Showing papers by "Swedish Institute published in 2006"
TL;DR: Highly enriched primary IECs are used to analyze Toll-like receptor (TLR) signaling and mechanisms that prevent inappropriate stimulation by the colonizing microflora to acquire TLR tolerance immediately after birth to facilitate microbial colonization and the development of a stable intestinal host–microbe homeostasis.
Abstract: The role of innate immune recognition by intestinal epithelial cells (IECs) in vivo is ill-defined. Here, we used highly enriched primary IECs to analyze Toll-like receptor (TLR) signaling and mechanisms that prevent inappropriate stimulation by the colonizing microflora. Although the lipopolysaccharide (LPS) receptor complex TLR4/MD-2 was present in fetal, neonatal, and adult IECs, LPS-induced nuclear factor κB (NF-κB) activation and chemokine (macrophage inflammatory protein 2 [MIP-2]) secretion was only detected in fetal IECs. Fetal intestinal macrophages, in contrast, were constitutively nonresponsive to LPS. Acquisition of LPS resistance was paralleled by a spontaneous activation of IECs shortly after birth as illustrated by phosphorylation of IκB-α and nuclear translocation of NF-κB p65 in situ as well as transcriptional activation of MIP-2. Importantly, the spontaneous IEC activation occurred in vaginally born mice but not in neonates delivered by Caesarean section or in TLR4-deficient mice, which together with local endotoxin measurements identified LPS as stimulatory agent. The postnatal loss of LPS responsiveness of IECs was associated with a posttranscriptional down-regulation of the interleukin 1 receptor–associated kinase 1, which was essential for epithelial TLR4 signaling in vitro. Thus, unlike intestinal macrophages, IECs acquire TLR tolerance immediately after birth by exposure to exogenous endotoxin to facilitate microbial colonization and the development of a stable intestinal host–microbe homeostasis.
439 citations
TL;DR: Findings show that Toxoplasma is able to subvert the regulation of host cell motility and likely exploits the host’s natural pathways of cellular migration for parasite dissemination.
Abstract: The processes leading to systemic dissemination of the obligate intracellular parasite Toxoplasma gondii remain unelucidated. In vitro studies on human and murine dendritic cells (DC) revealed that active invasion of DC by Toxoplasma induces a state of hypermotility in DC, enabling transmigration of infected DC across endothelial cell monolayers in the absence of chemotactic stimuli. Infected DC exhibited upregulation of maturation markers and co-stimulatory molecules. While modulation of cell adhesion molecules CD11/CD18 was similar for Toxoplasma-infected DC and lipopolysaccharide (LPS)-matured DC, Toxoplasma-infected DC did not exhibit upregulation of CD54/ICAM-1. Induction of host cell migration in vitro required live intracellular parasite(s) and was inhibited by uncoupling the Gi-protein signalling pathway with pertussis toxin, but did not depend on CCR5, CCR7 or Toll/interleukin-1 receptor signalling. When migration of Toxoplasma-infected DC was compared with migration of LPS-stimulated DC in vivo, similar or higher numbers of Toxoplasma-infected DC reached the mesenteric lymph nodes and spleen respectively. Adoptive transfer of Toxoplasma-infected DC resulted in more rapid dissemination of parasites to distant organs and in exacerbation of infection compared with inoculation with free parasites. Altogether, these findings show that Toxoplasma is able to subvert the regulation of host cell motility and likely exploits the host's natural pathways of cellular migration for parasite dissemination.
263 citations
TL;DR: It is demonstrated that hantavirus transmission does not require direct contact between rodents, or between rodents and humans, and that the indirect transmission of PUUV through contaminated environment takes place among the rodents for a prolonged period of time.
