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Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.

We present a complicated case of mixed mechanism glaucoma in the setting of failed corneal transplant and aphakia. The patient was a 54-year old male with HLA B27 uveitis and prior open globe injury. He was left aphakic after cataract extraction and had a subsequent corneal transplant for bullous keratopathy. Due to elevated intraocular pressure in the setting of a failed corneal graft, the decision was made to insert a pars plana tube shunt and perform repeat penetrating keratoplasty as a combined case with the glaucoma, cornea, and retina services. We illustrate the surgical steps and decision making and in this complex case.

Desalination offers options to augment water supplies for growing urban and industrial demand. Yet these facilities and related infrastructure projects have significant impacts on environmental, economic, and social sustainability. However, few studies examine how key actors in the sector understand or incorporate sustainability ideas and practices into the design, construction, and operation of desalination facilities. This study fills this gap by examining stakeholder perspectives on sustainability in the desalination sector using Q-method. We identified three dominant social perspectives on these topics. Factor 1 views desalination as important for the long-term sustainability of water supply. Factor 2 sees the social and environmental impacts of desalination as too big of a sustainability risk when there are other water resources to consider. Factor 3 indicates that the parties pursuing desalination have the responsibility of addressing sustainability concerns through their proposals and project specifications. These perspectives reveal how desalination stakeholders understand sustainability, key challenges, and responsibility for ensuring sustainable desalination projects. The findings provide insight into how desalination stakeholders can improve sustainability processes and outcomes.

Misinformation related to vaccines has been shown to potentially negatively impact public perceptions and intentions to vaccinate in many contexts including COVID-19 vaccination in Ghana. Psychological inoculation – where recipients are warned about the misleading techniques used in misinformation – is a potential intervention which could preemptively boost public resistance against misinformation. Cranky Uncle Vaccine is an interactive, digital game that applies inoculation, offering a scalable tool building public resilience against vaccine misinformation and promoting positive health-related behaviors. In this study, we document the process of developing and testing a West African version of Cranky Uncle Vaccine, with co-design workshops and a pilot test conducted in urban and peri-urban areas of the Greater Accra region of Ghana with 829 young people who had access to mobile and computer devices. The average age was 21.8 and participants were highly educated (median education level “Some/all university”) with slightly more females (51.2%) than males (48.4%). Pilot participants filled out surveys before and after playing the game, measuring vaccine attitudes (pre-game M = 3.4, post-game M = 3.6), intent to get vaccinated (pre-game M = 3.5, post-game M = 3.6), and discernment between vaccine facts and fallacies (pre-game AUC = 0.72, post-game AUC = 0.75). We observed a significant improvement in attitudes toward vaccines, with players demonstrating increased likelihood to get vaccinated after completing the game. Among players who indicated that they were unlikely to get vaccinated in the pre-game survey (N = 52, or 6.3% of participants), just over half of these participants (53%) switched to likely to get vaccinated after playing the game. Perceived reliability of vaccine facts remained the same, while perceived reliability of vaccine fallacies significantly decreased, indicating improved ability to spot misleading arguments about vaccines. These results demonstrate the effectiveness of a digital game in building public resilience against vaccine misinformation as well as improving vaccine attitudes and intent to get vaccinated.

Fusarium verticillioides represents a major phytopathogenic threat to maize crops worldwide. In this study, we present genomic sequence data of a phytopathogen isolated from a maize stem that shows obvious signs of vascular rot. Using rigorous microbiological identification techniques, we correlated the disease symptoms observed in an affected maize region with the presence of the pathogen. Subsequently, the pathogen was cultured in a suitable fungal growth medium and extensive morphological characterization was performed. In addition, a pathogenicity test was carried out in a DCA model with three treatments and seven repetitions. De novo assembly from Illumina Novaseq 6000 sequencing yielded 456 contigs, which together constitute a 42.8 Mb genome assembly with a GC % content of 48.26. Subsequent comparative analyses were performed with other Fusarium genomes available in the NCBI database.

The advent of remote learning and the over-representation of international students in contract cheating literature have contributed to the beliefs that a digital pathway to higher education necessitates academic malpractice, and that this phenomenon is more prevalent among non-native students. This study seeks to contribute to the existing literature on international students and contract cheating by providing both holistic and nuanced student perspectives from survey and interview data. An online survey distributed to 117 students, of which 103 international students participated and a supplementary interview conducted with 6 additional participants from a UK university reveal a holistic and nuanced insight into the student perspective of contract cheating definitions and causes. The results support the currently scarce but emerging literature that a fear of failure and lack of self-confidence due to weak academic writing skills in English have a greater contribution to a student’s susceptibility to outsource their work than students’ automatic international status. This paper advocates for university support systems for academic writing skills in English to be shared among universities, and further suggests that these systems should be tailored and further promoted to the postgraduate student demographic.

Objectives The widespread adoption of wearables, for example, smartphones and smartwatches in the daily lives of the general population, allows passive monitoring of physiological and behavioural data in the real world. This qualitative study explores the perspective of psoriatic arthritis (PsA) patients towards these so-called digital biomarkers (dBMs).Methods As part of a Design Thinking approach, six focus groups were conducted involving 27 PsA patients. The semistructured topic guide included disease activity, coping strategies, care needs, and potential advantages and disadvantages of dBMs. Thematic analysis followed an abductive coding method.Results PsA daily permeates patients’ lives, both physically and mentally. Participants discussed how their lives are focused on minimising the impact of the disease on their daily routines. Their attempts to gain control over their disease highly depend on trial and error. Flare-ups are related to physiological as well as behavioural micro and macro changes. Understanding these changes could enable the detection of (early) flare. Participants elicited pros and cons of the use of dBMs, discussed their intended use and made practical remarks. This led to three main themes: ‘Perceived dBM opportunities’, ‘Mapping Disease activity’ and ‘Perceived dBM barriers and pitfalls’.Conclusion PsA patients are receptive to dBMs for tracking the disease symptoms. Disease activity is regarded multifaceted and thus, dBMs should include a broad range of features to truly reflect the disease activity status. Reducing the time of trial and error in learning to manage the disease is regarded beneficial. Establishing and maintaining the relationship with their attending physicians is a prerequisite, even if remote patient monitoring becomes an alternative for some physical hospital visits.

