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The topic of consent within interpersonal relationships is sensitive and complex. A serious game can provide a safe medium for the exploration of the topic of consent. In this paper, we aim to alleviate the challenges of designing a serious game artefact with the implicit goal of exploring the topic of consent. The resulting artefact, “Case By Case”, is a VR-based serious game targeting university students, which uses an allegory-based approach to achieve its goal. The participants play the role of a detective who is tasked with determining if individuals have committed theft, which serves as an allegory for breach of consent. “Case By Case” provides the users an opportunity to reflect on their decisions within the game and apply them to the complex situations of consent such as victim-blaming and bystander awareness. To evaluate the effectiveness of the game in achieving its implicit goal, we ran a user study (n = 24). The results show that “Case By Case” provided a safe environment for the users to reflect on the concept of consent and increase their understanding about the topic further.

Over the past decade, focused ultrasound (FUS) has emerged as a promising therapeutic modality for various medical conditions. However, the exponential growth in the published literature on FUS therapies has made the literature review process increasingly time-consuming, inefficient, and error-prone. Machine learning approaches offer a promising solution to address these challenges. Therefore, the purpose of our study is to (1) explore and compare machine learning techniques for the text classification of scientific abstracts, and (2) integrate these machine learning techniques into the conventional literature review process. A classified dataset of 3588 scientific abstracts related and unrelated to FUS therapies sourced from the PubMed database was used to train various traditional machine learning and deep learning models. The fine-tuned Bio-ClinicalBERT (Bidirectional Encoder Representations from Transformers) model, which we named FusBERT, had comparatively optimal performance metrics with an accuracy of 0.91, a precision of 0.85, a recall of 0.99, and an F1 of 0.91. FusBERT was then successfully integrated into the literature review process. Ultimately, the integration of this model into the literature review pipeline will reduce the number of irrelevant manuscripts that the clinical team must screen, facilitating efficient access to emerging findings in the field.

Zoo enclosure design, and housing and husbandry protocols, will always be a compromise between what a species has evolved to do and what is possible to offer in a human-created environment. For some species, behaviours that are commonly performed in the wild may be constrained by husbandry practices that are used for ease or aesthetics or are accepted conventions. As zoos place more emphasis on positive animal welfare states, zoo enclosures should be scrutinised to check that what is provided, in terms of useful space, appropriate replication of habitat features, and maximal potential for natural behaviour performance, is relevant to the species and individuals being housed. For some species, zoos need to grapple with tough questions where the answer may not seem immediately obvious to ensure they are continuously improving standards of care, opportunities for the performance of species-typical behaviours, and advancing the attainment of positive welfare states. Determining the importance of flight, for example, and what this behaviour adds to the quality of life of a zoo-housed bird, is an important question that needs addressing to truly advance aviculture and how we determine bird welfare. This paper provides questions that should be answered and poses measures of what flight means to a bird, to provide evidence for the development and evolution of zoo bird housing. If we can devise some way of asking the animals in our care what they need, we can more firmly support decisions made that surround enclosure design, and housing decisions. Ultimately, this means gathering evidence on whether birds like to fly (e.g., from birds in training or demonstration activities) by applying mixed methods approaches of behavioural analysis, data on wild ecology, qualitative behavioural assessment, and cognitive bias testing to develop a robust suite of tools to address avian welfare considerations. Avian welfare scientists should attempt to define what meaningful flight is (i.e., flight that truly suggests a bird is flying) in order to support guidelines on aviary dimensions, space allowance, and welfare outputs from birds in both flighted and flight-restricted populations, and to determine what is most appropriate for an individual species. Changing the term “best practice” husbandry guidelines to “better practice” husbandry guidelines would instil the importance of regular review and reassessment of housing and management suitability for a species to ensure such care regimes remain appropriate. With an increasingly welfare-savvy public visiting zoos, it is essential that we seek more evidence to support and justify how birds are kept and ultimately use such evidence to enact changes to practices that are shown to infringe on avian welfare.

An experiment was conducted to determine the apparent metabolizable energy (AME) and nitrogen-corrected AME (AMEn) of defatted black soldier fly larvae meal (BSM), full-fat dry larvae meal (BSL), and larvae fat (LF) for broiler chickens. The BSM, BSL, and LF contained on a g/kg basis, respectively, crude protein, 459, 399, 0; crude fat, 171, 240, 923; dry matter, 963, 940, 997; neutral detergent fiber, 210, 333, 0; acid detergent fibers, 95, 93, 0; and gross energy (MJ/kg), 22.04, 22.78, 38.16. An AME bioassay was performed wherein broilers were fed four experimental diets (a maize–wheat–soy basal diet and three test diets containing 100 g/kg BSM, BSL, or LF, respectively). The AME of BSM, BSL, and LF was calculated based on the differences between the AME values of basal and test diets (substitution method). The AME and AMEn for BSM, BSL, and LF were determined to be 18.20 and 17.40; 17.60 and 16.50; and 36.50 and 35.60 MJ/kg DM, respectively. There were no significant differences (p > 0.05) between nutrient retention coefficients of dry matter, N, and fat. The results showed that the examined products from black soldier fly larvae are a good source of available energy and crude protein (BSL and BSM) and can be incorporated in broiler diets as alternative protein and energy sources.

This study explored conceptualizations of disability pertaining to peer relationships versus romantic relationships, as well as type of physical disability, using story-completion methods. Seventy-four graduate and undergraduate students from a Canadian university completed one of two versions of a story stem featuring an individual with a physical disability who was either a classmate or a potential romantic partner. Through the process of thematic analysis, three themes were generated as patterns across stories: (1) assumptions about disability present from first glance; (2) uncertainty in navigating negative assumptions of disability; and (3) from discomfort to acceptance of disability through social connection. Storylines differed depending on the type of relationship (i.e., peer or romantic) in both story length and outcome of the relationship. Findings suggest the usefulness of the relatively infrequently used method of story completion for assessing students’ narratives and discussion of meanings surrounding differing relationships with persons with a disability. This study further develops our understanding of cultural norms of disability, as well as highlights the importance of disability knowledge and interaction between persons with and without a disability, to foster positive change in representations and perceptions of disability.

