This protocol describes a step-by-step approach for the synthesis of a periodic mesoporous organosilica (PMO) with wall-embedded nitroxide monoradicals. It starts with the synthesis of an isoindoline-based nitroxide monoradical and its silylationa critical requirement for the condensation with the PMO's bisilylated building block. We also provide detailed instructions on how to synthesize the phenylene (Ph)-PMO's bisilylated precursor, 1,4-bis-(triethoxysilyl)-benzene (BTEB), and subsequent preparation of the Ph-PMO with in situ incorporation of the silylated nitroxide monoradical. The incorporation of the nitroxide into the Ph-PMO was monitored by electron paramagnetic resonance (EPR) spectroscopy, which clearly revealed the decrease in free radical concentration in solution as the condensation progressed. A comparison of the radical-containing Ph-PMO to a reference Ph-PMO, prepared from the same organic precursor in the absence of the radical, by powder X-ray diffraction (PXRD), N2 adsorption-desorption isotherms, thermal gravimetric analysis (TGA), and Fourier transform infrared with attenuated total reflectance (FTIR-ATR), showed that the radical did not induce structural changes to the PMO. All reactions and methodologies described in this protocol were performed at least in triplicate, demonstrating their reproducibility. Completion of the entire protocol takes 22 days (∼3 weeks).
Drawing on the extensive correspondence between Pei-sung Tang and B. F. Skinner, this article traces their friendship and the main trajectory of Skinner's unfinished lecture visit to China. Building on these materials, it briefly examines the potential significance of the visit for Skinner himself and for the development of psychology in China. Finally, the article highlights the importance of harnessing public interest in psychology to advance the discipline. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Addiction consult services (ACSs) are a growing hospital-based care model that increases quality of care for patients with substance use disorders (SUDs). One implementation barrier has been concern about negative financial impacts for health systems. To examine whether starting an ACS changes hospital length-of-stay and 30-day readmissions for patients with opioid use disorder (OUD) served in a large academic health system. Quasi-experimental difference-in-differences study of opioid-related hospital admissions from January 2018 to December 2024, comparing one hospital that implemented an ACS to three hospitals in the same urban, academic system in Philadelphia, PA without ACSs. Adults (≥ 18 years) with opioid-related hospitalizations. A fully staffed, hospital-based, multidisciplinary ACS launched in July 2023. Primary outcomes were hospital length-of-stay and 30-day readmissions. Secondary outcomes were receipt of any medication for opioid use disorder (MOUD) during hospitalization, discharge on a therapeutic MOUD dose, emergency department visits within 6 months of discharge, and discharges before medically advised. In unadjusted analyses, ACS implementation was associated with a 5 percentage point increase in MOUD receipt (95% CI 0-10) and a 9 percentage point increase in discharge on therapeutic MOUD (95% CI 5-13), without significant changes in length-of-stay or 30-day readmissions. In adjusted analyses, therapeutic MOUD at discharge increased by 8 percentage points (95% CI 4-12), with no significant differences in length-of-stay or 30-day readmission. Results were robust to sensitivity analyses with alternative comparison groups and after accounting for the COVID-19 pandemic. Implementation of an ACS improved evidence-based care for hospitalized patients with OUD without prolonging length-of-stay or increasing readmissions.
