Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic Glucose Handling.

Insulin resistance is a hallmark of diabetes and an unmet clinical need. Insulin inhibits hepatic glucose production and promotes lipogenesis by suppressing FOXO1-dependent activation of G6pase and inhibition of glucokinase, respectively. The tight coupling of these events poses a dual conundrum: mechanistically, as the FOXO1 corepressor of glucokinase is unknown, and clinically, as inhibition of glucose production is predicted to increase lipogenesis. Here, we report that SIN3A is the insulin-sensitive FOXO1 corepressor of glucokinase. Genetic ablation of SIN3A abolishes nutrient regulation of glucokinase without affecting other FOXO1 target genes and lowers glycemia without concurrent steatosis. To extend this work, we executed a small-molecule screen and discovered selective inhibitors of FOXO-dependent glucose production devoid of lipogenic activity in hepatocytes. In addition to identifying a novel mode of insulin action, these data raise the possibility of developing selective modulators of unliganded transcription factors to dial out adverse effects of insulin sensitizers.

Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones.

BACKGROUND: Fluoroquinolones lack approval for treatment of tularemia but have been used extensively for milder illness. Here, we evaluated fluoroquinolones for severe illness. METHODS: In an observational study, we identified case-patients with respiratory tularemia from July to November 2010 in Jämtland County, Sweden. We defined severe tularemia by hospitalization for >24 hours and severe bacteremic tularemia by Francisella tularensis subsp. holarctica growth in blood or pleural fluid. Clinical data and drug dosing were retrieved from electronic medical records. Chest images were reexamined. We used Kaplan-Meier curves to evaluate time to defervescence and hospital discharge. RESULTS: Among 67 case-patients (median age, 66 years; 81% males) 30-day mortality was 1.5% (1 of 67). Among 33 hospitalized persons (median age, 71 years; 82% males), 23 had nonbacteremic and 10 had bacteremic severe tularemia. Subpleural round consolidations, mediastinal lymphadenopathy, and unilateral pleural fluid were common on chest computed tomography. Among 29 hospitalized persons with complete outcome data, ciprofloxacin/levofloxacin (n = 12), ciprofloxacin/levofloxacin combinations with doxycycline and/or gentamicin (n = 11), or doxycycline as the single drug (n = 6) was used for treatment. One disease relapse occurred with doxycycline treatment. Treatment responses were rapid, with median fever duration 41.0 hours in nonbacteremic and 115.0 hours in bacteremic tularemia. Increased age-adjusted Charlson comorbidity index predicted severe bacteremic tularemia (odds ratio, 2.7 per score-point; 95% confidence interval, 1.35-5.41). A 78-year-old male with comorbidities and delayed ciprofloxacin/gentamicin treatment died. CONCLUSIONS: Fluoroquinolone treatment is effective for severe tularemia. Subpleural round consolidations and mediastinal lymphadenopathy were typical findings on computed tomography among case-patients in this study.

Completed genome and emergence scenario of the multidrug-resistant nosocomial pathogen Staphylococcus epidermidis ST215.

BACKGROUND: A multidrug-resistant lineage of Staphylococcus epidermidis named ST215 is a common cause of prosthetic joint infections and other deep surgical site infections in Northern Europe, but is not present elsewhere. The increasing resistance among S. epidermidis strains is a global concern. We used whole-genome sequencing to characterize ST215 from healthcare settings. RESULTS: We completed the genome of a ST215 isolate from a Swedish hospital using short and long reads, resulting in a circular 2,676,787 bp chromosome and a 2,326 bp plasmid. The new ST215 genome was placed in phylogenetic context using 1,361 finished public S. epidermidis reference genomes. We generated 10 additional short-read ST215 genomes and 11 short-read genomes of ST2, which is another common multidrug-resistant lineage at the same hospital. We studied recombination's role in the evolution of ST2 and ST215, and found multiple recombination events averaging 30-50 kb. By comparing the results of antimicrobial susceptibility testing for 31 antimicrobial drugs with the genome content encoding antimicrobial resistance in the ST215 and ST2 isolates, we found highly similar resistance traits between the isolates, with 22 resistance genes being shared between all the ST215 and ST2 genomes. The ST215 genome contained 29 genes that were historically identified as virulence genes of S. epidermidis ST2. We established that in the nucleotide sequence stretches identified as recombination events, virulence genes were overrepresented in ST215, while antibiotic resistance genes were overrepresented in ST2. CONCLUSIONS: This study features the extensive antibiotic resistance and virulence gene content in ST215 genomes. ST215 and ST2 lineages have similarly evolved, acquiring resistance and virulence through genomic recombination. The results highlight the threat of new multidrug-resistant S. epidermidis lineages emerging in healthcare settings.

