluate whether an ARCHITECT® 2nd Generation Testosterone fully automated immunoassay is equally suited for this purpose., Methods: Testosterone was measured in serum obtained daily during the menstrual cycle of 25 healthy women, characterized by biochemical and physical examination., Results: Performance of the ID-LC-MS/MS method was concordant with a published reference method (y=1.007x-0.056 nmol/L; r=0.9998). Comparison of the immunoassay to ID-LC-MS/MS yielded y=1.095x+0.104 nmol/L (r=0.9031). Overall, testosterone concentrations were higher mid-cycle, but a peak was not discernible in each individual. Apart from a persistent positive bias, the immunoassay measured the same testosterone profiles as the ID-LC-MS/MS method. The reference interval in women was 0.30-1.69 nmol/L (8.7-48.7 ng/dL) for ID-LC-MS/MS and 0.50-2.00 nmol/L (14.4-57.7 ng/dL) for the immunoassay., Conclusion: The elevation of mid-cycle testosterone concentrations is statistically significant, although not clinically relevant since day-to-day variation is higher and independent of the menstrual cycle. In this light, a single testosterone measurement might not be reflective of the overall testosterone status in an individual. Measurements obtained using the 2nd generation immunoassay gave comparable results across the menstrual cycle., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Androgen deprivation therapy by bilateral orchiectomy (surgical castration) or luteinizing hormone-releasing hormone agonist therapy (medical castration) is recommended for advanced or metastatic prostate cancer. Both methods aim at reducing serum testosterone concentrations to a castrate level which is currently defined as less than 50 ng/dl. The results of previous studies are based on testosterone immunoassays that have insufficient accuracy in the low range. In this study we reevaluated serum testosterone concentrations in men on androgen deprivation therapy using isotope dilution-liquid chromatography-tandem mass spectrometry, an accurate method of measuring testosterone in the castrate range., Materials and Methods: Subjects underwent surgical castration (34) or received a luteinizing hormone-releasing hormone agonist (32). Serum samples were obtained more than 3 months after surgery or initiation of luteinizing hormone-releasing hormone agonist therapy. Testosterone levels were determined using isotope dilution-liquid chromatography-tandem mass spectrometry. Dihydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and inhibin B levels were determined., Results: All subjects had serum testosterone values less than 50 ng/dl and 97% had testosterone concentrations less than 20 ng/dl. Medically castrated men had significantly lower testosterone levels (median 4.0 ng/dl, range less than 2.9 to 20.2) than those surgically castrated (median 9.2 ng/dl, range less than 2.9 to 28.8, p <0.001). No difference was found in dehydroepiandrosterone sulfate, androstenedione and sex hormone-binding globulin levels between the groups, whereas inhibin B levels were significantly higher in the luteinizing hormone-releasing hormone agonist treated group., Conclusions: Using an accurate technique for testosterone measurement, subjects on luteinizing hormone-releasing hormone agonist therapy had significantly lower testosterone concentrations than men who underwent surgical castration. The clinical relevance of these findings remains to be determined., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Androgen deprivation therapy (ADT) and 5-α-reductase (5AR) inhibition are used in the treatment of men with advanced or metastatic prostate cancer and benign prostatic hyperplasia (BPH), respectively. These drugs exert their effect by lowering androgen levels in the serum and allegedly, the prostate gland. It is, however, unknown whether (increased) intraprostatic androgen levels are associated with the pathogenesis of BPH and with the initiation and progression of prostate cancer. Also, it is unclear whether intraprostatic dihydrotestosterone (DHT) levels correlate with a response to initial hormonal therapy or with patient outcome. These uncertainties have resulted from the finding that serum testosterone levels do not necessarily reflect those in the prostate gland. Intraprostatic DHT levels of men being treated with 5AR inhibition, of those treated with ADT for hormone-naive prostate cancer, and of those with castration-resistant prostate cancer are all altered in an equivalent manner because of hormonal manipulation. Increased knowledge of the mechanisms of the androgenic steroid pathways in prostatic diseases, with a special focus on intraprostatic androgen levels, may lead to treatment that is tailored to the needs of the individual patient, and probably to new therapeutic targets as well., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Owing to inconsistencies and methodological differences, the present peer-reviewed literature lacks conclusive data on the intraprostatic levels of androgens, in particular dihydrotestosterone (DHT), in untreated benign prostatic hyperplasia (BPH) and prostate cancer. To date, no difference has been shown between DHT concentrations in normal