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.
AIMS: To systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.
DESIGN: A scoping review was carried out by adhering to Arksey and O'Malley's 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levac et al. DATA SOURCES: Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.
ELIGIBILITY CRITERIA: All peer-reviewed studies in English, reporting the enablers and the challenges of implementing PGx in the primary care settings were included.
DATE EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data. Information was synthesised based on the reported enablers and the challenges of implementing PGx testing in the primary care settings. Information was then presented to stakeholders for their inputs.
RESULTS: 78 studies discussing the implementation of PGx testing are included, of which 57% were published between 2019 and 2023. 68% of the studies discussed PGx testing in the primary care setting as a disease-specific themes. Healthcare professionals were the major stakeholders, with primary care physicians (55%) being the most represented. Enablers encompassed various advantages such as diagnostic and therapeutic benefits, cost reduction and the empowerment of healthcare professionals. Challenges included the absence of sufficient scientific evidence, insufficient training for healthcare professionals, ethical and legal aspects of PGx data, low patient awareness and acceptance and the high costs linked to PGx testing.
CONCLUSION: PGx testing integration in primary care requires increased consumer awareness, comprehensive healthcare provider training on legal and ethical aspects and global feasibility studies to better understand its implementation challenges. Managing high costs entails streamlining processes, advocating for reimbursement policies and investing in research on innovation and affordability research to improve life expectancy.
METHODS: This is a retrospective cohort study of 9-year-old Singaporean children. The primary outcome was the success of prophylactic management of asymptomatic DE premolars with a single session of tubercle grinding and composite overlay, as determined by the absence of clinical signs or symptoms. The factors associated with survival of DE premolars treated were evaluated using Cox proportional hazard regression.
RESULTS: The prevalence of DE among Singaporean children was 7.1% (12,677/178,801). DE premolars were more prevalent among females (56.1%) and those of Chinese ethnicity (87.1%). At the tooth level, 26,875 asymptomatic DE premolars were prophylactically managed with tubercle grinding and composite overlay and 2471 DE premolars did not receive any intervention. The mean review period was 46.2 ± 20.2 months. The success rate for DE premolars that received the intervention was significantly higher (p
METHODS: Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6 months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed.
RESULTS: One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8 months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p
METHODS: This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.
FINDINGS: Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff.
INTERPRETATION: Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors.
FUNDING: Novo Nordisk.