Karolinska Institutet
  • Stockholm, Sweden
Recent publications
Diarrheal disease pathogens often spread through water-borne routes. Enterotoxigenic Escherichia coli (ETEC) is a major bacterial agent causing diarrheal disease in children, adults, and travelers in endemic areas. In addition, ETEC is responsible for outbreaks of water and food-borne gasteroenteritis globally, ETEC isolates also show robust survival capacity in various environmental settings, including aquatic environments. During the last decade, studies of ETEC isolates have indicated a rapid increase in multi-drug resistant and extended-spectrum β-lactamase (ESBL)-positive human-specific ETEC strains. These have been found in both environmental water sources and human patients, warranting the urgent need for focused monitoring of antibiotic resistance development in ETEC. Whole genome sequencing (WGS) of isolates from environmental, animal, and human sources enables in silico surveillance of emerging pathogenic and multi-drug resistant strains. This method allows for re-analysis of genomic data, aiding in identification of new variants of pathogenic clones. By integrating data from diverse sources inclusing sequenced isolates, we found that certain ETEC clonal lineages e.g., those expressing certain toxin-colonization factor profiles including STp/CS6, LT STh/CS2 + CS3, and LT STh/CFA/I are more at risk to develop multi-drug resistance than other ETEC lineages. Comparizon of multi-locus sequence types from papers with WGS data indicated ST182, ST4, ST2332 and new ST types to be emerging multi-drug resistant ETEC. We conclude that further studies on sequenced ETEC/E. coli genomes are needed to enhance our understanding of the dynamics of ETEC evolution, and the relation of virulence and resistance profiles in both environmental and clinical isolates.
Resumo Introdução: Pesquisa multicêntrica em centros de diálise brasileiros são escassas. Descrevemos as fases de recrutamento e implementação do estudo SARC-HD, visando investigar a sarcopenia e seu impacto em desfechos clínicos adversos. Métodos: O SARC-HD é um estudo de coorte realizado com pacientes em hemodiálise no Brasil. A fase de recrutamento foi considerada o período entre convite ao centro e início da inclusão de pacientes, enquanto a fase de implementação durou a partir de então até a conclusão do recrutamento e coleta de dados basais. Após a implementação, um questionário estruturado foi distribuído para coletar feedback dos principais pesquisadores. Resultados: 21 centros de três regiões brasileiras consentiram em participar, com duas desistências. Dez pesquisadores principais supervisionaram 19 locais. Nove centros (47%) eram totalmente financiados por planos de saúde. 1525 pacientes foram avaliados para elegibilidade e 1008 foram incluídos, com taxa de recrutamento de 66,1%. Recrutamento e coleta de dados basais levaram 12 semanas [intervalo interquartil: 5–15]. A análise qualitativa de conteúdo identificou barreiras como falta de infraestrutura e logística para pesquisa. Os facilitadores incluíram gestão e organização do comitê gestor. Os desafios da coleta de dados foram relatados principalmente quanto à avaliação global subjetiva de 7 pontos e o questionário internacional de atividade física. O principal desafio para a fase de manutenção será a falta de informações padronizadas nos prontuários eletrônicos. Conclusões: As fases de recrutamento e implementação do estudo multicêntrico SARC-HD foram viáveis. Barreiras e facilitadores identificados pelos pesquisadores principais podem auxiliar futuras iniciativas multicêntricas a integrar tarefas relacionadas à pesquisa na rotina clínica, facilitando experiências bem-sucedidas.
