MAIN METHODS: A pull-down assay was performed to identify the binding partner of the L-SP40 peptide. Co-immunoprecipitation and co-localization assays with the L-SP40 peptide were employed to confirm the receptor partner in RD cells. The outcomes were validated using receptor knockdown and antibody blocking assays. The L-SP40 peptide was further evaluated for the protection of neonatal mice against lethal challenge by mouse-adapted EV-A71.
KEY FINDINGS: The L-SP40 peptide was found to interact and co-localize with nucleolin, the key attachment receptor of Enteroviruses A species, as demonstrated in the pull-down, co-immunoprecipitation and co-localization assays. Knockdown of nucleolin from RD cells led to a significant reduction of 3.5 logs of viral titer of EV-A71. The L-SP40 peptide demonstrated 80% protection of neonatal mice against lethal challenge by the mouse-adapted virus with a drastic reduction in the viral loads in the blood (~4.5 logs), skeletal muscles (1.5 logs) and brain stem (1.5 logs).
SIGNIFICANCE: L-SP40 peptide prevented severe hind limb paralysis and death in suckling mice and could serve as a potential broad-spectrum antiviral candidate to be further evaluated for safety and potency in future clinical trials against EV-A71.
OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.
METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.
RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.
CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.
METHODS: We retrieved data from patients who experienced seizures before age 12 months and were followed for over two years, using electronic patient records at Hospital Raja Perempuan Zainab II in Kelantan, a state in Malaysia's east coast. We retrospectively reviewed these records and assessed clinical outcomes based on the last follow-up.
RESULTS: Of 75 patients, 61 (81.3%) achieved good seizure control or remission. At the last follow-up, 24 (32%) exhibited developmental delay, whereas 19 (25.3%) displayed abnormal neuroimaging. Patients with abnormal background electroencephalographic (EEG) activity, as well as abnormal radiological findings, were more likely to experience poor seizure control and unfavorable developmental outcomes (P
METHODS: This questionnaire development study involved four phases: (i) exploring and understanding the subject matter, (ii) questionnaire development, (iii) content validity testing, and lastly, (iv) field-testing of the questionnaire. For the field-testing phase, a cross-sectional self-administered survey of JoinCT was conducted among cancer patients with various socio-demographic backgrounds and medical conditions. Besides content validity, Cronbach's alpha was used to evaluate the internal consistency of domains, and confirmatory factor analysis was used to evaluate the model fit of the JoinCT framework.
RESULTS: A total of 389 respondents participated in the survey. Based on the results obtained from a field data collection phase, JoinCT consisted of four independent variables domains, namely "knowledge", "perception of benefits", "perception of risks", and "confidence". The only dependent variable was the willingness to participate in a clinical trial. The minimum Cronbach's alpha was 0.937, and the model fit for the overall framework of JoinCT is also excellent with Comparative Fit Index (> 0.90), root mean square error approximation (
OBJECTIVE: The aim of this study was to compare the perioperative outcome of posterior spinal fusion (PSF) between overweight (OW) adolescent idiopathic scoliosis (AIS) patients and the healthy-weight (HW) patients using propensity score matching analysis.
SUMMARY OF BACKGROUND DATA: Obesity was found to increase postoperative surgical complications compared with the nonobese group. In scoliosis correction surgery, association of OW and perioperative risks had been explored, but most studies were retrospective in nature.
METHODS: From 374 patients, two comparable groups were matched using propensity score matching analysis with one-to-one nearest neighbor matching and a caliper of 0.2. There were 46 HW and OW patients in each group. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay post-surgery, total patient-controlled analgesia (PCA) morphine usage, perioperative complications, side bending flexibility (SBF), and correction rate (%).
RESULTS: The mean age was 13.3 ± 1.7 and 13.2 ± 1.7 years for HW and OW groups, respectively. The majority of the patients were Lenke 1 curves; 32.6% (HW) and 26.1% (OW) with an average Cobb angle of 69.0 ± 19.1° and 68.8 ± 18.4° for each group, respectively. The two groups were comparable. The operation time was 145.2 ± 42.2 and 154.4 ± 48.3 minutes for HW and OW groups, respectively (P > 0.05). The intraoperative blood loss was almost similar in both groups; 955.1 ± 497.7 mL (HW group) and 1011.8 ± 552.7 mL (OW group) (P > 0.05). Total PCA morphine used was higher in OW group (30.4 ± 22.7 mg) than in the HW group (16.2 ± 11.3 mg). No complication was observed in HW group, while in OW group, one patient (2.2%) developed intraoperative seizure.