Harm reduction vending machines (HRVMs) can expand low-barrier access to overdose prevention, sexual health, safer-use, and basic self-care supplies; however, practical guidance for implementing HRVMs in health system and supportive housing settings is limited. This practice report describes a clinical pharmacist practitioner (CPP)-led deployment of 15 HRVMs across a Veterans Affairs (VA) system and Veterans supportive housing in California. Beginning in December 2021, the CPP conducted site engagement, market research, and funding applications; convened cross-departmental stakeholders (logistics, engineering, biomedical, environmental management, information security/technology); and completed contracting. Contracts were awarded to VendNovation, LLC, for HRVMs which were placed in 7 community-based outpatient clinics, 6 supportive-housing sites, and 2 hospital locations. The CPP designed the HRVM wrap and interior layout; curated product assortments (eg, fentanyl/xylazine test strips, syringes, safer-sex supplies, wound-care, and hygiene items; naloxone added after launch) based on prior quality improvement interventions and Veteran feedback surveys; and established barcode-based user access and software-enabled inventory management. Implementation challenges included staff concerns (eg, stigma, not in my backyard attitudes), connectivity barriers (eg, Wi-Fi requirements), and added costs for deliveries to non-VA locations. HRVMs within VA clinics were accessible during business hours; supportive-housing HRVMs operate 24/7. Planning and installation required nearly 2 years, underscoring the need for dedicated staffing (CPP plus logistics technician), braided funding for start-up and recurring costs, and standardized purchasing and installation pathways. HRVMs seem feasible and acceptable in VA clinical and housing settings and may increase anonymous, low-barrier access to harm-reduction supplies. Implications for scale-up include development of centralized or prevetted procurement pathways, clearer implementation guidance, and operational supports to reduce site-level contracting burden.
While alkylated and acylated aporphine derivatives are well-represented in the literature, O-arylated analogues remain scarce. We report here a practical and regioselective methodology for the synthesis of 9-O-arylboldine derivatives. Our approach utilizes a copper-catalyzed Chan-Lam coupling reaction, enabling the efficient preparation of 30 novel 9-O-arylboldine derivatives. This operationally simple procedure proceeds at room temperature under ambient air conditions, employing readily available phenylboronic acids as coupling partners. Extensive one- and two-dimensional NMR studies unequivocally confirmed the desired 9-O-regioselectivity. Further demonstrating the scope of this method, we synthesized five new 3-bromo-9-O-arylboldine derivatives starting from 3-bromoboldine. Additionally, some 9-O-phenylboldine derivatives served as versatile intermediates, undergoing transformations to access N,N-dimethylammonium derivatives and enabling the conversion of 4'-formylphenyl derivative 6w into four aminoaporphine derivatives via reductive amination. This study confirms the usefulness of the Chan-Lam cross-coupling reaction as a powerful and flexible synthetic tool for the derivatization of natural products, particularly with the goal of expanding the chemical diversity of aporphine alkaloids.
ObjectiveTo evaluate changes in antipsychotic treatment patterns and healthcare utilization before and after initiation of long-acting injectable antipsychotics (LAI-APs) in a large Québec population cohort, comparing individuals with schizophrenia (SCZ) to those with other psychotic disorders (non-SCZ).MethodWe conducted a retrospective cohort study using linked Québec administrative databases (RAMQ, MED-ECHO, and public drug insurance) to identify 6,221 adults who initiated a LAI-AP between April 2013 and December 2016, after a 12-month LAI-free period. Participants were followed for 12 months before and after the index date. The cohort was stratified into SCZ and non-SCZ, and were further divided by regimen at initiation (LAI only; LAI + clozapine; LAI + other oral antipsychotic). Antipsychotic exposure and health-service usage (hospitalizations, emergency visits, outpatient and community care) trajectories were analyzed weekly using state-sequence analysis; pre- versus post-initiation comparisons used paired statistical tests.ResultsOf 6,221 patients (63.4% male; mean age 41.6 years), initial treatments consisted of paliperidone LAI (55.7%), aripiprazole LAI (21.5%), risperidone LAI (6.9%), first-generation LAI (15.6%), and LAI combinations (0.2%); 40% received LAI only, 5% LAI + clozapine, 55% LAI + an oral antipsychotic. SCZ patients were more often male, economically disadvantaged, and more likely to receive clozapine. After LAI initiation, hospital days fell sharply by almost 70% and outpatient and community-care visits increased substantially. Use of oral antipsychotics decreased overall post-initiation, except for clozapine (which rose) and first-generation oral drugs (which remained stable).ConclusionsIn this real-world Québec cohort, LAI-AP initiation was followed by a marked reduction in hospitalizations and a shift toward outpatient and community care, regardless of diagnosis. Observed differences in sociodemographic and clinical profiles between SCZ and non-SCZ patients-and among SCZ treatment subgroups-suggest the need for tailored care pathways. These findings support LAI-AP effectiveness in reducing healthcare utilization and inform resource planning. How Injectable Medications Reduce Hospital Visits for Patients With PsychosisA Quebec study of 6,221 patients reveals that starting long-acting injectable antipsychotics (LAIs) reduces hospital stays by 70% while increasing community-based follow-ups. These results demonstrate the effectiveness of LAIs in improving patient stability and highlight the need to tailor care according to the diagnosis, whether for schizophrenia or other psychotic disorders. This research supports the use of LAIs to optimize the use of healthcare services.
