Assessing the discharge instructing in the emergency department: Patient perspective.

OBJECTIVE: The objective of the study is to assess how well the emergency department (ED) personnel succeed in instructing the patient at discharge. METHODS: In November and December 2016 at Peijas Hospital ED, Finland, a structured questionnaire was conducted during a phone interview on patients the day after discharge. RESULTS: A total of 132 patients interviewed. Ninety percent had received discharge instructions from the ED staff, most of them (75%) about medication. Almost half of the patients (45%) were satisfied with the communication at discharge, those not satisfied (47%) felt that the staff did not know enough of their background to give discharge instructions. Of the patients, 20% thought that they did not have the opportunity to ask questions during the guidance session, and 41% thought that the session was too short and restricted. Some patients (20%) felt that the instructions were ambiguous, but 63% (83/132) felt they were able to follow them well or very well. CONCLUSION: The pace of care in the ED is fast and duration of the stay is short. The patients must be able to take responsibility of their self-care. Failure to follow medical discharge instructions could lead to non-compliance. Attention should be paid to enhancing the quality of discharge instructing and the instructions provided by the ED personnel, as recurring visits and inquiry calls add to the ED workload.

Identification of human, rat and mouse hydrolyzing enzymes bioconverting amino acid ester prodrug of ketoprofen.

Alkyl ester prodrugs are well known to be bioconverted by carboxylesterases, particularly in rodents' by first-pass metabolism in the systemic circulation and liver. However, the bioconversion of structurally more complex esters with polar functional groups is less well understood, especially in humans. Therefore, it is not clear if ester prodrugs can be utilized for targeted drug delivery. In the present study a brain-targeted ester prodrug (1) of ketoprofen, utilizing the l-type amino acid transporter 1 (LAT1) was prepared and the enzymes involved in its metabolism in human plasma and liver S9 subcellular fraction as well as rat brain S9 fraction were identified. Furthermore, species differences among mouse, rat and human plasma and liver S9 fraction were compared. The results showed that bioconversion of the ester prodrug was much faster in mouse plasma compared to human, while it's half-life in rat plasma was closer to the one of human. Moreover, both rodent species showed more efficient bioconversion in the liver S9 fractions compared to human and relatively efficient bioconversion in the brain S9 fractions. More specifically, butyrylcholinesterase (BChE) and paraoxygenase 1 (PON1) were the main hydrolyzing enzymes of the prodrug 1 in human plasma, while carboxylesterases 1 and 2 (CES1 and CES2) as well as PONs were the main bioconverting enzymes in human liver S9 fractions. In rat brain S9 fraction, acetylcholinesterase (AChE) was hydrolyzing the prodrug 1, although also other unidentified metal-and pH-dependent enzyme(s) were recognized to be participating to the total bioconversion of the compound 1 in the brain.

Habitat connectivity and in-stream vegetation control temporal variability of benthic invertebrate communities.

One of the key challenges to understanding patterns of ß diversity is to disentangle deterministic patterns from stochastic ones. Stochastic processes may mask the influence of deterministic factors on community dynamics, hindering identification of the mechanisms causing variation in community composition. We studied temporal ß diversity (among-year dissimilarity) of macroinvertebrate communities in near-pristine boreal streams across 14 years. To assess whether the observed ß diversity deviates from that expected by chance, and to identify processes (deterministic vs. stochastic) through which different explanatory factors affect community variability, we used a null model approach. We observed that at the majority of sites temporal ß diversity was low indicating high community stability. When stochastic variation was unaccounted for, connectivity was the only variable explaining temporal ß diversity, with weakly connected sites exhibiting higher community variability through time. After accounting for stochastic effects, connectivity lost importance, suggesting that it was related to temporal ß diversity via random colonization processes. Instead, ß diversity was best explained by in-stream vegetation, community variability decreasing with increasing bryophyte cover. These results highlight the potential of stochastic factors to dampen the influence of deterministic processes, affecting our ability to understand and predict changes in biological communities through time.

Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age.

Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.

Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years.

BACKGROUND: Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. OBJECTIVE: To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. METHODS: We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-γ), inflammatory (IL-1ß, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. RESULTS: The unstimulated PBMCs of farm children produced more IL-10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-γ (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-γ (test for trends, P = 0.013) and lower LPS-induced production of TNF (test for trends, P = 0.025). CONCLUSION AND CLINICAL RELEVANCE: Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.

Inflammatory potential in relation to the microbial content of settled dust samples collected from moisture-damaged and reference schools: results of HITEA study.