Monotherapy with infusion therapies - useful or not?

Infusion pump-based therapies are an effective treatment option for patients with advanced Parkinson´s disease. Achieving monotherapy with infusion-based therapies could simplify the treatment regimen, provide better medication adherence, reduce adverse events and drug interactions. This review presents the literature data on the efficacy, safety, and achievability of monotherapy with all available infusion-based therapies, including apomorphine, levodopa-carbidopa-intestinal gel (LCIG), levodopa-entacapone-carbidopa intestinal gel (LECIG), and foslevodopa-foscarbidopa (LDp/CDp). In summary, monotherapy is achievable and effective in most patients on intestinal levodopa infusion therapy and in some patients on apomorphine infusion. There is a need for further investigation of monotherapy compared to polytherapy, especially in new pump treatment options (LECIG and LDp/CDp). Future research should reveal which patients on infusion-based therapies could benefit from monotherapy, including identification of potential baseline predictors of achieving monotherapy in patients treated with specific infusion-based therapies.

Time trends in herpesvirus seroepidemiology among Swedish adults.

BACKGROUND: Human herpesviruses are widespread among the human population. The infections often occur unnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence varies among subpopulations and with time. The aim of this study was to describe the seroprevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish population over a time period of several decades. METHODS: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old men and 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibodies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linear regression analysis was used to differentiate between other factors such as age and gender. RESULTS: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1 and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus (p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the prevalence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women, and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011). CONCLUSIONS: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virus decreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a child and adolescent.

Traditionally removed mandibular central incisors and oral health-related quality of life: a cross-sectional study among adolescents in Maasai populated areas, Northern Tanzania.

BACKGROUND: The traditional removal of mandibular anterior teeth has been existing for many years in the Sub-Saharan African countries. This study aimed to assess the prevalence and sociodemographic distribution of traditionally removed mandibular central incisors (TRMCI) and its association with oral impact on daily performance (OIDP) among adolescents in Maasai populated areas in the Northern part of Tanzania. METHODS: Using a two-stage cluster sample design, with schools as the primary sampling unit, 23 out of 66 eligible rural schools were randomly selected. From each selected school, one class, expected to contain adolescents aged 12-14 years, was identified. The students from these selected classes were invited to participate in the study. A total of 989 adolescents were invited and 906 (91.6%) accepted to participate and completed both an interview and a clinical oral examination. RESULTS: Mean age was 13.4 years (12-17 years, SD 1.2) and 43.9% were males (n = 398). The participants from Longido district amounted to 47.1%. The Maasai group constituted 79.6% of the study participants. The frequency of the participants missing at least one mandibular central incisor were 18.5%. Multivariable logistic regression revealed that adolescents from Longido district were more likely to report at least one TRMCI (OR = 2.5, 95% CI 1.4-3.3). Adolescents from non-Maasai group were less likely to have atleast one TRMCI compared to adolescents from Maasai ethnic group (OR = 0.02, 95% CI 0.002-0.15). Adolescents with at least one TRMCI were more likely to report impacts on OIDP (OR = 3.3, 95% CI 1.9-5.7) than those without TRMCI. Independent of the TRMCI status, adolescents from Longido district were less likely than their counterparts to report oral impacts (OR = 0.4, 95% CI 0.2-0.6). Similarly, adolescents from non-Masaai group were more likely than their counterparts to report oral impacts (OR = 2.2, 95% CI 1.4-3.5). CONCLUSION: TRMCI is common among adolescents in the Maasai populated areas in the Northern part of Tanzania and strongly associated with the district of residence and Maasai ethnicity and has a negative impact on oral health related quality of life. There is a need for oral health education in the rural Maasai communities in Tanzania to increase awareness of the negative consequences of this practice.

