Guided bone regeneration (GBR) is a widely used clinical approach for managing bone defects associated with periodontal disease in dogs, employing barrier membranes to selectively direct tissue regeneration. The performance of these membranes is influenced by composition, structural design, and degradation behavior, which together determine biological responses and clinical outcomes. Biodegradable GBR membranes, fabricated from natural polymers, synthetic polymers, or composite materials, offer advantages over non-biodegradable membranes, including controlled resorption, elimination of secondary surgery, and the potential for delivery of bioactive agents. Preclinical studies in dogs have demonstrated that GBR membranes can promote periodontal regeneration, including bone and cementum formation and space maintenance; however, optimization of degradation behavior remains critical to align membrane resorption with tissue healing in some cases. Clinical studies in dogs with naturally occurring periodontal disease remain scarce, and only two biodegradable membranes (Ossiflex® and Doxirobe®) are commercially approved for veterinary use, while all others are applied off-label. These limitations highlight the need for more adaptable and cost-effective regenerative strategies, including membranes that can be customized to different defect sizes and multifunctional membranes incorporating bioactive agents that will offer an advanced regenerative potential and improved predictability in veterinary periodontal therapy.

Municipal animal shelters play a crucial role in rescuing abandoned animals, managing free-roaming populations, and promoting animal welfare. This seven-year retrospective study analyzed 2291 animals (1132 dogs, 1159 cats) admitted to a Portuguese municipal shelter (CVM Feira) between 2018 and 2024 to identify predictors of live outcomes. Descriptive and regression analyses were performed on 1325 adoptable animals. Adoption occurred for 58.9% of these animals, while 41.1% remained in long-term housing, reflecting growing shelter capacity pressures. Length of Stay (LOS) was the strongest predictor of adoption, with extended stays markedly reducing adoption odds and contributing to overcrowding. For dogs, female sex and owner or animal protection association (APA) surrender increased adoption likelihood. Microchipped animals were 71 times more likely to be returned to their owners, although only a small proportion entered the shelter with identification. The overall Live Release Rate (LRR) was 79.7% and Save Rate (SR) 84.7%, highlighting effective life-saving efforts, while the Population Balance Calculation (PBC) of 75.6% revealed challenges in population flow-through. These findings provide evidence that data-driven strategies, including reducing LOS, enforcing microchipping, and applying species-specific management, are essential to optimize municipal shelter operations and improve animal welfare, with insights applicable to broader European and international contexts.

Chronic wounds represent a significant global healthcare burden due to the limited effectiveness of current therapeutic strategies. To address this critical need, we developed 3D-printed regenerative wound dressings that can be customized with antimicrobial drugs tailored to individual patient requirements. A novel semisolid extrusion ink combining the biocompatibility and printing properties of alginate (Alg) with the regenerative properties of zinc oxide (ZnO) and hydroxypropyl cellulose (HPC) was produced. Two types of dressings were successfully printed by varying the concentrations of ZnO and HPC: ZnO:HPC at 11:10 and 20:20 % (w/v). Both inks presented an adequate rheological shear-thinning behavior, resulting in wound dressings with a stable matrix structure. Moreover, to grant antimicrobial and antibiofilm activity, an octenidine (OCT)-hydrogel was loaded into the dressing's macropores. The unloaded dressings with ZnO at 20 % (w/v) and all the OCT-loaded dressings presented antibiofilm activity, showing a biofilm reduction of ∼ 75 % against S. aureus. In vitro cellular assays indicated that the unloaded dressings provided regenerative potential by showing wound closure approximately completed in 48 h, highlighting the regenerative potential of the Alg:ZnO:HPC ink. These dressings exhibited in vitro and in vivo cytocompatibility, along with regenerative potential evidenced by collagen deposition and rapid wound closure. OCT-loaded matrices retained the regenerative potential and biocompatibility of the unloaded dressings, supporting their suitability as a platform for advanced wound management.

