Displaying publications 601 - 620 of 1094 in total

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  1. Nanomedicine and medicinal plants: Emerging symbiosis in managing lung diseases and associated infections
    Paudel KR, De Rubis G, Panth N, Singh SK, Chellappan DK, Hansbro PM, et al.
    EXCLI J, 2022;21:1299-1303.
    PMID: 36483911 DOI: 10.17179/excli2022-5376
  2. Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes
    Safar HF, Ali AH, Zakaria NH, Kamal N, Hassan NI, Agustar HK, et al.
    Trop Biomed, 2022 Dec 01;39(4):552-558.
    PMID: 36602215 DOI: 10.47665/tb.39.4.011
    Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.
  3. Fulltext The Effect of Intragastric Gavage of High Dose Green Tea Extract on Serum Status of Magnesium, Calcium, and Zinc
    Khaleel AK, Shaari RB, Nawi MAA, Al-Yassiri AMH
    Asian Pac J Cancer Prev, 2022 Sep 01;23(9):3195-3199.
    PMID: 36172684 DOI: 10.31557/APJCP.2022.23.9.3195
    OBJECTIVE: Green tea (GT) contains polyphenolic flavonoids, different minerals like magnesium, calcium, and zinc, vitamins, amino acids, carbohydrates, proteins, and others. It has a different health benefit. The aim of the present study was to investigate the effect of intragastric gavage of a high dose GT extract on serum biochemical analysis of magnesium, calcium, and zincin juvenile Wistar albino rats.

    METHODS: Twelve rats were used in the study and divided in to two equal groups. All the animals in the control group were intragastically gavaged by distilled water and continues for ten days, from day 24 to day 34 of age, while the animals in the study group were intragastically gavaged by GT extract (300mg/kg/day) which continues also for ten days from day 24 to day 34 of age. On day 34 of age, and two hours after the last dose, the rats were anaesthetized and blood collection by cardiac puncture was taken.

    RESULTS: The results showed that the intragastric gavage of a high dose of GT extract caused a non-significant increase in serum magnesium, and calcium levels (p>0.05), but a significant increase in zinc serum level was seen(p< 0.05).

    CONCLUSION: GT can cause a significant increase in zinc serum level, and this may explain the significant role of GT in the response to different oxidative stress. It is recommended to measure the Zn serum level in rats after a period longer than two hrs from the time of the last dose of intragastric gavage of GT extract.

  4. Targeting inflammation: a potential approach for the treatment of depression
    Bhatt S, Devadoss T, Jha NK, Baidya M, Gupta G, Chellappan DK, et al.
    Metab Brain Dis, 2023 Jan;38(1):45-59.
    PMID: 36239867 DOI: 10.1007/s11011-022-01095-1
    Major depressive disorder (MDD) or Depression is one of the serious neuropsychiatric disorders affecting over 280 million people worldwide. It is 4th important cause of disability, poor quality of life, and economic burden. Women are more affected with the depression as compared to men and severe depression can lead to suicide. Most of the antidepressants predominantly work through the modulation on the availability of monoaminergic neurotransmitter (NTs) levels in the synapse. Current antidepressants have limited efficacy and tolerability. Moreover, treatment resistant depression (TRD) is one of the main causes for failure of standard marketed antidepressants. Recently, inflammation has also emerged as a crucial factor in pathological progression of depression. Proinflammatory cytokine levels are increased in depressive patients. Antidepressant treatment may attenuate depression via modulation of pathways of inflammation, transformation in structure of brain, and synaptic plasticity. Hence, targeting inflammation may be emerged as an effective approach for the treatment of depression. The present review article will focus on the preclinical and clinical studies that targets inflammation. In addition, it also concentrates on the therapeutic approaches' that targets depression via influence on the inflammatory signaling pathways. Graphical abstract demonstrate the role of various factors in the progression and neuroinflammation, oxidative stress. It also exhibits the association of neuroinflammation, oxidative stress with depression.
  5. Fulltext Introgression of the QTL qSB11-1TT conferring sheath blight resistance in rice (Oryza sativa) into an elite variety, UKMRC 2, and evaluation of its backcross-derived plants
    Hossain MK, Islam MR, Sundaram RM, Bhuiyan MAR, Wickneswari R
    Front Plant Sci, 2022;13:981345.
    PMID: 36699836 DOI: 10.3389/fpls.2022.981345
    INTRODUCTION: Sheath blight (SB) is the most damaging fungal disease in rice caused by a soil-borne pathogenic fungus, Rhizoctonia solani Kuhn (R. solani). The disease resistance in rice is a complex quantitative trait controlled by a few major genes. UKMRC2 is a newly developed elite rice variety that possesses high yield potential but is susceptible to sheath blight disease indicating a huge risk of varietal promotion, mass cultivation, and large-scale adoption. The aim of our present study was the development of varietal resistance against R. solani in UKMRC2 to enhance its stability and durability in a wide range of environments and to validate the effects of an SB-resistance QTL on the new genetic background.

