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Bacterial vaginosis (BV) is highly prevalent in women of African origin and has been associated with adverse birth outcomes (ABO), particularly preterm birth (PTB). However, evidence from sub-Saharan Africa remains limited, and while a previous study conducted in this area examined the prevalence of BV, its impact on pregnancy outcomes was not assessed. This study assessed the prevalence and risk factors of BV in early pregnancy and examined its association with ABO in the middle belt of Ghana. This analysis was nested within a prospective cohort of pregnant women in the Kintampo North Municipality and Kintampo South District. Pregnant women <20 weeks' gestational age were screened, consented, enrolled and followed through delivery until one year after birth. At enrolment, sociodemographic, behavioural, and obstetric data were collected, along with biological samples, including vaginal swabs for Gram staining and Nugent scoring. BV status was categorized as BV-negative (0-6) or BV-positive (7-10) and ABO included PTB (<37 weeks), low birthweight (LBW&#x2009;<&#x2009;2.5 kg), and foetal loss. Data were double-entered in REDCap and analysed in R. Associations between BV and ABO were assessed using chi-square tests, and logistic regression was used to identify risk factors for BV. Of 1,180 pregnant women enrolled, 355 (30.1%) were BV-positive. PTB (9.9% vs. 8.7%; p&#x2009;=&#x2009;0.50), LBW (13.8% vs. 12.0%; p&#x2009;=&#x2009;0.39), and foetal loss (4.5% vs. 2.8%; p&#x2009;=&#x2009;0.14) were all higher among BV-positive women, but none reached statistical significance. Younger age and unmarried status were associated with BV. Unmarried women (AOR 1.63; 95% CI: 1.20-2.22) and those reporting one sexual encounter per week (AOR 1.55; 95% CI: 1.01-2.37) had increased odds of BV. BV is highly prevalent in early pregnancy in this Ghanaian cohort, particularly among younger and unmarried women, but was not significantly associated with ABO. Targeted screening among high-risk groups is necessary, and future molecular approaches may better characterise BV subtypes linked to ABO in African settings.

Fetal speckle tracking echocardiography is an ultrasound-based technique used to assess myocardial velocity and deformation of the fetal heart. Despite its potential, the method has not yet been integrated into routine pregnancy care, partly due to concerns about inconsistent reproducibility. This study aimed to evaluate the intra- and inter-observer reproducibility of global longitudinal strain measurements derived from a fixed fetal cardiac cycle, using speckle tracking echocardiography. Healthy women with singleton pregnancies were enrolled during the second trimester. From enrolment until delivery, four-chamber view clips of the fetal heart were acquired every four weeks. For intra-observer reproducibility, a single observer analyzed the same heart cycle in one DICOM clip twice for global longitudinal strain in the left and right ventricles, with a minimum interval of two weeks between assessments in a blinded manner. For inter-observer reproducibility, two independent observers analyzed the same cardiac cycle within one DICOM clip. A total of 124 women were included, yielding 632 ultrasound clips. Intra-observer reproducibility was poor to moderate for global longitudinal strain for the right and left ventricles. Inter-observer reproducibility demonstrated moderate to good reproducibility for global longitudinal strain in both ventricles. The reproducibility was generally higher in the left ventricle than in the right, and the highest reproducibility was observed before 32 weeks of gestation. In conclusion, speckle tracking echocardiography during pregnancy showed variable reproducibility of strain analysis when performed on a fixed cardiac cycle, with more consistent results in the left ventricle. These findings support the potential utility of fetal speckle tracking echocardiography, while highlighting the need for further refinement of reproducibility before clinical implementation.

