Occurrence of methicillin-resistant Staphylococcus aureus (MRSA) in 'coalho' cheese produced in Brazil.

The experiments reported in this research communication analysed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in 112 samples of 'coalho' cheese, from 56 dairy producing farms in 28 cities in all mesoregions of the State of Ceará, Brazil. To assess antimicrobial resistance we also examined the presence of genes encoding enterotoxins and toxic shock syndrome toxin, as well as the presence of the blaZ gene for ß-lactamases, and resistance to oxacillin. The research found 69 isolates of S. aureus, of which 13.04% had the mecA gene encoding the penicillin-binding protein, which confers resistance to methicillin, in cheese samples from 6 different cities. This included the state capital, Fortaleza, which had the largest prevalence (23.19%) of mecA positive isolates. It was also found that 55.07% of the isolates of S. aureus had the blaZ gene, and 7.25% demonstrated resistance to oxacillin in the plate disc diffusion tests. We did not show the presence of isolates carrying toxigenic genes. The findings suggest that strict supervision of production processes in the dairy industry is necessary in all production scale processes, thus preventing contamination and possible problems for consumers.

Non-Renal Lesions of Uraemia in Domestic Cats.

Uraemia is a clinical syndrome caused by an increase in uraemia-associated toxins in the bloodstream as a consequence of intrinsic kidney or lower urinary tract diseases. Cats seem to be more affected by urinary tract diseases than dogs, particularly considering that chronic kidney disease (CKD) is one of the most important conditions in cats. Considering the lack of information on the systemic lesions of uraemia in cats, the aim of this study was to investigate the prevalence and clinical and pathological aspects of non-renal lesions in uraemic cats, with special attention to the differences between cats and dogs. Cats necropsied between 2000 and 2019 (n = 1,330) were investigated for urinary tract diseases and non-renal lesions of uraemia. The prevalence of uraemic cats with non-renal lesions (n = 78) was 5.8%. Adult, elderly and male animals were predominantly affected. Anorexia, apathy and vomiting were the most common clinical signs and CKD was observed in the majority of uraemic cats. Pulmonary oedema was the most frequent non-renal lesion identified. In contrast with previous reports, haemorrhagic and ulcerative gastritis was frequently observed, whereas soft tissue mineralization and parathyroid hyperplasia were uncommon features. Fibrous osteodystrophy was not observed. Cats with urinary tract diseases did not have as wide a variety of non-renal uraemic lesions as uraemic dogs and multisystemic manifestation of uraemia was observed in only 24.4% of cases.

Sinonasal neoplasms in 49 dogs: clinical, macroscopic, and histopathological aspects / Neoplasmas nasossinusais em 49 cães: aspectos clínicos, macroscópicos e histopatológicos

This study aimed to quantify nasosinusal neoplasms diagnosed in dogs in 20 years (2000-2019) and characterize the main clinical, macroscopic, and histological aspects of these neoplasms. The sex, breed, age, skull conformation, the main clinical signs, and the anatomopathological characteristics (distribution, macroscopy, and histology) were computed. During this period, 49 dogs were affected by neoplasms in these regions, totaling 50 neoplasms (one dog had two neoplasms of different locations and histogenetic origins). Similar amounts of mixed-breed dogs (25/49) and purebred dogs (24/49) were affected, these distributed in 16 breeds. Among purebreds, it was noted that dogs with mesocephalic cranial conformation (12/24) were the most affected, followed by dolichocephalic (10/24) and brachycephalic (2/24). There were 22 cases in males and 27 in females, making a proportion of 1:1.23. There was an age variation from 11 months to 16 years old. The epithelial neoplasms have occurred in older dogs compared to those of other histogenic origins (mesenchymal and other origins/round cells). The main clinical signs were similar between the histogenetic categories, related to the involvement of the upper respiratory tract, sometimes accompanied by nervous signs (when there was brain invasion of nasal neoplasms or vice versa). The possible origin site was mostly in the nasal cavity concerning the paranasal sinuses (and other locations). Invasions occurred in different tissues adjacent to the nasal cavity and paranasal sinuses, resulting in cranial and facial deformities (21/49). The frequency was 48% of epithelial neoplasms, 32% of mesenchymal neoplasms, and 10% of neoplasms with other origins and round cells. The neoplasms most frequently observed, in decreasing order of frequency, were: adenocarcinoma (9/50), squamous cell carcinoma (9/50), transmissible venereal tumor (5/50), osteosarcoma (5/50), chondrosarcoma (4/50), and undifferentiated sarcoma (4/50). Through this study, it was possible to establish the frequency of these neoplasms in 20 years and their clinical, macroscopic, and histological characteristics.(AU)