Purpose: Human papillomavirus (HPV) vaccine uptake is lower in rural areas, particularly for boys. The purpose of the study was to demonstrate how a participatory approach to developing a series of videos about the HPV vaccine better meets the informational needs of rural parents. Methods: We recruited six rural parents to participate on a parent advisory board (PAB). The PAB met monthly spanning five months (n = 5 meetings) from February to May 2023. Each meeting focused on an element of video creation, including: 1) Providing feedback on existing HPV vaccine videos created by federal agencies and developing a tailored plan for local rural parents; 2) Providing feedback on the video plan so the study team could draft scripts; 3) Editing scripts; 4) Finalizing video concepts; and 5) Providing feedback to produced videos. Between meetings, parents completed tasks to facilitate the process, which also served as a way for parent input to be documented. We worked with a local, professional videographer to produce the videos. A local parent and a nurse practitioner were recruited as actors. Results: Six one-minute videos were produced on the following topics: What is HPV?; Does the vaccine prevent cancer?; How does the vaccine work?; Is the vaccine safe?; Who should get the vaccine?; and Where can you go to get the vaccine? The PAB was essential in clarifying source, message, channel and receiver throughout the video creation process. Conclusions: Engaging parents to co-create a series of one-minute videos supports HPV vaccine confidence efforts in rural areas.

Shigella spp. cause bacillary dysentery (shigellosis) with high morbidity and mortality in low- and middle-income countries. Infection occurs through the fecal-oral route and can be devastating for vulnerable populations, including infants and the elderly. These bacteria invade host cells using a type III secretion system (T3SS). No licensed vaccine yet exists for shigellosis, but we have generated a recombinant fusion protein, L-DBF, combining the T3SS needle tip protein (IpaD), translocator protein (IpaB), and the LTA1 subunit of enterotoxigenic E. coli labile toxin, which offers broad protection in a mouse model of lethal pulmonary infection. The L-DBF vaccine protects high-risk groups, including young and elderly mice. Here, we investigated how the gut microbiota of young and elderly mice responds to intranasal L-DBF vaccination formulated in an oil-in-water emulsion (ME). Samples from lungs, small intestines, and feces were collected on day 14 after 2 or 3 doses of L-DBF in ME. 16S rRNA gene sequencing revealed age-dependent changes in gut microbiota post-vaccination. The vaccine-induced changes were more prominent in the elderly mice and were most significant in the intestinal tract, indicating that vaccination by the intranasal route can have a tremendous impact on the gut environment. These findings provide insight into the communication between the intranasal mucosal surface following subunit vaccination and the microbiota at a distant mucosal site, thereby highlighting the impact of vaccination and the host’s microbiome.

The benefits of probiotics in foods are well-studied, but maintaining their effectiveness requires survival through various stress conditions like processing, storage, and digestion. Safety concerns, such as antibiotic resistance and potential infections, have raised questions about using live probiotics. Although traditionally, probiotic foods require live microorganisms for beneficial effects, research suggests that inactivated (non-viable) probiotic cells and their metabolic byproducts can also provide health benefits. This has led to the introduction of terms like postbiotics (cell-free metabolic byproducts of probiotics) and parabiotics (inactivated probiotic cells and cell compounds). Most studies focus on Lactic Acid Bacteria (LAB) as sources of postbiotics and parabiotics, but there is limited research on yeast-derived compounds. Yeasts can produce diverse metabolites and unique intracellular components, potentially enhancing shelf-life, sensory qualities, safety, and health benefits in food products. This review explores the advances in bacterial and yeast postbiotics and parabiotics and their applications in food, pharmaceuticals, and feed systems.

Objectives: Although the incidence of malaria is increased in women in endemic areas after delivery compared to non-pregnant women, no studies have assessed the benefit of presumptive antimalarial treatment given postpartum. Methods: A randomised controlled trial investigating the efficacy of antimalarial treatment in preventing postpartum malaria was performed in healthy Papua New Guinea mothers immediately following delivery. Participants were randomised 1:1 to no treatment (n = 90) or artemisinin combination therapy (ACT), with further 1:1 ACT randomisation to artemether-lumefantrine (AL; n = 45) or dihydroartemisinin-piperaquine (DP; n = 45). Standardised reviews were conducted monthly for 6 months, including clinical assessment, malaria screening and haemoglobin measurement. The primary endpoint was incidence of slide-positive malaria within 6 months of delivery. Results: Of 183 recruited participants, 151 completed study procedures and were included in per-protocol analyses (no treatment n = 71, AL n = 40, DP, n = 40). Those allocated to ACT were significantly less likely to develop slide-positive malaria during the 6-month follow-up period compared to those who were untreated (n = 17 (21%) vs n = 27 (38%); P = 0.016; hazard ratio 0.49 (95% confidence intervals 0.27-0.90). There was no significant difference in malaria incidence between the two ACT groups. Conclusion: A treatment course of ACT at time of delivery halved the incidence of malaria infection during the first 6-month postpartum.

Objective: Stress is a driver of depression, and people with depression often struggle to cope with stress and anxiety. This study directly compares the mental health effects of a Wim Hof Method intervention to an active control condition (slow breathing) in women with high stress and high depressive symptoms. Methods: We randomized 84 healthy midlife women with high stress and high depressive symptoms to either: 1) the hormetic stress condition based on the Wim Hof Method (WHM) involving a breathing technique designed to induce intermittent hypoxia and cold showers (n = 41) or 2) an active comparison condition involving slow-paced breathing and warm showers (n = 43). We provided participants with daily audio instructions (15 min) for three weeks during the COVID-19 pandemic (2020–2021). Our primary outcomes were depressive symptoms, anxiety symptoms, and perceived stress collected at pre-intervention, post-intervention, and 3 months later. We also assessed daily stress rumination and affect with daily diary during the intervention, and participants completed a laboratory stressor, the Trier Social Stress Test, before and after the intervention, and provided samples for salivary cortisol reactivity. Results: Participants in the active control condition perceived the intervention to be more credible and expected greater mental wellbeing benefits compared to those in the Wim Hof Method condition. Differential attrition was observed with six participants (7 %) dropping out -- all from WHM condition. Among the participants who completed the intervention, both groups improved on mental health outcomes immediately after the intervention with a 24 % reduction in depressive symptoms, a 27 % reduction in anxiety symptoms, and 20 % reduction in perceived stress. Improvements were maintained at the 3-month follow-up with 46 % of the sample reporting mild or no depressive symptoms. Participants in the WHM condition had significant reductions in rumination after daily stressful events compared to those in the active control group. Both conditions had reduced daily negative affect across the intervention and lower peak cortisol reactivity to the lab stressor post-intervention. Conclusions: Counter to the preregistered predictions, and despite participants’ differing expectations, the interventions led to equivalent reductions in depressive symptoms, anxiety symptoms, and perceived stress, which were sustained at three months. They also produced comparable reductions in cortisol reactivity and daily negative affect. However, the WHM condition was associated with greater reduction in reported rumination after daily stressful events than the active control, a finding that needs replication with larger and more diverse samples.

