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Aims Electroanatomical adaptations during the neonatal to adult phase have not been comprehensively studied in preclinical animal models. To explore the impact of age as a biological variable on cardiac electrophysiology, we employed neonatal and adult guinea pigs, which are a recognized animal model for developmental research. Methods and results Electrocardiogram recordings were collected in vivo from anaesthetized animals. A Langendorff-perfusion system was employed for the optical assessment of action potentials and calcium transients. Optical data sets were analysed using Kairosight 3.0 software. The allometric relationship between heart weight and body weight diminishes with age, it is strongest at the neonatal stage (R 2 = 0.84) and abolished in older adults (R 2 = 1E−06). Neonatal hearts exhibit circular activation, while adults show prototypical elliptical shapes. Neonatal conduction velocity (40.6 ± 4.0 cm/s) is slower than adults (younger: 61.6 ± 9.3 cm/s; older: 53.6 ± 9.2 cm/s). Neonatal hearts have a longer action potential duration (APD) and exhibit regional heterogeneity (left apex; APD30: 68.6 ± 5.6 ms, left basal; APD30: 62.8 ± 3.6), which was absent in adults. With dynamic pacing, neonatal hearts exhibit a flatter APD restitution slope (APD70: 0.29 ± 0.04) compared with older adults (0.49 ± 0.04). Similar restitution characteristics are observed with extrasystolic pacing, with a flatter slope in neonates (APD70: 0.54 ± 0.1) compared with adults (younger: 0.85 ± 0.4; older: 0.95 ± 0.7). Neonatal hearts display unidirectional excitation–contraction coupling, while adults exhibit bidirectionality. Conclusion Postnatal development is characterized by transient changes in electroanatomical properties. Age-specific patterns can influence cardiac physiology, pathology, and therapies for cardiovascular diseases. Understanding heart development is crucial to evaluating therapeutic eligibility, safety, and efficacy. [ABSTRACT FROM AUTHOR]

Guinea pigs have historically been used as a food source and are also an important model for studying the human intestines. Fasting is the act of temporarily stopping the intake of food. This process can alter the microbiota of various animals. This study is the first to investigate the impact of fasting on the cecum microbiome of three guinea pig breeds. We investigated the impact of fasting on the microbiome population structure in the cecum of three guinea pig breeds. This was done by sequencing and analyzing the V4 hypervariable region of the 16S rRNA gene in bacterial communities found in cecum mucosa samples. To achieve this, we established two treatment groups (fasting and fed), for each of the three guinea pig breeds: Andina, Inti, and Peru. The study involved twenty-eight guinea pigs, which were divided into the following groups: Andina-fed (five), Andina-fasting (five), Inti-fed (four), Inti-fasting (five), Peru-fed (five), and Peru-fasting (four). The results indicated a significant difference in beta diversity between the treatment groups for the Peru breed (P-value = 0.049), but not for the treatment groups of the Andina and Inti breeds. The dominant phyla across all groups were Firmicutes and Bacteroidetes. We observed variations in the abundance of different taxa in the cecum microbiota when comparing the treatment groups for each breed. Additionally, there was a higher number of unique taxa observed in the fasting groups compared to the fed groups. We discovered that the genus Victivallis was the only one present in all fasting groups across all breeds. Despite the findings, the resilience of the gutmicrobiome was not challenged in all three breeds, which can lead to disruptive changes that may affect the overall maintenance of the cecum microbiome. Based on the observed differences in the treatment groups of the Peru breed, it can be suggested that fasting has a greater impact on this particular breed. [ABSTRACT FROM AUTHOR]

