METHODS: We used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for ≥1 day and for whom time-to-appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups.
RESULTS: Among the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n = 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n = 477/1192) in inadequately treated patients (p
OBJECTIVE: In this work, various polysaccharide/gelatin amorphous hydrogels with the impregnation of oil palm leaf derived total flavonoid enriched extract (OPL-TFEE) were fabricated via one-pot synthesis method to provide multiple crosslinking networks.
METHOD: The bioflavonoids (OPL-TFEE) were derived from Elaeis guineensis leaf using an integrated green extraction and enrichment process. Amorphous hydrogels with good wound healing properties were developed by incorporating 0.3% antioxidant agent into the hybrid polymeric gelling system.
RESULT: The formulations appeared as a semi-solid dark yellow translucent hydrogel with good spreading and consistency characteristics and satisfying aesthetic properties. The FTIR analysis indicated that the bioflavonoid was compatible with the matrix, and the hydrogels showed porous morphological structures when observed under SEM. Furthermore, the hydrogels possessed shear thinning, pseudoplastic, and elastic properties. Bioflavonoids-impregnated polysaccharide/gelatin hydrogel release 95-98% bioflavonoids within 24 h, while the drug release profile followed the Korsmeyer-Peppas kinetic model. The hydrogels showed antioxidant and wound healing properties with no sign of cytotoxicity.
CONCLUSION: Overall, the results revealed bioflavonoid-loaded hydrogels exhibited good physicochemical and biological properties, thus could serve as new innovative formulation in the sustainable advancement of wound care product for promoting wound healing.
METHODS: The computational techniques involved dispersion-corrected density functional theory (DFT) with the B3LYP functional and the 6-311G** basis set. Grimme's D3 corrections were included to account for dispersion interactions. The calculations were performed via GAMESS-US software. Quantum descriptors of reactivity, such as ionization potential, electron affinity, chemical potential, and electrophilicity index, were derived from the HOMO and LUMO energies. Molecular docking studies were conducted via the CB-Dock server via AutoDock Vina software to predict binding affinities to cancer-related proteins. Petra/Osiris/Molinspiration (POM) analysis was used to predict the drug likeness and other pharmaceutical properties of the synthesized ILs.
METHODS: A systematic review and meta-analysis of 5-year postoperative GERD data comparing LVSG and LRYGB in adults were undertaken. Electronic databases were searched from January 2015 to March 2024 for publications meeting inclusion criteria. The Hartung-Knapp-Sidik-Jonkman random effects model was applied to estimate pooled odds ratio where meta-analysis was possible. Bias and certainty of evidence were assessed using the Cochrane Risk of Bias Tool 2 and GRADE.
RESULTS: Five RCTs were analysed (LVSG n = 554, LRYGB n = 539). LVSG was associated with increased adverse GERD outcomes compared to LRYGB at 5 years. The odds for revisional surgery to treat GERD in LVSG patients were 11 times higher compared to LRYGB (OR 11.47, 95% CI 1.83 to 71.69; p = 0.02; I2 = 0% High level of certainty). Similarly pharmacological management for increasing GERD was significantly more frequent in LVSG patients compared to LRYGB (OR 3.89, 95% CI 2.31 to 6.55; p ≤ 0.01; I2 = 0% Moderate level of certainty). Overall, LVSG was associated with significantly more interventions (both medical and surgical) for either worsening GERD and/or development of de novo GERD compared to LRYGB (OR 5.98, 95% CI 3.48 to 10.29; p ≤ 0.01; I2 = 0%) Moderate level of certainty).
CONCLUSIONS: The development and worsening of GERD symptoms are frequently associated with LVSG compared to LRYGB at 5 years postoperatively requiring either initiation or increase of pharmacotherapy or failing that revisional bariatric surgery. Appropriate patient/surgical selection is crucial to reduce these postoperative risks of GERD.
OBJECTIVES: Therefore, this study aims to evaluate and compare the antiviral effects of curcumin, BDHBC, and DHHPD in an in vitro model of RV infection.
METHODS: The inhibitory effects on RV-16 infection in H1 HeLa cells were assessed using cytopathic effect (CPE) reduction assay, virus yield reduction assay, RT-qPCR, and Western blot. Antiviral effects in different modes of treatment (pre-, co-, and post-treatment) were also compared. Additionally, intercellular adhesion molecule 1 (ICAM-1) expression, RV binding, and infectivity were measured with Western blot, flow cytometry, and virucidal assay, respectively.
