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Abstract Background Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. Results We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. Video Abstract Conclusions These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

Histopathological studies have been established as effectual and sensitive tools for monitoring fish health. This study evaluated histopathological changes in African catfish fed with herbal additives. African Catfish juveniles (210) with an average weight of 117.3g and average length of 26.7cm were randomized into ten sub-groups and fed diets containing Allium sativum, Chromoleana odorata, and Talinum triangulare; 0.5%, 1.0%, and 3% concentrations, each of the herbal plants and 0% (control) for 42 days and changes in the visceral organs were investigated. Fish were sacrificed on the 43rd day and their visceral organs were collected and fixed in bouin’s fluid for 24h, washed with 10% formalin, and dehydrated through a graded series of ethanol. Collected organs were embedded in paraffin, sectioned at 4-5um thickness, stained with Hematoxylin and Eosin, and scanned with a light microscope. The intestine, gill, liver, and kidney of control and fish fed with 0.5% Allium sativum showed no damage. However, effects ranging from slight lamellae hyperplasia to noticeable lamellae hyperplasia were detected in the gills of the fish nurtured with 3.0% inclusion rates of C. odorata and T. triangulare. Epithelial necrosis and atrophy of tubules in the kidney at a 3.0 % inclusion rate of C. odorata were detected. In conclusion, Allium sativum, Chromoleana odorata, and Talinum triangulare could be included at lower inclusion rates of 0.5 – 1% into Clarias gariepinus feed for prime performance.

Background. To investigate the impact of intrapatient variability (IPV) in the levels of immunosuppressant drugs on health outcomes after liver transplantation. Methods. A comprehensive systematic review and meta-analysis were conducted, examining literature from MEDLINE/PubMed, Embase, Web of Science, Cochrane Reviews, and Cochrane CENTRAL. Results. The analysis focused on acute rejection, graft survival, acute kidney injury, and cancer risk as health outcomes. Of 2901 articles screened, 10 met the inclusion criteria. The results indicate a 19% reduction in the risk of acute rejection in patients with lower IPV (RR = 0.81; 95% confidence interval, 0.66-0.99), although 6 studies found no significant association between high IPV and acute rejection. Contrasting results were observed for graft survival, with 1 study indicating worse outcomes for high IPV, whereas another reported no significant difference. High IPV was consistently associated with acute kidney injury across 3 studies. One study suggested a link between high IPV and hepatocellular carcinoma, although a meta-analysis for these outcomes was not feasible. Conclusions. These findings point to a marginal but statistically significant association between high IPV and an increased risk of acute rejection, highlighting the importance of precise management of immunosuppressive drugs in liver transplant recipients to enhance patient outcomes.

IntroductionChronic conditions, such as diabetes, obesity, heart disease and depression, are highly prevalent and frequently co-occur with food insecurity in communities served by community health centres in the USA. Community health centres are increasingly implementing 'Food as Medicine' programmes to address the dual challenge of chronic conditions and food insecurity, yet they have been infrequently evaluated.Methods and analysisThe goal of this quasi-experimental study was to evaluate the effectiveness of Recipe4Health, a 'Food as Medicine' programme. Recipe4Health includes two components: (1) a 'Food Farmacy' that includes 16 weekly deliveries of produce and (2) a 'Behavioural Pharmacy' which is a group medical visit. We will use mixed models to compare pre/post changes among participants who receive the Food Farmacy alone (n=250) and those who receive the Food Farmacy and Behavioural Pharmacy (n=140). The primary outcome, fruit and vegetable consumption, and secondary outcomes (eg, food security status, physical activity, depressive symptoms) will be collected via survey. We will also use electronic health record (EHR) data on laboratory values, prescriptions and healthcare usage. Propensity score matching will be used to compare Recipe4Health participants to a control group of patients in clinics where Recipe4Health has not been implemented for EHR-derived outcomes. Data from surveys, EHR, group visit attendance and produce delivery is linked with a common identifier (medical record number) and then deidentified for analysis with use of an assigned unique study ID. This study will provide important preliminary evidence on the effectiveness of primary care-based strategies to address food insecurity and chronic conditions.Ethics and disseminationThis study was approved by the Stanford University Institutional Review Board (reference protocol ID 57239). Appropriate study result dissemination will be determined in partnership with the Community Advisory Board.

Abstract Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient’s anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients’ data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Motivational interviewing (MI; Miller & Rollnick, 2012) has expanded from treating substance use disorders to other health concerns across a range of racial-ethnic groups and ages. The spirit of MI lends itself well to working with culturally diverse populations by eliciting the client's values and goals in a collaborative and client-centered approach in pursuit of behavior change. Additionally, MI has been further adapted for use with racial-ethnic minority groups to enhance its effectiveness with specific populations. The aim of this review was to investigate existing cultural adaptations of MI (CAMI), their effectiveness, and to provide directions for future cultural adaptations in both research and clinical settings. This systematic review identified studies of CAMI over the past 20 years using MEDLINE/Pubmed and Embase. The final dataset consisted of 25 peer review studies. In the randomized controlled trial (RCT) studies that utilized a control condition (n = 17), 10 studies showed that the CAMI condition performed significantly better on at least the primary outcome measure than the control condition. All 10 studies adapted Context, Content, and Concepts-three of the dimensions of cultural adaptation defined by the ecological validity framework used in this study (Bernal et al., 1995). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BackgroundAllergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.MethodsA murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.ResultsAlthough AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.ConclusionThis study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

