Background: Prenatal diagnosis of life-limiting fetal conditions often leads to counseling focused primarily on therapeutic abortion. Perinatal hospice has emerged as an alternative model of care for families who choose to continue the pregnancy. This paper has two primary aims. First, it discusses structured perinatal hospice programs and their role in supporting parental decision-making after such diagnoses, with attention to ethical and emotional complexities. Second, the paper introduces NOVA-L (Navigating Options & Vital Assistance for Life-limiting conditions), a conceptual Decision Support System (DSS) designed to complement perinatal hospice care. Methods: The paper provides a conceptual and descriptive analysis of the Comfort Care clinical model. It also outlines the proposed architecture of NOVA-L. DSSs combine clinical guidelines, research data, and outcome registries on digital platforms, providing evidence-based information and AI-supported analytical tools. Their potential adaptation to perinatal hospice care is explored. Results: The Comfort Care model involves interdisciplinary counseling, structured communication, and psychosocial support to facilitate clarification of parental values and care pathways. NOVA-L is presented as a complementary tool that may enhance transparency in risk evaluation and option comparison through accessible interfaces under professional supervision. Conclusions: Structured perinatal hospice programs may enhance clarity and compassion in decision-making. The conceptual integration of AI-supported DSS tools, such as NOVA-L, could strengthen ethically grounded, emotionally sensitive parental support.
This study has begun as exploratory research on freshwater planarians from southwestern Romania for faunal purposes. Specimens were sampled and processed for standard histology (paraffin wax embedding, horizontal and sagittal serial sections, and Haematoxylin-Eosin staining). The histological analysis provided evidence for a population belonging to the genus Schmidtea. The morphological and histological characteristics were compared with those of all other Schmidtea species. The histological slides reveal numerous diagnostic characters for Schmidtea nova: the presence of two nipples on the course of the ejaculatory duct; a partly sclerotized ejaculatory duct with a wide lumen; the knee-shaped bending of the distal part of the penis papilla in most specimens; the presence of the parovarium; and the egg-shaped distension of the bursal canal musculature. Unlike typical Schmidtea nova, this population shows a slightly different organization of the atrial space by the presence of a muscular atrial cavity named the atrial tube here. The newly discovered population shows affinities with other Schmidtea species: the presence of cephalic sensory fossae, similar to Schmidtea polychroa, and a potential asexual reproduction mechanism by fission, similar to Schmidtea mediterranea. The functional significance of the atrial tube and the taxonomic status of this population are hypothesized.
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Background: The market for plant-based yogurt alternatives has rapidly expanded, reflecting the growing popularity of plant-based diets. However, their nutritional profiles and micronutrient fortification often differ substantially from those of traditional dairy yogurt. Methods: This study conducted a cross-sectional audit of retail labels on fermented plant-based yogurt alternatives available in major Polish retail chains. Data were collected in 2024 from eight stores across four nationwide supermarket chains. Nutritional composition, primary plant ingredient, micronutrient fortification, and processing level (NOVA classification) were recorded from product labels, while nutrient values were summarized using descriptive statistics and compared across product categories. Results: A total of 62 plant-based yogurt alternatives were identified, including 49 fruit-flavored and 13 natural products. Coconut was the predominant plant ingredient (54.8%), followed by soy (24.2%) and oat (11.3%). Fruit-flavored products contained significantly higher carbohydrate and sugar levels than natural ones. Soy-based products exhibited the highest protein content, often approaching that of conventional dairy yogurt, whereas coconut-based products were characterized by the lowest protein and higher saturated fat content. Overall, 37.1% of products were fortified with at least one micronutrient, primarily calcium, vitamin D, and vitamin B12. Most products were classified as ultra-processed (NOVA 4). Conclusions: Plant-based yogurt alternatives available on the Polish market are nutritionally diverse. Their composition is heavily influenced by the primary plant ingredient and fortification practices. Many of these products cannot be considered direct nutritional equivalents to dairy yogurt, underscoring the need for careful formulation, effective micronutrient fortification, and transparent labeling.