Periodontal microbiology and microbial etiology of periodontal diseases: Historical concepts and contemporary perspectives.

This narrative review summarizes the collective knowledge on periodontal microbiology, through a historical timeline that highlights the European contribution in the global field. The etiological concepts on periodontal disease culminate to the ecological plaque hypothesis and its dysbiosis-centered interpretation. Reference is made to anerobic microbiology and to the discovery of select periodontal pathogens and their virulence factors, as well as to biofilms. The evolution of contemporary molecular methods and high-throughput platforms is highlighted in appreciating the breadth and depth of the periodontal microbiome. Finally clinical microbiology is brought into perspective with the contribution of different microbial species in periodontal diagnosis, the combination of microbial and host biomarkers for this purpose, and the use of antimicrobials in the treatment of the disease.

At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study.

BackgroundThe current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.AimThe aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.MethodsWe developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.ResultsWe demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.ConclusionImplementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.

Analysis of landing noise from Airbus A321neo using long term noise measurements and flight recorder data.

This article analyzes aircraft noise measurements from the Airbus A321neo at 7.5 and 5 nautical miles from the runway threshold. Using correlation, analysis of variance, and hierarchical regression analysis, we assessed the influence of flight data recorder variables and meteorological parameters on the measured sound level variations. A combination of aircraft speed and configuration of the high lift devices can predict approximately 60% of the sound level variations. Sound level dependence on speed ranges between 0.5 and 1.5 dB/10 kn for different configurations and landing gear deployment had a +3 dB impact on sound levels. At the same time, weather and wind conditions accounted for a relatively small proportion of the variation. Overall, this study sheds light on the factors contributing to aircraft noise during the final approach and provides insights into potential noise reduction strategies.

Xerostomia in 75-85-year-olds: A longitudinal population study.

BACKGROUND: Xerostomia can pose significant problems for many elderly people. OBJECTIVES: To investigate longitudinal changes in prevalence, persistence, progression, remission and incidence of xerostomia from age 75 to 85 years. METHODS: All 75-year-olds (born 1932) from two Swedish counties, Sweden were mailed a questionnaire in 2007 (N = 5195), and again in 2017 when they were aged 85 (N = 3323). The total response rates at ages 75 and 85 years were 71.9% and 60.8%, respectively. A 'panel', those who participated in both surveys, comprised 1701 individuals (response rate 51.2%). RESULTS: At age 85, there was almost a doubling of self-reported 'yes often' xerostomia compared with age 75 (from 6.2% to 11.3%) and was almost twice as common in women than men (p < .001). When combining 'yes often'/'yes sometimes', xerostomia increased from 33.4% to 49.0%, and was more so among women (p < .001). Xerostomia was commoner at night than daytime, with 23.4% reporting 'yes often' night-time xerostomia at 85 compared with 18.5% at 75, and was also higher in women (p < .001). Progression rates for daytime and night-time xerostomia were 34.2% and 38.1%, for persistence 67.4% and 68.6%, and for remission 24.4% and 16.5%. Average yearly incidence was higher in women than men for both daytime (3.6% vs. 3.2%) and night-time (3.9% vs. 3.7%). Regression analyses predicted protective factors for developing xerostomia reported at age 75 as good general and oral health, absence of medications/intraoral symptom/s, good chewing function and social interaction. CONCLUSIONS: Xerostomia increases markedly from age 75 to 85 years.

Pilus PilA of the naturally competent HACEK group pathogen Aggregatibacter actinomycetemcomitans stimulates human leukocytes and interacts with both DNA and proinflammatory cytokines.