The study emphasizes the need of implementing several ways to promote guinea pig farming in small family units. It highlights the relevance of enhanced nutrition, effective health management, genetic enhancement, and acceptable habitat conditions as essential factors for enhancing productivity and profitability. Suggestions encompass the adoption of advanced breeding methods, offering training and technical support, and expanding the range of goods and markets to ensure the long-term economic viability of guinea pig farming. The utilization of neutrosophic sets provided a strong framework for assessing these techniques, enabling a thorough study that considers the inherent uncertainties in decision-making processes. To enhance future study, it is recommended to improve and broaden neutrosophic approaches to comprehend the intricacies of guinea pig farming systems more effectively. It will be beneficial to create more advanced models that include a broader set of factors and extensive data, as well as to undertake longitudinal studies to evaluate the long-term effects. It is essential to work together with local communities to customize tactics that are suitable for specific geographical conditions and socioeconomic contexts. This is necessary to ensure that these interventions are practical and successful. [ABSTRACT FROM AUTHOR]

Simple Summary: Every year, the consumption of beef cattle increases, as does slaughter waste, including rumen content, blood, and other waste such as ears and cheeks. These can be converted into meals through heat treatment, so it is important to know their nutritional value. In this study, tests were carried out that allowed us to determine the chemical composition, the contribution of available nutrients, and the energy content of this slaughter waste to prepare rations for guinea pigs. After the study, it was verified that flours made from ruminal content, blood, ears, and cheeks are good sources of protein and energy for guinea pigs and are consumed without problems when included as one-fifth of a barley-based diet. This circular economy approach allows this type of waste to be recovered and valued, with the advantage of reducing its polluting power due to inadequate disposal or its disposal into rivers. Biowaste from slaughterhouses can be recovered to benefit food security and reduce contamination potential. More than 3 billion heads of livestock are consumed worldwide, which will increase by 17% by 2028, generating more biowaste, increasing infectious agents, and causing economic losses due to circular economy principles not being applied. This work evaluated the nutritional quality of four types of biowaste from bovine slaughter which were transformed into a meal for guinea pigs (rumen content (RCM), ears (EaM), blood (BM), and cheeks (CM)) according to their chemical composition, digestible components, energy contribution, and voluntary consumption. For the animal model, adult male guinea pigs were arranged in metabolic cages for feces collection without urinary contamination. Nine guinea pigs were used in each digestibility test. First, a direct digestibility test was conducted using a meal of barley as a reference diet (RD), the indigestibility coefficient of which allowed for the estimation of the digestibility of biowaste meals through indirect calculations; for this, diets composed of 80% of the RD and 20% of the corresponding biowaste meals were evaluated. The difference method was suitable for determining the digestibility of beef biowaste using the indigestibility coefficients of the reference diet to calculate the digestibility of ingredients which could not be offered as 100% of the meal but were incorporated as 20%. The digestible protein and metabolizable energy contents of RCM, EaM, BM, and CM were 10.2% and 2853 kcal/kg, 44.5% and 3325 kcal/kg, 70.7% and 2583 kcal/kg, and 80.8% and 3386 kcal/kg, respectively. The CM and BM feeds had the highest contributions of digestible protein due to their higher nitrogen content, and the CM and EaM feeds had the highest ME contents due to their higher fat contents. The biowaste meal consumption in descending order was CM > RCM > EaM > BM, which were consumed without problems. These results are indicative that these components can be part of guinea pigs' diets, and it is recommended to continue studies into guinea pig growth and fattening diets with different levels of these biowaste meals. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm2) to week 4 (28687 ± 2071/mm2) and week 8 (17977 ± 3697/mm2). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia. • Successful induction of glaucoma in guinea pigs via intracameral injection of magnetic microspheres. • Guinea pigs feature a collagen-based lamina cribrosa, superior to current rodent models. • Distinct patterns of eyeball enlargement exist in glaucomatous and myopic eyes. [ABSTRACT FROM AUTHOR]

