ABSTRACT
The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling their association with particles remains limited. We have found that a particle-associated isolate, Alteromonas sp. ALT199 strain 4B03, and the related type-strain A. macleodii 27126 both form large (>500 µm) aggregates while growing in rich medium. A non-clumping variant (NCV) of 4B03 spontaneously arose in the lab, and whole-genome sequencing revealed a partial deletion in the gene encoding UDP-glucose-4-epimerase (galEΔ308-324). In 27126, a knock-out of galE (ΔgalE::kmr) resulted in a loss of aggregation, mimicking the NCV. Microscopic analysis shows that both 4B03 and 27126 rapidly form large aggregates, whereas their respective galE mutants remain primarily as single planktonic cells or clusters of a few cells. Strains 4B03 and 27126 also form aggregates with chitin particles, but their galE mutants do not. Alcian Blue staining shows that 4B03 and 27126 produce large transparent exopolymer particles (TEP), but their galE mutants are deficient in this regard. This study demonstrates the capabilities of cell-cell aggregation, aggregation of chitin particles, and production of TEP in strains of Alteromonas, a widespread particle-associated genus of heterotrophic marine bacteria. A genetic requirement for galE is evident for each of the above capabilities, expanding the known breadth of requirement for this gene in biofilm-related processes. IMPORTANCE: Heterotrophic marine bacteria have a central role in the global carbon cycle. Well-known for releasing CO2 by decomposition and respiration, they may also contribute to particulate organic matter (POM) aggregation, which can promote CO2 sequestration via the formation of marine snow. We find that two members of the prevalent particle-associated genus Alteromonas can form aggregates comprising cells alone or cells and chitin particles, indicating their ability to drive POM aggregation. In line with their multivalent aggregation capability, both strains produce TEP, an excreted polysaccharide central to POM aggregation in the ocean. We demonstrate a genetic requirement for galE in aggregation and large TEP formation, building our mechanistic understanding of these aggregative capabilities. These findings point toward a role for heterotrophic bacteria in POM aggregation in the ocean and support broader efforts to understand bacterial controls on the global carbon cycle based on microbial activities, community structure, and meta-omic profiling.
Subject(s)
Alteromonas , UDPglucose 4-Epimerase , Alteromonas/genetics , Alteromonas/enzymology , Alteromonas/metabolism , UDPglucose 4-Epimerase/genetics , UDPglucose 4-Epimerase/metabolism , Polysaccharides, Bacterial/metabolism , Polysaccharides, Bacterial/biosynthesis , Polysaccharides, Bacterial/genetics , Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Seawater/microbiology , Whole Genome SequencingABSTRACT
In the period between 5,300 and 4,900 calibrated years before present (cal. BP), populations across large parts of Europe underwent a period of demographic decline1,2. However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3, others for the spread of an early form of plague4. Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline.
Subject(s)
Farmers , Genomics , Pedigree , Plague , Population Dynamics , Yersinia pestis , Female , Humans , Male , Cemeteries/history , Farmers/history , Genome, Bacterial/genetics , History, Ancient , Phylogeny , Plague/epidemiology , Plague/history , Plague/microbiology , Plague/mortality , Scandinavian and Nordic Countries/epidemiology , Time Factors , Virulence Factors/genetics , Yersinia pestis/genetics , Yersinia pestis/isolation & purificationABSTRACT
INTRODUCTION: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies. PATIENTS AND METHODS: Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age. RESULTS: The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres. CONCLUSIONS: The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals.
