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Natural Product Research Jun 2024The study explored DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known...
The study explored DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known bioactive metabolite glaucarubinone (). Mosquito larvicidal activity of glaucarubinone () against the three vector species viz. and was determined using a modified WHO 2005 protocol. It was observed that larvae were the most susceptible species with LC 13.88 ppm and LC 70.01 ppm followed by and at 24 h of exposure. The mode of action as observed microscopically is the lysis of midgut and thorax cells of the third instar larvae. The crystal structure of the glaucarubinone () is reported for the first time using X-ray crystallography. This phytochemical product has the potential to act as a green alternative to existing chemical-based insecticides for integrated vector management.
PubMed: 38940013
DOI: 10.1080/14786419.2024.2371569 -
Molecular Therapy. Nucleic Acids Sep 2024Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and...
Effective therapeutics are necessary for managing severe COVID-19 disease despite the availability of vaccines. Small interfering RNA (siRNA) can silence viral genes and restrict SARS-CoV-2 replication. Cell-penetrating peptides is a robust method for siRNA delivery, enhancing siRNA stability and targeting specific receptors. We developed a peptide HE25 that blocks SARS-CoV-2 replication by various mechanisms, including the binding of multiple receptors involved in the virus's internalization, such as ACE2, integrins and NRP1. HE25 not only acts as a vehicle to deliver the SARS-CoV-2 RNA-dependent RNA polymerase siRNA into cells but also facilitates their internalization through endocytosis. Once inside endosomes, the siRNA is released into the cytoplasm through the Histidine-proton sponge effect and the selective cleavage of HE25 by cathepsin B. These mechanisms effectively inhibited the replication of the ancestral SARS-CoV-2 and the Omicron variant BA.5 . When HE25 was administered , either by intravenous injection or inhalation, it accumulated in lungs, veins and arteries, endothelium, or bronchial structure depending on the route. Furthermore, the siRNA/HE25 complex caused gene silencing in lung cells . The SARS-CoV-2 siRNA/HE25 complex is a promising therapeutic for COVID-19, and a similar strategy can be employed to combat future emerging viral diseases.
PubMed: 38939051
DOI: 10.1016/j.omtn.2024.102227 -
Innovations in Clinical Neuroscience 2024Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
INTRODUCTION
Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.
OBJECTIVE
With new evidence suggesting a link between low high-density lipoprotein cholesterol (HDL-C) and risk of Parkinson's disease, this study sought to investigate if that link also translated to patients taking antipsychotics with low HDL-C and an increased risk for developing a movement disorder.
DESIGN
Adult patients (n=89) at an inpatient state psychiatric facility taking at least one antipsychotic with at least one HDL-C level were assessed for signs of a movement disorder through their history and physical, progress notes, and Abnormal Involuntary Movement Scale (AIMS) score.
RESULTS
There was no statistical significance when comparing a patient's movement disorder, AIMS scores, and HDL-C levels to suggest that the HDL-C level influenced a patient's movement disorder.
CONCLUSION
This study did not show a correlation between HDL-C levels and a patient's risk of developing a movement disorder while taking an antipsychotic.
PubMed: 38938537
DOI: No ID Found -
Journal of the National Cancer Institute Jun 2024Racial and ethnic minoritized groups report disproportionately lower trust in the healthcare system. Lower healthcare system trust is potentially related to increased...
BACKGROUND
Racial and ethnic minoritized groups report disproportionately lower trust in the healthcare system. Lower healthcare system trust is potentially related to increased exposure to racial discrimination in medical settings, but this association is not fully understood. We examined the association between racial discrimination in medical care and trust in the healthcare system among people with and without a personal cancer history.
METHODS
We examined racial discrimination and trust in a nationally representative American adult sample from the Health Information National Trends Survey 6. Racial discrimination was defined as any unfair treatment in healthcare based on race or ethnicity. Trust in the healthcare system (eg, hospitals and pharmacies) was grouped into low, moderate, and high trust. Multinomial logistic regression models were used to compare low and moderate trust relative to high trust in the healthcare system and estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
A total of 5,813 respondents (15% with a personal cancer history) were included 92% (n = 5,355) reported no prior racial discrimination experience during medical treatment. Prior experiences of racial discrimination were positively associated with low (OR = 6.12, 95% CI: 4.22-8.86) and moderate (OR = 2.70, 95% CI: 1.96-3.72) trust in the healthcare system, relative to high trust. Similar associations were observed when stratifying by personal cancer history.
CONCLUSION
Respondents who reported racial discrimination during medical encounters had lower trust in the healthcare system, especially respondents with a personal cancer history. Our findings highlight the need to address racial discrimination experiences during medical care to build patient trust and promote healthcare access.
PubMed: 38937274
DOI: 10.1093/jnci/djae154 -
Global Health, Science and Practice Jun 2024Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy...
Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.
