-
1.
Polypharmacy, Gender Disparities, and Ethnic and Racial Predispositions in Long QT Syndrome: An In-Depth Review.
Lima, B, Razmjouei, S, Bajwa, MT, Shahzad, Z, Shoewu, OA, Ijaz, O, Mange, P, Khanal, S, Gebregiorgis, T
Cureus. 2023;(9):e46009
Abstract
Long QT syndrome (LQTS) is a complex disorder of cardiac electrophysiology. It is characterized by delayed myocardial polarization leading to QT prolongation and alterations on the ST segment and T wave visible on electrocardiogram (ECG). Syncope is a common manifestation, and torsade de pointes (TdP) can lead to sudden cardiac death. Three major LQTS genes (KCI31, KCNH2, and SCN5) lead to most of the cases of LQTS. Lifestyle modifications, beta blockers, and implantable cardioverter defibrillator (ICD) placement are the main treatments for LQTS. Polypharmacy, including QT-prolonging drugs, has been shown to worsen LQTS. The impact on potassium channels and the human ether-a-go-go-related gene (hERG) is the mechanism behind the QT interval prolongation caused by these medications. There is an increased incidence of LQTS among African-American men and women as compared to Caucasians. Women with LQTS tend to have a higher mortality rate from the condition, especially during menstruation and shortly after giving birth. Genetic testing is reserved to those patientswho exhibit either a strong clinical index of suspicion or experience persistent QT prolongation despite their lack of symptoms. Knowing the genetics, racial, and gender discrepancies can help improve patient management and a better comprehension on each case. Proper understanding of how ion channels function and their interaction with medications will lead to a better comprehension and to develop effective forms to treat those patients.
-
2.
Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties.
Devkota, HP, Paudel, KR, Khanal, S, Baral, A, Panth, N, Adhikari-Devkota, A, Jha, NK, Das, N, Singh, SK, Chellappan, DK, et al
Molecules (Basel, Switzerland). 2022;(16)
Abstract
Stinging nettle (Urtica dioica L., Urticaceae) is commonly found in Asia, Africa, and Europe and has a long history of being used as food and traditional medicine. Recently, this plant is gaining attention as a highly nutritious food, where fresh leaves are dried and used as powder or in other forms. Leaves are rich in many bioactive compounds. This review aims to cover the traditional uses in food and medicine, as well as its nutritional composition, including its bioactive chemical constituents and reported food functional activities. Various bioactive chemical constituents have been isolated from stinging nettle to date, such as flavonoids, phenolic acids, amino acid, carotenoids, and fatty acids. Stinging nettle extracts and its compounds, such as rutin, kaempferol, and vitamin A, are also used for their nutritional properties and as anti-inflammatory and antioxidant agents. Future studies should focus on the proper formulation and stability testing of the functional foods containing stinging nettle and their detailed activities in clinical studies.
-
3.
Quantitative trait loci and candidate genes for iron and zinc bio-fortification in genetically diverse germplasm of maize (Zea mays L): A systematic review.
Basnet, B, Khanal, S
Heliyon. 2022;(12):e12593
Abstract
Genetically and economically, Maize plays a pivotal role in tackling Iron-Zinc mineral deficiency through the crop's biofortification approach to high-yielding cultivars. The objective of this study is to summarize quantitative trait loci (QTL) is useful for identifying novel genes of interest in diverse germplasm for understanding the exact genetic mechanism for Iron and zinc uptake, deposition, and biosynthesis in Zea mays L endosperm. various techniques like Germplasm Genetic Wide Association, QTL meta-analysis, and biparental linkage analysis are used by researchers in diverse germplasm of Maize for the gene of interest marking and are extracted as secondary information through a systematic review of scientific published sources in peer-reviewed sites. A literature review was focused on quantitative trait loci with candidate genes from different families like YS, NRAMP, ferritin, Cation efflux, etc., and cloned four phytase soluble genes which influence the concentration as well as bioavailability of Fe & Zn in the endosperm. More than 30 QTLs with 15-Fe, 17-Zn; 10 Meta QTLS are common and linked with micronutrient concentration as well 17 candidate genes from different families are responsible for the zinc-iron deposition on the endosperm. More than 46 Fe-Zn (20 + 26) SNPs and 22 SNPs (10 + 12) on nine different chromosomes play a significant role in the variation of the mineral value of inbreeds and Double haploid Bi-parental population of Zea mays L. In Rice and Maize, five different chromosomes are collinear for the uptake to deposition of these minerals in the endosperm. The success of marker-based biofortification depends upon the nature of germplasm, the gap between flanking marker and targeted genes, the selection of genotypes in each generation, and genotype-environment interaction which are the future area of study. This study can assist the breeders in fast-tracking Fe and Zn biofortification through frequency multiplication of these desired loci of Maize.