Introduction: Multicenter research initiatives in Brazilian dialysis centers are scarce. We described the recruitment and implementation phases of the SARC-HD study, aimed at investigating sarcopenia and its impact on adverse clinical outcomes. Methods: The SARC-HD is a cohort study being conducted with patients on hemodialysis in Brazil. The recruitment phase was defined as the period from the invitation to the center until the start of patient enrollment, whereas the implementation phase lasted from then until the completion of enrollment and baseline data collection. Upon implementation, a structured questionnaire was distributed to collect feedback from principal investigators. Results: 21 centers from three Brazilian regions consented to participate, with two dropping out. Ten principal investigators oversaw the 19 sites. Nine centers (47%) were funded entirely by health insurance companies. A total of 1525 patients were screened for eligibility and 1008 were enrolled, with a 66.1% recruitment rate. Recruitment and baseline data collection took 12 [interquartile range: 5–15] weeks. Qualitative content analysis identified barriers such as a lack of infrastructure and logistics for research. Facilitators included the management and organization of the steering committee. Data collection challenges were mainly reported with the subjective 7-point global assessment and the international physical activity questionnaire. The main challenge for the ongoing maintenance phase will be the lack of standardized information in electronic health records. Conclusions: The recruitment and implementation phases of the multicenter SARC-HD study were feasible. Barriers and facilitators identified by principal investigators may help future multicenter initiatives to integrate research-related tasks into clinical routine, facilitating successful experiences.
Objectives this study aims to provide an updated evaluation of the functional characteristics of the two Early Warning Systems (EWS) in Syria, EWARS (Early Warning, Alert, and Response System) and EWARN (Early Warning, Alert, and Response Network), and to test different alert threshold methods using World Health Organization guidelines against the data of selected diseases. Methods A retrospective analysis of EWARN and EWARS surveillance data assessed functional characteristics. The World Health Organization alert thresholds for measles, acute bloody diarrhea, acute jaundice syndrome, and severe acute respiratory infections were tested using three methods. Sensitivity, specificity, and Youden index determined threshold suitability for each syndrome. Results The annual average number of reported cases was 1,140,717 for EWARS and 10,189,415 for EWARN. This study found that the optimal alert thresholds varied among different diseases. The percentile method showed promising results with good sensitivity and specificity. For measles, the 85th percentile threshold had the best results (Youden index = 0.443), whereas for acute bloody diarrhea, it was 75th percentile (Y = 0.532) and for severe acute respiratory infections, it was 90th percentile (Y = 0.653). Conclusions This study supports the use of adaptable disease-specific alert thresholds such as the percentile approach. Further research is required to develop statistical methods that can be applied to various early warning systems in conflict contexts.
We easily distinguish self-touch from the touch of others. This distinction is suggested to arise because the brain predicts the somatosensory consequences of voluntary movements using an efference copy and attenuates the predicted self-touch. However, it remains unclear how these predictions impact somatosensory perception before or after the self-touch occurs. Here, participants discriminated forces applied to their left index finger at different phases of the right hand’s reaching movement toward the left hand.We observed that forces felt progressively weaker during the reaching, reached their minimum perceived intensity at the time of self-touch, and recovered after the movement ended. We further demonstrated that this gradual attenuation vanished during similar reaching movements that did not produce expectations of self-touch between the two hands. Our results indicate a temporal tuning of somatosensory perception during movements to self-touch and underscore the role of sensorimotor context in forming predictions that attenuate the self touch intensity.
Cognitive behavioural therapy for insomnia is the treatment of choice for patients with insomnia, but not all patients benefit, and novel psychological treatment approaches have emerged (e.g. acceptance and commitment therapy). Thus, the aim of the present study was to evaluate whether treatment modality, adherence, insomnia severity, anxiety, depression, beliefs about sleep or acceptance of sleep problems are factors associated with response to psychological insomnia treatment. The sample consisted of 152 adults (115 women; mean age = 40.6 years, SD = 10.2) with chronic insomnia, and they participated in a randomized clinical trial comparing acceptance and commitment therapy for insomnia (as a standalone) with cognitive behavioural therapy for insomnia. The outcome measure was proportion of treatment responders (8 points reduction or more) on the Insomnia Severity Index, assessed at pre‐ and post‐treatment and 6‐month follow‐up. The predictor variables were assessed at pre‐treatment. The final multivariate model showed that undergoing cognitive behavioural therapy for insomnia increased the chances of treatment response at post‐treatment by 2.70 times when compared with acceptance and commitment therapy for insomnia (odds ratio = 2.70 [1.14–6.38]). In addition, each additional point in pre‐treatment insomnia severity (odds ratio = 1.15 [1.01–1.30]) and dysfunctional beliefs about sleep (odds ratio = 1.02 [1.00–1.05]) scores increased the chances of response at post‐treatment. Treatment adherence increased the chances of treatment response at post‐treatment by 3.07 times (odds ratio = 3.07 [1.28–7.34]). Finally, each additional point on the Insomnia Severity Index pre‐treatment increased the chances of treatment response at the 6‐month follow‐up (odds ratio = 1.14 [1.01–1.29]). In conclusion, cognitive behavioural therapy for insomnia increases the chance of treatment response compared with acceptance and commitment therapy for insomnia. Moreover, higher adherence, insomnia severity and dysfunctional beliefs about sleep predict treatment outcome in both treatments.