Unusual or extraordinary circumstances can cause change to normal husbandry regimes and daily care of managed animals. Increased biosecurity due to disease risk, for example, results in animals experiencing restrictions. Outbreaks of Highly Pathogenic Avian Influenza (HPAI) have caused zoos to remove birds from their regular exhibits and manage them indoors or in covered enclosures to reduce the likelihood of an HPAI outbreak on site. To date, there has been little research on the impacts of such husbandry change on bird behaviour and welfare. This paper examines the effect of an HPAI-induced enforced housing order (HO) on the behaviour and physical condition of a flock of Chilean flamingos in a UK zoo. Using ZooMonitor to record flock-wide behaviour patterns and scoring plumage condition, we collected data on flamingos during a housing order, immediately after lifting of the HO, and after a period of acclimation to their regular routine. Results showed that flamingos were very inactive under a HO and after release, that abnormal, redirected foraging actions occurred during the HO and after release, and that flamingos were more alert under the HO. An increase in records of good plumage condition correlated with social behaviour, inactivity, higher temperatures, and rain. This research highlights the multifactorial influences on zoo animal behaviour and shows why information on the animals, their inputs, the behavioural outputs they present, and their physical attributes should all be gathered and evaluated together to best understand the influences of husbandry and management changes on behaviour and welfare.

Scars following burns can often prove complex to manage, particularly when crossing joints or special areas such as the head and neck, due to contractures. This case report discusses the individualised care and rehabilitation provided to a burn patient with a learning disability. The patient suffered both full and partial thickness burns equating to a total body surface area (%TBSA) of 7% of the face, neck, and anterior chest via the self-ignition of clothing. Acute treatment was provided at a regional burn unit followed by further in-patient care and rehabilitation at our burn facility. A motion rehabilitation instrument was employed to manage potential orofacial contracture; however, due to the patient’s impaired social functioning, this device was found to be unsuitable. Subsequently, a bespoke mouth-opening device replicating an ice lolly was fabricated utilising computer-aided design (CAD), enhancing the patient’s understanding along with encouraging independence. Microstomia was a risk in this case; however, this was prevented via the discussed regime, and successful patient rehabilitation was achieved.

Understanding animal behaviour can feel like deciphering a foreign language. In 1963, pioneering ethologist Nikolaas Tinbergen offered a key: four fundamental questions to dissect behaviour’s complexities and reduce interpretive bias. These “Four Questions” fall into two categories: Proximate (how?) and Ultimate (why?). The Proximate questions ask how the behaviour is triggered (Causation) and develops over time (Ontogeny). The Ultimate questions delve into its evolutionary history (Phylogeny) and purpose (Function). Traditionally used in behavioural ecology, Tinbergen’s framework finds new relevance in fields like sentience, welfare, conservation, and animal management. This paper illustrates how further integration of these Questions into applied research can improve outcomes. For example, captive animals can receive enrichment seemingly “unnatural” in origin and form. Does such enrichment trigger species-typical behaviours, fulfilling the same adaptive function as natural stimuli would? Understanding a species’ natural behaviour patterns and how the performance of such activities promotes positive welfare states is key to biologically relevant population management. Tinbergen’s Four Questions can help scientists to decipher the relevance of natural behaviour, and how a species’ responses to their environment indicate what individuals need and want at a specific time or place. By applying the Four Questions, we can answer this question and, in turn, refine husbandry practices and conserve behavioural diversity in managed populations. Sixty years after their conception, Tinbergen’s Four Questions remain a powerful tool for behavioural research. By embracing different biological disciplines within a unified framework, applied animal zoo science will continue to advance and provide credible evidence-based outputs.

The study aimed to quantify carcass fat and protein retention, and the efficiency of carcass energy utilization (Kre) resulting from feeding broiler chickens diets containing wheat, maize or mixtures of both as the major cereal ingredient. The apparent metabolizable energy (AME) of the four cereal samples was determined in adult cockerels. There was a linear (p < 0.001) increase in AME with increasing amounts of maize within the four cereal mixtures, with analyses indicating that the AME of maize was 1.4 MJ/kg greater than that of wheat. A second bioassay with growing chickens was used to determine Kre in each cereal, measured as carcass fat and protein from 7 to 21d age. Increasing proportions of maize resulted in linear increases in carcass fat and energy retained from fat (p < 0.001). However, the carcass protein and energy retained from protein did not follow the same pattern as fat (p = 0.121), but rather decreased numerically (L = 0.032). The Kre tended (p = 0.060) to increase with greater proportion of maize in a linear fashion (L = 0.009). Although AME values of cereals were confirmed to be additive, this could not be confirmed for Kre. This data can be used for optimizing energy utilization models for growing broilers.

A variety of hollow microneedle (HMN) designs has emerged for minimally invasive therapies and monitoring systems. In this study, a design change limiting the indentation depth of the (3D) printed custom microneedle assembly (circular array of five conical frusta with and without a stopper, aspect ratio = 1.875) fabricated using stereolithography has been experimentally validated and modeled in silico. The micro-indentation profiles generated in confined compression on 1 mm ± 0.073 mm alginate films enabled the generation of a Prony series, where displacement ranged from 100 to 250 µm. These constants were used as intrinsic properties simulating experimental ramp/release profiles. Puncture occurred on two distinct hydrogel formulations at the design depth of 150 µm and indentation rate of 0.1 mm/s characterized by a peak force of 3.5 N (H = 31 kPa) and 8.3 N (H = 36.5 kPa), respectively. Experimental and theoretical alignments for peak force trends were obtained when the printing resolution was simulated. Higher puncture force and uniformity inferred by the stopper was confirmed via microscopy and profilometry. Meanwhile, poroviscoelasticity characterization is required to distinguish mass loss vs. redistribution post-indentation through pycnometry. Results from this paper highlight the feasibility of insertion-depth control within the epidermis thickness for the first time in solid HMN literature.

The Antimalware Scan Interface (AMSI) plays a crucial role in detecting malware within Windows operating systems. This paper presents ScriptBlock Smuggling, a novel evasion and log spoofing technique exploiting PowerShell and .NET environments to circumvent the AMSI. By focusing on the manipulation of ScriptBlocks within the Abstract Syntax Tree (AST), this method creates dual AST representations, one for compiler execution and another for antivirus and log analysis, enabling the evasion of AMSI detection and challenging traditional memory patching bypass methods. This research provides a detailed analysis of PowerShell’s ScriptBlock creation and its inherent security features and pinpoints critical limitations in the AMSI’s capabilities to scrutinize ScriptBlocks and the implications of log spoofing as part of this evasion method. The findings highlight potential avenues for attackers to exploit these vulnerabilities, suggesting the possibility of a new class of AMSI bypasses and their use for log spoofing. In response, this paper proposes a synchronization strategy for ASTs, intended to unify the compilation and malware scanning processes to reduce the threat surfaces in PowerShell and .NET environments.