Physical inactivity increases with age, yet evidence on physical activity (PA) among older adults affected by forced displacement remains scarce, particularly in refugee camp settings. We aimed to assess PA levels and identify associated factors among Rohingya older adults aged &#x2265;60 years living in refugee camps in Southern Bangladesh. A cross-sectional survey was conducted between May and August 2024. PA was assessed using the Physical Activity Vital Sign (PAVS), alongside socio-demographic, health, and lifestyle variables collected via a pre-tested semi-structured questionnaire. in line with WHO guidelines, participants were classified as active (&#x2265;150 minutes of moderate to vigorous PA per week) or low active (<150 minutes of moderate to vigorous PA per week). Multivariable Firth penalised logistic regression was used to examine factors associated with meeting PA guidelines. The sample comprised 943 participants (mean age 67.5 years), of whom 70% were aged 60-69 years and 66% were male. Overall, 95% were classified as low active. In adjusted analyses, only older age (&#x2265;70 years) was significantly associated with lower odds of meeting PA guidelines (OR 0.31, 95% CI 0.11-0.70). Fewer than one in twenty Rohingya older adults met recommended PA levels. These findings highlight the need for tailored, culturally appropriate PA interventions, with particular attention to adults aged 70 years and older.

Mentha species are widely cultivated aromatic plants valued for their essential oils and antimicrobial properties. However, despite their agricultural and pharmacological significance, limited information is available on how different Mentha species influence rhizosphere microbial communities and their relationships with soil physicochemical parameters and essential oil composition. In this study, we examined the rhizosphere microbiota of three closely related taxa - Mentha&#x2009;&#xd7;&#x2009;villosa B10, M. spicata B17, and M. suaveolens J17 - cultivated under uniform field conditions. Rhizosphere and bulk soils were analyzed for physicochemical properties, microbial composition (16S rRNA, ITS sequencing), essential oils (gas chromatography-mass spectrometry), and arbuscular mycorrhizal colonization. Bacterial communities were dominated by the phyla Actinomycetota, Pseudomonadota, Acidobacteriota, Bacillota, and Chloroflexota, while fungal communities were primarily composed of Ascomycota, Mortierellomycota, Basidiomycota, and Rozellomycota. Rhizosphere soils exhibited higher fungal diversity than bulk soils, with Glomeromycota detected exclusively in rhizosphere. Microbial community composition differed significantly among Mentha taxa: M. spicata B17 displayed the lowest bacterial diversity, the most distinct microbial assemblages, and the highest arbuscular mycorrhiza colonization. Soil properties - particularly humus content, phosphorus, potassium, and sodium - were strongly correlated with bacterial diversity, while fungal communities showed weaker associations. Integration of essential oil data revealed genotype-dependent chemical profiles: Mentha&#x2009;&#xd7;&#x2009;villosa B10 and M. spicata B17 were characterized by high proportions of L-carvone and limonene, whereas M. suaveolens J17 was dominated by cis-piperitone epoxide and piperitenone oxide. Together, these findings demonstrate that even closely related Mentha cultivars can harbor distinct rhizosphere microbiota, associated with both plant chemical traits and soil characteristics. This study highlights the complex interactions between aromatic plants, soil chemistry, and microbial communities, offering novel insights into plant-soil-microbe interactions in medicinal and aromatic crop systems.

The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum. We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a "fight-or-flight"-like response.

CD4+ T cells that produce IFN-&#x3b3; (T helper 1 [Th1] cells) chiefly mediate vaccine acquired resistance to fungal infections. However, the key regulators of the development of Th1 cells and acquired resistance to fungi are incompletely understood. Here, we report that Natural Killer Cell Granule Protein (NKG7) acts as an unappreciated regulator inducing anti-fungal Th1 cells to produce IFN-&#x3b3; and converting plastic Th17 cells into polyfunctional memory Th1 cells.