ABSTRACT Indigenous lands are increasingly recognized for their critical role in biodiversity conservation. However, concerns persist about the sustainability of hunting practices within these territories. This study investigates the long‐term impact of Indigenous hunting practices on wildlife populations in the Cofán territory of Zábalo, Ecuador. We employed line transect surveys to estimate wildlife densities over three periods (2001–2003, 2006–2009, and 2018), focusing on 16 species that are integral to local livelihoods and subject to community management. Our results indicate generally stable or increasing populations for most species, particularly in nonhunted areas, where spatial restrictions are enforced. The Cofán's ability to sustainably manage relations between humans and wildlife is largely attributable to their adaptive management system, which includes species‐specific regulations and spatial zoning, and is realized through community decision‐making, knowledge sharing, and an ethos of care. These findings demonstrate that Indigenous stewardship can effectively sustain biodiversity in complex biocultural systems. The study underscores the importance of integrating Indigenous knowledge with scientific approaches to achieve long‐term conservation goals.

The diagnosis of anthrax, a zoonotic disease caused by Bacillus anthracis can be complicated by detection of closely related species. Conventional diagnosis of anthrax involves microscopy, culture identification of bacterial colonies and molecular detection. Genetic markers used are often virulence gene targets such as B. anthracis protective antigen (pagA, also called BAPA, occurring on plasmid pXO1), lethal factor (lef, on pXO1), capsule-encoding capB/C (located on pXO2) as well as chromosomal Ba-1. Combinations of genetic markers using real-time/quantitative polymerase chain reaction (qPCR) are used to confirm B. anthracis from culture but can also be used directly on diagnostic samples to avoid propagation and its associated biorisks and for faster identification. We investigated how the presence of closely related species could complicate anthrax diagnoses with and without culture to standardise the use of genetic markers using qPCR for accurate anthrax diagnosis. Using blood smears from 2012-2020 from wildlife mortalities (n = 1708) in Kruger National Park in South Africa where anthrax is endemic, we contrasted anthrax diagnostic results based on qPCR, microscopy, and culture. From smears, 113/1708 grew bacteria in culture, from which 506 isolates were obtained. Of these isolates, only 24.7% (125 isolates) were positive for B. anthracis based on genetic markers or microscopy. However, among these, merely 4/125 (3.2%) were confirmed B. anthracis isolates (based on morphology, microscopy, and sensitivity testing to penicillin and gamma-phage) from the blood smear, likely due to poor survival of spores on stored smears. This study identified B. cereus sensu lato, which included B. cereus and B. anthracis, Peribacillus spp., and Priestia spp. clusters using gyrB gene in selected bacterial isolates positive for pagA region using BAPA probe. Using qPCR on blood smears, 52.1% (890 samples) tested positive for B. anthracis based on one or a combination of genetic markers which included the 25 positive controls. Notably, the standard lef primer set displayed the lowest specificity and accuracy. The Ba-1+BAPA+lef combination showed 100% specificity, sensitivity, and accuracy. Various marker combinations, such as Ba-1+capB, BAPA+capB, Ba-1+BAPA+capB+lef, and BAPA+lef+capB, all demonstrated 100.0% specificity and 98.7% accuracy, while maintaining a sensitivity of 96.6%. Using Ba-1+BAPA+lef+capB, as well as Ba-1+BAPA+lef with molecular diagnosis accurately detects B. anthracis in the absence of bacterial culture. Systematically combining microscopy and molecular markers holds promise for notably reducing false positives. This significantly enhances the detection and surveillance of diseases like anthrax in southern Africa and beyond and reduces the need for propagation of the bacteria in culture.

Introduction In Canada, care for individuals with hereditary cancer is fragmented across the provinces and territories, with carriers of pathogenic variants in cancer-susceptibility genes seeing multiple doctors and often advocating for their own management plans. The need for a national registry of carriers has been well established. While other cancer consortia exist, barriers in clinical and genomic data sharing limit the utility of the information gathered.Methods and analysis Within the province of Ontario, the Ontario Hereditary Cancer Research Network (OHCRN), funded by and located at the Ontario Institute for Cancer Research, is being developed to fill this gap. The registry will hold clinical, genomic and self-reported data from consented carriers and will make this data available to qualified researchers in anonymised and aggregated form. Individuals must agree to certain components to participate in OHCRN; there are also optional consents participants can agree to without impacting their involvement in OHCRN. We plan to open the registry for participant enrolment in mid-2025.Ethics and dissemination Ethics approval for registry creation was obtained from the Ontario Cancer Research Ethics Board, a centralised body that streamlines reviews for cancer research studies in Ontario. Registry data will be disseminated to participants and researchers as aggregate data through the OHCRN website and presented at scientific conferences, made available to Ontario Health (Cancer Care Ontario) to inform policy and evidence-based practice, as well as be available to the scientific community for further analysis and answering relevant questions.

Circulating public discourses about mathematics and mathematics learning shape how families and students make sense of their experiences with schooling. In the United States, these discourses can play a large role in how public education policy is developed due to the commitment of public school boards to hearing community voices as well as a recent (but not new) increase in the organization of well-funded conservative parent groups working to maintain–and exacerbate–the inequitable educational opportunities that persist in this country. In this paper we analyze public discourse around mathematics learning in one New York City local school board meeting. Using tools from interaction analysis, we examined the discourse surrounding a proposal to reinstate test-based screening for middle school admissions. We delineated two key features of “common-sense” assumptions around mathematics learning that circulated in this meeting–math learners stay on a one-dimensional learning trajectory, and with varying rates of advancement–and investigated how these assumptions played out in the construction of a figured world of “schooled mathematics.” We argue that the consequences that necessarily follow from these common-sense assumptions construct mathematics as hierarchical and fixed, placing learners on a one-dimensional learning trajectory. Finally, we locate this set of emergent assumptions in the neoliberal racial project and consider the ways in which they shape a particular imagination of schooling and mathematics under neoliberalism.