Abstract: The capability of rodent-borne viruses to survive outside the host is critical for the transmission dynamics within rodent populations and to humans. The transmission of Puumala virus (PUUV) in colonized bank voles (Clethrionomys glareolus) was investigated and additional longevity studies in cell culture with PUUV and Tula (TULV) hantaviruses were performed. Wild-type PUUV excreted by experimentally infected donor bank voles was shown to be transmitted indirectly between rodents through contaminated beddings, and maintained its infectivity to recipient voles at room temperature for 12–15 days. In cell culture supernatants, PUUV and TULV remained infectious for 5–11 days at room temperature and up to 18 days at 4 °C, but were inactivated after 24 h at 37 °C. Interestingly, a fraction of dried virus was still infectious after 1 h at 56 °C. These results demonstrated that hantavirus transmission does not require direct contact between rodents, or between rodents and humans, and that the indirect transmission of PUUV through contaminated environment takes place among the rodents for a prolonged period of time. The results also have implications for safety recommendations for work with hantaviruses and for preventive measures.
263 citations
TL;DR: It is shown that one of these compounds, INP0400, inhibits intracellular replication and infectivity of C. trachomatis at micromolar concentrations resulting in small inclusion bodies frequently containing only one or a few reticulate bodies (RBs).
Abstract: The intracellular pathogen Chlamydia trachomatis possesses a type III secretion (TTS) system believed to deliver a series of effector proteins into the inclusion membrane (Inc-proteins) as well as into the host cytosol with perceived consequences for the pathogenicity of this common venereal pathogen. Recently, small molecules were shown to block the TTS system of Yersinia pseudotuberculosis. Here, we show that one of these compounds, INP0400, inhibits intracellular replication and infectivity of C. trachomatis at micromolar concentrations resulting in small inclusion bodies frequently containing only one or a few reticulate bodies (RBs). INP0400, at high concentration, given at the time of infection, partially blocked entry of elementary bodies into host cells. Early treatment inhibited the localization of the mammalian protein 14-3-3beta to the inclusions, indicative of absence of the early induced TTS effector IncG from the inclusion membrane. Treatment with INP0400 during chlamydial mid-cycle prevented secretion of the TTS effector IncA and homotypic vesicular fusions mediated by this protein. INP0400 given during the late phase resulted in the detachment of RBs from the inclusion membrane concomitant with an inhibition of RB to elementary body conversion causing a marked decrease in infectivity.
205 citations
TL;DR: It is concluded that carefully designed mass education campaigns could improve antibiotic use nationally and should be considered in countries with high antibiotic use, however, these campaigns should employ techniques of social marketing and use appropriate outcome measures.
Abstract: High levels of antibiotic consumption are driving levels of bacterial resistance that threaten public health. Nonetheless, antibiotics still provide highly effective treatments for common diseases with important implications for human health. The challenge for public education is to achieve a meaningful reduction in unnecessary antibiotic use without adversely affecting the management of bacterial infections. This paper focuses on the lessons learned from national campaigns in countries (Belgium and France) with high antibiotic use. Evaluation of these national campaigns showed the importance of television advertising as a powerful medium to change attitudes and perhaps also behaviour with regard to antibiotics. Moreover, in both countries, strong evidence suggested reduced antibiotic prescribing. However, adverse effects associated with a reduction in antibiotic prescribing were not monitored. We conclude that carefully designed mass education campaigns could improve antibiotic use nationally and should be considered in countries with high antibiotic use. However, these campaigns should employ techniques of social marketing and use appropriate outcome measures. The benefits and risks of such campaigns have been less well established in countries where antibiotic use is already low or declining.
200 citations
TL;DR: It is suggested that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
Abstract: Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid–binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid–dependent in vitro agglutination of erythrocytes (i.e., sialic acid–dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid–dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcα2–3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
184 citations
TL;DR: The sample seemed to reflect the ageing process in that the respondents were at different stages of ageing, and the fact that the level of social support, sense of coherence and self-rated health followed the same curve as QoL may indicate that some are more vulnerable to low presentQoL given the same health and these should be targeted in preventive programmes since they report low QOL.