Entrepreneurs in rural areas face much greater difficulties than those located in cities, also with respect to the access to entrepreneurial finance. Recent developments in the provision of capital, however, have opened new opportunities for small firms and start-ups to obtain funding. In this empirical work, I hypothesize that crowdfunding provides crucial resources and support for rural-based entrepreneurs and that rural areas characterized by greater (bridging) social capital are better positioned to benefit from the opportunities of crowdfunding. Using a newly developed database linking crowdfunding campaigns to industry and counties in the U.S. (KIUS), county-level information on social capital and official U.S. census data, I test these hypotheses. My findings indicate that crowdfunding is indeed positively related to the number of ventures operating in the industry-location in the following period. In addition, this relationship is stronger for counties with higher levels of bridging social capital and of civic engagement. The results are robust to a number of checks, including a placebo test and matching exercises. Access to capital through crowdfunding is critical for rural counties: obtaining funds through Kickstarter is associated with an increase in the number of business ventures operating in rural areas. Rural-based entrepreneurs have to face a number of challenges to establish their ventures. Among these challenges, a crucial one pertains access to capital, which is much less available and difficult to obtain outside the city. The use of crowdfunding however may represent an important alternative to traditional funding channels, like banks and venture capitalists. In this paper, I show that providing resources to rural entrepreneurs through crowdfunding is associated to a higher number of ventures operating in the industry in the location which received the funds. Interestingly, the effect of crowdfunding is strongest for those areas with higher rates of volunteering and higher connections between people with different socio-economic backgrounds. These results suggest to practitioners and policy-makers that, one the one hand, rural entrepreneurs can successfully exploit crowdfunding for their ventures; on the other hand, social connections are essential for taking advantage of opportunities offered by crowdfunding.
Advantages of using an intramedullary (IM) nail over a lateral plate for fixation of distal fibula fractures include the ability to allow for earlier weightbearing and return to sport, smaller incisions, and decreased hardware prominence. When comparing a fibular nail with an IM screw, the nail allows for syndesmosis fixation through the device and imparts rotational stability. Long-term studies support the viability and clinical outcomes of using an IM nail. In this technique video, a case is presented to illustrate the use of an IM nail for fixation of a distal fibula fracture. Distal fibula fractures should be treated operatively in the following cases: open fractures, bimalleolar fractures, or lateral malleolar fractures with medial clear space widening, displacement >3 mm, or decreased tib-fib overlap, increased talocrural angle, any talar displacement, fracture-dislocation, or nonunion. When treating these fractures operatively, it is crucial to get an anatomic reduction, as this will lead to a satisfactory outcome. By restoring the anatomy, the talar shift is decreased, and a normal tibiotalar contact area is approached. Percutaneous incisions are made around the fracture to place a clamp and hold anatomic reduction. Once reduced, a small incision is made 1cm distal to the fibular tip and in line with its axis. The start point is checked with the K-wire on anteroposterior and lateral views. An opening reamer is used, followed by a flexible guidewire and then a proximal reamer. Talons are deployed once the appropriate position is confirmed, and interlocking screws are placed through the guide. Syndesmosis fixation is added if necessary. The success rate for achieving good outcomes is high at 90%. Patients should be counseled that their braking time while driving is normal at around 9 weeks and that overall recovery is about 2 years. This technique should not be used if the 6.2-mm opening reamer will breach the cortex, and should not be used if a plate will provide superior fixation. Like with any nailing procedure, obtaining and maintaining the reduction is paramount. A proper start point is critical for optimal fixation. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Microbial rhodopsins exhibit diverse functions ranging from ion pumps and channels to light sensors, despite sharing a common seven-transmembrane (7TM) architecture. Understanding how this functional diversity evolved is a long-standing problem, and ancestral sequence reconstruction (ASR) offers a direct route to inferring and experimentally testing plausible ancestral rhodopsins. However, ASR of 7TM proteins is often limited by alignment ambiguity and insertion-deletion (indel) uncertainty, especially in extra-membrane (EM) loops and termini. As a result, many studies focus on trimmed transmembrane (TM) cores and treat EM regions by manual curation, leaving the evolutionary history of full-length architecture difficult to test experimentally. Here we reconstruct and resurrect full-length ancestral schizorhodopsins (Anc-SzR) and heliorhodopsins (Anc-HeR), two microbial rhodopsin families that share a retinal-binding 7TM core but differ in membrane topology and EM secondary-structure elements. Starting from untrimmed alignments, we combine structure-consistent multiple sequence alignments and profile-based evolutionary models with an explicit indel-aware refinement that merges amino-acid ancestral states with binary ancestral gap inference on a fixed topology. Indel-aware refinement prevents artificially overextended ancestors and yields compact full-length sequences. AlphaFold3 predictions for the indel-corrected ancestors support high-confidence 7TM folds and recover lineage-specific EM features, including characteristic β-strands and short helices. Both Anc-SzR and Anc-HeR can be expressed in Escherichia coli and recovered as stable, colored, retinal-binding holoproteins. In a whole-cell pH assay, Anc-SzR shows light-driven proton-transport activity, whereas Anc-HeR shows no detectable ion-pumping signal, consistent with extant heliorhodopsins. Together, these results show that full-length, indel-aware ASR can produce experimentally tractable ancestral microbial rhodopsins and enable direct tests of how EM architecture evolves alongside the 7TM core.
Contamination by heavy metals in mining area often leads to significant environmental hazards, with bioaccumulation of Cu in the food chain representing a critical pathway for human exposure. To investigate the characteristics of Cu content in major foodstuffs and assess the safety of dietary Cu exposure among residents living near mining areas in Nandan County, China.Dietary intake of Cu in mining-affected and reference area was investigated using the weighing method and chemical analysis. The Chronic Daily Intake (CDI) was calculated, and the potential non-carcinogenic health risks were evaluated. Results showed that Cu concentrations in various food categories were significantly higher in the mining-affected area compared to the reference area. Vegetables were identified as the primary source of dietary Cu exposure in both areas, contributing more than 46% to the total intake. The health risk assessment indicated that the Hazard Quotient (HQ) values for males and females in the mining-affected area were 1.02 and 1.13, respectively, both exceeding the safety threshold of 1. Residents in the mining-affected area of Nandan face potential health risks from dietary Cu exposure. These findings highlight the need for targeted attention and intervention measures to ensure public health safety.
Pneumonia virus of mice (PVM), the mouse homolog to respiratory syncytial virus (RSV), is increasingly used as a surrogate model to study pneumovirus pathogenesis in a more natural pathogen-host relationship. Two major strains of PVM, strain 15 and J3666, are currently used in laboratories, with preferences for either one or the other based on the well-documented isolation history of strain 15, or the suggested higher virulence of strain J3666. Using conventional and long-read sequencing, we found that the PVM strain J3666 represents two distinct virus populations, which are defined by the sequence and structure of the G and SH genes encoding the putative attachment and small hydrophobic proteins, in addition to further nucleotide polymorphisms. Specifically, a nucleotide polymorphism at position 65 in the G gene results in either an upstream open reading frame (uORF) preceding the main ORF in frame, or an extension of the major G ORF by 18 codons. The impact of the different forms of the J3666-G genes on PVM was examined by generating recombinant PVMs differing exclusively in the distinctive 5' portion of the respective G gene. This revealed that the population with an extended main G ORF was more virulent than the population with a G gene containing an uORF or the parental virus. The presence of a uORF was associated with decreased expression levels of G, whereas the virus with the extended G ORF appeared to express slightly increased levels of G, which suggests that expression levels of G may modulate virulence. The pneumonia virus of mice strain J3666 is considered a more virulent and more suitable model for severe lower respiratory tract infections. The organization of the gene for the attachment protein G is reported to contain a small upstream open reading frame (uORF) preceding the main G ORF in frame. The translated G protein is predicted to comprise 396 amino acids. We report that this virus strain may be a mixture of two different populations, each with differing virulence. The more virulent population encodes a G protein of potentially 414 amino acids instead of a small uORF. The usage of the first start codon in this G gene organization remains to be determined. Importantly, this organization of the G gene is in line with that of several newly identified pneumoviruses, i.e., canine and swine pneumoviruses. These viruses may comprise a distinct group within the Pneumoviridae family.