    METHODS: In our study, we developed 290 BC1F1 backcross progenies from a cross between UKMRC2 and Tetep to introgress the QTL qSBR11-1TT into the UKMRC2 genetic background. Validation of the introgressed QTL region was performed via QTL analysis based on QTL-linked SSR marker genotyping and phenotyping against R. solani artificial field inoculation techniques.

    RESULTS AND DISCUSSION: The QTL qSBR11-1TT was then authenticated with the results of LOD score (3.25) derived from composite interval mapping, percent phenotypic variance explained (14.6%), and additive effect (1.1) of the QTLs. The QTL region was accurately defined by a pair of flanking markers K39512 and RM7443 with a peak marker RM27360. We found that the presence of combination of alleles, RM224, RM27360 and K39512 demonstrate an improved resistance against the disease rather than any of the single allele. Thus, the presence of the QTL qSBR11-1TT has been validated and confirmed in the URMRC2 genetic background which reveals an opportunity to use the QTL linked with these resistance alleles opens an avenue to resume sheath blight resistance breeding in the future with marker-assisted selection program to boost up resistance in rice varieties.

  6. Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues
    Bhatt S, Kanoujia J, Mohana Lakshmi S, Patil CR, Gupta G, Chellappan DK, et al.
    CNS Neurol Disord Drug Targets, 2023;22(2):276-288.
    PMID: 35352640 DOI: 10.2174/1871527321666220329140804
    The human gut microbiota plays a significant role in the pathophysiology of central nervous system-related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamicpituitary- adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has an influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to normal subjects also induces depression-like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate on the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.
  7. Reliability and sensitivity of radiographic measures of hip dysplasia in childhood Charcot-Marie-Tooth disease
    Dwan LN, Gibbons P, Jamil K, Little D, Birke O, Menezes MP, et al.
    Hip Int, 2023 Mar;33(2):323-331.
    PMID: 34180253 DOI: 10.1177/11207000211027591
    BACKGROUND: Hip dysplasia is a lack of femoral head coverage and disruption of hip and acetabular alignment and congruency, with severity ranging from mild subluxation in nascent at-risk hips to complete dislocation. Presentation of hip dysplasia in neuromuscular conditions can be sub-clinical or associated with a limp with or without hip pain, abductor and flexor weakness and reduced hip range of motion. Untreated hip dysplasia leads to early onset osteoarthritis requiring hip arthroplasty in early adulthood. Hip dysplasia occurs in 6-20% of children with Charcot-Marie-Tooth disease, however little is known about the reliability and sensitivity of detection on plain film pelvic radiographs.

    METHODS: 14 common measures of hip dysplasia on anteroposterior pelvis radiographs were independently assessed by 2 orthopaedic specialists in 30 ambulant children with Charcot-Marie-Tooth disease. Hip health was also categorised based on clinical impression to assess the sensitivity of radiographic measures to identify hip dysplasia status.

    RESULTS: 8 measures (acetabular index, head width, lateral centre-edge angle, lateral uncoverage, medial joint width, migration percentage, neck shaft angle, triradiate status) exhibited 'excellent' reliability between clinical evaluators. 5 of the 30 patients (17%) were identified as having nascent hip dysplasia. Reliable radiographic measures that significantly distinguished between nascent hip dysplasia and healthy hips were acetabular index, lateral centre edge angle, medial joint width and migration percentage.