Objectives To determine the impact of alveolar socket surface area and number of root extractions for developing medication-related osteonecrosis of the jaw (MRONJ) in polypharmacy patients following multiple tooth extractions. Materials and methods A retrospective sample of 40 patients was recruited, including 20 polypharmacy patients (109 tooth extractions) who developed MRONJ in at least one of the extraction sites, matched with 20 controls (100 tooth extractions). Tooth-specific alveolar socket surface areas were assessed using CBCT scans from the control group to establish reference values for alveolar socket surface areas in polypharmacy patients with MRONJ. Correlations between the number of extracted tooth roots, alveolar socket surface area, and development of MRONJ were analysed within the polypharmacy group. Results 40% of tooth extractions in polypharmacy patients undergoing multiple extractions resulted in the development of MRONJ, with a higher prevalence observed in the mandible (44%). Among the extracted mandibular tooth roots, half were susceptible to MRONJ, and 45% of the exposed socket surface area was affected. Both jaws showed an increased risk (20%) of MRONJ following molar extraction. A strong positive correlation existed between extraction sites that developed MRONJ and both the number of mandibular tooth roots extracted (r = + 0.861; p < 0.001) and the total exposed alveolar socket surface area (r = + 0.757; p < 0.001). However, no significant correlations were observed in the upper jaw. Conclusions This study is the first to demonstrate that both mandibular alveolar socket surface area and number of extracted tooth roots are positively related to extraction sites developing MRONJ in polypharmacy patients undergoing multiple tooth extractions. Clinical relevance Identifying high-risk patients and implementing preventive strategies can reduce MRONJ incidence, underscoring the need for careful management of polypharmacy patients, especially those undergoing mandibular tooth extractions.
Background Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is highly associated with adverse perinatal outcomes and long‐term health problems for the mother and offspring. However, there are respective limitations in the pharmacological strategies for the current treatment of GDM. Glucokinase regulatory protein (GCKR) has been associated with GDM in observational studies and animal experiments and thus represents a potential drug target of interest for investigation. Methods We applied two‐sample Mendelian randomization (MR) and colocalization analysis using summary‐level data from genome‐wide association studies of GCKR and GDM. Two‐step MR was used to explore the mediating effects of several metabolic factors on the association. We also applied MR to explore the associations of GCKR levels with GDM‐related outcomes. Finally, we performed a phenome‐wide association study (PheWAS) to query the potential effects of altered GCKR levels across multiple health categories. Results We found a significant association between elevated GCKR levels and GDM (OR = 3.466, 95% CI = 2.401–5.002, p = 3.16 × 10⁻¹¹), also supported by the colocalization analysis ([Pcoloc] = 0.997). The estimates were replicated in an independent study (OR = 2.640, 95% CI = 1.983–3.513, p = 2.84 × 10⁻¹¹, Pcoloc = 0.983). Elevated GCKR levels were also associated with higher risk of type 2 diabetes (OR = 2.183, 95% CI = 1.846–2.581, p = 6.53 × 10⁻²⁰). Two‐step MR suggested that fasting glucose, fasting insulin, and triglycerides partly mediated the causal relationship. PheWAS found that targeting GCKR may improve renal function and glucose homeostasis but cause dyslipidemia and uric acid abnormalities. Conclusions This study provided novel evidence that circulating GCKR levels are causally implicated in GDM and related complications, suggesting that it may be a promising target for treatment.