Because the body is commonly described in a six-layered structural hierarchy starting from molecules and cells to tissues, organs, organ systems, and finally to the whole organism, bodily functions (physiological and pathophysiological) are often approached in the same layered way. This is familiar and convenient, but it has clear limitations. Many important functions, such as homeostasis, thermoregulation, stress responses, and so on, emerge from coordinated causal processes that span multiple levels. They cannot be understood by assigning them to a single anatomical layer, yet integrative physiology still lacks a functional framework that is both conceptually coherent and practically useful for representing such multi-level interactions. This article introduces a 5-domain functional framework, developed through logical analysis of how intracellular fluid compartment(s) (ICF or ICFs) operate collectively within the shared extracellular fluid compartment (ECF). From this enveloping ECF-ICF relationship, five relational functional domains emerge. This perspective organizes bodily processes according to their operational logic rather than their anatomical position, allowing multi-level coordination to be visualized in a unified and flexible way. This framework and logic further lead to the development of a second functional platform that can organize bodily functions described by quantitative/mathematical relationships (e.g., oxygen-hemoglobin dissociation curve, Nernst equation, Michaelis-Menten equation, etc.). The platform is named Blueprint for Quantitative Functional Organization (BQFO). When mathematical expressions of function are placed into the BQFO, they form a systematically organized hierarchy rather than remaining scattered across topics. Together, the 5-domain functional framework and the BQFO provide not only practical tools for integrating complex functions but also a more realistic epistemology and methodology for understanding how bodily functions operate. These developments potentially establish new principles and offer new tools for integrative physiology and interdisciplinary teaching and research.
Competency-based medical education (CBME) focuses on the attainment of defined skills independent of the time spent in training. Emergency Medicine (EM) is starting the long process of CBME implementation. In preparation for the 2025 Society for Academic Emergency Medicine (SAEM) Consensus conference whose goal is to define the research agenda around CBME, a diverse workgroup of expert educators convened. They conducted a literature review and developed a large roster of potential research questions. Through a modified Delphi process, they prioritized 10 research questions related to CBME implementation. The final group of questions fell into three broad categories: (1) Program evaluation, (2) Change management, and (3) System needs and resources. Implementation of CBME in EM will require intentional incorporation of change management strategies and systematic development of program evaluation. This will minimize the risk of negative outcomes resulting from ineffective implementation strategies and promote the successful uptake of CBME within the specialty.
The evidence from studies comparing 45 and 30 mg starting doses of first-line dacomitinib for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) remains limited. This study aimed to compare the clinical efficacy and safety of two starting-dose first-line dacomitinib strategies in patients with advanced EGFR-mutated NSCLC. This study employed a multicenter retrospective cohort design. A total of 189 patients with stage IIIB/IV EGFR-mutated NSCLC who received first-line dacomitinib between October 2020 and September 2023 at one of four Taiwanese centers were analyzed. Among them, 59 patients started with 45 mg and 130 patients started with 30 mg. The 45-mg group included significantly more male patients and had higher baseline body weight and body mass index. The objective response rate (ORR) and disease control rate were comparable between the 45-mg (72.9% and 94.9%) and 30-mg (66.9% and 91.5%) groups (p = 0.623). The median progression-free survival was 18.53 months for patients treated with 45 mg dacomitinib and 18.03 months for patients treated with 30 mg dacomitinib (hazard ratio (HR), 0.958; 95% confidence interval (CI), 0.681-1.349; p = 0.807). The median overall survival was 40.4 and 49.97 months, respectively (HR, 1.078; 95% CI, 0.640-1.815; p = 0.778). However, patients receiving a starting dose of 45 mg dacomitinib experienced significantly higher rates of skin toxicity, paronychia, diarrhea, stomatitis, and anorexia and required dose reduction more frequently (all p < 0.05). This study suggests that a 30-mg starting dose of dacomitinib may provide similar efficacy with improved tolerability compared with 45 mg. Prospective noninferiority studies are warranted to confirm these findings.