Each HACEK group pathogen, which can cause infective endocarditis, expresses type IVa pili. The type IVa major pilin PilA plays a role in bacterial colonization, virulence, twitching motility, and the uptake of extracellular DNA. The type IV prepilin homolog PilA of the periodontal pathogen A. actinomycetemcomitans (AaPilA) is linked to DNA uptake and natural competence. Our aim was to investigate the virulence properties and immunogenic potential of AaPilA. Since Neisseria meningitidis PilE, which shares sequence similarity with AaPilA, participates in sequestering host cytokines, we examined the ability of AaPilA to interact with various cytokines. Moreover, we investigated the structural characteristics of AaPilA with molecular modeling. AaPilA was conserved among A. actinomycetemcomitans strains. One of the 18 different natural variants, PilAD7S, is present in naturally competent strains. This variant interacted with DNA and bound interleukin (IL)-8 and tumor necrosis factor (TNF)-α. Specific anti-AaPilA antibodies were present in A. actinomycetemcomitans-positive periodontitis patient sera, and the production of reactive oxygen species from human neutrophils was less effectively induced by the ΔpilA mutant than by the wild-type strains. However, AaPilA did not stimulate human macrophages to produce proinflammatory cytokines, nor was it cytotoxic. The results strengthen our earlier hypothesis that the DNA uptake machinery of A. actinomycetemcomitans is involved in the sequestration of inflammatory cytokines. Furthermore, AaPilA stimulates host immune cells, such as B cells and neutrophils, making it a potential virulence factor.

Partner perceptions are associated with objective sensor-measured adherence to oral appliance therapy in obstructive sleep apnea.

The aims of the present prospective clinical study were to determine objective, sensor-measured adherence to a mandibular advancement device (MAD) in patients with obstructive sleep apnea (OSA) and to identify partner-specific adherence-related factors. A total of 77 eligible participants with mild, moderate, or severe OSA and who were non-adherent to continuous positive airway pressure (mean age 56.2 years) participated in the study (32.5% women). The mean (range) observation time between MAD delivery and final follow-up was 8.3 (3.4-16.5) months. The mean apnea-hypopnea index (AHI) was 26.6 events/hr at baseline and 12.5 events/hr at the 8-month follow-up (both p < 0.001). The mean sensor-measured adherence at the 8-month follow-up was 60.1% for ≥4 hr/night of appliance use for ≥5 days/week. Average usage was 6.4 hr/night, when worn. The mean reduction in the AHI was significantly greater in the "good adherence" (Δ 17.4) than the "poor adherence" group (Δ11.0; p < 0.05). From the partner's perspective, the appliance had a positive effect on sharing a bedroom in the good- (55%) compared to the poor-adherence group (25%; p < 0.05) and on their relationship (51.7% versus 17.9%, respectively; p < 0.05). Regression analyses identified the partner's snoring and apneas to be the most significant factor predicting good adherence to MAD (odds ratio 4.4, 95% confidence interval 1.4-14.0). In conclusion, social factors, like partner perceptions, were positively associated with adherence, which indicate that partner's attitudes and support may be a resource that can be utilised to improve adherence in oral appliance treatment of OSA.

Heterogeneity of Staphylococcus epidermidis in prosthetic joint infections: time to reevaluate microbiological criteria?

Prosthetic joint infection (PJI) is a feared and challenging to diagnose complication after arthroplasty, with Staphylococcus epidermidis as the major pathogen. One important criteria to define PJI is the detection of phenotypically indistinguishable microorganisms with identical antibiotic susceptibility pattern in at least two different samples. However, owing to phenotypical variation within genetic clones and clonal variation within a phenotype, the criteria may be ambiguous. We investigated the extent of diversity among coagulase-negative staphylococci (CoNS) in PJI and characterised S. epidermidis isolates from PJI samples, specifically multiple S. epidermidis isolates identified in individual PJI patients. We performed a retrospective cohort study on 62 consecutive patients with PJI caused by CoNS from two hospitals in Northern Sweden. In 16/62 (26%) PJIs, multiple S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in samples from 40/62 (65%) of the patients using a combination of pulsed-field gel electrophoresis and multilocus sequence typing. Whole-genome sequencing showed the presence of multiple sequence types (STs) in 7/16 (44%) PJIs where multiple S. epidermidis isolates were available. Within-patient phenotypical variation in the antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%) among isolates with the same ST. The results highlight the ambiguity of S. epidermidis phenotypic characterisation as a diagnostic method in PJI and call for larger systematic studies for determining the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and the therapeutic outcomes in patients.