Topics: Humans; Vietnam; COVID-19; Tuberculosis, Pulmonary; Mass Screening; SARS-CoV-2; Middle Aged; Radiography, Thoracic; Tuberculosis; Female; Pandemics; Male; Vulnerable Populations
PubMed: 38936961
DOI: 10.9745/GHSP-D-24-00024 -
Congenital Anomalies Jun 2024Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help...
Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help and advice on drug use at two teratology information institutes in Japan. The primary endpoint of the study was the incidence of major congenital anomalies. The study population included pregnant women exposed to (i) fluoroquinolones (fluoroquinolone group), (ii) β-lactams (infectious control group), or (iii) other agents considered to be nonteratogenic in humans (nonteratogenic control group) during the first trimester. The frequency of major congenital anomalies was compared across groups using a logistic regression model that adjusted for maternal age, smoking status, drinking status, facility consulted, and time of consultation. The fluoroquinolone group consisted of 411 women who had 383 children born alive. The infectious control and nonteratogenic control groups consisted of 1416 and 1482 women who had 1322 and 1401 children born alive, respectively. The incidence of major congenital anomalies was 1.5%, 2.0%, and 1.6% in the fluoroquinolone group, infectious control, and nonteratogenic control groups, respectively. Logistic regression showed that fluoroquinolone exposure is not a significant risk factor for major congenital anomalies. In conclusion, first-trimester exposure to fluoroquinolone antibiotics was not associated with increased maternal or fetal risks.
PubMed: 38936845
DOI: 10.1111/cga.12577 -
Respiratory Medicine Jun 2024Short-acting β-agonists (SABA) overuse is associated with poor asthma control. The Global Initiative for Asthma (GINA) 2019-updated guideline has therefore taken a...
BACKGROUND
Short-acting β-agonists (SABA) overuse is associated with poor asthma control. The Global Initiative for Asthma (GINA) 2019-updated guideline has therefore taken a paradigm shift in reliever therapy recommendations.
OBJECTIVES
(I) To investigate the status of SABA overuse and medication dispensing patters in asthma in the Netherlands (II) validate dispensing data for SABA overuse identification and (III) understand patients' perspectives towards this SABA-taking behavior to inform future improvement strategies.
METHODS
An annually repeated cross-sectional study was conducted from 2017-2021 using pharmacy dispensing data in a real-world setting, including asthma patients aged 18-45 with ≥ 1 inhaler. A following qualitative study was performed in identified SABA overusing patients with a questionnaire and semi-structured interviews, supported by theoretical frameworks.
RESULTS
Dispensing data was available from 87% of all community pharmacies (n=1,994) in 2017 and 95% (n=2,005) in 2021. SABA overuse prevalence was constant for the five study-years with 20.6% (±0.5%). Increased ICS-formoterol and decreased SABA dispenses were observed in starters of inhalation therapy in 2021. 53 asthma patients completed the questionnaire of whom 43 patients confirmed SABA overuse, generating a positive predictive value of 81%. Key behavioral drivers covered 7 themes regarding capability (knowledge; skills; memory, attention and decision process) motivation (emotion; beliefs about- capabilities; consequences) and opportunity (environmental context).
CONCLUSION
SABA overuse remains in one-fifth of asthma patients across the Netherlands, requiring careful attention from healthcare professionals. Dispensing data is a valid measure for SABA overuse in a clinical setting, facilitating patient selection. To meet patients' varied supporting needs, integration of tailored behavioral interventions is essential.
PubMed: 38936636
DOI: 10.1016/j.rmed.2024.107723 -
JCO Precision Oncology Jun 2024Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain genetic variants with standard dosing. We implemented... (Observational Study)
Observational Study
Real-World Impact of an In-House Dihydropyrimidine Dehydrogenase () Genotype Test on Fluoropyrimidine Dosing, Toxicities, and Hospitalizations at a Multisite Cancer Center.
PURPOSE
Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain genetic variants with standard dosing. We implemented genotyping at a multisite cancer center and evaluated its impact on dosing, toxicity, and hospitalization.
METHODS
In this prospective observational study, patients receiving (reactive) or planning to receive (pretreatment) fluoropyrimidine-based chemotherapy were genotyped for five variants as standard practice per provider discretion. The primary end point was the proportion of variant carriers receiving fluoropyrimidine modifications. Secondary end points included mean relative dose intensity, fluoropyrimidine-related grade 3+ toxicities, and hospitalizations. Fisher's exact test compared toxicity and hospitalization rates between pretreatment carriers, reactive carriers, and wild-type patients. Univariable and multivariable logistic regression identified factors associated with toxicity and hospitalization risk. Kaplan-Meier methods estimated time to event of first grade 3+ toxicity and hospitalization.