Current sperm sexing methods are costly and largely restricted to cattle, while immunological techniques targeting sex-specific membrane proteins may offer more economical alternatives. To advance these methods, understanding the proteomic differences between the cell membranes of X- and Y-chromosome-bearing spermatozoa is essential. This study aimed to characterize the cell surface proteome of bovine sperm and identify potential targets for sperm sexing through LC-MS/MS analysis. Cell surface protein lysates were extracted from unsexed, X-sperm (BX), and Y-sperm (BY) samples via biotinylation. Promising targets were identified through functional annotation (UniProt, eggNOG-mapper v.2.1.7) and topology prediction (DeepTMHMM v.1.0.13). Additionally, statistical overrepresentation (PANTHER 18.0) and orthology analyses were performed. Excluding contaminants, 130 proteins were detected, of which 64 proteins were detected in the BX samples and not in the BY samples. Of these, five transmembrane proteins stood out as potential X-sperm targets (ADAM2, ATP11C, DG1, MCT1, and PMCA4). They were identified as potential cell surface targets, based on GO terms and topology predictions, detected in at least two replicates of the BX samples, and shown to share orthology with other livestock species. These findings enhance our understanding of bovine sperm proteomics; however, further validation is required to confirm the utility of these five proteins in sperm sexing technologies.

Periodontal disease in dogs leads to progressive bone loss and adversely impacts overall health. However, cost-effective regenerative strategies are still limited in veterinary practice. This study aimed to develop and evaluate a novel tannic acid (TA)–gelatin-based hydrogel (Gel), incorporating graphene oxide (GO) and hydroxyapatite nanoparticles (HA), as a potential barrier material for guided tissue regeneration (GTR) applications. The hydrogels—Gel, Gel-GO, Gel-HA, and Gel-GO-HA—were characterized for chemical structure, molecular interactions, surface morphology, nanoparticle dispersion, and tensile strength. Cytotoxicity was assessed using L929 fibroblasts (ISO 10993-5), while cell viability/proliferation, morphology, and alkaline phosphatase (ALP) production were evaluated using canine periodontal ligament-derived cells. Results show that crosslinking with tannic acid enhanced the incorporation of graphene oxide and hydroxyapatite nanoparticles via hydrogen bonding into TA–gelatin-based hydrogels. This combination increased surface roughness, reduced degradation rate, and enabled shape memory behavior, critical for guided tissue regeneration (GTR) membranes. The extracts from Gel-HA-GO showed that cytotoxicity was both time- and concentration-dependent in L929 fibroblasts, whereas enhanced cell proliferation and increased ALP production were observed in cultures derived from canine periodontal ligament cells. These findings suggest that TA–gelatin-based hydrogels incorporating GO and HA demonstrated favorable mechanical and physicochemical properties, biocompatibility, and osteogenic potential. These attributes suggest their viability as a promising composite for the development of innovative GTR strategies to address periodontal tissue loss in veterinary medicine.

Stifle joint diseases present a significant challenge in companion animals that often lead to hind limb lameness, with osteoarthritis being a prevalent degenerative condition causing pain and reduced mobility. Regenerative medicine offers a promising avenue for improving treatment outcomes, with a range of emerging therapies showing potential to alleviate symptoms and promote joint health. Among these, hyaluronic acid and platelet-rich plasma have been widely used as intra-articular treatments to enhance joint lubrication, reduce inflammation, and provide symptomatic relief. Interleukin-1 receptor antagonist protein, autologous conditioned serum, and autologous protein solution represent the next generation of regenerative therapies, offering more disease-modifying effects by inhibiting key mediators of joint inflammation. More recently, the MSC-derived secretome has emerged as an innovative, cell-free approach that leverages the diverse bioactive factors secreted by MSCs to support tissue repair and modulate inflammation. This review highlights the evidence base behind these non-cellular orthobiologic treatments for stifle joint disease, aiming to inform veterinary practitioners and owners about available options and their efficacy in supporting conventional treatments.

Objective: Investigate the effect of bilateral ultrasound-guided quadratus lumborum block (QLB) in the need for additional opioid administration in response to intraoperative nociception during ovariectomy in cats. Methods: Thirty-six feral cats were randomly allocated to group control (C) or group QLB with 0.4 mL kg−1 of 0.25% bupivacaine per hemiabdomen. Hemodynamic data were collected at five intraoperative time points. A 20% increase in pulse rate or respiratory rate was treated with fentanyl. Results: Pulse rate and respiratory rate were higher in the C group compared to the QLB group during ovarian manipulation. No differences in systolic and mean arterial pressure and hypotension were comparable in both groups. The QLB group required less administration of intraoperative fentanyl than the C group at 4/16 and 10/16, respectively (p < 0.05). Conclusions: The bilateral QLB with bupivacaine led to a reduction in opioid consumption in feral cats undergoing elective ovariectomy.