    CONCLUSIONS: We have identified a subset of reliable and sensitive radiographic hip measures in children with Charcot-Marie-Tooth disease to prioritise during hip screening to mitigate the deleterious effects of hip dysplasia, pain and disability in adulthood.

  8. Comparative Drug Release Investigations for Diclofenac Sodium Drug (DS) by Chitosan-Based Grafted and Crosslinked Copolymers
    Chopra L, Thakur KK, Chohan JS, Sharma S, Ilyas RA, Asyraf MRM, et al.
    Materials (Basel), 2022 Mar 24;15(7).
    PMID: 35407737 DOI: 10.3390/ma15072404
    The hydrogels responding to pH synthesized by graft copolymerization only and then concurrent grafting and crosslinking of monomer N-isopropyl acrylamide (NIPAAM) and binary comonomers acrylamide, acrylic acid and acrylonitrile (AAm, AA and AN) onto chitosan support were explored for the percent upload and release study for anti-inflammatory diclofenac sodium drug (DS), w.r.t. time and pH. Diclofenac sodium DS was seized in polymeric matrices by the equilibration process. The crosslinked-graft copolymers showed the highest percent uptake than graft copolymers (without crosslinker) and chitosan itself. The sustainable release of the loaded drug was studied with respect to time at pH 2.2, 7.0, 7.4 and 9.4. Among graft copolymers (without crosslinking), Chit-g-polymer (NIPAAM-co-AA) and Chit-g-polymer (NIPAAM-co-AN) exhibited worthy results for sustainable drug deliverance, whereas Crosslink-Chit-g-polymer (NIPAAM-co-AA) and Crosslink-Chit-g-polymer (NIPAAM-co-AAm) presented the best results for controlled/sustained release of diclofenac sodium DS with 93.86 % and 96.30 % percent release, respectively, in 6 h contact time. Therefore, the grafted and the crosslinked graft copolymers of the chitosan showed excellent delivery devices for the DS with sustainable/prolonged release in response to pH. Drug release kinetics was studied using Fick’s law. The kinetic study revealed that polymeric matrices showed the value of n as n > 1.0, hence drug release took place by non-Fickian diffusion. Hence, the present novel findings showed the multidirectional drug release rate. The morphological changes due to interwoven network structure of the crosslinked are evident by the Scanning electron microscopy (SEM) analysis.
  9. Fulltext Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast
    Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.
    Singapore Med J, 2007 Jul;48(7):607-14.
    PMID: 17609820
    INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
    METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
    RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
    CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
  10. Fulltext Influence of gender and oral health knowledge on DMFT index: a cross sectional study among school children in Kaski District, Nepal
    Chapain KP, Rampal KG, Gaulee Pokhrel K, Adhikari C, Hamal D, Pokhrel KN
    BMC Oral Health, 2023 Feb 01;23(1):59.
    PMID: 36726123 DOI: 10.1186/s12903-023-02755-z
    BACKGROUND: Oral health problems are highly prevalent among school children in Nepal. Poor oral health condition may be influenced by various factors. However, little is known about the sociodemographic and awareness related factors on oral health problems among school children in Nepal. Therefore, this study aimed to assess the association of gender and knowledge on DMFT index among school children.

    METHODS: A cross-sectional study was conducted among school children of Grade Seven in 12 schools of Kaski district in Nepal. Schools were randomly selected from the urban and semi-urban areas in the district. Data were collected covering oral health knowledge, socio-demographic characteristics, oral health condition and practices. The factors of poor oral health condition and practices were examined using t-test, one-way ANOVA, and multiple linear regression.

