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125 result(s) for "Johnston, Monica"
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Patterns of war related trauma in Gaza during armed conflict: survey study of international healthcare workers
AbstractObjectiveTo systematically document the patterns of war related injuries in Gaza, Palestine.DesignSurvey study of international healthcare workers, August 2024 to February 2025.SettingGaza, Palestine.Participants78 international healthcare workers deployed to Gaza.Main outcome measuresThe main outcome was the type of injuries observed by international healthcare workers during the conflict in Gaza. A Delphi informed survey was distributed through non-governmental organisation rosters and secure WhatsApp and email groups. Respondents completed the survey using contemporaneous logbooks and shift records.ResultsThe survey collected data on 12 anatomical regions, mechanisms of trauma, and general medical conditions. 78 healthcare workers reported 23 726 trauma related injuries and 6960 injuries related to weapons. The most common traumatic injuries were burns (n=4348, 18.3%), lower limb injuries (n=4258, 17.9%), and upper limb injuries (n=3534, 14.9%). Explosive injuries accounted for most of the weapon related trauma (n=4635, 66.6%), predominantly affecting the head (n=1289, 27.8%), whereas firearm injuries disproportionately affected the lower limbs (n=526, 22.6%). Healthcare workers reported 4188 people with chronic disease across 11 domains requiring long term treatment.ConclusionHealthcare workers deployed to Gaza reported an injury phenotype defined by extensive polytrauma (≥2 anatomical regions), complex blast injuries from high yield explosives, firearm related injuries to upper and lower limbs, and severe disruption to primary care and the treatment of chronic diseases. The results provide actionable insights to tailor humanitarian response and highlight the urgent need for structured, resilient clinical surveillance systems.Editor’s noteThis paper is based on research from an active war zone, where conventional research methods may be impossible to apply.
Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes
Clostridioides difficile infection is a major cause of nosocomial and community illness. In this report from the Emerging Infections Program, associated with the U.S. CDC, the national burden of C. difficile infection is estimated from 2011 through 2017. In 2017, an estimated 462,100 cases of C. difficile infection occurred.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
The bed bug, Cimex lectularius , has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. The bed bug, Cimex lectularius , is a ubiquitous human ectoparasite with global distribution. Here, the authors sequence the genome of the bed bug and identify reductions in chemosensory genes, expansion of genes associated with blood digestion and genes linked to pesticide resistance.
Human proximal tubular epithelial cell interleukin-1 receptor signalling triggers G2/M arrest and cellular senescence during hypoxic kidney injury
Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O 2 ) or hypoxic (1% O 2 ) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 ‘unique’ differentially expressed genes (DEGs) compared to normoxic PTECs, with ‘cell cycle’ the most significantly enriched KEGG pathway based on ‘unique’ down-regulated DEGs (including CCNA2 , CCNB1 and CCNB2 ). Hypoxia+IL-1β-treated PTECs displayed signatures of cellular senescence, with reduced proliferation, G2/M cell cycle arrest, increased p21 expression, elevated senescence-associated β-galactosidase (SA-β-gal) activity and increased production of pro-inflammatory/fibrotic senescence-associated secretory phenotype (SASP) factors compared to normoxic conditions. Treatment of Hypoxia+IL-1β-treated PTECs with either a type I IL-1 receptor (IL-1RI) neutralizing antibody or a senolytic drug combination, quercetin+dasatinib, attenuated senescent cell burden. In vitro findings were validated in human CKD bio-specimens (kidney tissue, urine), with elevated PTEC IL-1RI expression and senescence (SA-β-gal activity) detected in fibrotic kidneys and numbers of senescent (SA-β-gal + ) urinary PTECs correlating with urinary IL-1β levels and severity of interstitial fibrosis. Our data identify a mechanism whereby hypoxia in combination with IL-1β/IL-1RI signalling trigger PTEC senescence, providing novel therapeutic and diagnostic check-points for restoring tubular regeneration in human CKD.