prostatic tissue and BPH, and nor has a difference been shown in DHT concentrations between the histologically distinct regions of the prostate. Recent literature has also failed to show a consistent difference in androgen level between BPH and prostate cancer. The role of intraprostatic DHT in the pathogenesis of BPH and in the initiation and progression of prostate cancer thus remains to be established. Increased knowledge of the mechanisms of the androgenic steroid pathways in prostatic diseases, with a special focus on intraprostatic androgen levels may lead to more optimized and more personalized forms of treatment, and probably new therapeutic targets as well., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: In critically ill patients with acute respiratory failure (ARF), fiberoptic bronchoscopy and bronchoalveolar lavage (FOB-BAL) are important tools in diagnostic strategies. In nonintubated patients, the patient's agitation may lead to desaturation and compromise the realization of FOB. The aim of this study was to assess the feasibility and safety of target-controlled (TCI) propofol sedation during FOB-BAL in nonintubated hypoxemic patients., Methods: The first end point in our prospective investigation within an intensive care unit (ICU) was the avoidance of endotracheal intubation within 24 h. Secondary end points were changes in the PaO(2)/FiO(2) ratio, hemodynamic stability, patient comfort, occurrence of adverse effects, and quality of FOB. Patients self-evaluated their comfort after FOB., Results: Twenty-four FOBs were performed in 23 patients with ARF. PaO(2)/FiO(2) before FOB was 181 ± 50 (range 85-286). All patients tolerated FOB with BAL. None was intubated during the 2 h after FOB. Loss of consciousness was obtained with an effect site concentration of propofol of 1.49 ± 0.46 μg/mL (range 2.6-0.6). No significant adverse events occurred. TCI propofol allowed us to obtain amnesia, patient comfort, and it did not impair airway protection. Any hemodynamic changes observed were modest and transient., Conclusions: FOB-BAL, under NIV and TCI with propofol, is feasible and safe in nonintubated patients with ARF. The TCI of propofol during FOB-BAL reduces patient discomfort with no significant adverse effects.

Study Objective: To investigate whether showering, to prevent the involuntary transfer of testosterone to others through skin contact, either 15 or 30 minutes after application of testosterone gel would significantly affect plasma testosterone levels., Design: Prospective 3-way crossover trial., Setting: University hospital in the Netherlands., Subjects: Ten agonadal female-to-male transsexuals who had sex-reassignment surgery at least 3 months earlier., Intervention: Subjects were randomized to one of three application regimens for testosterone gel 50 mg/day, each lasting 7 days: testosterone application after showering (standard regimen), shower was taken 30 minutes after testosterone application, or shower was taken 15 minutes after testosterone application. Subjects then crossed over to each of the other two application regimens for a total of 21 days of study participation., Measurements and Main Results: On day 7 of each application regimen, mean plasma testosterone levels were determined before testosterone application and at 1, 4, 7, and 10 hours after application. With the standard regimen, mean plasma testosterone levels at all time points after application were in the normal range: mean ± SD average concentration 994 ± 1026 ng/dl. When a shower was taken 30 or 15 minutes after application, plasma testosterone levels at 1, 4, 7, and 10 hours were significantly lower: mean ± SD average concentration 401 ± 231 ng/dl for 30 minutes after application (p<0.01) and 320 ± 248 ng/dl for 15 minutes after application (p<0.01)., Conclusion: Showering within 30 minutes after application of testosterone gel 50 mg/day reduces absorption of testosterone and results in unacceptably low plasma testosterone levels in most users. Therefore, this strategy cannot be recommended to prevent involuntary transfer of testosterone.

The assessment of severity. Severity assessment is a key element in the management of community-acquired pneumonia. This assessment will determine the level of diagnostic workup and treatment, as well as the site of care. Several tools have been developed to help this assessment. The Pneumonia Severity Index (PSI) or the CURB-65 can accurately identify patients with a low risk of death who might be considered for outpatient care while those with a high risk of death would be hospitalized. Nevertheless, PSI and CURB-65 are less accurate for identifying patients requiring admission to an intensive care unit (ICU). Different scores, such the American Thoracic Society criteria or the SMART-COP score, were built to predict need for admission to ICU, vasopressors or mechanical ventilation. Each score has its own strengths and weaknesses and physicians must be aware of these limitations. Although, severity assessment tools are useful guides in the management of patients with community acquired pneumonia, clinical judgment must remain decisive., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)