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The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Although it may better approximate ECW volume than the bromide space, a common alternative, SS measurement is limited by the need to administer a radioactive substance, sodium [35S]sulfate. In this paper, we demonstrate the measurement of the SS using the stable isotope, sodium [34S]sulfate. Eight healthy nonobese men ingested 0.50-0.78 mg (3.47-5.42 micromol) Na234SO4/kg body weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34SO4 enrichments were measured by electrospray tandem mass spectrometry before and during the 5 h after tracer administration. SS was calculated by linear extrapolation of the natural logarithm of serum 34SO4 concentrations obtained at h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3 and 5 (187 +/- 17 mL/kg) was similar to published determinations using intravenous or oral radiosulfate, and was 80% of the simultaneously measured corrected bromide space (234 +/- 10 mL/kg, P = 0.01). Oral sodium [34S]sulfate administration is a suitable technique for measuring ECW and avoids radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Determinants of COVID-19 vaccine acceptance among healthcare workers (HCW) remains poorly understood. We assessed HCWs' willingness to be vaccinated and reasons underlying hesitancy., Methods: Cross-sectional survey across 17 healthcare institutions. HCWs eligible for vaccination (Pfizer-BioNTech mRNA) in December 2020 were invited to receive immunization. Multivariate logistic regression was performed to identify predictors of acceptance. Reasons for refusal among those who never intended to be vaccinated (ie, firm refusers) and those who preferred delaying vaccination (ie, vaccine hesitants) were assessed., Results: Among 2,761 respondents (72% female, average age, 44), 2,233 (80.9%) accepted the vaccine. Physicians, environmental services workers and healthcare managers were more likely to accept vaccination compared to nurses. Male sex, age over 50, rehabilitation center workers, and occupational COVID-19 exposure were independently associated with vaccine acceptance by multivariate analysis. Factors for refusal included vaccine novelty, wanting others to receive it first, and insufficient time for decision-making. Among those who declined, 74% reported they may accept future vaccination. Vaccine firm refusers were more likely than vaccine hesitants to distrust pharmaceutical companies and to prefer developing a natural immunity by getting COVID-19., Conclusions: Vaccine hesitancy exists among HCWs. Our findings provide useful information to plan future interventions and improve acceptance., (Copyright © 2021. Published by Elsevier Inc.)

Background: Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens., Methods: In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy., Results: Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol., Conclusion: Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

Background: In-hospital hypovitaminosis C is highly prevalent but almost completely unrecognized. Medical awareness of this potentially important disorder is hindered by the inability of most hospital laboratories to determine plasma vitamin C concentrations. The availability of a simple, reliable method for analyzing plasma vitamin C could increase opportunities for routine plasma vitamin C analysis in clinical medicine., Methods: Plasma vitamin C can be analyzed by high performance liquid chromatography (HPLC) with electrochemical (EC) or ultraviolet (UV) light detection. We modified existing UV-HPLC methods for plasma total vitamin C analysis (the sum of ascorbic and dehydroascorbic acid) to develop a simple, constant-low-pH sample reduction procedure followed by isocratic reverse-phase HPLC separation using a purely aqueous low-pH non-buffered mobile phase. Although EC-HPLC is widely recommended over UV-HPLC for plasma total vitamin C analysis, the two methods have never been directly compared. We formally compared the simplified UV-HPLC method with EC-HPLC in 80 consecutive clinical samples., Results: The simplified UV-HPLC method was less expensive, easier to set up, required fewer reagents and no pH adjustments, and demonstrated greater sample stability than many existing methods for plasma vitamin C analysis. When compared with the gold-standard EC-HPLC method in 80 consecutive clinical samples exhibiting a wide range of plasma vitamin C concentrations, it performed equivalently., Conclusion: The easy set up, simplicity and sensitivity of the plasma vitamin C analysis method described here could make it practical in a normally equipped hospital laboratory. Unlike any prior UV-HPLC method for plasma total vitamin C analysis, it was rigorously compared with the gold-standard EC-HPLC method and performed equivalently. Adoption of this method could increase the availability of plasma vitamin C analysis in clinical medicine.

