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Introduction: Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real-world impact at the population level remains unclear., Methods: Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long-term trends in the incidence, incidence-based mortality (IBM), and survival of lung cancer patients in the United States., Results: The incidence and IBM of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1-year survival (1-YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1-YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%-0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%-1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%-2.47%) from 2014 to 2019. The same two turning points in 1-YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1-YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period., Conclusion: This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real-world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Although triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance and cardiometabolic disease, its effectiveness in predicting mortality risk has not been adequately validated. We aimed to investigate the association between the TyG-related indices and all-cause and cause-specific mortality in the general population., Methods: A total of 27,642 individuals were included from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. Three indicators were constructed, including the TyG index, TyG combined with waist-to-height ratio (TyG-WHtR), and TyG combined with waist circumference (TyG-WC). Mortality data was acquired through the linkage of NHANES data with National Death Index records. Weighted Cox proportional hazards models were used to estimate the independent association between the TyG-related indices and mortality. Nonlinear associations were explored using restricted cubic splines., Results: Multivariable adjusted models showed a progressive increase in all-cause and cause-specific mortality across quartiles of the TyG-related indices. Compared with the lowest quartile of the TyG index, the highest quartile had adjusted hazard ratios of 1.26 (95% CI 1.04-1.52) for all-cause mortality, 1.38 (1.04-1.74) for cardiovascular mortality, and 1.23 (1.01-1.50) for non-cardiovascular mortality, respectively. For the TyG-WHtR index, the corresponding hazard ratios were 1.60 (1.25-2.05), 1.86 (1.26-2.50), and 1.48 (1.10-1.99), respectively. For the TyG-WC index, the corresponding hazard ratios were 1.42 (1.11-1.75), 1.48 (1.04-1.96), and 1.38 (1.05-1.72), respectively. The associations between the three TyG-related indices and all-cause, cardiovascular and non-cardiovascular mortality were J-shaped. Interaction tests revealed significant effect modification by age, low-density lipoprotein cholesterol (LDL-C) level, and statin use (all P values < 0.05)., Conclusions: The TyG-related indices were independent predictors of all-cause and cause-specific mortality in the general population. Young individuals should be particularly vigilant, whereas low LDL-C levels and statin use are potentially protective., (© 2024. The Author(s).)

Objective: Our study aims to characterize the ocular safety profiles of phosphodiesterase type 5 (PDE5) inhibitors and explore the differences among different PDE5 inhibitors., Methods: We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles., Results: Among 61,211 reports qualifying for analysis, 5,127 involved sildenafil, 832 vardenafil, and 3,733 tadalafil. All PDE5 inhibitors showed increased reporting odds ratios (ROR) for ocular adverse events, with vardenafil highest (ROR 4.47) followed by sildenafil and tadalafil. Key ocular adverse events included cyanopsia, optic ischemic neuropathy, visual field defects, unilateral blindness and blindness. Sildenafil showed the highest disproportionality for cyanopsia (ROR 1148.11) while vardenafil and tadalafil showed the highest disproportionality for optic ischemic neuropathy. Time-to-onset analysis also revealed significant differences, with sildenafil having a later median time-to-onset compared to vardenafil and tadalafil., Conclusions: This comprehensive pharmacovigilance study reveals distinct patterns of ocular adverse events associated with PDE5 inhibitors. These findings contribute to a better understanding of the safety profiles of PDE5 inhibitors and may guide healthcare professionals in clinical decision-making.

Objective: We analyze and identify the signals of gender differences in adverse events (ADEs) related to Osimertinib and provide reference for clinical implementation of individualized drug use., Methods: ADE reports of Osimertinib received from FAERS database from the first quarter of 2016 to the fourth quarter of 2022 were extracted. Reporting odds ratio (ROR) data analysis strategy was used for mining of signal strength that represents gender differences in ADEs related to Osimertinib., Results: The number of Osimertinib ADE reports included in the analysis was 7968 in females and 7570 in males, respectively. According to ROR, men were more likely to develop pneumonia aspiration, lung infection, interstitial lung disease, pulmonary toxicity, dyspnea, ventricular extrasystoles, and pulmonary thrombosis, while women were more likely to develop cardiac failure congestive, stomatitis, diarrhea, muscle spasms, nail disorder, onycholysis, skin disorder, dry skin, and rash., Conclusion: Gender differences existed in ADE signals related to Osimertinib. The higher risk of ADEs in male patients was lung diseases that seem more serious than those nail toxicities or skin problems that occurred in female patients. In order to ensure the safety of medication, we should be alert to the differences between different genders and take corresponding preventive measures to reduce the occurrence of serious ADEs.