Este estudo teve como objetivo quantificar os neoplasmas nasossinusais diagnosticados em cães em 20 anos (2000-2019) e caracterizar os principais aspectos clínicos, macroscópicos e histológicos desses neoplasmas. Foram computados sexo, raça, idade, conformação do crânio, principais sinais clínicos e características anatomopatológicas (distribuição, macroscopia e histologia). Nesse período, 49 cães foram acometidos por neoplasmas nessas regiões, totalizando 50 neoplasmas (um cão tinha dois neoplasmas de localização e origens histogenéticas distintas). Foram acometidas quantidades semelhantes de cães sem raça definida (25/49) e de cães com raça definida (24/49), estes distribuídos em 16 raças. Entre os cães com raça definida, notou-se que os cães com conformação craniana mesocefálica (12/24) foram os mais acometidos, seguidos pelos dolicocefálicos (10/24) e braquicefálicos (2/24). Foram observados 22 casos em machos e 27 em fêmeas, perfazendo a relação de 1:1,23. Ocorreu uma variação de idade de 11 meses a 16 anos; tendo os neoplasmas epiteliais ocorrido em cães mais velhos quando comparado aos de outras origens histogênicas (mesenquimais e outras origens/células redondas). Os principais sinais clínicos foram semelhantes entre as categorias histogenéticas, sendo relacionados ao comprometimento do trato respiratório superior, por vezes acompanhados de sinais nervosos (quando houve invasão encefálica de neoplasmas nasais ou vice-versa). O possível local de origem em sua maioria foi na cavidade nasal em relação aos seios nasais (e de outras localizações). Ocorreram invasões para diferentes tecidos adjacentes à cavidade nasal e seios paranasais, tendo como consequência deformidades cranianas e faciais (21/49). A frequência foi de 48% de neoplasmas epiteliais, 32% de neoplasmas mesenquimais e 10% de neoplasmas com outras origens e de células redondas. Os neoplasmas mais frequentemente observados, em ordem decrescente de frequência, foram: adenocarcinoma (9/50), carcinoma de células escamosas (9/50), tumor venéreo transmissível (5/50), osteossarcoma (5/50), condrossarcoma (4/50) e sarcoma indiferenciado (4/50). Com isso, pode-se estabelecer a frequência desses neoplasmas em 20 anos, bem como suas características clínicas, macroscópicas e histológicas.(AU)

Effects of Yoga Respiratory Practice (Bhastrika pranayama) on Anxiety, Affect, and Brain Functional Connectivity and Activity: A Randomized Controlled Trial.

Pranayama refers to a set of yoga breathing exercises. Recent evidence suggests that the practice of pranayama has positive effects on measures of clinical stress and anxiety. This study explored the impact of a Bhastrika pranayama training program on emotion processing, anxiety, and affect. We used a randomized controlled trial design with thirty healthy young adults assessed at baseline and after 4 weeks of pranayama practices. Two functional magnetic resonance imaging (MRI) protocols were used both at baseline and post-intervention: an emotion task as well as a resting-state acquisition. Our results suggest that pranayama significantly decreased states of anxiety and negative affect. The practice of pranayama also modulated the activity of brain regions involved in emotional processing, particularly the amygdala, anterior cingulate, anterior insula, and prefrontal cortex. Resting-state functional MRI (fMRI) showed significantly reduced functional connectivity involving the anterior insula and lateral portions of the prefrontal cortex. Correlation analysis revealed that changes in connectivity between the ventrolateral prefrontal cortex and the right anterior insula were associated with changes in anxiety. Although it should be noted that these analyses were preliminary and exploratory, it provides the first evidence that 4 weeks of B. pranayama significantly reduce the levels of anxiety and negative affect, and that these changes are associated with the modulation of activity and connectivity in brain areas involved in emotion processing, attention, and awareness. The study was registered at https://www.ensaiosclinicos.gov.br/rg/RBR-2gv5c2/(RBR-2gv5c2).

