Toxicity and biokinetics following pulmonary exposure to aluminium (aluminum): A review.

During the manufacture and use of aluminium (aluminum), inhalation exposure may occur. We reviewed the pulmonary toxicity of this metal including its toxicokinetics. The normal serum/plasma level based on 17 studies was 5.7 ± 7.7µg Al/L (mean ± SD). The normal urine level based on 15 studies was 7.7 ± 5.3µg/L. Bodily fluid and tissue levels during occupational exposure are also provided, and the urine level was increased in aluminium welders (43 ± 33µg/L) based on 7 studies. Some studies demonstrated that aluminium from occupational exposure can remain in the body for years. Excretion pathways include urine and faeces. Toxicity studies were mostly on aluminium flakes, aluminium oxide and aluminium chlorohydrate as well as on mixed exposure, e.g. in aluminium smelters. Endpoints affected by pulmonary aluminium exposure include body weight, lung function, lung fibrosis, pulmonary inflammation and neurotoxicity. In men exposed to aluminium oxide particles (3.2µm) for two hours, lowest observed adverse effect concentration (LOAEC) was 4mg Al2O3/m3 (= 2.1mg Al/m3), based on increased neutrophils in sputum. With the note that a similar but not statistically significant increase was seen during control exposure. In animal studies LOAECs start at 0.3mg Al/m3. In intratracheal instillation studies, all done with aluminium oxide and mainly nanomaterials, lowest observed adverse effect levels (LOAELs) started at 1.3mg Al/kg body weight (bw) (except one study with a LOAEL of ~0.1mg Al/kg bw). The collected data provide information regarding hazard identification and characterisation of pulmonary exposure to aluminium.

Remission of hypersensitivity pneumonitis after allogeneic hematopoietic stem cell transplantation.

A 50-year-old man was diagnosed with hypersensitivity pneumonitis caused by the environment of his bar owing to worsening symptoms, laboratory test results, and computed tomography images after an environmental inhalation challenge test. His hypersensitivity pneumonitis exacerbated despite receiving prednisolone 20 mg/day. The patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor for myelodysplastic syndrome. No exacerbation of hypersensitivity pneumonitis was observed after HSCT. An environmental inhalation challenge test involving exposure to his bar confirmed the remission of hypersensitivity pneumonitis after HSCT. This case demonstrates that hypersensitivity pneumonitis can be remitted by HSCT.

Effect of airflow rate on droplet deposition of an impinging-jet inhaler in the human respiratory tract.

This paper presents a numerical investigation to understand the transport and deposition of sprays emitted by an impinging-jet inhaler in the human respiratory tract under different inhalation flow rates. An injection model is used for the numerical simulations considering the spreading angles of the spray in the two directions, which are measured from experiments. The model parameter is adjusted to match the mean droplet size measured in the previous experiment. A time-varying sinusoidal inhalation flow rate is utilized as airflow conditions, which is closer to the actual situation when using an inhaler. The results demonstrate that the inhalation airflow rate significantly affects the spray's transport behavior and deposition results in the respiratory tract. Both excessively high and low inhalation flow rates lead to an increase in deposition in the mouth-throat. A moderate inhalation flow rate reduces throat deposition while maximizing lung deposition. Higher inhalation flow rates enable faster delivery of the droplets to the lungs, whereas lower inhalation flow rates achieve a more uniform deposition over time in the lungs. The amount of deposition in different parts of the lung lobes follows a fixed order. This study provides valuable insights for optimizing the inhalation flow rate conditions of the impinging-jet inhaler for clinical applications.

Severity of inhalation injury and risk of nosocomial pneumonia: a retrospective cohort study.