Background: The triglyceride-lowering drug, icosapent ethyl (IPE), was granted a new indication for the reduction of atherosclerotic cardiovascular disease risk in 2019. This study aimed to investigate the safety profile of IPE by mining the FDA Adverse Event Reporting System (FAERS) database., Methods: The reporting odds ratio was used to analyze IPE's adverse events (AEs) based on the FAERS data from July 2012 to December 2022. We described the characteristics of AE reports and evaluated the clinical prioritization of AEs. Then we defined and analyzed nine interested adverse drug reactions (ADRs) in both overall and subgroups, and investigated the times to onset., Results: The findings of our study strengthen the evidence for an increased risk of atrial fibrillation using IPE. IPE alone may not increase the risk of bleeding unless combined with antithrombotic drugs. Similar to statins, IPE alone can increase the risk of musculoskeletal pain, drug-related hepatic disorders, and hyperglycemia, but the risk could not double when IPE was combined with statins. Most ADRs occur in the early stage of treatment., Conclusions: This study provides a comprehensive real-world safety profile of IPE, which indicates that IPE is well-tolerated.

Background: Cutaneous malignant melanoma (CMM) causes most skin cancer deaths in the United States (US). The mortality has been decreasing in the US population. We hypothesize that this population-level reduction is mainly attributable to the treatment advances, rather than the successful primary and secondary prevention., Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we collected the incidence, incidence-based mortality (IBM), and 5-year survival (5-YS) rates of CMM from 1994 to 2019. Trends by stage and sex were examined by joinpoint regression analyses and age-period-cohort analyses., Results: The overall incidence of CMM rose by 1.6% yearly from 1994 to 2006 (95% confidence interval [CI]: 0.9% to 2.2%) and then increased with a numerical trend. And we projected the incidence will continue to increase until 2029. In contrast, the IBM for all CMM has decreased yearly by 2.8% (95% CI: -3.9% to -1.8%) since 2010 after continuously increasing by 3.8% annually (95% CI: 3.2% to 4.4%) from 1996 to 2010. For early-stage (localized and regional) CMM, we found the incidence since 2005 plateaued without further increase, while the incidence for CMM at distant stage continuously increased by 1.4% per year (95% CI: 0.9% to 2.0%). Improvements in 5-YS were observed over the study period for all CMM and were most obvious in distant stage. And significant period effects were noted around the year 2010., Conclusion: This study demonstrated improved survival and reduced mortality of CMM at the US population level since 2010, which were consistent with the introduction of novel therapies. Encouraging effects of primary prevention among adolescents in the most recent cohorts were found. However, the plateaued overall incidence and early diagnosis rates indicated that advances in primary and secondary prevention are very much needed to further control the burden of CMM., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: UMOD is exclusively produced by renal epithelial cells. Recent genome-wide association studies (GWAS) suggested that common variants in UMOD gene are closely connected with the risk of CKD. However, a comprehensive and objective report on the current status of UMOD research is lacking. Therefore, we aim to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of UMOD research in the past., Methods: We collected data from the Web of Science Core Collection database and used the Online Analysis Platform of Literature Metrology, the Online Analysis Platform of Literature Metrology and Microsoft Excel 2019 to perform bibliometricanalysis and visualization., Results: Based on the data from the WoSCC database from 1985 to 2022, a total of 353 UMOD articles were published in 193 academic journals by 2346 authors from 50 different countries/regions and 396 institutions. The United States published the most papers. Professor Devuyst O from University of Zurich not only published the greatest number of UMOD-related papers but also is among the top 10 co-cited authors. KIDNEY INTERNATIONAL published the most necroptosis studies, and it was also the most cited journal. High-frequency keywords mainly included 'chronic kidney disease', 'Tamm Horsfall protein' and 'mutation'., Conclusions: The number of UMOD-related articles has steadily increased over the past decades Current UMOD studies focused on Biological relevance of the UMOD to kidney function and potential applications in the risk of CKD mechanisms, these might provide ideas for further research in the UMOD field., (© 2023. The Author(s).)

