AIM OF THE STUDY: This study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans.
MATERIALS AND METHODS: A cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay.
RESULTS: Various glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K+ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%.
CONCLUSIONS: These findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.
METHODS: A micelle was prepared using the film hydration method, and the micellar solution was lyophilized. The cake formed was analyzed. The factors investigated include the concentrations of the surfactants, ratio of vitamin E TPGS/Poloxamer 407, temperature of the hydrating solution, duration of hydration, and freezing temperature before lyophilization. The effects of these factors on the encapsulation efficiency and particle size of the micelle were also studied. The encapsulation efficiency was measured using a UV-Vis spectrophotometer, while particle size was measured using dynamic light scattering.
RESULTS: The optimized micelle was found to have 90% encapsulation efficiency with a particle size of less than 40 nm, which was achieved using a 10% concentration of surfactants at a vitamin E TPGS/Poloxamer 407 ratio of 3:1. The optimized temperature for hydrating the micellar film was 40 °C, the optimized mixing time was 1 h, and the optimized freezing temperature was -80 °C. The solubility of the luteolin-loaded micelles increased 459-fold compared to pure Lut in water. The critical micelle concentration of the vitamin E TPGS/Poloxamer 407 micelle was 0.001 mg/mL, and the release study showed that luteolin-loaded micelles exhibited sustained release behavior. The release of luteolin from a micelle was found to be higher in pH 6.8 compared to pH 7.4, which signified that luteolin could be accumulated more in a tumor microenvironment compared to blood.
CONCLUSION: This study demonstrated that several factors need to be considered when developing such nanoparticles in order to obtain a well-optimized micelle.
METHODS: Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied.
RESULTS: The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days (p
EXPERIMENTAL PROCEDURE: This study investigated the protective effects of xLr® and its high, medium, and low molecular weight (HLR, MLR, and LLR, respectively) fractions against UVB irradiation using in vivo Caenorhabditis elegans (C. elegans) model.
RESULTS AND CONCLUSION: The investigation revealed a significant lifespan extension of xLr® and its fractions in UVB-irradiated C. elegans, which could be mediated by the regulation of genes associated with anti-oxidant (daf-16 and sod-3) and apoptosis (cep-1, hus-1, ced-13, and egl-1) pathways. xLr® significantly reduced the ROS production in C. elegans and increased the DAF-16 nuclear translocation compared to untreated worms. Additionally, the SOD-3 expression was increased in the xLr®-treated worms. Hence, it suggests that the different components in xLr® work synergistically to protect against UVB irradiation. Our findings may be beneficial for the application of xLr® as a treatment against UVB-induced cellular damage and photoaging.
OBJECT: The ethanolic extract of Rhodiola rosea roots, rich in bioactive compounds like alkaloids and flavonoids, was optimized into a phytosomal complex to improve absorption and dermal retention.
METHOD: Characterization through GC-MS revealed compounds, such as 2-Heptadecenal and Bicyclo[ 4.1.0]Heptane and 7-Pentyl. FTIR confirmed the successful encapsulation within the phospholipid bilayer, while SEM showed smooth, spherical particles.
RESULT: The Box-Behnken design optimized formulation parameters, achieving high yield (92.64%), small particle size (355 nm), and high entrapment efficiency (93.98%). In vitro release studies displayed a consistent release profile, aligning with Zero-order and Hixson-Crowell models. In vivo evaluation on Wistar rats showed that the phytosomal gel significantly enhanced wound healing, achieving 98.16% wound reduction by day 14, compared to 95.17% for R. rosea extract and 97.13% for standard treatment. Histopathological analysis demonstrated complete tissue regeneration and well-organized collagen fibers in the phytosomal gel group.
CONCLUSION: This research highlights the potential of Rhodiola rosea phytosomal gel as an effective wound healing therapy, with future studies suggested for extended stability tests and human skin permeation studies.
Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.
Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.
Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.
Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.
Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P
METHODS: This is an investigator-initiated, prospective, international, multicenter, open-label, randomized control clinical trial that plans to recruit 80 patients, who require fistuloplasty from dysfunctional arteriovenous fistula (AVF) from CAS. Eligible participants are randomly assigned to receive treatment with SG and PCB or PCB alone in a 1:1 ratio post-angioplasty (n = 40 in each arm). Randomization is stratified by de novo or recurrent lesion, and the participants are followed up for 1 year. The primary endpoints of the study are target lesion primary patency (TLPP) and access circuit primary patency (ACPP) rates at 6-months. The secondary endpoints are TLPP and ACPP at 3- and 12-month; target lesion and access circuit assisted primary and secondary patency rates at 3, 6, and 12-months and the total number of interventions; complication rate; and cost-effectiveness.
DISCUSSION: This study will evaluate the clinical efficacy and safety of combination SG and PCB implantation compared to PCB alone in the treatment of CAS for hemodialysis patients.
MATERIALS AND METHODS: A prospective cohort study of cancer patients and healthy individuals receiving vaccines was conducted in Malaysia. All participants were aged 18 or above at recruitment and received at least two doses of vaccine. We excluded patients who had missing serum antibody data post-first dose and post-second dose. Sociodemographic and clinical data were collected at baseline, prior to vaccination. Data on self-reported breakthrough infection was collected at six months. Multivariable linear mixed-effects regression models were used to investigate the association between the type of vaccine and serum IgG titer.
RESULTS: A total of 389 patients with solid (n=276, 71.0%) or hematologic cancers (n=113, 29.0%) were included, along with 246 healthy individuals. Most cancer patients received BNT162b2 (n=358, 92.0%), followed by AZ1222 (n=19, 4.9%) and Coronavac (n=12, 3.1%). Most healthy individuals received BNT162b2 (n=151, 61.4%), followed by Coronavac (n=95, 38.6%). Vaccination, after adjustment for confounders (pre-vaccine infection, age, ethnicity, comorbidity, timepoint, income, cancer type, and booster), with Coronavac was associated with lower log IgG titer (-3.09 U/ml, 95% confidence interval=-4.37 to -1.80, p<0.01) than that of BNT162b2 in patients with cancer and also lower log IgG titer (-2.64 U/ml, 95% confidence interval=-2.97 to -2.30, p<0.01) than that of BNT162b2 in healthy individuals. No effect modification by sex was observed. Among the cancer cohort, 76 patients (19.5%) reported breakthrough infections after vaccination, while 33 (13.4%) participants in the healthy cohort reported breakthrough infections after vaccination. Coronavac was associated with greater odds of breakthrough infection among healthy individuals (odds ratio=7.34 compared to BNT162b2, confidence interval=1.40 to 33.49, p=0.02).
CONCLUSION: Vaccination with BNT162b2 yields higher IgG titer than Coronavac in all groups and fewer breakthrough infections in healthy subjects. The effect of vaccination is not modified by sex.
MAIN BODY: We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of "graduation" of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact.
CONCLUSION: The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.
METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey.
RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel.
CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.