BACKGROUND: Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing.
METHODS: In the control group, 8 male Sprague-Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05.
RESULTS: The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear.
CONCLUSIONS: The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.

OBJECTIVE: The aim of this study was to evaluate whether thermal implant removal of osseointegrated implants is possible using a diode laser with an specific temperature-time interval.
METHODS: First, tooth extraction of the first three premolars was performed in the maxilla and mandible on both sides of 10 pig. After 3 months, implants were inserted into the upper and lower jaws of 10 pigs. After 3 more months, osseointegrated implants were heated with a laser device to a temperature of 50 °C for 1 min. After 14 days, the implant stability quotient (ISQ), torque-out values, and bone-to-implant contact (BIC) ratio were assessed using resonance frequency analysis.
RESULTS: ISQ values showed no significant differences within each group or between the control and test groups. Furthermore, torque-out and BIC value measurements presented no significant differences between the groups.
CONCLUSIONS: At 50°C, changes in the BIC values were noticeably smaller; however, these differences were not significant. Future studies should evaluate the same procedures at either a higher temperature or longer intervals.
CONCLUSIONS: With only 50 °C for 1 min, a dental implant will not de-integrate predictably.

BACKGROUND: Rabbits are routinely used as a natural model of fetal growth restriction (FGR); however, no studies have confirmed that rabbits have FGR. This study aimed to characterize the fetoplacental unit (FPU) in healthy pregnant rabbits using diffusion-weighted MRI and stereology. A secondary objective of the study was to describe the associations among findings from diffusion-weighted MRI (DW-MRI), fetal weight measurement and histological analysis of the placenta.
METHODS: Pregnant rabbits underwent DW-MRI under general anesthesia on embryonic day 28 of pregnancy. MR imaging was performed at 3.0 T. The apparent diffusion coefficient (ADC) values were calculated for the fetal brain, liver, and placenta. The placenta was analyzed by stereology (volume density of trophoblasts, the maternal blood space and fetal vessels). Each fetus and placenta were weighed. Two groups of fetuses were defined according to the position in the uterine horn (Cervix group versus Ovary group).
RESULTS: We analyzed 20 FPUs from 5 pregnant rabbits. Fetuses and placentas were significantly lighter in the Cervix group than in the Ovary group (34.7 ± 3.7 g vs. 40.2 ± 5.4 g; p = 0.02). Volume density analysis revealed that the percentage of fetal vessels, the maternal blood space and trophoblasts was not significantly affected by the position of the fetus in the uterine horn. There was no difference in ADC values according to the position of the fetus in the uterine horn, and there was no correlation between ADC values and fetal weight.
CONCLUSIONS: The findings of a multimodal evaluation of the placenta in a rabbit model of FGR suggested is not a natural model of fetal growth restriction.

BACKGROUND: Information about the volumizing effects of dermal fillers is critical for physicians\' understanding of product features and prudent decision-making in clinical practice. It is important for material engineers to develop and optimize new dermal fillers, especially when comparing the physiochemical properties of a new product with those of existing fillers that are used worldwide.
OBJECTIVE: This study aimed to establish a reliable, noninvasive method for in vivo quantitative evaluation of the filling effect in order to predict possible effectiveness after filler injection and to evaluate the degradation trend over time.
METHODS: A rabbit model of ear injection with dermal fillers was established. Hyaluronic acid (HA) filler was injected into the subcutaneous layer of rabbit ears, resulting in a stable skin bulge. Ultrasonography was used to noninvasively measure the skin bulge for volume calculation; the volume change was analyzed periodically until 38 weeks. Pathological examination, the gold standard, was performed to confirm degradation.
RESULTS: The immediate volumizing effect of HA filler injection was macroscopically observed as a local skin bulge. Ultrasound was able to precisely detect the shape of the filler and calculate the length, width, and height of the skin bulge at each time point. The degree of uplift and amount of residual samples in the pathological evaluation were consistent with the results of morphological observation using ultrasound.
CONCLUSIONS: Evaluation of the volume impact of dermal filler through the rabbit ear injection model evaluation enables material science evaluation in the early stage of material development, and has certain clinical reference value.
METHODS: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oral lichen planus (OLP) is a prevalent oral mucosal disease characterized by an unknown etiology and a complex pathogenesis. Patients with OLP endure a chronic course marked by alternating non-erosive and erosive lesions, with no definitive cure currently available. Particularly challenging is the treatment of recalcitrant erosive OLP, highlighting an urgent need for therapies targeting specific pathogenic pathways. In diseases like OLP, where the etiopathogenesis is intricate and elusive, animal models are indispensable for hypothesis testing and elucidating disease mechanisms. To date, only three animal models for oral lichenoid lesions have been reported in the literature. This Perspective paper evaluates these existing models, along with a novel OLP mouse model introduced at the 3rd International Conference on Oral Mucosal Immunity and Microbiome. The validity of these models is critically assessed, and their potential future applications in advancing our understanding of OLP are discussed.