Ultra-processed foods (UPF) have become a central topic in nutrition science, with extensive observational research linking higher intake to adverse health outcomes. More recent randomized controlled trials have been presented as strengthening causal claims, yet closer examination reveals a pattern of interpretation that extends beyond what the data support. This perspective reviews four trials that directly compared ultra-processed diets with minimally processed diets, examining both their findings and how those findings have been represented in scientific commentary. Across all studies, the comparison group limited the ability to isolate processing as the causal factor, as multiple dietary features differed simultaneously. Reporting consistently emphasized findings aligning with expectations of harm while downplaying neutral or contradictory evidence, including favorable clinical markers and higher adherence in some ultra-processed conditions. Methodological limitations were also underrepresented in secondary interpretations. The current experimental evidence therefore require cautious interpretation. Specifically, four actionable recommendations follow from this analysis: (1) future trials should match intervention arms on nutrient composition so that processing effects can be disaggregated from nutritional quality effects; (2) adherence and dropout rates should be reported as primary, not secondary, outcomes; (3) terms such as "excess consumption" and "overeating" should be reserved for conditions of positive energy balance and weight gain; and (4) the heterogeneity within Nova Group 4 warrants sub-category analyses rather than class-wide causal claims. Without these changes, the evidentiary basis for UPF policy risks overstating certainty and misdirecting intervention targets.
Modern healthcare demands warrant the reconceptualization of pharmaceutical practitioners as primary caregivers capable of addressing contemporary medical challenges. Their specialized knowledge in molecular therapeutics, computational medicine tools, and physiological surveillance technologies uniquely qualifies them to oversee complicated treatment protocols for cutting-edge interventions, including genomic modifications and targeted biological agents. Historical success in managing long-term metabolic and cardiovascular conditions establishes credibility for supervising precision medicine applications. Digital innovations (e.g., remote consultation systems, algorithmic forecasting, and distributed ledger prescription tracking) enhance their capacity to coordinate fragmented services while responding to infectious outbreaks and polypharmacy challenges in elderly populations. This evolution promises decreased emergency admissions, improved therapeutic compliance, and more cost-effective care delivery. Regulatory reform must eliminate practice limitations, enabling these accessible professionals to address population health requirements fully.
Nanotechnology continues to redefine the boundaries of science, medicine, energy, and environmental stewardship [...].
Allergic rhinitis and asthma can impair work productivity. To validate a daily work productivity visual analog scale (VAS work), comparing it with the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI+CIQ:AS). We also aimed to quantify how allergy control relates to work impairment and indirect costs. We conducted a cross-sectional study using data from the MASK-air® app. Patients recorded daily VAS and weekly WPAI+CIQ:AS responses. We calculated correlations between VAS work and WPAI+CIQ:AS outcomes. Mixed-effects regression models assessed associations between disease control, measured by the Combined Symptom-Medication Score (CSMS) and the electronic daily asthma control score (e-DASTHMA), and VAS work. Indirect costs were estimated using the human capital approach, applying VAS-based productivity losses to country-specific wage distributions. VAS work correlated strongly with the WPAI+CIQ:AS, with Spearman coefficients ≥0.70 for total work impairment and presenteeism. Each 1-point increase in CSMS and e-DASTHMA was associated with mean 0.97 and 0.79-point increases in VAS work, respectively. In poorly controlled days, the estimated daily indirect cost based on CSMS ranged from 12.50 US$ PPP (P25-P75=5.60-26.70) in Brazil to 129.90 US$ PPP (P25-P75=80.40-199.40) in Iceland. Based on e-DASTHMA, daily estimates ranged from 9.30 US$ PPP (P25-P75=3.70-21.50) in Brazil to 101.90 US$ PPP (P25-P75=51.20-172.40) in Iceland. VAS work is a valid simple daily measure of work impairment due to rhinitis and asthma. CSMS and e-DASTHMA can be used to estimate productivity losses attributable to poor disease control.
A complex, dynamic microbiota inhabits cheese and cheesemaking environments. Such microorganisms can move across the dairy chain, from the microbiomes of production animals, through humans and environments which they interact with. These interactions impact all sectors of the One Health continuum. They may contribute to disseminate beneficial bacteria that enhance cheese quality, sustainability, and consumer health, but they also promote spread of pathogenic strains, along with their genetic determinants of virulence and antibiotic resistance across the milk and cheese production chain. This comprehensive, narrative review aims at providing a current view on cheese, its microbes, their roles, genetic determinants of virulence and antibiotic resistance, their relevance within the scope of the One Health approach and proposes using enterococci as sentinel microorganisms for monitoring AMR in cheese production chains.