Canine hip dysplasia (CHD) screening relies on radiographic assessment, but traditional scoring methods often lack consistency due to inter-rater variability. This study presents an AI-driven system for automated measurement of the femoral head center to dorsal acetabular edge (FHC/DAE) distance, a key metric in CHD evaluation. Unlike most AI models that directly classify CHD severity using convolutional neural networks, this system provides an interpretable, measurement-based output to support a more transparent evaluation. The system combines a keypoint regression model for femoral head center localization with a U-Net-based segmentation model for acetabular edge delineation. It was trained on 7967 images for hip joint detection, 571 for keypoints, and 624 for acetabulum segmentation, all from ventrodorsal hip-extended radiographs. On a test set of 70 images, the keypoint model achieved high precision (Euclidean Distance = 0.055 mm; Mean Absolute Error = 0.0034 mm; Mean Squared Error = 2.52 × 10−5 mm2), while the segmentation model showed strong performance (Dice Score = 0.96; Intersection over Union = 0.92). Comparison with expert annotations demonstrated strong agreement (Intraclass Correlation Coefficients = 0.97 and 0.93; Weighted Kappa = 0.86 and 0.79; Standard Error of Measurement = 0.92 to 1.34 mm). By automating anatomical landmark detection, the system enhances standardization, reproducibility, and interpretability in CHD radiographic assessment. Its strong alignment with expert evaluations supports its integration into CHD screening workflows for more objective and efficient diagnosis and CHD scoring.

Cell surface proteins, targeted by approximately 70 % of current pharmaceuticals, offer promising prospects for therapeutic and biotechnological advancements. The recent identification of cell surface proteins, differentially expressed by rabbit spermatozoa, could support technologies to enable sperm sex selection. However, a more detailed knowledge of the rabbit sperm plasma membrane proteome is crucial to such developments. Hence, the primary objective of this study was to conduct a shotgun proteomic (LC-MS/MS) analysis of New Zealand White rabbit spermatozoa protein lysates enriched in cell surface proteins isolated through biotinylation. This approach was designed to provide an overall characterization of this proteome and so determine an expanded list of protein candidates with potential for rabbit sperm sexing. The most promising targets were identified through functional annotation (UniProt and eggNOG-mapper v.2.1.9) and topology prediction (DeepTMHMM v.1.0.13). Additionally, a statistical overrepresentation test (PANTHER 18.0) and analysis of protein-protein interactions (STRING v.12.0) were conducted. Among the 859 detected proteins, 803 had Gene Ontology information, with 574 predicted as globular proteins, 152 as transmembrane proteins, and 133 possessing only a signal peptide. The combined data identified 107 proteins as potential cell surface targets, including three transmembrane proteins encoded by the X chromosome (ADGRG2, ATP6AP2, and VSIG1). Furthermore, two proteins (BCAP31 and PGRMC1), previously identified as putative rabbit X-targets, were recognized. This study enhances our comprehension of rabbit spermatozoa proteomics. Further validation of the utility of these five proteins to differentiate between X- and Y-sperm will determine their suitability for integration into sperm sexing technologies.

The clinical use of topical hemostatic agents has become increasingly widespread. While these agents primarily serve to control bleeding, their direct contact with bone and surrounding tissues raises concerns about biological compatibility and potential interference with bone healing and regeneration. Given their growing use in osseous surgical procedures, it is critical to characterize and compare the osteogenic properties of these materials. This study evaluated four commercially available gelatin-based hemostatic sponges: Hemospon®, Clinix®, Gelatamp®, and Octocolagen®, for their osteogenic potential. Leachables derived from each sponge were prepared according to ISO 10993-12:2021 guidelines and tested at 12.5% and 50% concentrations inin vitroassays using human osteoblastic populations. Assessed parameters included metabolic activity, proliferation, osteogenic gene expression, alkaline phosphatase (ALP) activity, and extracellular matrix production. Additionally, intact sponges were directly applied to bone defects in anex vivoorganotypic bone culture model, enabling the tissue characterization within a physiologically relevant environment. Results demonstrated marked material-dependent differences. Gelatamp® significantly enhanced osteogenic gene expression, ALP activity, and matrix productionin vitro, and promoted mature collagen depositionex vivo. Hemospon® also showed favorable, though more limited, effects. Octocolagen® exhibited a neutral biologically profile, while Clinix® consistently impaired osteoblastic activity, gene expression, and extracellular matrix formation in both models. These findings demonstrate that gelatin-based hemostatic agents are not biologically equivalent. Material composition and processing influence their regenerative performance, underscoring the need for informed selection when used in bone-contact surgical applications.