RESULTS
Of the 757 patients who received genotyping (median age 63, 54% male, 74% White, 19% Black, 88% GI malignancy), 45 (5.9%) were heterozygous carriers. Fluoropyrimidine was modified in 93% of carriers who started treatment. In 442 patients with 3-month follow-up, 64%, 31%, and 30% of reactive carriers, pretreatment carriers, and wild-type patients had grade 3+ toxicity, respectively ( = .085); 64%, 25%, and 13% were hospitalized ( < .001). Reactive carriers had 10-fold higher odds of hospitalization compared with wild-type patients ( = .001), whereas no significant difference was noted between pretreatment carriers and wild-type patients. Time-to-event of toxicity and hospitalization were significantly different between genotype groups ( < .001), with reactive carriers having the earliest onset and highest incidence.
CONCLUSION
genotyping prompted fluoropyrimidine modifications in most carriers. Pretreatment testing reduced toxicities and hospitalizations compared with reactive testing, thus normalizing the risk to that of wild-type patients, and should be considered standard practice.
Topics: Humans; Male; Female; Dihydrouracil Dehydrogenase (NADP); Middle Aged; Hospitalization; Prospective Studies; Genotype; Aged; Fluorouracil; Neoplasms; Antimetabolites, Antineoplastic; Cancer Care Facilities; Adult
PubMed: 38935897
DOI: 10.1200/PO.23.00623 -
PloS One 2024Understanding patient satisfaction is key to advancing pharmacy services and improving health outcomes. There is a lack of a translated and psychometrically validated...
Translation, cultural adaptation and validation of Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ) 2.0 into the Arabic language among people with diabetes.
BACKGROUND
Understanding patient satisfaction is key to advancing pharmacy services and improving health outcomes. There is a lack of a translated and psychometrically validated tool in the Arabic language to measure patient satisfaction with pharmacy services.
OBJECTIVE
To translate the English version of the PSPSQ 2.0 into Arabic language, culturally adapt, and verify its reliability and validity.
SETTING
A community pharmacy in Riyadh, Saudi Arabia.
METHOD
A cross-sectional study was conducted between April 2021 and June 2022 among patients with diabetes attending a community pharmacy. The International Society for Pharmacoeconomics and Outcomes Research good practice guidelines for linguistic translation and cultural adaptation were used to translate and culturally adapt the English version of PSPSQ 2.0 into Arabic. The Arabic version of PSPSQ 2.0 was subjected to factor analysis using principal component analysis with varimax rotation to evaluate its validity and Cronbach's alpha was used to assess the reliability of PSPSQ 2.0.
RESULTS
A total of 129 (68.2% male, and mean age 50 (SD: 11.9) years) patients with diabetes participated in the study. The analysis was undertaken for the items in each of the three domains of PSPSQ 2.0: quality of care, interprofessional relationship and overall care. Exploratory factor analysis revealed validity of 92.7%, 80.5% and 96.2%, respectively. The Arabic version of PSPSQ 2.0 had high internal consistency with Cronbach's alpha scores 0.99, 0.95 and 0.98 for the three measured domains, respectively. The sample adequacy was 0.924.
CONCLUSION
The PSPSQ 2.0 was successfully translated and culturally adapted into the Arabic language and had acceptable validity and reliability to measure patient satisfaction with services provided by pharmacists in community pharmacies.
Topics: Humans; Male; Female; Patient Satisfaction; Middle Aged; Surveys and Questionnaires; Diabetes Mellitus; Saudi Arabia; Language; Adult; Cross-Sectional Studies; Translations; Reproducibility of Results; Psychometrics; Pharmacists; Translating; Community Pharmacy Services
PubMed: 38935668
DOI: 10.1371/journal.pone.0298848 -
GeroScience Jun 2024Healthy Longevity Medicine aims to optimize health by targeting aging processes across the lifespan. Addressing accelerated aging involves adaptation of lifestyle and...
Healthy Longevity Medicine aims to optimize health by targeting aging processes across the lifespan. Addressing accelerated aging involves adaptation of lifestyle and the use of geroprotective drugs and supplements, including nutritional supplements and bioactive compounds. The Food and Drug Administration, under the Dietary Supplement Health and Education Act, categorizes bioactive compounds and medicinal products as dietary supplements. While numerous companies sell ingredients that can be deemed geroprotectors, there's limited oversight in their quality control. Governmental safety authorities only verify the presence of prohibited compounds, not the accuracy of ingredients listed on labels.Here, Nicotinamide mononucleotide and Urolithin A supplements, easily accessible online or in pharmacies, were tested for their active ingredient content. Results showed a significant deviation from the labeled amounts, ranging from + 28.6% to -100%. This indicates a considerable disparity in the quality of geroprotective supplements.To address this variability, collaboration between and within societies representing healthcare professionals, industry and regulatory bodies is imperative to ensure the quality of geroprotective supplements.
PubMed: 38935229
DOI: 10.1007/s11357-024-01257-2