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COFcap2, a recyclable tandem catalysis reactor for nitrogen fixation and conversion to chiral amines
No full textTwo or more catalysts conducting multistep reactions in the same reactor, concurrent tandem catalysis, could enable (bio)pharmaceutical and fine chemical manufacturing to become much more sustainable. Herein we report that co-immobilization of metal nanoparticles and a biocatalytic system within a synthetic covalent organic framework capsule, COFcap-2, functions like an artificial cell in that, whereas the catalysts are trapped within 300-400 nm cavities, substrates/products can ingress/egress through ca. 2 nm windows. The COFcap-2 reactor is first coated onto an electrode surface and then used to prepare eleven homochiral amines using dinitrogen as a feedstock. The amines, including drug product intermediates and active pharmaceutical ingredient, are prepared in >99% enantiomeric excess under ambient conditions in water. Importantly, the COFcap-2 system is recycled 15 times with retention of performance, addressing the relative instability and poor recyclability of enzymes that has hindered their broad implementation for energy efficient, low waste production of chemicals and (bio)pharmaceuticals.</p
Mapping stakeholders, services, data, and the information system for adolescent health in the West Bank
No full textBackground Adolescent health plays a crucial role in shaping lifelong well-being, yet significant gaps exist in addressing adolescent health needs. In confict-affected regions like the West Bank, fragmented service delivery, inconsistent data collection, and lack of coordination between providers undermine the effectiveness of health ser‑ vices. An efficient health information system ensures accurate data collection, stakeholder integration, and evidence-based decision-making. This study aims to map the landscape of available adolescent health services in the West Bank, clarify the key service providers, determine the existing data sources, and describe the health information system supporting adolescent health. Methods This study utilized a comprehensive landscape analysis to assess adolescent health services in the West Bank. Stakeholder mapping and interviews identified key stakeholders and assessed their roles in service delivery and the health information system. Ethical approval was obtained, and all participants provided informed consent. Data were collected from diferent healthcare organizations, including governmental bodies, non-governmental organizations, and private facilities. Thematic analysis was performed on interview data, and geospatial analysis was used to visualize the distribution of services and providers across 11 governorates using ArcMap 10.5. Results Governmental bodies, non-governmental organizations, and private entities were the predominant provid‑ ers of adolescent health services in the West Bank. These services were primarily delivered through healthcare facilities, educational institutions, youth centers, and select population-based programs, including vaccination initiatives and the 121 hotline, which provides free psychological support to victims of violence. The adolescent health information system in the West Bank was fragmented, with inconsistent data collection across providers. Governmental, NGO, and private sector organizations use different data systems. Each type of provider used population-based surveys as the primary source of health data. However, there were limitations in the availability of routine data. Conclusions This study represents the frst comprehensive mapping of adolescent stakeholders and services in the West Bank. Identifying the existing services accessible to adolescents and their providers establishes a foundation for developing target policies and programs that address the current gap and needs of adolescents in the West Bank.</p
Purinergic system transcript changes in the dorsolateral prefrontal cortex in suicide and major depressive disorder