Subject(s)
Brain Neoplasms , Glioma , Neurosurgical Procedures , Humans , Child , Glioma/surgery , Glioma/pathology , Female , Male , Neurosurgical Procedures/methods , Germany , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Adolescent , Child, Preschool , Infant , Neoplasm GradingABSTRACT
Egg dehydration can kill terrestrial frog embryos, and this threat is increasing with climate change and deforestation. In several lineages that independently evolved terrestrial eggs, and retained aquatic tadpoles, embryos accelerate hatching to escape from drying eggs, entering the water earlier and less developed. However, the cues that stimulate drying-induced early hatching are unknown. Ammonia is a toxic, water-soluble metabolic waste that accumulates within eggs as embryos develop and concentrates as eggs dehydrate. Thus, increasing ammonia concentration may be a direct threat to embryos in drying eggs. We hypothesized that it could serve as a cue, stimulating embryos to hatch and escape. The embryos of red-eyed treefrogs, Agalychnis callidryas, hatch early to escape from many threats, including dehydration, and are known to use mechanosensory, hypoxia, and light cues. To test if they also use high ammonia as a cue to hatch, we exposed stage-matched pairs of hatching-competent, well-hydrated sibling embryos to ammonia and control solutions in shallow water baths and recorded their behavior. Control embryos remained unhatched while ammonia-exposed embryos showed a rapid, strong hatching response; 95% hatched, on average in under 15 min. This demonstrates that elevated ammonia can serve as a hatching cue for A. callidryas embryos. This finding is a key step in understanding the mechanisms that enable terrestrial frog embryos to escape from egg drying, opening new possibilities for integrative and comparative studies on this growing threat.
Subject(s)
Ammonia , Anura , Cues , Embryo, Nonmammalian , Ovum , Animals , Ammonia/toxicity , Anura/embryology , Anura/physiology , Ovum/physiology , Embryo, Nonmammalian/physiology , Dehydration , Escape Reaction/physiology , Escape Reaction/drug effectsABSTRACT
OBJECTIVE: This study aimed to evaluate the effect of a new health communication intervention focusing on knowledge management skills on health literacy and medication adherence during the first year following kidney transplantation. METHODS: We randomized 195 patients during 2020-2021, to either intervention- or control group. Questionnaires were completed at baseline and at 12 months post-transplantation with a 12-month response rate of 84%. Health literacy was measured by the multidimensional Health Literacy Questionnaire (HLQ) instrument. Medication adherence was measured by the self-reported questionnaire (BAASIS©). RESULTS: Results showed that the intervention group had a significant increase in 2 HLQ domains compared to the control group capturing the "ability to appraise health information" Domain 5, (p-value = 0.002) and the "ability to navigate the healthcare system" Domain 7, (p-value <0.04). The effect sizes of SRM were 0.49 (Domain 5) and 0.33 (Domain 7). Medication adherence was comparable in the groups at any measure points. CONCLUSIONS: This study contributes to important knowledge about how a health communication intervention focusing on knowledge translation using motivational interviewing techniques positively strengthens health literacy in kidney transplant recipients. PRACTICAL IMPLICATIONS: Current patient education practice may benefit from focusing on knowledge translation in combination with motivational interview technique.
Subject(s)
Health Communication , Health Literacy , Kidney Transplantation , Humans , Research Design , Surveys and Questionnaires , Medication AdherenceABSTRACT
OBJECTIVE: To compare the effect of motivational interviewing (MI) and tailored health literacy (HL) follow-up with usual care on hospitalization, costs, HL, self-management, Quality of life (QOL), and psychological stress in people with chronic obstructive pulmonary disease (COPD). METHODS: A RCT was undertaken in Norway between March 2018-December 2020 (n = 127). The control group (CG, n = 63) received usual care. The intervention group (IG, n = 64) received tailored HL follow-up from MI-trained COPD nurses with home visits for eight weeks and phone calls for four months after hospitalization. Primary outcomes were hospitalization at eight weeks, six months, and one year from baseline. The trial was registered with ClinicalTrials.gov (NCT03216603) and analysed per protocol. RESULTS: Compared with the IG, the CG had 2.8 higher odds (95% CI [1.3 to 5.8]) of hospitalization and higher hospital health costs (MD= -6230, 95% CI [-6510 to -5951]) and lower QALYs (MD=0.1, 95% CI [0.10 to 0.11]) that gives an ICER = - 62,300. The IG reported higher QOL, self-management, and HL (p = 0.02- to <0.01). CONCLUSION: MI-trained COPD nurses using tailored HL follow-up is cost-effective, reduces hospitalization, and increases QOL, HL, and self-care in COPD. PRACTICE IMPLICATION: Tailored HL follow-up is beneficial for individuals with COPD and the healthcare system.
