A NOVEL APPROACH TO INCREASE THE BIOAVAILABILITY OF CANDESARTAN CILEXETIL BY PRONIOSOMAL GEL FORMULATION: IN-VITRO AND IN-VIVO EVALUATION

Objective: The oral bioavailability of Candesartan cilexetil is less (<15%), so in this study an approach has been made to increase its bioavailability by proniosomal gel formulation.Methods: The proniosomal formulation of Candesartan cilexetil was prepared by slurry method, using span 60 and Tween 60 as non-ionic surfactants, maltodextrin as carrier and cholesterol and soya lecithin as stabilizers. Prepared gel formulations were evaluated for compatibility study, entrapment efficiency, vesicle size, surface morphology, in-vitro diffusion studies, in-vitro skin permeation studies, in-vivo pharmacokinetics studies, various release kinetic studies and stability studies.Results: FT-IR study showed no interaction between drugs and other excipients, drugs and excipients are compatible. Mean vesicles size of proniosome derived niosome was found in the range of 16.34 µm-32.48 µm and 7.25-16.45 µm before and after shaking. An optimized formulation A3 containing a 2:1 ratio of span 60 and cholesterol showed maximum entrapment (86.17%) and in-vitro drug release (93.8%) compared to other formulations. In-vitro skin permeation studies were carried out using Albino rat skin and results showed that formulation A3 exhibited 88.65% drug permeation in a steady-state manner over a period of 24 h with a flux value of 1.94 µg/cm2/h and enhancement ratio of 3.73. In-vivo pharmacokinetics studies of proniosomal gel formulation A3 showed a significant increase in bioavailability (1.425 folds) compared with an oral formulation of Candesartan cilexetil. Stability studies showed that proniosomal gel formulation was stable throughout its study period.Conclusion: Physiochemically stable Candesartan cilexetil proniosomal gel was formulated, which could deliver significant amount of the drug across the skin in a steady-state manner for the prolong period of time in the treatment of hypertension.Â

Preparation of floral calendar of bee flora available in Lamjung district, Nepal

Between March and May 2022, researchers conducted a broad survey in the Lamjung district to ascertain the presence and accessibility of bee-friendly flora to compile a floral calendar. In the PMAMP Bee Zone, 62 respondents were chosen for the interview through a simple random sampling approach, from a pool of 382 registered beekeepers. Primary data collection involved using personal interviews, focus group discussions, and key informant surveys. Secondary data were gathered from publications related to the topic from various institutions. The collected data were then analyzed using IBM SPSS V.26 and Microsoft Excel. Nearly all farmers in the study area kept Apis cerana bees, but due to insufficient irrigation, the crop fields provided limited forage for the bees during certain periods. The lowest number of frames covers by bees was four during the dearth period. Farmers in the Lamjung district did not practice migratory foraging. The majority of the respondents reported an increase in productivity compared to the previous year. However, only 37.1 percent of them cultivated bee flora. The colony carrying capacity of the forage area was not estimated. Additionally, an increase in deforestation was identified as the major problem affecting bee foraging. To address these issues, it was recommended to plant and cultivate perennial trees such as butter trees (Vitellaria paradox), bottle brush (Callistemon speciosus), litchi (Litchi chinensis), sissoo (Dalbergia sissoo), and sunflower (Helianthus annus) with assured irrigation. This approach could ensure year-round forage availability and reduce the need for artificial feeding. The research aimed to explore the current status of honey bee flora and investigate major flora that could be introduced in the study area

Clinical Proteomics of the Neglected Human Malarial Parasite Plasmodium vivax

Recent reports highlight the severity and the morbidity of disease caused by the long neglected malaria parasite Plasmodium vivax. Due to inherent difficulties in the laboratory-propagation of P. vivax, the biology of this parasite has not been adequately explored. While the proteome of P. falciparum, the causative agent of cerebral malaria, has been extensively explored from several sources, there is limited information on the proteome of P. vivax. We have, for the first time, examined the proteome of P. vivax isolated directly from patients without adaptation to laboratory conditions. We have identified 153 proteins from clinical P. vivax, majority of which do not show homology to any previously known gene products. We also report 29 new proteins that were found to be expressed in P. vivax for the first time. In addition, several proteins previously implicated as anti-malarial targets, were also found in our analysis. Most importantly, we found several unique proteins expressed by P. vivax.This study is an important step in providing insight into physiology of the parasite under clinical settings

A longitudinal multi-centric cohort study assessing infant neurodevelopment delay among women with persistent postpartum depression in Nepal.