IntroductionThe olfactory system acts as an interface between the environment and the brain. Its direct neural connection makes it a target for xenobiotics and a suitable model for studying olfactory dysfunction and related neurotoxic effects. This study aimed to characterize an animal model of olfactory dysfunction induced by nose-to-brain (NTB) delivery of vanadium pentoxide (V2O5).MethodsRats received 182 or 273 μg intranasally, thrice weekly over 4 weeks, followed by behavioral, histological, and biochemical analysis of the olfactory epithelium (OE), olfactory bulbs (OBs), and hippocampus.ResultsBehavioral tests showed significant olfactory deficits, longer latencies, and reduced investigation times in exposed groups. Histological analysis revealed coagulative necrosis in the OE, disrupted cellular organization, reduced number and size of OB glomeruli, and hippocampal neuronal loss with gliosis. Immunohistochemistry revealed increased proliferating cell nuclear antigen (PCNA) expression in the OE, dopaminergic neuron loss and astroglial proliferation in the OB, and hippocampal astroglial proliferation at the highest dose. Myelin basic protein (MBP) expression remained unchanged. Oxidative stress markers were largely unaltered, except for increased superoxide dismutase (SOD) in OBs and glutathione S-transferase (GST) in the hippocampus, especially at the high dose.DiscussionThe results reveal dose-dependent vanadium-induced neurotoxicity in the olfactory system. The higher dose induced pronounced structural damage, neuroinflammation, and oxidative stress, resulting in olfactory and cognitive impairments relevant to advanced olfactory dysfunction and neurodegeneration. The lower dose induced milder yet significant effects, supporting its use in early-stage dysfunction studies. This NTB-based model offers a valuable tool for investigating olfactory dysfunction mechanisms in toxicological and neurodegenerative contexts.

Hip dysplasia (HD) is a prevalent disease in medium- to large-breed dogs, characterized by joint laxity and degenerative joint changes. The early diagnosis of HD poses significant challenges, as radiographic imaging often identifies the disease only in advanced stages. Conversely, ultrasonography, a non-invasive and cost-effective imaging modality, offers the potential for earlier detection by evaluating the surrounding soft tissues and synovial changes. This study aimed to assess the relationship between the ventral hip ultrasonographic findings, and hip joint laxity evaluated through stress radiographs on 22 young Estrela Mountain dogs (n = 44 hips) aged 4 to 8 months. Key ultrasound measurements included synovial fluid in the cranial femoral neck recess (CFNR) and capsular-synovial fold thickness (CFT). Radiographic laxity was estimated by measuring the distraction index (DI). The median (quartile 25-75%) of the CFNR area, CFT, and DI were 44.00 (27.00-52.25) mm2, 3.10 (2.68-3.55) mm, and 0.38 (0.34-0.40), respectively. The Spearman correlation coefficient was statistically significant between all of these variables (p < 0.05). The ventral ultrasonographic approach to the hip joint revealed potential, considering the early diagnosis of HD in dogs, by showing relationships between changes in periarticular soft tissues and joint laxity. Further studies are needed to associate ultrasonographic findings with radiographic signs of HD and related clinical signs in dogs.

Hip dysplasia (HD) is an arthropathy with an incompletely understood pathophysiology. Existing induction HD models fall short of providing feasible data to test new therapeutic strategies. This study aimed to characterize and validate a new surgical model of HD in rabbits. Seventeen 6-week-old male New Zealand white rabbits were randomly assigned to 3 groups: GI (n = 3) - control group, with six normal hips (NH); GII (n = 7) - seven left instability surgery hips (ISH) and seven right surgery sham hips (SSH); GIII (n = 7) - seven left instability surgery hips, followed by hindlimb bandage immobilization for 3 days (ISHI) and seven right hips without surgery (HWS). The instability surgery was performed by sectioning the teres ligament and the sham by accessing the capsule without its section. After 14 weeks following the induction surgery, the rabbits underwent radiographic and computed tomographic studies and histopathological characterization of the hip joint based on the severity of cartilage structure and chondrocyte pathology. In the imaging assessment, the ISHI group was the only group presenting statistically significant differences in all four parameters, consistent with HD development (P < 0.05). In the histopathologic evaluation, the ISHI group showed a higher severity of cartilage damage and chondrocyte pathology with statistically significant differences when compared with the NH group (P < 0.05). As a result, the proposed rabbit model can be recommended for HD studies aiming to test therapeutic responses to osteoarthritis in vivo, representing a valuable tool in veterinary research fields.