Concentrations of specific secondary metabolites can be higher in organically grown crops. This may be linked to organic nitrogen (N) nutrition that provides a gradual supply of N to crops over the growing season. This study examined whether organic N nutrition influenced the concentration of glucosinolates in broccoli crops. Nitrogen release patterns were determined from three synthetic (Rustica, 12% N; calcium nitrate, 15.5% N; urea, 46% N) and two organic fertilizers in an incubation experiment. Broccoli seedlings were then grown in two N dose response pot trials with different N source or application timing treatments to investigate growth and glucosinolate responses. Synthetic fertilizers released 84 to 89% of total N after 28 days, while chicken manure pellets and composted cow manure had only released 52% and 13% of total N, respectively, after 91 days. Broccoli yield and N content were generally higher in synthetic fertilizer treatments. Glucosinolate concentrations were generally higher in the synthetic fertilizer treatments, and only sinigrin and glucoiberin concentrations in the 800 kg ha−1 N application rate of organic fertilizer matched those in the corresponding synthetic fertilizer treatment. Broccoli head weight was reduced when N was applied fortnightly compared to basal and weekly N applications, but glucosinolate concentrations were not significantly different. Overall, there was no evidence that organic (chicken manure) N nutrition, or the rate of N supply to broccoli plants, affect glucosinolate concentrations.

Introduction: As a result of the protective measures taken to contain the COVID-19 pandemic, German students experienced home study in the spring of 2020. The present study addressed the relation between coping with the home study situation and personality. Methods: The interrelations of the Big Five factors with students’ well-being, study satisfaction and academic performance were examined in 287 German online participants. Results: The results showed significant positive correlations of positive affect and conscientiousness, as well as of better academic performance and academic satisfaction. For extraversion, a positive supporting effect on the affective level emerged, although previous studies suggested negative influences of extraversion on affect in home study settings in other phases of the pandemic. Furthermore, in contrast, neuroticism showed a negative relation to study satisfaction and mood in home study. Conclusion: In summary, the personalities of students should be considered in order to provide protective measures and avoid negative coping effects.

This study presents an in-depth analysis of 69 case studies focusing on the energy retrofit of historic buildings, uncovering challenges, best practices, and lessons learned to balance energy efficiency improvements with heritage preservation. The findings highlight several challenges encountered during renovations, such as complex heritage evaluations, restrictions on alterations, coordination issues with authorities, technical limitations, higher investment costs, and knowledge gaps. On the other hand, identifying factors promoting renovation, including demonstrating energy savings while respecting heritage, early collaboration between planners and authorities, and quantifying investments, could incentivize owners and authorities. The limitations of a still-limited sample size, occasional incomplete data, and potential sample bias call for cautious interpretation of the presented analysis. Despite these, the study provides valuable insights into successful projects, emphasizing the need for scalability, knowledge transfer from innovative policies, and targeted policy-making for successful replication. The study concludes with a call for further development of the HiBERatlas (Historic Building Energy Retrofit atlas), an extensive resource for historic building renovation, expanding its database, collaborating with agencies, and tailoring guidance for stakeholders to foster energy retrofits in heritage buildings.

Cancer stands out as a major global public health concern and a significant impediment to increasing life expectancy worldwide. Natural bioactives derived from plants are renowned for their efficacy in treating various types of cancer. Andrographis paniculata (Burm.f.) is a well-known plant traditionally employed in diverse medical systems across the globe. The 2-AEH2P monophosphoester, a molecule intricately involved in phospholipid turnover, demonstrates antiproliferative effects across a broad spectrum of cancer types. This study aims to assess the antitumor, antiproliferative, and pharmacological effects of andrographolide at different concentrations, both individually and in conjunction with 2-aminoethyl dihydrogen phosphate. The cytotoxicity of the treatments was evaluated using the colorimetric MTT method, cell cycle phases, mitochondrial electrical potential, and markers expression via flow cytometry, while the pharmacological effects were assessed using SynergyFinder software 3.0. Treatments with A. paniculata, isolated at concentrations of 10%, 30%, and 50% of andrographolide, induced cell death in tumor cells, resulting in a reduction in mitochondrial electrical potential and alterations in cell cycle phases, particularly a decrease in the population of MDA MB-231 cells in the G0/G1 phase. The combination treatments exhibited significant cytotoxicity toward tumor cells, with minimal toxicity observed in normal fibroblast cells FN1. This led to a reduction in mitochondrial electrical potential and cell cycle arrest in the S phase for MDA MB-231 cells. Across all concentrations, the combined treatments demonstrated a synergistic pharmacological effect, underscoring the efficacy of the association. There was a change in the markers involved in cell death, such as p53, caspase 3, Bcl-2, and cytochrome c, suggesting the induction of regulated cell death. Markers associated with progression and proliferation, such as cyclin D1 and p21, corroborate the findings for cytotoxicity and cell cycle arrest.

Breastfeeding is internationally recognized as the optimal form of infant nutrition. The Baby-Friendly Initiative (BFI) is an evidence-informed program that leads to improved breastfeeding outcomes. Despite the benefits of breastfeeding, Nova Scotia has one of the lowest breastfeeding rates in Canada. Additionally, only two birthing hospitals in the province have BFI designation. We aim to address this gap using a sequential qualitative descriptive design across three phases. In Phase 1, we will identify barriers and facilitators to BFI implementation through individual, semi-structured interviews with 40 health care professionals and 20 parents. An analysis of relevant policy and practice documents will complement these data. In Phase 2, we will develop implementation interventions aimed at addressing the barriers and facilitators identified in Phase 1. An advisory committee of 10–12 administrative, clinical, and parent partners will review these interventions. In Phase 3, the interventions will be reviewed by a panel of 10 experts in BFI implementation through an online survey. Feedback on the revised implementation interventions will then be sought from 20 health system and parent partners through interviews. This work will use implementation science methods to support integrated and sustained implementation of the BFI across hospital/community and rural/urban settings in Nova Scotia. This study was not registered.

An overview of internationally published literature on what works for co-production in youth mental health services is missing, despite a practice and policy context strongly recommending this approach. The proposed rapid realist review aims to develop a theory about how and why co-production methods in youth mental health services work (or do not work), for whom, in which contexts, and through what mechanisms. Relevant evidence will be synthesised to develop context–mechanism–outcome (CMO) configurations that can inform policy and practice. Stakeholders will be iteratively involved in the development of these theories (CMO configurations) by engaging an expert panel and youth advisory group. The review results will be reported according to the RAMESES guidelines and are intended to be published in an academic journal. Additionally, a plain English summary will be produced with the support of the youth advisory group.

