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Equine influenza is a highly contagious viral disease, specially among 1-5 years old naive horses. Vaccination is considered the best way to control the disease spread and outbreaks. Although foals are the main animal used for evaluation of equine influenza vaccines, guinea pigs were chosen as an alternative model in the present work, as they have a negligible antibody titer against equine influenza virus and are cheaper and easier to handle than foals. Five equine influenza vaccine batches were evaluated in two animal models, foals and guinea pigs, by injection of two doses/animal with 4 weeks apart using 2 mL/animal/dose and evaluation of immune responses by hemagglutination inhibition test and enzyme-linked immunosorbent assay. On the 7th week post vaccination, equine influenza antibodies titers reached maximum values of 9-10.2 and 8.7-10 hemagglutination inhibition units for foals and guinea pigs, respectively; sample/negative ratios were 0.126-0.464 and 0.128-0.445 for both animals, respectively. The use of guinea pigs as an animal model for the evaluation of equine influenza vaccines could be recommended instead of foals.

Maternal stress and glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain. In the present study, we hypothesized that maternal prenatal synthetic glucocorticoid (sGC) exposure in the F0 pregnancy will result in differences in miRNA levels in testes germ cells and sperm across multiple generations, and that these changes will associate with modified microRNA (miRNA) profiles and gene expression in the prefrontal cortex (PFC) of subsequent generations. Pregnant guinea-pigs (F0) were treated with multiple courses of the sGC betamethasone (Beta) (1 mg kg -1 ; gestational days 40, 41, 50, 51, 60 and 61) in late gestation. miRNA levels were assessed in testes germ cells and in F2 PFC using the GeneChip miRNA 4.0 Array and candidate miRNA measured in epididymal sperm by quantitative real-time PCR. Maternal Beta exposure did not alter miRNA levels in germ cells derived from the testes of adult male offspring. However, there were significant differences in the levels of four candidate miRNAs in the sperm of F1 and F2 adult males. There were no changes in miRNA levels in the PFC of juvenile F2 female offspring. The present study has identified that maternal Beta exposure leads to altered miRNA levels in sperm that are apparent for at least two generations. The fact that differences were confined to epididymal sperm suggests that the intergenerational effects of Beta may target the epididymis. KEY POINTS: Paternal glucocorticoid exposure prior to conception leads to profound epigenetic changes in the brain and somatic tissues in offspring, and microRNAs (miRNAs) in sperm may mediate these changes. We show that there were significant differences in the miRNA profile of epididymal sperm in two generations following prenatal glucocorticoid exposure that were not observed in germ cells derived from the testes. The epididymis is a probable target for intergenerational programming. The effects of prenatal glucocorticoid treatment may span multiple generations., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objectives: Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant., Design: We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing., Results: Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear., Conclusions: Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity., Objectives: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model., Methods: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 10 8 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 μg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 μg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days., Results: The MIC 90 of APRN and enilconazole against T. verrucosum was 4 and 2 μg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC., Conclusion: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Consistent elicitation of serum antibody responses that neutralize diverse clades of HIV-1 remains a primary goal of HIV-1 vaccine research. Prior work has defined key features of soluble HIV-1 Envelope (Env) immunogen cocktails that influence the neutralization breadth and potency of multivalent vaccine-elicited antibody responses including the number of Env strains in the regimen. We designed immunization groups that consisted of different numbers of SOSIP Env strains to be used in a cocktail immunization strategy: the smallest cocktail (group 2) consisted of a set of two Env strains, which were a subset of the three Env strains that made up group 3, which, in turn, were a subset of the six Env strains that made up group 4. Serum neutralizing titers were modestly broader in guinea pigs that were immunized with a cocktail of three Envs compared to cocktails of two and six, suggesting that multivalent Env immunization could provide a benefit but may be detrimental when the cocktail size is too large. We then adapted the LIBRA-seq platform for antibody discovery to be compatible with guinea pigs, and isolated several tier 2 neutralizing monoclonal antibodies. Three antibodies isolated from two separate guinea pigs were similar in their gene usage and CDR3s, establishing evidence for a guinea pig public clonotype elicited through vaccination. Taken together, this work investigated multivalent HIV-1 Env immunization strategies and provides a novel methodology for screening guinea pig B cell receptor antigen specificity at a high-throughput level using LIBRA-seq. IMPORTANCE Multivalent vaccination with soluble Env immunogens is at the forefront of HIV-1 vaccination strategies but little is known about the influence of the number of Env strains included in vaccine cocktails. Our results suggest that adding more strains is sometimes beneficial but may be detrimental when the number of strains is too high. In addition, we adapted the LIBRA-seq platform to be compatible with guinea pig samples and isolated several tier 2 neutralizing monoclonal antibodies, some of which share V and J gene usage and >70% CDR3 identity, thus establishing the existence of public clonotypes in guinea pigs elicited through vaccination. [ABSTRACT FROM AUTHOR]