Proline is a chemically unique amino acid that influences protein structure and slows peptide-bond formation during translation. While its enrichment in intrinsically disordered regions is well known, the functional importance of its organization along protein sequences remains unclear. Here, we performed a proteome-wide analysis of inter-domain linkers in human proteins to investigate how proline organization relates to domain architecture and folding demands. We find that clustered and consecutive prolines are enriched in linkers following topologically complex domains that require the formation of long-range contacts. This suggests that proline clusters may act as intrinsic sequence-encoded pauses during translation, helping coordinate co-translational folding. We further show that linkers with enriched proline clusters frequently flank aggregation-prone domains and that proteins containing such linkers tend to have longer cellular half-lives. Together, our results demonstrate that the organization of proline residues, beyond their overall abundance, is an important determinant of protein folding, aggregation, and stability, revealing a general mechanism by which amino acid sequences regulate protein behavior.

Remote patient monitoring (RPM) expanded dramatically during the COVID-19 pandemic and continues to be implemented. However, no standardized method for classifying them exists which has implications for comparative evaluations. Our goal was to design and develop a disease-agnostic RPM typology tool as a first step towards a standardized approach for understanding and implementing RPM programs for different clinical use-cases. Guided by the Knowledge-To-Action framework, we conducted a rapid review of RPM programs from Canada, the United States, Europe, the United Kingdom, and Australia that were used to manage diabetes, chronic obstructive pulmonary disease, congestive heart failure, hypertension, and COVID-19. We identified 87 articles to define common characteristics of real-world RPM interventions to enable comparison across different programs through pattern recognition, information mapping, and sensemaking. We extracted data with a macros-enabled Excel template. Design sessions with key stakeholders (researchers, clinical advisors, provincial RPM managers, and patient partners) provided iterative feedback on the typology and we defined a glossary of characteristics. The 12 most reported characteristics of RPM programs (including size, resources, monitoring team, data flow, alert protocol, workflow, and equity considerations) were clustered into four domains. Integration and equity domains were recognised as ideal aspirations of all RPM programs. Technology and touch domains were considered to exist on a spectrum from low-to-high- neither inherently superior to the other. 16 distinct RPM typologies were expressed through a 4x4 matrix (i.e., high or low on each of the four domains). Using this tool can inform insights on program maturity, implementation, and continued investments in RPM. We anticipate this typology will help new initiatives have greater potential to be robustly evaluated and sustained to scale. Future directions include further validity testing and exploring feasibility to systematically categorise real-world RPM programs with this tool.

Typhoid is a significant global health challenge due to its high pathogenicity and antimicrobial resistance. Salmonella typhi (S.typhi)&#xa0;can switch its lifestyles between biofilm and planktonic phase which allows it to evade host defenses and develop resistance to antibiotics. Salmonella sp. harbors multiple genes encoding efflux-pumps systems whose up-regulation contributes to multi-drug resistance (MDR) and extensive drug-resistance (XDR). To overcome the battle against resistant S. typhi strains, novel non-antibiotics inhibitors are required for inhibitory application. This study assesses the inhibitory effect of lignans against drug resistance of S. typhi. Clinical resistant and sensitive strains of S. typhi were obtained and characterized. The inhibitory effect of lignans, specifically Schisandrin A and B, purified from the plant Schisandra chinensis, are found to be effective non-antibiotic inhibitors were evaluated through standard microbiological techniques like growth curve and time-kill assays. Impact on bacterial morphology was analyzed using scanning electron microscopy (SEM). Our study explores two approaches, such as efflux pumps (EPs) inhibition and antibiofilm assays. Using colony-forming unit (CFU) assays, growth curve analysis, and SEM imaging, we observed significant bacteriostatic effects, with Schisandrin B causing notable membrane disruption. Schisandrin B also showed remarkable biofilm inhibition (90.33%) and strong efflux pumps inhibition. This study offers a strong basis for future research on addressing antibiotic resistance in clinically relevant pathogens.