Background: Obesity is associated with polycystic ovary syndrome (PCOS). We aimed to elucidate the research status and explore research trends and future directions of research on obesity and PCOS., Methods: A bibliometric analysis of the published papers in the field of obesity and PCOS between 2012 and 2022 was conducted on the basis of the Web of Science Core Collection database. The collaboration networks, research trends, literature sources, citation analysis, co-citation analysis, and keywords analysis were statistically analyzed and visualized using the VOSviewer software., Results: We retrieved 2843 records from 681 journals by 12307 authors from 2942 institutes in 99 countries. The number of published papers and citations had a roughly increasing trend annually. The United States and China contributed the majority of the records. Monash University, Shanghai Jiaotong University, Aristotle University of Thessaloniki, Karolinska Institute, University of São Paulo, and Tehran University of Medical Sciences were the biggest nodes in their cluster of the collaboration network map, and Moran LJ, Teede HJ, Joham AE, Escobar-Morreale HF, and Macut D were prolific authors. Research trends and hotspots were identified and visualized in the field of obesity and PCOS. Research hotspots in this field focused on insulin resistance (IR), metabolic syndrome, metformin, and inflammation. Bariatric surgery, mitochondrial dysfunction, binding globulins, and comorbidities may be the frontiers of future research., Conclusions: We concluded the research status and trends in the field of obesity and PCOS. A better understanding of collaboration patterns, research hotspots, and frontiers may be useful for researchers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Li, Li, Wang, Li, Song, Sun, Fu, Zhou, Yi, Zhu and Zhu.)

Background and Aims: The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination., Approach and Results: Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence-based mortality (IBM), and 1-year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute's Joinpoint Regression Program. Age-period-cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990-2019) as a likely validation set. Joinpoint and age-period-cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992-2011 and sharply decreased thereafter by -2.3% annually (95% CI: -3.5% to -1.1%). IBM peaked in 2013 (age-standardized mortality rate: 6.98 per 100,000 person-years) in the US population. IBM started to decrease significantly in 2013 by -3.2%/year (95% CI: -5.4% to -1.1% per year) after a continuous increase of 3.5% annually during 1993-2013. Overall, the 1-year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60-69 and born between 1952-1957 were found., Conclusions: We found significantly decreased overall HCC-specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States., (© 2022 American Association for the Study of Liver Diseases.)

Due to the large amount of greenhouse gas emissions and the high dependence on fossil fuels, the sustainable development of aviation industry has attracted worldwide attention. Bio-jet fuel is considered to be a promising alternative to traditional aviation fuel. This article summarizes the representative technological route, development status, opportunities and challenges faced by the development of bio-jet fuel industry. So far, several bio-jet fuel production technologies have been certified by the American Society for Testing and Materials (ASTM). Hydroprocessed esters and fatty acids is currently the most mature process that can be fully commercialized. Considering economic characteristics and technology maturity, Fischer-Tropsch is promising in near term.

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg ® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as "biological missiles", is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs., (© 2022. The Author(s).)

Recent foodborne illness outbreaks have heightened pressures on growers to deter wildlife from farms, jeopardizing conservation efforts. However, it remains unclear which species, particularly birds, pose the greatest risk to food safety. Using >11,000 pathogen tests and 1565 bird surveys covering 139 bird species from across the western United States, we examined the importance of 11 traits in mediating wild bird risk to food safety. We tested whether traits associated with pathogen exposure (e.g., habitat associations, movement, and foraging strategy) and pace-of-life (clutch size and generation length) mediated foodborne pathogen prevalence and proclivities to enter farm fields and defecate on crops. Campylobacter spp. were the most prevalent enteric pathogen (8.0%), while Salmonella and Shiga-toxin producing Escherichia coli (STEC) were rare (0.46% and 0.22% prevalence, respectively). We found that several traits related to pathogen exposure predicted pathogen prevalence. Specifically, Campylobacter and STEC-associated virulence genes were more often detected in species associated with cattle feedlots and bird feeders, respectively. Campylobacter was also more prevalent in species that consumed plants and had longer generation lengths. We found that species associated with feedlots were more likely to enter fields and defecate on crops. Our results indicated that canopy-foraging insectivores were less likely to deposit foodborne pathogens on crops, suggesting growers may be able to promote pest-eating birds and birds of conservation concern (e.g., via nest boxes) without necessarily compromising food safety. As such, promoting insectivorous birds may represent a win-win-win for bird conservation, crop production, and food safety. Collectively, our results suggest that separating crop production from livestock farming may be the best way to lower food safety risks from birds. More broadly, our trait-based framework suggests a path forward for co-managing wildlife conservation and food safety risks in farmlands by providing a strategy for holistically evaluating the food safety risks of wild animals, including under-studied species., (© 2021 The Ecological Society of America.)

