Untreated Research Articles

Early donepezil monotherapy or combination with metoprolol significantly prevents subsequent chronic heart failure in rats with reperfused myocardial infarction

Despite the presence of clinical guidelines recommending that β-blocker treatment be initiated early after reperfused myocardial infarction (RMI), acute myocardial infarction remains a leading cause of chronic heart failure (CHF). In this study, we compared the effects of donepezil, metoprolol, and their combination on the progression of cardiac remodeling in rats with RMI. The animals were randomly assigned to untreated (UT), donepezil-treated (DT), metoprolol-treated (MT), and a combination of donepezil and metoprolol (DMT) groups. On day 8 after surgery, compared to the UT, the DT and DMT significantly improved myocardial salvage, owing to the suppression of macrophage infiltration and apoptosis. After the 10-week treatment, the DT and DMT exhibited decreased heart rate, reduced myocardial infarct size, attenuated cardiac dysfunction, and decreased plasma levels of brain natriuretic peptide and catecholamine, thereby preventing subsequent CHF. These results suggest that donepezil monotherapy or combined therapy with β-blocker may be an alternative pharmacotherapy post-RMI.

Study on impact of parboiled rice mill effluents on biochemical constituents of Labeo rohita (Hamilton 1822)

The parboiled rice mill effluents (PRME) are among the major contributors of chemical pollutants that enter into various aquatic bodies and affect the aquatic biota, accounting for several types of chemicals released in the nearby areas. The present investigation (2021-22), fingerlings of Labeo rohita was exposed to acute (96 hrs) and chronic (30 days) dose of parboiled rice mill effluents (PRME). The PRME collected from the parboiled rice mills were analyzed for Physico-chemical parameters and chronic and acute toxicity tests in Labeo rohita fish. The results showed that the severity in the Physico-chemical parameters and toxicity levels cause moderate to massive destruction in gills, liver and muscle, which is concentration and time-dependent. In acute toxicity experiments (96hrs) the fingerlings of fresh water fish Labeo rohita was exposed to different concentrations of (12.5%, 25%, 50%, 75% and 100%) parboiled rice mill effluents. The LC50 value for various exposure times was determined and analyzed by using Finney probit method. The value of LC50 of untreated (UT) parboiled rice mill effluents after 96hrs was calculated as 88%.

Improving the corrosion and stress corrosion cracking resistance of 316 L stainless steel in high temperature water by water jet cavitation peening

Water jet cavitation peening (WJP) was used to improve the corrosion and stress corrosion cracking (SCC) of cold worked 316L stainless steel (316L SS) in high temperature water. WJP induced changes in residual stress and microstructure of the surface layer on corrosion and SCC were investigated. The investigation was conducted by comparing the corrosion and SCC of the un-treated (UT) and WJP treated specimens by exposure tests and slow strain rate tensile (SSRT) tests. The results revealed that WJP obviously improved the corrosion and SCC resistance of 316L SS, which is attributed to the increase of residual compressive stress and the change of the microstructure of the surface layer.

Photobiomodulation for Lowering Pain after Tonsillectomy: Low Efficacy and a Possible Unexpected Adverse Effect.

Background: Tonsillectomy is one of the most common surgical procedures performed in children as a treatment for obstructive sleep apnea due to tonsil hypertrophy or highly recurrent tonsillitis. Odynophagia, associated with food refusal for the first few days, is a common post-operative complaint. Available drugs for pain management, while efficacious, present some drawbacks, and a novel strategy would be welcome. Photobiomodulation (PBMT), in this context, can represent a possible choice, together with pharmacological therapy. The aim of this study was to evaluate PBMT effects compared to standard pain therapy on nociceptive sensation at different time points and administration of painkiller. Methods: A registered, controlled, randomized, double-blind clinical trial was performed. Twenty-two patients were recruited and divided into laser-treated (T) or untreated (UT) groups, based on random assignment. In T group, immediately after tonsillectomy, performed with cold dissection technique, laser light was applied to the surgery site (using a Cube 4 from Eltech K-Laser s.r.l., Treviso, Italy), and then hemostasis was performed using bismuth subgallate paste. In C group, the same procedure was performed, except that laser light was switched off. The primary outcome was the difference in pain scores between subject receiving photobiomodulation (PBMT) and subjects receiving standard care after 24 h; the secondary outcomes were pain scores at awakening and at 48 h together with distress (delirium) at awakening. Results: Two patients from the T group experienced a post-surgery bleeding, and one of them required revision of the hemostasis under general anesthesia. A preliminary analysis of pain sensation reported by the patients or caregivers did not show differences between treated and untreated subjects. Conclusion: These data suggest that PBMT could increase post-surgical bleeding.