Social capital I: measurement and associations with economic mobility
Social capital—the strength of an individual’s social network and community—has been identified as a potential determinant of outcomes ranging from education to health 1 – 8 . However, efforts to understand what types of social capital matter for these outcomes have been hindered by a lack of social network data. Here, in the first of a pair of papers 9 , we use data on 21 billion friendships from Facebook to study social capital. We measure and analyse three types of social capital by ZIP (postal) code in the United States: (1) connectedness between different types of people, such as those with low versus high socioeconomic status (SES); (2) social cohesion, such as the extent of cliques in friendship networks; and (3) civic engagement, such as rates of volunteering. These measures vary substantially across areas, but are not highly correlated with each other. We demonstrate the importance of distinguishing these forms of social capital by analysing their associations with economic mobility across areas. The share of high-SES friends among individuals with low SES—which we term economic connectedness—is among the strongest predictors of upward income mobility identified to date 10 , 11 . Other social capital measures are not strongly associated with economic mobility. If children with low-SES parents were to grow up in counties with economic connectedness comparable to that of the average child with high-SES parents, their incomes in adulthood would increase by 20% on average. Differences in economic connectedness can explain well-known relationships between upward income mobility and racial segregation, poverty rates, and inequality 12 – 14 . To support further research and policy interventions, we publicly release privacy-protected statistics on social capital by ZIP code at https://www.socialcapital.org . Analyses of data on 21 billion friendships from Facebook in the United States reveal associations between social capital and economic mobility.
Correlated evolution of mating system and floral display traits in flowering plants and its implications for the distribution of mating system variation
Reduced allocation to structures for pollinator attraction is predicted in selfing species. We explored the association between outcrossing and floral display in a broad sample of angiosperms. We used the demonstrated relationship to test for bias against selfing species in the outcrossing rate distribution, the shape of which has relevance for the stability of mixed mating. Relationships between outcrossing rate, flower size, flower number and floral display, measured as the product of flower size and number, were examined using phylogenetically independent contrasts. The distribution of floral displays among species in the outcrossing rate database was compared with that of a random sample of the same flora. The outcrossing rate was positively associated with the product of flower size and number; individually, components of display were less strongly related to outcrossing. Compared with a random sample, species in the outcrossing rate database showed a deficit of small floral display sizes. We found broad support for reduced allocation to attraction in selfing species. We suggest that covariation between mating systems and total allocation to attraction can explain the deviation from expected trade-offs between flower size and number. Our results suggest a bias against estimating outcrossing rates in the lower half of the distribution, but not specifically against highly selfing species.
6821 Patient reported experiences of a tertiary post COVID service
ObjectivesPost COVID Syndrome is a poorly understood disorder affecting around 62,000 children and young people (CYP) in the UK.1 Our tertiary regional CYP Post COVID service was established to provide holistic medical, rehabilitative, and psychological assessment and management for the most severely affected CYP. Here we evaluate the experience of CYP and their families who have accessed the service.MethodsWe requested feedback from all patients seen in our CYP Post COVID clinic via a QR code provided in person at clinic appointments and on clinical correspondence. We collected quantitative data scoring outcomes from 1–5 on a Likert scale and qualitative data on patients‘ experience of the service and how it could be improved.Results18 patients and 33 parents/carers completed the survey between March 2022 – October 2023. 91% felt listened to; 90% got the consultation they needed; 82% felt the service helped them understand their difficulties and 94% felt involved in decisions about their care.Three key themes were noted: 1) Participants reported the importance of being listened to and having their concerns taken seriously: ‘We were properly listened to and heard/understood by people who know how tough it’s been and how much effort it took to get to the appointment.’ 2) They felt input from a multidisciplinary team was beneficial: ‘Having experts of different specialties in the same room and combining their experience was very helpful.’ 3) They would like access to additional investigations, research and advice on medical interventions: ‘It’s depressing that more can’t be done. Physiotherapy and pacing is helpful but doesn’t really address the root cause.’More than half of those surveyed reporting accessing other resources prior to their clinic appointment including websites, leaflets and other clinical services. Several participants commented on treatments they had obtained privately.ConclusionThis provides further understanding of what CYP and their families want from a Post COVID service. The value of a multidisciplinary approach, listening to patients, helping them understand their condition and involving them in decisions should not be underestimated. However many patients want further investigation and trials of/management with unlicenced novel treatments. We are increasingly performing prolonged heart rate and blood pressure monitoring to detect autonomic dysfunction which informs our diagnosis of comorbidities and management plans. We aim to improve resources on novel treatments to enable patients to make informed choices about treatments offered outside our service while continuing to advocate for CYP research in Post COVID syndrome.ReferencesPrevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK, Office for National Statistics (ONS), 30 March 2023
NAP1 Strain Type Predicts Outcomes From Clostridium difficile Infection
Background. Studies are conflicting regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. Methods. CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15 000 cells/μL within 1 day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. Results. Strain typing results were available for 2057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%), and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [AOR], 1.74; 95% confidence interval [CI], 1.36–2.22), severe outcome (AOR, 1.66; 95% CI, 1.09–2.54), and death within 14 days (AOR, 2.12; 95% CI, 1.22–3.68). Conclusions. NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.
A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma
IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.