Ozone enhancement of lower airway allergic inflammation is prevented by γ-tocopherol

Ozone is a commonly encountered environmental oxidant which has been linked to asthma exacerbation in epidemiological studies. Ozone induces airway inflammation and enhances response to inhaled allergen. It has been suggested that antioxidant therapy may minimize the adverse effects of ozone in asthma. We have previously shown that the antioxidant gamma-tocopherol (γT), an isoform of vitamin E, also has anti-inflammatory effects. We employed a Brown Norway rat model of ozone-enhanced allergic responses to test the therapeutic effects of γT on O3-induced airway inflammation. Ovalbumin (OVA) -sensitized rats were intranasally challenged with 0 or 0.5% OVA on Days 1 and 2, and exposed to 0 or 1 ppm ozone (8h/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg γT on Days 2 through 5. Pulmonary tissue and bronchoalveolar lavage fluid (BALF) were collected on Day 6. OVA challenge caused increased total cells (267% increase) and eosinophils (4000%) in BALF that was unaffected by ozone exposure. Morphometric evaluation of lung tissue revealed increases in intraepithelial mucosubstances (IM) (300%) and subepithelial eosinophils (400%) in main axial airways. Ozone exposure of allergic rats enhanced IM increases in proximal axial airways (200%), induced cys-leukotrienes, MCP-1 and IL-6 production in BALF, and upregulated expression of IL-5 and IL-13 mRNA. γT treatment had no effect on IM increases by allergen, but blocked enhancement by ozone. γT attenuated both OVA- or ozone –stimulated eosinophilic infiltration, and increases of BALF cys-leukotrienes, MCP-1 and IL-6, as well as IL-5 and IL-13 mRNA. These data demonstrate broad anti-inflammatory effects of a γT and suggest it may be an effective therapy of allergic airway inflammation

Evaluating prompt engineering on GPT-3.5’s performance in USMLE-style medical calculations and clinical scenarios generated by GPT-4

Abstract This study was designed to assess how different prompt engineering techniques, specifically direct prompts, Chain of Thought (CoT), and a modified CoT approach, influence the ability of GPT-3.5 to answer clinical and calculation-based medical questions, particularly those styled like the USMLE Step 1 exams. To achieve this, we analyzed the responses of GPT-3.5 to two distinct sets of questions: a batch of 1000 questions generated by GPT-4, and another set comprising 95 real USMLE Step 1 questions. These questions spanned a range of medical calculations and clinical scenarios across various fields and difficulty levels. Our analysis revealed that there were no significant differences in the accuracy of GPT-3.5's responses when using direct prompts, CoT, or modified CoT methods. For instance, in the USMLE sample, the success rates were 61.7% for direct prompts, 62.8% for CoT, and 57.4% for modified CoT, with a p-value of 0.734. Similar trends were observed in the responses to GPT-4 generated questions, both clinical and calculation-based, with p-values above 0.05 indicating no significant difference between the prompt types. The conclusion drawn from this study is that the use of CoT prompt engineering does not significantly alter GPT-3.5's effectiveness in handling medical calculations or clinical scenario questions styled like those in USMLE exams. This finding is crucial as it suggests that performance of ChatGPT remains consistent regardless of whether a CoT technique is used instead of direct prompts. This consistency could be instrumental in simplifying the integration of AI tools like ChatGPT into medical education, enabling healthcare professionals to utilize these tools with ease, without the necessity for complex prompt engineering

Retrospective Study of Reported Adverse Events Due to Complementary Health Products in Singapore From 2010 to 2016

The objective of this study is to collate and analyse adverse event reports associated with the use of complementary health products (CHP) submitted to the Health Sciences Authority (HSA) of Singapore for the period 2010–2016 to identify various trends and signals for pharmacovigilance purposes. A total of 147,215 adverse event reports suspected to be associated with pharmaceutical products and CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3%) were associated with chemical drugs, 1,807 (1.2%) with vaccines, 1,324 (0.9%) with biological drugs (biologics), and 893 (0.6%) with CHP. The number of adverse event reports associated with Chinese Proprietary Medicine, other complementary medicine and health supplements are presented. Eight hundred and ninety three adverse event reports associated with CHP in the 7-year period have been successfully collated and analyzed. In agreement with other studies, adverse events related to the “skin and appendages disorders” were the most commonly reported. Most of the cases involved dermal allergies (e.g., rashes) associated with the use of glucosamine products and most of the adulterated products were associated with the illegal addition of undeclared drugs for pain relief. Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants detected. Reporting suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The findings from this study help to create greater awareness on the health risks, albeit low, when consuming CHP and dispelling the common misconception that “natural” means “safe.” In particular, healthcare professionals and the general public should be aware of potential adulteration of CHP. The analysis of spontaneously reported adverse events is an important surveillance system in monitoring the safety of CHP and helps in the understanding of the risk associated with the use of such products. Greater collaboration and communication between healthcare professionals, regulators, patients, manufacturers, researchers, and the general public are important to ensure the quality and safety of CHP

Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans

The chemokine receptor CX3CR1 is a proinflammatory leukocyte receptor specific for the chemokine fractalkine (FKN or CX3CL1). In two retrospective studies, CX3CR1 has been implicated in the pathogenesis of atherosclerotic cardiovascular disease (CVD) based on statistical association of a common receptor variant named CX3CR1-M280 with lower prevalence of atherosclerosis, coronary endothelial dysfunction, and acute coronary syndromes. However, the general significance of CX3CR1-M280 and its putative mechanism of action have not previously been defined. Here we show that FKN-dependent cell-cell adhesion under conditions of physiologic shear is severely reduced in cells expressing CX3CR1-M280. This was associated with marked reduction in the kinetics of FKN binding as well as reduced FKN-induced chemotaxis of primary leukocytes from donors homozygous for CX3CR1-M280. We also show that CX3CR1-M280 is independently associated with a lower risk of CVD (adjusted odds ratio, 0.60, P = 0.008) in the Offspring Cohort of the Framingham Heart Study, a long-term prospective study of the risks and natural history of this disease. These data provide mechanism-based and consistent epidemiologic evidence that CX3CR1 may be involved in the pathogenesis of CVD in humans, possibly by supporting leukocyte entry into the coronary artery wall. Moreover, they suggest that CX3CR1-M280 is a genetic risk factor for CVD