No previous studies have reported the presence of sleep disturbances or their association with baseline factors in elderly patients with distal radius fracture (DRF). This study aimed to describe the proportion of patients with sleep disturbances and analyze their association with baseline factors in patients older than 60 years with conservatively treated DRFs. This prospective observational study included 220 patients with extra-articular DRFs who completed the Pittsburgh Sleep Quality Index at two time points: two weeks after cast removal and at the one year follow-up. Sociodemographic, anthropometric, clinical, radiological, and patient-reported outcome measures were analyzed as baseline predictors, with measurements performed two weeks after cast removal. At two weeks after cast removal, 166 (75.5%) patients had sleep disturbances. Sleep disturbances were associated with the affected dominant hand (β = 1.6; p = 0.04), high-energy injury (β = 3.8; p < 0.001), extra-articular comminuted metaphyseal DRFs (β = 2.3; p < 0.001), higher Tampa Scale of Kinesiophobia scores (β = 2.4; p < 0.001), higher Pain Catastrophizing Scale scores (β = 2.4; p < 0.001), higher Pain Anxiety Symptoms Scale-20 scores (β = 2.1; p < 0.001), and higher visual analogue scale scores (β = 4.1; p < 0.001). At the one year follow-up, 85 (38.6%) patients had sleep disturbances, which were associated with higher Tampa Scale of Kinesiophobia scores (β = 2.6; p < 0.001), higher Pain Catastrophizing Scale scores (β = 2.5; p < 0.001), and higher Pain Anxiety Symptoms Scale-20 scores (β = 1.8; p = 0.02). A high proportion of elderly patients with DRF experienced sleep disturbances. Expanding our understanding of the interplay between sleep disturbances and baseline risk factors may lead to improved care and clinical outcomes for these patients. Future studies should incorporate the clinical management of sleep disturbances in patients with DRFs.
A decreasing trend in asthma hospitalisations among Finnish and Swedish children has been reported. However, possible changes in asthma hospitalisations among adults are incompletely characterised. We aimed to investigate the incidence of adult asthma hospitalisations in Finland and Sweden from 2006 to 2022 using Finland’s National Hospital Discharge Register and Sweden’s National Patient Register. During the study period, the incidence of asthma hospitalisations decreased by 65.8% in Finland (from 84.9 to 29.0 per 100 000 person-years) and by 52.5% in Sweden (from 31.4 to 14.9 per 100 000 person-years). The incidences of asthma hospitalisations were distinctly higher in Finland compared with Sweden at the start of the study period but approached parity among both sexes.
Background The impact of COVID-19 on specific populations, including gay, bisexual, and other men who have sex with men (GBMSM), varies based on a range of factors such as access to health care, underlying health behaviors and conditions, and social determinants of health. Our community-based participatory research partnership sought to better understand perspectives about and experiences with the COVID-19 pandemic, COVID-19 vaccination, and related health care among GBMSM. Methods We collected, analyzed, and interpreted qualitative in-depth interview data from a diverse sample of GBMSM (N = 30) in North Carolina, USA. Using purposive sampling, we recruited native English (n = 15) and Spanish (n = 15) speakers and persons with HIV (n = 13) and persons without HIV (n = 17). We analyzed interview data using constant comparison, an approach to grounded theory. Results Participant mean was 33.4 (SD = 8.5) years. Sixteen themes emerged that were categorized into five domains: trust/mistrust of politicians, healthcare professionals, and the US government (n = 4 themes); engagement in COVID-19 prevention strategies (n = 2 themes); attitudes towards COVID-19 vaccination (n = 3 themes); access to and use of health care (n = 4 themes); and impact of COVID-19 on social determinants of health and mental health (n = 3 themes). Conclusions This research increases our understanding of the COVID-19 pandemic among particularly minoritized and underserved communities: racially and ethnically diverse, English- and Spanish-speaking GBMSM with and without HIV in the US South. By addressing the unique needs and concerns of these communities, we can promote more equitable public health responses; enhance preventive healthcare delivery; improve preparedness for subsequent outbreaks (e.g., mpox), epidemics, and pandemics; and be better equipped to support delivery and uptake of potential future preventive HIV vaccines among communities impacted by health disparities.