Timely and contextually relevant evidence is essential for decision-making in policy domains, especially during crisis or outbreaks like the COVID-19 pandemic. While systematic reviews provide methodological rigor, their cost and duration limit their policy utility. Rapid reviews offer a pragmatic alternative but are typically static and quickly become outdated as new studies, grey literature, and local knowledge emerge, leading to duplication of effort and losing track of policy decisions and use of evidence. This paper presents a pragmatic framework for converting rapid reviews into living evidence synthesis (LES) systems within policy contexts, especially in low- and middle-income countries (LMICs). Drawing on the experience of eBASE Africa, the framework demonstrates how LES functions can be incrementally embedded within conventional rapid-review workflows. It integrates PRISMA-aligned methods with continuous evidence surveillance across academic literature, grey literature, and non-traditional evidence sources such as social media and Indigenous Ways of Knowing, treating these as structured and systematically incorporated evidence streams, supported by responsible use of artificial intelligence and digital tools with human oversight. The framework reconceptualizes rapid reviews as entry points to living evidence systems, offering a scalable pathway to improve efficiency, continuity, and policy relevance, particularly in LMIC settings. Good decisions in health, education, and other policy areas depend on having the right information at the right time. This became especially clear during the COVID-19 pandemic, when policymakers needed quick answers to urgent questions. Researchers often provide this information through systematic reviews, which carefully collect and analyze existing studies. While these reviews are thorough and reliable, they usually take a long time to complete and can be expensive. This makes them less useful when decisions need to be made quickly. To respond to urgent needs, many organizations use rapid reviews. These are faster versions of systematic reviews that provide timely insights for decision-makers. However, rapid reviews have an important limitation: they are usually done once and then left unchanged. As new studies, reports, and local experiences become available, the findings of these reviews can quickly become outdated. This means that policymakers may rely on information that no longer reflects the latest evidence. It can also lead to duplication of effort, as new reviews are started from scratch instead of building on existing work. This paper explores a practical way to solve this problem by transforming rapid reviews into what are called “living evidence synthesis” systems. A living evidence system is one that is continuously updated as new information becomes available. Instead of treating a review as a one-time product, it becomes an ongoing process that evolves over time. Drawing on the experience of eBASE Africa, this study presents a step-by-step framework for making this transition, particularly in low- and middle-income countries. These settings often face resource constraints, making it even more important to use time and funding efficiently. The framework shows how organizations can gradually build living evidence systems into their existing rapid review processes, rather than starting from scratch. One key feature of this approach is the use of continuous evidence monitoring. This means regularly searching for and incorporating new information from a wide range of sources. In addition to academic research, this includes grey literature such as policy reports, as well as non-traditional sources like social media and Indigenous knowledge. These sources are treated as valuable forms of evidence and are systematically included in the review process. The framework also emphasizes the careful use of digital tools and artificial intelligence to support this work. These tools can help identify new studies, organize information, and reduce the workload for researchers. However, human oversight remains essential to ensure that the information is accurate, relevant, and ethically used. Another important aspect is maintaining transparency and methodological rigor. The approach aligns with established standards such as PRISMA, ensuring that the process remains systematic and credible even as it becomes more flexible and continuous. Overall, this paper argues that rapid reviews should not be seen as final products, but as starting points for ongoing learning. By turning them into living systems, it is possible to keep evidence up to date, reduce duplication, and make better use of available resources. This approach can improve the relevance and usefulness of evidence for policymakers, especially in fast-changing situations and resource-limited settings. Thus, the proposed framework offers a practical and scalable way to ensure that evidence remains current, inclusive, and responsive to real-world needs. It highlights how combining traditional research methods with continuous updating and diverse knowledge sources can lead to better-informed decisions and more effective policies.
