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Chinese Medical Journal Jun 2024Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This...
BACKGROUND
Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.
METHODS
Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.
RESULTS
ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for CL/F was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively).
CONCLUSIONS
Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.
TRIAL REGISTRATION
Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).
PubMed: 38934053
DOI: 10.1097/CM9.0000000000002917 -
China CDC Weekly Jun 2024() is a species of toxic mushroom known to induce symptoms of photosensitive dermatitis.
WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?
() is a species of toxic mushroom known to induce symptoms of photosensitive dermatitis.
WHAT IS ADDED BY THIS REPORT?
In the months of May and June 2023, a total of four patients in Chuxiong Yi Autonomous Prefecture, Yunnan Province, were affected by poisoning, occurring over two distinct incidents. The condition of two patients deteriorated after they were re-exposed to sunlight on the seventh day following the initial poisoning. Separately, an additional two patients reported experiencing a mild, needle-like sensation on areas of their skin exposed to the sun, recorded on the twelfth day subsequent to the poisoning.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
Given that symptoms of photosensitive dermatitis, a potential severe consequence of poisoning, can manifest up to a week post-sun exposure, it is advisable to avoid sunlight for a minimum of two weeks following poisoning.
PubMed: 38934025
DOI: 10.46234/ccdcw2024.091 -
Frontiers in Molecular Biosciences 2024Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them...
BACKGROUND
Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain.
OBJECTIVE
Conduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk.
METHOD
Genome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method.
RESULT
There were 103 SNPs utilized as instrumental variables ( < 5 × 10). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, = 0.5772). There was no heterogeneity and pleiotropy in the statistical models.
CONCLUSION
The present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.
PubMed: 38933368
DOI: 10.3389/fmolb.2024.1390814 -
Fundamental Research May 2024Land public transport is an important link within and between cities, and how to control the transmission of COVID-19 in land public transport is a critical issue in our... (Review)
Review
Land public transport is an important link within and between cities, and how to control the transmission of COVID-19 in land public transport is a critical issue in our daily lives. However, there are still many inconsistent opinions and views about the spread of SARS-CoV-2 in land public transport, which limits our ability to implement effective interventions. The purpose of this review is to overview the literature on transmission characteristics and routes of the epidemic in land public transport, as well as to investigate factors affecting its spread and provide feasible measures to mitigate the infection risk of passengers. We obtained 898 papers by searching the Web of Science, Pubmed, and WHO global COVID database by keywords, and finally selected 45 papers that can address the purpose of this review. Land public transport is a high outbreak area for COVID-19 due to characteristics like crowding, inadequate ventilation, long exposure time, and environmental closure. Different from surface touch transmission and drop spray transmission, aerosol inhalation transmission can occur not only in short distances but also in long distances. Insufficient ventilation is the most important factor influencing long-distance aerosol transmission. Other transmission factors (e.g., interpersonal distance, relative orientation, and ambient conditions) should be noticed as well, which have been summarized in this paper. To address various influencing factors, it is essential to suggest practical and efficient preventive measures. Among these, increased ventilation, particularly the fresh air (i.e., natural ventilation), has proven to effectively reduce indoor infection risk. Many preventive measures are also effective, such as enlarging social distance, avoiding face-to-face orientation, setting up physical partitions, disinfection, avoiding talking, and so on. As research on the epidemic has intensified, people have broken down many perceived barriers, but more comprehensive studies on monitoring systems and prevention measures in land public transport are still needed.
PubMed: 38933205
DOI: 10.1016/j.fmre.2023.10.013 -
Fundamental Research May 2024Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major... (Review)
Review
Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.