Antimicrobial resistance (AMR) is a major global health threat, and environmental reservoirs such as wastewater (WWTPs) and drinking water treatment plants (DWTPs) may facilitate its persistence and spread despite reducing bacterial loads. We investigated 152 antibiotic-resistant Escherichia coli strains collected across treatment stages from two WWTPs and one DWTP in Barcelona, Spain. Strains were characterized through antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, biofilm assays, and screening of antimicrobial resistance genes (ARGs), virulence factors (VFGs), biocide and heavy-metal tolerance genes (HMTGs). Although E. coli bacterial loads decreased along treatment, AMR remained highly prevalent: 85.5% of strains were multidrug-resistant (MDR), 5.3% extensively drug-resistant, and 11.2% carbapenemase-producers. Strains harboring integrase genes were 2.4 to 11.8 times more likely to harbor ARGs for sulfonamide, aminoglycoside, phenicol, trimethoprim, mercury and quaternary-ammonium compounds. Strains carrying blaCTX-M genes were 3.0 to 20.3 times more likely to carry VFGs, while high-risk clones were 3.2 to 7.0 times more associated with VFGs. Some MDR and high-risk E. coli clones persisted in reclaimed water, and one MDR strain was detected at the DWTP inlet. These findings highlight environmental AMR reservoirs as a public health concern and support a One Health approach integrating antibiotic stewardship and environmental monitoring.

Prostate cancer (PCa) is characterized by molecular heterogeneity and metabolic reprogramming, but the relationships among transcriptomic, proteomic, and metabolic signals remain incompletely defined. Here, we present a human-centered, cross-dataset analysis of public RNA, protein, and metabolomics data in PCa. We analyzed RNA and protein profiles from PC3 parental and drug-resistant cells together with an independent human matched tissue metabolomics dataset from Metabolomics Workbench (ST000784). RNA-protein overlap analysis identified seven genes that were significant at both layers, including five concordantly upregulated genes: UPP1, IGF2R, FLNC, DSP, and PLEC. Among these, UPP1 provided the most direct metabolic interpretation because it encodes uridine phosphorylase 1, an enzyme linked to pyrimidine salvage. Independent ST000784 matched prostate tissue metabolomics supported broader nucleotide metabolism remodeling, including significant changes in N-carbamoyl-L-aspartate, guanosine monophosphate, and adenosine 3,5-cyclic monophosphate. In contrast, uracil was not significantly altered and uridine 5'-monophosphate showed only a trend after multiple-testing correction. Repeated stratified cross-validation showed that UPP1-containing candidate gene sets achieved high within-layer AUC values in RNA and protein data, while nested statistical benchmark models also performed strongly. These results prioritize a UPP1-associated nucleotide remodeling hypothesis in PCa, but do not establish causal regulation of metabolite abundance or clinical diagnostic utility. Future matched multi-omics and perturbation experiments are required.

Primary care physicians (PCPs) are on the front lines of health promotion and disease prevention, yet evidence supports a longstanding gap in physicians' capacity to counsel about diet, a key factor in patient health and chronic disease risk. Momentum to address the nutrition training needs of physicians is growing; however, challenges PCPs experience due to inadequate training are further complicated by clinical practice barriers. This study seeks to better understand the complex problem PCPs face addressing nutrition with patients to inform potential solutions. This qualitative study takes a design thinking approach to understanding the problem by learning from PCPs about their experience, challenges, and priorities addressing nutrition with patients. Findings from semi-structured interviews with 32 PCPs revealed that while they value nutrition and believe they have an important role in addressing diet with patients, their role as a generalist in addressing nutrition lacks clarity. PCPs describe learning their current approach to nutrition primarily outside of formal medical training, resulting in variability and inconsistency in approaches and recommendations and general frustrations about their ability to give actionable guidance. While registered dietitians (RDs) are often viewed as valuable support for patients, PCPs describe multiple challenges to RD utilization and subsequently at times may be the only ones with the opportunity to address diet with patients. Additional system- and societal-level barriers, such as time limitations and the food environment, further complicate PCPs' experiences advising patients about nutrition. Main limitations of this study are limited generalizability from recruiting graduates of a single medical school and PCPs with greater interest in nutrition or more frustration with their current approach to nutrition may have been more likely to participate. Our results support the need to clearly define a realistic role for PCPs as generalists addressing nutrition. Clarified expectations in turn can inform nutrition training of physicians and guiding frameworks and strategies for giving practical, evidence-based nutrition guidance. PCPs also need increased support through access to resources, strategies to improve RD collaboration, and attention to system- and societal-level challenges influencing dietary interventions in primary care.