Abstract: Public health policies in most European countries are concerned with how to keep older people living independently with a qualitatively good life in the community as long as possible. However, knowledge about what may characterise those seemingly 'healthy' older people is sparse. The aim of the study was to investigate the characteristics of a sample of people (75+) reporting various degrees of Quality of Life (QoL) with respect to QoL in different areas, as well as self-rated health, health problems, social support, everyday activities and sense of coherence. A postal questionnaire was sent out in spring 2001 to a randomly selected population-based sample (n= 600) in the southern parts of Sweden. A two-step cluster analysis was performed (n= 385, mean age 84.6, SD = 5.7) with 'present QoL' as clustering attribute. Three groups were disclosed, classified as high, intermediate and low present QoL, of which 33.8% could be regarded being at risk of low QoL. Those with low present QoL (18.4%) were the oldest and most vulnerable, a majority were women with 'poor or bad' self-rated health, high frequencies of health problems, low total QoL, low social support and sense of coherence and less physically active. Those with high present QoL (47.8%) reported more 'excellent or good' self-rated health, physical activity, satisfactory social support and higher sense of coherence and total QoL than the other two groups. Those with intermediate present QoL (33.8%) had more of 'poor or bad' self-rated health, more health problems were less physically active, had lower total QoL and sense of coherence, and less social support than those with high present QoL. The sample seemed to reflect the ageing process in that the respondents were at different stages of ageing. However, the fact that the level of social support, sense of coherence and self-rated health followed the same curve as QoL may indicate that some are more vulnerable to low present QoL given the same health and these should be targeted in preventive programmes since they report low QoL.
140 citations
TL;DR: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lackOf signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse, and the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti–inflammatory cytokine IL–10 response suggest immunologically–mediated pathogenicity.
Abstract: Objectives
To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune– mediated events
137 citations
TL;DR: Some of the more recent efforts aimed at increasing the immunogenicity of DNA vaccines, including the use of genetic adjuvants and plasmid-based expression of viral replicons are described.
Abstract: The field of DNA vaccines continues to advance and several new strategies to augment the immunogenicity of DNA vaccines are under evaluation. The majority of these studies are in the early preclinical stage, but some DNA vaccines have moved into clinical trials. In this review, we describe some of the more recent efforts aimed at increasing the immunogenicity of DNA vaccines, including the use of genetic adjuvants and plasmid-based expression of viral replicons. In addition, we discuss the possibility of using DNA vaccines to address emerging infectious agents where they may provide an advantage over other vaccine strategies and we review some areas where DNA vaccines have been used to target self-antigens.
134 citations
TL;DR: In this paper, a full-scale injector was developed and evaluated in a field experiment on grassland, where cattle slurry was either injected in closed slots 5 cm below ground or band spread on the soil surface above the crop canopy at a rate of 25 t ha -1.
Abstract: In Sweden, 90% of ammonia (NH 3 ) emissions to the atmosphere originate from agriculture, predominantly from animal manure handling. It is well known that incorporation of manure into soil can reduce NH 3 emissions after spreading. However, there is a risk of increased nitrous oxide (N 2 O) and methane (CH 4 ) emissions caused by bacterial activity and limited oxygen availability under these conditions. A full-scale injector was developed and evaluated in a field experiment on grassland. Cattle slurry was either injected in closed slots 5 cm below ground or band spread on the soil surface above the crop canopy at a rate of 25 t ha -1 . In a control treatment, no slurry was applied. During a 5-day period after application, NH 3 emissions were measured using an equilibrium concentration method. Gas samples for estimating CH 4 and N 2 O emissions were also collected during 7 weeks following slurry application. Injection in closed slots resulted in no detectable NH 3 emissions. After band spreading, however, NH 3 emissions corresponded to nearly 40% of the total ammoniacal nitrogen in the applied slurry. The injection of slurry gave rise to a broad peak of N 2 O emissions during the first 3 weeks after application. In total, for the measuring period, N 2 O emissions corresponded to 0.75 kg N ha -1 . Band spreading resulted in only a very small N 2 O release of about 0.2 kg N ha -1 during the same period. Except for the first sampling occasion, the soil was predominantly a sink for CH 4 in all the treatments. The use of the injector without slurry application reduced grass yield during unfavourable growing conditions. In conclusion, shallow injection in closed slots seems to be a promising technique to reduce negative environmental impacts from NH 3 emissions with a limited release of N 2 O and CH 4 .
