Knowledge, attitudes, and practices related to dengue among public school teachers in a Central Luzon Province in the Philippines: an analytic cross-sectional study.

BACKGROUND: Dengue has become a major health issue in tropical regions as the numbers of reported cases and estimated infections continuously increase. In the Philippines, many challenges remain in preventing and controlling the disease amidst all the mitigation efforts of the government. This study sought to measure the health literacy of Filipino teachers and determine the associations among teachers' knowledge, attitudes, and selected practices (KAP) against dengue. METHODS: Elementary and secondary school teachers from the consistently declared dengue hotspots in the City of San Fernando, Pampanga, Philippines, from the years 2017 to 2019 were selected as target participants in this cross-sectional study. A self-administered online survey tool was used in this study for both screening of participants and the KAP survey proper. STATA, descriptive statistics, and multiple logistic regression were used for the data analysis. Odds Ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: The study comprised 604 participants whose mean age was 38.4 years. Television was determined as the top media source of information, and various health staff were the most trusted and common source of information. Good knowledge on dengue treatment (OR = 1.81; 95% CI 1.18-2.78) and dengue prevention (OR = 1.85; 95% CI 1.26-2.71) were positively associated with having good practices on protection against mosquito bites. Good knowledge on dengue signs and symptoms (OR = 1.56; 95% CI 1.02-2.37) and dengue prevention (OR = 2.38; 95% CI 1.59-3.58) were positively associated with having good practices on preventing breeding sites. Those with positive perceived susceptibility to dengue had lower odds of having good practices on protection against mosquito bites (OR = 0.64; 95% CI 0.41-0.99) and of having good practices on preventing breeding sites (OR = 0.46; 95% CI 0.26-0.81). CONCLUSION: Even with the existing dengue policies, programs, and strategies, and the high disease literacy rate of Filipinos, dengue remains a struggle with an increasing case rate. Therefore, specific concepts should be emphasized, and interventions should be fine-tuned to better reach and influence the target population to attain a dengue-free Philippines.

Factors associated with memory of informal caregivers: A scoping review protocol.

The ability to retain and remember information (memory) is essential to caregiving tasks. There is evidence that caregivers are at greater risk for experiencing deteriorations in cognitive status than non-caregivers, especially memory; however, we have a limited understanding of factors that are related to changes in caregiver memory. This scoping review intends to comprehensively map factors related to caregiver memory reported in the literature within the chronic caregiving context. Specific aims include (1) identifying factors related to caregiver memory; (2) examining how caregiver memory has been measured; and (3) describing changes in caregiver memory during their caregiving period. This review will be conducted following Arksey and O'Malley's framework and reported using the PRISMA guidelines for Scoping Reviews (PRISMA-ScR). Studies will be included if (1) the studies focus on home-based unpaid long term family caregiving; (2) study participants (patients), of any age, have one (or more) chronic illness or disability and receive care from a caregiver for 6 months or more; (3) caregivers are adults (> = 18 years of age). Any chronic disease or condition will be included. The search will encompass gray literature and peer-reviewed literature in MEDLINE (via Ovid), CINAHL Plus with Full Text (via EBSCOhost), Embase (via Elsevier), APA PsycINFO (via EBSCOhost), Sociology Source Ultimate (via EBSCOhost), and ProQuest Dissertations and Theses Global. Data extraction will include specific details about the participants, concept, context, study methods, and key caregiver-related findings. The Caregiver Health Model will provide a framework to categorize factors that impact caregivers' memory including caregiver health promotion activities, caregiver attitudes and beliefs, caregiver task, and caregiver needs. Factors that do not fall into the Caregiver Health Model domains will be organized by emerging themes.

Healthcare Workers' Knowledge and Attitude Toward Telemedicine During the COVID-19 Pandemic: A Global Survey.

Introduction Telemedicine is the utilization of communication technologies to provide healthcare services remotely. It has an increasingly pivotal role in enabling medical professionals to extend the provision of care to patients facing geographical barriers. The benefits of telemedicine have become more apparent during the coronavirus pandemic. To maximize its application, it is crucial to ascertain the understanding and attitudes of healthcare professionals toward its use. The aim of this study is to collect data and evaluate the current knowledge and perceptions of medical staff toward the use of telemedicine. Methods In this cross-sectional study, we conducted a global survey of 1091 healthcare workers. Data were collected through a questionnaire after an extensive literature review. Frequency, percentages, and cumulative percentages were calculated to portray the profile of the participants. Results Of the respondents, the majority had heard about (90.9%), witnessed (65.3%), or were familiar with (74.6%) how telemedicine is used in practice. Seventy-two point two percent (72.2%) were familiar with the tools that may be used in this technology. The familiarity with telemedicine was noted to be consistently higher in those with a medical degree and experience of less than five years. Furthermore, attitudes toward providing healthcare remotely were generally positive with 80% thinking that telemedicine reduced staff workload, 80.6% reporting that it reduces the unnecessary transportation cost, and 83% believing that it saves clinicians' time. However, 20% of respondents said that telemedicine increases staff workload and 40.5% of healthcare workers believed telemedicine threatens information confidentiality and patient privacy. Conclusion Although telemedicine is a novel and emerging practice in many countries, it appears to have a promising contribution to healthcare services. This is particularly important during a pandemic, as it ensures effective healthcare with the maintenance of social distancing measures. Moreover, the respondents of this study showed good knowledge and positivity in their attitude toward telemedicine.

Anesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylate.

INTRODUCTION: Hydrocarbons with sufficient water solubility allosterically modulate anesthetic-sensitive ion channels. Mint extracts L-carvone and methyl salicylate water solubility exceeds modulation cutoff values for γ-amino butyric acid type A (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, and type-2 voltage-gated sodium (Nav1.2) channels. We hypothesized that mint extracts modulate these channels at concentrations that anesthetize rats. METHODS: Channels were expressed separately in frog oocytes and studied using 2-electrode voltage clamp techniques at drug concentrations up to 10 mM. Normalized current effects were fit to Hill equations. Mint compounds were formulated in a lipid emulsion and administered IV to rats. When unresponsive to the tail clamp, rats were exsanguinated, and plasma drug concentrations were measured. RESULTS: Both mint compounds caused concentration-dependent inhibition of all channels except for methyl salicylate which inhibited GABAA receptors at low concentrations and potentiated at high concentrations. Plasma drug concentrations in anesthetized rats were 7.9 mM for L-carvone and 2.7 mM for methyl salicylate. This corresponded to ≥53% NMDA receptor inhibition and ≥78% Nav1.2 channel inhibition by both compounds and 30% potentiation of GABAA receptors by methyl salicylate. CONCLUSION: L-Carvone and methyl salicylate allosterically modulate cell receptor targets important to molecular actions of conventional anesthetics at concentrations that also induce general anesthesia in rats.

Two-Part Phase 1 Multiple-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of TRV734 in Healthy Adults.

TRV734, an oral G-protein biased ligand at the µ-opioid receptor has demonstrated differentiated pharmacology in preclinical studies compared to unbiased ligands. First-time-in-human data suggested that TRV734 was safe and well tolerated and caused effective pain relief after single doses of 150 to 250 mg. In this study, safety and tolerability of multiple ascending doses of TRV734, and single doses of TRV734 125 mg following various administration paradigms, in healthy subjects were evaluated. In both parts of the study, TRV734 was generally well tolerated with no serious adverse events. Pharmacokinetics of TRV734 were similar when TRV734 125 mg was administered following a high-fat or standard meal. Compared to either of the fed conditions, maximum concentration and area under the plasma concentration-time curve did not change, and time to maximum concentration was 1.5 hours later when TRV734 125 mg was administered as 3 split portions over 120 minutes under fasted conditions. Split doses of TRV734 delayed time to peak decrease in pupil diameter. Following multiple-dose administration of TRV734 60 to 175 mg every 6 hours, there was a trend of slightly less-than-dose proportional increase of maximum concentration, and area under the plasma concentration-time curve and accumulation was modest. Time to maximum concentration was ≈1 to 2 hours and elimination half-life ≈1.9 to 2.5 hours. The analgesic effect of TRV734 on the cold pain test was generally dose proportional and similar to that of oxycodone 10 mg immediate release, after both the first and last doses. There was a dose-related decrease in pupil diameter following administration of TRV734 up to TRV734 125 mg every 6 hours. A favorable trend in bowel function index for TRV734 warrants continued study.

Emergence of highly infectious SARS-CoV-2 variants in Bangladesh: the need for systematic genetic surveillance as a public health strategy.

Bangladesh, a low-middle-income country in South Asia is facing one of its worst public health emergencies due to the COVID-19 pandemic. The increase in the number of cases from the disease, since the second half of March 2021, can potentially cause the health system overload, and has, as one of the main reasons, the non-compliance with measures of social distance and the emergence of the variants of concern in the country. This increase in the contagion curve can also provide a favorable environment for the occurrence of more mutations in the structure and genome of the virus. Therefore, there is an urge to carry out genomic surveillance programs in order to identify, monitor and characterize these variants, and understand whether the vaccines currently used are effective against them.

Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW.

Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

Tuning Crystal Structures of Iron-Based Metal-Organic Frameworks for Drug Delivery Applications.