Objectives: Parkinson’s disease psychosis (PDP) is a prevalent non-motor symptom associated with Parkinson’s disease. The treatment options for PDP are limited, and its pharmacological management remains ambiguous. This study aimed to evaluate the existing evidence in relation to clinical practice. Methods: This multi-methods study consisted of a systematic review of reviews, adhering to the PRISMA guidelines. The review was registered with PROSPERO. Following data extraction and assessment using the AMSTAR 2 tool, a narrative synthesis was performed. In the second phase of the study, a questionnaire was developed, validated, piloted, and distributed to the heads of specialized PD clinics in Germany and Austria. Results: The search resulted in the inclusion of eleven reviews. The quality of eight of these reviews was rated as high (n = 7) or moderate (n = 1). The reviews indicated that clozapine and pimavanserin demonstrated the highest efficacy and tolerability. Other antipsychotic medications either failed to alleviate PDP symptoms or resulted in distinct motor complications. The survey findings also favored clozapine for its efficacy in managing PDP and improving quality of life, although quetiapine was regarded as effective and pimavanserin was not available. Clinicians reported initiating antipsychotic treatment at various stages of PDP, with a tendency to reduce the dosage or discontinue D2 agonists or anticholinergics. Conclusions: The reviewed literature and the survey results consistently favored clozapine for its efficacy and tolerability in treating PDP. It may be considered the first-line treatment, with pimavanserin as an alternative option.

Green soybean (Glycine max L.) seed contains a high procyanidin content and high antioxidant activity. Moreover, ultrasound-assisted extraction (UAE) has proved to be advantageous in providing high extraction efficiency. Hence, this study aimed to extract procyanidins from green soybean seeds (GSSs) using UAE. This study also evaluated the inhibitory activities of tyrosinase and the cytotoxic effects of crude procyanidin extract. The extract exhibited maximum levels of bioactive components and antioxidant capacity when subjected to a temperature of 15 °C and an extraction time of 20 min. The crude procyanidin extract at a concentration of 10 mg/mL inhibited the tyrosinase enzyme by more than 60%, and the half-maximal inhibitory concentration (IC50) value obtained for the extract was 6.85 ± 0.81 mg/mL. This result was much greater than the IC50 value obtained for kojic acid (0.089 ± 0.08 mg/mL), which was used as a positive control. For the cytotoxicity assessment, the results indicated that the crude procyanidin extract showed no cytotoxicity and actually stimulated the growth of human skin fibroblast cells. More than 80% of the bioactive compounds (total phenolic content (TPC), total flavonoid content (TFC), procyanidin content (PC)) and antioxidant activities (DPPH and FRAP) of the crude extract powder were retained at 38.68 ± 0.01 mg GAE/g, 16.07 ± 0.01 mg CAE/g, 9.24 ± 0.01 mg PC/g, 359.8 ± 0.72 μM Trolox eq/g, and 1640 ± 2.86 μM Trolox eq/g, respectively, after 12 weeks of storage at 25 °C. The crude procyanidin extract powder was then included in a facial serum formulation and tested for pH value and physical evaluation. The stability of the crude procyanidin extract facial serum was shown to be greater for bioactive compounds and antioxidant activity when stored at a temperature of 4 °C than when stored at a temperature of 25 °C. These results suggest that the GSS extracts obtained via ultrasonication show promise for use in cosmeceutical formulations for whitening skincare products.

Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and its potential use as a prognostic biomarker. We performed in situ hybridization for miRNA-211-5p on 109 FFPE melanoma samples from 76 patients, including 31 paired primary tumor/metastasis samples. For validation, we performed in silico analyses of TCGA skin cutaneous melanoma (SKCM) cohort. High miR-211-5p expression was more frequent in primary tumors (70.8%) compared to metastases (39.3%). In metastases, it was associated with a significantly worse overall survival. Data from TCGA SKCM cohort confirmed that high miR-211-5p expression in melanoma metastases, but not primary tumors, is associated with worse overall survival. MiR-211-5p expression in metastases is associated with a shorter survival, emphasizing the potential of miR-211-5p as a risk predictor for a less favorable clinical outcome in metastatic disease. In situ hybridization could be implemented in a routine laboratory workflow and can be performed on diagnostic tissue.

Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1–3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.

A simplified axisymmetric model of a transfemoral osseointegration implant was used to investigate the influence of the contact condition at the bone–implant interface on the vibrational response. The experimental setup allowed the degree of implant tightness to be controlled using a circumferential compression device affixed to the bone. Diametrically placed sensors allowed torsional modes to be distinguished from flexural modes. The results showed that the structural resonant frequencies did not shift significantly with tightness levels. The first torsional mode of vibration was found to be particularly sensitive to interface loosening. Harmonics in the vibrational response became prominent when the amplitude of the applied torque increased beyond a critical level. The torque level at which the third harmonic begins to rise correlated with implant criticality, suggesting a potential strategy for early detection of implant loosening based on monitoring the amplitude of the third harmonic of the torsional mode.

Pakistan is one of those nations that is suffering from the complications of higher fertility and lower levels of education and struggling to improve these demographic factors. In any country, education is considered the reason to control fertility levels. To shed some light on the importance of this fact, education attainment and total children ever born have been considered by taking micro-level data from the Pakistan Demographic Health Survey (PDHS) of 2017–2018 to examine the relationship of education with fertility for women. Due to the nature of the response variable, children ever born, which is a count variable, Poisson regression was used. The results provide evidence that women with secondary and higher education have a negative and significant association with fertility and thus support the hypothesis that educated women have lower fertility. Women with secondary and higher education have fewer children compared to women with no education, while female education at the primary level did not significantly affect fertility in the research. Furthermore, the age of first cohabitation, age at first birth, and wealth index were revealed to be significant determinants of fertility. It interprets that the increase in education is related to greater opportunities and facilitates the participation of women in other activities of the economy.

Thailand is a prominent global producer of mangoes, providing a wide range of mango cultivars and dealing with the challenge of managing biomass. Thus, biorefining mango peel to extract valuable components has the potential to reduce organic waste and create a new revenue source for the mango processing sector. This study aims to examine the physiology, physiochemical, and chemical characteristics in peel of nine Thai mango cultivars, along with the relationship between their characteristics. The Thai mango cultivars Mahachanok, Chok anan, and Rad exhibited a yellow appearance, while the other six cultivars appeared yellow-green. However, the firmness of the fruit was directly correlated with the firmness of the pulp. A proximate composition study revealed that the predominant constituent of mango peel was carbohydrates, comprising up to 75% of its composition. This was followed by fibre, which accounted for up to 13%. The Nga mango had the highest levels of total phenolic content (220 mgGAE/g) and total flavonoid content (5.5 mgCE/g). The primary phenolic acids identified in Thai mango peel were epicatechin, caffeic acid, catechin, and gallic acid. The Mahachanok cultivar exhibited the highest antioxidant activity, as determined by the ABTS and DPPH assays, with values of 85.67% and 85.78%, respectively. This study demonstrated the connections between the physiochemical characteristics of mangoes and their chemical compositions in different cultivars, indicating the possibility of choosing particular cultivars for extracting targeted bioactive compounds. The multivariate analyses revealed that there was no correlation between the physiochemical and chemical profiles of mangoes. This study highlights the significance of mango peel as a valuable by-product that has significant environmental and economic ramifications for the mango processing industry.

