Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus).

The knowledge of viral shedding patterns and viraemia in the reservoir host species is a key factor in assessing the human risk of zoonotic viruses. The shedding of hantaviruses (family Bunyaviridae) by their host rodents has widely been studied experimentally, but rarely in natural settings. Here we present the dynamics of Puumala hantavirus (PUUV) shedding and viraemia in naturally infected wild bank voles (Myodes glareolus). In a monthly capture-mark-recapture study, we analysed 18 bank voles for the presence and relative quantity of PUUV RNA in the excreta and blood from 2 months before up to 8 months after seroconversion. The proportion of animals shedding PUUV RNA in saliva, urine and faeces peaked during the first month after seroconversion, but continued throughout the study period with only a slight decline. The quantity of shed PUUV in reverse transcription quantitative PCR (RT-qPCR) positive excreta was constant over time. In blood, PUUV RNA was present for up to 7 months but both the probability of viraemia and the virus load declined with time. Our findings contradict the current view of a decline in virus shedding after the acute phase and a short viraemic period in hantavirus infection - an assumption widely adopted in current epidemiological models. We suggest the life-long shedding as a means of hantaviruses to survive over host population bottlenecks, and to disperse in fragmented habitats where local host and/or virus populations face temporary extinctions. Our results indicate that the kinetics of pathogens in wild hosts may differ considerably from those observed in laboratory settings.

Gender differences in health-related quality of life, blood pressure and heart rate among patients with paroxysmal atrial fibrillation after performing MediYoga.

Introduction: Patients with paroxysmal atrial fibrillation experience low health-related quality of life which can be improved by performing yoga. The aim of this study was to evaluate gender differences in health-related quality of life, blood pressure and heart rate among patients with paroxysmal atrial fibrillation after performing MediYoga. Methods: This is a secondary analysis of subgroups, investigating the yoga groups, from two randomized controlled trials (RCT 1: yoga group versus control group, RCT 2: a three-armed randomized study with yoga, control and relaxation groups). The yoga groups performed MediYoga for one hour/week over a 12-week period in both studies. Quality of life (SF-36), blood pressure and heart rate were collected at baseline and end of study. Results: No differences were found between the women and men. Within the women's group, there were improvements in vitality (p = 0.011), social function (p = 0.022), mental health (p = 0.007) and Mental Components Summary (p = 0.022). There were differences within the men's group in bodily pain (p = 0.005), general health (p = 0.003), vitality (p = 0.026), social function (p = 0.005), role-emotion (p = 0.011) and Mental Components Summary (p = 0.018). Within the women's group, differences were observed in systolic blood pressure (p = 0.010) and diastolic blood pressure (p = <0.001). The men's group also showed improvement in diastolic blood pressure (p = 0.021). Conclusion: MediYoga improved mental health as well as diastolic blood pressure in both men and women with PAF. This study suggests that both men and women, with PAF, may benefit from complementary treatment such as yoga.Clinical Trial Gov Id: NCT01789372.

Perceptions of delay when afflicted by an acute myocardial infarction during the first wave of the COVID-19 pandemic.

AIMS: To describe the perceptions of delay in medical care-seeking, when afflicted by an acute myocardial infarction (AMI) during the first wave of the pandemic. METHODS AND RESULTS: A qualitative descriptive study with an inductive approach. Fourteen semi-structured interviews were conducted, analysed by qualitative content analysis with a manifest approach. One category and six sub-categories emerged. The decision was reached when the health threat was perceived as critical, which made the earlier thoughts of the pandemic fade away. The risk of infection during medical visits caused fear of contracting the disease. This resulted in hesitation, neglect of symptoms, and avoidance of healthcare visits. Following recommendations from authorities and media about personal responsibility was motivated by fear, affecting the care-seeking. CONCLUSION: It appears that the COVID-19 pandemic raised the threshold for deciding to seek medical care when presenting with an AMI. The pandemic led to increased patient delay due to several reasons among which fear of contracting the disease was prominent. The emotion of fear was related to the external threat to one's own health, due to COVID-19, and not fear of symptoms related to an AMI. The media reporting the healthcare system as overloaded increased insecurity and may have had an influence on delay.