Background: Serving as a reservoir, the gastric fundus can expand significantly, with an initial receptive and a following adaptive relaxation, controlled by extrinsic and intrinsic reflex circuits, respectively. We hypothesize that mechanosensitive enteric neurons (MEN) are involved in the adaptive relaxation, which is initiated when a particular gastric volume and a certain stretch of the stomach wall is reached. To investigate whether the responsiveness of MEN in the gastric fundus is dependent on tissue stretch, we performed mechanical stimulations in stretched versus ganglia "at rest". Methods: Responses of myenteric neurons in the guinea pig gastric fundus were recorded with membrane potential imaging using Di‐8‐ANEPPS. MEN were identified by small‐volume intraganglionic injection in ganglia stretched to different degrees using a self‐constructed stretching tool. Immunohistochemical staining identified the neurochemical phenotype of MEN. Hexamethonium and capsaicin were added to test their effect on recruited MEN. Key Results: In stretched compared to "at rest" ganglia, significantly more MEN were activated. The change in the ganglionic area correlated significantly with the number of additional recruited MEN. The additional recruitment of MEN was independent from nicotinic transmission and the ratio of active MEN in stretched ganglia shifted towards a nitrergic phenotype. Conclusion and Inferences: The higher number of active MEN with increasing stretch of the ganglia and their greater share of nitrergic phenotype might indicate their contribution to the adaptive relaxation. Further experiments are necessary to address the receptors involved in mechanotransduction. [ABSTRACT FROM AUTHOR]

The effects of enhanced late INa, a persistent component of the Na+ channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late INa, caused increases in the basal Na+ and Ca2+ concentrations, increases in the number of Ca2+ sparks and Ca2+ waves, and the generation of repetitive Ca2+ transients. These phenomena were inhibited by eleclazine, a blocker of the late INa; SEA0400, an inhibitor of the Na+/Ca2+ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late INa in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca2+-dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium. [ABSTRACT FROM AUTHOR]

Aim: Alzheimer's disease (AD) is the most common form of dementia. However, while 150+ animal models of AD exist, drug translation from preclinical models to humans for treatment usually fails. One factor contributing to low translation is likely the absence of neurodegenerative models that also encompass the multi‐morbidities of human aging. We previously demonstrated that, in comparison to the PigmEnTed (PET) guinea pig strain which models "typical" brain aging, the Hartley strain develops hallmarks of AD like aging humans. Hartleys also exhibit age‐related impairments in cartilage and skeletal muscle. Impaired mitochondrial respiration is one driver of both cellular aging and AD. In humans with cognitive decline, diminished skeletal muscle and brain respiratory control occurs in parallel. We previously reported age‐related declines in skeletal muscle mitochondrial respiration in Hartleys. It is unknown if there is concomitant mitochondrial dysfunction in the brain. Methods: Therefore, we assessed hippocampal mitochondrial respiration in 5‐ and 12‐month Hartley and PET guinea pigs using high‐resolution respirometry. Results: At 12 months, PETs had higher complex I supported mitochondrial respiration paralleling their increase in body mass compared to 5 months PETs. Hartleys were also heavier at 12 months compared to 5 months but did not have higher complex I respiration. Compared to 5 months Hartleys, 12 months Hartleys had lower complex I mitochondrial efficiency and compensatory increases in mitochondrial proteins collectively suggesting mitochondrial dysfunction with age. Conclusions: Therefore, Hartleys might be a relevant model to test promising therapies targeting mitochondria to slow brain aging and AD progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Is our ability to discriminate speech in noise an innate and fixed ability, or can it be increased by a perceptual learning task? And if this is the case, can we find neural correlates of this improved perceptual ability? To address this question, we trained adult mice to discriminate between acoustically similar calls from guinea pigs, first in quiet, then in two types of masking noise at three different signal-to-noise ratios. The mice performance was excellent in quiet and decreased when the signal-to-noise became negative. After three months of training, we recorded the auditory responses in auditory brainstem neurons (inferior colliculus) and found that their responses tended to be stronger and more discriminative than those of passively exposed mice and, more surprisingly, sometimes stronger and more discriminative than those of guinea pigs. These results exemplify the fact that extensive practice in a perceptual learning task can improve the way auditory neurons process speech-like sounds in noise. Humans and animals maintain accurate discrimination between communication sounds in the presence of loud sources of background noise. In previous studies performed in anesthetized guinea pigs, we showed that, in the auditory pathway, the highest discriminative abilities between conspecific vocalizations were found in the inferior colliculus. Here, we trained CBA/J mice in a Go/No-Go task to discriminate between two similar guinea pig whistles, first in quiet conditions, then in two types of noise, a stationary noise and a chorus noise at three SNRs. Control mice were passively exposed to the same number of whistles as trained mice. After three months of extensive training, inferior colliculus (IC) neurons were recorded under anesthesia and the responses were quantified as in our previous studies. In quiet, the mean values of the firing rate, the temporal reliability and mutual information obtained from trained mice were higher than from the exposed mice and the guinea pigs. In stationary and chorus noise, there were only a few differences between the trained mice and the guinea pigs; and the lowest mean values of the parameters were found in the exposed mice. These results suggest that behavioral training can trigger plasticity in IC that allows mice neurons to reach guinea pig-like discrimination abilities. [ABSTRACT FROM AUTHOR]