Aiming to identify factors causing the adverse health effects associated with moisture-damaged indoor environments, we analyzed immunotoxicological potential of settled dust from moisture-damaged and reference schools in relation to their microbiological composition. Mouse RAW264.7 macrophages were exposed to settled dust samples (n = 25) collected from moisture-damaged and reference schools in Spain, the Netherlands, and Finland. After exposure, we analyzed production of inflammatory markers [nitric oxide (NO), tumor necrosis factor-α (TNF-)α, interleukin (IL)-6, and macrophage inflammatory protein (MIP)2] as well as mitochondrial activity, viability, apoptosis, and cell cycle arrest. Furthermore, particle counts, concentration of selected microbial groups as well as chemical markers such as ergosterol, 3-hydroxy fatty acids, muramic acid, endotoxins, and glucans were measured as markers of exposure. Dust from moisture-damaged schools in Spain and the Netherlands induced stronger immunotoxicological responses compared to samples from reference schools; the responses to Finnish samples were generally lower with no difference between the schools. In multivariate analysis, IL-6 and apoptosis responses were most strongly associated with moisture status of the school. The measured responses correlated with several microbial markers and numbers of particles, but the most important predictor of the immunotoxicological potential of settled dust was muramic acid concentration, a marker of Gram-positive bacteria.

The preclinical pharmacokinetic disposition of a series of perforin-inhibitors as potential immunosuppressive agents.

The cytolytic protein perforin is a key component of the immune response and is implicated in a number of human pathologies and therapy-induced conditions. A novel series of small molecule inhibitors of perforin function have been developed as potential immunosuppressive agents. The pharmacokinetics and metabolic stability of a series of 16 inhibitors of perforin was evaluated in male CD1 mice following intravenous administration. The compounds were well tolerated 6 h after dosing. After intravenous administration at 5 mg/kg, maximum plasma concentrations ranged from 532 ± 200 to 10,061 ± 12 ng/mL across the series. Plasma concentrations were greater than the concentrations required for in vitro inhibitory activity for 11 of the compounds. Following an initial rapid distribution phase, the elimination half-life values for the series ranged from 0.82 ± 0.25 to 4.38 ± 4.48 h. All compounds in the series were susceptible to oxidative biotransformation. Following incubations with microsomal preparations, a tenfold range in in vitro half-life was observed across the series. The data suggests that oxidative biotransformation was not singularly responsible for clearance of the compounds and no direct relationship between microsomal clearance and plasma clearance was observed. Structural modifications however, do provide some information as to the relative microsomal stability of the compounds, which may be useful for further drug development.

The changing role of gesture in linguistic development: a developmental trajectory and a cross-cultural comparison between British and Finnish children.

We studied how gesture use changes with culture, age and increased spoken language competence. A picture-naming task was presented to British (N = 80) and Finnish (N = 41) typically developing children aged 2-5 years. British children were found to gesture more than Finnish children and, in both cultures, gesture production decreased after the age of two. Two-year-olds used more deictic than iconic gestures than older children, and gestured more before the onset of speech, rather than simultaneously or after speech. The British 3- and 5-year-olds gestured significantly more when naming praxic (manipulable) items than non-praxic items. Our results support the view that gesture serves a communicative and intrapersonal function, and the relative function may change with age. Speech and language therapists and psychologists observe the development of children's gestures and make predictions on the basis of their frequency and type. To prevent drawing erroneous conclusions about children's linguistic development, it is important to understand developmental and cultural variations in gesture use.

Directed electron transfer in Langmuir-Schäfer layers of porphyrin-fullerene and phthalocyanine-fullerene dyads in inverted organic solar cells.

In this study double linked porphyrin-fullerene and phthalocyanine-fullerene dyads and a single linked phthalocyanine-fullerene dyad were studied as components in inverted organic solar cells (OSCs) equipped with the well known P3HT:PCBM bulk heterojunction as the photoactive layer. The dyad monolayers were deposited onto a surface of P3HT:PCBM by using the Langmuir-Schäfer method, therefore forming oriented monolayers in which the electron donor (D) and the acceptor (A) exist as a close proximity pair in a 1:1 molar ratio. As a result of this structure short circuit current density (J(sc)), open circuit voltage (V(oc)), and power conversion efficiency (η) increased, while the fill factor (FF) remained the same. The devices which contained dyads with double linkage produced higher efficiencies than the one with a single linked dyad. This result can be explained in terms of molecular orientation. It was also verified that the prepared OSC devices have promising long term air stability.