No full textSuicide is a major public health priority, and its molecular mechanisms appear to be related to imbalanced purine metabolism in the brain. This exploratory study in?vestigates purinergic gene expression in the postmortem dorsolateral prefrontal cortex (DLPFC) tissue isolated from subjects with major depressive disorder (MDD) who died by suicide (MDD-S, n = 10), MDD subjects who did not die by suicide (MDD-NS, n = 6) and non-psychiatrically ill controls (CTL, n = 9–10). Purinergic system transcripts were assayed by quantitative polymerase chain reactions (qPCR) in superficial and deep gray matter as well as white matter DLPFC cortical layers using laser microdissection (LMD). Across all subjects, regardless of sex, P2RY12 (F(2,23) = 5.40, p = 0.004) and P2RY13 (KW statistic = 11.82, p = 0.001) transcript levels were significantly greater in MDD-S compared to MDD-NS subjects. Several other perturbations were observed in the white matter tissue isolated from females: NT5E (F(2,10) = 13.37, p = 0.001) and P2RY13 (F(2,9) = 3.99, p = 0.011, controlled for age) transcript expression was significantly greater in MDD-S vs. MDD-NS female groups. ENTPD2 (F(2,10) = 5.20, p = 0.03), ENTPD3 (F(2,10) = 28.99, p < 0.0001), and NT5E (F(2,10) = 13.37, p = 0.001) were among the transcripts whose expression was significantly elevated in MDD-S vs. CTL female groups. Transcripts that exhibited signifi?cantly altered expression in the superficial and deep gray matter included ENTPD2, NT5E, PANX1, and P2RY13 (p ≤ 0.05). Our medication analysis revealed that the expression of these transcripts was not significantly altered by antidepressants. This is the first study to holistically quantify the purinergic metabolic pathway transcripts in suicide and MDD utilizing human postmortem brain tissue. Our preliminary findings support evidence implicating changes in purinergic P2 receptors in the brain in suicide and provide support for broader purinergic system dysregulation in mood disorders.</p
Understanding the synthon preferences in molecular ionic cocrystals of trimethoprim - an experimental and computational study
No full textMolecular ionic cocrystals (ICCs) are cocrystals of composition A−BH+ HA or A−BH+ C with charge-assisted hydrogen bonding between A− and BH+ and with HA, B, and C being organic solids at ambient temperature. In contrast to the numerous works on the rational design of ternary A·B·C cocrystals, the application of synthon preferences and hierarchies in the synthesis of molecular ICCs is not widely reported. The antibiotic trimethoprim (tmp) readily forms molecular salts with carboxylic acid coformers including nonsteroidal anti-inflammatory drugs. The carboxylate anion interacts with the protonated N1H+ /C2-NH2 site of Htmp+ leaving the N3/C4-NH2 site as a second binding site for potential ICC formation. In this work, we investigated the synthesis of ternary molecular ICCs of tmp. Solution crystallization experiments led to the single crystal structure of Htmp+ dif−·H2fum (dif− = diflunisal anion; H2fum = fumaric acid). Hirshfeld surface analysis, molecular electrostatic potential, and site interaction energy calculations were conducted to understand the hydrogen bonding propensity of the N3/C2-NH2 site in Htmp+ X−. Proton transfer from HX to the N1 nitrogen of tmp leads to a decrease in the electrostatic potential of N3 and thus to a reduced hydrogen bond acceptor strength. The data obtained in this study highlight the challenges of developing strategies for the rational synthesis of molecular ICCs of complex molecules.</p
Lived Experience of Men with prostate cancer in Ireland: A qualitative descriptive study
No full textBackground: Prostate cancer is recognised as the second most common diagnosed cancer in men and remains a significant global public health concern. In Ireland, the incidence of prostate cancer continues to rise, with approximately 1 in 6 men being diagnosed in their lifetime. Men’s experiences with prostate cancer are complex, necessitating further research into the factors influencing diagnosis and treatment. Therefore, this study aims to explore men’s experiences with prostate cancer, emphasising the interplay between screening, diagnosis, and the lived experiences of those affected. Methods: A qualitative descriptive study was conducted among men with prostate cancer in Ireland. Using a purposive sampling (n = 11) were interviewed with data saturation guiding sample size determination. A semi-structured interview guide was used for data collection either face-to-face or via Microsoft Teams and phone calls. Data were analysed using Braune and Clarke’s thematic analysis approach after transcription, with NVivo 12.0 software supporting analysis. Results: Thematic analysis identified five themes: systemic obstacle in timely cancer detection, the role of efficient system in cancer care, emotional resilience in cancer recovery, redefining normalcy post treatment and harnessing specialised support network in coping strategies. These themes were examined through the lens of the Biopsychosocial Model to understand their interconnected nature and impact on patient experiences. Conclusions: This study highlights the complex factors affecting prostate cancer patients’ experiences, emphasizing the need for a patient-centred approach, addressing systemic disparities, and promoting multidisciplinary care. It suggests implementing evidence-based survivorship care frameworks to improve quality of life for survivors, with future research exploring long-term effects of integrated care models.</p