Iron-based metal-organic frameworks (Fe-MOFs) have emerged as promising candidates for drug delivery applications due to their low toxicity, structural flexibility, and safe biodegradation in a physiological environment. Here, we studied two types of Fe-MOFs: MIL-53 and MIL-88B, for in vitro drug loading and releasing of ibuprofen as a model drug. Both Fe-MOFs are based on the same iron clusters and organic ligands but form different crystal structures as a result of two different nucleation pathways. The MIL-53 structure demonstrates one-dimensional channels, while MIL-88B exhibits a three-dimensional cage structure. Our studies show that MIL-53 adsorbs more ibuprofen (37.0 wt %) compared to MIL-88B (19.5 wt %). A controlled drug release was observed in both materials with a slower elution pattern in the case of the ibuprofen-encapsulated MIL-88B. This indicates that a complex cage structure of MIL-88 is beneficial to control the rate of drug release. A linear correlation was found between cumulative drug release and the degree of material degradation, suggesting the biodegradation of Fe-MILs as the main drug elution mechanism. The cytotoxicity of MIL-88B was evaluated in vitro with NIH-3T3 Swiss mouse fibroblasts, and it shows that MIL-88B has no adverse effects on cell viability up to 0.1 mg/mL. This low toxicity was attributed to the morphology of MIL-88B nanocrystals. The very low toxicity and controlled drug release behavior of Fe-MIL-88B suggest that better materials for drug-delivery applications can be created by controlling not only the composition but also the crystal structure and nanoparticle morphology of the material.

A First-in-Human Clinical Study With TRV734, an Orally Bioavailable G-Protein-Biased Ligand at the µ-Opioid Receptor.

TRV734 is an orally bioavailable G-protein-biased ligand at the µ-opioid receptor. In nonclinical studies it was potently analgesic while causing less gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A 2-part, first-in-human study was conducted with ascending doses of TRV734 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV734 was well tolerated over the dose range 2 to 250 mg when administered orally. Plasma TRV734 maximum concentration and area under the plasma concentration-time curve generally increased with dose, while time to maximum concentration was similar across doses (0.5-1.3 h). The half-life increased with dose from 10 mg through 150 mg (0.75-2.28 h) but was similar from 150 mg through 250 mg. Pupil constriction, confirming central nervous system µ-opioid receptor engagement, correlated with higher plasma TRV734 concentrations; the greatest reductions in pupil diameter occurring between 0 and 4 hours after dosing (-2.9 mm/h, with reduction peaking at 1 hour, and returning to baseline by 8 hours). Following administration of TRV734 125 mg under fasted or fed conditions, there was no significant difference in bioavailability when given as a solution or drug in capsule to fasted subjects. When drug in capsule was given to subjects following a high-fat meal, absorption was slowed, resulting in decreased peak concentrations, but area under the plasma concentration-time curve was not affected.

Synthesis, in vitro evaluation, and in vivo metabolism of fluor/quencher compounds containing IRDye 800CW and Black Hole Quencher-3 (BHQ-3).

Protease-cleavable peptides containing a suitable fluor/quencher (Fl/Q) pair are optically dark until cleaved by their target protease, generating fluorescence. This approach has been used with many Fl/Q pairs, but little has been reported with IRDye 800CW, a popular near-infrared (NIR) fluor. We explored the use of the azo-bond-containing Black Hole Quencher 3 (BHQ-3) as a quencher for IRDye 800CW and found that IRDye 800CW/BHQ-3 is a suitable Fl/Q pair, despite the lack of proper spectral overlap for fluorescence resonance energy transfer (FRET) applications. Cleavage of IRDye 800CW-PLGLK(BHQ-3)AR-NH(2) (8) and its D-arginine (Darg) analogue (9) by matrix metalloproteinases (MMPs) in vitro yielded the expected cleavage fragments. In vivo, extensive metabolism was found. Significant decomposition of a "non-cleavable" control IRDye 800CW-(1,13-diamino-4,7,10-trioxatridecane)-BHQ-3 (10) was evident in plasma of normal mice by 3 min post injection. The major metabolite showed a m/z and UV/vis spectrum consistent with azo bond cleavage in the BHQ-3 moiety. Preparation of an authentic standard of this metabolite (11) confirmed the assignment. Although the IRDye 800CW/BHQ-3 constructs showed efficient contact quenching prior to enzymatic cleavage, BHQ-3 should be used with caution in vivo, due to instability of its azo bond.

Automated synthesis, characterization and biological evaluation of [(68)Ga]Ga-AMBA, and the synthesis and characterization of (nat)Ga-AMBA and [(67)Ga]Ga-AMBA.

Ga-AMBA (Ga-DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R). Syntheses for (nat)Ga-AMBA, [(67)Ga]Ga-AMBA and [(68)Ga]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [(68)Ga]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated (68)Ge/(68)Ga generator elution and purification. The total synthesis time, including the fractional elution of the generator, was 20 min for Sep-Pak purified material and 40 min for HPLC-purified [(68)Ga]Ga-AMBA. Both [(67)Ga]Ga-AMBA and [(177)Lu]Lu-AMBA showed comparable high affinity for GRP-R in the human prostate cancer cell line PC-3 in vitro (k(D)=0.46+/-0.07; 0.44+/-0.08 nM), high internalization (78; 77%) and low efflux from cells at 2 h (2.4+/-0.7; 2.9+/-1.8%). Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [(177)Lu]Lu-, [(111)In]In-, [(67)Ga]Ga- and [(68)Ga]Ga-AMBA.