Background: One of the primary obstacles to measure clinical quality is the lack of configurable solutions to make computers understand and compute clinical quality indicators. The paper presents a solution that can help clinical staff develop clinical quality measurement more easily and generate the corresponding data reports and visualization by a configurable method based on openEHR and Clinical Quality Language (CQL)., Methods: First, expression logic adopted from CQL was combined with openEHR to express clinical quality indicators. Archetype binding provides the clinical information models used in expression logic, terminology binding makes the medical concepts consistent used in clinical quality artifacts and metadata is regarded as the essential component for sharing and management. Then, a systematic approach was put forward to facilitate the development of clinical quality indicators and the generation of corresponding data reports and visualization. Finally, clinical physicians were invited to test our system and give their opinions., Results: With the combination of openEHR and CQL, 64 indicators from Centers for Medicare & Medicaid Services (CMS) were expressed for verification and a complicated indicator was shown as an example. 68 indicators from 17 different scenes in the local environment were also expressed and computed in our system. A platform was built to support the development of indicators in a unified way. Also, an execution engine can parse and compute these indicators. Based on a clinical data repository (CDR), indicators were used to generate data reports and visualization and shown in a dashboard., Conclusion: Our method is capable of expressing clinical quality indicators formally. With the computer-interpretable indicators, a systematic approach can make it more easily to define clinical indicators and generate medical data reports and visualization, and facilitate the adoption of clinical quality measurements., (© 2022. The Author(s).)

Objective: To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China. Methods: The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated. Results: A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs. Conclusions: The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Objective: To explore the relationships of serum 25-hydroxyvitamin D (25(OH)D) with obesity and metabolic parameters in US children., Design: Cross-sectional analysis. We evaluated the associations between serum 25(OH)D and multiple measurements of adiposity, serum lipid concentrations, fasting glucose and insulin resistance in children aged 6-18 years with adjustments for multiple covariates., Setting: The National Health and Nutrition Examination Survey, 2001-2006., Participants: A nationally representative sample of 6311 children and adolescents aged 6-18 years., Results: Among US children and adolescents, the prevalence of vitamin D deficiency has been especially high in older children, girls and the non-Hispanic Black population. Higher odds of obesity were found at a 25(OH)D concentration of <30 nmol/l (deficiency) than at >50 nmol/l under both criteria for obesity in children (OR = 3·27, Ptrend ≤ 0.001). Moreover, increased odds of having abnormal HDL-cholesterol (OR = 1·71, Ptrend ≤ 0.001) and impaired insulin resistance (OR = 4·15, Ptrend ≤ 0·001) were found for children deficient in 25(OH)D compared with those with normal 25(OH)D concentrations. When the children and adolescents were stratified by gender, we found stronger associations between serum 25(OH)D concentration and both HDL-cholesterol and insulin resistance in girls. No association of 25(OH)D with any other metabolic parameter was found., Conclusions: Our results suggest a potential harmful association between low serum 25(OH)D concentration and the risk of obesity among children. However, the underlying mechanisms require further investigation.

Objectives: The role of palliative gastrectomy in the management of metastatic gastric cancer remains inadequately clarified., Methods: We analyzed patients with metastatic gastric cancer enrolled in the Surveillance, Epidemiology, and End Results registry from January 2004 to December 2012. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of the groups of patients who undergone gastrectomy and those without gastrectomy. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival and cancer-specific survival rates with corresponding 95% confidence intervals (CIs)., Results: In general, receiving any kind of gastrectomy was associated with an improvement in survival in the multivariate analyses (hazard ratio [HR]os = 0.64, 95% CI = 0.59-0.70, HRcss = 0.63, 95% CI = 0.57-0.68) and PS matching (PSM) analyses (HRos = 0.63, 95% CI = 0.56-0.70, HRcss = 0.62, 95% CI = 0.55-0.70). After PSM, palliative gastrectomy was found to be associated with remarkably improved survival for patients with stage M1 with only 1 metastasis but not associated with survival of patients with stage M1 with extensive metastasis (≥2 metastatic sites)., Discussion: The results obtained from the Surveillance, Epidemiology, and End Results database suggest that patients with metastatic gastric cancer might benefit from palliative gastrectomy on the basis of chemotherapy. However, a PSM cohort study of this kind still has a strong selection bias and cannot replace a properly conducted randomized controlled trial.

