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Levoatriocardinal vein is a rare venous anomaly occasionally presenting as a bidirectional shunt in structurally normal hearts. We describe two unique systemic connections of levoatriocardinal vein without intracardiac defects, one causing paradoxical embolism via the hemiazygos vein, and the other draining from the left jugular vein to the pulmonary vein, requiring surgical correction to preserve cerebral venous return.
Rural America remains deeply under-represented in clinical trials. St Lawrence Health (SLH) was the sole rural site and one of the top recruiters in the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-1 trial, which was a large international trial that studied the efficacy of three immune modulators in hospitalized patients with COVID-19. In this article, we analyze the structural and clinical factors that enabled SLH’s success in the context of previously described barriers to research participation in rural areas. We conclude with lessons learned from the SLH experience and offer a broader replicable model for developing clinical research capacity in rural areas. SLH’s success in ACTIV-1 can be attributed to early and sustained support from the ACTIV-1 network, a small and integrated inpatient COVID-19 treatment team, regular and consistent communication between this team and the clinical research team at SLH, and SLH’s ongoing support and development of its clinical research department. SLH was, in turn, able to overcome several known barriers to implementation of clinical trials at community sites, including lack of provider time and a lack of trained research and clinical staff, and its experience in ACTIV-1 offers a replicable model for developing clinical research capacity in rural communities.
Previous studies have shown that low-fat diet (LFD) is associated with various health benefits, and that lipid and fatty acid metabolism is linked to telomere shortening. However, no epidemiological studies have examined the association between LFD and telomere length (TL). Dietary information was collected using 24-h recalls among 6981 adults from a nationwide cross-sectional study. Diet quality was assessed using overall LFD, healthful LFD (hLFD) and unhealthful LFD (uLFD). TL was measured using quantitative PCR. Linear regression was employed to evaluate the association between LFD and log-transformed TL, and ordinal logistic regression was performed to assess the association of LFD with ordinal quintiles of TL in descending order. In both fully adjusted linear and ordinal regression models, higher overall LFD (Tertile 3 v. Tertile 1: percentage change = 2·48 %, 95 % CI: 0·60 %, 4·40 %, Ptrend = 0·003; OR = 0·79, 95 % CI: 0·68, 0·93; Ptrend = 0·001) and hLFD (Tertile 3 v. Tertile 1: percentage change = 2·71 %, 95 % CI: 0·87 %, 4·58 %; Ptrend = 0·002; OR = 0·84, 95 % CI: 0·72, 0·97; Ptrend = 0·003) scores were significantly associated with longer TL. The positive association between hLFD and TL was observed in other racial/ethnic groups, but not in non-Hispanic whites (Pinteraction < 0·005). There was no significant association between uLFD and TL in all the models. Our results suggest that LFD rich in high-quality carbohydrates, unsaturated fat and plant protein is associated with longer TL and underscore the need to consider the quality and dietary sources of the macronutrients.
Low enrollment of racial/ethnic minorities in clinical trials is a persistent problem. This study explores community health workers’ (CHWs) potential to increase research participation by Black people. We interviewed 12 CHWs and 12 Black community members, and after multidisciplinary analysis, held a CHW focus group to refine themes and make recommendations. Most participants mistrusted research, but many valued its potential for generativity. CHW involvement in research was seen as an opportunity to bring community relationships and context to all aspects of research, including recruitment. Participants proposed steps to build trustworthy research experiences and develop CHWs as full research team members.