BACKGROUND: The impact of inhalation injury on risk of nosocomial pneumonia, an important complication in burn patients, is not well established. RESEARCH QUESTION: Is more severe inhalation injury associated with increased risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of patients with suspected inhalation injury admitted to a regional burn center from 2011 to 2022 who underwent diagnostic bronchoscopy within 48 hours of admission. We estimated the association of high-grade inhalation injury (abbreviated injury score [AIS] 3-4) versus low-grade inhalation injury (AIS 1-2) with nosocomial pneumonia (NP) adjusted for age, burn size, and comorbid obstructive lung disease. Death and hospital discharge were considered competing risks. RESULTS: Of the 245 patients analyzed, 51 (21%) had high-grade injury, 180 (73%) had low-grade injury, and 14 (6%) had no inhalation injury. Among the 236 patients hospitalized for >48 hours, NP occurred in 24/50 (48%) patients in the high-grade group, 54/172 (31%) in the low-grade group, and 2/14 (14%) in the no inhalation injury group. High-grade (vs low-grade) inhalation injury was associated with higher hazard of NP in both the proportional cause-specific hazard model (CSHR 2.04; 95% CI, 1.26-3.30; p=0.004) and Fine-Gray subdistribution hazards model (SHR for NP, 2.24; 95% CI, 1.38-3.64; p=0.001). INTERPRETATION: Among patients with inhalation injury, more severe injury was associated with higher hazard of NP in competing risk analysis. Additional research is needed to investigate mechanisms that may explain the relationship between inhalation injury and NP and to identify more effective prevention strategies.

Impact of Pharmacist-Led Intervention on Adherence to Inhalers, Inhalation Technique, and Disease Control Among Asthma/COPD Patients in a Resource Limited Center: An Interventional Study.

Background: Asthma and Chronic obstructive pulmonary disease (COPD) are chronic respiratory conditions characterized by airflow obstruction and respiratory symptoms. Adherence to prescribed inhaler therapy and correct inhalation technique are essential for effective disease management and optimal disease control. However, non-adherence and incorrect inhalation technique are common challenges faced by patients with asthma and COPD, leading to suboptimal treatment outcomes and increased healthcare burden. Purpose: To study the impact of a pharmacist-led intervention on inhaler adherence, inhalation technique, and disease control among patients with asthma and COPD. Patients and Methods: A pre-post interventional design assessed the effects of pharmacist-led intervention on inhaler adherence, inhalation techniques, and disease control in asthma and COPD patients at Dhulikhel Hospital in Nepal. Inclusion criteria: adult patient clinically diagnosed with asthma or COPD patients of all genders. The intervention comprised counseling patients with aids like videos, and informational leaflets. Impact was measured using checklist method for inhalation technique, the Test of Adherence to Inhaler (TAI) questionnaire for adherence to inhaler, and "Asthma Control Test (ACT)" or "COPD Assessment Test (CAT)" for disease control. Results: The pharmacist-led intervention significantly increased adherence to inhalers, evidenced by a notable rise in the proportion of patients with good adherence (P<0.001). Sporadic, deliberate, and unwitting noncompliance pattern also improved significantly after the intervention (P<0.001, P<0.001 and P=0.001). Inhalation technique exhibited substantial improvement after intervention (P<0.001). The analysis indicated significant moderate negative correlations between "TIA" and "CAT" [ρ=-0.31; P=0.01], and between "inhalation technique score" and "CAT score" [ρ=-0.31; P=0.01] suggesting that as adherence to inhaler usage and inhalation technique improve, CAT scores tend to decrease, indicating reduced disease impact on the patient. Conclusion: This study shows the potential efficacy of pharmacist-led intervention in enhancing adherence to inhaler, inhalation technique, and disease control in respiratory conditions such as asthma and COPD.

Evaluation of airborne asbestos concentrations associated with the maintenance of brakes on an industrial overhead crane.

OBJECTIVES: To evaluate potential airborne asbestos exposures during brake maintenance and repair activities on a P&H overhead crane, and during subsequent handling of the mechanic's clothing. METHODS: Personal (n = 27) and area (n = 61) airborne fiber concentrations were measured during brake tests, removal, hand sanding, compressed air use, removal and reattachment of chrysotile-containing brake linings, and reinstallation of the brake linings. The mechanic's clothing was used to measure potential exposure during clothes handling. RESULTS: All brake linings contained between 19.9% to 52.4% chrysotile asbestos. No amphibole fibers were detected in any bulk or airborne samples. The average full-shift airborne chrysotile concentration was 0.035 f/cc (PCM-equivalent asbestos-specific fibers, or PCME). Average task-based personal air samples collected during brake maintenance, sanding, compressed air use, and brake lining removal tasks ranged from 0 to 0.48 f/cc (PCME). The calculated 30-minute time-weighted average (TWA) airborne chrysotile concentration associated with 5-15 minutes of clothes handling was 0-0.035 f/cc PCME. CONCLUSION: The results indicated that personal and area TWA fiber concentrations measured during all crane brake maintenance and clothes handling tasks were below the current OSHA 8-h TWA Permissible Exposure Limit for asbestos of 0.1 f/cc. Further, no airborne asbestos fibers were measured during routine brake maintenance tasks following the manufacturer's maintenance manual procedures. All short-term airborne chrysotile concentrations measured during non-routine tasks were below the current 30-minute OSHA excursion limit for asbestos of 1 f/cc. This study adds to the available data regarding chrysotile exposure potential during maintenance on overhead cranes.

