Personalized Microbial Fingerprint Associated with Differential Glycemic Effects of a Whole Grain Rye Intervention on Chinese Adults.

SCOPE: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an "enterotype - metabolic" model. METHODS AND RESULTS: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7ß-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis. CONCLUSION: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.

Prevalence of Subgingival Aggregatibacter actinomycetemcomitans: Descriptive Cross-Sectional Study.

This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. The identification of A. actinomycetemcomitans was performed using quantitative polymerase chain reaction. A descriptive analysis, a chi-square test, and a binary logistic regression statistical evaluation were performed. The prevalence of A. actinomycetemcomitans in this population of 156 participants was 17.30% (27 patients). The prevalence of stage-III periodontitis was 75.6% and greater in older men, while the prevalence of stage-IV periodontitis was 22.4% and greater in younger women. We observed a significant relation between the risk of severe periodontitis (stage-IV) and poor oral hygiene (p = 0.006), attendance at dental appointments (p ≤ 0.001), and familial history of periodontitis (p = 0.032). In conclusion, twenty-seven individuals were positive for A. actinomycetemcomitans. Poor oral hygiene, family history of periodontitis, and irregular attendance at dental appointments were identified as potential risk factors for severe periodontitis in this cohort.

Leukotoxin A Production and Release by JP2 and Non-JP2 Genotype Aggregatibacter actinomycetemcomitans in Relation to Culture Conditions.

Aggressive forms of periodontitis, especially in young patients, are often associated with an increased proportion of the Gram-negative bacterium Aggregatibacter actinomycetemcomitans of the microbiota of the affected periodontal sites. One of the virulence factors of A. actinomycetemcomitans is a leukotoxin (LtxA) that induces a pro-inflammatory cell death process in leukocytes. A. actinomycetemcomitans exhibits a large genetic diversity and different genotypes vary in LtxA production capacity. The genotype JP2 is a heavy LtxA producer due to a 530-base pair deletion in the promoter for the toxin genes, and this trait has been associated with an increased pathogenic potential. The present study focused on the production and release of LtxA by different A. actinomycetemcomitans genotypes and serotypes under various growth conditions. Four different strains of this bacterium were cultured in two different culture broths, and the amount of LtxA bound to the bacterial surface or released into the broths was determined. The cultures were examined during the logarithmic and the early stationary phases of growth. The JP2 genotype exhibited the highest LtxA production among the strains tested, and production was not affected by the growth phase. The opposite was observed with the other strains. The composition of the culture broth had no effect on the growth pattern of the tested strains. However, the abundant release of LtxA from the bacterial surface into the culture broth was found in the presence of horse serum. Besides confirming the enhanced leucotoxicity of the JP2 genotype, the study provides new data on LtxA production in the logarithmic and stationary phases of growth and the effect of media composition on the release of the toxin from the bacterial membrane.

Transferability and Accuracy of Ionic Liquid Simulations with Equivariant Machine Learning Interatomic Potentials.

Ionic liquids (ILs) are an exciting class of electrolytes finding applications in many areas from energy storage to solvents, where they have been touted as "designer solvents" as they can be mixed to precisely tailor the physiochemical properties. As using machine learning interatomic potentials (MLIPs) to simulate ILs is still relatively unexplored, several questions need to be answered to see if MLIPs can be transformative for ILs. Since ILs are often not pure, but are either mixed together or contain additives, we first demonstrate that a MLIP can be trained to be compositionally transferable; i.e., the MLIP can be applied to mixtures of ions not directly trained on, while only being trained on a few mixtures of the same ions. We also investigated the accuracy of MLIPs for a novel IL, which we experimentally synthesize and characterize. Our MLIP trained on ∼200 DFT frames is in reasonable agreement with our experiments and DFT.

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.

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.

Automated surveillance of antimicrobial consumption in intensive care, northern Sweden: an observational case study.