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

The rapid, sensitive, and specific identification of infectious pathogens from clinical isolates is a critical need in the hospital setting. Mass spectrometry (MS) has been widely adopted for identification of bacterial pathogens, although polymerase chain reaction remains the mainstay for the identification of viral pathogens. Here, we explored the capability of MS for the detection of human metapneumovirus (HMPV), a common cause of respiratory tract infections in children. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) sequencing of a single HMPV reference strain (CAN97-83) was used to develop a multiple reaction monitoring (MRM) assay that employed stable isotope-labeled peptide internal standards for quantitation of HMPV. Using this assay, we confirmed the presence of HMPV in viral cultures from 10 infected patients and further assigned genetic lineage based on the presence/absence of variant peptides belonging to the viral matrix and nucleoproteins. Similar results were achieved for primary clinical samples (nasopharyngeal aspirates) from the same individuals. As validation, virus lineages, and variant coding sequences, were confirmed by next-generation sequencing of viral RNA obtained from the culture samples. Finally, separate dilution series of HMPV A and B lineages were used to further refine and assess the robustness of the assay and to determine limits of detection in nasopharyngeal aspirates. Our results demonstrate the applicability of MRM for identification of HMPV, and assignment of genetic lineage, from both viral cultures and clinical samples. More generally, this approach should prove tractable as an alternative to nucleic-acid based sequencing for the multiplexed identification of respiratory virus infections.

Background: Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail., Methods and Findings: We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement., Conclusions: Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials., Trial Registration: ClinicalTrials.gov NCT01050621.

A number of theorists, as well as plain common sense, suggest that future-oriented thinking (FOT) should be involved in decision making; therefore, the development of FOT should be related to better quality decision making. FOT and quality of the decision making were measured in adolescents as well as adults in 2 different experiments. Though the results of the first experiment revealed an increase in quality of decision making across adolescence into adulthood, there was no relationship between FOT and decision making. In the second experiment, FOT predicted performance on a more deliberative decision-making task independent of age, but not performance on the Iowa Gambling Task (IGT). Performance on the IGT was instead related to emotion regulation. The study's findings suggest that FOT can be related to reflective decision making but not necessarily decision making that is more intuitive.

Streptococcus pneumoniae serotype epidemiology is essential since serotype replacement is a concern when introducing new polysaccharide-conjugate vaccines. A novel PCR-based automated microarray assay was developed to assist in the tracking of the serotypes. Autolysin, pneumolysin and eight genes located in the capsular operon were amplified using multiplex PCR. This step was followed by a tagged fluorescent primer extension step targeting serotype-specific polymorphisms. The tagged primers were then hybridized to a microarray. Results were exported to an expert system to identify capsular serotypes. The assay was validated on 166 cultured S. pneumoniae samples from 63 different serotypes as determined by the Quellung method. We show that typing only 12 polymorphisms located in the capsular operon allows the identification at the serotype level of 22 serotypes and the assignation of 24 other serotypes to a subgroup of serotypes. Overall, 126 samples (75.9%) were correctly serotyped, 14 were assigned to a member of the same serogroup, 8 rare serotypes were erroneously serotyped, and 18 gave negative serotyping results. Most of the discrepancies involved rare serotypes or serotypes that are difficult to discriminate using a DNA-based approach, for example 6A and 6B. The assay was also tested on clinical specimens including 43 cerebrospinal fluid samples from patients with meningitis and 59 nasopharyngeal aspirates from bacterial pneumonia patients. Overall, 89% of specimens positive for pneumolysin were serotyped, demonstrating that this method does not require culture to serotype clinical specimens. The assay showed no cross-reactivity for 24 relevant bacterial species found in these types of samples. The limit of detection for serotyping and S. pneumoniae detection was 100 genome equivalent per reaction. This automated assay is amenable to clinical testing and does not require any culturing of the samples. The assay will be useful for the evaluation of serotype prevalence changes after new conjugate vaccines introduction.

