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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 -
Photochemistry and Photobiology Jun 2024Tree shade, particularly shade that obscures direct sunlight near peak periods of midday solar exposure can have a pronounced effect on potentially harmful ultraviolet...
Tree shade, particularly shade that obscures direct sunlight near peak periods of midday solar exposure can have a pronounced effect on potentially harmful ultraviolet radiation, and in turn, strongly influence the maximum daily UV index (UVI). In this study, the seasonal influence of tree shade on the UVI is evaluated from 210 hemispherical sky view images collected alongside public walkways and footpaths from 10 residential Brisbane suburbs. The effective sidewalk UV index is calculated underneath planted tree canopies, adjacent residential gardens, buildings and background tree species. Results are presented with respect to seasonal variations in the diurnal solar elevation for each month of the year at Brisbane's latitude. The research also examines the total reduction in UVI due to the presence of individual tree species, showing reductions in the midday UVI of up to 91% of an equivalent unimpeded sky hemisphere when overhead tree canopies are present. Important footpath tree species for peak midday UVI mitigation include Pongamia pinnata, Xanthostemon chrysanthus, Senna siamea, and Libidibia ferrea. The planting and maintenance of existing tree species already growing alongside residential Brisbane streets will improve the shade characteristics of suburbs and enhance UV protection for local residents.
PubMed: 38926941
DOI: 10.1111/php.13988 -
Cancer Jun 2024Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ...
BACKGROUND
Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ inhibitor) and assessed the recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics in relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs).
METHODS
Oral TQ-B3525 was given at eight dose levels on a 28-day cycle. Primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety.
RESULTS
TQ-B3525 showed high selectivity and suppressed tumor growth. Between June 12, 2018, and November 18, 2020, 80 patients were enrolled (63 in dose-escalation cohort; 17 in dose-expansion cohort). Two DLTs occurred in two (two of 63, 3.2%) DLT-evaluable patients; MTD was not identified. TQ-B3525 at 20 mg once daily was selected as RP2D. Grade 3 or worse treatment-related adverse events mainly included hyperglycemia (16.3%), neutrophil count decreased (15.0%), and diarrhea (10.0%). Two (2.5%) treatment-related deaths were reported. Sixty patients with R/R lymphoma and 11 advanced STs demonstrated objective response rates of 68.3% and 9.1%, disease control rates of 91.7% and 54.6%, median progression-free survivals of 12.1 and 1.1 months; median overall survivals were not reached.
CONCLUSION
TQ-B3525 exhibited rapid absorption and a nearly proportional increase in exposure. Acceptable safety and promising efficacy support further investigation of TQ-B3525 (20 mg once daily) for R/R lymphoma.
PubMed: 38926891
DOI: 10.1002/cncr.35453 -
Discovery Medicine Jun 2024Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to...
BACKGROUND
Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear.
METHODS
C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues.
RESULTS
The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group.
CONCLUSIONS
Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.
Topics: Animals; Endoplasmic Reticulum Stress; Autophagy; Female; Pregnancy; Mice; Lung; Mice, Inbred C57BL; Maternal Exposure; Male; Endoplasmic Reticulum Chaperone BiP; Prenatal Exposure Delayed Effects; Apoptosis; Tobacco Smoke Pollution
PubMed: 38926111
DOI: 10.24976/Discov.Med.202436185.115 -
Journal of Applied Microbiology Jun 2024This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant P. multocida mutants and to...
AIMS
This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant P. multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis.
METHODS AND RESULTS
Danofloxacin at seven dosing regimens and five days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h danofloxacin area under the concentration-time curve to MIC ratios (AUC24h/MIC) associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/MPC (mutant prevention concentration)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of 3 times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants.
CONCLUSIONS
The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.
PubMed: 38925653
DOI: 10.1093/jambio/lxae154 -
American Journal of Kidney Diseases :... Jun 2024Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with...
RATIONALE & OBJECTIVE
Social disconnection has been associated with poor cardiometabolic health. This study sought to investigate the associations of social isolation and loneliness with diabetic microvascular complications (DMC) among individuals with type 2 diabetes mellitus (T2DM) and compare these associations to those related to traditional risk factors.
STUDY DESIGN
Prospective cohort study.
SETTING & PARTICIPANTS
A total of 24,297 UK Biobank participants with T2DM and no DMC at baseline.
EXPOSURE
Social isolation and loneliness measured using self-reported questionnaires.