Symphony orchestra musicians' use of hearing protection and attenuation of custom-made hearing protectors as measured with two different real-ear attenuation at threshold methods.

Despite a high level of sound exposure and a fairly large selection of earplugs available, musicians have often been reported to use personal hearing protectors only seldom. For better hearing conservation, it is important to identify and eliminate the causes for the low motivation to use hearing protection. We explored the usage rate of custom-molded musician's earplugs (ER-15) among 15 symphony orchestra musicians with a questionnaire, and measured the attenuation properties of their earplugs with a Real-Ear Attenuation at Threshold (REAT) procedure in a sound field. Earplug use was found to be low, and the musicians reported that earplugs hampered listening to their own and their colleagues' playing; earplugs affected either timbre or dynamics, or both. Additionally, several reasons related to discomfort of use were itemized, but the musicians who consistently used their earplugs did so in spite of problems with use. The REAT values obtained in sound field were relatively close to the manufacturer's nominal specifications, being 13.7 dB, on average. In the frequency range studied (0.125-8 kHz), individual variation in REAT was, however, up to 15 dB across the measured frequencies. Fluctuation in attenuation might be related to low use of hearing protectors, and REAT measured at fixed center frequencies may be too robust a method to uncover it. We therefore tested 10 additional subjects to find out whether a sweeping signal used in Bιkιsy audiometry would bring more detailed information on earplug attenuation. Mean attenuation was found to be somewhat closer to the nominal attenuation of the ER-9 and ER-15 earplugs up to about 1 kHz, whereas REAT measurements in sound field revealed more even attenuation at frequencies between 1 and 6 kHz. No significant association was found between earplug attenuation properties and earplug use. It was concluded that support and determination to get accustomed to hearing protector use are important factors in hearing conservation.

Exposure to dogs is associated with a decreased tumour necrosis factor-α-producing capacity in early life.

BACKGROUND: It appears that contacts with furred animals early in life and already during gestation contribute to the immunological development in humans, but the mechanisms and relevant exposures are not clear. OBJECTIVE: To investigate whether exposure to animals during pregnancy and the first year of life is associated with early immune development, determined as stimulated cytokine responses of children at birth and at age 1 year. METHODS: Cord blood (n=228) and peripheral venous blood (n=200) samples 1 year after birth were collected and stimulated with Gram-positive superantigen Staphylococcal enterotoxin B, Gram-negative bacterial lipopolysaccharide (LPS) and the combination of mitogenic phorbol 12-myristate 13-acetate and calcium ionophore ionomycin (P/I) for 24 and 48 h. TNF-α, IFN-γ, IL-5, IL-8 and IL-10 responses were measured by ELISA. For each cytokine, the time-point with the highest response was chosen for further analyses. Animal contacts were surveyed by self-administered questionnaires. RESULTS: Dog ownership was associated with decreased TNF-α-producing capacity at birth (P/I: median 841 vs. 881 pg/10(6) WBC, P=0.05) and 1 year after birth (P/I: 1290 vs. 1530, P=0.01; LPS: 425 vs. 508, P=0.02). Associations remained significant after adjustment for potential confounders. Cat ownership was not associated with cytokine production. CONCLUSION: Having a dog in the household in infancy and already during pregnancy may be associated with reduced innate immune responses in early childhood. The observed attenuation of cytokine production may help in preventing exaggerated immune responses against harmless antigens later in life. Thus, intensive exposure to dogs in early life may be beneficial during normal immune maturation.

Parents' views on the quality of life of their children 2-3 years after cochlear implantation.

OBJECTIVE: Cochlear implants for children are known to have impact on the lives of recipients and their families in a variety of ways. To obtain a clearer picture of these benefits, we explored the quality of life of 36 Finnish children and their families 2-3 years after unilateral cochlear implantation. METHODS: The studied children were, on average 5 years old, and had received their implant at the median age of 2 years:5 months (range 1:6 to 12:3). Most (67%) of the children used speech, eight (22%) used speech and signs, and four (11%) used sign language as their main communication mode. A third of the children had concomitant problems in addition to their profound hearing impairment. A validated closed-set questionnaire "Children with cochlear implants: parental perspectives" (available, e.g., at http://www.earfoundation.org.uk/research/questionnaires.html) was used to find out parents' views and experiences on implantation and explore life after it. RESULTS: Parents were most satisfied with improved/expanded social relations, improved communication (the development of spoken language), general functioning with the help of hearing and improved self-reliance of the child. Benefit of cochlear implantation was also detected with the Categories of Auditory Performance (CAP), which was concordant with views of the parents on the progress of their child in the areas of communication and education. When deciding on implantation, the parents particularly expected auditory information to enhance their child's safety in traffic, joining socially the hearing world, and better employment prospects as adults. Concerning the process of implantation, parents especially valued the know-how and fluent services of the implant centre, positive attitude within the family and information received from other families during the time they were considering the implant decision. Parents also found it important that they have the possibility to influence the communication mode that is used in their child's educational setting. CONCLUSIONS: Parents report that cochlear implants affect their children in a wide variety of ways that cannot be summarized by a single scale. A broader descriptive framework is required to capture their experiences adequately.