Assessing departmental scholarly output remains challenging, as traditional bibliometric metrics incompletely capture academic productivity at the department level and are often poorly suited for year-on-year evaluation. The Departmental Scholarly Index (DSI) provides a framework for evaluating aggregate and publication-adjusted departmental academic output over short-term intervals. This study examined year-on-year changes in DSI within an academic plastic surgery department between academic years (AY) 2024 and 2025. Peer-reviewed publications produced by the Department of Plastic Surgery at a tertiary academic center during AY 2024 and 2025 were retrieved from PubMed. Aggregate DSI was calculated as the sum of journal impact factors across departmental publications following outlier handling, with publication-adjusted DSI defined as aggregate DSI divided by total publications. Year-on-year changes were quantified using absolute and relative percentage differences. A total of 57 in AY 2024 and 138 peer-reviewed articles in AY 2025 were included. Aggregate DSI increased from 142.9 to 298.2, representing a 109% year-on-year increase, with increases in basic science research (19.3 to 45.0), clinical research (83.6 to 162.6), and reviews or commentaries (40.0 to 90.6). In contrast, overall publication-adjusted DSI decreased from 2.51 in AY 2024 to 2.16 in AY 2025, with declines observed in basic science research (6.43 to 2.50) and reviews or commentaries (3.08 to 2.27), while clinical research remained relatively stable (2.04 to 2.03). Utilization of the DSI revealed exponential year-on-year growth in overall departmental academic output. The DSI framework offers a practical approach for longitudinal assessment and benchmarking of departmental academic productivity.
The pathological assessment of breast cancer resection specimens with neoadjuvant therapy (NAT) offers invaluable information for prognosis and further management. At times, these cases are difficult to pathologically evaluate, at least partly due to tumour bed obscuration after NAT. This study aimed to compare time and resource utilization by surgical pathology laboratories when handling breast specimens treated with NAT against those without NAT. We secondarily aimed to identify features associated with tumour bed identifiability at gross assessment. In this retrospective, single-institution study, we identified 241 breast resection specimens with systemic NAT between 2019 and 2025. A 1:1 non-NAT control group was randomly selected. The NAT cohort had a higher median number of tissue blocks (20.0 versus 13.0, P < 0.001), as well as larger proportions requiring gross resampling (23.7% versus 7.1%, P < 0.001) and pathologist review (16.2% versus 4.6%, P < 0.001) compared with the control. The NAT cohort had a longer median pathology report turnaround time (17.0 days versus 15.0 days, P < 0.001). In NAT cases, pretreatment clinical stage was associated with macroscopic identifiability of the tumour bed. Breast cancer resection specimens with NAT required significantly more time and laboratory resources than similar specimens without NAT. As NAT becomes more frequent across breast and other cancer types, pathological assessment of the excisional specimens from these patients is expected to become more challenging and time-consuming. By recognizing these trends early, healthcare systems can plan and allocate resources accordingly.
Ischemic stroke (IS) is the most prevalent cerebrovascular disease, with a high proportion of patients developing lifelong disability. Cerebral microcirculatory dysfunction is a key driver of poor IS prognosis. Hypoxia-induced cerebral angiogenesis could improve cerebral perfusion but risks blood-brain barrier (BBB) disruption, worsening outcomes. We previously found that intermittent hypoxia (IH) promotes cerebral angiogenesis and improves IS outcomes, but whether it maintains BBB integrity during angiogenesis and the underlying mechanism remains unclear. This study established mouse hypoxia models, including IH and continuous hypoxia (CH) treatment groups. We found that both IH and CH transiently increased cerebrovascular permeability via angiogenesis activation. However, IH restored permeability to baseline over time, with astrocyte end-foot wrapping, pericyte coverage, and tight junction protein ZO-1 level in neovessels comparable to controls. In contrast, CH failed to recover vascular leakage and BBB integrity within the same period. Mechanistically, IH uniquely activated both hypoxia-inducible factor (HIF)-1α and HIF-2α, while CH only activated HIF-2α. HIF-1α-specific activation in the IH group promoted downstream vascular endothelial growth factor (VEGF)-B transcription, which antagonized VEGFA-mediated endothelial barrier disruption and adhesion molecule upregulation. This study demonstrates that IH maintains neovascular BBB integrity via the HIF-1α/VEGFB pathway, providing a theoretical basis for novel IS interventions and targeted drug development.