OUTCOME
The incidence of DMC defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy.
ANALYTICAL APPROACH
Multivariable cause-specific hazards regression. To compare the relative importance of social disconnection with other established factors, the R values of the Cox models were calculated.
RESULTS
During a median follow-up of 12.6 years, 5,530 patients were documented to develop DMC (3,458 with diabetic kidney disease, 2,255 with diabetic retinopathy, and 1,146 with diabetic neuropathy). The highest level of social isolation was associated with an increased risk of any DMC component (most vs. least: HR: 1.13; 95% CI: 1.05-1.22), especially diabetic kidney disease (HR: 1.14, 95% CI: 1.04-1.25) and neuropathy (HR: 1.31, 95% CI: 1.11-1.53). Any level of loneliness was associated with an increased risk of any DMC component (HR: 1.12; 95% CI: 1.02-1.23) and diabetic kidney disease (HR: 1.16, 95% CI: 1.03-1.30). Social isolation and loneliness exhibited associations with DMC comparable to other conventional risk factors including smoking, blood pressure, and physical activity.
LIMITATIONS
Limited generalizability related to the composition of participants in the UK Biobank Study.
CONCLUSIONS
Social isolation and loneliness were independently associated with a higher risk of incident DMC among individuals with T2DM, with comparable importance to other traditional risk factors. These findings underscore social isolation and loneliness as novel and potentially modifiable risk factors for DMC.
PubMed: 38925507
DOI: 10.1053/j.ajkd.2024.05.004 -
Environmental Research Jun 2024Most studies analyzing the effects of air pollution on disadvantaged populations use ground air quality measurements. However, ground stations are generally limited,...
Most studies analyzing the effects of air pollution on disadvantaged populations use ground air quality measurements. However, ground stations are generally limited, with nearly 40% of countries having no official PM stations, not allowing air quality analysis for a significantly large share of the world's population. Furthermore, limited studies analyze community data from a geodemographic perspective, in other words, to delineate the sociodemographic profiles and geographically locate the socioeconomic groups more exposed to ambient air pollution. Therefore, a significant question arises: How can we trace vulnerable communities to air pollution in areas lacking air-quality ground data? Here, we propose a novel methodology to respond to this question. We use NO, SO, CO, and HCHO tropospheric column air-quality data from Sentinel-5P, a satellite that quantifies concentrations of atmospheric species from space operationally. We integrate them with census and environmental data and apply the local fuzzy geographically weighted clustering spatial machine learning method for segmentation analysis. Our findings for Bali, Indonesia, provide quantitative evidence for the benefits of this methodology in tracing and delineating the profiles of the communities most exposed to air pollution. For example, results show that communities with highly disadvantaged populations, such as unemployed (over 27.8%), low educated (over 27.9%), and children (over 22.1%) (mainly located around Bali's south and north coast touristic areas), exhibit very high values (over the 75th quartile) across the pollutants studied. The proposed method is reproducible easily, quickly, and at low cost, as it is based on freely available satellite data and not on costly ground station measurements. This will hopefully assist decision-makers in tracing the most vulnerable subpopulations, even in areas with inadequate air-quality monitoring networks, thus allowing local governments around the globe (even those that are financially weak) to achieve environmental justice and their sustainable development goals.
PubMed: 38925467
DOI: 10.1016/j.envres.2024.119491 -
Journal of Hazardous Materials Jun 2024Microplastics (MPs) are pervasive environmental contaminants that have infiltrated even the most remote ecosystems. Despite their widespread distribution, the transfer...
Microplastics (MPs) are pervasive environmental contaminants that have infiltrated even the most remote ecosystems. Despite their widespread distribution, the transfer patterns and impacts of MPs in remote lakes remain poorly understood. This study aimed to address the knowledge gap regarding the pathways and consequences of MP pollution in these isolated environments. Focusing on Kyêbxang Co, a remote salt lake in Tibet, this study investigated the transfer patterns, sources and ecological impacts of MPs, providing insights into their mobility and fate in pristine ecosystems. Water, sediment and biota (brine shrimp) samples from Kyêbxang Co, collected during the summer of 2020, were analyzed using µ-Raman spectroscopy to determine MP abundances, polymer types and potential sources. Findings indicated significant MP contamination in all examined media, with concentrations highlighting the role of runoff in transporting MPs to remote locations. The majority of detected MPs were small fragments (<0.5 mm), constituting over 93 %, with polypropylene being the predominant polymer type. The presence of a halocline may slow the descent of MPs, potentially increasing the exposure and ingestion risk to brine shrimp. Despite the currently low ecological risk estimated for MPs, this study underscores the need for long-term monitoring and development of a comprehensive ecological risk assessment model for MPs.