The World Health Organisation (WHO) recommends ≥8 antenatal care (ANC) contacts to improve detection of pregnancy risks and maternal newborn outcomes. However, uptake of the 8-contact model remains low in many low-resource settings. To assess compliance with the WHO-recommended ≥8 ANC contacts and associated factors among women attending primary health facilities in Mbarara District, south-western Uganda. Facility-based cross-sectional study. Postnatal women attending postnatal and immunisation clinics at five randomly selected primary health facilities in Mbarara district were recruited between April and May 2025. Data were collected using interviewer-administered questionnaires and verified with antenatal cards. Data were analysed using Stata version 18 software. Descriptive statistics summarised participant characteristics. Bivariate and multivariable logistic regression analyses identified factors associated with compliance with the WHO-recommended ≥8 ANC contacts. Of 433 participants enrolled (median age 27 years; interquartile range 23-31 years), the majority (67%; 290/433) were aged 21-34 years. Overall compliance with WHO-recommended ≥8 ANC Contacts was 15.0% (65/433; 95% CI: 11.8%-18.7%). The factors significantly associated with compliance with the WHO-recommended ≥8 Antenatal Contacts were initiating ANC in the first trimester of the index pregnancy (aOR = 43.08; 95% CI:14.84-124.97; p<0.001), staying within a distance of less than 5 km (aOR = 2.00; 95% CI:1.05-3.77; p=0.034), and monthly income of ≥100,000 Uganda shillings (aOR = 1.13; 95% CI:1.03-4.33; p=0.041). Compliance with the WHO-recommended ≥8 ANC contacts was low. Higher compliance was observed among women who initiated ANC early, lived closer to health facilities, and had higher incomes. Future strategies focus on factors associated with compliance, including early ANC initiation, geographic accessibility, and socioeconomic barriers. Pregnancy is a critical time when regular contact with health workers can prevent illness and save the lives of mothers and babies. Antenatal care visits allow health providers to detect problems early, offer treatment, and support women to have safer pregnancies and deliveries. To improve these outcomes, the World Health Organisation recommends that every pregnant woman should attend at least eight antenatal care contacts. However, in many low-resource settings such as Uganda, women often start care late or do not complete all the recommended visits, putting both mothers and newborns at risk. From April to May 2025, we investigated five primary health facilities in Mbarara District, south-western Uganda, and interviewed 433 women. We also checked their antenatal cards to confirm how many visits they attended during their most recent pregnancy. We found that only 65 women (about one in seven) completed the recommended eight or more Antenatal care (ANC) contacts. Most women attended fewer visits than recommended. Women were much more likely to complete all eight contacts if they had started ANC early, in the first three months of their most recent pregnancy. Living close to a health facility (within five kilometres) and having a higher monthly income also increased the chance of completing all visits. Our findings show that many women are missing out on the full benefits of antenatal care. Therefore, starting ANC attendance in the first three months of pregnancy, bringing services closer to communities, and supporting women economically could help more mothers complete the recommended visits, leading to healthier pregnancies and good birth outcomes.
Verification stages are recommended for maximal oxygen consumption (V̇O₂max) determination, but there is currently no standardization of verification stage design. We sought to determine if the length of recovery and the initial intensity of subsequent exercise influence the effectiveness of verification stages during testing for V̇O₂max. Twenty-seven participants (20 males, 7 females) completed four graded exercise tests (GXT). Each session included an identical incremental V̇O₂max (iV̇O₂max) protocol, followed by one of four verification stages with combinations of short (5 min) and long (15 min) rest periods, and submaximal (one stage below maximal workload) and supramaximal (one stage above maximal workload) starting intensities. Although iV̇O₂max and verification V̇O₂max (vV̇O₂max) were similar across all protocols, 11-19% of participants achieved higher values during verification. About 24% of individuals who did not exhibit a V̇O₂ plateau during the GXT exhibited a vV̇O₂max > iV̇O₂max in the submaximal verification protocols compared to 6-14% for the supramaximal protocols. Verification stages using initial submaximal intensities may increase the likelihood of achieving V̇O₂max.