111 citations
TL;DR: In this paper, the authors evaluated the energy balance and environmental load for systems based on rape methyl ester (RME), ethanol and biogas using a life cycle perspective.
TL;DR: In the last few years, there has been a move away from burning fossil fuels through the co-utilisation of biomass and coal and finally to 100% biomass such as wood and waste wood products as mentioned in this paper.
Abstract: In the last few years, there has been a move away from burning fossil fuels through the co-utilisation of biomass and coal and finally to 100% biomass such as wood and waste wood products. Unfortun ...
TL;DR: Evidence for a role of malaria in preferentially activating the memory B cell compartment is provided and the gene expression profiles induced by CIDR1α and anti-Ig activation using a cDNA microarray demonstrated a low degree of homology in the signatures imposed by both stimuli.
Abstract: Chronic malaria infection is characterized by polyclonal B cell activation, hyperglobulinemia, and elevated titers of autoantibodies. We have recently identified the cysteine-rich interdomain region 1α (CIDR1α) of the Plasmodium falciparum erythrocyte membrane protein 1 as a T cell-independent polyclonal B cell activator and Ig binding protein. Here, we show that, although the binding affinity of CIDR1α to human IgM and IgG is relatively low, B cell activation still proceeds. CIDR1α rescues tonsillar B cells from apoptosis, and increases the proportion of cycling cells. Comparison of the impact on naive and memory B cell compartment indicated that CIDR1α preferentially activates memory B lymphocytes. Analysis of the gene expression profiles induced by CIDR1α and anti-Ig activation using a cDNA microarray demonstrated a low degree of homology in the signatures imposed by both stimuli. The microarray data correlate with the functional analysis demonstrating that CIDR1α activates various immunological pathways and protects B cells from apoptosis. Together, the results provide evidence for a role of malaria in preferentially activating the memory B cell compartment. The polyclonal B cell activation and augmented survival induced by CIDR1α is of relevance for understanding the mechanisms behind the increased risk of Burkitt’s lymphoma in malaria endemic areas.
TL;DR: Lower life satisfaction was associated with not being employed, low social resources, not refreshed after a night's sleep, overall poor health and frequent caregiving in the entire sample.
Abstract: Being a caregiver with responsibility for someone with reduced health compared with not being a caregiver may mean different views of life satisfaction. Knowledge of what leads to reduced life satisfaction in caregivers may be helpful in interventions. Informal caregivers gainfully employed or not, aged 50-89 years, were studied with regard to life satisfaction depending on the extent of caregiving to identify types of social support of value for caregivers. A cross-sectional study was conducted including a sample of 151 informal caregivers with a high caregiving extent, 392 caregivers with a lower caregiving extent and 1258 non-caregivers. The sample was randomly selected to correspond with older Swedes as a whole aged 50-89 years. A questionnaire containing a modified form of Older Americans' Resources Schedule (OARS) and Life Satisfaction Index Z (LSIZ) was used; 19.6% helped someone with activities of daily living and of these 27% stated that they did so frequently. Frequent caregiving implied significantly higher age, being more often married and retired, than less frequent caregivers and non-caregivers. Frequent caregivers also performed personal activities of daily living (PADL) to a higher extent than less frequent caregivers and had significantly lower LSIZ (mean 14.8) than less frequent caregivers (mean 17.6) and non-caregivers (mean 17.7). No significant differences were found between less frequent caregivers and non-caregivers in LSIZ. One-fourth had support from others, the commonest type being able to converse with a next of kin, and help and advice from professionals. Lower life satisfaction was associated with not being employed, low social resources, not refreshed after a night's sleep, overall poor health and frequent caregiving in the entire sample. High caregiving extent was associated with lower life satisfaction. The most important factors explaining lower life satisfaction among frequent caregivers were having low social resources and having poor health. Economic compensation or payment was the support most desired.
TL;DR: The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation, and the positive plasma samples clustered around 7-9 years of age, the peak incidence of BL.
Abstract: Children living in malaria-endemic regions have a high incidence of Burkitt lymphoma (BL), the etiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. In the present study, we compared EBV DNA loads in plasma and saliva samples from Ugandan children with acute malaria (M + ) at the time of diagnosis and 14 days after antimalaria treatment, children without malaria (M), and children with BL. EBV DNA was detected, by real-time polymerase chain reaction, in 31% of the plasma and in 79% of the saliva samples from children in the M + group. Antimalaria treatment led to clearance of plasma viral load in 85% of the cases but did not affect the levels in saliva. There was a significant difference in plasma EBV loads across the groups. The lowest levels were detected in samples from the M group, increased levels were detected in samples from the M + group, and levels reached the highest values in samples from children with BL. The same trend was evident in the frequency and levels of anti-BZLF1 antibodies, which is indicative of viral reactivation. In the M + group, the positive plasma samples clustered around 7‐9 years of age, the peak incidence of BL. The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation.
TL;DR: Increased levels of serum perforin, granzyme B, and the epithelial cell apoptosis marker caspase-cleaved cytokeratin-18 during Puumala hantavirus infection suggest tissue damage is due to an immune reaction and that epithelial apoptosis contributed significantly to the damage.
Abstract: Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome are two diseases caused by hantaviruses. Capillary leakage is a hallmark of hantavirus infection. Pathogenic hantaviruses are not cytotoxic, but elevated levels of serum lactate dehydrogenase (LDH), indicative of cellular damage, are observed in patients. We report increased levels of serum perforin, granzyme B, and the epithelial cell apoptosis marker caspase-cleaved cytokeratin-18 during Puumala hantavirus infection. Significant correlation was observed between the levels of LDH and perforin and the levels of LDH and caspase-cleaved cytokeratin-18, suggesting that tissue damage is due to an immune reaction and that epithelial apoptosis contributed significantly to the damage.
TL;DR: No significant effect on case fatality rate was revealed when a macrolide/ß-lactam regimen was used as initial therapy and identified predictors of death in a multivariate regression model were age >65 years, two or more lung lobes affected, and severity of disease as estimated using the acute physiology score (APS).
Abstract: In the study presented here, data collected prospectively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a s-lactam +/− a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination. Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/s-lactam regimen was used as initial therapy. Results were not affected by severity of illness, or by excluding patients who died within 2 days of admission. Identified predictors of death in a multivariate regression model were age >65 years (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as estimated using the acute physiology score (APS)>8.
TL;DR: It is shown that NO has strong antiviral effects on hantavirus replication, and peroxynitrite on mature free virions, suggesting that different RNI can have different effects on various parts of the replication cycle for the same virus.
Abstract: Reactive nitrogen intermediates (RNI), like nitric oxide (NO) and peroxynitrite, have antiviral effects against certain viruses. Hantaviruses, like other members of the Bunyaviridae family, have previously not been shown to be sensitive to RNI. In this study, we compared the effects of NO and peroxynitrite on hantavirus replication and free mature virions in vitro, and of inducible nitric oxide synthase (iNOS) in hantavirus-infected suckling mice. The NO-generating compound S-nitroso-N-acetylpenicillamine (SNAP), as well as cytokine-induced NO, strongly inhibited hantavirus replication in Vero E6 cells, while pretreatment of free virions with SNAP only had a limited effect on their viability. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited virus replication only to a very low extent in vitro, but pretreatment of virus with SIN-1 led to a considerably lowered viability of the virions. Infections of various human cell types per se did not induce NO production. The viral titers in iNOS(-/-) mice were higher compared to the controls, suggesting that NO inhibits hantavirus replication in vivo. In conclusion, we show that NO has strong antiviral effects on hantavirus replication, and peryoxynitrite on mature free virions, suggesting that different RNI can have different effects on various parts of the replication cycle for the same virus.
TL;DR: The MRSA incidence in Sweden increased over the years 2000–2003 and now poises on the rim of the same development that was seen in the United Kingdom some ten years ago, reflecting that international transmission is now increasingly important in a low-endemic setting.
Abstract: The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) has gradually become more frequent in most countries of the world. Sweden has remained one of few exceptions to the high occurrence of MRSA in many other countries. During the late 1990s, Sweden experienced a large health-care associated outbreak which with resolute efforts was overcome. Subsequently, MRSA was made a notifiable diagnosis in Sweden in 2000. From the start of being a notifiable disease in January 2000, the Swedish Institute for Infectious Disease Control (SMI) initiated an active surveillance of MRSA. The number of reported MRSA-cases in Sweden increased from 325 cases in 2000 to 544 in 2003, corresponding to an overall increase in incidence from 3.7 to 6.1 per 100000 inhabitants. Twenty five per cent of the cases were infected abroad. The domestic cases were predominantly found through cultures taken on clinical indication and the cases infected abroad through screening. There were considerable regional differences in MRSA-incidence and age-distribution of cases. The MRSA incidence in Sweden increased over the years 2000–2003. Sweden now poises on the rim of the same development that was seen in the United Kingdom some ten years ago. A quarter of the cases were infected abroad, reflecting that international transmission is now increasingly important in a low-endemic setting. To remain in this favourable situation, stepped up measures will be needed, to identify imported cases, to control domestic outbreaks and to prevent transmission within the health-care sector.
TL;DR: In this paper, the authors show that EBNA-3 interacts specifically with AhR and the stability of this interaction is determined by the activation state of AhR, and its association with XAP2.
TL;DR: The resistance rate in a random population has not been studied previously and information on antimicrobial susceptibility is important for selection of an optimum treatment regimen.
Abstract: Background and Aim: Antimicrobial resistance in Helicobacter pylori is a growing problem and has become an important factor leading to eradication failure. Information on antimicrobial susceptibility is important for selection of an optimum treatment regimen. The resistance rate in a random population has not been studied previously.
Methods: A random Swedish population sample (n = 3000, age 20–81 years) was surveyed using a mailed validated questionnaire assessing gastrointestinal symptoms (response rate of 74%). One-third of the responders was invited, in random order, and accepted an esophagogastroduodenoscopy with biopsies for H. pylori culture and histology. Subjects were not treated for their H. pylori infection but a minimum inhibitory concentration of metronidazole, clarithromycin, amoxicillin, and tetracycline for the H. pylori isolates (n = 333) was determined by agar dilution. Prescribed antibiotic in the area was recorded.
Results: Irrespective of symptomatology, 16.2% of the isolated H. pylori strains were resistant to metronidazole, 1.5% to clarithromycin, 0% to amoxicillin, and 0.3% to tetracycline. The antibiotic consumption was low from an international perspective.
Conclusion: The resistance to the antibiotics was lower than expected from patient sample studies, especially for clarithromycin, most probably due to a restrictive prescription policy in the area. Introduction of a test-and-treat strategy in Sweden would only marginally affect the usage of clarithromycin.
TL;DR: PCR results showed that E. histolytica and E. dispar were clearly overdiagnosed, with the consequence of overtreatment in patients with diarrhea.
TL;DR: In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD.
Abstract: Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.
TL;DR: The results suggest the importance of two independent UL18 regions for LIR‐1 binding, one localized on the tip of the α3 domain, and another composed of two loops that emerge from the α1 domain.
Abstract: Human cytomegalovirus (HCMV) down-regulates cell surface expression of HLA class I molecules (HLA-I). UL18, an HCMV-encoded HLA-I homologue, has been proposed to protect virus-infected cells against NK cell recognition by engaging the inhibitory receptor leukocyte Ig-like receptor (LIR)-1, which also binds a broad spectrum of HLA-I alleles, including HLA-G1. Because genetic and biological differences exist among HCMV strains, we characterized laboratory (AD169) and clinical (4636, 13B, 109B) strain-derived UL18 proteins. Compared to the known AD169-derived UL18, mutations were found in clinical strain-derived UL18. They were clustered in the alpha3 domain (13B), previously shown to be critical for LIR-1 binding, or in the alpha1 domain (4636). Iotan cytotoxicity assays, pretreatment of LIR-1+ NKL with soluble 4636-UL18 completely abolished LIR-1-dependent protection from NK lysis, conferred by the expression of HLA-G1 on target cells (721.221-HLA-G1+). Similarly, flow cytometry, Biacore and ELISA experiments showed 4636-UL18 and 13B-UL18 to have the strongest binding capacity to LIR-1. Our results suggest the importance of two independent UL18 regions for LIR-1 binding, one localized on the tip of the alpha3 domain, and another composed of two loops that emerge from the alpha1 domain. Strain variations in these domains may result in different UL18-mediated effects on LIR-1+ cells during the course of HCMV infection.
TL;DR: This model provides information for the protection of workers against the risk of cold injury by establishing the temperature limits of cold touchable surfaces for a broad range of materials, and it is now proposed as guidance values in a new international standard.
Abstract: Objectives: At the request of the European Commission and in the framework of the European Machinery Directive, research was performed in five different laboratories to develop specifications for surface temperature limit values for the short-term accidental touching of the fingertip with cold surfaces. Methods: Data were collected in four laboratories with a total of 20 males and 20 females performing a grand total of 1655 exposures. Each touched polished blocks of aluminium, stainless steel, nylon-6 and wood using the distal phalanx of the index finger with a contact force of 1.0, 2.9 and 9.8 N, at surface temperatures from +2 to -40C for a maximum duration of 120 s. Conditions were selected in order to elicit varying rates of skin cooling upon contact. Contact temperature (TC) of the fingertip was measured over time using a T-type thermocouple. Results: A database obtained from the experiments was collated and analysed to characterize fingertip contact cooling across a range of materials and surface temperatures. The database was subsequently used to develop a predictive model to describe the contact duration required for skin contact temperature to reach the physiological criteria of onset of pain (15C), onset of numbness (7C) and onset of frostbite risk (0C). Conclusions: The data reflect the strong link between the risk of skin damage and the thermal properties of the material touched. For aluminium and steel, skin temperatures of 0C occurs within 2-6 s at surface temperatures of -15C. For non-metallic surfaces, onset of numbness occurs within 15-65 s of contact at -35C and onset of cold pain occurs within 5 s of contact at -20C. The predictive model subsequently developed was a non-linear exponential expression also reflecting the effects of material thermal properties and initial temperature. This model provides information for the protection of workers against the risk of cold injury by establishing the temperature limits of cold touchable surfaces for a broad range of materials, and it is now proposed as guidance values in a new international standard. Keywords: Cold surfaces; contact temperature; finger touching; machine safety
TL;DR: In recent weeks, three people in Blekinge County in southeast Sweden were reported to have developed mild to severe wound.
Abstract: In recent weeks, three people in Blekinge County in southeast Sweden were reported to have developed mild to severe wound
TL;DR: This study confirmed that results for anti-VZV obtained by different ELISA methods can be converted into common units, enabling the comparison of the seroprevalence profiles obtained in the participant countries.
TL;DR: It is demonstrated that the BarA-UvrY two-component system is a determinant for virulence in a monkey cystitis model and thatability to efficiently switch between the carbon sources may provide an explanation to the reduced fitness of the uvrY mutant in the cyStitis model.
Abstract: The Salmonella enterica BarA-SirA, the Erwinia carotovora ExpS-ExpA, the Vibrio cholerae BarA-VarA and the Pseudomonas spp GacS-GacA all belong to the same orthologous family of two-component systems as the Escherichia coli BarA-UvrY. In the first four species it has been demonstrated that disruption of this two-component system leads to a clear reduction in virulence of the bacteria. Our aim was to determine if the Escherichia coli BarA-UvrY two-component system is connected with virulence using a monkey cystitis model. Cystitis was generated in Macaque fascularis monkeys by infecting the bladder with a 1:1 mixture of the uropathogenic Escherichia coli isolate DS17 and a derivative where the uvrY gene had been disrupted with a kanamycin resistance gene. Urine was collected through bladder punctuation at subsequent time intervals and the relative amount of uvrY mutant was determined. This showed that inactivation of the UvrY response regulator leads to a reduced fitness. In similar competitions in culture flasks with Luria Broth (LB) the uvrY mutant rather had a higher fitness than the wild type. When the competitions were done in flasks with human urine the uvrY mutant initially had a lower fitness. This was followed by a fluctuation in the level of mutant in the long-term culture, with a pattern that was specific for the individual urines that were tested. Addition of LB to the different urine competition cultures however clearly led to a consistently higher fitness of the uvrY mutant. This paper demonstrates that the BarA-UvrY two-component system is a determinant for virulence in a monkey cystitis model. The observed competition profiles strengthen our previous hypothesis that disruption of the BarA-UvrY two-component system impairs the ability of the bacteria to switch between different carbon sources. The urine in the bladder contains several different carbon sources and its composition changes over time. Inability to efficiently switch between the carbon sources may thus provide an explanation to the reduced fitness of the uvrY mutant in the cystitis model.
TL;DR: Hand function was profoundly affected at diagnosis of RA, but improved significantly within 3 months and remained stable (but still affected) over 3 years, as expected, women on average had significantly lower grip force than men.
Abstract: Objective: To describe the course of hand function in women and men during the first 3 years after diagnosis of recent-onset rheumatoid arthritis (RA), to investigate sex differences in hand functi ...
TL;DR: In this paper, the authors analyzed the environmental impact and resource use in a life cycle perspective for three systems, each including both wastewater handling and agricultural production, and found that high substitution of mineral fertiliser, optimal spreading technique and well designed collection and storage facilities were important factors for the environmental outcome in the blackwater system.
Abstract: Recycling of plant nutrients in sewage products to arable land is considered to be a step towards a more sustainable society. Sewage sludge is the predominant sewage fertiliser product available today, but the use of sewage sludge in agriculture has been questioned as regards hazardous substances. In this respect, blackwater from separating systems seems to better fulfil agricultural requirements regarding fertiliser products. The objective of this paper was to analyse the environmental impact and resource use in a life cycle perspective for three systems, each including both wastewater handling and agricultural production. In the reference system, food waste disposers were installed in houses. Milled food waste and wastewater were treated in a wastewater treatment plant and the sewage sludge was used for producing a soil conditioner. In the sludge utilisation system, food waste from households was composted, wastewater was treated conventionally and sewage sludge was used in oat production. In the blackwater system, toilet water from low-flush toilets and milled organic waste were digested together and spread in growing oats. Data on the wastewater system were derived from simulations by the substance-flow model URWARE/ORWARE. The blackwater system required slightly more primary energy than the other two systems. In particular, construction of storage facilities contributed considerably to energy use. The emissions of greenhouse gases and SO2 were of the same magnitude for all three systems, while the eutrophying emissions were reduced significantly in the blackwater system. As regards NH3 and NOX, the emissions were highest for the blackwater system. High substitution of mineral fertiliser, optimal spreading technique and well-designed collection and storage facilities were important factors for the environmental outcome in the blackwater system.