Reconstruction of large segmental bone defects remains challenging because current grafting strategies often fail to coordinate angiogenesis, neurogenesis, and osteogenesis. Here we developed a functional scaffold (peptide/Talin1 plasmid/PLA-HA/GelMA, PTPG) capable of simultaneously delivering peptides and Talin1 plasmids. We hypothesized that this scaffold enables neurovascularized bone regeneration through bidirectional activation of integrin β1 (ITGB1). The REDV-IKVAV (Arg-Glu-Asp-Val-Gly-Gly-Gly-Ile-Lys-Val-Ala-Val) peptide triggers "outside-in" ITGB1 signaling in endothelial and Schwann cells, while Talin1 plasmid-mediated "inside-out" activation. This PTPG scaffold synergistically enhances cell proliferation, migration and secretion, which are eliminated by ITGB1 silencing. In vivo, PTPG scaffold promotes aligned neurovascular networks guiding bone deposition. Single-cell RNA sequencing demonstrates enrichment of endothelial H-type signatures and repair-associated Schwann cell phenotypes, with activation of ITGB1-focal adhesion kinase-paxillin signaling. Collectively, this scaffold integrates structural support with peptide and genetic cues to promote coordinated angiogenesis, neurogenesis, and osteogenesis, offering a promising strategy for functional bone regeneration.
Microbial sulfur-containing secondary metabolite thienodolin (1) features a unique tricyclic thieno[2,3-b]indole scaffold, yet its biosynthesis has remained enigmatic. Here, we uncover an unexpected enzymatic logic in which a consortium of distinct oxidoreductases cooperatively orchestrates indolethiophene skeleton formation and subsequent bioactivation, ultimately generating the authentic antibacterial metabolite thienoxidolin (10). Following thiotryptophan formation by SDR enzyme TndE, the heme-dependent DUF6875 enzyme TndD initiates C-S bond formation via N-hydroxylation to yield a dearomatized tricyclic species, which is efficiently driven forward and stabilized by aromatization catalyzed by the FAD-dependent oxidoreductase TndG. Notably, TndD functions as a bidirectional redox enzyme, reverting the N-hydroxyl group to the stable N-H form to complete the indolethiophene scaffold construction. After amide formation, late-stage N-hydroxylation by the cytochrome P450 enzyme TndC, previously misassigned as the C-S bond-forming enzyme, produces the bioactive product 10. Intriguingly, TndD may also mediate the deactivation of 10 back to 1, representing an intrinsic self-protection mechanism. Together, these results expand the catalytic repertoire of heme-dependent enzymes and highlight reversible N-hydroxylation as a pivotal strategy for heterocycle formation and bioactivity regulation in microbial secondary metabolism.