Alpha-ketoglutarate (AKG) is a well-known intermediate of the tricarboxylic acid cycle and plays an important role in the catabolism of branched-chain amino acids (BCAAs: leucine, isoleucine, and valine). While previous study suggested that AKG enhances glucose metabolism, its effect on the adaptation of muscles and adipocytes has not been well studied in diabetic condition. This study aimed to determine whether AKG improves glucose metabolism in the skeletal muscles and adipose tissues in diabetic mice. Male institute of cancer research mice were divided into control, diabetic, and diabetic + AKG groups. Diabetes (DM) was induced by a high fat diet consumption and streptozotocin (STZ) injection. Mice in the DM + AKG group were administered 1% AKG in drinking water for 6 weeks. The non-fasting plasma glucose level was significantly higher in the diabetic group than that in the control and DM + AKG groups (P < 0.05). No significant difference was observed in glucose transporter 4 (GLUT4) protein levels in the muscles between the DM and DM + AKG groups. AKG supplementation attenuated the decrease in peroxisome proliferator-activated receptor γ coactivator 1 alpha and GLUT4 protein levels in inguinal and epididymal adipose tissues in diabetic condition. In conclusion, the study findings suggested that AKG supplementation increased protein levels related to mitochondrial biogenesis and glucose transporters in adipocyte tissue accompanied with improved whole-body glucose metabolism in STZ and high-fat diet-induced diabetic mice.
Cognitive problems represent one of the most common symptom dimensions in functional neurological disorder (FND; >80% of patients) and are frequently associated with distress, disability, and difficulties engaging in evidence-based treatments such as psychotherapy. Cognitive difficulties occur across the FND subtypes (eg, seizures, movement disorders, dizziness) but are largely underrecognized and undertreated by healthcare providers. That is, although a variety of interventions are available for primary functional symptoms and mental health comorbidities, there have not been any systematic efforts to date to specifically target cognitive functioning in FND, leaving an important gap in the literature.
Cognitive rehabilitation is a flexible approach utilizing diverse techniques aimed at improving cognition and enhancing functional independence in people with neuropsychiatric disorders. Cognitive rehabilitation can have positive impacts (moderate effect sizes) on cognition and everyday functioning across a variety of conditions, including traumatic brain injury, mild cognitive impairment, long COVID, PTSD, and others. Given the transdiagnostic clinical utility of cognitive rehabilitation, it has potential for benefit in many patients with FND if adapted and applied appropriately.
In this review, we highlight the utility of cognitive rehabilitation for FND, with a focus on clinically actionable advice and guidance. We describe fundamental principles of cognitive rehabilitation, evidence for its efficacy and effectiveness across neuropsychiatric disorders, and methods for avoiding potential pitfalls when applying it in FND. We then discuss a Case Vignette in order to emphasize the application of cognitive rehabilitation principles in an individual patient. We conclude with future directions for research and clinical care.
Decades of research have identified a strong association between heavy cannabis use and schizophrenia (SCZ), with evidence of correlated genetic factors. However, many studies on the genetic relationship between cannabis use and psychosis have lacked data on both phenotypes within the same individuals, creating challenges due to unmeasured confounding. We aimed to address this by using multimodal data from the All of Us Research Program, which contains genetic data as well as information on SCZ diagnosis and cannabis use.
Methods
We tested the association between cannabis use disorder (CUD) and SCZ polygenic scores (PGSs) with SCZ and heavy cannabis use. We tested models where both CUD and SCZ PGSs were included as joint predictors of heavy cannabis use and SCZ case status. We defined three sets of cases based on comorbidities: relaxed (assessing for only the primary condition), strict (excluding comorbidity), and dual-comorbidity.
Results
CUD and SCZ polygenic liability were independently associated with heavy cannabis use; the SCZ PGS effect was very modest. In contrast, both SCZ and CUD PGSs were independently associated with SCZ, with independent significant effects of CUD PGS. Polygenic liability to CUD was associated with SCZ in individuals without a documented history of cannabis use, suggesting widespread pleiotropy.
Conclusions
These findings underscore the need for comprehensive models that integrate genetic risk factors for heavy cannabis use to advance our understanding of SCZ etiology.