High-quality alternative food reduces cannibalism in the predatory mite Amblyseius herbicolus (Acari: Phytoseiidae).

Predatory mites of the Phytoseiidae family are important biological control agents. Many species of this family are omnivores, i.e., besides on prey, they can feed on plant resources such as nectar and pollen. It has been shown that the addition of alternative food for predators to a crop enhances biological control. However, factors such as food availability and quality can also affect interactions such as cannibalism, and thus influence biological control. We investigated the role of quality of the alternative food in the tendency of Amblyseius herbicolus to engage in cannibalism, a common ecological interaction in many phytoseiid mite species. Cannibalism on eggs by A. herbicolus was significantly reduced in the presence of high-quality food (cattail pollen) compared to egg cannibalism without alternative food, whereas this was not the case in the presence of low-quality food (cotton pollen). This suggests that cattail pollen is a high-quality alternative food, not only because it results in increased development and reproduction of predators, but also because it can minimize cannibalism.

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). CONCLUSIONS: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke.

BACKGROUND: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms. PURPOSE: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session. RESULTS: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI ß-values and increased MEP amplitude post-MT, in the affected hemisphere. CONCLUSION: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.

Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs.

Background: This is the first report demonstrating the antibiotic-modifying activity of cholecalciferol. AIM: In this study, cholecalciferol was evaluated against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. METHODS: The antibacterial and modulatory effects of cholecalciferol, ergosterol, and cholesterol (8-512 µg/mL) were evaluated by microdilution assay against multiresistant bacterial strains. RESULTS: Cholecalciferol, when combined with aminoglycosides, was more effective against P. aeruginosa, reducing the concentration of amikacin and gentamicin necessary to inhibit bacterial growth from 156.25 to 39.06 µg/mL and from 39.06 to 9.76 µg/mL, respectively. It is possible that cholecalciferol, due to its lipid-soluble nature, had a lipophilic interaction with the cell membrane, enhancing antibiotic uptake. Cholesterol and ergosterol were used to see if the mechanism of action of cholecalciferol was similar to that of these lipid compounds. Ergosterol and cholesterol increased aminoglycoside activity, where the effect was greater with higher subinhibitory concentration of sterol. CONCLUSIONS: There is no reported study on the use of cholesterol and ergosterol as modulators of antibiotics or any other drug, making this the first study in this area highlighting the interaction between cholesterol, ergosterol, and cholecalciferol with regard to modifying aminoglycoside activity.

Menadione (vitamin K) enhances the antibiotic activity of drugs by cell membrane permeabilization mechanism.

Menadione, vitamin K3, belongs to the class of lipid-soluble vitamins and lipophilic substances as menadione cause disturbances in the bacterial membrane, resulting in damage to the fundamental elements for the integrity of the membrane, thus allowing increased permeability. Accordingly, the aim of this study was to evaluate in vitro the antibiotic-modifying activity of menadione in multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, with a gradual increase in its subinhibitory concentration. In addition, menadione was compared with cholesterol and ergosterol for similarity in mechanism of drug modulatory action. Antibiotic-modifying activity and antibacterial effect were determined by the broth microdilution assay. Menadione, cholesterol and ergosterol showed modulatory activity at clinically relevant concentrations, characterizing them as modifiers of bacterial drug resistance, since they lowered the MIC of the antibiotics tested. This is the first report of the antibacterial activity of menadione and its potentiation of aminoglycosides against multiresistant bacteria.

Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study.

Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS.

Evaluation of the biocompatibility of regenerated cellulose hydrogels with high strength and transparency for ocular applications.

Prompt emergency treatment for ocular injury, particularly in a battlefield setting, is essential to preserve vision, reduce pain, and prevent secondary infection. A bandage contact lens that could be applied in the field, at the time of injury, would protect the injured ocular surface until hospital treatment is available. Cellulose, a natural polymer, is widely used in biomedical applications including bandage materials. Hydrogels synthesized from different cellulose sources, such as plants, cotton, and bacteria, can have the optical transparency and mechanical strength of contact lenses, by tailoring synthesis parameters. Thus, we optimized the fabrication of cellulose-based hydrogels and evaluated their in vivo biocompatibility and related physical properties. Our data demonstrate that along with tailorable physical properties, our novel cellulose-based hydrogels could be made with contact lens geometry, exhibit no significant signs of material toxicity after 22 days of in vivo testing, and show significant promise for use as a corneal bandage immediately following ocular trauma.

