METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.
RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.
CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.
METHODS: Nine full-text articles in English that reported the clinical and radiological outcomes of KA TKA were included. Five studies had a control group of patients who underwent MA TKA. Data on patient demographics, clinical scores, and radiological results were extracted. There were two level I, one level II, three level III, and three level IV studies. Six of the nine studies used patient-specific instrumentation, one study used computer navigation, and two studies used manual instrumentation.
RESULTS: The clinical outcomes of KA TKA were comparable or superior to those of MA TKA with a minimum 2-year follow-up. Limb and knee alignment in KA TKA was similar to those in MA TKA, and component alignment showed slightly more varus in the tibial component and slightly more valgus in the femoral component. The JLOA in KA TKA was relatively parallel to the floor compared to that in the native knee and not oblique (medial side up and lateral side down) compared to that in MA TKA. The implant survivorship and complication rate of the KA TKA were similar to those of the MA TKA.
CONCLUSION: Similar or better clinical outcomes were produced by using a KA TKA at early-term follow-up and the component alignment differed from that of MA TKA. KA TKA seemed to restore function without catastrophic failure regardless of the alignment category up to midterm follow-up. The JLOA in KA TKA was relatively parallel to the floor similar to the native knee compared to that in MA TKA. The present review of nine published studies suggests that relatively new kinematic alignment is an acceptable and alternative alignment to mechanical alignment, which is better understood. Further validation of these findings requires more randomized clinical trials with longer follow-up.
LEVEL OF EVIDENCE: Level II.
METHODS: Cancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.
RESULTS: Phyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.
CONCLUSIONS: Phyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.
METHODS: This is an 18-month cluster-randomized, open-label, parallel-arm controlled trial conducted at 14 public hospitals in the Perak state of Malaysia. Patients aged 60 and above, who have at least one medication and one comorbidity are eligible. A stratified-cluster randomization design is employed, with 7 hospitals assigned to the control arm and 7 hospitals assigned to the intervention arm. The MALPIP screening tool will be used in the intervention group to review the medications. If PIM is detected, the pharmacists will discuss with doctors and decide whether to stop or reduce the dose. The primary outcomes of this trial are the total number of medications and number of PIM. The secondary outcomes include fall, emergency department visits, readmissions, quality of life and mortality. Outcomes will be measured during enrolment, discharge, 6, 12, and 18 months.
DISCUSSION: This REVMED trial aims to test the hypothesis that a pharmacist-led deprescribing intervention initiated in the hospital will reduce the total number of medications and PIM 18 months after hospital discharge, reducing fall, emergency department visits, readmissions, mortality and lead to improvement in quality of life. Trial findings will quantify the clinical outcomes associated with reducing medications and PIM for hospitalized older adults with polypharmacy.
TRIAL REGISTRATION NUMBER: This trial was prospectively registered at clinicaltrials.gov (NCT05875623) on the 25th of May 2023. NCT05875623 Clinicaltrials.gov URL: NCT05875623 registered on 25th July 2023.
METHOD: This cross-sectional study was conducted in 14 Perak state hospitals and 12 primary health clinics through an online survey. All ward pharmacists and trainee pharmacists with at least 1 month of ward pharmacy experience and working in government-funded health facilities were included. The validated survey tool consisted of demographic characteristics, pharmacists' experience towards challenges (22 items), and their attitude towards adaptive measures (9 items). Each item was measured based on a 5-point Likert scale. One-way ANOVA and logistic regression were employed to determine the association of pharmacists' characteristics against their experience and attitude.
RESULTS: Out of 175 respondents, 144 (81.8%) were female, and 84 (47.7%) were Chinese. Most pharmacists served in the medical ward (124, 70.5%). Commonly reported perceived challenges were difficulties in counselling medication devices (3.63 ± 1.06), difficulties in clerking medication history from family members (3.63 ± 0.99), contacting family members (3.46 ± 0.90), patient's digital illiteracy in virtual counselling (3.43 ± 1.11) and completeness of the electronic records (3.36 ± 0.99). For attitude towards adaptive measures, improving internet connection (4.62 ± 0.58), ensuring availability of multilingual counselling videos (4.45 ± 0.64), and provision of internet-enabled mobile devices (4.39 ± 0.76) were the most agreeable by the pharmacists. Male (AOR: 2.63, CI 1.12-6.16, p = 0.026) and master's degree holders (AOR: 2.79, CI 0.95-8.25, p = 0.063) had greater odds of high perceived challenging experience scores. Master's degree holders (AOR: 8.56, CI 1.741-42.069, p = 0.008) were also more likely to have a positive attitude score towards adaptive measures.
CONCLUSION: Pharmacists faced multiple challenges in the ward pharmacy practice during the COVID-19 pandemic, especially in medication history assessment and patient counselling. Pharmacists, especially those with higher levels of education and longer tenure, exhibited a higher level of agreement towards the adaptive measures. The positive attitudes of pharmacists towards various adaptive measures, such as improvement of internet infrastructure and digital health literacy among patients and family members, warrant immediate action plans from health authorities.
METHODS: A literature review of PubMed with a focus on historical and landmark studies was undertaken to classify the evidence according to the different stages of the IDEAL Framework.
RESULTS: Several different transoral approaches were developed by a small of number of surgeon-innovators on animals and cadavers, and subsequently in first-in-human studies. The trivestibular approach emerged as the safest technique, with further refinements of this technique culminating in TOETVA. The basic steps and indications for this technique have been standardized and it is now being replicated by early adopters in many centres worldwide. The development of TOETVA has closely aligned with the IDEAL Framework, and is currently at stage 2B (Exploration).
CONCLUSION: There is need for multi-institutional collaborations and international registry studies to plan high-quality randomized trials comparing TOETVA with other remote-access approaches and collect long-term follow-up data. In countries where TOETVA has yet to be adopted, the IDEAL Framework will be a useful roadmap for government regulators and professional societies to evaluate, regulate, and provide best practice recommendations for the adoption of this technique.
METHODS: Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.
RESULTS: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.
CONCLUSIONS: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.