    RESULTS: Of the total participants (n = 669), 54.9% were females and their mean DMFT score was 1.82 (SD = 1.07). Total decayed score was higher among those who did not have knowledge that fluoride prevents decay compared to those who had knowledge about it (Being aware of fluoride prevents decay: Mean = 1.21 (SD = 1.54) versus not being aware of that: mean = 2.13 (SD = 2.13); p = 0.029). Females were more likely to have higher DMFT scores compared to males (β-coefficient = 0.43, 95% CI 0.13, 0.73, p = 0.005). In addition, higher knowledge score was negatively associated with higher DMFT score (β-coefficient = - 0.09, 95% CI - 0.20, -0.01, p = 0.047).

    CONCLUSION: Being female students and those having lower level of knowledge on oral health attributed to higher DMFT index. Periodic dental check-up coupled with oral health education on regular brushing, use of fluoridated paste, tongue cleaning and care of gum diseases are recommended in schools.

  11. Advancements in nanotherapeutics targeting senescence in chronic obstructive pulmonary disease
    Paudel KR, Mehta M, Shukla SD, Panth N, Chellappan DK, Dua K, et al.
    Nanomedicine (Lond), 2022 Oct;17(23):1757-1760.
    PMID: 35060764 DOI: 10.2217/nnm-2021-0373
  12. Removal of chloride ion from drinking water using Ag NPs-Modified bentonite: Characterization and optimization of effective parameters by response surface methodology-central composite design
    Moradi H, Sabbaghi S, Mirbagheri NS, Chen P, Rasouli K, Kamyab H, et al.
    Environ Res, 2023 Apr 15;223:115484.
    PMID: 36775091 DOI: 10.1016/j.envres.2023.115484
    The presence of chloride ion as an environmental pollutant is having a devastating and irreversible effect on aquatic and terrestrial ecosystems. To ensure safe and clean drinking water, it is vital to remove this substance using non-toxic and eco-friendly methods. This study presents a novel and highly efficient Ag NPs-modified bentonite adsorbent for removing chloride ion, a common environmental pollutant, from drinking water using a facile approach. The surface chemical properties and morphology of the pristine Na-bentonite and Ag NPs-Modified bentonite were characterized by field emission scanning electron microscopy (FESEM) and X-ray spectroscopy (EDX), X-Ray diffraction (XRD), Fourier transform infrared (FTIR), and zeta potential (ζ). To achieve maximum chloride ion removal, the effects of experimental parameters, including adsorbent dosage (1-9 g/L), chloride ion concentration (100-900 mg/L), and reaction time (5-25 h), were examined using the Response Surface Methodology (RSM). The chloride ion removal of 90% was obtained at optimum conditions (adsorbent dosage: 7 g/L, chloride ion concentration: 500 mg/L, and reaction time: 20 h). The adsorption isotherm and kinetics results indicated that the Langmuir isotherm model and pseudo-second-order kinetics were found suitable to chloride ion removal. Additionally, the regeneration and reusability of the Ag NPs-modified bentonite were further studied. In the regeneration and reusability study, the Ag NPs-modified bentonite has shown consistently ≥90% and ≥87% chloride ion removal even up to 2 repeated cycles, separately. Thus, the findings in this study provided convincing evidence for using Ag-NPs modified bentonite as a high-efficiency and promising adsorbent to remove chloride ion from drinking water.
  13. The versatility of 18ß-glycyrrhetinic acid in attenuating pulmonary inflammatory disorders
    Mohamad MSB, Reyes RJ, De Rubis G, Paudel KR, Hansbro PM, Dua K, et al.
    EXCLI J, 2023;22:188-190.
    PMID: 36998703 DOI: 10.17179/excli2023-5845
  14. Fulltext Foaming properties, wettability alteration and interfacial tension reduction by saponin extracted from soapnut (Sapindus Mukorossi) at room and reservoir conditions
    Yekeen N, Malik AA, Idris AK, Reepei NI, Ganie K
    J Pet Sci Eng, 2020 Dec;195:107591.
    PMID: 32834477 DOI: 10.1016/j.petrol.2020.107591