An Ig γ Marker Genotype Is a Strong Risk Factor for Alzheimer Disease, Independent of Apolipoprotein E ε4 Genotype.

Increasing evidence implicates HSV type 1 (HSV1) in the pathogenesis of late-onset Alzheimer disease (AD). HSV1 has evolved highly sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fcγ receptor (FcγR), which blocks Fc-mediated effector functions, such as Ab-dependent cellular cytotoxicity. Ig γ marker (GM) allotypes, encoded by highly polymorphic IGHG genes on chromosome 14q32, modulate this immunoevasion strategy, and thus may act as effect modifiers of the HSV1-AD association. In this nested case-control human study, 365 closely matched case-control pairs-whose blood was drawn on average 9.6 y before AD diagnosis-were typed for GM alleles by a TaqMan genotyping assay. APOE genotype and a genetic risk score based on nine additional previously known AD risk genes (ABCA7, BIN1, CD33, CLU, CR1, EPHA1, MS4A4E, NECTIN2, and PICALM) were extracted from a genome-wide association study analysis. Antiviral Abs were measured by ELISA. Conditional logistic regression models were applied. The distribution of GM 3/17 genotypes differed significantly between AD cases and controls, with higher frequency of GM 17/17 homozygotes in AD cases as compared with controls (19.8 versus 10.7%, p = 0.001). The GM 17/17 genotype was associated with a 4-fold increased risk of AD (odds ratio 4.142, p < 0.001). In conclusion, the results of this study demonstrate that Ig GM 17/17 genotype contributes to the risk of later AD development, independent of apolipoprotein ε4 genotype and other AD risk genes, and explain, at least in part, why every HSV1-infected person is not equally likely to develop HSV1-associated AD.

Eating Disorders: An Analysis of Self-Induced Vomiting, Binge Eating, and Oral Hygiene Behavior.

Background: Self-induced vomiting (SIV) is often present in patients with eating disorders (ED) and potentially damaging for oral health. Related behaviors, such as binge eating and oral hygiene habits, may equally increase the risk for dental damage. This study aimed to investigate behaviors and habits in patients with ED and SIV in relation to oral health. Methods: All patients enlisting for treatment in an ED clinic for 1 year were offered to take part in the study. Fifty-four of 65 patients were accepted to participate, and a questionnaire included questions on dietary and oral hygiene habits was included. A subgroup consisting of only those 17 ED patients who reported SIV during the previous six months comprised the sample for this study and received additional questions related to other compensatory behaviors and oral hygiene habits in relation to oral health. Results: Binge eating before SIV was common (14/17 patients). Time point for SIV after binge eating and the procedures performed after vomiting varied. Tooth brushing after vomiting was common (7/17). Food and drinks during binge eating included mainly items rich in calories (sugar/fat) or acid. All 17 patients believed that vomiting could damage their teeth, but only one of them had informed the dentist about having an ED. A number of oral symptoms were reported. Ten patients considered their oral health to be good/fairly good, while the remaining seven patients reported their oral health as not so good/bad/very bad. Information on how ED could affect their teeth was commonly received from the media. Conclusions: The dental team should be made aware of the likely detrimental effects of binge eating and vomiting on oral health in patients with eating disorders. The team should also be aware of the cyclical nature of the disease and the similarities and diversities that exist within this group of ED patients. Since ED patients hide their disease from the dental team, this stresses the importance of open and trustful communication between patients and health workers. An organized collaboration between ED clinics and dental professionals is suggested as well as a development of avenues for information about ED and oral health.

Satisfaction with dental appearance in two cohorts of 75-year-olds examined in 2007 and 2017: A repeated cross-sectional study.