Background and Aim: Despite the plethora of drugs currently available, neurodegenerative diseases are leading cause of morbidity and mortality globally. Hence, there is a need for the development of more alternatives that are safe, efficient, and effective. In Nigeria, the leaves of Cnidoscolus aconitifolius are used ethnomedicinally for the management of central nervous system related disorders such as convulsion and anxiety. In this study, we evaluated some neuropharmacological effects of the methanol leaf extract of C. aconitifolius (CAE) in mice. Methods: Different groups of mice (n = 5) were administered 100, 200 and 400 mg/kg of CAE and then evaluated for sedative-hypnotic, anxiolytic, antidepressant, anticonvulsant, and muscle relaxant properties using standard protocols. Results: The onset of sleep was significantly reduced (P < 0.001), and sleep duration was significantly (P < 0.01) prolonged at doses of 200 and 400 mg/kg. All doses of the extract significantly (P < 0.05) reduced the number of head dips in hole-board test. In elevated plus maze test, the dose of 400 mg/kg increased (P < 0.05) the number of open arm entries without altering the time spent in the open arms of the maze. At 400 mg/kg, there was a significant (P < 0.05) reduction in the duration of immobility in forced swimming test. Doses of 200 and 400 mg/kg of the extract reduced (P < 0.05) the duration of immobility in the tail suspension test. The extract did not exhibit any anticonvulsant effect either in chemically induced or electrically induced models, and there was no significant alteration in motor coordination in extract-treated mice. Conclusion: Our results showed that CAE possesses sedative-hypnotic and antidepressant properties but lack anticonvulsant, anxiolytic and muscle relaxant actions in mice.

Pesticide residues and heavy metal content of cassava, yam, cocoyam, potato, water yam and carrot were evaluated by gas chromatography–mass spectrometry and atomic absorption spectroscopy. The detected pesticide residues in the samples were 2,4-dichlorophenoxyacetic acid, glyphosate, hexachlorobenzene (HCB), dichlorobiphenyl, aldrin, endosulfan, profenofos, g-chlordane, carbofuran, biphenyl, heptachlor, lindane and t-Nonachlor. The concentration of HCB ranged between 0.0799 ± 0.06 mg/kg and 0.1596 ± 0.00 mg/kg, which was greater than the permitted maximum limit of 0.5 mg/kg established by the US Environmental Protection Agency. The concentration of aldrin and profenofos detected was lower than the predetermined maximum allowed limits. Endosulfan concentrations in cocoyam (0.2500 mg/kg) and potato (0.3265 mg/kg) were higher than the limits allowed by the Canadian Department of Industrial Research. The heavy metals detected in these samples include cobalt, nickel, lead, manganese, chromium, arsenic and mercury in at least one of the samples evaluated. There was not much difference between the concentration of cobalt in yam (0.036 mg/kg) and the maximum allowed concentration (0.043 mg/kg). Lead was detected in potatoes and carrots but was below detectable concentration in cassava, yam, cocoyam and water yam. Similarly, cocoyam was found to have a significant mercury content (0.658 mg/kg), but mercury content was below detectable concentrations in cassava, yam and water yam. Significance: Heavy metal pollutants and pesticide residues can impair human health, and their presence in food can cause various illnesses and health issues. It is important to prevent exposure to these contaminants and ensure that food is safe by identifying and monitoring them. Farmers may provide consumers with more assurance that their products are safe by identifying and monitoring pesticide residues and heavy metal contamination in these food crops. Overall, it is crucial to find and monitor pesticide residues and heavy metal contamination in food to safeguard customer confidence, ensure legal compliance and preserve human health.

This research provides a comprehensive literature overview and bibliometric evaluation of multi-agent system (MAS) implementation in energy demand response (DR) to identify gaps. The review encompasses 39 relevant papers from searches in three academic databases, focusing on studies published from 2012 to the middle of 2023. The review includes MAS frameworks, optimization algorithms, communication protocols, market structures and evaluation methodologies. Bibliometric analysis of 587 documents from the search on the Scopus database identified prolific authors, influential articles and collaborative networks within the field. The findings reveal growing research interest in implementing an MAS for DR, focusing on integrating intelligent agents into electricity grids to enable effective load management and enhance grid stability. Additionally, the review outlines potential research directions, including exploring advanced MAS techniques, interoperability challenges, policy implications and the integration of renewable energy sources.

Abstract Providing intravenous (IV) fluids to a patient with signs or symptoms of hypoperfusion is common. However, evaluating the IV fluid ‘dose–response’ curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation (i.e., ‘fluid responsive’). The other patient manifested diminishing arterial response, suggesting depressed SV (i.e., ‘fluid unresponsive’) with evidence of ventricular asynchrony. In this short communication, we describe how a wireless, wearable Doppler ultrasound simultaneously tracks surrogates of cardiac preload and output within a ‘Doppler Starling curve’ framework; implications for IV fluid dosing are discussed.