    In this study, a natural surfactant, saponin was isolated from soapnut (Sapindus Mukorossi). The extracted surfactant was characterized by Fourier-transform infrared spectroscopy (FTIR) analysis. The effectiveness of the isolated surfactant as EOR agent was evaluated from foam generation/stabilization properties, wettability alteration of the rock surfaces, as well as oil-water interfacial tension (IFT) reduction characteristics. The performance of the extracted saponin was compared with that of a commercial saponin and sodium dodecyl sulfate (SDS). The foaming properties of the saponin with carbon dioxide (CO2) was characterized using Teclis Foamscan instrument at room condition and 60 °C. The IFT and contact angles at room conditions and reservoir conditions were measured using KRŰSS Drop Shape Analyzer (DSA 25 and DSA 100) via pendant drop and sessile drop techniques respectively. The foamability of the saponin-stabilized foam was good at ambient condition and 60 °C. Moreover, the time taken for almost 100% liquid drainage was higher in saponin-stabilized foam than the SDS-stabilized foam. The optimum concentration for attaining maximum foam stability decreased from 0.4 wt% at room temperature to 0.1 wt% at 60 °C. Signifying that the quantity of the surfactant to be used in foam generation could reduce at high temperature. The isolated saponin exhibited relatively good interfacial activities individually and in synergistic interaction with silicon dioxide (SiO2) nanoparticles at reservoir conditions. Precisely, at 8 MPa and 80 °C, the crude-oil water IFT was reduced from 23.24 mN/m to 1.59 mN/m (about 93.2%) by 0.2 wt% saponin concentration. The IFT was further reduced to 0.87 mN/m (about 96.3%) by a mixed system of 0.5 wt% saponin and 0.05 wt% SiO2 nanoparticles concentration. Increasing IFT with increasing temperature were observed at very high temperature due to phase separation resulting from clouding phenomenon. However, the clouding temperature increased with 0.1 wt% saponin concentration, and in presence of SiO2 nanoparticles (0.05 wt% and 0.1 wt%). The study suggests that the extracted saponin could be considered as supplementary alternative to conventional EOR surfactants.
  15. Fulltext Determination of Median Lethal Concentration (LC50) for Endosulfan, Heptachlor and Dieldrin Pesticides to African Catfish, Clarias gariepinus and Their Impact on Its Behavioral Patterns and Histopathological Responses
    Islam MA, Amin SMN, Brown CL, Juraimi AS, Uddin MK, Arshad A
    Toxics, 2021 Dec 08;9(12).
    PMID: 34941774 DOI: 10.3390/toxics9120340
    Pesticides such as endosulfan, heptachlor and dieldrin persist in aquatic environments as a result of their resistance to biodegradation. However, there is no adequate information about the toxicity of endosulfan, heptachlor and dieldrin to the aquatic organism, African catfish (Clarias gariepinus)-a high valued widely distributed commercially interesting species. The current experiment was performed with the aim to determine the median lethal concentration (LC50) of endosulfan, heptachlor and dieldrin to African catfish (Clarias gariepinus); their behavioral abnormalities and histopathological alterations in several vital organs. A total of 324 juvenile fish were exposed for 96 h to six concentrations of endosulfan and dieldrin at 0, 0.001, 0.002, 0.004, 0.008 and 0.016 ppm, and to heptachlor at concentrations of 0, 0.02, 0.04, 0.08, 0.16 and 0.32 ppm for dose-response tests. The study demonstrated that the species is highly susceptible to those contaminants showing a number of behavioral abnormalities and histopathological changes in gill, liver and muscle. The 96-h LC50 value of endosulfan, dieldrin and heptachlor for the African catfish was found as 0.004 (0.001-0.01) mg/L, 0.006 mg/L and 0.056 (0.006-0.144) mg/L, respectively. Abnormal behaviors such as erratic jerky swimming, frequent surfacing movement with gulping of air, secretion of mucus on the body and gills were observed in response to the increasing exposure concentrations. Histopathological alterations of liver, gill and muscle tissues were demonstrated as vacuolization in hepatocytes, congestion of red blood cells (RBCs) in hepatic portal vein; deformed secondary lamellae and disintegrated myotomes with disintegrated epidermis, respectively. These findings are important to monitor and responsibly manage pesticide use in and around C. gariepinus aquacultural areas.
  16. Procurement process and shortages of essential medicines in public health facilities: A qualitative study from Nepal
    Adhikari B, Ranabhat K, Khanal P, Poudel M, Marahatta SB, Khanal S, et al.
    PLOS Glob Public Health, 2024;4(5):e0003128.
    PMID: 38696399 DOI: 10.1371/journal.pgph.0003128