Caregivers to stroke survivors often experience a multifaceted strain defined as caregiver burden. Low health literacy among caregivers may contribute to increased caregiver burden but there is limited research specifically examining the association between stroke survivors’ health literacy and caregiver burden. Therefore, the aim here is to explore if there is an association between stroke survivors’ health literacy and caregiver burden one year after stroke. Participants were 50 caregivers and 50 stroke survivors who were followed up in a longitudinal study on care transitions after stroke. Data were collected one year after the stroke survivors’ discharge from hospital and analysed using ordinal logistic regression. Most of the caregivers, median age 71 years, reported being satisfied with their lives (85%) and a low caregiver burden (74%). Stroke survivors’ health literacy was not associated with caregiver burden. However, lower needs of assistance in daily activities, lower levels of depression, higher levels of participation and increased age in stroke survivors were associated with lower caregiver burden. In conclusion, stroke survivors’ health literacy was not associated with caregiver burden one year after stroke. Future studies with larger samples, focusing on populations with lower functioning after stroke and higher caregiver burden, are recommended.
Introduction A revised cardiotocography (CTG) classification was implemented in Sweden in 2017. Simultaneously, an updated version of the lactate meter, Lactate Pro 2™, proved to measure 50% higher than the previous, necessitating new cutoffs for fetal blood sampling (FBS). We aimed to investigate frequencies of FBS, delivery modes, and neonatal outcomes. We hypothesized that with the revised CTG classification, which accepts more fetal heart rate patterns as normal than the previous, the frequency of FBS would be lower, the proportion of acidemia at FBS and adverse neonatal outcomes would be higher among sampled fetuses, but not among the entire laboring population, and the higher lactate readings might increase the proportion of cesarean delivery in general anesthesia and cesarean delivery above vacuum extraction. Material and Methods A population‐based cohort study of electronic medical records of labors in Stockholm‐Gotland during 2014–2015 and 2018–2019, including singleton pregnancies >34 weeks, cephalic presentation, with spontaneous or induced start of labor. Outcome measures were FBS frequency, proportion of fetal acidemia, delivery modes, and neonatal outcomes with comparison between the two periods among sampled and nonsampled fetuses. Results There were 28 841 and 30 192 births during the two periods. In the latter period, the FBS frequency was lower (8.2% vs. 11.9% [p < 0.001]), and the proportion of acidemia at FBS was higher, both among sampled fetuses (12.5% vs. 7.1% [p < 0.001]), and in the total population (1.0% vs. 0.8% [p = 0.022]). Immediate cesareans in general anesthesia due to fetal distress were more frequent among sampled fetuses (3.1% vs. 2.0% [p = 0.006]) but not among nonsampled fetuses (0.4 vs. 0.4%). Incidence of Apgar scores < 4 at 5 min was unchanged after FBS (p = 0.66) but higher among nonsampled newborns (0.2 vs. 0.1 [p = 0.033]). Apgar scores <7 at 5 min were more frequent among both sampled and nonsampled groups. Conclusions After implementation of a revised CTG classification and a differently calibrated lactate meter in Sweden, the use of FBS was substantially lower. Acidemia at FBS and immediate cesarean due to fetal distress were more frequent among sampled fetuses but still low in the total laboring population. Low Apgar scores were more frequent among newborns both with and without FBS.