Background There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI).Methods Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested in vitro. The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs in vivo.Results The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release in vitro, while it reduced fibrous tissue growth around the cochlear implant in vivo.Conclusions We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI’s safety and efficacy, with potential implications for future clinical translation.

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases. In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases. In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17β-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women. A) The Caf-induced transient Ca2+ peak is produced by the release of Ca2+ from the SR by the RyR and the decrease of cytosolic Ca2+ by the PMCA and SERCA. B) The inhibition of PMCA by E2 modifies the Ca2+ response to Caf, inducing a Ca2+ plateau. C) this sustained [Ca2+] i leads to airway hyperresponsiveness. PMCA, plasma membrane Ca2+ ATPase; Caf, caffeine; RyR, ryanodine receptor; SERCA, sarcoplasmic reticulum Ca2+ ATPase; SR, sarcoplasmic reticulum; E2, 17β-estradiol; ASM, airway smooth muscle. [Display omitted] • Acute exposure to 17β-estradiol (E2) induces airway hyperresponsiveness (AHR) in the airway smooth muscle (ASM). • The acute incubation of E2 in ASM cells modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. • The sustained Ca2+ increment induced by E2 is through the inhibition of the plasma membrane Ca2+-ATPase pump (PMCA). • The inhibition of PMCA by the acute exposure of E2 induces AHR in the ASM. [ABSTRACT FROM AUTHOR]

The emergence of high-resistance strains to known antifungal drugs has highlighted the urgency of developing novel therapies for chronic dermatophytosis as a global health problem. An experimental dermatophytosis model in guinea pigs was developed to investigate the in vivo wound healing effects of cold atmospheric plasma (CAP) on T. rubrum skin invasion. Guinea pigs were experimentally infected with T. rubrum and wound healing was evaluated at 1, 4, 8 and 12 days post infection in the CAP-treated, terbinafine-treated and non-treated controls. Our results showed that CAP strongly inhibited the fungal virulence in vitro in culture media and in vivo on the skin lesions of experimentally infected guinea pigs even more efficient than that of terbinafine, resulting in complete wound healing at 8 days post infection. These results indicate that CAP would be considered as a promising tool comparable to conventional chemical therapies, for the treatment of drug-resistant chronic dermatophytosis caused by T. rubrum. [Display omitted] [ABSTRACT FROM AUTHOR]

Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of β2-adrenergic receptors/AC/cAMP pathway. [ABSTRACT FROM AUTHOR]

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models. [ABSTRACT FROM AUTHOR]