BACKGROUND: Satisfaction with dental appearance plays an important role in the self-esteem and psychological well-being of the elderly, the significance of which the attending dentist may not always be fully cognisant of. OBJECTIVES: To assess the level of satisfaction with dental appearance, its associated factors and temporal changes in two cohorts of 75-year-old Swedes born 10 years apart. METHODS: In 2007, a questionnaire was mailed to all those living in Örebro and Östergötland counties, Sweden, who were born in 1932 (n = 5195), and in 2017 to all born in 1942 (n = 7204). The evaluation was carried out with a global question 'Are you satisfied with the appearance of your teeth?', and four attitude-related statements about dental appearance. RESULTS: About 80% in both cohorts were 'very satisfied' or 'to large extent satisfied' with their dental appearance. The 1932 cohort was significantly more concerned about their dental appearance than the 1942 cohort, and women were generally also significantly more concerned than men. In the regression analysis, 'very satisfied' with dental appearance was predicted by good chewing efficiency, having complete dentures, no impact from Oral Impacts on Daily Performance, disagreement that 'minor esthetic imperfections of the teeth have no importance, only they should function well', better perceived general health than same-aged peers and belonging to the 1932 cohort. CONCLUSION: Satisfaction with dental appearance among 75-year-olds was generally high, with attitudes varying by gender and temporally. Women and the earlier-born generation (1932) were more concerned about dental appearance than men and the later-born generation (1942), respectively.

Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments.

Francisella tularensis, the causative agent of the zoonotic disease tularemia, can cause seasonal outbreaks of acute febrile illness in humans with disease peaks in late summer to autumn. Interestingly, its mechanisms for environmental persistence between outbreaks are poorly understood. One hypothesis is that F. tularensis forms biofilms in aquatic environments. We utilized two fully virulent wild-type strains: FSC200 (Francisella tularensis subsp. holarctica) and Schu S4 (Francisella tularensis subsp. tularensis) and three control strains, the attenuated live vaccine strain (LVS; F. tularensis subsp. holarctica), a Schu S4 ΔwbtI mutant that is documented to form biofilms, and the low-virulence strain U112 of the closely related species Francisella novicida Strains were incubated in saline solution (0.9% NaCl) microcosms for 24 weeks at both 4°C and 20°C, whereupon viability and biofilm formation were measured. These temperatures were selected to approximate winter and summer temperatures of fresh water in Scandinavia, respectively. U112 and Schu S4 ΔwbtI formed biofilms, but F. tularensis strains FSC200 and Schu S4 and the LVS did not. All strains exhibited prolonged viability at 4°C compared to 20°C. U112 and FSC200 displayed remarkable long-term persistence at 4°C, with only 1- and 2-fold log reductions, respectively, of viable cells after 24 weeks. Schu S4 exhibited lower survival, yielding no viable cells by week 20. At 24 weeks, cells from FSC200, but not from Schu S4, were still fully virulent in mice. Taken together, these results demonstrate biofilm-independent, long-term survival of pathogenic F. tularensis subsp. holarctica in conditions that mimic overwinter survival in aquatic environments.IMPORTANCE Tularemia, a disease caused by the environmental bacterium Francisella tularensis, is characterized by acute febrile illness. F. tularensis is highly infectious: as few as 10 organisms can cause human disease. Tularemia is not known to be spread from person to person. Rather, all human infections are independently acquired from the environment via the bite of blood-feeding arthropods, ingestion of infected food or water, or inhalation of aerosolized bacteria. Despite the environmental origins of human disease events, the ecological factors governing the long-term persistence of F. tularensis in nature between seasonal human outbreaks are poorly understood. The significance of our research is in identifying conditions that promote long-term survival of fully virulent F. tularensis outside a mammalian host or insect vector. These conditions are similar to those found in natural aquatic environments in winter and provide important new insights on how F. tularensis may persist long-term in the environment.

Francisella tularensis human infections in a village of northwest Iran.