BACKGROUND: The digitalization of information systems allows automatic measurement of antimicrobial consumption (AMC), helping address antibiotic resistance from inappropriate drug use without compromising patient safety. OBJECTIVES: Describe and characterize a new automated AMC surveillance service for intensive care units (ICUs), with data stratified by referral clinic and linked with individual patient risk factors, disease severity, and mortality. METHODS: An automated service collecting data from the electronic medical record was developed, implemented, and validated in a healthcare region in northern Sweden. We performed an observational study from January 1, 2018, to December 31, 2021, encompassing general ICU care for all ≥18-years-olds in a catchment population of 270000 in secondary care and 900000 in tertiary care. We used descriptive analyses to associate ICU population characteristics with AMC outcomes over time, including days of therapy (DOT), length of therapy, defined daily doses, and mortality. RESULTS: There were 5608 admissions among 5190 patients with a median age of 65 (IQR 48-75) years, 41.2% females. The 30-day mortality was 18.3%. Total AMC was 1177 DOTs in secondary and 1261 DOTs per 1000 patient days and tertiary care. AMC varied significantly among referral clinics, with the highest total among 810 general surgery admissions in tertiary care at 1486 DOTs per 1000 patient days. Case-mix effects on the AMC were apparent during COVID-19 waves highlighting the need to account for case-mix. Patients exposed to more than three antimicrobial drug classes (N = 242) had a 30-day mortality rate of 40.6%, with significant variability in their expected rates based on admission scores. CONCLUSION: We introduce a new service and instructions for automating local ICU-AMC data collection. The versatile long-term ICU-AMC metrics presented, covering patient factors, referral clinics and mortality outcomes, are expected to be beneficial in refining antimicrobial drug use.

Motor Efficacy of Subcutaneous DIZ102, Intravenous DIZ101 or Intestinal Levodopa/Carbidopa Infusion.

BACKGROUND: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. OBJECTIVES: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. METHODS: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). RESULTS: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. CONCLUSION: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.

Presence and Immunoreactivity of Aggregatibacter actinomycetemcomitans in Rheumatoid Arthritis.

The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present study is to examine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium. The salivary presence of Aa was analyzed with quantitative PCR and serum LtxA ab in a cell culture-based neutralization assay. The analyses were performed on samples from a well-characterized RA cohort (n = 189) and a reference population of blood donors (n = 101). Salivary Aa was present in 15% of the RA patients and 6% of the blood donors. LtxA ab were detected in 19% of RA-sera and in 16% of sera from blood donors. The correlation between salivary Aa and serum LtxA ab was surprisingly low (rho = 0.55 [95% CI: 0.40, 0.68]). The presence of salivary Aa showed no significant association with any of the RA-associated parameters documented in the cohort. A limitation of the present study is the relatively low number of individuals with detectable concentrations of Aa in saliva. Moreover, in the comparison of detectable Aa prevalence between RA patients and blood donors, we assumed that the two groups were equivalent in other Aa prognostic factors. These limitations must be taken into consideration when the result from the study is interpreted. We conclude that a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. In addition, the association between RA-associated parameters and the presence of Aa was negligible in the present RA cohort.

Low-index mesoscopic surface reconstructions of Au surfaces using Bayesian force fields.

Metal surfaces have long been known to reconstruct, significantly influencing their structural and catalytic properties. Many key mechanistic aspects of these subtle transformations remain poorly understood due to limitations of previous simulation approaches. Using active learning of Bayesian machine-learned force fields trained from ab initio calculations, we enable large-scale molecular dynamics simulations to describe the thermodynamics and time evolution of the low-index mesoscopic surface reconstructions of Au (e.g., the Au(111)-'Herringbone,' Au(110)-(1 × 2)-'Missing-Row,' and Au(100)-'Quasi-Hexagonal' reconstructions). This capability yields direct atomistic understanding of the dynamic emergence of these surface states from their initial facets, providing previously inaccessible information such as nucleation kinetics and a complete mechanistic interpretation of reconstruction under the effects of strain and local deviations from the original stoichiometry. We successfully reproduce previous experimental observations of reconstructions on pristine surfaces and provide quantitative predictions of the emergence of spinodal decomposition and localized reconstruction in response to strain at non-ideal stoichiometries. A unified mechanistic explanation is presented of the kinetic and thermodynamic factors driving surface reconstruction. Furthermore, we study surface reconstructions on Au nanoparticles, where characteristic (111) and (100) reconstructions spontaneously appear on a variety of high-symmetry particle morphologies.

Bacterial symbionts in oral niche use type VI secretion nanomachinery for fitness increase against pathobionts.