Dimensional stability and mechanical properties of bio-based composites produced from hydro-thermal treated wheat straw

Bio-composites were produced from untreated (UT) and hydro-thermally treated (HTT) wheat straw (WS) particles and wood, and their dimensional stability and mechanical properties were investigated. The HTT treatment consisted of subjecting the WS particles to a steam explosion process for 8 min at 180 °C. The HTT and UT WS particles were mixed with the wood particles at 10, 20, 30, and 40% ratios. The physical properties, including density, water absorption (WA), and thickness swelling (TS), were determined for the bio-based composites. The mechanical properties evaluated included the modulus of rupture, modulus of elasticity, and internal bond strength. Statistical analyses showed that the hydro-thermal treatment and the WS ratio had significant effects on the dimensional stability and mechanical properties of the bio-composites. The WA of the composites after 2-h and 24-h rose significantly when the HTT WS particle ratio was increased from 10 to 40%. The 2-h and 24-h WA values of HTT-10 were 6.3% and 5.3% lower than those of UT-10, respectively. Improvements in the 2-h TS value were achieved by the HTT WS particles at the 10% ratio, and in the 24-h TS value at the 10 and 40% ratios. The mechanical properties of the composites were higher in the HTT group, but decreased in both the UT and HTT groups as the WS ratio increased.

Safety assessment of bio-synthesized iodine-doped silver nanoparticle wound ointment in experimental rats

BackgroundIn the wake of antibiotic resistance, treatment of intractable wound have been very challenging and any alternative treatment which may lead to less use of antibiotics deserves further exploitation. Nanoparticle conjugates has potentially not only reduce antibiotic use but it has been considered safe and effectively disinfect wounds already colonized with resistant bacteria as well as promoting granulation tissue formation. In this study, Iodine-doped silver nanoparticle Ointment (Ag-I NPs) was investigated for its toxicological effect on excisional wound of albino rats.MethodsAqueous extraction of Piper guineense leaf was carried out and used for the synthesis of Ag-I NPs. The synthesized Ag-I NPs were characterized by Ultraviolet visible spectrophotometer which confirmed the availability of silver nanoparticles. The particles were then used to prepare a wound healing ointment for treating excision wound inflicted on wistar rat model. Blood samples, liver and kidney biopsies were collected on the 21st day of the experiment from all the rats for hematology, biochemical and histopathological analysis.ResultIn the hematological and biochemical analysis, hemoglobin (Hb), packed cell volume (PCV) and mean corpuscular hemoglobin (MCH), superoxide dismutase (SOD), alkaline phosphatase (ALP) of experimental rats treated with Ag-I NPs were significantly different (p < 0.05) compared to the untreated group. In the histopathology, the photomicrograph of the liver showed the normal control, PEG, Ag-NP, and Ag-I NP groups remained intact displaying distinctive histo-morphological appearance and stable cell density while the untreated (UTD) group showed fatty liver and reduced cellular density. The kidney photomicrograph of the normal control and Ag- I NP groups were present with intact renal corpuscles while the other photomicrographs displayed corpuscular degeneration marked by the large halo-spaced bowman space.ConclusionSilver nanoparticles (Ag NPs) and iodine-doped silver nanoparticle (Ag-I NP) altered haematological parameters in the rats and also influenced some biochemical changes in the serum of the rats. While in the histopathological study, the antioxidant present in the plant extract used to synthesize Ag NPs and Ag I-NPs may have functioned in synergy to maintain and preserve the integrity of the hepatocytes and renal corpuscles of the rats.

Comparison of limestone calcined clay cement and ordinary Portland cement for stabilization/solidification of Pb-Zn smelter residue.