    Ensuring access to essential medicines remains a formidable challenge in Nepal. The specific reasons for the shortage of essential medicines within Nepal have not been extensively investigated. This study addresses challenges associated with access to essential medicines, procurement process difficulties, and functionality of inventory management systems at different levels of public health facilities. Fifty-nine semi-structured in-depth interviews were conducted with health managers and service providers at provincial and local levels in six randomly selected districts of Bagmati province, Nepal. Interviews were audiotaped and transcribed verbatim, and the results were analyzed using the inductive approach and were later mapped within the four domains of "Procurement of essential medicines". The major barriers for the effective management of essential medicines included delays in the procurement process, primarily locally, leading to frequent stock-out of essential drugs, particularly at the health post level. Additionally, challenges arise from storage problems, mainly due to insufficient storage space and the need to manage additional comorbidities related to COVID-19. Other identified challenges encompass the absence of training on logistics management information systems, a lack of information technology resources in primary health facilities, inadequate qualified human resources to operate the IT system, and insufficient power backup. Moreover, unrealistic demand estimation from the service points, inadequate transportation costs, and manual inventory management systems further contributed to the complex landscape of challenges. This study identified procurement delays as the primary cause of essential medicine shortages in Bagmati Province, Nepal. We recommend implementing comprehensive procurement guidelines, collaborative training, and dedicated budgets to address this issue. Improving the procurement and inventory management process in low-resource settings requires a well-trained workforce, suitable storage spaces, and enhanced coordinated administrative tiers within health facilities at different levels to ensure the year-round availability of essential medicines in these settings.
  17. Cationic cycloamylose based nucleic acid nanocarriers
    Prasher P, Sharma M, Agarwal V, Singh SK, Gupta G, Dureja H, et al.
    Chem Biol Interact, 2024 Apr 12;395:111000.
    PMID: 38614318 DOI: 10.1016/j.cbi.2024.111000
    Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.
  18. Physio-chemical, microbiological properties of tempoyak and molecular characterisation of lactic acid bacteria isolated from tempoyak
    Chuah LO, Shamila-Syuhada AK, Liong MT, Rosma A, Thong KL, Rusul G
    Food Microbiol, 2016 Sep;58:95-104.
    PMID: 27217364 DOI: 10.1016/j.fm.2016.04.002
    This study aims to determine physio-chemical properties of tempoyak, characterise the various indigenous species of lactic acid bacteria (LAB) present at different stages of fermentation and also to determine the survival of selected foodborne pathogens in tempoyak. The predominant microorganisms present in tempoyak were LAB (8.88-10.42 log CFU/g). Fructobacillus durionis and Lactobacillus plantarum were the dominant members of LAB. Other LAB species detected for the first time in tempoyak were a fructophilic strain of Lactobacillus fructivorans, Leuconostoc dextranicum, Lactobacillus collinoides and Lactobacillus paracasei. Heterofermentative Leuconostoc mesenteroides and F. durionis were predominant in the initial stage of fermentation, and as fermentation proceeded, F. durionis remained predominant, but towards the end of fermentation, homofermentative Lb. plantarum became the predominant species. Lactic, acetic and propionic acids were present in concentrations ranging from 0.30 to 9.65, 0.51 to 7.14 and 3.90 to 7.31 mg/g, respectively. Genotyping showed a high degree of diversity among F. durionis and Lb. plantarum isolates, suggesting different sources of LAB. All tested Lb. plantarum and F. durionis (except for one isolate) isolates were multidrug resistant. Salmonella spp., Listeria monocytogenes and Staphylococcus aureus were not detected. However, survival study showed that these pathogens could survive up to 8-12 days. The results aiming at improving the quality and safety of tempoyak.
  19. Fulltext The Potential and Concerns of Using AI in Scientific Research: ChatGPT Performance Evaluation
    Khlaif ZN, Mousa A, Hattab MK, Itmazi J, Hassan AA, Sanmugam M, et al.
    JMIR Med Educ, 2023 Sep 14;9:e47049.
    PMID: 37707884 DOI: 10.2196/47049
    BACKGROUND: Artificial intelligence (AI) has many applications in various aspects of our daily life, including health, criminal, education, civil, business, and liability law. One aspect of AI that has gained significant attention is natural language processing (NLP), which refers to the ability of computers to understand and generate human language.