PubMed: 38925053
DOI: 10.1016/j.jhazmat.2024.134959 -
Ecotoxicology and Environmental Safety Jun 2024As the global aging process accelerates, the health challenges posed by sarcopenia among middle-aged and older adults are becoming increasingly prominent. However, the...
BACKGROUND
As the global aging process accelerates, the health challenges posed by sarcopenia among middle-aged and older adults are becoming increasingly prominent. However, the available evidence on the adverse effects of air pollution on sarcopenia is limited, particularly in the Western Pacific region. This study aimed to explore relationships of multiple air pollutants with sarcopenia and related biomarkers using the nationally representative database.
METHODS
Totally, 6585 participants aged over 45 years were enrolled from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 3443 of them were followed up until 2015. Air pollutants were estimated from high-resolution satellite-based spatial-temporal models. In the cross-sectional analysis, we used generalized linear regression, unconditional logistic regression analytical and restricted cubic spline (RCS) methods to assess the single-exposure and non-linear effects of multiple air pollutants on sarcopenia and related surrogate biomarkers (serum creatinine and cystatin C). Several popular mixture analysis techniques such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile-based g-computation (Qgcomp) were further used to examinate the combined effects of multiple air pollutants. Logistic regression was used to further analyze the longitudinal association between air pollution and sarcopenia.
RESULTS
Each interquartile range increase in PM, PM and NO was significantly associated with an increased risk of sarcopenia, with adjusted odds ratios (aORs) of 1.09 [95 % confidence interval (CI): 1.01, 1.20], 1.24 (95 % CI: 1.14, 1.35) and 1.18 (95 % CI: 1.08, 1.28), respectively. Our findings also showed that five air pollutants were significantly associated with the sarcopenia index. In addition, employing a mixture analysis approach, we confirmed significant combined effects of air pollution mixtures on sarcopenia risk and associated biomarkers, with PM and PM identified as major contributors to the combined effect. The results of the exposure-response (E-R) relationships, subgroup analysis, longitudinal analysis and sensitivity analysis all showed the unfavorable impact of air pollution on sarcopenia risk and related vulnerable populations.
CONCLUSIONS
Single-exposure and co-exposure to multiple air pollutants were positively associated with sarcopenia among middle-aged and older adults in China. Our study provided new evidence that air pollution mixture was significantly associated with sarcopenia related biomarkers.
PubMed: 38925034
DOI: 10.1016/j.ecoenv.2024.116634 -
Epilepsy & Behavior : E&B Jun 2024Though unified by challenges in the treatment of status epilepticus (SE), rural Canada is simultaneously massive and diverse, spanning the Pacific, Atlantic, and Arctic... (Review)
Review
Though unified by challenges in the treatment of status epilepticus (SE), rural Canada is simultaneously massive and diverse, spanning the Pacific, Atlantic, and Arctic Oceans. According to the national statistical agency, the most rural jurisdiction in Canada is the Arctic territory of Nunavut. In particular, the Kivalliq region of Nunavut represents a unique epidemiologic SE space because any treatment beyond typical first-line lorazepam and second-line phenytoin by a non-neurologist locum tenens requires airborne evacuation over a thousand kilometers away to a single hospital with a single electroencephalographic (EEG) laboratory. This distinctive mode of healthcare delivery affords unique insights into the challenges of treating SE in rural Canada, such as lack of EEG infrastructure, a markedly high incidence of SE, the struggles of enduring cultural and socioeconomic trauma, and a relative lack of local epilepsy care as recommended by the World Health Organization. For example, despite empiric treatment and waiting over 2 days on average for EEG, 1 in 5 patients still had ongoing or possible electrographic seizures. At the same time, Kivalliq experiences routine dramatic changes in light-dark exposure each year to afford unique insights into circannual SE chronobiology in relation to the chief human zeitgeber of sunlight. This shows that challenges may also represent opportunities, such as for existing and emerging technologies to synergistically address enormous treatment gaps to improve SE care for the people of Kivalliq, while providing novel insights that may also help improve SE clinical care around the world.
PubMed: 38924966
DOI: 10.1016/j.yebeh.2024.109901