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This study investigates the chemical structure of proanthocyanidin-rich crude extracts from willow bark and these materials were tested initially as adsorbents for artificial (waste)water treatment. The crude extracts were obtained through mild water extraction and the colorant fractions were further chromatographically fractionated to understand the chemical structure of the willow bark proanthocyanidins. The chemistry of crude extracts and purified fractions were investigated using nuclear magnetic resonance (NMR) and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Both NMR (liquid and solid-state) and UPLC-MS/MS suggest that the crude extracts constitute of interflavan linked flavan-3-ols, i.e. proanthocyanidins with both procyanidin (PC)-type and prodelphinidin (PD)-type subunits, with the PC/PD ratio of approximately 2.3–2.5. PD-type proanthocyanidins were detected from the purified colorant fractions only with UPLC-MS/MS. Both the UPLC-MS/MS and size exclusion chromatography suggest that the crude extracts have an average oligomerization degree of roughly 5–6 flavan-3-ol units. Adsorption experiments showed that the activated foams made of crude extracts were effective in removing both zinc and Bisphenol A (BPA) with removal efficiencies of roughly 80–90% and thus these willow bark-derived proanthocyanidins are promising in water treatment. The significance of this study suggests the upgrading use of crude extracts for water treatment could significantly improve the value of willow bark.

Asthma development and exacerbation is linked to respiratory virus infections. There is limited information regarding the presence of viruses during non-exacerbation/infection periods. We investigated the nasopharyngeal/nasal virome during a period of asymptomatic state, in a subset of 21 healthy and 35 asthmatic preschool children from the Predicta cohort. Using metagenomics, we described the virome ecology and the cross-species interactions within the microbiome. The virome was dominated by eukaryotic viruses, while prokaryotic viruses (bacteriophages) were independently observed with low abundance. Rhinovirus B species consistently dominated the virome in asthma. Anelloviridae were the most abundant and rich family in both health and asthma. However, their richness and alpha diversity were increased in asthma, along with the co-occurrence of different Anellovirus genera. Bacteriophages were richer and more diverse in healthy individuals. Unsupervised clustering identified three virome profiles that were correlated to asthma severity and control and were independent of treatment, suggesting a link between the respiratory virome and asthma. Finally, we observed different cross-species ecological associations in the healthy versus the asthmatic virus-bacterial interactome, and an expanded interactome of eukaryotic viruses in asthma. Upper respiratory virome “dysbiosis” appears to be a novel feature of pre-school asthma during asymptomatic/non-infectious states and merits further investigation.

Background: Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers. Aim: To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection. Methods: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes. Results: In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (< 50 nmol/liter) was present in 59% and hypoalbuminemia (< 3.5 g/dL) in 55% of the study patients. Low serum albumin level was associated to one, two- and five-year mortality after hospital stay (all P <.05). In addition, it was associated with pneumonia, dyspnea, over 13-night long stay at ward and death at ward (all P < .05). No associations were seen between serum 25(OH)D and LL-37 levels and disease severity, short-term clinical outcome, or long-term survival. Associations between serum 25(OH)D, albumin, and LL-37 levels and respiratory virus presence were not seen. Conclusions: Serum albumin level on admission seems to give valuable information about the patients’ general health and recovery potential in treating older adults with respiratory symptoms. Se

Adenoids and tonsils have gained interest as a new in vivo model to study local immune functions and virus reservoirs. Especially herpesviruses are interesting because their prevalence and persistence in local lymphoid tissue are incompletely known. Our aim was to study herpesvirus and common respiratory virus infections in nonacutely ill adenotonsillar surgery patients. Adenoid and/or palatine tonsil tissue and nasopharyngeal aspirate (NPA) samples were collected from elective adenoidectomy (n = 45) and adenotonsillectomy (n = 44) patients (median age: 5, range: 1–20). Real-time polymerase chain reaction was used to detect 22 distinct viruses from collected samples. The overall prevalence of herpesviruses was 89% and respiratory viruses 94%. Human herpesviruses 6 (HHV6), 7 (HHV7), and Epstein–Barr virus (EBV) were found, respectively, in adenoids (33%, 26%, 25%), tonsils (45%, 52%, 23%), and NPA (46%, 38%, 25%). Copy numbers of the HHV6 and HHV7 genome were significantly higher in tonsils than in adenoids. Patients with intra-adenoid HHV6 were younger than those without. Detection rates of EBV and HHV7 showed agreement between corresponding sample types. This study shows that adenoid and tonsil tissues commonly harbor human herpes- and respiratory viruses, and it shows the differences in virus findings between sample types.

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.

Background: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta₂-agonist in this clinical scenario. Objective: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2–4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). Conclusions: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact w

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

The article introduces a detailed model for carbohydrate chemistry in kraft pulping. This article is continuation to the modeling work carried out for hot water extraction and chemical pulp bleaching. The model includes galactoglucomannan, xylan, and cellulose acid–base equilibria, in addition to peeling, stopping, and alkaline hydrolysis reactions of the same carbohydrates, as well as hexenuronic acid formation and degradation reactions. The Arrhenius parameters were applied from the literature or regressed against experimental data in the present study. The model is very successful in predicting the experimental data of carbohydrate reactions during kraft pulping. Many features of the pulping-related model can be applied to specific fractionation chemistry considerations. The detailed knowledge on carbohydrates composition at any stage of pulping gives possibility for further development of biorefinery cases based on kraft pulping, such as biofuel and chemicals production.

This work introduces a phenomena-based model for delignification in the kraft pulping process. The solubilization of lignin is described as a set of chemical reactions representing the entire chemistry of lignin degradation as well as dissolution of the degraded lignin. For modeling, reaction mechanisms and reactions kinetics derived mainly from the literature were used. Each reaction was simulated separately and then combined for the overall degradation. The model was validated with experimental results from pine wood meal pulping under a wide range of reaction parameters. The experimental data presented a good fit with the model. With the aid of the model, the structure and the amount of wood components, in fibers and black liquor, can be determined at any pulping stage. Several engineering parameters can be computed from the detailed chemical composition of liquor and wood or chemical pulp. These include, e.g., kappa number, brightness, yield, active alkali, effective alkali, sulfidity, and higher heating value.

Background: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. Methods: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. Results: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. Conclusions: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies.

An electrocardiography (ECG) monitoring can be used to detect heart‐related abnormalities by recording cardiac activity over a period of time. The conventional 12‐lead ECG measurement system is the standard practice for the evaluation of the heart’s electrical activity. However, a recent trend is to develop patch‐type measurement devices for unobtrusive ECG monitoring by reducing device size and number of electrodes on the skin. This development aims to minimize the discomfort for the user from the wearable recording devices. A printed, bandage‐type hybrid system for continuous ECG monitoring to allow as much comfort as possible while maintaining the signal quality required for medical evaluation is proposed. Movement artifacts in recorded ECG signals are a challenge in long‐term monitoring while the patients are engaged in their everyday activities. The movement artifacts from the printed skin‐conformable electrode are compared to commercial exercise stress‐test ECG electrodes during different physical activities and stationary periods. The results show that the signal quality obtained with the multilead patch ECG electrode, manufactured with printing technologies, is comparable to electrodes currently used in healthcare.

Aims/Hypothesis: Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)‐conferred T1D risk. Methods: A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV‐specific IgG antibodies during early childhood. All the children carried HLA‐DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D‐associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen‐2 [IA‐2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan‐Meier survival analysis and Log‐rank test. Results: Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D‐associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015). Conclusion: Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at‐risk children and may thus protect these children from progressing to T1D during childhood.