BACKGROUND The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses. METHODS To detail the role of T cell EZH2 in atherosclerosis, we used human carotid endarterectomy specimens to reveal plaque expression and geography of EZH2. Atherosclerosis-prone Apoe (apolipoprotein E)–deficient mice with CD (cluster of differentiation) 4 ⁺ or CD8 ⁺ T cell–specific Ezh2 deletion (Ezh2 cd4 -knockout [KO], Ezh2 cd8 -KO) were analyzed to unravel the role of T cell Ezh2 in atherosclerosis and T cell–associated immune status. RESULTS EZH2 expression is elevated in advanced human atherosclerotic plaques and primarily expressed in the T cell nucleus, suggesting the importance of canonical EZH2 function in atherosclerosis. Ezh2 cd4 -KO, but not Ezh2 cd8 -KO, mice showed reduced atherosclerosis with fewer advanced plaques, which contained less collagen and macrophages, indicating that Ezh2 in CD4 ⁺ T cells drives atherosclerosis. In-depth analysis of CD4 ⁺ T cells of Ezh2 cd4 -KO mice revealed that absence of Ezh2 results in a type 2 immune response with increased Il-4 (interleukin 4) gene and protein expression in the aorta and lymphoid organs. In vitro, Ezh2 -deficient T cells polarized macrophages toward an anti-inflammatory phenotype. Single-cell RNA-sequencing of splenic T cells revealed that Ezh2 deficiency reduced naive, Ccl5 ⁺ (C-C motif chemokine ligand 5) and regulatory T cell populations and increased the frequencies of memory T cells and invariant natural killer T (iNKT) cells. Flow cytometric analysis identified a shift toward Th2 (type 2 T helper) effector CD4 ⁺ T cells in Ezh2 cd4 -KO mice and confirmed a profound increase in splenic iNKT cells with increased expression of Plzf (promyelocytic leukemia zinc finger), which is the characteristic marker of the iNKT2 subset. Likewise, Zbtb16 ([zinc finger and BTB domain containing 16], a Plzf-encoding gene) transcripts were elevated in the aorta of Ezh2 cd4 -KO mice, suggesting an accumulation of iNKT2 cells in the plaque. H3K27me3–chromatin immunoprecipitation followed by quantitative polymerase chain reaction showed that T cell–Ezh2 regulates the transcription of the Il-4 and Zbtb16 genes. CONCLUSIONS Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4 ⁺ T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.
Ineffective medication is a major healthcare problem causing significant patient suffering and economic costs. This issue stems from the complex nature of diseases, which involve altered interactions among thousands of genes across multiple cell types and organs. Disease progression can vary between patients and over time, influenced by genetic and environmental factors. To address this challenge, digital twins have emerged as a promising approach, which have led to international initiatives aiming at clinical implementations. Digital twins are virtual representations of health and disease processes that can integrate real-time data and simulations to predict, prevent, and personalize treatments. Early clinical applications of DTs have shown potential in areas like artificial organs, cancer, cardiology, and hospital workflow optimization. However, widespread implementation faces several challenges: (1) characterizing dynamic molecular changes across multiple biological scales; (2) developing computational methods to integrate data into DTs; (3) prioritizing disease mechanisms and therapeutic targets; (4) creating interoperable DT systems that can learn from each other; (5) designing user-friendly interfaces for patients and clinicians; (6) scaling DT technology globally for equitable healthcare access; (7) addressing ethical, regulatory, and financial considerations. Overcoming these hurdles could pave the way for more predictive, preventive, and personalized medicine, potentially transforming healthcare delivery and improving patient outcomes.
The current understanding of crew health maintenance is founded upon decades of physiological research conducted in terrestrial spaceflight analogues and in low Earth orbit, particularly on the International Space Station. However, as we progress towards the Lunar Gateway and interplanetary missions, it is imperative that the tools employed to maintain crew health are redefined, including the utilisation of exercise countermeasures. The successful implementation of exercise countermeasures for deep space missions must address a number of challenges, including those posed by new environments with elevated levels of cosmic radiation and solar particle events, extended mission durations and constrained space availability. In this Topical Review, the authors address points that are important (and sometimes critical), but often ignored, in order to define future exercise countermeasures for long‐duration space missions. Multi‐organ countermeasures, countermeasure enjoyment, time‐dependent load variability, the relationship between nutrition and the success of exercise countermeasures, and the individual variability in response to a given countermeasure are presented and discussed. The aim of this article is to raise awareness of important aspects that can profoundly influence the efficacy of exercise countermeasures, thereby affecting the health of the crew and the success of the mission during prolonged spaceflight.
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10,386 members
Christopher R. Cederroth
  • Department of Physiology and Pharmacology
André Görgens
  • Department of Laboratory Medicine
Johanna Viiliäinen
  • Department of Cell and Molecular Biology
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Stockholm, Sweden
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Ole Petter Ottersen