Splenic abscess secondary to Actinomyces species is an exceedingly rare condition that presents with a constellation of nonspecific symptoms often leading to delayed presentation, diagnostic uncertainty, and misidentification. While Actinomyces is typically an indolent infection, splenic abscess has a high mortality when untreated due to the risk of splenic rupture. This case report highlights a rare instance of isolated Actinomyces splenic abscess in a 52-year-old man with a history of intravenous drug use, hepatitis C, and recent incarceration who presented with several weeks of hemoptysis, fevers, night sweats, pleuritic chest pain, and left upper quadrant abdominal pain. The history and clinical presentation were most concerning for malignancy, tuberculosis, or other pulmonary infectious etiologies. Computed tomography imaging revealed a 14.9 x 7.7 x 12.1 cm splenic abscess with associated pleural effusion. A percutaneous drain was placed by interventional radiology, and the resulting fluid culture grew Actinomyces meyeri. In consultation with infectious disease specialists, prolonged antibiotic therapy was started with four weeks of intravenous piperacillin-tazobactam followed by six months of oral amoxicillin. This case highlights both the diagnostic challenge of splenic actinomycosis and the importance of maintaining a broad differential diagnosis to avoid anchoring bias or early diagnostic closure in high-risk patients with nonspecific symptoms.
Chlorophylls (Chls) harvest the solar energy that drives photosynthesis, which underpins most of the food chains on our planet. Starting from protoporphyrin IX, just seven biosynthetic reactions culminate in the synthesis of Chl a, the major light-absorbing pigment on Earth. Other such pigments, Chls b, c, d and f, widen the absorption range in the visible and red regions of the spectrum, and several bacteriochlorophylls (BChls), BChls a, b and g in particular, open new spectral windows allowing organisms to harvest near infra-red light. This perspective surveys the structural features of porphyrins, chlorins and bacteriochlorins that impart their characteristic absorption features, then presents a similar analysis of the biosynthetic intermediates leading to Chls a, b, c, d and f. The interlinked Chl and BChl biosynthetic pathways are summarised, then the rest of the perspective focusses on the enzymes that synthesise Chls a, b, c, d and f. AlphaFold 3 was used to model a complete set of structures for Chl biosynthesis enzymes, predicting intersubunit associations and the arrangements of cofactors and bound substrates, and providing insights into catalytic mechanisms. A new scheme for binding substrates and transferring products between pathway enzymes suggests how synthetic biology approaches can assemble hybrid Chl and BChl pathways to expand the spectral range for harvesting and using solar energy.
Allogeneic cell-based immunotherapies generated from pluripotent stem cells show considerable promise for the treatment of oncological, autoimmune, and viral diseases, however discovery platforms for induced pluripotent stem cell (iPSC)-derived cell therapies do not translate well to scalable manufacturing platforms. We applied a high-throughput combinatorial screening platform (CombiCult®) to identify novel, manufacturing-ready, feeder-free protocols for the generation of mature, functional NK cells from human iPSCs. We validated seven CombiCult®-derived differentiation protocols for the production of highly cytotoxic, phenotypically mature iPSC-derived NK (iNK) cells, which are comparable to donor-derived NK cells. Translation to a Stirred Tank Bioreactor (STR) system resulted in a 10x increase in productivity, from ∼20 to ∼190 iNK cells per starting iPSC. iNK cells demonstrate mature transcriptomic signatures, retained after translation to bioreactor-based production. The three-dimensional, bead-based screening approach enables seamless translation to bioreactor-based production of iNK cells exhibiting high cytotoxic activity against a range of cancer cell types.