Recently, onychectomy, the “declaw” surgery in which all or part of the distal phalanges are removed, has been shown to have significant effects on the forearm muscles of felids. While this surgery should clearly affect the limb muscles (especially those that insert on the removed or modified bone), these effects have not been studied beyond felids or in the hindlimb. To that end, we herein evaluated the muscle architecture of a kinkajou (Potos flavus) that was declawed on all four of its limbs and compared its anatomy to that of intact specimens and the felid findings. As expected, some of the declawed kinkajou’s muscles were substantially different from those of the intact specimens, and as was seen in felids, its digital muscles appear to have been weaker. However, unlike in the felids, the declawed kinkajou had relatively larger forearm muscles. Also, contrary to expectation, the leg muscles of the declawed kinkajou were not substantially different, perhaps reflecting important differences in limb use. Future analyses should examine this anatomy in other declawed kinkajou specimens and also look at the effects of this surgery in other taxa, for instance, non-arboreal relatives of the kinkajou as well as other arboreal taxa.

Background: Assisted partner services (APS) is a recommended public health approach to promote HIV testing for sexual partners of individuals diagnosed with HIV. We evaluated the cost and cost-effectiveness of integrating oral HIV self-testing (HIVST) into existing APS programs. Methods: Within the APS-HIVST study conducted in western Kenya (2021–2022), we conducted micro-costing, time-and-motion, and provider surveys to determine incremental HIVST distribution cost (2022 USD). Using a decision tree model, we estimated the incremental cost per new diagnosis (ICND) for HIVST incorporated into APS, compared to APS with provider-delivered testing only. Scenario, parameter and probabilistic sensitivity analyses were conducted to explore influential assumptions. Results: The cost per HIVST distributed within APS was USD 8.97, largest component costs were testing supplies (38%) and personnel (30%). Under conditions of a facility-based testing uptake of Conclusions: Implementers and policy makers should ensure that HIVST programs are implemented under conditions that guarantee efficiency by focusing on facilities with low uptake for provider-delivered facility-based testing, while deliberately targeting HIVST utilization among the few likely to benefit from remote testing. Additional measures should focus on minimizing costs relating to personnel and testing supplies.

This study investigated the germination response to temperature of seeds of nine Arabidopsis thaliana ecotypes. They are characterized by a similar temperature dependency of seed germination, and 10 °C and 29 °C were found to be suboptimal low and high temperatures for all nine ecotypes, even though they originated from regions with diverse climates. We tested the potential of four PGPR strains from the genera Pseudomonas and Bacillus to stimulate seed germination in the two ecotypes under these suboptimal conditions. Biopriming of seeds with only the biofilm-forming strain Pseudomonas putida KT2440 significantly increased the germination of Cape Verde Islands (Cvi-0) seeds at 10 °C. However, biopriming did not significantly improve the germination of seeds of the widely utilized ecotype Columbia 0 (Col-0) at any of the two tested temperatures. To functionally investigate the role of KT2440’s biofilm formation in the stimulation of seed germination, we used mutants with compromised biofilm-forming abilities. These bacterial mutants had a reduced ability to stimulate the germination of Cvi-0 seeds compared to wild-type KT2440, highlighting the importance of biofilm formation in promoting germination. These findings highlight the potential of PGPR-based biopriming for enhancing seed germination at low temperatures.

The entire classical cosmological history between two extreme de Sitter vacuum solutions is discussed based on Einstein’s equations and non-equilibrium thermodynamics. The initial non-singular de Sitter state is characterised by a very high energy scale, which is equal or smaller than the reduced Planck mass. It is structurally unstable, and all of the continuous created matter, energy, and entropy of the material component comes from the irreversible flow powered by the primeval vacuum energy density. The analytical expression describing the running vacuum is obtained from the thermal approach. It opens a new perspective to solve the old puzzles and current observational challenges plaguing the cosmic concordance model driven by a rigid vacuum. Such a scenario is also modelled through a non-canonical scalar field. It is demonstrated that the resulting scalar field model is shown to be a step-by-step a faithful analytical representation of the thermal running vacuum cosmology.

Background: In many countries, an increase in influenza and pneumococcal vaccination rates was observed during the COVID-19 pandemic. We examined how attitude, risk perception and knowledge towards influenza and pneumococcal vaccines of at-risk patients developed when the COVID-19 pandemic subsided and if COVID-19 vaccination attitude (VA) was still associated with the attitudes towards the two other vaccines. Methods: We used longitudinal data from two surveys conducted in Germany in 2021 and 2023 among persons with chronic diseases. We assessed VA, risk perception, vaccination knowledge and further psychological determinants of vaccine acceptance. Structural equation modelling using full information maximum likelihood was used to estimate multivariate regressions with planned missing data. Results: Among 543 respondents, the influenza and pneumococcal vaccination rates remained relatively stable between 2021 and 2023. VA also remained unchanged at a moderately positive level, while COVID-19 VA decreased. A constantly positive association between COVID-19 VA and influenza as well as pneumococcal VA was found, independent from a general VA. The perceived danger of influenza increased between 2021 and 2023 and was among the strongest predictors of influenza VA. Conclusions: Also at the subsiding pandemic, COVID-19 VA was constantly associated with the influenza and pneumococcal VA. It seems sensible to take these aspects into account when designing future vaccination campaigns for at-risk patients. Trial registration: DRKS00024561. Registered 9 March 2021.

Depression affects several aspects of life, including socioeconomic status, relationships, behavior, emotions, and overall health. The etiology of depression is complex and influenced by various factors, with obesity emerging as a significant contributor. This narrative review aims to investigate the factors associated with the development of depression, with a particular focus on the role of obesity. The literature search was conducted on PubMed, Embase, and PsycINFO from May to July 2024. The review highlights the impact of environmental and socioeconomic conditions; lifestyle choices, including physical activity and dietary habits; stress; traumatic experiences; neurotransmitter imbalances; medical and psychological conditions; hormone fluctuations; and epigenetic factors on depression. A key emphasis is placed on the inflammatory processes linked to obesity, which may drive the bidirectional relationship between obesity and depression. The findings suggest that obesity is associated with an increased risk of depression, potentially due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management. Understanding these interconnected factors is important for developing targeted interventions to address both obesity and depression, leading to improved quality of life for those affected.

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely driven by poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (p < 0.001. VS was 85.1% on a DTG-based regimen versus 80.0% on efavirenz/nevirapine and 65.6% on lopinavir/ritonavir or atazanavir/ritonavir. VS was higher in females versus males (85.8% versus 78.2%, p < 0.001). The VS rate remained stable around 85% at 12 and 24 months but dropped to about 80% at 36 months after ART initiation, p < 0.009. Independent predictors of non-VS were younger age, longer ART duration (>36 months), backbone drug (non-TDF/3TC) and anchor drug (non-DTG based). In this Cameroonian paediatric population with varying levels of transition to DTG, overall VS remains below the 95% targets. Predictors of non-VS are younger age, non-TDF/3TC- and non-DTG-based regimens. Thus, efforts toward eliminating paediatric AIDS should prioritise the transition to a DTG-based regimen in this new ART era.

Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body’s immune system to specifically target and destroy malignant cells. This review explores the scope and impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapy, and therapeutic vaccines. Monoclonal antibodies, such as Rituximab and Trastuzumab, have revolutionized treatment paradigms for lymphoma and breast cancer by offering targeted interventions that reduce off-target effects. CAR-T cell therapy presents a potentially curative option for refractory hematologic malignancies, although challenges remain in effectively treating solid tumors. Checkpoint inhibitors have redefined the management of cancers like melanoma and lung cancer; however, managing immune-related adverse events and ensuring durable responses are critical areas of focus. Cytokine therapy continues to play a vital role in modulating the immune response, with advancements in cytokine engineering improving specificity and reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based vaccines, represent a frontier in personalized cancer treatment, aiming to generate robust, long-lasting immune responses against tumor-specific antigens. Despite these advancements, the field faces significant challenges, including immune resistance, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Future research should address these obstacles through emerging technologies, such as next-generation antibodies, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, and AI-driven drug discovery. By integrating these novel approaches, cancer immunotherapy holds the promise of offering more durable, less toxic, and highly personalized treatment options, ultimately improving patient outcomes and survival rates.

Sirtuin-2 (Sirt2), an NAD+-dependent lysine deacylase enzyme, has previously been implicated as a regulator of glucose metabolism, but the specific mechanisms remain poorly defined. Here, we observed that Sirt2−/− males, but not females, have decreased body fat, moderate hypoglycemia upon fasting, and perturbed glucose handling during exercise compared to wild type controls. Conversion of injected lactate, pyruvate, and glycerol boluses into glucose via gluconeogenesis was impaired, but only in males. Primary Sirt2−/− male hepatocytes exhibited reduced glycolysis and reduced mitochondrial respiration. RNAseq and proteomics were used to interrogate the mechanisms behind this liver phenotype. Loss of Sirt2 did not lead to transcriptional dysregulation, as very few genes were altered in the transcriptome. In keeping with this, there were also negligible changes to protein abundance. Site-specific quantification of the hepatic acetylome, however, showed that 13% of all detected acetylated peptides were significantly increased in Sirt2−/− male liver versus wild type, representing putative Sirt2 target sites. Strikingly, none of these putative target sites were hyperacetylated in Sirt2−/− female liver. The target sites in the male liver were distributed across mitochondria (44%), cytoplasm (32%), nucleus (8%), and other compartments (16%). Despite the high number of putative mitochondrial Sirt2 targets, Sirt2 antigen was not detected in purified wild type liver mitochondria, suggesting that Sirt2’s regulation of mitochondrial function occurs from outside the organelle. We conclude that Sirt2 regulates hepatic protein acetylation and metabolism in a sex-specific manner.

Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10–50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable. A 5-year retrospective review was conducted at the American University of Beirut Medical Center to identify children who underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Data on patient demographics, neurodevelopment, seizures, and treatments were collected. Forty-nine children underwent NGS with an overall diagnostic rate of 68.9% (27/38 for WES, and 4/7 for WGS). Most children (42) had neurodevelopmental delays with (18) or without (24) refractory epilepsy, and only three had refractory epilepsy without delays. The diagnostic yield was 77.8% in consanguineous families (18), and 61.5% in non-consanguineous families (26); consanguinity information was not available for one family. Genetic test results led to anti-seizure medication optimization or dietary therapies in six children, with subsequent improvements in seizure control and neurodevelopmental trajectories. Not only is the diagnostic rate of NGS high in children with unexplained epilepsy and neurodevelopmental delays, but also genetic testing in this population may often lead to potentially life-altering interventions.

The upcoming Euro 7 regulation for Heavy-Duty (HD) vehicles is calling for a further tightening of the Solid Particle Number (SPN) emissions by means of both lowering the applicable limits and shifting the lowest detectable size from 23 nm (SPN23) to 10 nm (SPN10). A late-technology diesel HD truck was tested on a chassis dynamometer in order to assess the necessary particle filtration requirements for a continuously regenerating system. The study showed that passive regeneration under real-world operating conditions can lead to a significant release of SPN10 particles from the current technology Diesel Particulate Filter (DPF) when soot-loaded, even exceeding the currently applicable emission limits. The actual emissions during passive regeneration and following the clean-up of the DPF exceeded the proposed Euro 7 limits by more than an order of magnitude. A prototype DPF, exhibiting a 99% filtration efficiency when clean, was shown to effectively control SPN10 emissions under both operating conditions. The shift to SPN10 also necessitates control of nanoparticles forming inside the Selective Catalytic Reduction (SCR) system, which for the tested truck exceeded the proposed (hot) limit by up to 56%. A dedicated particle filter specifically designed to capture these particles was also evaluated, showing a better than 60% efficiency. The key message of this study is that SPN emissions can be kept at low levels under all conditions.

The COVID-19 pandemic instigated a paradigm shift in healthcare delivery with a rapid adoption of technology-enabled models of care, particularly within the general practice primary care setting. The emergence of the Metaverse and its associated technology mediums, specifically extended reality (XR) technology, presents a promising opportunity for further industry transformation. Therefore, the objective of this study was to explore the current application and utilisation of XR technologies within the general practice primary care setting to establish a baseline for tracking its evolution and integration. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was conducted and registered with the international database of prospectively registered systematic reviews as PROSPERO-CRD42022339905. Eleven articles met the inclusion criteria and were quality appraised and included for review. All databases searched, inclusive of search terms, are supplied to enhance the transparency and reproducibility of the findings. All study interventions used virtual reality technology exclusively. The application of virtual reality within the primary care setting was grouped under three domains: (1) childhood vaccinations, (2) mental health, and (3) health promotion. There is immense potential for the future application of XR technologies within the general practice primary care setting. As technology evolves, healthcare practitioners, XR technology specialists, and researchers should collaborate to harness the full potential of implementing XR mediums.

From a public health standpoint, a stringent visitation policy was necessary during the COVID-19 pandemic, but it had unforeseen communicative and emotional health consequences for family members. This study explored family members’ experiences regarding implementing a restricted visitation policy when a patient was admitted with COVID-19 at public hospitals in the Vhembe district. Researchers used an exploratory, descriptive, and contextual qualitative technique. Twelve family members made up the population. Unstructured telephone interviews were used to obtain the data, and open coding was used to analyse data. Ethics were consistently followed. Before taking part, participants provided verbal informed consent, acknowledging that they could withdraw from the study if necessary. Three themes emerged: inadequate measures for temporary communication channels and techniques, the mental health effects of COVID-19 admission, and poor/lack of standardised visitation policy during the COVID 19-pandemic. There was a need to balance safety from contracting COVID-19 infection and promoting family-centred care. Virtual visits through telecommunication solutions could reduce fear and anxiety as the family could be updated on the progress of the hospitalised relative. Alternatively, hospital managers must allocate a dedicated person in the unit to update families when they call and enquire about the conditions.