This study delves into the concepts of forgiveness, reconciliation, and nonviolence through the experiences of victims, social leaders, and academics involved in Colombia's peacebuilding initiatives. Using focus groups, audio/video recordings, and thematic analysis, the research developed comprehensive categories situated within Bronfenbrenner's bioecological framework. The results indicate that the journey towards forgiveness, reconciliation, nonviolence, and peace encompasses a gradient extending from individual subjective experiences to broader sociocultural contexts. These findings underscore the critical importance of addressing structural inequalities and upholding rights, with implications that resonate profoundly within Colombia's ongoing peacebuilding efforts. Victims provided narratives in a deeply personal and communitarian manner, while leaders and academics emphasized the pivotal role of the State in ensuring rights and addressing inequalities to facilitate forgiveness and reconciliation processes. Overall, the study underscores the complex interplay between personal, societal, and governmental factors in Colombia's peacebuilding efforts, offering valuable insights for future research and policy development.

Aim: Exploring the healthcare costs and resource use among privately insured US patients with posttraumatic stress disorder (PTSD). Methods: This study used Merative MarketScan data. The index date was defined as the first PTSD claim. Study period included a 1-year pre-index and 2-year post-index follow-up. Cases with only acute PTSD, cancer, or insurance gap during the study period were excluded. The PTSD with (PwC) and PTSD without comorbidities (PwoC) cohorts were defined by the presence/absence of comorbid mental health conditions (schizophrenia, bipolar and major depressive disorder). Baseline PTSD (BP) cohort included PwoC cases with only index PTSD event and without FDA-approved PTSDmedications or psychotherapy. Sub-analysis is conducted among patients with PTSD and substance/alcohol use disorder. Study cohorts were matched in a 1:1:1 ratio. Results: The matched sample included 5076 patients (1681 PwC, 1681 PwoC, 1714 BP). PwC patients had higher 2-year PTSD-related costs than PwoC and BP patients ($3762 vs $1750 and $841; all p < 0.001). The same trend was noted among all-cause and anxiety-related costs. PwC patients had higher 2-year PTSD-related inpatient and emergency department (ED) rates than PwoC (10.2% vs 1.7% and 6.8% vs 2.6%, all p < 0.001) and inpatient and outpatient rates than BP (10.2% vs 2.1% and 98.0% vs 93.1%; all p ≤ 0.004). The sub-analysis had 3776 patients (3154 PwC, 537 PwoC, 85 BP). PwC had higher 2-year PTSD-related costs than PwoC and BP ($7668 vs $2919 and $1,483; all p < 0.001). The same trend was noted in all-cause and anxiety-related costs. PwC also had higher 2-year PTSD-related inpatient and ED rates than PwoC (25.6% vs 10.4% and 12.7% vs 5.2%; all p < 0.001) and inpatient and outpatient rates than BP (25.6% vs 8.2% and 95.5% vs 84.7%; all p < 0.001). Conclusion: PTSD is associated with high healthcare costs and resource use. The highest economic burden was observed in patients with PTSD and mental health comorbidities.

Comprender las prácticas que hacen posible la existencia del encarcelamiento masivo en el Perú es una tarea mandatoria de abordar, aún más cuando esta habitualidad persiste en el marco de la pandemia por COVID-19. Con ese propósito, la autora presenta, desde la mirada de los actores, un análisis del modo de funcionamiento del sistema penal peruano, a través de la evaluación de las medidas que se emitieron para hacer frente a la pandemia, del juego político que hubo detrás de su creación y de las dificultades y/o limitaciones que se generaron para su implementación. El artículo se divide en tres secciones: la primera muestra el cuadro clínico del encarcelamiento masivo en el Perú y las características reales de la cárcel peruana; la segunda apunta al análisis y evaluación de la gestión de la problemática carcelaria desde una perspectiva cuantitativa y cualitativa y la tercera presenta las evidencias de la inconmovilidad del sistema penal en el Perú.

Summary:. Although the representation of women and ethnic minority students in the US medical schools has recently increased, discrepancies in representation among plastic surgery residents and faculty continue. The state of sex and ethnic diversity in academic microsurgery remains minimally investigated. We aimed to evaluate the sex, race, and ethnicity demographics among academic microsurgeons and identify underrepresentation along the leadership pathway. The US-based microsurgery fellowship programs provided contact information of fellowship graduates from 2006 to 2020. An anonymous electronic survey was distributed, and demographic, training background, mentorship, and career path data were collected. Program websites were reviewed to collect data on academic microsurgery faculty nationwide. We found that women and non-White surgeons reported similar rates of effective mentorship in training. Compared with White surgeons, non-White surgeons had lower probability of holding an academic position directly after fellowship (odds ratio = 0.28, P = 0.023) and reported fewer perceived opportunities for professional advancement (61% versus 91%, P = 0.007). The majority of academic leadership positions were held by White surgeons (72%). Overall, women faculty were earlier in their careers than men (mean time out of fellowship 7.2 years for women versus 14.8 years for men, P < 0.001), signifying a lack of senior female faculty. Male faculty had higher rates of leadership than female faculty (24.7% versus 8.0%, P = 0.01). Our results demonstrate that women and non-White surgeons are not adequately represented in academic microsurgery faculty and leadership positions. Future interventions seeking to increase diversity can help improve the delivery of equitable reconstructive care.

Thirteen studies were included in the current systematic review and meta-analysis with 1131 participants. Both within- and between-group comparisons demonstrated reductions in depressive and PTSD symptoms with medium effect sizes post MBSR intervention. Additionally, MBSR demonstrated small effects in improving mindfulness in veterans at post-intervention. Maintenance of treatment effects were observed at follow-up for the three outcomes during within-group comparisons. Treatment effects were maintained at follow-up between-groups for depression and mindfulness, but not for PTSD symptoms. Furthermore, there were no significant differences between MBSR and cognitive behavioural therapy/person-centred group therapy intervention groups in the three outcomes.