PubMed: 38933199
DOI: 10.1016/j.fmre.2023.05.022 -
Nutrients Jun 2024Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental... (Review)
Review
Depression is a major global health concern expected to worsen by 2030. In 2019, 28 million individuals were affected by depressive disorders. Dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression. B vitamins are crucial for neurological function and mood regulation. Deficiencies in these vitamins are linked to depression. Studies on individual B vitamins show promise in improving depressive symptoms, particularly thiamin, riboflavin, niacin, and folate. Vitamin C deficiency may heighten depressive symptoms, but its exact role is not fully understood. Seasonal Affective Disorder (SAD) is associated with insufficient sunlight exposure and vitamin D deficiency. Vitamin D supplementation for SAD shows inconsistent results due to methodological variations. Further investigation is needed to understand the mechanisms of vitamins in depression treatment. Moreover, more research on SAD and light therapy's efficacy and underlying mechanisms involving photoreceptors, enzymes, and immune markers is needed. Although dietary and supplemental vitamins show overall favorable preventative and therapeutic effects on depression, dietitians treating psychiatric disorders face challenges due to diverse study designs, making direct comparisons difficult. Therefore, this article reviews the current literature to assess the role of dietary and supplemental vitamins in the prevention and treatment of depression. This review found that, although evidence supports the role of B vitamins and vitamins C and D in preventing and treating depression, further research is needed to clarify their mechanisms of action and determine the most effective intervention strategies.
Topics: Humans; Seasonal Affective Disorder; Vitamin D; Dietary Supplements; Vitamins; Depression; Adult; Ascorbic Acid; Vitamin B Complex; Vitamin D Deficiency; Female; Solubility
PubMed: 38931257
DOI: 10.3390/nu16121902 -
Molecules (Basel, Switzerland) Jun 2024Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is...
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of . The effect of COE on UVB damage was assessed using . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the downstream gene and the extension of the lifespan in mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in via the SKN-1/Nrf2 pathway.
Topics: Animals; Caenorhabditis elegans; Triterpenes; Ursolic Acid; Ultraviolet Rays; Plant Extracts; Caenorhabditis elegans Proteins; Oxidative Stress; Cornus; Antioxidants; Reactive Oxygen Species; Skin Aging; Transcription Factors; DNA-Binding Proteins; Longevity; NF-E2-Related Factor 2
PubMed: 38930783
DOI: 10.3390/molecules29122718 -
Life (Basel, Switzerland) May 2024Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity....
BACKGROUND
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
METHODS
Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS
A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment ( < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS
This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
PubMed: 38929673
DOI: 10.3390/life14060689 -
International Journal of Molecular... Jun 2024UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure...
UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure (T1, 1.40 kJ·m·day; T2, 2.81 kJ·m·day; and T3, 5.62 kJ·m·day) on the growth biomass, physiological characteristics, and secondary metabolites were studied. Our results indicated that leaf thickness was significantly ( < 0.05) reduced under T3 relative to the control (natural light exposure, CK); The contents of 6-BA and IAA were significantly reduced ( < 0.05); and the contents of ABA, 10-deacetylbaccatin III, and baccatin III were significantly ( < 0.05) increased under T1 and T2. The paclitaxel content was the highest (0.036 ± 0.0018 mg·g) under T3. The cephalomannine content was significantly increased under T1. gene expression was upregulated under T1 and T3. The gene expressions of and were significantly ( < 0.05) upregulated under sUV-B exposure, and the gene expressions of , , and were significantly ( < 0.05) downregulated. A correlation analysis showed that the 6-BA content had a significantly ( < 0.05) positive correlation with gene expression. The IAA content had a significantly ( < 0.05) positive correlation with the gene expression of , , , and . The ABA content had a significantly ( < 0.05) positive correlation with gene expression. gene expression had a significantly ( < 0.05) positive correlation with the 10-deacetylbaccatin content. gene expression was positively correlated with the contents of baccatin III and cephalomannine. gene expression had a significantly ( < 0.01) positive correlation with the paclitaxel content. A factor analysis showed that the accumulation of paclitaxel content was promoted under T2, which was helpful in clarifying the accumulation of taxane compounds after sUV-B exposure.
Topics: Taxus; Taxoids; Ultraviolet Rays; Gene Expression Regulation, Plant; Paclitaxel; Plant Leaves; Bridged-Ring Compounds; Indoleacetic Acids; Plant Growth Regulators; Abscisic Acid; Alkaloids
PubMed: 38928114
DOI: 10.3390/ijms25126407 -
Cancers Jun 2024Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated...
Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.
Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.
PubMed: 38927988
DOI: 10.3390/cancers16122284