Abstract Background Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. Method Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. Results The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis. [ABSTRACT FROM AUTHOR]

A 2-year-3-month-old female guinea pig (Cavia porcellus) was referred for lethargy, weight gain and severe abdominal pain. Ultrasound examination revealed thickening and enlargement of the left uterine horn and an unremarkable right uterine horn. The animal died during ovariohysterectomy due to respiratory and cardiac arrest. Necropsy revealed unilateral segmental uterine horn hypoplasia and aplasia of the fallopian tube of the corresponding side. This is the first report of a congenital uterine malformation in the guinea pig and we describe the clinical and pathological presentation of segmental uterine horn hypoplasia and fallopian tube aplasia. Congenital uterine malformations are rare in guinea pigs but should be considered as differential diagnoses for the more common acquired uteropathies. [ABSTRACT FROM AUTHOR]

Skin is the main barrier to protect against harmful environmental influences, one of which is ultraviolet radiation (UVR) which comes from sunlight. Therefore, skin damage due to UVR (photodamage) has gained prominence in dermatology and aesthetic medicine, especially in tropical countries. Guinea pig (GP) as tropical mammal is potential to serve as animal model for skin-related research due to the similarity of their coat pigmentation to that of humans. This research aims to study the skin condition and histomorphometric structure of GP skin with coat color variations. Samples consisted of six adult female GP with tricolor and tortoiseshell patterns. After neatly shaved in 2 x 2 cm² area, skin condition is then evaluated using Skin Analyzer. Skin samples were processed into histological preparations using paraffin method with 10 % NBF as fixative and stained with Hematoxylin & Eosin (H&E) to measure the thickness of epidermis and dermis. Results demonstrated that skin moisture levels do not significantly differ between coat colors, higher levels of sebum and pigmentation correspond with darker coat colors, whereas lower levels of elasticity and collagen are associated with lighter coat colors. Histomorphometric examination showed that in tortoiseshell GP, the thickness of the epidermis and dermis increased with the coat color, but in tricolor GP, the thickness of epidermis and dermis varied. Furthermore, tortoiseshell GP have thicker epidermis and dermis than tricolor GP. It can be concluded that coat color influences the thickness of epidermis and dermis as well as pigmentation pattern of tortoiseshell is suitable as animal model for humans. [ABSTRACT FROM AUTHOR]

Abstract Objective Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel expressed on a subset of sensory neurons. TRPA1 is activated by a host of noxious stimuli including pollutants, irritants, oxidative stress and inflammation, and is thought to play an important role in nociception and pain perception. TRPA1 is therefore a therapeutic target for diseases with nociceptive sensory signaling components. TRPA1 orthologs have been shown to have differential sensitivity to certain ligands. Cinnamaldehyde has previously been shown to activate sensory neurons via the selective gating of TRPA1. Here, we tested the sensitivity of cinnamaldehyde-evoked responses in mouse and guinea pig sensory neurons to the pore blocker ruthenium red (RuR). Results Cinnamaldehyde, the canonical TRPA1-selective agonist, caused robust calcium fluxes in trigeminal neurons dissociated from both mice and guinea pigs. RuR effectively inhibited cinnamaldehyde-evoked responses in mouse neurons at 30 nM, with complete block seen with 3 μM. In contrast, responses in guinea pig neurons were only partially inhibited by 3 μM RuR. We conclude that RuR has a decreased affinity for guinea pig TRPA1 compared to mouse TRPA1. This study provides further evidence of differences in ligand affinity for TRPA1 in animal models relevant for drug development.