Inhaled polystyrene microplastics impaired lung function through pulmonary flora/TLR4-mediated iron homeostasis imbalance.

Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 µm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.

Next generation risk assessment of biocides (PHMG-p and CMIT/MIT)-induced pulmonary fibrosis using adverse outcome pathway-based transcriptome analysis.

Next-generation risk assessment (NGRA) has emerged as a promising alternative to non-animal studies owing to the increasing demand for the risk assessment of inhaled toxicants. In this study, NGRA was used to assess the inhalation risks of two biocides commonly used as humidifier disinfectants: polyhexamethylene guanidine phosphate (PHMG-p) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT). Human bronchial epithelial cell transcriptomic data were processed based on adverse outcome pathways and used to establish transcriptome-based points of departure (tPODs) for each biocide. tPOD values were 0.00500-0.0510 µg/cm2 and 0.0342-0.0544 µg/cm2 for PHMG-p and CMIT/MIT, respectively. tPODs may provide predictive power comparable to that of traditional animal-based PODs (aPODs). The tPOD-based NGRA determined that both PHMG-p and CMIT/MIT present a high inhalation risk. Moreover, the identified PHMG-p posed a higher risk than CMIT/MIT, and children were identified as more susceptible population compared to adults. This finding is consistent with observations from actual exposure events. Our findings suggest that NGRA with transcriptomics offers a reliable approach for risk assessment of specific humidifier disinfectant biocides, while acknowledging the limitations of current models and in vitro systems, particularly regarding uncertainties in pharmacokinetics (PK) and pharmacodynamics (PD).

Vaporized Δ9-tetrahydrocannabinol exposure in utero has negative effects on attention in a dose- and sex-dependent manner.

There has been an increasing use of cannabis during pregnancy in recent years. Studies have indicated that THC exposure in utero may increase the risk of attention deficits and memory impairments in adolescence. The goal of the present study is to investigate the effects of vaporized THC exposure during pregnancy on offspring memory and attention performance in early and late adolescence. Pregnant dams were exposed to vaporized THC (10 mg or 40 mg) daily from gestational day 2 until labor. Pups were given either a standard or a high-fat diet at weaning and tested in early and late adolescence in two memory tests, the Novel Object Recognition (NOR) test and the Morris Water Maze (MWM) test, and a test of attention, the Object-Based Attention (OBA) test. Rats exposed to low-dose THC showed significantly decreased object exploration in both the NOR and OBA tests, indicating decreased attention. Object exploration time in OBA was significantly lower in females than males. Additionally, post hoc analysis of MWM tests showed some differences in learning patterns for HD THC offspring in early adolescence, possibly due to diet interaction, but ultimate performance was not impacted. While there are existing studies examining prenatal exposure to THC in rodents, this is the first to our knowledge examining memory and attention in adolescence following vaporized THC exposure in utero, and we find indications that prenatal THC exposure may lead to attention deficits and altered memory performance.

Characterization of Wildland Firefighters' Exposure to Coarse, Fine, and Ultrafine Particles; Polycyclic Aromatic Hydrocarbons; and Metal(loid)s, and Estimation of Associated Health Risks.