The production of soybean meal (SBM) has a substantial impact on the environment and reducing its inclusion in poultry diets by using alternative protein sources, such as insect meal, is an important challenge for nutritionists. This study aimed to compare the productive performance of broiler chickens fed one of two isonitrogenic (195 g/kg CP) and isocaloric (12.91 MJ/kg) diets. The first diet contained SBM as the main protein source, whereas SBM was completely replaced by defatted meal from Black Soldier Fly larvae (Hermetia illucens L.; BSFL) in the second diet. Compared to the BSFL diet, the final body weight (BW) and weight gain (WG) of birds fed the SBM diet was ~17% greater and feed was utilised 19% more efficiently (p < 0.05). The differences in WG and FCR were supported by improved energy metabolism metrics, fat digestibility and digestibility of acid detergent fibres (ADFD) (p < 0.05). The present study shows that a complete replacement of dietary SBM with BSFL meal must be achieved with care, ensuring that all other factors (e.g., insect processing technology, feed additive supplementation, non-protein nitrogen accounting, mineral balance, fatty acid profile, amino acid supplementation) have been considered.

Globally, zoonoses have serious consequences due to their socioeconomic impacts. Ngorongoro District is home to a diverse range of wildlife and domestic animals, including rodents and dogs, which often coexist in close proximity with humans. The aim of the study was to identify the zoonotic bacteria present in wild rodents, domestic dogs, and humans using metagenomics next-generation sequencing technology. A cross-sectional study was conducted in 2022. This study used both Illumina and Oxford Nanopore sequencing technologies to identify bacteria in 530 blood samples collected from humans (n = 200), wild rodents (n = 230), and dogs (n = 100). Several zoonotic airborne/contagious bacteria, including Mycobacterium spp., Mycoplasma spp., Bordetella spp., and Legionella spp., were detected in wild rodents, domestic dogs, and humans. Arthropod-borne zoonotic bacteria such as Bartonella spp., Borrelia spp., and Rickettsia spp. were detected in all three hosts, while Orientia spp. was found in wild rodents and domestic dogs. Yersinia pestis, Streptobacillus spp. and Anaplasma spp. were found only in wild rodents. Other zoonotic bacteria found shared among wild rodents, domestic dogs, and humans are Leptospira spp., Brucella spp., and Salmonella spp. Generally, wild rodents had the highest prevalence of zoonotic bacterial species when compared to domestic dogs and humans. The detection of zoonotic bacteria in rodents, dogs, and humans supports the hypothesis that infections can spread between animals and humans sharing the same environment.

The aim of this study was to evaluate prediction equations to estimate 1RM in different exercises in older men and women with osteopenia/osteoporosis. Forty well-trained older women and men (73 ± 8 years) with osteopenia/osteoporosis performed 1RM dynamic and isometric maximum strength tests on resistance devices. In addition, each participant performed repetitions-to-fatigue (RTF) in the 5–8RM, 9–12RM, and 13–16RM zones. After evaluating the predictive performance of available 1RM prediction equations from the literature, new prediction equations were developed for all seven exercises. One of the available equations that focus on postmenopausal women already acceptably predicted 1RM from RTF for all but one exercise. Nevertheless, new exercise-specific prediction equations based on a cubic polynomial most accurately predict 1RM from RTF in the 5–8 reps range with mean absolute differences between predicted and actual 1RM of 3.7 ± 3.7% (leg-press) to 6.9 ± 5.5% (leg flexion) that is roughly within the acceptable coefficient of variation. For some exercises, the inclusion of the isometric maximum strength tests slightly increases the prediction performance of the 5–8RM. In conclusion, the present prediction equation accurately estimates 1RM in trained, older women and men with osteopenia/osteoporosis. Further evaluation of this new equation is warranted to determine its applicability to different age groups and populations.

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers.

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

Malaria is a serious health problem worldwide affecting mainly children and socially vulnerable people. The biological particularities of P. vivax, such as the ability to generate dormant liver stages, the rapid maturation of gametocytes, and the emergence of drug resistance, have contributed to difficulties in disease control. In this context, developing an effective vaccine has been considered a fundamental tool for the efficient control and/or elimination of vivax malaria. Although recombinant proteins have been the main strategy used in designing vaccine prototypes, synthetic immunogenic peptides have emerged as a viable alternative for this purpose. Considering, therefore, that in the Brazilian endemic population, little is known about the profile of the humoral immune response directed to synthetic peptides that represent different P. vivax proteins, the present work aimed to map the epitope-specific antibodies’ profiles to synthetic peptides representing the linear portions of the ookinete and sporozoite cell passage protein (CelTOS), thrombospondin-related adhesive protein (TRAP), and cysteine-rich protective antigen (CyRPA) proteins in the acute (AC) and convalescent phases (Conv30 and Conv180 after infection) of vivax malaria. The results showed that the studied subjects responded to all proteins for at least six months following infection. For IgM, a few individuals (3–21%) were positive during the acute phase of the disease; the highest frequencies were observed for IgG (28–57%). Regarding the subclasses, IgG2 and IgG3 stood out as the most prevalent for all peptides. During the follow-up, the stability of IgG was observed for all peptides. Only one significant positive correlation was observed between IgM and exposure time. We conclude that for all the peptides, the immunodominant epitopes are recognized in the exposed population, with similar frequency and magnitude. However, if the antibodies detected in this study are potential protectors, this needs to be investigated.

The most studied cavefish in the world is Astyanax mexicanus, and the most frequently used specimens in research come from the Pachón cave in Northeast Mexico. A recent study using the capture–mark–recapture technique revealed that the Pachón population size is only in the hundreds of individuals, not in the thousands. This result raises serious concerns about their long-term survival and highlights the need to accurately estimate the population size of other Astyanax caves. In our study, we used a well-established, non-invasive method for estimating population size: the transect sampling method, which counts the abundance of organisms along a line at regular intervals. We used the 310 m long Sabinos Cave’s Pool #1 for measurements and estimated a population of 1142 individuals. Most importantly, we found that cavefish are not distributed uniformly: 68% of the individuals were clustered under a bat roost. To corroborate this observation, we used drones to explore submerged galleries inaccessible to scientists. Results from the Toro/Calera Cave system confirmed that most galleries were essentially void of cavefish, except for in those few areas with high amounts of nutrients. Scientists visiting the most studied Astyanax localities (Pachón, Sabinos, Tinaja, and Chica) experience what appear to be high-density populations of about 10 fish/m2, possibly because the pool they visit happens to be under bat roosts. Our study shows that one cannot extrapolate the density at these localities to the rest of the habitat, where densities might be two orders of magnitude lower. Future studies should consider that the apparent high density at visited sites is overrepresenting the total population size when calculating the number of fish specimens to be captured.