Summary: Background: The Global Breast Cancer Initiative (GBCI) Framework, launched by the World Health Organisation (WHO) in 2023, emphasises assessing, strengthening, and scaling up services for the early detection and management of breast cancer. This study aims to determine the feasibility of monitoring the status of breast cancer control in the 21 Asian National Cancer Centers Alliance (ANCCA) countries based on the three GBCI Framework key performance indicators (KPIs): stage at diagnosis, time to diagnosis, and treatment completion. Methods: We reviewed published literature on breast cancer control among 21 ANCCA countries from May to July 2023 to establish data availability and compiled the latest descriptive statistics and sources of the indicators using a standardised data collection form. We performed bivariate Pearson's correlation analysis to measure the strength of correlation between stage at diagnosis, mortality and survival rates, and universal health coverage. Findings: Only 12 (57%) ANCCA member countries published national cancer registry reports on breast cancer age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR). Indonesia, Myanmar, and Nepal had provincial data and others relied on WHO's Global Cancer Observatory (GLOBOCAN) estimates. GLOBOCAN data differed from the reported national statistics by 5–10% in Bhutan, Indonesia, Iran, the Republic of Korea, Singapore, and Thailand and >10% in China, India, Malaysia, Mongolia, and Sri Lanka. The proportion of patients diagnosed in stages I and II strongly correlated with the five-year survival rate and with the universal health coverage (UHC) index. Three countries (14%) reported national data with >60% of invasive breast cancer patients diagnosed at stages I and II, and a five-year survival rate of >80%. Over 60% of the ANCCA countries had no published national data on breast cancer staging, the time interval from presentation to diagnosis, and diagnosis to treatment. Five (24%) countries reported data on treatment completion. The definition of delayed diagnosis and treatment completion varied across countries. Interpretation: GBCI's Pillar 1 KPI correlates strongly with five-year survival rate and with the UHC index. Most ANCCA countries lacked national data on cancer staging, timely diagnosis, and treatment completion KPIs. While institutional-level data were available in some countries, they may not represent the nationwide status. Strengthening cancer surveillance is crucial for effective breast cancer control. The GBCI Framework indicators warrant more detailed definitions for standardised data collection. Surrogate indicators which are measurable and manageable in country-specific settings, could be considered for monitoring GBCI indicators. Ensuring UHC and addressing health inequalities are essential to early diagnosis and treatment of breast cancer. Funding: Funding for this research article's processing fee (APC) will be provided by the affiliated institution to support the open-access publication of this work. The funding body is not involved in the study design; collection, management, analysis and interpretation of data; or the decision to submit for publication. The funding body will be informed of any planned publications, and documentation provided.

Abstract Background Medicinal plant contains multiple bioactive compounds with therapeutic potentials. Due to their availability, affordability, and minimal known side effects, they are widely practiced. Identification, quantification, and establishment of their interaction with physiological enzymes help in the standardization of plant-based medicinal extracts. In this study, gas chromatography/flame ionization detector (GC–FID) and high-performance liquid chromatography (HPLC) analysis were used to determine the bioactive components in the ethanol extract of Newbouldia laevis stem bark. The antioxidant activity of the extract was determined. Enzyme inhibitory potency of the flavonoids’ components was investigated against acetylcholinesterase, butyrylcholinesterase, phospholipase A2, α-glucosidase, and α-amylase. Results Analysis of ethanol extract of N. laevis stem-bark revealed alkaloids (0.37%), tannins (1.82 mg/TEq/g), flavonoids (5.85 mg/QEq), steroids (0.11 mg/10 g) and glycosides (0.08 mg/10 g). The HPLC fingerprint of flavonoids showed high concentrations (mg/100 g) of catechin (47.11), apigenin (15.68), luteolin (18.90), kaempferol (41.54), and quercetin (37.64), respectively. In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability of the extract was exhibited at 150 and 200 mg/mL, respectively. At 300 mg, most in vitro antioxidant potentials (lipid peroxidation, metal chelating ability, hydroxyl, nitric oxide, sulfide oxide radicals scavenging abilities) were obtained. The extract showed varying inhibitory abilities (> 50%) on acetylcholinesterase, butyrylcholinesterase, phospholipase A2, α-glucosidase and α-amylase at 300 mg/mL, IC50 of 129.46, 237.10, 169.50, 251.04 and 243.06 mg/mL, respectively, with inhibition constants (Ki) of 3.92, 1.63, 1.11, 2.95 and 2.11. Results showed an affinity for the targeted enzymes with free energies higher than the standard drugs. Conclusion The results revealed that the N. laevis stem bark possesses antioxidant activity and enzyme inhibitory activity on the physiological enzyme that has been implicated in diabetes. In vitro and in silico inhibition of these physiological enzymes by extract suggests that the stem bark can be effective in ameliorating the complications associated with diabetes mellitus.