Regeneration of corneal epithelium utilizing a collagen vitrigel membrane in rabbit models for corneal stromal wound and limbal stem cell deficiency.

PURPOSE: This study was performed to evaluate the potential of a collagen-based membrane, collagen vitrigel (CV), for reconstructing corneal epithelium in the stromal wound and limbal stem cell deficiency (LSCD) models. METHODS: Three groups of rabbits were used in the stromal wound model: CV affixed using fibrin glue (CV + FG group, n = 9), fibrin glue only (FG group, n = 3) and an untreated control group (n = 3). In the LSCD model, one group received CV containing human limbal epithelial cells (CV + hLEC group, n = 2) and the other was an untreated control (n = 1). Gross observation, including fluorescent staining, pathological examination, immunohistochemistry and electron microscopy, was used to evaluate the effect of CV on the corneal epithelium. RESULTS: In the stromal wound model, fluorescent staining showed that epithelial reconstruction occurred as rapidly in the CV + FG group as it did in the control group. The pathological examination proved that the CV supported a healthy corneal epithelium in the CV + FG group, whereas FG led to hypertrophy and inappropriate differentiation of corneal epithelium in the FG group. In the LSCD model, the corneas in the CV + hLEC group showed sustained tissue transparency with good epithelialization, low inflammatory response and reduced neovascularization. However, the control cornea was translucent and showed high amounts of inflammation and neovascularization. CONCLUSION: We have demonstrated that CV supports corneal epithelial differentiation and prevents epithelial hypertrophy, in addition to serving as a scaffold for hLEC transplantation, without complications.

Application of a collagen-based membrane and chondroitin sulfate-based hydrogel adhesive for the potential repair of severe ocular surface injuries.

This study was performed to evaluate the potential of a chondroitin sulfate-polyethylene glycol (CS-PEG) adhesive and collagen-based membrane (collagen vitrigel, CV) combination as a method to treat penetrating ocular injuries on the battlefield and to improve this method with two technologies: an antibiotic releasing CS-PEG adhesive and a corneal shaped CV. Burst testing using porcine cadaveric eyes, high-performance liquid chromatography, the Kirby-Bauer bacterial inhibition test, and CV implantations on the live and cadaveric rabbit eyes were performed. The ocular burst test showed CS-PEG adhesive could successfully repair 5-mm to 6-mm length wounds in the corneal and corneoscleral regions but would require CS-PEG + CV to treat larger wounds similar to those seen on the battlefield. In addition, high performance liquid chromatography and the Kirby-Bauer bacterial inhibition test presented evidence suggesting the vancomycin incorporated CS-PEG could inhibit Staphylococcus infection for 9 days. Furthermore, the curved CV showed an advantage by matching the corneal contour without any wrinkle formation. Although this pilot study showed a limited range of possible applications, we demonstrated that the combination of CS-PEG adhesive + CV is a promising method and the 2 technologies improve their applicability to the special demands of the battlefield.

Modulation of keratocyte phenotype by collagen fibril nanoarchitecture in membranes for corneal repair.

Type I collagen membranes with tailored fibril nanoarchitectures were fabricated through a vitrification processing, which mimicked, to a degree, the collagen maturation process of corneal stromal extracellular matrix in vivo. Vitrification was performed at a controlled temperature of either 5 °C or 39 °C at a constant relative humidity of 40% for various time periods from 0.5 wk up to 8 wk. During vitrification, the vitrified collagen membranes (collagen vitrigels, CVs) exhibited a rapid growth in fibrillar density through the evaporation of water and an increase in fibrillar stiffness due to the formation of new and/or more-stable interactions. On the other hand, the collagen fibrils in CVs maintained their D-periodicity and showed no significant difference in fibrillar diameter, indicating preservation of the native states of the collagen fibrils during vitrification. Keratocyte phenotype was maintained on CVs to varying degrees that were strongly influenced by the collagen fibril nanoarchitectures. Specifically, the vitrification time of CVs mainly governed the keratocyte morphology, showing significant increases in the cell protrusion number, protrusion length, and cell size along with CV vitrification time. The CV vitrification temperature affected the regulation of keratocyte fibroblasts' gene expressions, including keratocan and aldehyde dehydrogenase (ALDH), demonstrating a unique way to control the expression of specific genes in vitro.