-
4.
Enhancement of blood-brain barrier penetration and the neuroprotective effect of resveratrol.
Katila, N, Duwa, R, Bhurtel, S, Khanal, S, Maharjan, S, Jeong, JH, Lee, S, Choi, DY, Yook, S
Journal of controlled release : official journal of the Controlled Release Society. 2022;:1-19
Abstract
Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. The specific molecular mechanisms through which PD-associated neuronal loss occurs remain unclear, and there is no available effective treatment against PD-related neurodegeneration. Resveratrol (RSV) has exhibited promising neuroprotective effects via antioxidant and anti-inflammatory activity. However, its poor bioavailability in the brain represents a challenge for its application in PD treatment. In this study, we synthesized RSV-loaded PLGA nanoparticles (RSV-PLGA-NPs) conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models. The Lf-conjugated RSV-PLGA-NPs (Lf-RSV-PLGA-NPs) exhibited enhanced internalization into SH-SY5Y and human brain microvascular endothelial cells as compared to RSV-PLGA-NPs and free RSV. Further, Lf-RSV-PLGA-NPs were more effective than RSV-PLGA-NPs and free RSV in attenuating the MPP+-induced generation of reactive oxygen species, reduction of mitochondrial membrane potential, and cell death. Importantly, Lf conjugation specifically increased the accumulation of RSV-PLGA-NPs in the brain as determined via bioluminescent imaging analyses. Our formulation substantially enhanced the neuroprotective effects of RSV in the MPTP-induced PD model. Hence, Lf-RSV-PLGA-NPs represent a promising tool for improving RSV bioavailability and neuroprotection within the brain.
-
5.
Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID-19: A review.
Adhikari, B, Marasini, BP, Rayamajhee, B, Bhattarai, BR, Lamichhane, G, Khadayat, K, Adhikari, A, Khanal, S, Parajuli, N
Phytotherapy research : PTR. 2021;(3):1298-1312
-
-
Free full text
-
Abstract
The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.
-
6.
Coronary vasospasm: A narrative review.
Jewulski, J, Khanal, S, Dahal, K
World journal of cardiology. 2021;(9):456-463
Abstract
Coronary artery vasospasm (CAVS) plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries. Pathophysiology of the disease remains incompletely understood, with autonomic and endothelial dysfunction thought to play an important role. Due to the dynamic nature of the disease, its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population. Cigarette smoking remains a prominent risk factor, although CAVS does not follow traditional coronary artery disease risk factors. Many triggers continue to be identified, with recent findings identifying chemotherapeutics, allergens, and inflammatory mediators as playing some role in the exacerbation of CAVS. Provocative testing with direct visualization is currently the gold-standard for diagnosis, but non-invasive tests, including the use of biomarkers, are being increasingly studied to aid in the diagnosis. Treatment of the CAVS is an area of active research. Apart from risk factor modification, calcium channel blockers are currently the first line treatment, with nitrates playing an important adjunct role. High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator (ICD), although timing criteria for escalated therapy require further investigation. The role of pharmaceuticals targeting oxidative stress remains incompletely understood.
-
7.
Piloting a Telephone Based Health Coaching Program for Pregnant Women: A Mixed Methods Study.
Rissel, C, Khanal, S, Raymond, J, Clements, V, Leung, K, Nicholl, M
Maternal and child health journal. 2019;(3):307-315
-
-
Free full text
-
Abstract
Objectives Get Healthy in Pregnancy (GHiP) is a telephone based lifestyle coaching service for pregnant women, in New South Wales, Australia. GHiP had two service options; a telephone-based health coaching program consisting of up to 10 calls and information only (including one call). This study sought to compare the outcomes of the two GHiP options, to determine the characteristics of women likely to use the service and to explore the feedback from women and health professionals. Methods A pragmatic stratified clustered randomised controlled trial was conducted. Two metro and three rural hospitals were randomised into health coaching or information only arms. Self-reported measures of height and weight and health behaviours (dietary and physical activity) were collected at baseline and 36 weeks gestation. Process evaluation included descriptive analysis of routine program data, and semi-structured interviews with participants and health professionals. Results Of 3736 women screened, 1589 (42.5%) were eligible to participate, and of those eligible, 923 (58.1%) were recruited. More women in the health coaching arm gained weight within the target range for their BMI at 36 weeks gestation (42.9%) compared with information only (31.9%). Women found GHiP to be useful and supportive and midwives and doctors said that it facilitated conversations about weight with pregnant women. Conclusions for Practice Telephone-based lifestyle programs integrated with routine clinical care show promise in helping pregnant women achieve healthy gestational weight gain, but in this case was not significantly different from one information telephone call. Strong positive feedback suggests that scaled-up service delivery would be well received. TRIAL REGISTRATION ACTRN12615000397516 (retrospectively registered).