    OBJECTIVE: This study aims to examine the potential for, and concerns of, using AI in scientific research. For this purpose, high-impact research articles were generated by analyzing the quality of reports generated by ChatGPT and assessing the application's impact on the research framework, data analysis, and the literature review. The study also explored concerns around ownership and the integrity of research when using AI-generated text.

    METHODS: A total of 4 articles were generated using ChatGPT, and thereafter evaluated by 23 reviewers. The researchers developed an evaluation form to assess the quality of the articles generated. Additionally, 50 abstracts were generated using ChatGPT and their quality was evaluated. The data were subjected to ANOVA and thematic analysis to analyze the qualitative data provided by the reviewers.

    RESULTS: When using detailed prompts and providing the context of the study, ChatGPT would generate high-quality research that could be published in high-impact journals. However, ChatGPT had a minor impact on developing the research framework and data analysis. The primary area needing improvement was the development of the literature review. Moreover, reviewers expressed concerns around ownership and the integrity of the research when using AI-generated text. Nonetheless, ChatGPT has a strong potential to increase human productivity in research and can be used in academic writing.

    CONCLUSIONS: AI-generated text has the potential to improve the quality of high-impact research articles. The findings of this study suggest that decision makers and researchers should focus more on the methodology part of the research, which includes research design, developing research tools, and analyzing data in depth, to draw strong theoretical and practical implications, thereby establishing a revolution in scientific research in the era of AI. The practical implications of this study can be used in different fields such as medical education to deliver materials to develop the basic competencies for both medicine students and faculty members.

  20. Fulltext Mpropred: A machine learning (ML) driven Web-App for bioactivity prediction of SARS-CoV-2 main protease (Mpro) antagonists
    Ferdous N, Reza MN, Hossain MU, Mahmud S, Napis S, Chowdhury K, et al.
    PLoS One, 2023;18(6):e0287179.
    PMID: 37352252 DOI: 10.1371/journal.pone.0287179
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in 2019 and still requiring treatments with fast clinical translatability. Frequent occurrence of mutations in spike glycoprotein of SARS-CoV-2 led the consideration of an alternative therapeutic target to combat the ongoing pandemic. The main protease (Mpro) is such an attractive drug target due to its importance in maturating several polyproteins during the replication process. In the present study, we used a classification structure-activity relationship (CSAR) model to find substructures that leads to to anti-Mpro activities among 758 non-redundant compounds. A set of 12 fingerprints were used to describe Mpro inhibitors, and the random forest approach was used to build prediction models from 100 distinct data splits. The data set's modelability (MODI index) was found to be robust, with a value of 0.79 above the 0.65 threshold. The accuracy (89%), sensitivity (89%), specificity (73%), and Matthews correlation coefficient (79%) used to calculate the prediction performance, was also found to be statistically robust. An extensive analysis of the top significant descriptors unveiled the significance of methyl side chains, aromatic ring and halogen groups for Mpro inhibition. Finally, the predictive model is made publicly accessible as a web-app named Mpropred in order to allow users to predict the bioactivity of compounds against SARS-CoV-2 Mpro. Later, CMNPD, a marine compound database was screened by our app to predict bioactivity of all the compounds and results revealed significant correlation with their binding affinity to Mpro. Molecular dynamics (MD) simulation and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) analysis showed improved properties of the complexes. Thus, the knowledge and web-app shown herein can be used to develop more effective and specific inhibitors against the SARS-CoV-2 Mpro. The web-app can be accessed from https://share.streamlit.io/nadimfrds/mpropred/Mpropred_app.py.
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