Decreasing carbon emissions by replacing Portland cement (PC) with supplementary cementitious materials (SCMs), such as low-grade limestone (LS) and calcined clays (CC), has tremendous potential for stabilization/solidification (S/S) of industrial hazardous waste primarily with heavy metals. Recently, a low-carbon-based cementitious binder, namely, limestone calcined clay cement (LC), has emerged as an alternative for S/S treatment of wastes. However, comprehensive comparison between LC and PC application in solidifying/stabilizing wastes has not been conducted. This study aims to investigate the S/S efficiency of Pb-Zn smelter residue (LZSR) comprising heavy metals lead (Pb), zinc (Zn), and cadmium (Cd) at higher concentrations. LZSR is treated with LC and PC for capturing strength and leaching toxicity. The test results indicate that low-grade CC and LS in the LC binder can promote the alkaline environment, and act as fillers in solidifying heavy metals. The toxicity characteristic leaching procedure leaching concentrations of untreated (UT) LZSR were 503 mg/kg, 1266 mg/kg, and 251 mg/kg for Pb, Zn, and Cd, respectively. After a 28-day curing, the leaching concentrations in LC-treated LZSR reduced to 4.33 mg/kg, 189.68 mg/kg, and 0.46 mg/kg, while the leaching concentrations of PC-treated LZSR reduced to 29 mg/kg, 338 mg/kg, and 6 mg/kg for Pb, Zn, and Cd, respectively. The maximum immobilization efficiencies for Pb, Zn, and Cd reached 85%, 99%, and 99%, respectively. Moreover, the insoluble phases for Pb, Zn, and Cd obtained from the sequential extraction test results were 63.5%, 72.1%, and 42.4% for LC-treated LZSR and 35.7%, 38%, and 43% for PC-treated LZSR with binder content of 8% binder and curing time of 28 days. Increasing curing time and binder content reduced leaching concentrations, and the underneath mechanisms were interpreted by XRD, SEM-EDS, and FTIR analyses. Overall, the results indicate that Pb, Zn, and Cd can be successfully immobilized using 8% LC binder by transforming soluble heavy metals to insoluble hydroxides and their complexes.

Effects on the interfacial and mechanical properties of reed leaf fibers reinforced agar composites induced by hot water, Na2CO3 solution and ultrasound treatment

ABSTRACT To investigate the feasibility of preparing biodegradable composites as food packing materials from reed leaf fibers to substitute disposable plastic, the fibers were treated by hot water (HWT), Na2CO3 solution (NCT) and ultrasound (UST), respectively and then combined with agar to prepare biodegradable composites through compression molding technique. The effects on the morphology, thermal properties of reed leaf fibers and the tensile cross-section morphology, the mechanical properties, the thermal conductivity and the moisture absorption profiles of the composites were studied. The amorphous components such as lignin and hemicellulose in reed leaf fibers were removed after HWT, NCT and UST. The fibers had a rough surface after hot water treatment which can lead to a better combination with agar induce an obvious improvement on the mechanical properties of the composites. The tensile strength, flexural strength and the impact strength of the HWT composite were 3.37 MPa, 19.7 MPa and 14.01 MPa, higher than that of the untreated (UT) composite and 22.99%, 16.36% and 69%, respectively. The HWT composite had a better hydrophobicity which equilibrium moisture absorption rate was 32.12%. The thermal conductivity of all the composites were less than 0.23 W·m−1·k−1, which were thermal insulating.

Kochia (Bassia scoparia) harvest date impacts nutrient composition, in vitro degradability, and feed value more than pre-harvest herbicide treatment or herbicide resistance traits

Kochia is a summer-annual tumbleweed that is drought, saline, and heat tolerant, and often resistant to several herbicides. Glyphosate-resistant kochia exhibits indeterminate growth and remains green during senescence, making it difficult to harvest crops that are contaminated with this weed. Removing dense patches of kochia from contaminated crops can aid in downstream harvest operations while also generating a potential source of livestock feed. This study evaluated the effects of two kochia populations [glyphosate-resistant (GR) and glyphosate-susceptible (GS) kochia] with or without pre-harvest treatment using glyphosate + saflufenacil [untreated (UN) vs treated 10 d pre-harvest (PRE)] on nutrient composition and in vitro degradability when it was harvested at advancing maturities. Kochia (GR-UN, GR-PRE, GS-UN, and GS-PRE) was harvested on 6 dates (HD) corresponding to pre-bloom (HD 1), mid-bloom (HD 2), full-bloom with 50% open flowers (HD 3), developing seeds (HD 4), mid-mature seeds (HD 5) and fully mature seeds (HD 6). In most cases, harvest date affected the chemical composition and in vitro degradability to a greater extent than the kochia population or herbicide treatment. The dry matter (DM) yield increased (P < 0.001) from HD 1–5 and decreased thereafter. The crude protein (CP) content decreased (P < 0.001) while the acid (ADF) and neutral detergent fiber (NDF) content increased (P < 0.001) with advancing HD. Overall, the CP content was higher (P = 0.014), and ADF content lower (P < 0.001) for GS than GR. Total in vitro gas (mL) (P < 0.001) and methane (CH4) production (mL L−1 of gas production) (P < 0.001) after 6 h incubation was greater for GR-UN than GR-PRE across HD. A decrease in acetate (P < 0.001) and an increase (P < 0.001) in propionate concentration with advancing HD led to reduced (P < 0.001) CH4 production after 48 h of in vitro incubation. Dry matter degradability (DMD; %) of GR-UN was greater (P = 0.003) than GR-PRE, while DMD and NDF degradability decreased (P < 0.001) with advancing HD. Pre-harvest application of glyphosate tended to increase the cell wall and decrease non-fibrous carbohydrate fractions, resulting in a slight decline in degradability and an increase (P < 0.05) in in vitro CH4 production. Further in vivo digestibility and growth performance studies using kochia harvested at the optimal maturity are required to define the value of this weed as forage in ruminant production systems.

Graph Theory and Matrix Approach for Machinability Enhancement of Cryogenic Treated Cobalt Bonded Tungsten Carbide Inserts

Cryogenic treatment is a sustainable manufacturing process preferred to improve the properties of the material. In the present study, the effect of cryo treated tungsten carbide cobalt bonded insert (WC-Co) measured in terms of tool life and surface finish on dry turning on high strength AISI4340 steel at different machine parametric conditions. The observations of Untreated (UT) and Deep Cryo Treated (DCT) inserts were compared. Formation and the distribution of eta phase carbides are verified by Scanning Electron Micrograph (SEM). The DCT insert shows a reduction in 27.27% tool wear with an acceptable level of surface finish. Taguchi's coupled Graph Theory and Matrix Approach (TC-GTMA) is used to predict the optimum machining condition and to substantiate the results the validation experiment is conducted and found satisfactory.

Viability Status-Dependent Effect of Bifidobacterium longum ssp. longum CCM 7952 on Prevention of Allergic Inflammation in Mouse Model

The classical definition of probiotics states that bacteria must be alive to be beneficial for human organism. However, recent reports show that inactivated bacteria or their effector molecules can also possess such properties. In this study, we investigated the physical and immunomodulatory properties of four Bifidobacterium strains in the heat-treated (HT) and untreated (UN) forms. We showed that temperature treatment of bacteria changes their size and charge, which affects their interaction with epithelial and immune cells. Based on the in vitro assays, we observed that all tested strains reduced the level of OVA-induced IL-4, IL-5, and IL-13 in the spleen culture of OVA-sensitized mice. We selected Bifidobacterium longum ssp. longum CCM 7952 (Bl 7952) for further analysis. In vivo experiments confirmed that untreated Bl 7952 exhibited allergy-reducing properties when administered intranasally to OVA-sensitized mice, which manifested in significant suppression of airway inflammation. Untreated Bl 7952 decreased local and systemic levels of Th2 related cytokines, OVA-specific IgE antibodies and simultaneously inhibited airway eosinophilia. In contrast, heat-treated Bl 7952 was only able to reduce IL-4 levels in the lungs and eosinophils in bronchoalveolar lavage, but increased neutrophil and macrophage numbers. We demonstrated that the viability status of Bl 7952 is a prerequisite for the beneficial effects of bacteria, and that heat treatment reduces but does not completely abolish these properties. Further research on bacterial effector molecules to elucidate the beneficial effects of probiotics in the prevention of allergic diseases is warranted.

Distinctive Platelet Features and Lymphocyte Sets Distribution in Immune Thrombocytopaenia Patients Responders to Thrombopoietin Receptor Agonists

Background: The heterogeneous pathophysiology of immune thrombocytopaenia (ITP) may explain the wide variation in the presentation of the disease, the clinical course and the response to therapeutic treatments. Among them, agonists of thrombopoietin receptor (TPO-RA) were incorporated as a second line agent for the management of ITP patients who do not respond to other treatments. We hypothesized that platelet and white cells from these patients might present some characteristics different from those observed in ITP patients who don't need to be treated and those responders to a first line therapeutic agent. In order to test this hypothesis we designed this study to evaluate platelet function and distribution of lymphocyte´s compartments in three ITP patient's groups: 1) untreated (UT) and treated with 2) TPO-RA or 3) corticoids.Materials and Methods: We recruited 33 UT ITP patients (30% male), 35 treated with TPO-RA (45% male), 15 with corticoids (25 % male) and 96 healthy controls (42% male).The La Paz Universitary Hospital Ethics Committee approved the experimental protocol.Platelet-activation, granule's content release, surface exposure of phosphatidylserine (PS) and activities of caspase-3, -8 or -9 were assessed by flow cytometry (respectively performed with PAC1, anti P-selectin and anti-CD63 antibodies, from BD; Annexin V from BD Pharmingen and Millipore kit).The frequency of T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes, natural killer (NK) CD56bright and CD56dim and regulatory T (Treg) [CD4+CD25+ forkhead box protein 3(FoxP3)+] were determined by multi-parametric flow cytometry panels (BD Biosciences).The statistical analysis of the experimental data was using SPSS 9.0 software (SPSS Inc., Chicago, Illinois, USA).Results: Platelet count were similar in all ITP groups but lower than controls (p<0.001). Platelet activation, evaluated by binding of PAC1 (antibody that only recognizes the active form of fibrinogen receptor) after the stimulation with TRAP (an agonist for PAR-1 receptors), were equally reduced in all ITP groups. Platelet activation with ADP was only reduced in the TPO-RA ITP patients. A diminished exposure of P-selectin and CD63 was also observed in UT and TPO-RA ITP patients after platelet stimulation with TRAP (Table 1). No differences were observed in surface expression of CD41, CD61, CD42a and CD42b between ITP patients and healthy controls. Platelet apoptosis evaluation showed that ITP patients tended to have an increased activity of caspases -3,7,-8 and -9 activities, but this observation was significant only in the ITP group of treated with TPO-RA (Table 1).Regarding lymphocytes, no differences were observed in LT subsets among all groups. Intermediate (IM, CD14++CD16+), but not non-classical (NCM, CD14+CD16++) and classical (CM, CD14++CD16-) monocytes were increased in UT and TPO-RA ITP patients. CD56brightCD16- NKand CD56brightCD16+NK, abundant cytokine producers with a weak cytotoxic activity, were increased only in TPO-RA ITP patients. In this group a diminution was observed in memory LB cells. Regarding LTreg population, their count was reduced in UT and corticoid-treated patients, whereas their values reach normality in the TPO-RA treated group (Table 2).Conclusions: All ITP patients, untreated or responders to treatment with TPO-RA and corticoids recovered platelet count but not its function. TPO-RA-responders patients showed an increased apoptosis compared to the other ITP patients recruited. Nevertheless, TPO-RA seems to have a beneficial regulatory effect on immune system that might counteract platelet destruction.Work supported by grant from FIS-FEDER PI15/01457. NVB holds a Miguel Servet II (FIS-FEDER CP14/00024). [Display omitted] DisclosuresÁlvarez-Roman:Shire: Consultancy; Novo Nordisk: Consultancy. Jimenez-Yuste:Novo Nordisk: Consultancy, Honoraria, Research Funding; Roche: Consultancy.

Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1

Limb girdle muscular dystrophy (LGMD) 2A/R1, caused by mutations in the CAPN3 gene and CAPN3 loss of function, is known to play a role in disease pathogenicity. In this study, AAVrh74.tMCK.CAPN3 was delivered systemically to two different age groups of CAPN3 knockout (KO) mice; each group included two treatment cohorts receiving low (1.17 × 1014 vg/kg) and high (2.35 × 1014 vg/kg) doses of the vector and untreated controls. Treatment efficacy was tested 20 weeks after gene delivery using functional (treadmill), physiological (in vivo muscle contractility assay), and histopathological outcomes. AAV.CAPN3 gene therapy resulted in significant, robust improvements in functional outcomes and muscle physiology at low and high doses in both age groups. Histological analyses of skeletal muscle showed remodeling of muscle, a switch to fatigue-resistant oxidative fibers in females, and fiber size increases in both sexes. Safety studies revealed no organ tissue abnormalities; specifically, there was no histopathological evidence of cardiotoxicity. These results show that CAPN3 gene replacement therapy improved the phenotype in the CAPN3 KO mouse model at both doses independent of age at the time of vector administration. The improvements were supported by an absence of cardiotoxicity, showing the efficacy and safety of the AAV.CAPN3 vector as a potential gene therapy for LGMDR1.

Static magnetic field treatment enhanced photosynthetic performance in soybean under supplemental ultraviolet-B radiation.

The study was performed to analyze the impact of seed pretreatment by static magnetic field (SMF) of 200 mT for 1h on photosynthetic performance of soybean (Glycine max) seedlings under ambient (aUV-B) and supplemental ultraviolet-B (a+sUV-B) stress. Ambient and supplemental UV-B were found to decrease the plant growth, chlorophyll concentration, PSII efficiency, selected JIP-test parameters such as Fv/Fm, φEo, ΔV(I-P), PIABS, PItotal, and rate of photosynthesis in the leaves of soybean seedlings emerged from untreated (UT) seeds. aUV-B and a+sUV-B were observed to increase the synthesis of UV-B-absorbing substances (UAS), reactive oxygen species (ROS) like superoxide radical (O2·-) and hydrogen peroxide (H2O2), antioxidants like ascorbic acid and α-tocopherol and decrease the nitrate reductase (NR) activity; subsequently, it results in a decreased rate of photosynthesis, biomass accumulation, and yield. However, our results provided evidence that SMF pretreatment increased the tolerance of soybean seedlings to UV-B radiation by increased NO content and NR activity; higher efficiency of PSII, higher values of φEo, ΔV(I-P), PIABS, and PItotal, decreased intercellular CO2 concentration, lower amount ofUAS, ROS, and antioxidants that consequently improve the yield of soybean plants under aUV-B as well as a+sUV-B stress. Thus, our results suggested that SMF pretreatment mitigates the adverse effects of UV-B stress by the enhancement in photosynthetic performance along with higher NO content which may be able to protect the plants from the deleterious effects of oxidative stress caused by UV-B irradiation.

Inducing dry eye disease using a custom engineered desiccation system: Impact on the ocular surface including keratin-14-positive limbal epithelial stem cells

PurposeDry eye disease (DED) is characterized by loss of tear film stability that becomes self-sustaining in a vicious cycle of pathophysiological events. Currently, desiccation stress (DS) is the dominant procedure for inducing DED in mice, however its’ effect on limbal epithelial stem cells (LESCs) has been overlooked. This study aimed to establish a DS model via the use of a novel hardware to investigate the impact on the ocular surface including LESCs. MethodsA mouse transporter unit was customized to generate a dehumidified environment. C57BL/6J mice were exposed to mild DS and injected with scopolamine hydrobromide (SH) or remained untreated (UT) under standard vivarium conditions for 10 consecutive days (n = 28/group). Clinical assessments included phenol red tear-thread test, fluorescein staining and optical coherence tomography assessments. Histopathological and immunofluorescence was used to evaluate tissue architecture, goblet cell (GC) status, lacrimal gland (LG) inflammation and epithelial phenotype on the ocular surface. Whole flat-mounted corneas were immunostained for keratin-14 (K14), then imaged by confocal microscopy and analyzed computationally to investigate the effect of DS on LESCs. ResultsCustom modifications made to the animal transporter unit resulted in dehumidified cage relative humidity (RH) of 43.5 ± 4.79% compared to the vivarium 53.9 ± 1.8% (p = 0.0243). Under these conditions, aqueous tear production in mice was suppressed whilst corneal permeability and corneal irregularity significantly increased. H&E staining indicated stressed corneal basal epithelial cells and increased desquamation. DS-exposed mice had reduced GC density (41.0 ± 5.10 GC/mm vs 46.9 ± 3.88 GC/mm, p = 0.0482) and LGs from these mice exhibited elevated CD4+ cell infiltration compared to controls. DS elicited K14+ epithelial cell displacement, as indicated by increased fluorescence signal at a distance of 50–100 μm radially inwards from the limbus [0.63 ± 0.053% (DS) vs 0.54 ± 0.060% (UT), p = 0.0317]. ConclusionsApplication of mild DS using customized hardware and SH injections generated features of DED in mice. Following DS, ocular surface epithelial cell health decreased and LESCs appeared stressed. This suggested that potential downstream effects of DS on corneal homeostasis are present, a phenomenon that is currently under-investigated. The method used to induce DED in this study enables the development of a chronic model which more closely resembles disease seen in the clinic.

Biochemical and histopathological effects in muscular tissue of carp fish (Labeo rohita, Hamilton 1822) following exposure to untreated and treated sewage water.

Present work describes a laboratory study aiming at assessing the impact of sewage treatment plant (STP) effluents on fish health by means of biochemical and histopathological biomarkers in muscular tissue of fish. Labeo rohita (7.62 ±0.25 cm, 8.25±0.32 g) was exposed to sub-lethal concentrations of untreated (UT) and treated (T) sewage water obtained from STP, Ludhiana, India. Following the determination of the 96h lethal concentration (LC50), the fish were exposed to control (de-chlorinated tap water), treated sewage water, 1/10th of LC50 UT and 1/20th of LC50 UT sewage water. The experiment was conducted for the period of 60 days. Experimental results depicted significant reduction (p<0.05) in muscle-somatic index of 1/10th LC50 UT and 1/20th LC50 UT groups compared to control and treated groups. Fish toxicity induced by untreated sewage water was evident from the significant decrease (p<0.05) in the levels of proteins and significant increase (p<0.05) in content of total lipids in muscular tissue of exposed group fingerlings. Drastic changes in the fatty acids profile and severe histological abnormalities viz. shortening of muscle bundles, edema, hyper-vacuolization, elongation of muscle bundles, gap formation in myofibrils, degenerated myotomes, hemorrhage, inter-myofibrillar space, necrosis, were also recorded in muscular tissue of exposed fingerlings. The intensity of muscular damage in L.rohita was found to increase with increase in duration of exposure. Results demonstrated that untreated sewage water could potentially induce physiological stress and somatic cell toxicity in fish L.rohita. Genotoxicity studies on germ cells of L.rohita fingerlings are further suggested to examine the genotoxic potential of untreated sewage water at high concentrations; this is especially of interest given that many effluents are genotoxic to fish.

Digital Image Correlation of Tensile Properties for Monel 400/SS 316L Dissimilar Metal Welding Joints.

Dissimilar metal weld joints of Monel 400 and Stainless Steel 316L stainless steel were carried out using Gas Tungsten Arc Welding (GTAW). Conventional annealing and cryogenic treatment were performed on the welded joints. Weld joints of this combination of materials have enormous potential applications in power industry and the available related literature is limited. In the present study, the tensile properties of heat treated (HT), cryotreated (CT), and untreated (UT) specimens were studied. The engineering stress and strain were determined experimentally as per Standard Test Methods for Tension Testing of Metallic Materials (ASTM E8). The strain distribution was evaluated at different zones of weld joint was evaluated using Digital Image Correlation (DIC). Significant difference was noticed between the zones. Weld zone of all samples had less local stress and strain and SS 316L heat affected zone (HAZ) zone had more local stress and strain when compared to other zones. The local strain distribution along distance from weld center line and local stress-strain curves of different zones are also predicted. Scanning Electron Microscopy was used to analyze the fracture behavior of welded samples for HT, CT, and UT specimens.

Heartbeat optical coherence elastography: corneal biomechanics in vivo

.Significance: Mechanical assessment of the cornea can provide important structural and functional information regarding its health. Current clinically available tools are limited in their efficacy at measuring corneal mechanical properties. Elastography allows for the direct estimation of mechanical properties of tissues in vivo but is generally performed using external excitation force.Aim: To show that heartbeat optical coherence elastography (Hb-OCE) can be used to assess the mechanical properties of the cornea in vivo.Approach: Hb-OCE was utilized to detect Hb-induced deformations in the rabbit cornea in vivo without the need for external excitation. Furthermore, we demonstrate how this technique can distinguish corneal stiffness between untreated (UT) and crosslinked (CXL) tissue.Results: Our results demonstrate that stiffness changes in the cornea can be detected using only the Hb-induced deformations in the cornea. Additionally, we demonstrate a statistically significant difference in strain between the UT and CXL corneas.Conclusions: Hb-OCE may be an effective tool for assessing the mechanical properties of the cornea in vivo without the need for external excitation. This tool may be effective for clinical assessment of corneal mechanical properties because it only requires optical coherence tomography imaging and data processing.

Mechanical, Histological, and Scanning Electron Microscopy Study of the Effect of Mixed-Acid and Heat Treatment on Additive-Manufactured Titanium Plates on Bonding to the Bone Surface.

The additive manufacturing (AM) technique has attracted attention as one of the fully customizable medical material technologies. In addition, the development of new surface treatments has been investigated to improve the osteogenic ability of the AM titanium (Ti) plate. The purpose of this study was to evaluate the osteogenic activity of the AM Ti with mixed-acid and heat (MAH) treatment. Fully customized AM Ti plates were created with a curvature suitable for rat calvarial bone, and they were examined in a group implanted with the MAH-treated Ti in comparison with the untreated (UN) group. The AM Ti plates were fixed to the surface of rat calvarial bone, followed by extraction of the calvarial bone 1, 4, 8, and 12 weeks after implantation. The bonding between the bone and Ti was evaluated mechanically. In addition, AM Ti plates removed from the bone were examined histologically by electron microscopy and Villanueva–Goldner stain. The mechanical evaluation showed significantly stronger bone-bonding in the MAH group than in the UN group. In addition, active bone formation was seen histologically in the MAH group. Therefore, these findings indicate that MAH resulted in rapid and strong bonding between cortical bone and Ti.

MUSCLE FUNCTION & HOMEOSTASIS / MOLECULAR THERAPEUTIC APPROACHES: P.63 AAV.CAPN3 gene therapy for Limb-girdle muscular dystrophy type 2A (LGMD2A): Phenotypic improvements in the calpain3 (CAPN3)-null mouse

LGMD2A is caused by mutations in CAPN3 gene. CAPN3 loss of function is shown to play a role in disease pathogenicity, which might be improved by CAPN3 gene therapy. rAAVrh74.tMCK.CAPN3 vector was systemically delivered to young (YC, 6-10 week-old) and old cohorts (OC, 21-23 week-old) of CAPN3-KO mice. Each cohort included two treatment groups receiving low dose (LD; 3E12 vg, n=12) and high dose (HD; 6E12 vg, n=12) of the vector and age-matched untreated (UT) control groups (UT-YC, n=13;UT-OC, n=15). Outcome measures were performed at 20 weeks post-injection. AAV.CAPN3 improved treadmill performance in both cohorts, at both LD and HD subgroups (p<0.0001). There was no significant age-related effect on treadmill activity and the average performance of the treatment groups, HD vs. LD did not differ significantly. In the OC however, females (n=5) from the HD group run longer distance than males from same group (n=7; p<0.01). In the LD and HD treatment groups from OC, in vivo muscle contractility assay showed an improvement in both Twitch (p=0.001) and Tetanic Max responses (p=0.047) at the endpoint. The average of percent change between baseline and endpoint tetanic responses increased in the treated-YC while there was a decline in the UT cohort (p=0.002). Histological analyses of the skeletal muscle (gastroc, tibialis anterior, quadriceps and triceps) showed remodeling of muscle, a switch to fatigue resistant oxidative fibers in both cohorts along with fiber size increase. In-house toxicology studies in the HD cohort revealed no organ tissue abnormalities; specifically, there was no histopathological evidence of cardiotoxicity. AAV.CAPN3 gene therapy improved the LGMD2A-related phenotype in the CAPN3-KO mouse model in both low and high doses tested, independent of age at the time of vector-administration. Improvements shown were supported with the absence of cardiotoxicity, enhancing the efficacy and safety of AAV.CAPN3 vector as a potential gene therapy for LGMD2A.