Clinicians evaluating gender-affirming voice patients often use voice quality-of-life questionnaires. The Trans Woman Voice Questionnaire (TWVQ), formerly the Transsexual Voice Questionnaire Male to Female, evaluates vocal functioning and social participation. Our goal was to find which questions had the most impact, defined by higher distress/symptom burden and greater frequency of severe responses, for the patient. Our secondary, more exploratory goal was to identify items to inform, potentially formulate, and validate a preliminary 11-question version of the same questionnaire. TWVQ responses from transgender women presenting for initial evaluation were retrospectively analyzed. Each of the 30 items was scored on a four-point Likert scale. Statements were ranked by the frequency of severe endorsement ("usually or always"). Item-total correlations were calculated using Pearson correlation to evaluate association with the overall questionnaire burden. Internal consistency for the full questionnaire and the proposed exploratory abbreviated version was evaluated using Cronbach's alpha as a preliminary estimate of internal consistency. Twenty-six participants completed the 30-item TWVQ. Twelve items were endorsed as severe by at least 40% of respondents, with the highest frequencies observed among statements related to vocal identity. Item-total correlations ranged from r = 0.21 to r = 0.81, with multiple items demonstrating moderate to strong associations with overall questionnaire burden. Items with low correlations were excluded, even if they had moderate endorsement frequency. The full questionnaire demonstrated excellent internal consistency (Cronbach's α = 0.95). The proposed preliminary 11-item abbreviated version maintained good internal consistency (α = 0.89) while retaining representation across vocal identity, anxiety and avoidance, and vocal function domains. This exploratory analysis identified candidate items that may inform the future development of an abbreviated version of the TWVQ. The proposed preliminary short form demonstrates good internal consistency and retains items most indicative of patient-reported voice-related burden. Further validation in larger independent cohorts is required before clinical implementation, and a more detailed analysis of a larger patient cohort may yield a different short-form questionnaire. A future short-form instrument may serve as a practical tool for screening and monitoring in time-limited clinical settings, while the full TWVQ remains suitable for comprehensive assessment.
Access to musculoskeletal healthcare services in Sub-Saharan Africa is inadequate. As osteoarthritis is the most prevalent chronic osteoarticular disease globally, it's essential to understand its social and economic impact, as well as the determinants of inequities in access to healthcare services in Sub-Saharan Africa. The absence of systematised knowledge on this topic makes this review pertinent. However, due to data scarcity, assessing this burden is challenging. The objective of this scoping review is to map and summarise the available literature up to 2025 on the socioeconomic burden and health inequity determinants among the Sub-Saharan African population with osteoarthritis. A predefined search strategy will be applied to MEDLINE (via PubMed), Embase, African Journals Online and African Index Medicus to incorporate articles relevant to adults diagnosed with osteoarthritis who are residents of sub-Saharan Africa. We will also include grey literature sources such as Google Scholar, Research Square, manuals, books, medical society websites, secondary databases, theses and dissertation repositories and conference proceedings. Study selection will be conducted in two stages by a pair of reviewers who will independently screen titles and abstracts according to the eligibility criteria, followed by a full-text review of the selected studies. The search period was from October 2025 to January 2026. Data extraction will be performed using a standardised charting form developed by the review team. This scoping review maps evidence on OA-related socioeconomic impacts and healthcare inequities in Sub-Saharan Africa. As a secondary data analysis, ethical approval is not required. Findings will be disseminated via peer-reviewed journals and academic conferences to clinicians and policymakers.
Objectives: In this study, we aimed to evaluate the changes suggestive of maxillary anterior displacement in adults undergoing 3D-guided midpalatal piezocorticotomy-assisted Miniscrew-Assisted Rapid Palatal Expansion (MARPE), in addition to the contributing factors for forward maxillary movement and the subsequent immediate shift in the mandible. Methods: In this retrospective quasi-experimental study, cephalometric records of 80 adult patients (mean age 35.23 ± 8.76 years; 52 females and 28 males) were analyzed. Maxillary anterior displacement was assessed via SNA and A-Nperp(FH), while intermaxillary changes were measured using the ANB angle. Vertical and rotational changes were tracked through SN-MP, FH-MP, and various occlusal plane angles (OcP-FH, OcP-SN, OcP-GoMe). Facial height dimensions (TAFH, UAFH, LAFH, PFH) and dento-alveolar positions (U1-MP, U1LENGTH) were also recorded. Results: Following intervention, significant increases were observed in SNA (0.96°; 95% CI [0.48, 1.43]), ANB (1.42°; 95% CI [1.04, 1.80]), and A-Nperp(FH) (0.81 mm; 95% CI [0.24, 1.39]). The SN-GoMe angle increased by 0.98°, and Posterior Facial Height (PFH) decreased by 1.57 mm, while the upper incisor length (U1LENGTH) significantly decreased by 0.71 mm. Conclusions: In adults, 3D-guided midpalatal piezocorticotomy-assisted MARPE is associated with an increase in SNA, ANB, SN-GoMe, and A-Nperp(FH), and decreases in Posterior Facial Height (PFH) and the maxillary incisor length. The amount of mean midpalatal separation is moderately associated with the increase in SNA, while the increase in SNA is not associated with age or gender. Further 3D cephalometric studies would be beneficial to confirm the current findings.