Substance use disorder (SUD) is a persistent public health issue that necessitates the exploration of novel therapeutic interventions. Low-intensity focused ultrasound (LIFU) is a promising modality for precise and invasive modulation of brain activity, capable of redefining the landscape of SUD treatment. The review overviews effective LIFU neuromodulatory parameters and molecular mechanisms, focusing on the modulation of reward pathways in key brain regions in animal and human models. Integration of LIFU with established therapeutics holds promise for augmenting treatment outcomes in SUD. The current research examines LIFU’s efficacy in reducing cravings and withdrawal symptoms. LIFU shows promise for reducing cravings, modulating reward circuitry, and addressing interoceptive dysregulation and emotional distress. Selecting optimal parameters, encompassing frequency, burst patterns, and intensity, is pivotal for balancing therapeutic efficacy and safety. However, inconsistencies in empirical findings warrant further research on optimal treatment parameters, physiological action mechanisms, and long-term effects. Collaborative interdisciplinary investigations are imperative to fully realize LIFU’s potential in revolutionizing SUD treatment paradigms and enhancing patient outcomes.

IntroductionBiochar has gained significant attention as a possible anti-methanogenic supplement for ruminants due to its potential to reduce methane (CH₄) emissions from enteric fermentation. However, its effects on rumen methanogenesis have been inconsistent and, in some cases, contradictory. These variations are likely influenced by factors such as the type of biochar used, its source material, and how it is administered, including the form in which it is provided and the dosage needed to achieve desired outcomes. This study aimed to examine the effects of two fit-for-purpose biochars on rumen fermentation, CH4 emissions, and the rumen microbiome of cattle-fed roughage-based diets. Two experiments were conducted to assess the potential of biochar in mitigating CH4 emissions.Experiment 1This was a controlled pen trial conducted over 56 days, involving 12 steers that were fed Rhodes grass hay ad libitum. The animals were assigned to one of four treatment groups: control (no biochar, only molasses), low dose (50 g biochar/animal/day), mid dose (100 g biochar/animal/day), or high dose (200 g biochar/animal/day). Two types of biochar, Biochar 1 and Biochar 2, were administered with molasses (200 mL per animal/day). Methane emissions were measured using open-circuit respiration chambers, and rumen fluid samples were collected for analysis of the rumen microbial community and fermentation metabolite.Experiment 2In this trial, 45 heifers were selected and grazed together in a single paddock for 60 days to assess the effects of biochar on productivity and CH4 emissions under grazing conditions. The animals were allocated to one of three treatment groups (15 animals per group): control (no biochar, only molasses), Biochar 1, or Biochar 2. Each group was administered biochar at an estimated single dose of 100 g per animal/day mixed with molasses. Methane emissions were measured using GreenFeed systems in the field to monitor CH₄ production from individual animals.ResultsIn the controlled pen trial (Experiment 1), biochar supplementation resulted in a reduction of CH₄ emissions by 8.8–12.9% without any negative effects on rumen fermentation or dry matter intake (DMI). Minor changes were observed in the rumen bacterial community, particularly in the Christensenellaceae and Prevotellaceae families. However, in the grazing trial (Experiment 2), no significant differences in CH₄ emissions or productivity were detected with biochar supplementation.ConclusionWhile the results from controlled feeding conditions suggest that biochar has the potential to reduce enteric CH₄ emissions, the lack of significant findings under grazing conditions highlights the need for further research. Future studies should focus on identifying biochar types, doses, and delivery methods that are effective in reducing CH₄ emissions in grazing systems without compromising cattle productivity.

IntroductionElderly dogs often suffer from chronic diseases, in part attributed to immunosenescence, characterized by reduced blood CD4+ T cells (helper T cells) and elevation in the CD8+ T cells subset (cytotoxic T cells). Studies conducted in adult dogs suggested that supplementing short chain fructo-oligosaccharides (scFOS) or postbiotics derived from yeasts may positively influence the immune response. The aim of the current study was to investigate whether dietary supplementation with a combination of scFOS with a new yeast postbiotic (Profeed ADVANCED® called scFOS+) could have a positive influence on the immune status of senior dogs subjected to an immune challenge (Lyme disease vaccination).MethodsTo this end, 22 healthy senior client-owned dogs were divided into two groups: one group received a placebo diet without scFOS+ and the other group the basal diet supplemented with 1.1% scFOS+. In order to assess immune function, complete blood count, serum acute phase proteins, immunoglobulins, cytokines, T-cell subsets and antibody secreting cells were analyzed. Furthermore, faecal score and pH were recorded.Results and discussionDogs fed the scFOS+ supplement had decreased total serum IgA concentrations (p

Stress physiology contributes to health outcomes. Hair cortisol concentration (HCC) is an objective measure of cumulative cortisol secretion associated with health, including pain. The aim of the current study was to describe associations between pre-injury stress physiology (as measured by HCC), acute pain characteristics and relevant demographic factors (i.e., BMI, age, sex, days since injury) in youth with an acute musculoskeletal (MSK) injury. Participants were 58 youth aged 11 to 17 with acute MSK pain. Participants completed self-report measures assessing pain intensity, pain catastrophizing, and pain interference. Hair was collected within 1 month after injury using hair cortisol collection procedures adapted from published research protocols. Correlations examining associations among HCC values and clinical/demographic factors revealed that higher HCC was associated with lower body mass index (BMI) and male sex. HCC was not associated with pain variables or age. Additional research is needed to clarify the relation between HCC and psychosocial variables to aid researchers in studying the role of pre-injury stress in acute MSK injury and pain recovery in youth.

Background Despite the frequent co-occurrence of depression and diabetes, gender differences in their relationship remain unclear. Aims This exploratory study examined if gender modifies the association between depressive symptoms, prediabetes and diabetes with cognitive-affective and somatic depressive symptom clusters. Method Cross-sectional analyses were conducted on 29 619 participants from the 2007–2018 National Health and Nutrition Examination Survey. Depressive symptoms were measured by the nine-item Patient Health Questionnaire. Multiple logistic regression was used to analyse the relationship between depressive symptoms and diabetes. Multiple linear regression was used to analyse the relationship between depressive symptom clusters and diabetes. Results The odds of having depressive symptoms were greater in those with diabetes compared to those without. Similarly, total symptom cluster scores were higher in participants with diabetes. Statistically significant diabetes–gender interactions were found in the cognitive-affective symptom cluster model. Mean cognitive-affective symptom scores were higher for females with diabetes (coefficient = 0.23, CI: 0.10, 0.36, P = 0.001) than males with diabetes (coefficient = −0.05, CI: −0.16, 0.07, P = 0.434) when compared to the non-diabetic groups. Conclusions Diabetes was associated with higher cognitive-affective symptom scores in females than in males. Future studies should examine gender differences in causal pathways and how diabetic states interact with gender and influence symptom profiles.