Approximately 39.9 million people are living with HIV worldwide, most in sub-Saharan Africa. Effective antiretroviral therapy has shifted attention to metabolic comorbidities, and emerging evidence links integrase inhibitors such as dolutegravir to elevated serum uric acid, yet the global burden of hyperuricemia and gout in this population is unquantified. This protocol describes a systematic review and meta-analysis of observational studies (cross-sectional, cohort, and case-control) published from inception to May 2026. We will search PubMed/MEDLINE, EMBASE, Web of Science, and CINAHL. Studies involving adults (&#x2265;18 years) living with HIV that report the prevalence or incidence of hyperuricemia or gout will be included. Two independent reviewers will screen studies, extract data, and assess risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Checklist and the Newcastle-Ottawa Scale (NOS). Primary outcomes are the pooled prevalence of hyperuricemia and gout in PLHIV. Secondary outcomes include risk factors associated with urate dysregulation (ART regimen, Cluster of Differentiation 4 [CD4] count, viral load, metabolic comorbidities, and HIV duration), and gout as an immune reconstitution inflammatory syndrome (IRIS) manifestation. A random-effects meta-analysis using the DerSimonian-Laird method with Freeman-Tukey double-arcsine transformation for prevalence data will be performed in R software. Heterogeneity will be assessed using the I2 statistic and Cochran's Q test. Subgroup analyses will explore variation by ART class (pre-ART, PI, NNRTI, INSTI/dolutegravir era), geographic region, CD4 category, and study quality. CRD420261360734.

Frontline health workers in humanitarian settings play a critical role in pandemic response, yet evidence on what sustains response readiness beyond the emergency is limited. This study examined factors associated with primary healthcare workers' sustained self-reported knowledge, skills, and confidence to respond to future outbreaks or pandemics, with the configurational analysis focused on confidence. A retrospective cross-sectional survey was conducted among 118 health workers in Honduras, Syria, and South Sudan who received COVID-19 training. Coincidence analysis was applied with a set of associated predictors to identify combinations of conditions linked to high sustained confidence. COVID-19 training that covered five or more core topics was associated with high sustained self-rated capacities; topics included proper use of personal protective equipment, transmission routes, procedures for case screening, and facility infection prevention and control. Continuity of primary healthcare services after emergency funding ended, fewer disruptions from conflict or natural disasters, and supportive team structures were linked to confidence. Coincidence analysis indicated multiple sufficient causal pathways to sustained confidence, the first being very high self-rated post-training knowledge as a standalone pathway (consistency: 0.66, coverage: 0.62). Other pathways included health workers with higher education combined with either case-screening training or working in facilities that continued services post-funding (consistency: 0.604, coverage: 0.64). Applying COVID-19 practices to other outbreaks (e.g., dengue, cholera) further reinforced capacities and illustrated the pathogen-agnostic value of core infection prevention and response competencies. Results underscore that durable preparedness at the primary healthcare level in fragile contexts depends on comprehensive, practice-oriented training for all types of frontline health workers, as well as enabling conditions that maintain service delivery. This study contributes to emerging literature using implementation science frameworks and coincidence analysis to understand complex causal pathways. The findings should inform global health security investments, including in the world's most fragile health systems.