There is a gap in the understanding of meal patterns offered to students targeted by the National School Feeding Programme (PNAE). This study aimed to identify and analyse the menu patterns planned in schools participating in the PNAE. This observational cross-sectional study was carried out from a database consisting of 557 weekly menus from primary schools across Brazilian municipalities. We used factor analysis (FA) with principal components analysis (PCA) to identify menu patterns. Nutritional quality assessment of the menus was based on the Revised School Feeding Menu Quality Index (IQCAE-R). Differences in nutritional quality and associations with sociodemographic factors were analysed using the Kruskal–Wallis test, followed by Wilcoxon post hoc testing with Bonferroni correction. Two menu patterns were identified: (1) ‘Traditional’, predominantly composed of cereals and pasta, roots and tubers, legumes, vegetables, and meats and eggs; and (2) ‘Snack’, with a higher occurrence of bread, cakes, and biscuits, milk and dairy products, chocolate powder, and coffee and tea. The ‘Traditional’ pattern, consisting of food items commonly found in Brazilian food culture, and the ‘Snack’ pattern, characterised by the presence of sweets and highly processed foods, showed significant relationships with sociodemographic variables and nutritional quality of menus. Stimulating schools to provide meals that resemble the ‘Traditional’ pattern may contribute to the adoption of healthier dietary patterns, thus benefiting and strengthening health promotion through PNAE.
In-hospital strokes comprise a small but high-risk subgroup of patients and are associated with worse outcomes compared to community-onset strokes. We compared clinical characteristics, workflow metrics and clinical outcomes of adult patients with in-hospital strokes and those with community-onset strokes in Alberta.
Methods:
We conducted a retrospective cohort study (INPATIENTS: IN-hosPitAl sTrokes InAlbErta iNcidence and ouTcomeS) from Jan 1, 2018–Dec 31, 2022 using provincial administrative data and chart review to compare in-hospital and community-onset acute ischemic and hemorrhagic strokes. We performed multivariable logistic regression to determine the association of stroke onset location (in-hospital vs community-onset) with the following outcomes: in-hospital mortality, prolonged hospital stay and in-hospital complications. Negative binomial regression was conducted to compare workflow metrics between cohorts. All models were adjusted for age, sex, comorbidities, facility type and admission year.
Results:
Among 24,039 stroke admissions, 2,545 (10.6%) were in-hospital strokes and 20,895 (86.9%) were ischemic. In-hospital strokes had higher rates of comorbidities and were associated with higher in-hospital mortality (adjusted OR [aOR] 3.09; 95% CI 2.80–3.41), prolonged hospital stays (aOR 5.47; 95% CI 4.89–6.112) and increased in-hospital complications. In-hospital ischemic stroke patients receiving thrombectomy showed lower odds of in-hospital mortality (aOR 0.46; 95% CI, 0.28–0.75) and pneumonia (aOR 0.38; 95% CI, 0.20–0.71) compared to non-treated patients. Workflow times were significantly longer in in-hospital ischemic strokes compared to community-onset strokes.
Discussion:
Patients with in-hospital stroke experience higher rates of mortality, poorer clinical outcomes and significant delays in management. Targeted quality improvement efforts are needed to address care gaps and improve outcomes in this population.
Antidepressants are the primary treatment for major depressive disorder (MDD), yet their precise neurobiological mechanisms remain incompletely understood. This study aimed to elucidate neural differences between medicated and unmedicated MDD patients by analyzing resting-state functional magnetic resonance imaging data.
Methods
We conducted a coordinate-based meta-analysis, complemented by behavioral, genetic, and neurotransmitter-level evaluations to identify potential therapeutic targets and diagnostic biomarkers. Using seed-based d-mapping with permutation of subject images (SDM-PSI), we assessed brain activation changes associated with antidepressant treatment. The identified regions were further characterized using large-scale molecular and functional brain databases.
Results
A total of 59 studies on unmedicated MDD (2,618 patients, 2,486 controls) and 15 studies on medicated MDD (541 patients, 483 controls) were included. The meta-analysis revealed significantly increased activation in the left striatum among medicated patients, a region linked to cognitive functions such as memory and perception. Gene expression analysis highlighted SLC5A7 and prolactin (PRL) as key genes in this region, while neurotransmitter mapping showed associations with serotonin (5-HT1a, 5-HT2a) and dopamine (D1, D2) receptors. Additionally, reduced activation in the left middle occipital gyrus (MOG) was observed across both medicated and unmedicated groups. This region, implicated in recognition and face processing, showed high expression of TFAP2B and PRL and was associated with serotonin and norepinephrine transporter distributions.