Objective: To demonstrate whether radiotherapy has an effect on the survival of patients with stage IVb (M1) cervical cancer, as it has not been adequately clarified., Methods: We analyzed International Federation of Gynecology and Obstetrics (FIGO) stage M1 cervical cancer diagnosed in patients between 1992 and 2013 using population-based data from the Surveillance, Epidemiology, and End Results registry. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of comparison groups. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival (OS) and cancer-specific survival (CSS) months with corresponding 95% confidence intervals (95% CIs)., Results: In general, receiving radiotherapy significantly improved OS and CSS both before and after PS matching (PSM) (P < 0.001), with significantly improved OS (hazard ratio, 0.69; 95% CI, 0.62-0.76) and CSS (hazard ratio, 0.79; 95% CI, 0.70-0.89) after PSM in patients with stage M1 cervical cancer. Before PSM, radiotherapy was found to be associated with improved survival even for the patients with stage M1 cervical cancer with extensive metastasis (≥2 metastatic sites) (P < 0.001). Although P value was not significant for brain metastasis, the survival month was numerically improved before PSM (OS and CSS, 1 month vs 4 months). Overall, radiotherapy still significantly improved survival for patients with one metastatic site (ie, oligometastases) either before or after PSM (P < 0.05), with the survival month improved more than 6 months., Conclusions: The large Surveillance, Epidemiology, and End Results results support that radiotherapy might improve the survival of patients with metastatic cervical cancer. It might be prudent to carefully select suitable patients for radiation therapy for metastatic cervical cancer.

Little is known regarding the effects of environmental lead exposure on cardiovascular risk factors in the adolescent population. We studied 11,662 subjects included in the National Health and Nutrition Examination Survey (NHANES) 1999-2012. Blood lead levels were analysed for their association with cardiovascular risk factors (CVRF). Regression coefficients (Beta) and 95% confidence intervals (CIs) of blood lead in association with CVRF (e.g., total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure) were estimated using multivariate and generalized linear regression after adjusting for age, gender, ethnicity, serum cotinine, body mass index (BMI), physical activity, and household income. We identified a strong positive association between blood lead (coefficient = 0.022, 95% CI 0.003, 0.041; P = 0.022) and LDL-cholesterol in adolescents (age 12-19 years). However, no associations with other CVRFs were found in the overall population. In the generalized linear models, participants with the highest lead levels demonstrated a 1.87% (95% CI 0.73%, 3.02%) greater increase in serum LDL-cholesterol (p for trend = 0.031) when compared to participants with the lowest lead levels. These results provide epidemiological evidence that low levels of blood lead are positively associated with LDL-cholesterol in the adolescent population.

The silver-haired bat variant of rabies virus (SHBRV) has been identified as the etiological agent of a number of recent human rabies cases in the United States that are unusual in not having been associated with any known history of conventional exposure. Comparison of the different biological and biochemical properties of isolates of this virus with those of a coyote street rabies virus (COSRV) revealed that there are unique features associated with SHBRV. In vitro studies showed that, while the susceptibility of neuroblastoma cells to infection by both viruses was similar, the infectivity of SHBRV was much higher than that of COSRV in fibroblasts (BHK-21) and epithelial cells (MA-104), particularly when these cells were kept at 34 degrees C. At this temperature, low pH-dependent fusion and cell-to-cell spread of virus is seen in BHK-21 cells infected with SHBRV but not with COSRV. It appears that SHBRV may possess an unique cellular tropism and the ability to replicate at lower temperature, allowing a more effective local replication in the dermis. This hypothesis is supported by in vivo results which showed that while SHBRV is less neurovirulent than COSRV when administered via the intramuscular or intranasal routes, both viruses are equally neuroinvasive if injected intracranially or intradermally. Consistent with the above findings, the amino acid sequences of the glycoproteins of SHBRV and COSRV were found to have substantial differences, particularly in the region that contains the putative toxic loop, which are reflected in marked differences in their antigenic composition. Nevertheless, an experimental rabies vaccine based on the Pittman Moore vaccine strain protected mice equally well from lethal doses of SHBRV and COSRV, suggesting that currently used vaccines should be effective in the postexposure prophylaxis of rabies due to SHBRV.

Sera from 295 horses in the USA were examined by an indirect immunofluorescence assay and Western blot assays to determine the prevalence of Borna disease virus infection. Eight (2.7 per cent) of the samples were positive in both assays, and 18 (6.1 per cent) were positive only in the Western blot assay. The indirect fluorescence titres ranged from 1:20 to 1:80 of antibodies recognising the virus-specific antigen from Borna disease virus-infected cells. The purified virus-specific proteins isolated from infected rat brains were recognised by positive equine serum samples after immunostaining by a Western blot technique. Information obtained from the owners about the history of the seropositive horses revealed that they were either clinically normal or had a pathological diagnosis of disease unrelated to Borna disease. This is the first report of the detection of antibodies to Borna disease virus in horses in the USA. The disease may be more widespread in a subclinical form, with very long incubation periods, and may not necessarily be restricted to historically endemic areas.