Firefighters' occupational activity causes cancer, and the characterization of exposure during firefighting activities remains limited. This work characterizes, for the first time, firefighters' exposure to (coarse/fine/ultrafine) particulate matter (PM) bound polycyclic aromatic hydrocarbons (PAHs) and metal(loid)s during prescribed fires, Fire 1 and Fire 2 (210 min). An impactor collected 14 PM fractions, the PM levels were determined by gravimetry, and the PM-bound PAHs and metal(loid)s were determined by chromatographic and spectroscopic methodologies, respectively. Firefighters were exposed to a total PM level of 1408.3 and 342.5 µg/m3 in Fire 1 and Fire 2, respectively; fine/ultrafine PM represented more than 90% of total PM. Total PM-bound PAHs (3260.2 ng/m3 in Fire 1; 412.1 ng/m3 in Fire 2) and metal(loid)s (660.8 ng/m3 versus 262.2 ng/m3), distributed between fine/ultrafine PM, contained 4.57-24.5% and 11.7-12.6% of (possible/probable) carcinogenic PAHs and metal(loid)s, respectively. Firefighters' exposure to PM, PAHs, and metal(loid)s were below available occupational limits. The estimated carcinogenic risks associated with the inhalation of PM-bound PAHs (3.78 × 10-9 - 1.74 × 10-6) and metal(loid)s (1.50 × 10-2 - 2.37 × 10-2) were, respectively, below and 150-237 times higher than the acceptable risk level defined by the USEPA during 210 min of firefighting activity and assuming a 40-year career as a firefighter. Additional studies need to (1) explore exposure to (coarse/fine/ultrafine) PM, (2) assess health risks, (3) identify intervention needs, and (4) support regulatory agencies recommending mitigation procedures to reduce the impact of fire effluents on firefighters.

In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFß/ROS/Akt signaling pathway.

BACKGROUND: In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood. METHODS: Pregnant rats were exposed to chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21. Experiments were performed on 6-month-old adult offspring. RESULTS: CINA exposure increased ischemia-induced cardiac injury and cardiac dysfunction compared to the control group, which was associated with over- expression of angiotensin II receptor (ATR) protein in the left ventricle (LV) of adult offspring. Meanwhile, CINA exposure up-regulated cardiac TGF-ß/SMADs family proteins in the LV. In addition, CINA exposure enhanced cardiac reactive oxygen species (ROS) production and increased the DNA methylation level. The levels of phosphorylated-Akt were upregulated but LC3B-II/I protein abundances were downregulated in the hearts isolated from the CINA-treated group. CONCLUSION: Fetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFß-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.

Effect of aerosol inhalation of budesonide on respiratory symptoms and inflammatory factors in patients with asthma: a meta-analysis.

OBJECTIVE: To review the efficacy, symptoms, inflammatory factors and pulmonary function of different doses of budesonide aerosol inhalation in the treatment of patients with asthma. METHODS: The Chinese and English literature databases were searched with "Effects of different doses of budesonide aerosol inhalation on the efficacy, lung function, inflammation, symptoms and adverse reactions in patients with asthma" as the search direction, and a Meta-analysis was performed. RESULTS: Compared with the low dose group, the efficacy, PEF and FEV1 were significantly increased and the clinical symptom score, TNF-α and IL-4 were significantly decreased in the high dose group (p < 0.05). There was no significant difference in IFN-γ level and the incidence of adverse reactions between the two groups (p > 0.05). CONCLUSION: High-dose budesonide aerosol inhalation therapy can improve the efficacy and lung function of patients, reduce inflammation and clinical symptoms, and does not increase the risk of adverse reactions, which is worthy of clinical promotion.

Mycobacteriophages: therapeutic approach for mycobacterial infections.

Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising. Bacteriophages and their gene products have garnered interest as potential therapeutic options for bacterial infections. Here, we have compiled information on bacteriophages and their products that can kill Mycobacterium tuberculosis or NTM. We summarize the mechanisms whereby viable phages can access macrophage-resident bacteria and not elicit immune responses, review methodologies of pharmaceutical product development containing mycobacteriophages and their gene products, mainly lysins, in the context of drug regulatory requirements and we discuss industrially relevant methods for producing pharmaceutical products comprising mycobacteriophages, emphasizing delivery of mycobacteriophages to the lungs. We conclude with an outline of some recent case studies on mycobacteriophage therapy.

Ancillary and instrumental body movements during inhalation in clarinetists.