Adaptive strategies of a medical school during Sudan’s armed conflict
No full textBackground Medical schools play a vital role in healthcare, educating future professionals while upholding a moral and societal duty to address community health needs. In armed conflicts, these responsibilities intensify as health system failures, infrastructure damage, and educational disruptions increase the demand for medical training and community support. This study examines how the Faculty of Medicine, University of Gezira (FMUG), employs adaptive strategies, crisis management, and collaboration to sustain education, research, and community engagement while addressing evolving health challenges during the Sudan conflict. Methods We used a qualitative approach, combining document analysis and interviews with nine key informants. Document analysis applied the WHO Social Accountability Grid Framework, assessing relevance, equity, quality, and cost-effectiveness across education, research, and service in planning, doing, and impacting phases. Interview data were analyzed using Braun and Clarke’s six-step thematic analysis. Results Document analysis identified five themes: curriculum innovation, technology use, community service, collaboration, and research-driven policy. Interviews with faculty and administrators further highlighted five themes on FMUG’s adaptive strategies: impact on education, crisis management, flexible learning, implementation challenges, and sustainability. Conclusion This study highlights the critical role of educational innovation in sustaining academic continuity and addressing community needs in conflict zones. FMUG’s integration of flexible learning, technology, and strategic partnerships enabled both immediate crisis response and long-term resilience. Future research should examine the lasting impact of these adaptive strategies on medical education and healthcare systems.</p
Understanding urban climate-resilient cyclists: A solution to reducing individual motorized transport
No full textClimate change has increasingly adverse effects on cycling, especially in relation to climate-sensitive hazards such as heatwaves, natural disasters, and air pollution [1]. Modal shifting from cars to bikes is an evidence-based strategy for reducing local greenhouse gas emissions and air pollution in cities [2]. The development of connected and secure cycling infrastructure and improved accessibility to cycle-sharing programs have contributed to an increase in daily cycling trips. Bike supportive policies have further boosted cycling in the US, China, Europe, South America, and Asia [3]. For instance, Amsterdam saw a 15% increase in cycling following infrastructure improvements, while Sevilla and Bogotá had 10% gains, and Vancouver and Paris saw smaller (~5%) increases [3]. Despite the progress, climate change and climate-sensitive hazards increasingly threaten bike use in cities [1]. Here, we summarize current evidence on the effects of heatwaves, natural disasters, and air pollution on urban cycling, highlighting the critical threat to its use. Investigating conditions facilitating the climate resilience of cyclists, defined as their ability to bounce back from climate-sensitive hazards, is essential [4].</p
‘Fat’, female and unprivileged: exploring intersectionality, perceiver characteristics, and eye movements
No full textThe aim of this research was to examine the role of body self-esteem, Body Mass Index (BMI), and the tendency toward social desirability as predictors of anti-fat stereotypes and prejudices, and gender, ‘fat’ status, and social status as moderators of this relationship, as well as eye movements of subjects when observing ‘fat’ individuals. Three studies examined the research aims. In the first study (N=311; 60.8% female), body self-esteem, self-reported BMI, and social desirability were assessed as predictors of anti-fat stereotypes and prejudice, with ‘fat’ status as a moderating variable. The second study (N=311; 60.8% female) replicated this approach, adding perceived social status as a moderator. The third study (N=191; 61.5% female) assessed body self-esteem and collected precise body-related measurements (weight, body fat, visceral fat, muscle percentage, metabolism, and BMI) using the