Subject(s)
Health Literacy , Pulmonary Disease, Chronic Obstructive , Self-Management , Humans , Quality of Life , Hospitalization , Health Care Costs , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/psychologyABSTRACT
BACKGROUND: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). PATIENTS AND METHODS: Following surgery, patients (0-36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. RESULTS: We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001-.019; d = 0.79-1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. CONCLUSION: Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.
Subject(s)
Brain Neoplasms , Central Nervous System Neoplasms , Glioma , Neoplasms, Neuroepithelial , Rhabdoid Tumor , Teratoma , Child , Infant , Humans , Rhabdoid Tumor/complications , Rhabdoid Tumor/therapy , Retrospective Studies , Quality of Life , Teratoma/complications , Teratoma/therapy , Brain Neoplasms/complications , Brain Neoplasms/therapy , Central Nervous System Neoplasms/pathology , Disease Progression , Visual Perception , Cognition , SurvivorsABSTRACT
The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.
Subject(s)
Asian , European People , Genome, Human , Selection, Genetic , Humans , Affect , Agriculture/history , Alleles , Alzheimer Disease/genetics , Asia/ethnology , Asian/genetics , Diabetes Mellitus/genetics , Europe/ethnology , European People/genetics , Farmers/history , Genetic Loci/genetics , Genetic Predisposition to Disease , Genome, Human/genetics , History, Ancient , Human Migration , Hunting/history , Multigene Family/genetics , Phenotype , UK Biobank , Multifactorial Inheritance/geneticsABSTRACT
Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.
Subject(s)
Genetic Predisposition to Disease , Genome, Human , Grassland , Multiple Sclerosis , Humans , Datasets as Topic , Diet/ethnology , Diet/history , Europe/ethnology , Genetic Predisposition to Disease/history , Genetics, Medical , History, 15th Century , History, Ancient , History, Medieval , Human Migration/history , Life Style/ethnology , Life Style/history , Multiple Sclerosis/genetics , Multiple Sclerosis/history , Multiple Sclerosis/immunology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/history , Neurodegenerative Diseases/immunology , Population DensityABSTRACT
Background: Norway has a long coastline, steep mountains, and wide fjords, which presents some challenges to the prehospital emergency healthcare system. In recent years, the prehospital emergency medical services (EMS) have undergone significant changes, structurally, in terms of professionalisation of the services and in the education level of the personnel. In this article, we aim to describe the current structure for handling prehospital medical emergencies. Methods: For healthcare, Norway is divided into four Regional Health Authorities, consisting of 19 Health Trusts, where 18 have an EMS. There is a dedicated medical emergency number, 113, that terminates in 16 emergency medical communication centres. The use of air and boat ambulances, in addition to traditional ambulances, seeks to meet the challenges in the EMS system. Strengths and limitations: The Norwegian EMS is an advanced system with highly educated staff; however, this level of care comes with an equally high cost. Conclusion: The Norwegian EMS can handle emergencies nationwide, providing advanced care at the scene and during transport. The geography and demography challenge the idea of equal care, but the open publishing of data from national quality registries seeks to identify and address potential differences.
ABSTRACT
Call centers can be found in various industries. However as a Medical Subject Heading (MeSH) the term "Call centers" does not reflect the critical purpose of handling emergency calls. We recommend "emergency medical communication center(s)", as this provides clarity and precision regarding the primary function and purpose of the center.
Subject(s)
Call Centers , Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Emergency Medical Service Communication Systems , Medical Subject Headings , CommunicationABSTRACT
BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.