Canine hip dysplasia (CHD) is a common orthopedic condition characterized by joint laxity, abnormal femoral head development, and osteoarthritis. Radiography remains the gold standard in diagnosis; however, ultrasonography (US) can detect changes in bone and periarticular soft tissue earlier in CHD progression. Forty-four hips from twenty-two adult dogs of various breeds were graded according to the Fédération Cynologique Internationale (FCI) grading system, and grouped as normal (A, B) or dysplastic (C, D, E). Canine hip US evaluation, using the ventral femoral head–neck approach, included the following: capsule thickness at the femoral head index (CTFHi) and capsule thickness at the femoral head–neck index (CTFHNi), both measured in mm/body weight × 100; femoral head shape score (FHSs) and femoral head–neck transition score (FHNTs); and osteophyte score (Os). These findings were evaluated qualitatively and then converted into numerical scores. Twenty-three hips were graded on the FCI system as being normal, and twenty-one as dysplastic. Median values of the US parameters CTFHi, CTFHNi, FHSs, FHNTs, and Os were 2.02, 7.79, 1.00, 1.00, and 0.00 in the normal-hips group, and 3.11, 9.32, 3.00, 2.00, and 1.00 in the dysplastic-hips group. Significant differences were observed between most US parameters evaluated. Strong associations were found between CTFHi, FHNTs, and Os, indicating progressive bone remodeling. These findings support US usage as a potential tool for CHD diagnosis and monitoring.

Radiographic canine hip dysplasia (CHD) diagnosis is crucial for breeding selection and disease management, delaying progression and alleviating the associated pain. Radiography is the primary imaging modality for CHD diagnosis, and visual assessment of radiographic features is sometimes used for accurate diagnosis. Specifically, alterations in femoral neck shape are crucial radiographic signs, with existing literature suggesting that dysplastic hips have a greater femoral neck thickness (FNT). In this study we aimed to develop a three-stage deep learning-based system that can automatically identify and quantify a femoral neck thickness index (FNTi) as a key metric to improve CHD diagnosis. Our system trained a keypoint detection model and a segmentation model to determine landmark and boundary coordinates of the femur and acetabulum, respectively. We then executed a series of mathematical operations to calculate the FNTi. The keypoint detection model achieved a mean absolute error (MAE) of 0.013 during training, while the femur segmentation results achieved a dice score (DS) of 0.978. Our three-stage deep learning-based system achieved an intraclass correlation coefficient of 0.86 (95

Background: The monitoring of nociception/antinociception poses a significant challenge during anesthesia, making the incorporation of new tools like the Parasympathetic Tone Activity (PTA) monitor an added value in feline anesthesia. Objectives: To compare the effectiveness and speed of PTA monitoring when compared to heart rate (HR) in detecting surgical stimuli (SS) during the intraoperative period in 49 female cats undergoing ovariectomy (OV). Methods: Instantaneous Parasympathetic Tone Activity (PTAi) values, HR, fR, and non-invasive SAP and MAP were continuously monitored and systematically assessed. The time required for HR (HR time) and PTAi (PTAi time) to reach their minimum peak values following each surgical stimulus was collected at five points for each anaesthetized cat. Each collected surgical stimulus was categorized into 3 groups for statistical analysis: no nociception detection, no hemodynamic reaction and a PTAi > 50 (Nhre); no hemodynamic reaction and a PTAi < 50 (Nhre < 50); and hemodynamic reaction and PTAi < 50 (Hre < 50). Results: PTAi response demonstrated effectiveness in detecting nociception compared to HR. The SS were categorized as 36.1% in the Nhre group, 50% in the Nhre < 50 group, and only 13.9% in the Hre < 50 group. In the Hre < 50 group, PTAi time and HR time had similar speeds in detecting the SS (p = 0.821); however, PTA time was significantly slower in the Nhre < 50 group when compared to the Hre < 50 group (p = 0.001). Conclusions: PTA monitoring may be a useful tool to complement HR monitoring for detecting nociception. PTA monitoring demonstrated a superior diagnostic value compared to HR for detecting nociception in cats undergoing OV and a similar speed to HR in detecting SS when HR increases above 20%. Future studies are needed to understand in a clinical setting the meaning of sympathetic activation/nociception detected using the PTA monitor when the HR increase is not clinically relevant.