OMRON body composition monitor. Additionally, it measured anti-fat stereotypes, prejudice, and eye movements in response to ‘fat’ and ‘non-fat’ stimuli. The results of the first study suggest that body self-esteem, BMI, and the tendency toward social de?sirability can predict anti-fat stereotypes and prejudices. ‘Fat’ women were evaluated most negatively. The second study indicates that the social status of stimulus individuals is also a significant moderator of the relationships described above. ‘Fat’ women of low social status are evaluated most negatively. In the third study, we obtained information on the following eye movement parameters: (1) First view, (2) Duration of fixations, (3) Fixations and (4) Revisits. Eye movement parameters can be predicted by body self-esteem and body condition parameters, while gender and ‘fat’ status of stimuli are significant moderators in this relationship. The study explains the role of BMI and body self-esteem in anti-fat bias, highlights the importance of gender and social status in perceiving ‘fat’ individuals, as well as the importance of considering nuanced body composition measures, such as visceral fat and muscle percentage, in understanding individual differences in perceptual bias. Differences in viewing patterns between genders underscore the interplay of stereotypes.</p
On levodopa interactions with brain disease amyloidogenicproteins at the nanoscale
No full textThe cerebral accumulation of α-synuclein (α-Syn) and amyloid β-1−42 (Aβ-42) proteins is known to play a key role in the pathology of Parkinson’s disease (PD). Currently, levodopa (L-dopa) is the first-line dopamine replacement therapy for treating bradykinetic symptoms (i.e., difficulty initiating physical movements), which become visible in PD patients. Using atomic force microscopy, we evidence at nanometer length scales the differential effects of L-dopa on the morphology of α-Syn and Aβ-42 protein fibrils. L-dopa treatment was observed to reduce the length and diameter of both types of protein fibrils, with a stark reduction mainly observed for Aβ-42 fibrils in physiological buffer solution and human cerebrospinal fluid. The insights gained on Aβ-42 fibril disassembly from the label-free nanoscale imaging experiments are substantiated by using atomic-scale molecular dynamics simulations. Our results indicate L-dopa-driven reversal of amyloidogenic protein aggregation, which might provide leads for designing chemical effector-mediated disassembly of insoluble protein aggregates.</p
3D printed lightweight breast prostheses for a patient of breast size 38F who was unhappy with the heavy weight of their silicone prosthesis
No full textBreast prostheses offer symmetry and femininity restoration for women post-mastectomy. They are fitted to an individual’s bra size, but standard prostheses can be heavy and uncomfortable on the scar site. Custom-made breast prosthesis offers improved fit, contour matching, and reduced weight, which is beneficial to patients. We report a case of a specific patient with a large prosthesis who experienced significant comfort issues with her standard silicone prosthesis, and how a bespoke prosthesis was created from a scan of her residual contralateral breast and created using 3D printing such that it was lightweight. Two 3D scans were taken, one of the patient’s residual contralateral breast while wearing a comfortable and well-fitting bra, and the other of the mastectomy site. The scans were processed using STL file editing software Meshmixer and Nomad Sculpt, and the residual breast profile was isolated and mirrored across the centerline of the patient’s body. This profile was then aligned with the mastectomy surgery site scan and combined to create the anterior side of the prosthesis. A Vat Polymerisation (VP) 3D printing technology was used to produce the breast prosthesis, which was 3D printed on a FormLabs 3B+ using the FormLabs Flexible 80A material. The new 3d printed prosthesis design is lightweight and flexible and mirrors the existing breast to achieve anatomical symmetry. The bespoke prosthesis is 62 % lighter than the patient’s previous silicone prosthesis. Additionally, the anterior of the prosthesis is a bespoke match of the mastectomy scar site, providing for a secure fit. The patient has worn her custom-made breast prosthesis for over one year up to the time of writing, and continues to do so. She describes the prosthesis as comfortable, lightweight, and secure in her bra. The use of 3D printing presents an opportunity to enhance the quality of breast prosthesis according to individual patient preferences.</p