RESULTS: When used as a post-treatment, BDHBC (EC50: 4.19 µM; SI: 8.32) demonstrated stronger antiviral potential on RV-16 compared to DHHPD (EC50: 18.24 µM; SI: 1.82) and curcumin (less than 50% inhibition). BDHBC also showed the strongest inhibitory effect on RV-induced CPE, virus yield, vRNA, and viral proteins (P1, VP0, and VP2). Furthermore, BDHBC pre-treatment has a prophylactic effect against RV infection, which was attributed to reduced basal expression of ICAM-1. However, it did not affect virus binding, but exerted virucidal activity on RV-16, contributing to its antiviral effect during co-treatment.
CONCLUSION: BDHBC exhibits multiple antiviral mechanisms against RV infection and thus could be a potential antiviral agent for RV.
METHOD: This randomized controlled trial was conducted on 80 nulliparous pregnant women who gave birth in four low-risk maternity clinics in Samarinda, Indonesia, from February to May 2022. The women were randomized into intervention (N=40) and control (N=40) groups based on random allocation. Certified midwives performed shiatsu massages following standard protocols. Pain was assessed using the Numeric Rating Scale, and anxiety was assessed using the Hamilton Anxiety Rating Score at three times including before the intervention (T0), the latent phase (T1), and at transition phase (T2). The impact of the intervention was analyzed using repeated measures analysis of variance by SPSS 26. A p-value less than 0.05 was considered statistically significant.
RESULTS: The intervention group showed a significant reduction in labour pain scores from 6.85±1.00 (T0) to 6.13±0.88 (T1) and 4.78±0.83 (T2) (P<0.001), while the control group showed an increase from 6.85±1.00 (T0) to 8.05±0.64 (T1) and 8.85±0.48 (T2) (P<0.001). Anxiety scores in the intervention group decreased from 28.53±4.41 (T0) to 26.15±3.59 (T1) and 20.65±2.69 (T2) (P<0.001), whereas the control group experienced an increase from 25.55±3.16 (T0) to 27.05±3.36 (T1) and 31.73±3.27 (T2) (P<0.001). The between-subject effects in time levels for labour pain and anxiety in the two study groups had a significant impact (P<0.001).
CONCLUSION: Findings showed that shiatsu massage was effective and safe for relieving pain and reducing anxiety during childbirth of nulliparous women. This research suggests that shiatsu massage can be used as an effective alternative method to relieve pain and anxiety during labour in low risk pregnancies, particularly in settings with limited access to pharmaceutical analgesics.Trial Registration Number: IRCT20220317054316N1.
METHODS: A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium's Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.
RESULTS: Of 11 860 participants (median age: 52 (IQR: 41-62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.
CONCLUSION: Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.
METHODS: The study utilized the docked dataset (Induced Fit Docking with Glide XP scoring function) from Loo et al., consisting of 46 ligands-23 agonists and 23 antagonists. The equilibrated structures from Loo et al. were subjected to 30 ns production simulations using GROMACS 2018 at 300 K and 1 atm with the velocity rescaling thermostat and the Parinello-Rahman barostat. AMBER ff99SB*-ILDN was used for the proteins, General Amber Force Field (GAFF) was used for the ligands, and Slipids parameters were used for lipids. MM/PBSA and MM/GBSA binding free energies were then calculated using gmx_MMPBSA. The solute dielectric constant was varied between 1, 2, and 4 to study the effect of different solute dielectric constants on the performance of MM/PB(GB)SA. The effect of entropy on MM/PB(GB)SA binding free energies was evaluated using the interaction entropy module implemented in gmx_MMPBSA. Five GB models, GBHCT, GBOBC1, GBOBC2, GBNeck, and GBNeck2, were evaluated to study the effect of the choice of GB models in the performance of MM/GBSA. Pearson correlation coefficients were used to measure the correlation between experimental and predicted binding free energies.
METHODOLOGY/PRINCIPAL FINDINGS: Spatiotemporal analysis of national notified CHIKV case addresses was performed. Between 2009-2022, 12,446 CHIKV cases were reported, with peaks in 2009 and 2020, and a significant shift from predominantly rural cases in 2009-2011 (85.1% rural), to urban areas in 2017-2022 (86.1% urban; p<0.0001). Two Ae. aegypti strains, field-collected MC1 and laboratory Kuala Lumpur (KL) strains, were fed infectious blood containing constructed CHIKV clones, pCMV-p2020A (E1-226A) and pCMV-p2020V (E1-226V) to measure CHIKV replication by real-time PCR and/or virus titration. The pCMV-p2020A clone replicated better in Ae. aegypti cell line Aag2 and showed higher replication, infection and dissemination efficiency in both Ae. aegypti strains, compared to pCMV-p2020V.
CONCLUSIONS/SIGNIFICANCE: This study revealed that a change in circulating CHIKV variants can be associated with changes in vector competence and outbreak epidemiology. Continued genomic surveillance of arboviruses is important.