1,5-Anhydrohexitol nucleic acid (HNA) is a promising xeno nucleic acid (XNA) for applications such as aptamers and catalysts, due to its favourable physico-chemical properties. Realizing this potential requires efficient and high-fidelity polymerases capable of processing HNA. A key component are HNA reverse transcriptases that convert HNA into DNA, an essential step in standard SELEX workflows. Although HNA reverse transcriptases have been generated by directed evolution, structural insight is essential to guide further enzyme engineering. Here, we report the 2.8 &#xc5; crystal structure of the engineered HNA reverse transcriptase KOD-H4, derived from the B-family DNA polymerase of Thermococcus kodakarensis, captured in a closed ternary complex with dATP, a 3'-terminated primer and a mixed HNA/DNA template. Compared to a previously reported open ternary KOD-H4 structure, the presented structure adopts a more closed conformation with increased finger and thumb domain closure and formation of a canonical Watson-Crick-Franklin base pair at the insertion site. Direct downstream nucleotides show more distorted base pairing and one HNA residue transits from the unusual 1C4 conformation it adopted in the open complex to the 4C1 hexitol sugar conformation. These findings demonstrate that KOD-H4 can form a closed, pre-catalytic complex resembling that of the wildtype enzyme with natural substrates, and reveal state-dependent conformational flexibility of HNA. Such flexibility should be considered in the design and optimization of enzymes that process HNA.

Plastic consumption has become pervasive in modern society, with over 300 million metric tonnes produced annually worldwide, contributing significantly to municipal waste. In Bangladesh, where annual per capita plastic use has risen to 22 kg as of 2022, innovative solutions for managing plastic waste are urgently needed. This research introduces a novel approach to the pyrolysis of various plastics (PET, PVC, PP, HDPE) within a temperature range of 300 &#xb0;C to 550 &#xb0;C to produce pyrolytic bio-oil and biochar. We established optimal conditions for each plastic type-500 &#xb0;C for PET, PVC, and HDPE, and 450 &#xb0;C for PP-resulting in maximized yields of high-quality liquid oils (61.3% for PP and 47.23% for HDPE). Unique to this study, we innovatively adjust the pyrolysis process parameters to enhance the yield and quality of the derived bio-oils, tailored specifically to the types of plastics treated. The liquid products were characterized as predominantly consisting of C6-C16 hydrocarbons, aligning them closely with naphtha, gasoline, and diesel specifications, suitable for use as renewable fuels. Furthermore, our research applies FTIR and GC-MS analyses in a novel way to provide a detailed examination of these bio-oils, revealing significant quantities of paraffinic hydrocarbons in PP and olefins and naphthenes in HDPE, contributing to their potential fuel applications. The solid char byproducts were also comprehensively characterized using SEM and XRD, providing insights into their suitability for various industrial applications. This study not only demonstrates the potential of pyrolysis to transform waste plastics into valuable renewable energy resources but also advances the technological framework for sustainable waste management practices, marking a significant leap forward in the efficiency and application of plastic waste conversion technologies.

Although bar charts are widely used in scientific publications, their rasterized format within Portable Document Format (PDF) files complicates automated data extraction, hindering large-scale evidence synthesis and meta-analysis. To address this, we developed and evaluated an automated pipeline for extracting quantitative data from bar charts embedded in the biomedical literature. The four-stage pipeline comprises (1) image extraction and panel segmentation, (2) optical character recognition (OCR)-based text detection, (3) image disassembly to identify chart components, and (4) data reconstruction using numeric parsing and axis-based interpolation. The system combines edge detection, morphological operations, and convolutional neural network (CNN)-based figure classification using a transfer-learned Inception v3 model. Performance was validated on randomized controlled trials in age-related macular degeneration, with manually annotated values from a semi-automated labeling tool as the reference standard, and agreement was assessed using Bland-Altman analysis. Across 28 bar charts from ten publications, the pipeline correctly recognized 92.9% (95% confidence interval [CI], 77.4-98.0) of figure types, 96.0% (95% CI, 94.2-97.3) of text blocks, and 79.1% (95% CI, 74.7-83.0) of bars. For numerical reconstruction, 81.2% (95% CI, 76.3-85.2) of bar values fell within &#xb1;5% of the reference standard, 63.0% (95% CI, 57.3-68.3) within &#xb1;2%, and 48.6% (95% CI, 43.0-54.3) within &#xb1;1%. Bland-Altman analysis showed a small negative bias of -0.18 (95% CI, -0.34 to -0.02), with 94.9% of differences within the limits of agreement. Most outliers arose from OCR digit misclassification or ambiguous bar boundaries. This proof-of-concept study demonstrates the feasibility of automated data extraction from bar charts using a hybrid approach that combines image-processing heuristics with CNN-based classification. Although currently limited to bar charts and a single clinical domain, the pipeline represents a step toward scalable, end-to-end systems for automated evidence extraction to support meta-analyses across the biomedical literature.