ObjectiveThe guinea pig serves as a well-established animal model for inner ear research, offering valuable insights into the anatomy, physiology, and therapeutic interventions of the auditory system. However, the heterogeneity of results observed in both in-vivo experiments and clinical studies poses challenges in understanding and optimizing pharmacotherapy outcomes. This heterogeneity may be due to individual differences in the size of the guinea pig cochlea and thus in the volume of the scala tympani (ST), which can lead to different drug concentrations in the ST, a fact that has been largely overlooked thus far. To address this issue, we aimed to develop an approach for calculating the individual volume of perilymph within the ST before and after cochlear implant insertion.MethodIn this study, high-resolution μCT images of a total of n = 42 guinea pig temporal bones were used to determine the volume of the ST. We compared fresh, frozen, and fixed tissues from both colored and albino strains to evaluate the potential influence of tissue condition and strain on the results.ResultsOur findings demonstrate a variability in mean ST volume with a relative standard deviation (RSD) of 14.7%, comparable to studies conducted with humans (range RSD: 5 to 20%). This indicates that the guinea pig cochlea exhibits similar variability to that of the human cochlea. Consequently, it is crucial to consider this variability when designing and conducting studies utilizing the guinea pig as an animal model. Furthermore, we successfully developed a tool capable of estimating ST volume without the need for manual segmentation, employing two geometric parameters, basal diameter (A) and width (B) of the cochlea, corresponding to the cochlear footprint. The tool is available for free download and use on our website.ConclusionThis novel approach provides researchers with a valuable tool to calculate individual ST volume in guinea pigs, enabling more precise dosing strategies and optimization of drug concentrations for pharmacotherapy studies. Moreover, our study underscores the importance of acknowledging and accounting for inter-individual variability in animal models to enhance the translational relevance and applicability of research outcomes in the field of inner ear investigations.

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PURPOSE: The guinea pig is widely used in studies of refractive error development and myopia which often involve experimental optical manipulations. The study described here investigated the optical quality of the guinea pig eye, for which there are limited data, despite its fundamental importance to understanding visually guided eye growth. METHODS: The ocular aberrations of eight adolescent New Zealand pigmented guinea pigs (6-11 weeks old) were measured after cycloplegia using a custom-built Shack-Hartmann aberrometer and fit with a Zernike polynomial function to the 10th order (65 terms). The optical quality of their eyes was assessed in terms of individual Zernike coefficients, and data were further analyzed to derive root-mean-square (RMS) wavefront errors, modulation transfer functions (MTFs), point spread functions (PSFs), Strehl ratios, and depth of focus. A 4-mm pupil was used in all computations. The derived data are compared with equivalent data from normal young adult human eyes. RESULTS: The guinea pigs exhibited low hyperopia and a small amount of positive spherical aberration, with other aberration terms decreasing with increasing order. Their average depth of focus, estimated from through-focus modulation, was 3.75 diopters. The RMS wavefront error of the guinea pig eye was found to be larger than that of the human eye for the same pupil size, reflecting a higher degree of aberrations, although the PSF (area) on the retina was smaller and sharper due to its shorter focal length. The radial average best-focus MTF derived for the guinea pig eye showed good performance at very low spatial frequencies, with a steeper decline with increasing frequency than for the human eye, dropping below 0.3 at 9 cpd. When converted to linear units (cycles/mm), the guinea pig eye had a higher spatial frequency cutoff and a slight contrast advantage for low spatial frequencies compared to the human eye. CONCLUSIONS: The optical quality of the guinea pig eye is far superior to their reported behavioral visual acuity. This implies a neuroanatomical limit to their vision, which contrasts with the close match of optical and neural limits to spatial resolution in human eyes. The significance for eye growth regulation of the relative optical advantages exhibited by guinea pig eyes, when optical quality is expressed in linear rather than angular retinal units, warrants further consideration.

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.

Sex seems to be a contributing factor in the pathogenesis of bronchial asthma. This study aimed to find sex-related differences in metabolome measured by hydrogen-1 nuclear magnetic resonance (1H NMR) spectroscopy in healthy and ovalbumin (OVA)-sensitized guinea pigs. Adult male and female animals were divided into controls and OVA-sensitized groups. OVA-sensitization was performed by OVA systemic and inhalational administration within 14 days; on day 15, animals were killed by anesthetic overdose followed by exsanguination. Blood was taken and differential white blood cell count was measured. Left lung was saline-lavaged and differential cell count in the bronchoalveolar lavage fluid (BALF) was measured. After blood centrifugation, plasma was processed for 1H NMR analysis. Metabolomic data was evaluated by principal component analysis (PCA). Eosinophil counts elevated in the BALF confirming eosinophil-mediated inflammation in OVA-sensitized animals of both sexes. Sex differences for lactate, glucose, and citrate were found in controls, where these parameters were lower in males than in females. In OVA-sensitized males higher glucose and lower pyruvate were found compared to controls. OVA-sensitized females showed lower lactate, glucose, alanine, 3-hydroxybutyrate, creatine, pyruvate, and succinate concentrations compared to controls. In OVA-sensitized animals, lactate concentration was lower in males. Data from females (healthy and OVA-sensitized) were generally more heterogeneous. Significant sex differences in plasma concentrations of metabolites were found in both healthy and OVA-sensitized animals suggesting that sex may influence the metabolism and may thereby contribute to different clinical picture of asthma in males and females. [ABSTRACT FROM AUTHOR]