The pharmacy profession stands at a pivotal moment, as emerging scientific advancements and evolving healthcare demands require adept pharmacy practitioners and scientists. The integration of precision medicine, cellular and acellular regeneration, nano and bioengineering (e.g., 3D/4D bioprinting), digital therapeutics, artificial intelligence (AI)-point-of-care testing, and treating is starting to reshape pharmacy education, practice, and patient care. Pharmacy education needs to embrace these innovations to prepare graduates for the future of practice, to optimize therapeutic outcomes, and contribute meaningfully to translational medicine. This review elaborates on the historical evolution toward the incoming wave of the pharmacy profession and considers the necessary educational models that might be associated with its practice. Expanded patient care roles are essential in this new era, with clinical pharmacists increasingly working alongside physicians under collaborative practice agreements. Additionally, prescriptive authority for pharmacists is gaining traction, enhancing healthcare accessibility and medication management. The integration of digital health technologies (e.g., telepharmacy, automation, wearable medical devices, and AI-driven decision support systems) further empowers pharmacists to deliver efficient, patient-centered care. Certain prospective concentrations (e.g., precision/personalized medicine, industrial pharmacy, drug discovery and development, drug compounding and formulation, and advanced drug delivery systems and devices) can further empower pharmacy education towards healthcare needs. By embracing technological and scientific advancements, pharmacists can solidify their roles as integral healthcare providers, ensuring that the profession remains dynamic, relevant, and impactful in an evolving healthcare landscape.
Out-of-hospital blood transfusion (OHBT) trials in trauma face unique ethical and operational challenges. Patients are often incapacitated, time-critical interventions preclude traditional consent, and surrogate decision-makers are rarely accessible in the out-of-hospital environment. The Canadian Prehospital and Transport Transfusion Network (CAN-PATT) supports the use of alternative models of consent to enable rigorous evaluation of OHBT strategies. This position statement outlines the ethical and regulatory justification for an exception from prospective consent with opt-out notification model used in the SWiFT Canada (Study of Whole Blood in Frontline Trauma) pilot randomized controlled trial. Grounded in the Tri-Council Policy Statement 2 (TCPS2) Article 3.8 governing research in medical emergencies, the SWiFT Canada model uses multi-modal notification and post-enrollment withdrawal options to balance feasibility with respect for autonomy. We argue this approach is essential to advance evidence-based transfusion practice in Canadian out-of-hospital care and serves as a national template for emergency research.
It has been suggested that peripheral inflammation and immune-mediated neuronal dysfunction play a decisive role in the pathophysiology of obsessive-compulsive disorder (OCD). However, work addressing this hypothesis is mostly based on small samples and heterogeneous methodologies, and has led to inconsistent results. Here we conducted the largest study to date comparing an extensive panel of immune markers in the peripheral blood between adult patients with OCD and healthy controls. One-hundred and thirty-nine patients with OCD and 131 age and sex-matched controls were assessed cross-sectionally for sociodemographic and clinical characteristics, and collection of peripheral blood. The concentration of high-sensitivity C-reactive protein (main outcome), of twelve cytokines, and the prevalence of positivity for anti-nuclear, anti-thyroid peroxidase, anti-thyroglobulin, and anti-basal ganglia antibodies (secondary outcomes), were assessed in the serum or plasma using ELISA. In a subsample of 176 participants, we further compared cytokine gene expression using RT-qPCR, between groups. While patients had a significantly higher prevalence of self-reported general medical disorders, we consistently found similar levels of immune markers when comparing patients and controls, with only minor, non-significant, differences. In stratified analyses according to age of onset, current depressive episode, recruitment centre and medication status, the lack of group differences was consistent, except for higher IL-8 gene expression in patients with co-morbid depression, while subgroup analyses within the patient group revealed lower TGF-β concentration in patients with early-onset OCD. Our findings support that, contrary to what has been shown in mood and psychotic disorders, in symptomatic and medicated adults with OCD there are only minor differences relative to healthy volunteers in cross-sectional assessments of peripheral immune markers, that may reflect co-morbid depression and/or early-onset of the disorder.