Microbial ecosystems experience spatial and nutrient restrictions leading to the coevolution of cooperation and competition among cohabiting species. To increase their fitness for survival, bacteria exploit machinery to antagonizing rival species upon close contact. As such, the bacterial type VI secretion system (T6SS) nanomachinery, typically expressed by pathobionts, can transport proteins directly into eukaryotic or prokaryotic cells, consequently killing cohabiting competitors. Here, we demonstrate for the first time that oral symbiont Aggregatibacter aphrophilus possesses a T6SS and can eliminate its close relative oral pathobiont Aggregatibacter actinomycetemcomitans using its T6SS. These findings bring nearer the anti-bacterial prospects of symbionts against cohabiting pathobionts while introducing the presence of an active T6SS in the oral cavity.

Association of Filifactor alocis and its RTX toxin gene ftxA with periodontal attachment loss, and in synergy with Aggregatibacter actinomycetemcomitans.

The Gram-positive bacterium, Filifactor alocis is an oral pathogen, and approximately 50% of known strains encode a recently identified repeat-in-toxin (RTX) protein, FtxA. By assessing a longitudinal Ghanaian study population of adolescents (10-19 years of age; mean age 13.2 years), we recently discovered a possible correlation between deep periodontal pockets measured at the two-year follow-up, presence of the ftxA gene, and a high quantity of F. alocis. To further understand the contribution of F. alocis and FtxA in periodontal disease, we used qPCR in the present study to assess the carriage loads of F. alocis and the prevalence of its ftxA gene in subgingival plaque specimens, sampled at baseline from the Ghanaian cohort (n=500). Comparing these results with the recorded clinical attachment loss (CAL) longitudinal progression data from the two-year follow up, we concluded that carriers of ftxA-positive F. alocis typically exhibited higher loads of the bacterium. Moreover, high carriage loads of F. alocis and concomitant presence of the ftxA gene were two factors that were both associated with an enhanced prevalence of CAL progression. Interestingly, CAL progression appeared to be further promoted upon the simultaneous presence of F. alocis and the non-JP2 genotype of Aggregatibacter actinomycetemcomitans. Taken together, our present findings are consistent with the notion that F. alocis and its ftxA gene promotes CAL during periodontal disease.

Integrated Proteomics Characterization of NLRP3 Inflammasome Inhibitor MCC950 in Monocytic Cell Line Confirms Direct MCC950 Engagement with Endogenous NLRP3.

Inhibition of the NLRP3 inflammasome is a promising strategy for the development of new treatments for inflammatory diseases. MCC950 is a potent and selective small-molecule inhibitor of the NLRP3 pathway and has been validated in numerous species and disease models. Although the capacity of MCC950 to block NLRP3 signaling is well-established, it is still critical to identify the mechanism of action and molecular targets of MCC950 to inform and derisk drug development. Quantitative proteomics performed in disease-relevant systems provides a powerful method to study both direct and indirect pharmacological responses to small molecules to elucidate the mechanism of action and confirm target engagement. A comprehensive target deconvolution campaign requires the use of complementary chemical biology techniques. Here we applied two orthogonal chemical biology techniques: compressed Cellular Thermal Shift Assay (CETSA) and photoaffinity labeling chemoproteomics, performed under biologically relevant conditions with LPS-primed THP-1 cells, thereby deconvoluting, for the first time, the molecular targets of MCC950 using chemical biology techniques. In-cell chemoproteomics with inlysate CETSA confirmed the suspected mechanism as the disruption of inflammasome formation via NLRP3. Further cCETSA (c indicates compressed) in live cells mapped the stabilization of NLRP3 inflammasome pathway proteins, highlighting modulation of the targeted pathway. This is the first evidence of direct MCC950 engagement with endogenous NLRP3 in a human macrophage cellular system using discovery proteomics chemical biology techniques, providing critical information for inflammasome studies.

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.

Change in health-related quality of life at early follow-up in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Symptoms associated with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) impact patient's health-related quality of life (HRQoL). Studies on change and if a minimal clinically important difference (MCID) in HRQoL is reached within a year after diagnosis are lacking. The aim was to investigate the change in HRQoL as well as the proportion of patients that reached MCID at an early postdiagnosis visit. The study included adult patients from the Swedish PAH & CTEPH registry, diagnosed 2008-2021, with Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) at time of diagnosis and a follow-up. Data were analyzed as total population and dichotomized for sex, age (<65 vs. ≥65 years), time of diagnosis (≤2015 vs. >2015) and pulmonary hypertension (PH) subgroups. Data reported as median, interquartile range (IQR), and proportions (%). There were 151 patients (PAH = 119, CTEPH = 32) with an available CAMPHOR score at diagnosis and follow-up. CAMPHOR total sum was 31 (IQR: 21-43) and 25 (14-36); (p < 0.001) at diagnosis and follow-up, respectively. At follow-up, 56% had reached MCID in total sum, while for domains activity, symptoms, and QoL 27%, 33%, and 39% reached MCID, respectively. These results were independent of PH subgroup, diagnosis before or after 2015 and sex. Age below 65 years was related to improvements in activity and worsening of symptoms. In conclusion on a group level, improvements in CAMPHOR total sum as well as all domains were seen in the first year after diagnosis, however, only slightly more than half of the patients reached MCID for CAMPHOR total sum.