BACKGROUND: Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months. METHODS: Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO's Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups. RESULTS: In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression. CONCLUSIONS: Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay

High-throughput spatial sensitive quantitative phase microscopy using low spatial and high temporal coherent illumination

High space-bandwidth product with high spatial phase sensitivity is indispensable for a single-shot quantitative phase microscopy (QPM) system. It opens avenue for widespread applications of QPM in the field of biomedical imaging. Temporally low coherence light sources are implemented to achieve high spatial phase sensitivity in QPM at the cost of either reduced temporal resolution or smaller field of view (FOV). In addition, such light sources have low photon degeneracy. On the contrary, high temporal coherence light sources like lasers are capable of exploiting the full FOV of the QPM systems at the expense of less spatial phase sensitivity. In the present work, we demonstrated that use of narrowband partially spatially coherent light source also called pseudo-thermal light source (PTLS) in QPM overcomes the limitations of conventional light sources. The performance of PTLS is compared with conventional light sources in terms of space bandwidth product, phase sensitivity and optical imaging quality. The capabilities of PTLS are demonstrated on both amplitude (USAF resolution chart) and phase (thin optical waveguide, height ~ 8 nm) objects. The spatial phase sensitivity of QPM using PTLS is measured to be equivalent to that for white light source and supports the FOV (18 times more) equivalent to that of laser light source. The high-speed capabilities of PTLS based QPM is demonstrated by imaging live sperm cells that is limited by the camera speed and large FOV is demonstrated by imaging histopathology human placenta tissue samples. Minimal invasive, high-throughput, spatially sensitive and single-shot QPM based on PTLS will enable wider penetration of QPM in life sciences and clinical applications

High spatially sensitive quantitative phase imaging assisted with deep neural network for classification of human spermatozoa under stressed condition

Sperm cell motility and morphology observed under the bright field microscopy are the only criteria for selecting a particular sperm cell during Intracytoplasmic Sperm Injection (ICSI) procedure of Assisted Reproductive Technology (ART). Several factors such as oxidative stress, cryopreservation, heat, smoking and alcohol consumption, are negatively associated with the quality of sperm cell and fertilization potential due to the changing of subcellular structures and functions which are overlooked. However, bright field imaging contrast is insufficient to distinguish tiniest morphological cell features that might influence the fertilizing ability of sperm cell. We developed a partially spatially coherent digital holographic microscope (PSC-DHM) for quantitative phase imaging (QPI) in order to distinguish normal sperm cells from sperm cells under different stress conditions such as cryopreservation, exposure to hydrogen peroxide and ethanol. Phase maps of total 10,163 sperm cells (2,400 control cells, 2,750 spermatozoa after cryopreservation, 2,515 and 2,498 cells under hydrogen peroxide and ethanol respectively) are reconstructed using the data acquired from the PSC-DHM system. Total of seven feedforward deep neural networks (DNN) are employed for the classification of the phase maps for normal and stress affected sperm cells. When validated against the test dataset, the DNN provided an average sensitivity, specificity and accuracy of 85.5%, 94.7% and 85.6%, respectively. The current QPI + DNN framework is applicable for further improving ICSI procedure and the diagnostic efficiency for the classification of semen quality in regard to their fertilization potential and other biomedical applications in general

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Endodontic treatment of a mandibular first molar with 8 canals: a case report

Presented here is a case where 8 canals were located in a mandibular first molar. A patient with continuing pain in mandibular left first molar even after completion of biomechanical preparation was referred by a dentist. Following basic laws of the pulp chamber floor anatomy, 8 canals were located in three steps with 4 canals in each root. In both of the roots, 4 separate canals commenced which joined into two canals and exited as two separate foramina. At 6 mon follow-up visit, the tooth was found to be asymptomatic and revealed normal radiographic periapical area. The case stresses on the fact that understanding the laws of pulp chamber anatomy and complying with them while attempting to locate additional canals can prevent missing canals