Guinea Pig Herpes-Like Virus (GPHLV) is a virus isolated from leukemic guinea pigs with herpes virus-like morphology described by Hsiung and Kaplow in 1969. GPHLV transformed embryonic cells from Syrian hamsters or rats, which were tumorigenic in adult animals. Herein, we present the genomic sequence of GPHLV strain LK40 as a reference for future molecular analysis. GPHLV has a broad host tropism and replicates efficiently in Guinea pig, Cat, and Green African Monkey-derived cell lines. GPHLV has a GC content of 35.45%. The genome is predicted to encode at least 75 open-reading frames (ORFs) with 84% (63 ORFs) sharing homology to human Kaposi Sarcoma Associated Herpes Virus (KSHV). Importantly, GPHLV encodes homologues of the KSHV oncogenes, vBCL2 (ORF16), vPK (ORF36), viral cyclin (v-cyclin, ORF72), the latency associated nuclear antigen (LANA, ORF73), and vGPCR (ORF74). GPHLV is a Rhadinovirus of Cavia porcellus, and we propose the formal name of Caviid gamma herpesvirus 1 (CaGHV-1). GPHLV can be a novel small animal model of Rhadinovirus pathogenesis with broad host tropism. [ABSTRACT FROM AUTHOR]

Background: Intrauterine growth restriction (IUGR) is an obstetrical condition where a fetus has not achieved its genetic potential. A consequence of IUGR is a decrease in brain myelin content. Myelin water imaging (MWI) has been used to assess fetal myelin water fraction (MWF) and might potentially assess myelination changes associated with IUGR. Purpose: To quantify and compare the MWF of non‐IUGR and IUGR fetal guinea pigs (GPs) in late gestation. Study Type: Prospective animal model. Animal Model: Dunkin‐Hartley GP model of spontaneous IUGR (mean ± SD: 60 ± 1.2 days gestation; 19 IUGR, 52 control). Field Strength/Sequence: Eight spoiled gradient‐recalled (SPGR) gradient echo volumes (flip angles [α]: 2°–16°), and two sets of eight balanced steady‐state free precession (bSSFP) gradient echo volumes (α: 8° – 64°), at 0° and 180° phase increments, at 3.0 T. Assessment: MWF maps were generated for each fetal GP brain using multicomponent driven equilibrium single pulse observation of T1/T2 (mcDESPOT). MWF was quantified in the fetal corpus callosum (CC), fornix (FOR), parasagittal white matter (PSW), and whole fetal brain. Statistical Tests: Linear regression was performed between five fetal IUGR markers (body volume, body‐to‐pregnancy volume ratio, brain‐to‐liver volume ratio, brain‐to‐placenta volume ratio, and brain‐to‐body volume ratio) and MWF (coefficient of determination, R2). A t‐test with a linear mixed model compared the MWF of non‐IUGR and IUGR fetal GPs (significance was determined at α < 0.05). Results: The MWF of the control fetuses are (mean ± SD): 0.23 ± 0.02 (CC), 0.31 ± 0.02 (FOR), 0.28 ± 0.02 (PSW), and 0.20 ± 0.01 (whole brain). The MWF of the IUGR fetuses are (mean ± SD): 0.19 ± 0.02 (CC), 0.27 ± 0.01 (FOR), 0.24 ± 0.03 (PSW), and 0.16 ± 0.01 (whole brain). Significant differences in MWF were found between the non‐IUGR and IUGR fetuses in every comparison. Data Conclusion: The mean MWF of IUGR fetal GPs is significantly lower than non‐IUGR fetal GPs. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic had a disproportionate impact on ethnically minoritised and other marginalised communities, yet little is known about the impacts of long COVID‐19 (LC) on this group. Living with LC takes its toll both physically, emotionally and financially and even more so when a diagnosis is hard to come by. By using qualitative interviews centring the view of undiagnosed and marginalised communities already classed as 'underserved' in the medical literature, we show the range of barriers and impacts faced by these groups in the UK, and the strategies of resilience they use. Whether trapped on a 'diagnostic odyssey' at the level of primary care, struggling to maintain employment and businesses, or managing family commitments, we argue many minoritised communities are caught in a liminal space of misrecognition, invalidation and ambiguity. We show how these impacts are generated by tensions and challenges in the process and categorisation of diagnosis, and how this effects the daily lives of many individuals already on the receiving end of health inequity. We also offer some examples and suggestions for best practices. [ABSTRACT FROM AUTHOR]