Abstract Glyphosate formulations, widely applied non‐selective systemic herbicides, are progressively becoming the most controversial pesticides on the market due the adverse effects they pose to humans and environment. The information on these potential hazardous effects to the handlers of the pesticide remains obscure. This study investigated effects of glyphosate‐based herbicide on growth performance, seminal parameters and hemato‐biochemical profiles in male guinea pig. Forty sexually mature male guinea pigs weighing between 393.3 and 418.4 g were divided into four groups of 10 animals each and orally administered 0, 186, 280 and 560 mg/kg body weight of WILLOSATE daily for 60 days. Daily feed intake and body weight gain were recorded. At the end of experimental period all animals were humanely sacrificed, and blood samples and vital organs were collected for appropriate analysis. Results showed a significant decrease (p

PurposeIt has been proposed that the peripheral retina, responding to local optical defocus, contributes to myopia and associated altered eye growth in humans. To test this hypothesis, we measured the changes in central (on-axis) and peripheral ocular dimensions in guinea pigs wearing a concentric bifocal spectacle lens design with power restricted to the periphery.MethodsFive groups of guinea pigs (n = 83) wore either a unifocal (UF) spectacle lens (-4, 0, or +4 Diopters [D]), or a peripheral defocus (PF) spectacle lens that had a plano center (diameter of 5 mm) with either -4 or +4 D in the surround (-4/0 or +4/0 D). The overall optical diameter of all lenses was 12 mm. Lenses were worn over one eye from 8 to 18 days of age for negative and plano lenses, or from 8 to 22 days of age for positive lenses. Refractive error was measured centrally and 30° off-axis in the temporal and nasal retina. The shape of the eye was analyzed from images of sectioned eyes.ResultsLenses of -4 D UF induced myopia, reflecting enhanced ocular elongation, which was centered on the optic nerve head and included the surrounding peripapillary zone (PPZ, 18° in diameter). Some ocular expansion, including within the PPZ, also was recorded with -4/0 and +4/0 D PF lenses while the +4 D UF lens inhibited rather than enhanced elongation, centrally and peripherally.ConclusionsPeripheral defocus-induced ocular expansion encompasses the PPZ, irrespective of the sign of the inducing defocus. Understanding the underlying mechanism potentially has important implications for designing multifocal lenses for controlling myopia in humans and also potentially for understanding the link between myopia and glaucoma.

PurposeTo investigate the biocompatibility of an injectable hydrogel and its ability to control myopia progression in guinea pigs.MethodsThe study used a hydrogel synthesized from acrylated hyaluronic acid with a conjugated cell-binding peptide and enzymatically degradable crosslinker. Seven-day-old guinea pigs were first form deprived (FD) with diffusers for 1 week. One group was kept as an FD-only control; two groups received a sub-Tenon's capsule injection of either hydrogel or buffer (sham surgery) at the posterior pole of the eye. Form deprivation treatments were then continued for 3 additional weeks. Treatment effects were evaluated in terms of ocular axial length and refractive error. Safety was evaluated via intraocular pressure (IOP), visual acuity, flash electroretinograms (ERG), and histology.ResultsBoth hydrogel and sham surgery groups showed significantly reduced axial elongation and myopia progression compared to the FD-only group. For axial lengths, net changes in interocular difference (treated minus control) were 0.04 ± 0.06, 0.02 ± 0.09, and 0.24 ± 0.08 mm for hydrogel, sham, and FD-only groups, respectively (P = 0.0006). Intraocular pressures, visual acuities, and ERGs of treated eyes were not significantly different from contralateral controls. Extensive cell migration into the implants was evident. Both surgery groups showed noticeable Tenon's capsule thickening.ConclusionsSub-Tenon's capsule injections of both hydrogel and buffer inhibited myopia progression, with no adverse effects on ocular health. The latter unexpected effect warrants further investigation as a potential novel myopia control therapy. That the hydrogel implant supported significant cell infiltration offers further proof of its biocompatibility, with potential application as a tool for drug and cell delivery.