CONCLUSION: OW AIS patients (≥85th percentile) had similar mean operative time, intraoperative blood loss, allogeneic transfusion rate, length of stay, and perioperative complications compared with HW AIS patients.
LEVEL OF EVIDENCE: 3.
OBJECTIVE: To evaluate the perioperative outcome of dual attending surgeon strategy for severe adolescent idiopathic scoliosis (AIS) patients with Cobb angle more than or equal to 90°.
SUMMARY OF BACKGROUND DATA: The overall complication rate for AIS remains significant and is higher in severe scoliosis. Various operative strategies had been reported for severe scoliosis. However the role of dual attending surgeon strategy in improving the perioperative outcome in severe scoliosis has not been investigated.
METHODS: The patients were stratified into two groups, Cobb angles 90° to 100° (Group 1) and more than 100° (Group 2). Demographic, intraoperative, preoperative, and postoperative day 2 data were collected. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay postsurgery, and documentation of any perioperative complications.
RESULTS: Eighty-five patients were recruited. The mean age for the whole cohort was 16.2 ± 5.2 years old. The mean age of Group 1 was 16.7 ± 5.7 and Group 2 was 15.6 ± 4.8 years old. The majority of the patients in both groups were Lenke 2 curves with the average Cobb angle of 93.9 ± 3.0° in Group 1 and 114.2 ± 10.2° in Group 2. The average operative time was 198.5 ± 47.5 minutes with an average blood loss of 1699.5 ± 939.3 mL. The allogeneic blood transfusion rate was 17.6%. The average length of stay postoperation was 71.6 ± 22.5 hours. When comparing the patients between Group 1 and Group 2, the operating time, total blood loss, allogeneic transfusion rate showed significant intergroup differences. Five complications were documented (one intraoperative seizure, one massive blood loss, one intraoperative loss of somatosensory evoked potential (SSEP) signal, and two superficial wound breakdown).
CONCLUSION: Dual attending surgeon strategy in severe AIS more than or equal to 90° demonstrated an average operative time of 199 minutes, intraoperative blood loss of 1.7 L, postoperative hospital stay of 71.6 hours, and a complication rate of 5.9% (5/85 patients). Curves with Cobb angle more than 100° lead to longer operating time, greater blood loss, and allogeneic transfusion rate.
LEVEL OF EVIDENCE: 4.
RESULTS: All HPs of B. lehensis G1 were grouped according to their predicted functions based on the presence of functional domains in their sequences. From the metal-binding group of HPs of the cluster, an HP termed Bleg1_2507 was discovered to contain a thioredoxin (Trx) domain and highly-conserved metal-binding ligands represented by Cys69, Cys73 and His159, similar to all prokaryotic and eukaryotic Sco proteins. The built 3D structure of Bleg1_2507 showed that it shared the βαβαββ core structure of Trx-like proteins as well as three flanking β-sheets, a 310 -helix at the N-terminus and a hairpin structure unique to Sco proteins. Docking simulations provided an interesting view of Bleg1_2507 in association with its putative cytochrome c oxidase subunit II (COXII) redox partner, Bleg1_2337, where the latter can be seen to hold its partner in an embrace, facilitated by hydrophobic and ionic interactions between the proteins. Although Bleg1_2507 shares relatively low sequence identity (47%) to BsSco, interestingly, the predicted metal-binding residues of Bleg1_2507 i.e. Cys-69, Cys-73 and His-159 were located at flexible active loops similar to other Sco proteins across biological taxa. This highlights structural conservation of Sco despite their various functions in prokaryotes and eukaryotes.
CONCLUSIONS: We propose that HP Bleg1_2507 is a Sco protein which is able to interact with COXII, its redox partner and therefore, may possess metallochaperone and redox functions similar to other documented bacterial Sco proteins. It is hoped that this scientific effort will help to spur the search for other physiologically relevant proteins among the so-called "orphan" proteins of any given organism.