BACKGROUND: Recent seroepidemiological studies have suggested that tularemia could be an endemic bacterial zoonosis in Iran. METHODS: From January 2016 to June 2018, disease cases characterized by fever, cervical lymphadenopathy and ocular involvement were reported in Youzband Village of Kaleybar County, in the East Azerbaijan Province, northwestern Iran. Diagnostic tests included Francisella tularensis serology (including tube agglutination test and ELISA), PCR, and culture. RESULTS: Among 11 examined case-patients, the tularemia tube agglutination test was positive in ten and borderline in one. PCR detected the F. tularensis ISFtu2 elements and fopA gene in one rodent and a spring water sample from the same geographic area. CONCLUSIONS: Based on the clinical manifestations of the disease suggesting an oropharyngeal form of tularemia, serology results in case patients, and F. tularensis detection in the local fauna and aquatic environment, the water supply of the village was the likely source of the tularemia outbreak. Intervention such as dredging and chlorination of the main water storage tank of the village and training of villagers and health care workers in preventive measures and treatment of the illness helped control the infection.

Experience of using video support by prehospital emergency care physician in ambulance care - an interview study with prehospital emergency nurses in Sweden.

INTRODUCTION: When in need of emergency care and ambulance services, the ambulance nurse is often the first point of contact for the patient with healthcare. This role requires comprehensive knowledge of the ambulance nurse to be able to assign the right level of care and, if necessary, to provide self-care advice for patients with no further conveyance to hospital. Recently, an application was developed for transmitting real-time video to facilitate consultation between ambulance nurses and prehospital physicians in the role of regional medical support (RMS) for ambulance care. The use of video communication as a complement of medical support when referring to self-care is still an unexplored method in a prehospital setting. Our study aimed to elucidate ambulance nurses' experience of video consultation with RMS physician during the assessment of patients considered to be triaged to self-care. METHOD: We conducted a qualitative design study using semi-structured interviews with open questions. Twelve ambulance nurses were included in the study. To explore the ambulance nurses' experience of performing video consultation with RMS physician, in cases when a patient was assessed and triaged to self-care, a content analysis was performed. RESULTS: A main category emerged from the results: " Video consultation as decision support in the ambulance care promotes increased patient participation and for the ambulance nurses, it creates a feeling of increased patient safety ". The main category was based and formed on the following categories: " Simultaneous presence of ambulance nurse and a physician increases patient participation during the assessment resulting in a confident care decision ". "Interprofessional collaboration strengthens the medical assessment". "Video technology promotes accessibility for patients needs in the ambulance care regardless of emergency level". CONCLUSIONS: Ambulance nurses experienced that the use of video consultation increases patient involvement and confidence in healthcare when both the ambulance nurse and the physician were present when deciding on self-care advice. The live imaging allowed the ambulance nurse and prehospital physician to reach a consensus on the patient's current medical care needs, which in turn led to a feeling of increased patient safety for the ambulance nurses.

Acoustic pharyngometry - A new method to facilitate oral appliance therapy.

BACKGROUND: There is lack of reliable and accurate methods to predict treatment outcomes of oral appliance (OA) treatment. Acoustic pharyngometry (AP) is a non-invasive technique to evaluate the volume and minimal cross-sectional area of the upper airway, which may prove useful to locate the optimal position of OAs. OBJECTIVE: This retrospective study aimed to evaluate the effect of applying AP to OA treatment of patients with obstructive sleep apnoea (OSA). METHODS: All patients (n = 244) treated with OAs following an AP protocol at two dental clinics between 2013 and 2018 were invited to participate. A total of 129 patients accepted the invitation, and 120 patients (75 men, 45 women) were included in the analyses. Mean baseline age, BMI and apnoea hypopnea index (AHI) were 59.1 ± 0.9 years, 27.8 ± 0.4 and 21.9 ± 1.1, respectively. Mean follow-up time was 318 ± 24 days. RESULTS: AHI at follow-up was 6.4 ± 0.7, resulting in a treatment success rate of 86.7% (≥50% reduction of baseline AHI). The number of failures (<50% reduction of baseline AHI) did not differ significantly among patients with mild, moderate and severe OSA. 87.6% of the patients reported OA usage every night, and 95.5% reported > 5 hours usage per night, when worn. CONCLUSION: The AP protocol applied seems to contribute to the excellent effect of OA treatment in this study. Further research on the application of AP in OA treatment is necessary in order to clarify its possible beneficial contribution to improving OA therapy.