Background: Hypovitaminosis C and D are highly prevalent in acute-care hospitals. Malnutrition with regard to these vitamins has been linked to mood disturbance and cognitive dysfunction., Objective: The objective was to determine whether vitamin C or D supplementation improves mood state or reduces psychological distress in acutely hospitalized patients with a high prevalence of hypovitaminosis C and D., Design: A randomized, double-blind, active-control clinical trial compared the effects of vitamin C (500 mg twice daily) with those of high-dose vitamin D (5000 IU/d) on mood (Profile of Mood States) and psychological distress (Distress Thermometer)., Results: Vitamin C provided for a mean of 8.2 d increased plasma vitamin C concentrations to normal (P < 0.0001) and was associated with a 71% reduction in mood disturbance (P = 0.0002) and a 51% reduction in psychological distress (P = 0.0002). High-dose vitamin D provided for a mean of 8.1 d increased plasma 25-hydroxyvitamin D [25(OH)D] concentrations (P < 0.0001), but not into the normal range, and had insignificant effects on mood (P = 0.067) and distress (P = 0.45). The changes in mood and distress in the vitamin C group were greater than those in the vitamin D group (P = 0.045 for mood; P = 0.009 for distress)., Conclusions: Short-term therapy with vitamin C improves mood and reduces psychological distress in acutely hospitalized patients with a high prevalence of hypovitaminosis C and D. No conclusion is possible regarding the effects of vitamin D because the dose and duration of therapy were insufficient to raise 25(OH)D concentrations into the normal range. This trial was registered at clinicaltrials.gov as NCT01630720.

Background: Community-acquired pneumonia (CAP) is a serious cause of morbidity among children in developed countries. The real impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal pneumonia is difficult to assess accurately., Methods: Children aged ≤16 years with clinical and radiological pneumonia were enrolled in a multicenter prospective study. Children aged ≤16 years admitted for a minor elective surgery was recruited as controls. Nasopharyngeal samples for PCR serotyping of S. pneumoniae were obtained in both groups. Informations on age, gender, PCV7 vaccination status, day care/school attendance, siblings, tobacco exposure were collected., Results: In children with CAP (n=236), 54% of the nasopharyngeal swabs were PCR-positive for S. pneumoniae compared to 32% in controls (n=105) (p=0.003). Serotype 19A was the most common pneumococcal serotype carried in children with CAP (13%) and in controls (15%). Most common serotypes were non-vaccine types (39.4% for CAP and 47.1% for controls) and serotypes included only in PCV13 (32.3% for CAP and 23.5% for controls). There was no significant difference in vaccine serotype distribution between the two groups. In fully vaccinated children with CAP, the proportion of serotypes carried only in PCV13 was higher (51.4%) than in partially vaccinated or non vaccinated children (27.6% and 28.6% respectively, p=0.037)., Conclusions: Two to 4 years following introduction of PCV7, predominant S. pneumoniae serotypes carried in children with CAP were non PCV7 serotypes, and the 6 new serotypes included in PCV13 accounted for 51.4% of carried serotypes in fully vaccinated children.

Bioengineering approaches have been intensively applied to create small diameter vascular grafts using artificial materials. However, a fully successful, high performing and anti-thrombogenic structure has not been achieved yet. In this study, we present the first step of a process aiming at biofunctionalizing previously designed compliant polyethylene terephthalate (PET) scaffolds (Moreno et al., 2011). The main challenge of such a surface modification is to prevent the bulk polymer from any damage, so that it preserves the mechanical properties that the structures have been designed for. In that endeavor, an aminated long-chain polymer (polyvinylamine, PVAm) was used as an aminolysis reagent to get amine (-NH 2 ) moieties only on the very surface of PET. Different reaction conditions were assayed, leading to a large range of amino group densities associated with slight variations of the planar tensile properties. These results were in stark contrast with those generated with a common small diamine substrate (ethylenediamine, EtDA), as the latter yielded a strong degradation of the mechanical properties for comparable amine densities. Tubular mechanical assays were then carried out on PVAm-functionalized PET scaffolds. The latter showed a compliance match with arteries under the chosen reaction conditions, as initially observed for pristine PET tubular scaffolds.