Developmental toxicology is a constantly evolving research field which needs to attend to a complex underlying regulatory network. In order to ensure human health and environmental safety, new substances have to be tested for toxic effects on reproduction and development, before being commercialized. Traditional in vivo mammalian models represent the intricacy of human development and provide more adequately an assessment of the interaction of chemical compounds with the reproductive system. However, in the last years, the directives are to reduce the use of vertebrate animals, promoting their use only as a last resort. Consequently, the interest on the development and validation of alternative tests, able to cover the various aspects of the reproductive cycle, has significantly increased. Reproductive toxicity is probably the most difficult endpoint to be replaced by alternative assays, since it should provide information on mechanism interactions essential for female and male fertility and also knowledge on the animal development during the first phases of its life cycle. This complexity explains the slow progress in implementing alternative models for reproductive toxicity safety assays. Alternative test models may be based on in vitro systems and nonmammalian animal models. Many biological processes have been successfully addressed using in vitro models, opening the possibility to study the interference of teratogenic compounds. Their validation and implementation have lagged behind, in part because of difficulties in establishing their predictability. Nevertheless, the advance toward the process of validation is crucial to replace and reduce the use of living animals. Based on the present state of the art, it is not probable that such testing strategies will completely replace the need to assess reproductive toxicity in vivo in the near future, but they will contribute to reduce animal tests and will provide important information. In this chapter, the approved guidelines for standard methods and alternative methods, according to their regulatory and scientific status, are enumerated and briefly described.

The intranasal route enables direct delivery of multiple substances from the nose to the brain, through olfactory and trigeminal pathways, bypassing the blood–brain barrier and avoiding systemic absorption. Despite the potential of this route, the various administration approaches make data reproducibility and interpretation challenging, emphasizing the necessity to establish a consistent methodology. Considering this, the aim of our study was to assess and compare the distribution of two dye volumes (30 µl and 50 µl) in the nasal cavity of rat cadavers. We employed three distinct methods of intranasal delivery: nose drops, by pipette tip, or cannula inserted into the nasal cavity. The results indicated that for both volumes, using the nose drops and the pipette tip methods, the dye dispersion occurred mainly in the vestibule, respiratory and olfactory regions, without reaching the olfactory bulbs. Using the cannula method, the deposition predominantly occurred in the respiratory and olfactory regions, with the dye reaching 66.7% and 100% of the olfactory bulbs, respectively, to low and high volume. Furthermore, the results demonstrated differences between the two volumes, in the pharynx, larynx, trachea, septal window, and incisive papilla, where an increased dye presence was observed with the 50 µl instillation across all three methods. According to our results, the intranasal delivery with a cannula was the most effective method for dye deposition in the olfactory region. However, further studies in live animals will be necessary to determine and refine the administration method that consistently allows specific deposition in the olfactory system.

Radiography is the primary modality for diagnosing canine hip dysplasia (CHD), with visual assessment of radiographic features sometimes used for accurate diagnosis. However, these features typically constitute small regions of interest (ROI) within the overall image, yet they hold vital diagnostic information and are crucial for pathological analysis. Consequently, automated detection of ROIs becomes a critical preprocessing step in classification or segmentation systems. By correctly extracting the ROIs, the efficiency of retrieval and identification of pathological signs can be significantly improved. In this research study, we employed the most recent iteration of the YOLO (version 8) model to detect hip joints in a dataset of 133 pelvic radiographs. The best-performing model achieved a mean average precision (mAP50:95) of 0.81, indicating highly accurate detection of hip regions. Importantly, this model displayed feasibility for training on a relatively small dataset and exhibited promising potential for various medical applications.