OBJECTIVE: To histologically compare osseointegration and crestal bone healing between newly introduced tapered, self-cutting bone-level test implants and tapered bone-level control implants in sites with fully healed sites.
METHODS: Sixty-six implants (33 test, 33 control) were placed 1 mm subcrestally in a minipig model and underwent qualitative histologic and quantitative histometric analyses after 3, 6 and 12 weeks of submerged healing. The primary and secondary outcomes were the bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC). Outcomes between the test and control implants were statistically compared.
RESULTS: The BIC values of the test implants were comparable and non-inferior over the time points studied, except for the 12 weeks time point which showed statistically significantly higher BIC values of the test (88.07 ± 5.35%) compared to the control implants (80.88 ± 7.51%) (p = .010). Similarly comparable and non-inferior were the fBIC values, except for the 6-week outcome, which showed statistically higher values for the test (-546.5 ± 450.80 μm) compared to the control implants (-75.7 ± 100.59 μm). fBIC results for the test implants were qualitatively more stable and consistent between test time points.
CONCLUSIONS: Novel self-cutting bone-level test implants demonstrated superior osseointegration and similar bone levels compared to conventional bone-level implants after a healing period of 12 weeks in healed ridges.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model.
METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied.
RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs.
CONCLUSIONS: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

OBJECTIVE: The aims of this study were 1) to investigate the effects of a subepithelial connective tissue graft (SCTG) and a volume-stable collagen matrix (VCMX) on soft-tissue volume gain in the immediate implant placement protocol, and 2) to determine whether polydeoxyribonucleotide (PDRN) can enhance the effects of a VCMX.
METHODS: Dental implants were placed in 4 mongrel dogs immediately after extracting the distal roots of their third and fourth mandibular premolars. The gap between the implant and the buccal bone plate was filled with synthetic bone substitute particles. The following soft-tissue augmentation modalities were applied buccally: 1) control (no augmentation), 2) SCTG, 3) VCMX, and 4) VCMX/PDRN. After 4 months, histomorphometric analysis was performed. Tissue changes were evaluated using superimposed standard tessellation language (STL) files.
RESULTS: Wound dehiscence was found in more than half of the test groups, but secondary wound healing was successfully achieved in all groups. Histomorphometrically, tissue thickness was favored in group SCTG at or above the implant platform level (IP), and group SCTG and the groups with VCMX presented similar tissue thickness below the IP. However, the differences in such thickness among the groups were minor. The keratinized tissue height was greater in group VCMX/PDRN than in groups SCTG and VCMX. Superimposing the STL files revealed a decrease in soft-tissue volume in all groups.
CONCLUSIONS: Wound dehiscence after soft-tissue volume augmentation might be detrimental to obtaining the expected outcomes. PDRN appears not to have a positive effect on the soft-tissue volume gain.

UNASSIGNED: The increasing overuse of antibiotics in recent years has led to antibiotics being the most prescribed drugs for pediatric patients, and 72% of patients in the neonatal intensive care unit are treated with antibiotics. One effect of antibiotic use is the alteration of the microbiota, which is associated with metabolic disorders, including obesity.
UNASSIGNED: This experimental study in newborn rats compared the administration of ampicillin/meropenem (Access/Watch groups) at 100/10 μg/g every 12 h, cefotaxime 200 μg/g every 24 h (Watch group), and amikacin 15 μg/g every 24 h (Access group) versus saline solution as the control. Each antibiotic was adjusted to the required dosages based on weight, and the doses were administered intraperitoneally daily for 5 days to 10-14 newborn male rats per group. A comparison of the morphometric and biochemical parameters registered on day 28 was performed using ANOVA.
UNASSIGNED: Amikacin had the largest effect on morphometric measurements, and low-density lipoprotein cholesterol, while cefotaxime had the largest effect on glucose and triglycerides, whereas ampicillin/meropenem produced the weakest effect on the measured parameters.
UNASSIGNED: The administration of antibiotics in the neonatal stage can affect the body composition of rats as well as the lipid and carbohydrate serum levels. Future studies should evaluate the toxicity of antibiotics in immature neonatal organs and could help to improve therapeutic decisions and prevent the unjustified use of antibiotics in newborns, thereby reducing metabolic consequences.

The primary criteria for diagnosing mild cognitive impairment (MCI) due to Alzheimer\'s Disease (AD) or probable mild AD dementia rely partly on cognitive assessments and the presence of amyloid plaques. Although these criteria exhibit high sensitivity in predicting AD among cognitively impaired patients, their specificity remains limited. Notably, up to 25% of non-demented patients with amyloid plaques may be misdiagnosed with MCI due to AD, when in fact they suffer from a different brain disorder. The introduction of anti-amyloid antibodies complicates this scenario. Physicians must prioritize which amyloid-positive MCI patients receive these treatments, as not all are suitable candidates. Specifically, those with non-AD amyloid pathologies are not primary targets for amyloid-modifying therapies. Consequently, there is an escalating medical necessity for highly specific blood biomarkers that can accurately detect pre-dementia AD, thus optimizing amyloid antibody prescription.
The objective of this study was to evaluate a predictive model based on peripheral biomarkers to identify MCI and mild dementia patients who will develop AD dementia symptoms in cognitively impaired population with high specificity.
Peripheral biomarkers were identified in a gene transfer-based animal model of AD and then validated during a retrospective multi-center clinical study.
Participants from 7 retrospective cohorts (US, EU and Australia).
This study followed 345 cognitively impaired individuals over up to 13 years, including 193 with MCI and 152 with mild dementia, starting from their initial visits. The final diagnoses, established during their last assessments, classified 249 participants as AD patients and 96 as having non-AD brain disorders, based on the specific diagnostic criteria for each disorder subtype. Amyloid status, assessed at baseline, was available for 82.9% of the participants, with 61.9% testing positive for amyloid. Both amyloid-positive and negative individuals were represented in each clinical group. Some of the AD patients had co-morbidities such as metabolic disorders, chronic diseases, or cardiovascular pathologies.
We developed targeted mass spectrometry assays for 81 blood-based biomarkers, encompassing 45 proteins and 36 metabolites previously identified in AAV-AD rats.
We analyzed blood samples from study participants for the 81 biomarkers. The B-HEALED test, a machine learning-based diagnostic tool, was developed to differentiate AD patients, including 123 with Prodromal AD and 126 with mild AD dementia, from 96 individuals with non-AD brain disorders. The model was trained using 70% of the data, selecting relevant biomarkers, calibrating the algorithm, and establishing cutoff values. The remaining 30% served as an external test dataset for blind validation of the predictive accuracy.
Integrating a combination of 19 blood biomarkers and participant age, the B-HEALED model successfully distinguished participants that will develop AD dementia symptoms (82 with Prodromal AD and 83 with AD dementia) from non-AD subjects (71 individuals) with a specificity of 93.0% and sensitivity of 65.4% (AUROC=81.9%, p<0.001) during internal validation. When the amyloid status (derived from CSF or PET scans) and the B-HEALED model were applied in association, with individuals being categorized as AD if they tested positive in both tests, we achieved 100% specificity and 52.8% sensitivity. This performance was consistent in blind external validation, underscoring the model\'s reliability on independent datasets.
The B-HEALED test, utilizing multiomics blood-based biomarkers, demonstrates high predictive specificity in identifying AD patients within the cognitively impaired population, minimizing false positives. When used alongside amyloid screening, it effectively identifies a nearly pure prodromal AD cohort. These results bear significant implications for refining clinical trial inclusion criteria, facilitating drug development and validation, and accurately identifying patients who will benefit the most from disease-modifying AD treatments.