El presente artículo es parte de un proyecto de investigación cuyo objetivo es describir la relación entre las creencias de los formadores de profesores de Matemáticas, sobre las matemáticas, su enseñanza y aprendizaje, y su actuación en el aula. Se realizó un estudio de casos instrumental utilizando métodos cualitativos. En el estudio participaron dos formadores experimentados. Los datos se analizaron utilizando el instrumento denominado concepciones sobre la enseñanza y el aprendizaje de las matemáticas. Los resultados revelan una relación entre las creencias de los formadores y su actuación en el aula, sin embargo, dicha relación no es directa. Además, se evidenciaron varios aspectos que influyen en la formulación de las creencias de los formadores, lo que a su vez impacta en la manera de actuar de estos en el aula.

BackgroundPerivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer’s disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment.MethodsUsing brain MRI scans acquired at 1.5 T, PVS were quantified in a cohort of 461 individuals, consisting of cognitively healthy controls (n = 48), people with mild cognitive impairment (MCI, n = 322) and Alzheimer’s disease (AD, n = 91). PVS volume fraction was calculated in the basal ganglia and centrum semiovale using a semi-automated segmentation approach. Stress was quantified with levels of salivary cortisol. Inflammatory biomarkers measured from plasma included cytokines, matrix metalloproteinases and C-reactive protein. General linear models were used to test the relationship between PVS and cortisol, when interacting with inflammatory markers. This was done on the whole cohort and within each clinical cognitive group.ResultsIn the centrum semiovale, higher inflammation levels reduced the relationship of cortisol with PVS. In basal ganglia, higher levels of C-reactive protein reduced the negative relationship of cortisol with PVS. All analyses were accounted for age, sex, body mass index (BMI) and total hippocampal volume. There was a significant interaction effect between cortisol and C-reactive protein on PVS volume fraction in the MCI group.DiscussionThese findings suggest an influence of neuroinflammation on the PVS structure in Alzheimer’s disease spectrum, and offer insight for better understanding physiological processes of cognitive impairment onset.

ABSTRACT Introduction Multicancer detection tests (MCDs) are blood‐based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs. Methods We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi‐structured guide containing open‐ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified. Results Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow‐ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result. Conclusions There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools.

BackgroundGames are increasingly used in eHealth as a strategy for user engagement. There is an enormous diversity of end users and objectives targeted by eHealth. Hence, identifying game content that drives and sustains engagement is challenging. More openness in the game design process and motivational strategies could aid researchers and designers of future game-based apps. ObjectiveThis study aims to provide insights into our approach to develop game-based eHealth in practice with a case study (Personalised ICT Supported Services for Independent Living and Active Ageing [PERSSILAA]). PERSSILAA is a self-management platform that aims to counter frailty by offering training modules to older adults in the domains of healthy nutrition and physical and cognitive training to maintain a healthy lifestyle. We elaborate on the entire game design process and show the motivational strategies applied. MethodsWe introduce four game design phases in the process toward game-based eHealth: (1) end-user research, (2) conceptualization, (3) creative design, and (4) refinement (ie, prototyping and evaluations). ResultsFirst, 168 participants participated in end-user research, resulting in an overview of their preferences for game content and a set of game design recommendations. We found that conventional games popular among older adults do not necessarily translate well into engaging concepts for eHealth. Recommendations include focusing game concepts on thinking, problem-solving, variation, discovery, and achievement and using high-quality aesthetics. Second, stakeholder sessions with development partners resulted in strategies for long-term engagement using indicators of user performance on the platform’s training modules. These performance indicators, for example, completed training sessions or exercises, form the basis for game progression. Third, results from prior phases were used in creative design to create the game “Stranded!” The user plays a person who is shipwrecked who must gather parts for a life raft by completing in-game objectives. Finally, iterative prototyping resulted in the final prototype of the game-based app. A total of 35 older adults participated using simulated training modules. End users scored appreciation (74/100), ease of use (73/100), expected effectivity and motivation (62/100), fun and pleasantness of using the app (75/100), and intended future use (66/100), which implies that the app is ready for use by a larger population. ConclusionsThe study resulted in a game-based app for which the entire game design process within eHealth was transparently documented and where engagement strategies were based on extensive user research. Our user evaluations indicate that the strategies for long-term engagement led to game content that was perceived as engaging by older adults. As a next step, research is needed on the user experience and actual engagement with the game to support the self-management of older adults, followed by clinical studies on its added value.

Objective The objective of this study is to identify the top 10 research priorities on reducing and stopping psychiatric medication that reflect the perspectives and unmet needs of three key stakeholder groups (people with lived experience, family members/carers/supporters and healthcare professionals).Methods A priority-setting partnership was conducted using the James Lind Alliance’s seven-step process. This involved (1) creating an international Steering Group of key stakeholder representatives and (2) identifying potential partners; (3) gathering stakeholders’ uncertainties about reducing and stopping psychiatric medication using an online survey and summarising the survey responses; (4) checking the summary questions against existing evidence and verifying uncertainties; (5) shortlisting the questions using a second online survey; (6) determining the top 10 research questions through a prioritisation workshop; and (7) disseminating the results.Results A total of 3635 questions were collected in the initial survey from 884 respondents of which 32 questions were verified as uncertainties. These questions were then ranked in a second online survey by 526 respondents and the findings discussed in a final prioritisation workshop by 30 participants to produce the final top 10 list of research questions. These questions cover a range of areas including the most effective ways of safely reducing/stopping psychiatric medication and providing support to individuals undergoing the discontinuation process, as well as the best ways to educate healthcare professionals on this topic.Conclusion The top 10 list of research priorities was produced through extensive engagement with key stakeholders and highlights important uncertainties and gaps in the existing evidence base that need to be addressed by future research.

Introduction There are no established methods to identify children with atypical diabetes for further study. We aimed to develop strategies to systematically ascertain cases of atypical pediatric diabetes using electronic medical records (EMR).Research design and methods We tested two strategies in a large pediatric hospital in the USA. Strategy 1: we designed a questionnaire to rule out typical diabetes and applied it to the EMR of 100 youth with diabetes. Strategy 2: we built three electronic queries to generate reports of three atypical pediatric diabetes phenotypes: unknown type, type 2 diabetes (T2D) diagnosed

Abstract The widespread medicinal use of Kalanchoe daigremontiana and Kalanchoe × houghtonii, both popularly known as “mother-of-thousands”, often leads to their interchangeable use in folk medicine despite their distinct species status. This research aims to delineate the histochemical, chemical, and biological characteristics of these two Kalanchoe species to aid in their accurate identification. Through a comprehensive evaluation of histochemical markers (reaction patterns in hypodermis), alongside in vitro assessments (correlation of antioxidant activities and phenolic content), and metabolomic profiles (using HPTLC and UPLC-MS/MSE), this study has identified significant differences between K. daigremontiana and K. × houghtonii. The findings reveal distinct variations in all evaluated parameters, underscoring the importance of proper species identification to ensure the safety and efficacy of their medicinal use. These results contribute valuable insights into the phytochemical and pharmacological bases for the traditional uses of these plants and highlight the need for distinguishing between species to avoid potential therapeutic inefficacies or adverse effects in folk medicine practices.