Conclusions
These findings suggest that the left striatum may represent a core neurofunctional target of antidepressant treatment, while the left MOG may serve as a stable neurobiological marker for MDD diagnosis, independent of pharmacological status.
This study investigates the potential aerosol transmission of respiratory syncytial virus (RSV), a major cause of viral pneumonia and bronchiolitis in young children.
Methods:
Two hundred samples were collected in a long-term environmental surveillance program from January 2022 until January 2023. Samples were collected in a pediatric emergency corridor. The analyses were performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) targeting the RSV matrix gene. Information on the daily number of emergencies related with pediatric RSV infections was provided by the hospital.
Results:
Aerosol samples collected from a pediatric hospital corridor revealed detectable RSV RNA, particularly during peak infection seasons. RSV RNA was detected in 35 of 200 aerosol samples with a median concentration (interquartile range) of 1.8 (4.1) gc/m3. During the month of the peak season of RSV infections (November), RSV RNA was detected in 95% of the aerosol samples. Correlation analysis suggests a link between pediatric RSV cases and airborne RSV RNA concentration.
Conclusions:
RSV RNA has been detected in aerosols in a healthcare setting, particularly during peak infection periods. This does not constitute evidence of transmission of the RSV via aerosols. However, the observed correlation with pediatric RSV cases suggests that further research on viral viability and infectivity from RSV detected in aerosols should be conducted. It also shows the potential of characterizing RSV RNA in aerosols for environmental surveillance purposes.
In this post hoc analysis of a quasi-experimental pilot/feasibility trial, a bundled diagnostic stewardship intervention safely reduced respiratory culturing rates without increasing ventilator-associated events (VAEs). Using difference-in-differences methodology, we observed a significant reduction in possible ventilator-associated pneumonia (PVAP) events, suggesting the intervention may reduce pneumonia overdiagnosis without compromising patient safety.
Since the introduction of health technology assessment (HTA) in Ukraine, the international technical assistance project “Safe, Affordable, and Effective Medicines for Ukrainians” with financial contributions of the United States Agency for International Development has supported capacity building activities. In 2020, the main HTA stakeholders expressed interest in a comprehensive training program for HTA doers, users, and trainers.
Approach
To inform the design of a training program, the needs of forty HTA doers, users, and potential trainers were assessed using validated surveys. Identified knowledge gaps included comparative effectiveness, health economics, qualitative evidence synthesis, patient and public involvement, and ethical issues. Based on these results a tailored training program consisting of five modules was developed, including an introduction to HTA, as well as a train-the-trainers program.
Results
During January–July 2023, seventy-five persons participated in the training program, while twelve HTA professionals followed the train-the-trainer program. We evaluated participants’ self-reported knowledge and skill gains by asking about their confidence level in each learning objective at the beginning and end of each training module. For each module, a learning effect was observed among participants. Furthermore, the majority of trainers felt confident to provide the introductory module on HTA, while for the other modules only one or two trainers felt completely confident to teach the content.
Conclusion
Establishing a training program based on the needs of HTA doers, users, and trainers as developed for Ukraine can serve as inspiration for other countries that wish to attain sustainable HTA capacity.