This case study estimates the economic implications of enhancing animal welfare (AW) in Alpine dairy farming, specifically focusing on Simmental cattle in both conventional (CON) and organic (ORG) farms. Given the increasing demand for higher welfare standards from consumers and policymakers, it is important to assess the economic feasibility of implementing these practices. The primary aim of this study is to develop a proof of concept for estimating the costs involved in meeting specific AW standards. Data were collected from 30 dairy farms (15 CON and 15 ORG), and AW scores were evaluated using both resource-based and animal-based indicators (total score of 90 points). Additionally, AW costs were assessed by calculating the cumulative additional costs, offset by potential benefits. Results show ORG farms achieve higher AW scores (73.99) compared to CON farms (70.28) but incur significantly higher production costs (&#x20ac;1.263/kg ECM for ORG vs. &#x20ac;0.977/kg ECM for CON), primarily due to the dilution effect caused by lower milk production on ORG farms. A nonlinear relationship between AW scores and AW costs was also observed, indicating that higher AW scores in initial farm conditions could, in some cases, lead to cost savings, particularly in larger and more efficient farms. The study emphasizes the need for clearly defined AW standards and a corresponding scoring system that reflects both the welfare impacts on animals and the economic feasibility for farmers. Further, we argue that the aggregation of AW scores should not merely categorize welfare on a simple best-to-worst continuum. Rather, it should account for the specific targets and conditions that policymakers and consumers are willing to support financially.

Miltefosine, the only oral antileishmanial drug with regulatory approval, has expanded treatment options in several endemic settings but shows variable efficacy across Leishmania species, clinical forms, and host immune contexts. In Southeast Asia, where Leishmania (Mundinia) martiniquensis and L. (M.) orientalis&#xa0;are increasingly reported, amphotericin B formulations remain the main treatment despite toxicity, relapse, and implementation constraints. This review evaluates miltefosine's clinical relevance, mechanisms of action, and resistance pathways, with emphasis on Thailand and neighboring Southeast Asian settings. A Thai compassionate-use case using miltefosine with liposomal amphotericin B for refractory L. martiniquensis infection achieved repeated clinical improvement and culture negativity after combination induction, although monotherapy was insufficient to maintain remission in advanced immunosuppression. Evidence from other endemic regions indicates that poor adherence, unregulated access, prolonged subtherapeutic exposure, and inadequate monitoring can reduce treatment durability and favor reduced susceptibility. Mechanistic studies in non-Mundinia species identify transport disruption, lipid and sterol remodeling, mitochondrial stress adaptation, redox buffering, and host-parasite effects as resistance-relevant axes, while regional data raise concern for amphotericin B-associated reduced miltefosine susceptibility in L. martiniquensis. Wider implementation should therefore be linked to species-resolved diagnostics, baseline susceptibility testing, longitudinal phenotype-genotype surveillance, drug stewardship, and One Health monitoring. Miltefosine should be considered a rational but carefully monitored therapeutic addition for emerging Southeast Asian leishmaniasis.