Cardiomyocytes contract keeping their sarcomere length (SL) close to optimal values for force generation. Transmural heterogeneity in SL across the ventricular wall coordinates the contractility of the whole-ventricle. SL heterogeneity (variability) exists not only at the tissue (macroscale) level, but also presents at the level of a single cardiomyocyte (microscale level). However, transmural differences in intracellular SL variability and its possible dependence on the state of contraction (e.g. end-diastole or end-systole) have not been previously reported. In the present study, we studied three aspects of sarcomere-to-sarcomere variability in intact cardiomyocytes isolated from the left ventricle of healthy guinea-pig: 1) transmural differences in SL distribution between subepi- (EPI) and subendocardial (ENDO) cardiomyocytes; 2) the dependence of intracellular variability in SL upon the state of contraction; 3) local differences in SL variability, comparing SL distributions between central and peripheral regions within the cardiomyocyte. To characterize the intracellular variability of SL, we used different normality tests for the assessment of SL distributions, as well as nonparametric coefficients to quantify the variability. We found that individual SL values in the end-systolic state of contraction followed a normal distribution to a lesser extent as compared to the end-diastolic state of contraction (∼1.3-fold and ∼1.6-fold in ENDO and EPI, respectively). The relative and absolute coefficients of sarcomere-to-sarcomere variability in end-systolic SL were significantly greater (∼1.3-fold) as compared to end-diastolic SL. This was independent of both the transmural region across the left ventricle and the intracellular region within the cardiomyocyte. We conclude that the intracellular variability in SL, which exists in normal intact guinea-pig cardiomyocytes, is affected by the contractile state of the myocyte. This phenomenon may play a role in inter-sarcomere communication in the beating heart.

PISA test data from 2000 to today have shown Germany's education system is one of the most inequitable within the OECD, with high correlations between student background and achievement outcomes. Scholars have identified the highly differentiated school structure, which tracks students as young as 10 years old, as a central cause. This scholarship has not evaluated why German tracking has proved difficult to reform over the last 20 years, despite evidence of negative outcomes. Using a case study of parents' actions in Hamburg, this paper employs a discourse analysis of debates surrounding a tracking reform to argue that opportunity hoarding--that is, parents with more social capital maintaining certain advantages through ingrained systems that are theoretically open to all--may contribute to why Germany's early tracking system persists despite evidence showing that it increases educational inequality. The findings presented have implications for an international discussion of tracking reform and opportunity hoarding.

Despite calls for increased community engagement in autism research, the published evidence base suggests that participatory autism research remains rare. This study examined the extent and nature of community engagement in Australian research projects commissioned by the Autism CRC. Data were gathered using an online survey, comprising quantitative scale items and qualitative free-text responses, which was completed by 64 academic partners and 15 community partners. Quantitative findings indicated that autism research stakeholders in Australia are largely supportive of community engagement in research and have had positive experiences of participatory research. These findings were not wholly corroborated by the qualitative findings, however, which suggested that participants lacked understanding of participatory research, and held attitudes that may hinder the conduct of successful participatory research. Systemic issues within research settings were also perceived to impede community engagement in research. Both academic and community partners would benefit from better understanding of participatory research approaches, paired with practical and epistemological shifts at the systemic level, to ensure that future community engagement in autism research is respectful, equitable and beneficial to all stakeholders.

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea. The present study characterized the impact of changing electrical pulse shapes from the standard biphasic symmetric to the asymmetrical shape by quantifying the evoked firing rate and the spatial activation in the guinea pig primary auditory cortex (A1). At a fixed charge, the firing rate and the spatial activation in A1 decreased by 15 to 25 % when asymmetric pulses were used to activate the auditory nerve fibers, suggesting a potential reduction of the spread of excitation inside the cochlea. A strong "polarity-order" effect was found as the reduction was more pronounced when the first phase of the pulse was cathodic with high amplitude. These results suggest that the use of asymmetrical pulse shapes in clinical settings can potentially reduce the channel interactions in CI users., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)