Freshwater mussels (order: Unionida) are highly imperiled globally and are increasingly the focus of captive propagation efforts to protect and restore wild populations. The Upper Tennessee River Basin (UTRB) in Virginia is a freshwater biodiversity hotspot hosting at least 45 of North America’s ~300 species of freshwater mussels, including 21 threatened and endangered species listed under the U.S. Endangered Species Act. Recent studies have documented that viruses and other microbes have contributed to freshwater mussel population declines in the UTRB. We conducted a multi-year longitudinal study of captive-reared hatchery mussels released to restoration sites throughout the UTRB to evaluate their viromes and compare them to captive hatchery environments. We documented 681 viruses from 27 families. The hatchery mussels had significantly less viruses than those deployed to wild sites, with only 20 viruses unique to the hatchery mussels. After the hatchery mussels were released into the wild, their number of viruses initially spiked and then increased steadily over time, with 451 viruses in total unique to the mussels in the wild. We found Clinch densovirus 1 (CDNV-1), a virus previously associated with mass mortality events in the Clinch River, in all samples, but the wild site mussels consistently had significantly higher CDNV-1 levels than those held in the hatchery. Our data document substantial differences between the viruses in the mussels in the hatchery and wild environments and rapid virome shifts after the mussels are released to the wild sites. These findings indicate that mussel release programs might benefit from acclimatization periods or other measures to mitigate the potential negative effects of rapid exposure to infectious agents found in natural environments.

Recently, we showed that three months of resistance exercise significantly alters 18 canonical pathways related to chronic inflammation in PBMCs of older adults. In this exploratory sub-study, the aim is to explore whether resistance exercise enhances the PBMCs stress response by mimicking an acute infection through in vitro LPS stimulation. Women (≥65 years) were randomly divided into intensive strength training (IST), strength endurance training (SET), or flexibility training (as control group, CON) groups. PBMCs were isolated and cultured with and without LPS for 24 h. Their RNA was analyzed via targeted RNA sequencing of 407 inflammation-related genes, with relevant fold-changes defined as ≤0.67 or ≥1.5 (3 months vs. baseline). A pathway analysis using ingenuity pathway analyses identified significant pathways among 407 genes with p < 0.05 and z-scores of ≤−2 or ≥2. Fourteen women were included in the analyses. A total of 151 genes with a significant fold-change were identified. In the CON group, a less-pronounced effect was observed. Strength training altered 23 pathways in the LPS-stimulated PBMCs, none of which overlapped between the IST and SET groups. A balanced exercise program that includes both IST and SET could beneficially adapt the immune responses in older adults by inducing alterations in the inflammatory stress response of PBMCs through different genes and pathways.

Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown. In this study, PACAP/VIP levels were assessed in the brain of GFAP-IL6 mice. In addition, we utilised bi-genic GFAP-IL6 mice carrying the human sgp130-Fc transgene (termed GFAP-IL6/sgp130Fc mice) to determine whether trans-signalling inhibition rescued PACAP/VIP changes in the CNS. Transcripts and protein levels of PACAP and VIP, as well as their receptors PAC1, VPAC1 and VPAC2, were significantly increased in the cerebrum and cerebellum of GFAP-IL6 mice vs. wild type (WT) littermates. These results were paralleled by a robust activation of the JAK/STAT3, NF-κB and ERK1/2MAPK pathways in GFAP-IL6 mice. In contrast, co-expression of sgp130Fc in GFAP-IL6/sgp130Fc mice reduced VIP expression and activation of STAT3 and NF-κB pathways, but it failed to rescue PACAP, PACAP/VIP receptors and Erk1/2MAPK phosphorylation. We conclude that forced expression of IL-6 in astrocytes induces the activation of the PACAP/VIP neuropeptide system in the brain, which is only partly modulated upon IL-6 trans-signalling inhibition. Increased expression of PACAP/VIP neuropeptides and receptors may represent a homeostatic response of the CNS to an uncontrolled IL-6 synthesis and its neuroinflammatory consequences.

The control of metabolic networks is incompletely understood, even for glycolysis in highly studied model organisms. Direct real-time observations of metabolic pathways can be achieved in cellular systems with 13C NMR using dissolution Dynamic Nuclear Polarization (dDNP NMR). The method relies on a short-lived boost of NMR sensitivity using a redistribution of nuclear spin states to increase the alignment of the magnetic moments by more than four orders of magnitude. This temporary boost in sensitivity allows detection of metabolism with sub-second time resolution. Here, we hypothesized that dDNP NMR would be able to investigate molecular phenotypes that are not easily accessible with more conventional methods. The use of dDNP NMR allows real-time insight into carbohydrate metabolism in a Gram-positive bacterium (Lactoccocus lactis), and comparison to other bacterial, yeast and mammalian cells shows differences in the kinetic barriers of glycolysis across the kingdoms of life. Nevertheless, the accumulation of non-toxic precursors for biomass at kinetic barriers is found to be shared across the kingdoms of life. We further find that the visualization of glycolysis using dDNP NMR reveals kinetic characteristics in transgenic strains that are not evident when monitoring the overall glycolytic rate only. Finally, dDNP NMR reveals that resting Lactococcus lactis cells use the influx of carbohydrate substrate to produce acetoin rather than lactate during the start of glycolysis. This metabolic regime can be emulated using suitably designed substrate mixtures to enhance the formation of the C4 product acetoin more than 400-fold. Overall, we find that dDNP NMR provides analytical capabilities that may help to clarify the intertwined mechanistic determinants of metabolism and the optimal usage of biotechnologically important bacteria.

Hypertension is a major risk factor for heart disease and stroke. Garlic has a long history of use in traditional medicine for various conditions, including hypertension. This narrative review examined the scientific evidence on the efficacy of garlic in lowering blood pressure. It explores the historical uses of garlic in different cultures for medicinal purposes and delves into the phytochemical composition of garlic, highlighting key components, like allicin and ajoene, that are believed to contribute to its potential health benefits. Clinical studies that investigated the effects of garlic and garlic-based supplements on blood pressure are presented, with the findings suggesting that garlic consumption may modestly reduce blood pressure, particularly in individuals with mild hypertension. Potential mechanisms of action include increased nitric oxide production, improved endothelial function, and antioxidant properties. While garlic may offer some benefits for blood pressure management, it should not be considered a substitute for conventional antihypertensive medications. Further large-scale, long-term clinical trials are warranted to establish the efficacy of garlic in managing hypertension, including the optimal dosage and formulation.