Objectives Carotid intima–media thickness (CIMT) is a measurement for subclinical atherosclerosis and has been associated with overall cardiovascular diseases, especially in type 2 diabetes mellitus (T2DM). We aimed to assess the status of carotid health and lipid profile in T2DM.Design This systematic review and meta-analysis synthesised data published from clinical studies.Data sources Google Scholar, PubMed and Scopus were searched from inception to 18 January 2024.Eligibility criteria for selecting studies Studies conducted in patients with T2DM and those without T2DM were included. Studies conducted in T2DM adults evaluating carotid status and lipid profile were considered.Data extraction and synthesis Two authors independently used standardised methods to comprehensively search, screen and extract data from all relevant studies. The risk of bias was assessed using the Newcastle-Ottawa checklist. Meta-analysis was conducted using Review Manager and metaHun through random effects models. The random effect model was used due to high heterogeneity.Results Evidence was analysed from 57 studies with a sample size of 29 502 (8254 T2DM and 21 248 people without T2DM). There was a significantly higher CIMT, with a standardised mean difference (SMD) of 1.01 (95% CI 0.75, 1.26, p

People have influenced Earth’s biodiversity for millennia, including numerous introductions of domestic and wild species to islands. Here, we explore the origins and ecology of the Santa Catalina Island ground squirrel (SCIGS; Otospermophilus beecheyi nesioticus), one of only five endemic terrestrial mammals found on California’s Santa Catalina Island. We synthesized all records of archaeological/palaeontological SCIGS, conducted radiocarbon dating and stable isotope analysis of the potentially earliest SCIGS remains and performed genetic analysis of modern SCIGS. Squirrels were not identified in island palaeontological deposits, but at least 12 island archaeological sites contain SCIGS bones, including some that are butchered or burned. All directly dated SCIGS bones are Late Holocene in age and younger than approximately 1290 cal BP. The first mitochondrial genome for modern Otospermophilus beecheyi and 15 modern SCIGS mitogenomes document at least one introduction of squirrels. Stable isotope data indicate variable SCIGS diets and potential subsidies from marine environments to terrestrial plants consumed by some individuals. We cannot rule out a natural overwater dispersal, but the earliest SCIGS remains post-date the earliest evidence for people by several millennia and, along with other lines of evidence, support a human-assisted translocation of squirrels during the Late Holocene. These data illustrate the important role of Indigenous people in shaping and enhancing island biodiversity and ecology around the world.

BCL-2 protein overexpression, common in B-cell acute lymphoblastic leukemia (B-ALL), including the Philadelphia (Ph)-like subtype, mediates leukemic cell survival. We treated 24 patients with 14 days of BCL-2 inhibitor, venetoclax, 400 mg daily (dose level 1) during induction and consolidation cycles combined with the CALGB 10403 regimen in newly diagnosed adults with Ph-negative B-ALL. Median age was 31 (range: 18-53) years, 92% were Hispanic, and 12 (50%) patients had Ph-like ALL. No dose limiting toxicity occurred in the phase 1 part. Median times to neutrophil and platelet count recovery were 20 and 21 days from start of induction, respectively. The most common grade ≥3 treatment-related adverse events were leukopenia (96%), neutropenia (83%), anemia (83%), thrombocytopenia (79%), lymphopenia (71%), hyperbilirubinemia (38%), and elevated ALT (33%). One patient with non-Ph-like ALL died from asparaginase-associated pancreatitis, and 23 (96%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) following induction with or without extended induction phase. Of 22 patients who started consolidation, 20 (91%) achieved negative minimal residual disease status (MRD-) (

Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Background: The period following pregnancy is a critical time window when future habits with respect to physical activity (PA) and sedentary behavior (SB) are established; therefore, it warrants guidance. The purpose of this scoping review was to summarize public health-oriented country-specific postpartum PA and SB guidelines worldwide. Methods: To identify guidelines published since 2010, we performed a (a) systematic search of 4 databases (CINAHL, Global Health, PubMed, and SPORTDiscus), (b) structured repeatable web-based search separately for 194 countries, and (c) separate web-based search. Only the most recent guideline was included for each country. Results: We identified 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB guidelines. The continents with guidelines included Europe (n = 12), Asia (n = 5), Oceania (n = 2), Africa (n = 1), North America (n = 1), and South America (n = 1). The most common benefits recorded for PA included weight control/management (n = 10), reducing the risk of postpartum depression or depressive symptoms (n = 9), and improving mood/well-being (n = 8). Postpartum guidelines specified exercises to engage in, including pelvic floor exercises (n = 17); muscle strengthening, weight training, or resistance exercises (n = 13); aerobics/general aerobic activity (n = 13); walking (n = 11); cycling (n = 9); and swimming (n = 9). Eleven guidelines remarked on the interaction between PA and breastfeeding; several guidelines stated that PA did not impact breast milk quantity (n = 7), breast milk quality (n = 6), or infant growth (n = 3). For SB, suggestions included limiting long-term sitting and interrupting sitting with PA. Conclusion: Country-specific postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing specific guidance to public health practitioners.