Rattus rattus is a known reservoir of zoonotic pathogens, including Bartonella and Rickettsia, transmitted by ectoparasites such as fleas, mites, lice and ticks. The circulation of Bartonella and Rickettsia in these vectors in Chile remains poorly characterized. To evaluate the association between ectoparasite abundance, prevalence and diversity (including lice, fleas, mites and ticks) and the presence of Bartonella and Rickettsia within ectoparasites collected from R. rattus across different anthropogenic gradients in Chile, a total of 1,339 ectoparasites were collected from 411 R. rattus individuals across 27 localities. Ectoparasites were identified morphologically, and molecular detection of bacteria was performed using conventional and qPCR, targeting multiple genetic markers. Haplotype diversity and phylogenetic relationships were assessed. Bartonella and Rickettsia DNA were detected in fleas, ticks, mites and lice of R. rattus, with prevalence values reported separately for pooled and individually analysed ectoparasites. Bartonella tribocorum, B. rochalimae and B. mastomydis were identified. Rickettsia felis was confirmed in multiple ectoparasite groups. High haplotype diversity was observed in Bartonella but not in Rickettsia. Urbanization and tick prevalence were negatively associated with Bartonella occurrence; flea and tick prevalences were negatively associated with Rickettsia. Rattus rattus and their ectoparasites harbour a diverse range of potentially zoonotic Bartonella and Rickettsia species. These findings highlight the need for integrated surveillance and vector control strategies, especially in areas with variable human-wildlife interaction.
Cancer clinical research networks (CRNs) play a vital role in medical research globally by generating investigator-initiated research, pooling expertise, and enabling recruitment across multiple sites. Completing clinical trials is challenging. Delays can slow the generation of evidence needed to refine the best patient treatments. The aim of this review was to identify factors that have been either proposed or shown by research to influence the performance of cancer CRNs to improve trial success, outcomes and impact. A scoping review was conducted using a systematic search across five databases [PROSPERO CRD42023414241]. Records were screened for eligibility. For included articles, data on factors and research methods were extracted independently by up to three reviewers, and disagreements resolved by discussion. 1928 articles were returned, 13 were included. Articles reported on 11 membership-based cancer CRNs with headquarters in four countries (eight in the USA). Factors influencing CRN performance broadly fell into six categories: site, CRN, patient, regulatory, policy and industry factors, with subcategories in each case. These findings may help to inform future research to prioritize and improve the day-to-day performance of membership-based cancer CRNs and other trial sponsors to optimize clinical trial success. Further research is warranted.
Through an integrative approach that combined microscopy and molecular analyses of the 18S rDNA gene, this study describes a novel haemococcidian species, Lankesterella nucleoflexa sp. nov., and presents data on another Lankesterella sp. Both parasites were found in the green iguana (Iguana iguana) from Eastern Amazonia, Brazil. Lankesterella nucleoflexa sp. nov. is characterized by a unique nuclear plasticity; its nucleus exhibits variable shapes and condensation states, appearing condensed and seemingly divided when adjacent to the host cell nucleus and elongated when positioned opposite. This species infects erythrocytes, monocytes and heterophils, inducing significant nuclear deformities. Phylogenetic analysis placed both Lankesterella sequences in a clade with other Lankesterella parasites from lizards, highlighting the genetic diversity of this genus within this host group. These findings expand the knowledge about parasitic biodiversity in Neotropical reptiles and underscore the necessity of integrating morphological and molecular methodologies to elucidate the taxonomy of understudied groups such as haemococcidians.
Afro-Colombian adolescents in Tumaco face high mental-health risks due to armed conflict and structural marginalization. We tested the short-term efficacy of the 3C program to strengthen resilience, compassion, and prosocial behavior and to reduce anxiety, depression, and PTSD. Mixed-methods cluster RCT with concurrent triangulation; multilevel mixed-effects models with multiple imputation; assessments at baseline, 6, and 9 months. Resilience increased by 13.14 points at 6 months (large effect, d = 0.89) and remained elevated at 9 months. Anxiety and PTSD screenings were lower in the intervention group across follow-ups. Compassion and prosocial behavior improved at 6 months but attenuated by 9 months. Depression screenings decreased at 6 months and rebounded at 9 months. Qualitative data aligned with these patterns (students reported sustained use of stress-management skills and peer support). 3C demonstrated short-term efficacy for resilience, anxiety, and PTSD but showed limited durability for compassion, prosociality, and depression without ongoing reinforcement. The pattern of effect attenuation—particularly the complete depression rebound—indicates that 3C provides a foundational component requiring integration with booster sessions to sustain socioemotional gains.