Introduction. Based on data on the role of blood erythrocytes in the development and implementation of the vaccine and infectious processes in plague, it was of interest to evaluate changes in erythrocyte surface architecture from the position of searching for informative criteria for the preclinical evaluation of anti-plague vaccines. Aim — using atomic force microscopy to characterize the state of the blood erythrocyte membrane of guinea pigs in response to subcutaneous administration of the vaccine strain Yersinia pestis EV NIIEG and its isogenic derivatives. Materials and methods. For immunization of animals strain Y. pestis EV NIIEG (pYT+, pYV+, pYP+) and its isogenic derivatives Y. pestis KM216 (pYT–, pYV–, pYP+), Y. pestis KM217 (pYT–, pYV+, pYP–), Y. pestis KM218 (pYT–, pYV–, pYP–) were used. Analysis of the erythrocyte membrane was carried out using a Solver P47-PRO scanning probe microscope (NT-MDT, Russia). Results. The most pronounced changes in the surface architectonics of the membrane of guinea pig erythrocytes were established during the first three days of the formation of the immune response to the Y. pestis EV strain NIIEG and its isogenic variant Y. pestis KM217, in the genome of which the pYV plasmid is preserved, administered at a dose of 5 × 108 CFU. A significant increase (p 0.05) in the proportion of transformed cell forms (43.67 ± 3.63% and 37.83 ± 7.03% versus 4.08 ± 0.86% in the control group), root mean square roughness (319 ± 8 nm and 312 ± 7 nm versus 70 ± 6 nm in the control group), Young's modulus (125.73 ± 4.48 kPa and 113.8 ± 5.41 kPa versus 53.03 ± 1.47 kPa in the control group). By the 21st day, the value of these indicators decreased by an average of 2.7, 2.0 and 1.5 times, respectively, indicating restoration of the erythrocyte membrane. Conclusion. The dependence of the changes in the erythrocyte membrane and the rate of their restoration on the plasmid composition of Y. pestis strains has been established. The data obtained contribute to the understanding of the processes of interaction of Y. pestis with the erythrocyte membrane and can be used as additional characteristics in the development of new criteria for preclinical evaluation of plague candidate vaccines.

The increasing drive to understand the likelihood of skin sensitisation from plant protection products (PPPs) in workers and the general public has resulted in recent initiatives to establish a quantitative risk assessment (QRA) methodology applicable to these products and their exposure scenarios. The effective evaluation of skin sensitising substances requires not only the identification of that toxicological hazard, but also determination of relative sensitising potency. Typically, this has been achieved by interpretation of local lymph node assay (LLNA) dose response data, delivering what is known as the EC3 value. This permitted regulatory division of skin sensitisers into defined potency sub-categories, but more importantly enabled derivation of a no expected sensitisation induction level (NESIL) as the point of departure for QRA. However, for many existing substances there is no LLNA data, only older guinea pig results exist. To avoid additional (in vivo) testing, an approach has been outlined to employ guinea pig data and existing regulatory guidelines on the determination of potency sub-categorisation to provide a guinea pig based NESIL. The approach adopts a conservative extrapolation from LLNA NESIL benchmarks to deliver points of departure as the basis for the type of QRA process already in successful use by other industries. • Effective safety evaluation of sensitisers requires quantitative risk assessment. • Older guinea pig tests do not lend themselves to sensitiser potency measurement. • LLNA results give potency sub-categories and risk assessment points of departure. • Regulatory guidelines detail potency sub-categorisation based on guinea pig results. • The sub-categories can be extrapolated to give guinea pig based points of departure. [ABSTRACT FROM AUTHOR]