ABSTRACT
BACKGROUND: eHealth literacy is a key concept in the implementation of eHealth resources. However, most eHealth literacy definitions and frameworks are designed from the perceptive of the individual receiving eHealth care, which do not include health care providers' eHealth literacy or acceptance of delivering eHealth resources. AIMS: To identify existing research on eHealth literacy domains and measurements and identify eHealth literacy scores and associated factors among hospital health care providers. METHODS: This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. A systematic literature search was conducted in MEDLINE, Cinahl, Embase, Scopus, PEDro, AMED and Web of Science. Quantitative studies assessing eHealth literacy with original research, targeting hospital health care providers were included. Three eHealth literacy domains based on the eHealth literacy framework were defined a priori; (1) Individual eHealth literacy, (2) Interaction with the eHealth system, and (3) Access to the system. Pairs of authors independently assessed eligibility, appraised methodological quality and extracted data. RESULTS: Fourteen publications, of which twelve publications were conducted in non-Western countries, were included. In total, 3,666 health care providers within eleven different professions were included, with nurses being the largest group. Nine of the included studies used the eHealth literacy scale (eHEALS) to measure eHealth literacy, representing the domain of individual eHealth literacy. A minority of the studies covered domains such as interaction with the eHealth system and access to the system. The mean eHEALS score in the studies ranged from 27.8 to 31.7 (8-40), indicating a higher eHealth literacy. One study reported desirable eHealth literacy based on the Digital Health Literacy Instrument. Another study reported a relatively high score on the Staff eHealth literacy questionnaire. eHealth literacy was associated with socio-demographic factors, experience of technology, health behaviour and work-related factors. CONCLUSIONS: Health care providers have good individual eHealth literacy. However, more research is needed on the eHealth literacy domains dependent on interaction with the eHealth system and access to the system. Furthermore, most studies were conducted in Eastern and Central-Africa, and more research is thus needed in a Western context. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (CRD42022363039).
Subject(s)
Health Literacy , Telemedicine , Humans , Health Personnel , Surveys and Questionnaires , Health BehaviorABSTRACT
SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection. The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73-0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48-0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30-0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males. High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.
ABSTRACT
BACKGROUND: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. METHODS: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. RESULTS: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection. CONCLUSIONS: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.
Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2/genetics , Cohort Studies , Prospective Studies , Vaccination , COVID-19 Vaccines , Vaccines, Combined , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
Oxidative stress and formation of cytotoxic oligomers by the natively unfolded protein α-synuclein (α-syn) are both connected to the development of Parkinson's disease. This effect has been linked to lipid peroxidation and membrane disruption, but the specific mechanisms behind these phenomena remain unclear. To address this, we have prepared α-syn oligomers (αSOs) in vitro in the presence of the lipid peroxidation product 4-oxo-2-nonenal and investigated their interaction with live cells using in-cell NMR as well as stimulated emission depletion (STED) super-resolution and confocal microscopy. We find that the αSOs interact strongly with organellar components, leading to strong immobilization of the protein's otherwise flexible C-terminus. STED microscopy reveals that the oligomers localize to small circular structures inside the cell, while confocal microscopy shows mitochondrial fragmentation and association with both late endosome and retromer complex before the SOs interact with mitochondria. Our study provides direct evidence for close contact between cytotoxic α-syn aggregates and membraneous compartments in the cell.
Subject(s)
Parkinson Disease , alpha-Synuclein , Humans , alpha-Synuclein/chemistry , Aldehydes/chemistry , Lipid PeroxidationABSTRACT
BACKGROUND: Perceptions about expected outcome after out-of-hospital cardiac arrest (OHCA) influence treatment decisions, and there is a need for updated evidence about outcomes for the elderly. METHOD: We conducted a cross-sectional study of cases reported to the Norwegian Cardiac Arrest Registry from 2015 through 2021 of patients 60 years and older, suffering cardiac arrest in healthcare institutions or at home. We examined reasons for emergency medical service (EMS) withholding or withdrawing resuscitation. We compared survival and neurological outcome for EMS-treated patients and explored factors associated with survival using multivariate logistic regression. RESULT: We included 12,191 cases and the EMS started resuscitation in 10,340 (85%). The incidence per capita of OHCA the EMS were alerted to was 267/100,000 in healthcare institutions and 134/100,000 at home. Resuscitation was most frequently withdrawn due to medical history (n = 1251). In healthcare institutions, 72 of 1503 (4.8%) patients survived to 30 days compared to 752 of 8837 (8.5%) at home (P <.001). We found survivors in all age cohorts both in healthcare institutions and at home, and most of the 824 survivors had a good neurological outcome with a Cerebral Performance Category ≤2 (88%). CONCLUSION: Medical history was the most frequent reason for EMS not to start or continue resuscitation, indicating a need for a discussion about, and documentation of, advance directives in this age group. When EMS attempted resuscitation, most survivors had a good neurological outcome, both in healthcare institutions and at home.
Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Aged , Out-of-Hospital Cardiac Arrest/therapy , Cross-Sectional Studies , Registries , Norway/epidemiology , Delivery of Health CareABSTRACT
Childhood epilepsy is often complicated by neurobehavioral comorbidities, and parents are expected to actively engage in managing the condition. Insufficient parental health literacy (HL) has been associated with reduced health outcomes for children with epilepsy. Little is known about the parents' experiences of information seeking, social support, navigating the healthcare system, and interactions with healthcare professionals and how these skills may contribute to the development of sufficient HL. This study explored parents' experiences of their caregiver responsibility and the development of their HL in relation to caring for their child with epilepsy. Ten parents of children under 12 years of age with epilepsy were purposedly sampled and interviewed individually, using semi-structured interviews. The interviews were analyzed using qualitative content analysis, in line with Graneheim & Lundman. The analyses resulted in three themes, each comprising two sub-themes. The themes were: (1) Alone with the responsibility, (2) The combat for information and support, and (3) Developing vigilance and distrust in system competence. Lack of flexibility in healthcare services, insufficient multidisciplinary collaboration, and unclear treatment provider responsibility made the parents feel alone in the caregiver's responsibility. Poor local provider competence related to childhood epilepsy was a barrier to developing sufficient HL. A trusting relationship with professionals and timely access to competent health services were facilitators for developing HL. Higher HL made the parents more critical for the healthcare services, which triggered vigilance and reduced their trust in the professionals' information. For the parents, developing and maintaining HL was a continuous emotional, cognitive, and social process. Health information and care support need to be adjusted to the severity of the child's condition, the resources are available, and the parent's HL. The results of this study may contribute to the development of future interventions for strengthening parental HL in the childhood epilepsy context.
Subject(s)
Epilepsy , Health Literacy , Child , Humans , Parents/psychology , Emotions , Qualitative Research , CognitionABSTRACT
Neurofibromatosis type 1 (NF1) is a phenotypically heterogenous multisystem cancer predisposition syndrome manifesting in childhood and adolescents. Central nervous system (CNS) manifestations include structural, neurodevelopmental, and neoplastic disease. We aimed to (1) characterize the spectrum of CNS manifestations of NF1 in a paediatric population, (2) explore radiological features in the CNS by image analyses, and (3) correlate genotype with phenotypic expression for those with a genetic diagnosis. We performed a database search in the hospital information system covering the period between January 2017 and December 2020. We evaluated the phenotype by retrospective chart review and imaging analysis. 59 patients were diagnosed with NF1 [median age 10.6 years (range, 1.1-22.6); 31 female] at last follow-up, pathogenic NF1 variants were identified in 26/29. 49/59 patients presented with neurological manifestations including 28 with structural and neurodevelopmental findings, 16 with neurodevelopmental, and 5 with structural findings only. Focal areas of signal intensity (FASI) were identified in 29/39, cerebrovascular anomalies in 4/39. Neurodevelopmental delay was reported in 27/59 patients, learning difficulties in 19/59. Optic pathway gliomas (OPG) were diagnosed in 18/59 patients, 13/59 had low-grade gliomas outside the visual pathways. 12 patients received chemotherapy. Beside the established NF1 microdeletion, neither genotype nor FASI were associated with the neurological phenotype. NF1 was associated with a spectrum of CNS manifestations in at least 83.0% of patients. Regular neuropsychological assessment complementing frequent clinical and ophthalmologic testing for OPG is necessary in the care of each child with NF1.