Abstract Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

Abstract Background The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally. Methods An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations. Results A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15–2.02)], having an academic appointment [2.45 (1.78–3.27)], having multiple co-morbidities [1.86 (1.41–2.48)], perceived burnout [1.99 (1.54–2.56)] and moderate to very high level of psychological distress [1.68 (1.18–2.39)]. Perceived burnout was associated with being female [1.35 (1.12–1.63)], having multiple co-morbidities [1.53 (1.20–1.97)], perceived job insecurity [1.99 (1.55–2.57)], and moderate to very high levels of psychological distress [3.23 (2.42–4.30)]. Staff with multiple co-morbidities [1.46 (1.11–1.92)], mental health issues [2.73 (1.79–4.15)], perceived job insecurity [1.61 (1.13–2.30)], and perceived burnout [3.22 (2.41–4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69–4.19)] were more likely to have medium to high resilient coping. Conclusions Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

Abstract Background Scientific research and innovation can generate societal impact via different pathways. Productive interactions, such as collaboration between researchers and relevant stakeholders, play an important role and have increasingly gained interest of health funders around the globe. What works, how and why in research partnerships to generate societal impact in terms of knowledge utilisation is still not well-known. To explore these issues, the Netherlands Organization for Health Research and Development (ZonMw) initiated an exploratory research-on-research study with a focus on participatory knowledge infrastructures (PKIs) that they fund in the field of public health and healthcare. PKIs are sustainable infrastructures in which knowledge production, dissemination and utilisation takes place via committed collaboration between researchers and stakeholders from policy, practice and/or education. Examples are learning networks, academic collaborative centres, care networks and living labs. The aim of the study was twofold: to gain insights in what constitutes effective collaboration in PKIs; and to learn and improve the research governance, particularly of ZonMw as part of their dissemination and implementation activities. Methods During 2020–2022, we conducted a literature review on long-term research partnerships, analysed available documentation of twenty ZonMw-funded PKIs, surveyed participants of the 2021 European Implementation Event, interviewed steering committee members, organized a Group Decision Room with lecturers, and validated the findings with key experts. Results We identified eight mechanisms (‘how and why’) that are conditional for effective collaboration in PKIs: transdisciplinary collaboration; defining a shared ambition; doing justice to everyone’s interests; investing in personal relationships; a professional organisation or structure; a meaningful collaborative process; mutual trust, sufficient time for and continuity of collaboration. Several factors (‘what’) may hinder (e.g., lack of ownership or structural funding) or facilitate (e.g., stakeholder commitment, embeddedness in an organisation or policy) effective collaboration in research partnerships. Conclusion To use the study results in policy, practice, education, and/or (further) research, cultural and behavioural change of all stakeholders is needed. To facilitate this, we provide recommendations for funding organisations, particularly ZonMw and its partners within the relevant knowledge ecosystem. It is meant as a roadmap towards the realisation and demonstration of societal impact of (health) research and innovation in the upcoming years.

Abstract Background Comprehensive cancer care requires effective collaboration by interprofessional healthcare teams. The need to develop educational initiatives to improve interprofessional collaboration is increasingly recognised. However, there is no agreement regarding the interprofessional competencies required for effective cancer care leading to much variation on the focus of research, planning and managing change. A scoping review was conducted to identify the current status of IPE in cancer care and to summarise the results of previous research in order to guide the development of interprofessional education in cancer care. Methods The JBI Scoping Review guidelines were used to guide the process of the review. A search of the available literature was conducted in CINAHL, MEDLINE (Ovid), PubMed, PsycInfo, Scopus databases from January 2012 to March 2023 to investigate IPE for health professional clinicians working in cancer care. Results Of the 825 initial references and 153 studies imported for screening, a total of 28 studies were included in the final review. From those studies, seven focused on the need for IPE and interprofessional competence for oncology healthcare professionals, four reviewed existing IPE programs and 17 described the development and evaluation of interprofessional education. Findings show variation and lack of concept definitions underpinning research in IPE in cancer care settings. Variation also exists in the range of research activities in IPE, most notably related to communication, teamwork and the development of interprofessional practice. The evaluation of impact of IPE is mainly focused on health care professionals’ self-evaluation and general feedback. Impact on patient care was only evaluated in one study. Conclusions Based on the results, interprofessional education research in the field of cancer care is limited in Europe. Thus, there is a significant increase in publications in the last five years. A more systematic focus on the theoretical framework and definition of concepts would be of value. Research and programme development should be based on a shared understanding on what constitutes the interprofessional competences and IPE. Programmes to develop interprofessional practice should be developed and implemented systematically with inclusion of validated assessment methods, and evaluated and improved regularly.

Los deslizamientos de tierra representan un peligro importante en muchas regiones montañosas, incluidos los valles interandinos del Perú. En este estudio evaluamos la dinámica del deslizamiento de Cuenca, ubicado en Huancavelica en el centro de Perú, empleando fotogrametría y mediciones GNSS. Se ejecutaron mediciones interanuales en ocho zonas entre 2016 y 2023 para GNSS y dos campañas de levantamiento fotogramétrico en 2023 para comparar los cambios de la superficie en el tiempo. Los resultados mostraron desplazamientos del orden de los 3,7 a 11,7 cm con la técnica de nube de puntos y 2,7 a 15 cm con el análisis de los ortomosaicos, siendo concordantes entre sí. Los desplazamientos en los puntos donde se han realizado mediciones GNSS son similares en magnitud, sin embargo, difieren parcialmente en dirección. El estudio concluye que las técnicas fotogramétricas son aplicables para analizar la dinámica de deslizamientos.

Abstract Here, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Dual blockade led to HIF1α upregulation and CalR translocation, accompanied by massive impairment of mitochondrial function. Basal oxygen consumption rate, ATP synthesis, and maximal mitochondrial respiration decreased, confirming disrupted endoplasmic reticulum-mitochondrial homeostasis. This was paralleled by mitochondrial depolarization and upregulation of the UPR sensors PERK, ATF6α, and IRE1α. Notably, dual EZH2/CDK4/6 blockade also reduced 3D-spheroid invasion, partially inhibited tumor growth in ovo, and led to impaired viability of patient-derived organoids. Mechanistically, this was due to transcriptional changes in genes involved in mitotic aberrations/spindle assembly (Rb, PLK1, RRM2, PRC1, CENPF, TPX2), histone modification (HIST1H1B, HIST1H3G), DNA damage/replication stress events (TOP2A, ATF4), immuno-oncology (DEPDC1), EMT-counterregulation (PCDH1) and a shift in the stemness profile towards a more differentiated state. We propose a dual EZH2/CDK4/6 blockade for further investigation.

Abstract To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and long-lasting effects, increasing the risk of morbidity and mortality. Under and overnutrition can slow down the immune response to infections, which can delay recovery. To effectively defend against SARS-CoV-2 infection and enhance viral clearance, it is essential to maintain a healthy diet that includes sufficient macro and micronutrients. Several studies, most of which have been performed in adults, have shown that vitamins such as C, B12, folate, D, and E, as well as the minerals selenium, copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.