-
8.
pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium.
Khanal, S, Adhikari, U, Rijal, NP, Bhattarai, SR, Sankar, J, Bhattarai, N
Journal of functional biomaterials. 2016;(3)
Abstract
Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390-420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications.
-
9.
Effectiveness of a once per week delivery of a family-based childhood obesity intervention: a cluster randomised controlled trial.
Khanal, S, Welsby, D, Lloyd, B, Innes-Hughes, C, Lukeis, S, Rissel, C
Pediatric obesity. 2016;(6):475-483
Abstract
BACKGROUND The effectiveness of once per week (OPW) delivery of a family-based childhood obesity programme was compared with twice per week (TPW) delivery in achieving health and behavioural outcomes at a population level and in improving programme attendance. Both programmes were delivered over 10-weeks, and the contact hours in the OPW and TPW programmes were 20 and 35-h, respectively. METHODS A cluster-randomised controlled trial with stratification by local health district was conducted. Height, weight and global self esteem of participants and parent-reported diet and physical activity were measured at programme commencement and completion and at 6-month follow-up. Attendance was defined as the proportion of total sessions attended. RESULTS There were no differences between the OPW and TPW arms in changes from pre-programme baseline for body mass index (BMI) z-score and other health and behaviourial measures at programme completion and at follow-up, except for the increase in physical activity outside of the programme at programme completion (OPW, 3.5 h/week; TPW, 1.9 h/week; p = 0.03). OPW and TPW participants attended 71.2% and 69.2% of the total sessions, respectively. Attendance was the only contributing factor to a positive BMI z-score outcome (β = -2.45, p < 0.01) with no effects of child age and gender, language spoken at home or highest qualification of mother. CONCLUSIONS A family-based childhood obesity programme can be delivered OPW with no compromise to health or behavioural outcomes compared with TPW. Higher attendance, as a proportion of available sessions, leads to better outcomes for children.
-
10.
Pragmatic cluster randomised trial of a free telephone-based health coaching program to support women in managing weight gain during pregnancy: the Get Healthy in Pregnancy Trial.
Clements, V, Leung, K, Khanal, S, Raymond, J, Maxwell, M, Rissel, C
BMC health services research. 2016;(1):454
Abstract
BACKGROUND Excessive gestational weight gain can result in poor maternal and child health outcomes. Estimates from single studies indicate the prevalence of excessive gestational weight gain in Australia could lie between 38 and 67 %. The risk of excessive weight gain can be reduced through healthy eating and exercise. We describe the rationale and methods of the Get Healthy in Pregnancy Service, a trial service which aims to support women in achieving appropriate gestational weight gain through an existing telephone-based health coaching service. METHODS/DESIGN This study aims to compare the effectiveness of a telephone-based health coaching program versus provision of information only in supporting pregnant women to achieve appropriate gestational weight gain. A pragmatic stratified clustered randomised controlled trial will be conducted with 710 women who present to 5 hospitals for their first antenatal appointment during the recruitment period (6-8 months), have a pre-pregnancy body mass index (BMI) ≥ 18.50 (healthy weight or above), are 18 years and over, singleton gestation, English speaking, have no pre-existing medical conditions that may limit their ability to exercise or require a restricted diet and are 18 weeks or less gestation. Hospitals will be randomised into one of two intervention models: a) information only; or b) information plus 10 telephone-based health coaching sessions with a university qualified coach. Both interventions will set a weight-range target with pregnant women. The women attending antenatal clinics at participating hospitals will be screened at their initial hospital appointment to assess their eligibility. Women recruited to the trial will have a number of measures recorded including anthropometrics (self-reported height and weight) and dietary and physical activity scores during and following pregnancy. These measurements will be collected at baseline (prior to 18 weeks gestation), 36 weeks gestation and 12 months post-birth. DISCUSSION This study responds to a need for an effective intervention that targets excessive gestational weight gain at a population level. This study investigates the potential for an innovative intervention combining two existing services; a free state-wide telephone-based health coaching service and hospital-based antenatal care to support pregnant women to achieve healthy weight gain during pregnancy. The use of existing services provides the potential for immediate post-study implementation. While the impacts of telephone-based lifestyle programmes have been tested in a number of settings, there are few studies which evaluate the effectiveness and acceptability of telephone support in achieving healthy gestational weight gain in association with routine antenatal care. TRIAL REGISTRATION ACTRN12615000397516 (Registration date: 26 June 2014, retrospectively registered).