The ex vivo production of IL-6 and IL-21 by CD4+ T cells is directly associated with neurological disability in neuromyelitis optica patients.

Neuromyelitis optica (NMO), also known as Devic's disease, is an autoimmune, inflammatory disorder of the central nervous system (CNS) in which the immune system attacks myelin of the neurons located at the optic nerves and spinal cord, thus producing a simultaneous or sequential optic neuritis and myelitis. The objective of this study was evaluated the background T-cell function of patients suffering from neuromyelitis optica (NMO), an autoimmune disorder of the central nervous system. In our study, the in vitro T cell proliferation and the production of Th1 cytokines were significantly lower in cell cultures from NMO patients, as compared with healthy individuals. In contrast, a dominant Th17-like phenotype, associate with higher IL-23 and IL-6 production by LPS-activated monocytes, was observed among NMO patients. The release of IL-21 and IL-6 by polyclonally activated CD4+ T cells was directly correlated to neurological disability. In addition, the in vitro release of IL-21, IL-6 and IL-17 was significantly more resistant to glucocorticoid inhibition in NMO patients. In conclusion, the results indicate dominant Th17-related response in NMO patients that was directly proportional to neurological disability. Furthermore, our results can help to explain why NMO patients trend to be more refractory to corticoid treatment.

The impact of pregnancy on the HIV-1-specific T cell function in infected pregnant women.

Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.

High IL-10 production by aged AIDS patients is related to high frequency of Tr-1 phenotype and low in vitro viral replication.

This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1ß by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.

Method for obtaining simple shear material properties of the intervertebral disc under high strain rates.

Predicting spinal injury under high rates of vertical loading is of interest, but the success of computational models in modeling this type of loading scenario is highly dependent on the material models employed. Understanding the response of these biological materials at high strain rates is critical to accurately model mechanical response of tissue and predict injury. While data exists at lower strain rates, there is a lack of the high strain rate material data that are needed to develop constitutive models. The Split Hopkinson Pressure Bar (SHPB) has been used for many years to obtain properties of various materials at high strain rates. However, this apparatus has mainly been used for characterizing metals and ceramics and is difficult to apply to softer materials such as biological tissue. Recently, studies have shown that modifications to the traditional SHPB setup allow for the successful characterization of mechanical properties of biological materials at strain rates and peak strain values that exceed alternate soft tissue testing techniques. In this paper, the previously-reported modified SHPB technique is applied to characterize human intervertebral disc material under simple shear. The strain rates achieved range from 5 to 250 strain s-1. The results demonstrate the sensitivity to the disc composition and structure, with the nucleus pulposus and annulus fibrosus exhibiting different behavior under shear loading. Shear tangent moduli are approximated at varying strain levels from 5 to 20% strain. This data and technique facilitates determination of mechanical properties of intervertebral disc materials under shear loading, for eventual use in constitutive models.

Structure and properties of collagen vitrigel membranes for ocular repair and regeneration applications.

The frequency of ocular injuries on the battlefield has been steadily increasing during recent conflicts. Combat-related eye injuries are difficult to treat and solutions requiring donor tissue are not ideal and are often not readily available. Collagen vitrigels have previously been developed for corneal reconstruction, but increased transparency and mechanical strength are desired for improved vision and ease of handling. In this study, by systematically varying vitrification temperature, relative humidity and time, the collagen vitrigel synthesis conditions were optimized to yield the best combination of high transparency and high mechanical strength. Optical, mechanical, and thermal properties were characterized for each set of conditions to evaluate the effects of the vitrification parameters on material properties. Changes in denaturing temperature and collagen fibril morphology were evaluated to correlate properties with structure. Collagen vitrigels with transmittance up to 90%, tensile strength up to 12 MPa, and denaturing temperatures that significantly exceed the eye/body temperature have been synthesized at 40 °C and 40% relative humidity for one week. This optimal set of conditions enabled improvements of 100% in tensile strength and 11% in transmittance, compared to the previously developed collagen vitrigels.

Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.

Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 µm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye.