Neural changes after operant conditioning of the aerial respiratory behavior in Lymnaea stagnalis.

In this study, we demonstrate neural changes that occurred during operant conditioning of the aerial respiratory behavior of Lymnaea stagnalis. Aerial respiration in Lymnaea occurs at the water interface and is achieved by opening and closing movements of its respiratory orifice, the pneumostome. This behavior is controlled by a central pattern generator (CPG), the neurons of which, as well as the motoneurons innervating the pneumostome, have previously been identified and their synaptic connections well characterized. The respiratory behavior was operantly conditioned by applying a mechanical stimulus to the open pneumostome whenever the animal attempted to breathe. This negative reinforcement to the open pneumostome resulted in its immediate closure and a significant reduction in the overall respiratory activity. Electrophysiological recordings from the isolated CNSs after operant conditioning showed that the spontaneous patterned respiratory activity of the CPG neurons was significantly reduced. This included reduced spontaneous activity of the CPG interneuron involved in pneumostome opening (input 3 interneuron) and a reduced frequency of spontaneous tonic activity of the CPG interneuron [right pedal dorsal 1 (RPeD1)]. The ability to trigger the patterned respiratory activity by electrical stimulation of RPeD1 was also significantly reduced after operant conditioning. This study therefore demonstrates significant changes within a CPG that are associated with changes in a rhythmic homeostatic behavior after operant conditioning.     

Etiological spectrum of irreversible blindness in Kashmir in North India

Purpose:To determine the etiological spectrum of irreversible blindness in Kashmir Valley in India.Methods:Patients presenting to a tertiary care hospital in Kashmir, India, with unilateral or bilateral blindness from April 2019 to March 2020 were included in this cross-sectional study. Blindness was defined using the World Health Organization (WHO) criteria. All subjects had a complete ophthalmologic examination and information was gathered regarding their demographic profile, nature of ocular disorder whether primary or secondary and laterality, if the ocular involvement was unilateral.Results:248 patients were enrolled in the study. The mean age of the patients was 57.17 years. The male: female ratio was 2.17:1. The commonest cause of unilateral or bilateral blindness was glaucoma (22.58%) followed by diabetic retinopathy (DR) (17.74%). Unilateral blindness was seen in 78.62% of the patients. Unilateral blindness occurred mainly due to glaucoma (16.41%), DR (14.87%), age-related macular degeneration (13.33%), and trauma (pellet injury: 10.76%, non-pellet injury: 10.25%). The major causes of bilateral blindness were glaucoma (45.28%), DR (28.30%), and hereditary/congenital retinal diseases (16.98%). Socioeconomic status and educational status were significantly associated (P < 0.05 each) while age, gender, place of residence, and occupation were not significantly associated (P > 0.05 each) with the number of eyes affected by blindness.Conclusion:Glaucoma and DR are the foremost causes of irreversible blindness in Kashmir. Public health plans aimed at encouraging good health education of patients should be developed in this region. Moreover, patients should be screened effectively for glaucoma and diabetes at the level of primary health care facilities.     

Rothmund‐Thomson syndrome due to RECQ4 helicase mutations: Report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome

Rothmund‐Thomson syndrome (RTS), an autosomal recessive disorder, comprises poikiloderma, growth deficiency, some aspects of premature aging, and a predisposition to malignancy, especially osteogenic sarcomas. Two kindreds with RTS were recently shown to segregate for mutations in the human RECQL4 helicase gene. We report identification of a new RTS kindred in which both brothers developed osteosarcomas. Mutation analysis of the RECQL4 gene was performed on both brothers and both parents. The brothers were shown to be compound heterozygotes for mutations in the RECQL4 gene, including a single base‐pair deletion in exon 9 resulting in a frameshift and early termination codon and a base substitution in the 3‐prime splice site in the intron‐exon boundary of exon 8, which would be predicted to cause a deletion of at least part of a consensus helicase domain. Each parent was shown to be a heterozygote carrier for one mutation. This report strengthens the association between mutations in RECQL4 helicase gene and RTS. Two other recessive disorders, Bloom syndrome and Werner syndrome, are known to be due to other human RECQ helicase gene mutations. These three disorders all manifest abnormal growth, premature aging, and predisposition to site‐specific malignancies. The clinical and molecular aspects of RTS, Bloom syndrome, and Werner syndrome are compared and contrasted. Am. J. Med. Genet. 90:223–228, 2000. © 2000 Wiley‐Liss, Inc.     

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies

Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug–polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 2³ full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg.h/cm²). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles’ formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.     

Friction Stir Welding of Thick Plates of 4Y3Gd Mg Alloy: An Investigation of Microstructure and Mechanical Properties

Applications of non-ferrous light metal alloys are especially popular in the field of aerospace. Hence it is important to investigate their properties in joining processes such as welding. Solid state joining process such as friction stir welding (FSW) is quite efficient for joining non-ferrous alloys, but with thick plates, challenges increase. In this study, Mg alloy plates of thickness 11.5 mm were successfully welded via single-pass FSW. Due to the dynamic recrystallization, grain size in the stir zone was reduced to 16 µm which is ≈15 times smaller than the parent material. The optimized rotational speed and traverse speed for optimum weld integrity were found to be 710 rpm and 100 mm/min, respectively. A sound weld with 98.96% joint efficiency, having an Ultimate Tensile Strength (UTS) of 161.8 MPa and elongation of 27.83%, was accomplished. Microhardness of the nugget was increased by 14.3%.     

Design and development of highly sensitive PEDOT-PSS/AuNP hybrid nanocomposite-based sensor towards room temperature detection of greenhouse methane gas at ppb level

Herein, we present fabrication of a novel methane sensor based on poly (3,4-ethylenedioxythiophene:poly (styrene sulfonic acid)) (p-PEDOT-PSS) and gold nanoparticles (AuNPs) treated with dimethyl sulfoxide (DMSO) and Zonyl using a spin coating technique. The nanocomposite films were further post treated with H₂SO₄ to improve the charge transport mechanism. The structural and morphological features of the composites were analyzed through scanning electronic microscopy, transmission electron microscopy, Fourier transform infra-red spectroscopy, UV-Vis spectroscopy and thermogravimetric analysis. Treatment with organic solvents and post treatment of H₂SO₄ significantly enhances the conductivity of the composite to 1800 S cm⁻¹. The fabricated sensor shows an excellent sensing response, fast response and recovery time along with acceptable selectivity towards methane gas at ppb concentrations. Due to a simple fabrication technique, excellent conductivity, superior sensing performance and improved mechanical properties, the sensor fabricated in this study could potentially be used to detect greenhouse methane gas at low concentrations.

Fabrication of novel methane sensor based on PEDOT-PSS:AuNPs composite treated with DMSO and Zonyl using spin coating technique.     

Structural,Physical, and Mechanical Analysis of ZnO and TiO2 Nanoparticle-Reinforced Self-Adhesive Coating Restorative Material

This study aimed to modify an EQUIA coat (EC; GC, Japan) by incorporating 1 and 2 wt.% of zinc oxide (ZnO; EC-Z1 and EC-Z2) and titanium dioxide (TiO₂; EC-T1 and EC-T2) nanoparticles, whereby structural and phase analyses were assessed using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. Thermogravimetric analysis/differential scanning calorimetry, micro-hardness, and water absorption analyses were conducted, and the microstructure was studied by scanning electron microscopy/energy-dispersive spectroscopy. FTIR spectra showed a reduction in peak heights of amide (1521 cm⁻¹) and carbonyl (1716 cm⁻¹) groups. XRD showed peaks of ZnO (2θ ~ 31.3°, 34.0°, 35.8°, 47.1°, 56.2°, 62.5°, 67.6°, and 68.7°) and TiO₂ (2θ ~ 25.3°, 37.8°, 47.9, 54.5°, 62.8°, 69.5°, and 75.1°) corresponding to a hexagonal phase with a wurtzite structure and an anatase phase, respectively. Thermal stability was improved in newly modified materials in comparison to the control group. The sequence of obtained glass transitions was EC-T2 (111 °C), EC-T1 (102 °C), EC-Z2 (98 °C), EC-Z1 (92 °C), and EC-C (90 °C). EC-T2 and EC-T1 showed the highest (43.76 ± 2.78) and lowest (29.58 ± 3.2) micro-hardness values. EC showed the maximum water absorption (1.6%) at day 7 followed by EC-T1 (0.82%) and EC-Z1 (0.61%). These results suggest that EC with ZnO and TiO₂ nanoparticles has the potential to be used clinically as a coating material.     

Local urokinase delivery with the Channel balloon: Device safety,pharmacokinetics of intracoronary drug delivery,and efficacy of thrombolysis

The Channel balloon is a new local drug-delivery catheter that has the dual capability of high-pressure lesion dilation and low-pressure drug infusion. The purpose of this study was to assess the safety and efficacy of this device in the local delivery of urokinase in the porcine model. Three in vivo protocols were performed in 57 anesthetized swine to assess the safety of Channel balloon use in the coronary vasculature, the pharmacokinetics of local urokinase delivery, and the ability of the catheter to lyse intraluminal thrombus. First, safety studies were performed in 18 coronary vessels in 13 pigs to compare angiographic and histologic changes following use of the Channel balloon with conventional balloon angioplasty. Second, intramural deposition of ¹²³I-labeled urokinase was measured in 24 coronary arteries in 20 pigs to assess the efficiency and technical determinants of urokinase delivery and the time course of intramural drug retention. Finally, an in vivo thrombus model was used in 24 pigs to compare the thrombolytic capacity of local urokinase delivery with the Channel balloon in comparison with conventional urokinase infusion techniques. All balloon inflations and drug infusions with the Channel balloon were well tolerated in all animals without adverse angiographic, hemodynamic, or electrical sequelae. Comparative histologic studies with the Channel balloon demonstrated no additional vessel trauma beyond that seen with conventional balloon angioplasty. Between 0.09 and 0.35% of infused urokinase was intramurally deposited, with intracoronary persistence for at least 5 h. Drug infusion pressure did not significantly affect drug deposition, although larger amounts of urokinase were deposited with larger balloon:artery ratios and higher urokinase concentrations. In comparison to conventional systemic and guiding catheter infusions, local delivery of urokinase with the Channel balloon resulted in higher levels of clot dissolution. These studies have demonstrated safe intracoronary use of the Channel balloon in the porcine model. Local infusion of urokinase with this device results in significant intramural drug deposition that persists for at least 5 h. In comparison with conventional thrombolytic techniques, local urokinase delivery with the Channel balloon may result in enhanced intravascular thrombolysis. Cathet. Cardiovasc. Diagn. 41:254–260, 1997. © 1997 Wiley-Liss, Inc.     

Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats

Ethnopharmacological relevance

The aerial parts of Coccinia cordifolia L. are used to treat female infertility in West Bengal state of India.

Aim of the study

The present study was undertaken to evaluate the fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats.

Materials and methods

The effect of aqueous extract of Coccinia cordifolia L. on hyperprolactinemia induced infertility, endometriosis induced infertility and androgen-induced infertility was studied. The effect on serum estrogen level, serum progesterone level and reproductive tract was also evaluated in normal healthy female rats. The extract was administered orally at two different doses of 500 mg/kg and 1000 mg/kg.

Results

In hyperprolactinemia induced infertility model, the numbers of uterine implants were almost 10 times more in the extract treated groups as compared to control. The high dose of extract also produced a significant increase in serum estrogen levels (p < 0.01) and number of corpus luteum (p < 0.05) in healthy female rats. The extract at both doses was effective in reducing the weight of endometrial implants by 70–80%, but failed to induce fertility in rats with endometriosis. The extract was ineffective in inducing fertility in androgen-induced infertility model.

Conclusions

The aqueous extract of Coccinia cordifolia L. induces fertility in hyperprolactinemia induced infertility model in female rats.     

Evaluation of previous management against a developed clinical pathway for chronic rhinosinusitis with nasal polyposis in Universiti Kebangsaan Malaysia Medical Center

The study aims to evaluate previous management of CRSwNP patients in Universiti Kebangsaan Malaysia Medical Center (UKMMC) against a developed CP.Chronic rhinosinusitis with nasal polyposis (CRSwNP) has high economic burden and impacts patient''s quality of life. Implementation of clinical pathway (CP) can standardize care while optimizing resources.Analytical cross-sectionalThis study utilized medical records of 103 CRSwNP patients at UKMMC otorhinolaryngology clinic from 2010 to 2015. Patients were divided into groups who underwent or did not undergo surgery. Information was obtained regarding sociodemographic, follow-ups, pharmaceutical regimes, and treatment cost. Cost analysis was done using top-down analysis and activity-based costing and CP was formulated. Cost was calculated using year 2020 rates to adjust for inflation. (United States Dollars [USD]1 = Ringgit Malaysia [RM] 4.2015)Study showed non-CP patients were undertreated compared to CP. This affects clinical outcomes as optimal treatment demanded by CP was not achieved. Total cost for non-CP, non-surgery patients were lower (USD660) compared to CP (USD780) due to under treatment and shorter follow-ups. Meanwhile, total cost for non-CP surgery patients were higher (USD3600) compared to CP (USD2706) due to longer visit durations and hospital stays. Non-CP surgery group underwent lengthy follow-up duration (20.7 months) prior to operation compared to 12 months expected in CP.Study showed non-CP patients were undertreated compared to CP. We identified aspects which resulted in resource wastage and unnecessary burden to our healthcare system. This study enables development of a written CP by fine-tuning various aspects of CP which could be applied to our future practice.