Phenotypic characterization of patient dengue virus isolates in BALB/c mice differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome.

BACKGROUND: Dengue virus (DENV) infection is the most common arthropod-borne viral disease in man and there are approximately 100 million infections annually. Despite the global burden of DENV infections many important questions regarding DENV pathogenesis remain unaddressed due to the lack of appropriate animal models of infection and disease. A major problem is the fact that no non-human species naturally develop disease similar to human dengue fever (DF) or dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Apart from other risk factors for severe dengue such as host genetics and secondary infection with a heterologous DENV, virus virulence is a risk factor that is not well characterized. RESULTS: Three clinical DENV-1 isolates from Cambodian patients experiencing the various forms of dengue disease (DF, DHF, and DSS) were inoculated in BALB/c mice at three different concentrations. The DENV-1 isolates had different organ and cell tropism and replication kinetics. The DENV-1 isolate from a DSS patient infected the largest number of mice and was primarily neurotropic. In contrast, the DENV-1 isolates from milder clinical dengue cases infected predominantly lungs and liver, and to a lesser extent brain. In addition, infection with the DENV isolate derived from a DSS patient persisted for more than two weeks in a majority of mice compared to the other DENV-1 isolates that peaked during the first week. CONCLUSIONS: These results confirm the in vitro findings of the same DENV-1 isolates, that showed that the isolate derived from a DSS patient can be distinguished based on phenotypic characteristics that differ from the isolates derived from a DF and DHF case 1. We observed in this study that the DSS virus isolate persist longer in vivo with extensive neuroinvasion in contrast to the other DENV-1 isolates originating in milder human cases. Genomic characterization of the three clinical isolates identified six amino acid substitutions unique for the DSS isolates that were located both in structural genes (M and E) and in non-structural genes (NS1, NS3, and NS5). The characterization of these clinically distinct DENV-1 isolates highlight that DENVs within the same genotype may have different in vivo phenotypes. HIGHLIGHTS: • Clinical DENV-1 isolates have different organ tropism in BALB/c mice.• The isolate from a DSS patient is primarily neurotropic compared to the other isolates.• The DENV-1 isolates have different in vivo replication kinetics.• The isolate from a DSS patient persists longer compared to the other isolates.• These phenotypic differences confirm our earlier in vitro findings with the same DENV-1 isolates. Thus, DENVs within the same serotype and genotype may differ enough to affect clinical conditions in vivo.

Phenotypic and genotypic characterization of dengue virus isolates differentiates dengue fever and dengue hemorrhagic fever from dengue shock syndrome.

Dengue viruses (DENV) cause 50-100 million cases of acute febrile disease every year, including 500,000 reported cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Viral factors have been proposed to influence the severity of the disease, but markers of virulence have never been identified on DENV. Three DENV serotype-1 isolates from the 2007 epidemic in Cambodia that are derived from patients experiencing the various clinical forms of dengue were characterized both phenotypically and genetically. Phenotypic characteristics in vitro, based on replication kinetics in different cell lines and apoptosis response, grouped isolates from DF and DHF patients together, whereas the virus isolate from a DSS patient showed unique features: a lower level of replication in mammalian cells and extensive apoptosis in mosquito cells. Genomic comparison of viruses revealed six unique amino acid residues in the membrane, envelope, and in non-structural genes in the virus isolated from the DSS patient.

MediYoga as a part of a self-management programme among patients with paroxysmal atrial fibrillation - a randomised study.

BACKGROUND: Paroxysmal atrial fibrillation is associated with impaired health-related quality of life. Yoga has been suggested to improve health-related quality of life among patients with heart failure and hypertension. AIM: The aim of the study was to evaluate the effects of MediYoga, in respect of health-related quality of life, blood pressure, heart rate, as well as N-terminal pro b-type natriuretic peptide, among patients with symptomatic paroxysmal atrial fibrillation, compared with standard therapy or relaxation. METHODS: Patients with symptomatic paroxysmal atrial fibrillation, n=132, were stratified for gender and randomised to MediYoga, a relaxation group or a control group, 44 patients per group with a 12-week follow-up. Health-related quality of life, blood pressure, heart rate and N-terminal pro b-type natriuretic peptide were assessed. RESULTS: After 12 weeks, there were no differences in health-related quality of life between the groups. There were improvements in Short-Form Health Survey bodily pain, general health, social function, mental health and mental component summary scores within the MediYoga group (p=0.014, p=0.037, p=0.029, p=0.030, p=0.019, respectively). No change was seen in the relaxation and control groups. Systolic blood pressure decreased in the MediYoga group (134±18 to 127±13) compared with the control group (126±17 to 127±15, p=0.041); no difference compared with the relaxation group (131±17 to 125±12). Diastolic blood pressure decreased in the MediYoga group (79±9 to 74 ±9) compared with the control group (76±9 to 79±8, p=0.005); no difference compared with the relaxation group (76±9 to 77±8). There were no differences in heart rate and N-terminal pro b-type natriuretic peptide between the groups after 12 weeks. CONCLUSIONS: MediYoga improves health-related quality of life and decreases blood pressure in patients with paroxysmal atrial fibrillation. MediYoga may be used as a part of a self-management programme among patients with paroxysmal atrial fibrillation.

Dynamics of Puumala hantavirus outbreak in Black Sea Region, Turkey.

BACKGROUND: Some of the hantavirus species in Euro-Asia cause haemorrhagic fever with renal syndrome (HFRS) in humans. The first documented human hantavirus infection in Turkey was diagnosed in 2009. This report describes the dynamics of the first hantavirus outbreak that emerged in humans in the Western Black Sea Region of Turkey. METHODS: All the suspected cases of hantavirus infection were admitted to the Infectious Diseases and Clinical Microbiology Department at the Zonguldak Bülent Ecevit University Hospital in Zonguldak, Turkey. The patients were carefully interviewed, examined and evaluated using routine laboratory tests and hantavirus diagnostic tools. Hantavirus-reactive antibodies (IgM and IgG) in serum samples were detected via enzyme immune assay (EIA) and immunofluorescence assay (IFA) in the acute and convalescence stages of the disease. The presence of hantavirus ribonucleic acid (RNA) was analysed via reverse transcription polymerase chain reaction (RT-PCR) in serum and urine samples. A focus reduction neutralization test (FRNT) was performed to confirm specific hantavirus serotypes. In addition, a case-control study was conducted to identify possible risk factors for hantavirus transmission in the outbreak area. A control group was composed of asymptomatic individuals who were seronegative for hantavirus IgM and IgG and living in the outbreak area. RESULTS: A total of 55 suspected cases of hantavirus infection were admitted to the inpatient clinic between February and June of 2009. Twenty-four patients were diagnosed with acute HFRS via EIA or IFA. In 22 of the 24 infected patients, Puumala virus (PUUV) was identified as the causative hantavirus type by detecting IgM in the acute stage and an increase in the IgG level in follow-up serum samples. PUUV was also verified as the infecting agent by FRNT in two of the 24 cases. Among the 24 laboratory-confirmed HFRS cases, 21 (87.5%) were males and 3 (12.5%) were females, and the mean age was 45.92 years (standard deviation ± 16.90 years). Almost all these individuals were living in villages or rural areas. The 24 HFRS cases were matched with 26 healthy controls for statistical analyses and according to binary logistic regression analysis, and dealing with rodent control activities in gardens or in annexes of their homes (p = 0.021 and Odds ratio [OR] = 17.11) and being male (p = 0.019 and OR = 22.37) were detected as statistically significant risk factors for hantavirus infection. The most commonly observed clinical complaints were fatigue (95.8%), shivering (91.7%), fever (87.1%), headache (70.8%) and nausea (70.8%). Haemodialysis was required for four patients (16.7%). Except for the first case diagnosed with acute hantavirus infection, no patient died. The mean delay time to hospital admission from initiation of symptoms was 5.3 days, the mean duration of febrile days was 2.6 days, and the mean duration of hospital stay was 8.5 days. CONCLUSION: Hantaviruses are circulating in Turkey and causing sporadic or epidemic infection in humans. Additional investigations are needed to better understand the dynamics of hantaviruses in this country.

Perceptions and experiences of MediYoga among patients with paroxysmal atrial fibrillation-An interview study.

OBJECTIVES: We investigated the perceptions and experiences of a therapeutic yoga form, MediYoga, which is evolved from Kundaliniyoga among patients with symptomatic paroxysmal atrial fibrillation (PAF). DESIGN AND SETTING: an inductive exploratory design was chosen with individual semi-structured interviews. The study was conducted with 12 participants (7 men and 5 women, average age 63.5) at a university hospital, Sweden. Informed consent was obtained from all participants. The data were analyzed using a qualitative content analysis with an inductive method and a manifest approach. RESULTS: Three categories were found in the analysis. In the category "A time for a sense of existence and presence", the patients described an increased thoughtfulness and experiences of gaining access to an inner self. The category "A way of gaining well-being and increased consciousness" describes patients` feelings of relaxation and feeling of comfort, with components of mental and physical well-being. Furthermore, "Access to a tool to gain willpower and relieve symptoms" describes the perceptions from patients to obtained access to a tool for handling the emotions, such as fear and anxiety, as well as symptoms that they could struggling with between, and during, their episodes of atrial fibrillation. No adverse events were reported by the yoga group, during the study. CONCLUSIONS: Patients with PAF described MediYoga as an accessible tool to manage emotions and symptoms related to episodes of AF. MediYoga may also assist in enhancing body awareness, whereby physical, mental and spiritual components are integrated. MediYoga may strengthen self-management among patients with PAF.

Effects of yoga in patients with paroxysmal atrial fibrillation - a randomized controlled study.

BACKGROUND: Patients with atrial fibrillation often have an impaired quality of life (QoL). Practising yoga may decrease stress and have positive effects on mental and physical health. The aim of this study was to investigate whether yoga can improve QoL and decrease blood pressure and heart rate in patients with paroxysmal atrial fibrillation (PAF). METHODS: In this pilot study, 80 patients diagnosed with PAF were randomized to standard treatment (control group, n=40) or standard treatment in combination with yoga (yoga group, n=40) during a 12-week period. QoL, blood pressure and heart rate were evaluated at baseline and at the end of the study (12 (+2) weeks). EuroQoL-5D (EQ-5D) Visual Analogue Scale (VAS) and the two dimensions in Short-Form Health Survey (SF-36) were used to evaluate QoL. RESULTS: At baseline there was a significant difference in QoL between the groups in EQ-5D VAS- scale ( p=0.02) and SF-36 mental health score ( p<0.001) in which the control group had higher scores. At the end of the study, the yoga group averaged higher SF-36 mental health scores. There was a significant difference between the two groups ( p=0.016), but no differences in EQ-5D VAS- scale and physiological health score was seen between the two groups. At the end of the study, the yoga group had significantly lower heart rate ( p=0.024) and systolic ( p=0.033) and diastolic blood pressure ( p<0.001) compared to the control group. CONCLUSIONS: Yoga with light movements and deep breathing may lead to improved QoL, lower blood pressure and lower heart rate in patients with PAF compared to a control group. Yoga could be a complementary treatment method to standard therapy.

Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

Surveillance for West Nile virus in wild birds from northern Europe.

A total of 1935 migratory birds from 104 different species were captured in southeastern Sweden in 2005-2006 and tested for antibodies against West Nile virus (WNV). Overall, 46 birds (2.4%; binomial confidence limits, 1.8-3.2) were positive by blocking-ELISA, but only 2 (0.10%; binomial confidence limits, 0.0-0.4) had antibodies detectable by both blocking-ELISA and WNV neutralization test. ELISA-positive birds included long- and short-distance migrants likely exposed to WNV while wintering in or migrating through areas enzootic for WNV. Exposure to a cross-reactive Flavivirus was suspected for short-distance migrants of the Turdidae family, but no cross-neutralization with tick-borne encephalitis and Usutu viruses was observed.