Human B cells and macrophages cooperate in T-cell-independent type 2 response.

We have analysed separately the role of B-cell receptor (BCR) stimulation and the soluble second signal in the T-cell-independent type 2 (TI-2) B-cell response. We were able to show that human B cells and macrophages (Mphi) could function together in TI-type microbial response. Interestingly, BCR cross-linking of peripheral blood (PB) B cells enhanced IgG production induced by Mphi-derived growth factors whereas interleukin (IL)-12 + IL-18 had milder effect on IgG production. We demonstrated that B-cell-derived soluble mediators primed lipopolysaccharide (LPS)-stimulated Mphi for tumour necrosis factor-alpha (TNF-alpha) and IL-6 production significantly better than IFN-gamma, confirming the role of B cells in the activation of Mphi. We could show that human PB B cells were active cytokine producers and could be induced to produce interferon (IFN)-gamma mRNA in the presence of known Mphi cytokines, like IL-12 and IL-18. BCR stimulation also stabilized and enhanced the IFN-gamma mRNA production induced by IL-12 and IL-18. In addition, our novel finding was that a known Mphi cytokine, IL-10, induced the expression of IFN-gamma mRNA from human B-cell line (HF28R0) cells. In summary, we propose a model for the active role of B cells in the induction of the inflammatory response during TI antigen challenge in close collaboration with Mphi.

Bacterial strains from moldy buildings are highly potent inducers of inflammatory and cytotoxic effects.

UNLABELLED: We aimed to identify inflammatory and cytotoxic potential of individual indoor air bacterial and fungal strains, as well as extracts of indoor air filter samples containing bacteria and fungi. Mouse RAW264.7 macrophages were exposed in vitro to four bacterial strains; Streptomyces californicus, Mycobacterium terrae, Bacillus cereus and Pseudomonas fluorescens, and three fungal strains; Penicillium spinulosum, Aspergillus versicolor and Stachybotrys chartarum. Furthermore, RAW264.7 macrophages were exposed to indoor air filter sample extracts representing 'low' (n = 21) and 'high' (n = 20) exposure to viable fungi or bacteria. Production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as cell viability were measured after 24 h exposure. The results show that the bacterial strains induce more profound production of NO, TNF-alpha and IL-6 than the studied fungal strains. They also decrease the viability of mouse macrophages. Similarly, the indoor air filter samples with high concentration of bacteria induced a statistically significant increase in TNF-alpha and IL-6 production as well as a decrease in cell viability. Altogether, these results suggest that indoor air bacterial strains are potent inducers of inflammatory responses and thus possibly related to adverse health effects of the inhabitants. PRACTICAL IMPLICATIONS: There is abundant documentation of the association between building dampness and mold and adverse health effects on occupants, but the causal agents of the effects are still unclear. In order to reveal these causal links, experimental studies with in vitro and in vivo methods are needed. The present findings shed new light on studies of the microbial constituents of indoor air in moldy buildings responsible for adverse health effects. These results imply that bacteria should also be monitored in cases of suspected microbial contamination of indoor air.

Comparison of mycobacteria-induced cytotoxicity and inflammatory responses in human and mouse cell lines.