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.

General and orofacial symptoms associated with acute and long COVID in 80- and 90-year-old Swedish COVID-19 survivors.

OBJECTIVES: To describe acute and long COVID-19 symptoms among older elderly Swedes and to find predictive factors for the development symptoms associated with acute and long COVID. MATERIAL AND METHODS: A questionnaire about general and oral health was mailed to all 80-year-olds (born 1942, n = 6299) and 90-year-olds (born 1932, n = 1904) in two Swedish counties. Participants reporting COVID-19 were asked to complete an additional questionnaire. RESULTS: Overall response rate was 66 % (n = 5375). Affirmative responses to having been sick/tested positive for COVID-19 were reported by 577 persons. Response rate to the COVID-19 questionnaire was 49 %. The majority (88 %) reported some general symptoms during the acute stage while 44 % reported orofacial symptom/s. Reporting of any form of long-COVID general symptoms was 37 and 35 % for orofacial symptoms. Predictive factors for contracting COVID-19 (based on self-report from 2017) were living in elderly housing/senior care facility (OR 1.6, CI 1.0-2.3), large number (>10) of weekly social contacts (OR 1.5, CI 1.3-1.9), being married (OR 1.4, CI 1.1-1.7) and high school/university education (OR 1.3 CI 1.1-1-6). The highest odds ratio for general symptoms of long-COVID were a single complete denture (OR 5.0, CI 2.0-12.3), reporting bad breath (OR 3.7, CI 1.9-7.2) and daytime dry mouth (OR 2.2, CI 1.1-4.2). Regarding long-COVID orofacial symptoms, the highest risk factors were bad breath (OR 3.8, CI 1.9-7.5) and a single complete denture in one jaw (OR 3.4, CI 1.2-9.8). CONCLUSION: Long-COVID general and orofacial symptoms are common among older elderly COVID-19 survivors CLINICAL SIGNIFICANCE: Oral microorganisms may be responsible for development of long-COVID symptoms. Health personnel managing COVID-19 patients should carefully examine dental status, especially in those having acrylic-based removable dentures, for oral signs and symptoms. If found, rigorous oral hygiene procedures should be carried out including cleaning/disinfection of the denture.

Proximity-sensors on GPS collars reveal fine-scale predator-prey behavior during a predation event: A case study from Scandinavia.

Although the advent of high-resolution GPS tracking technology has helped increase our understanding of individual and multispecies behavior in wildlife systems, detecting and recording direct interactions between free-ranging animals remains difficult. In 2023, we deployed GPS collars equipped with proximity sensors (GPS proximity collars) on brown bears (Ursus arctos) and moose (Alces alces) as part of a multispecies interaction study in central Sweden. On 6 June, 2023, a collar on an adult female moose and a collar on an adult male bear triggered each other's UHF signal and started collecting fine-scale GPS positioning data. The moose collar collected positions every 2 min for 89 min, and the bear collar collected positions every 1 min for 41 min. On 8 June, field personnel visited the site and found a female neonate moose carcass with clear indications of bear bite marks on the head and neck. During the predation event, the bear remained at the carcass while the moose moved back and forth, moving toward the carcass site about five times. The moose was observed via drone with two calves on 24 May and with only one remaining calf on 9 June. This case study describes, to the best of our knowledge, the first instance of a predation event between two free ranging, wild species recorded by GPS proximity collars. Both collars successfully triggered and switched to finer-scaled GPS fix rates when the individuals were in close proximity, producing detailed movement data for both predator and prey during and after a predation event. We suggest that, combined with standard field methodology, GPS proximity collars placed on free-ranging animals offer the ability for researchers to observe direct interactions between multiple individuals and species in the wild without the need for direct visual observation.