Environmental mycobacteria, which are ubiquitous in nature, are also detected in moisture-damaged buildings. Their potential role inducing the adverse health effects associated with living in moisture damaged buildings requires clarification. To establish a model for these studies, we evaluated inflammatory responsiveness in different cell lines exposed to environmental mycobacterial species. Four mycobacterial isolates belonging to Mycobacterium avium complex and Mycobacterium terrae, recovered from the indoor air sampled when a moldy building was being demolished, were studied for their cytotoxicity and ability to stimulate the production of inflammatory mediators in mouse RAW264.7 and human 28SC macrophage cell lines, and human A549 lung epithelial cell line. Lipopolysaccharide (LPS) was used as a positive control. Production of cytokines (tumor necrosis factor alpha, TNF-alpha; interleukin 6, IL-6; and interleukin beta, IL-1beta) was analyzed immunochemically, nitric oxide (NO) by the Griess method, expression of inducible NO synthase with Western blot analysis, and cytotoxicity with the MTT test. Both human and mouse cells produced NO and IL-6 after mycobacterial exposure. Mouse macrophages also showed production of TNF-alpha induced by both mycobacteria and LPS, whereas the human cell lines failed to produce TNF-alpha after mycobacterial exposure and the human epithelial cell line also failed to respond to LPS. Similarly, only mouse macrophages produced IL-1beta. Mycobacterial exposure was not cytotoxic to human cells and was only slightly cytotoxic to mouse macrophages. The results indicate that environmental mycobacterial isolates from moldy buildings are capable of activating inflammatory mechanisms in both human and murine cells. The human and mouse cell lines, however, differ significantly in the grade and type of the responses.

Phonological development in 4-6-year-old moderately hearing impaired children.

The acquisition of clear phonological rules is of utmost importance for a child when he/she is learning to decode and convey meanings using spoken language. Fifteen Finnish-speaking children, five normally hearing (NH) 3-year-olds and 10 moderately hearing impaired (HId) 4-6-year-olds were studied here. Speech samples consisting of 62 words were collected from each child during a picture naming task. Frequent phonetic (articulation) errors together with normal (but delayed) and deviant phonological processes of HId children were found in this study. The frequency and quality of the processes seemed to be related more to the grade of HI than, for example, the age of the child. Implications for speech therapy are briefly discussed.

Long-term outcome of early childhood hearing impairments in northern Finland.

Early childhood hearing impairment (HI) may have a marked negative effect on educational outcome and employment status in adulthood. The late outcome of 51 Finnish mildly to profoundly HId children born in the period 1965-1979 was studied using a questionnaire posted to the subjects. Subjects included in the study had an early childhood sensorineural, non-syndromal hearing impairment with no known associated handicaps. The response rate to the inquiry was as high as 88% (45/51). The subjects had qualified educationally at a somewhat lower level than their age peers according to nationwide statistics; 48% of the respondents belonging to the labour force were currently unemployed (versus 15% of all the 25-to 29-year-olds in Finland in 1997), but their employment status was not associated with the HI grade. In particular, the severely and profoundly HId often had needed special support from the employment authorities to find work.

On the construction of a Finnish audiometric sentence test.

To respond to the demands of clinical practice and the needs of rehabilitation, a Finnish audiometric sentence test is being developed. The test consists of 10 sets of 10 sentences, each set serving as an independent test. The test is scored by words (50 per set). Homogeneity between the sets was guaranteed by a number of linguistic and phonetic criteria, controlled by using the Virko Sentence Analyzer, a programme especially constructed for the purpose. Recognition tests for the validation of the sentence sets were made with young normally hearing adults (n = 70; age group 18-25 years). Psychometric recognition properties of the test are described. The selection process of the final 10 sentence sets is illustrated.

HI-SIMv1.0--towards the virtual reality of hearing impairments.

The virtual reality of hearing impairments has obvious practical applications in areas such as audiology, speech therapy and hearing aid technology and serves as an informational tool for the family members of the hearing impaired. To simulate hearing impairment, a CD-ROM with filtered speech material accessible through a graphical user-interface was produced; the user-interface was created with standard multimedia tools. The CD-ROM, HI-SIMv1.0, intended as an interactive educational tool, offers a virtual experience of the effects of a selection of common types of hearing impairment. The options available in this simulation include grade of hearing impairment, audiometric configuration and the type and level of background noise. Word recognition scores can be computed for standard Finnish audiometric material.

Cochlear implant patients and quality of life.

During the last two decades, cochlear implants have been available for profoundly hearing-impaired patients who do not benefit from conventional hearing aids. The quality of life of these implantees has not been extensively studied, and has not been studied at all in Finland. To assess their quality of life, the Nottingham Health Profile questionnaire was sent to all adult implanted patients in Finland. Implantees tended to have more favourable average pain, emotional reaction and mobility indexes in each age group studied than the average population. Social-isolation seemed to be more common in the youngest and oldest age groups of implantees. Apparently, implantees are physically healthier than the average population. However, a bias caused by the strict selection of implant candidates cannot be excluded.