Background: Playing a musical instrument requires physical movements that are involved in sound production and movements with more expressive and communicative characteristics. Both movements co-occur during a performance; however, the interaction between the movements is still unclear. Methods: Using motion capture technology, the movement patterns of clarinetists were analyzed at certain points in a performance to investigate how instrumental and ancillary movements interplay. Movements in the arms and knees of clarinetists during a performance were recorded using this technology. The mean angular movements at specific points in the piece, where some players inhaled and others did not, were compared. Results: While the players who inhaled adopted significantly more upright body and neutral arm positions, the players who did not inhale seemed less interrupted in their performance. The results showed that the players performed rather individual ancillary movements, but at specific points, such as during melodic transitions, they performed similarly. At certain points in the melody, while some players needed to inhale, others adjusted their playing according to the inhalation moment to adopt a suitable body position. Discussion: The ancillary movement was consequently interrupted by the physiological necessity to inhale. The findings provide more insights into the interplay of instrumental and ancillary movements during a performance.

Assessing the effectiveness of inhalation therapy in patients with chronic airway diseases: A new digital measurement.

BACKGROUND: This study aimed to evaluate the effectiveness of inhalation therapy in patients with chronic airway diseases via the use of a new multiparametric inhalation assessment device. METHODS: A multiparametric inhalation evaluation device (PF810, UBREATH, Zhejiang, China) that could simulate common inhalation devices with 6 different levels (0-V) of resistance was used in this study. The device was considered suitable if the three parameters of peak inspiratory flow rate (PIFR), effective inspiratory time (EIT), and breath-hold time (BHT) after inspiration met the minimum requirements. RESULTS: A total of 4,559 tests were performed. The qualification rates of 0-V resistance gear from low to high were 3.38 % (I), 8.42 % (0), 15.31 % (II), 16.71 % (III), 20.27 % (IV), and 46.91 % (V). The COPD patients in the 3 experimental groups had the lowest percentages of isolates classified as resistant 0, III, and V, which were 5.65 %, 11.93 %, and 40.43 %, respectively. The lowest percentage was 39.67 % (V) for insufficient EIT and 18.40 % (V) for BHT less than 5 s after inspiration. The results of 149 subjects who had used the inhalation device showed that the VIE and EIT at 0 levels were significantly greater than those before training (Z= -5.651, -5.646, P < 0.001). The VIE and EIT at I-III and V significantly increased after training (all P < 0.05). CONCLUSIONS: Patients using portable inhaler devices do not always inhale with adequate flow patterns. The multiparametric inhalation assessment device may be useful in outpatient settings.

Monitoring cystic fibrosis airway infections with Pseudomonas aeruginosa with anti-OprF serum antibodies.

BACKGROUND: The management of cystic fibrosis (CF) requires knowledge of the patient's microbiological status. The serology of anti-Pseudomonas aeruginosa antibodies against exoenzymes or water-soluble antigens has gained diagnostic value, particularly to detect the onset of colonization with P. aeruginosa. However, the diversity and variable expression of these antigens, which was unknown when the ELISAs became common diagnostic procedures at CF clinics, prohibits the quantitative evaluation of bacterial antigen load during intermittent and chronic infection. METHODS: An ELISA was developed to measure the serum IgG antibody levels against P. aeruginosa porin OprF, a species-specific, conserved, immunogenic and constitutively expressed protein present in the outer membrane and extracellular vesicles. RESULTS: Serial serum samples were collected from 310 people with CF (pwCF) over a period of up to 15 years. Compared to a reference of P. aeruginosa - negative CF sera set to 1, OprF antibody titers ranged from 0.3 to 13.2 (median: 1.7) in 56 intermittently colonized patients and from 0.5 to 51.2 (median: 11.8) in 176 chronically colonized pwCF showing higher anti-OprF antibody levels during chronic than during intermittent colonization with P. aeruginosa (P = 0, Z = - 21.7, effect size 0.62). Inhalation with twice daily 80 mg tobramycin decreased OprF antibody titers (P = 5 × 10-5), particularly during the third and fourth year of chronic colonization. CONCLUSION: The OprF ELISA should be an appropriate tool to monitor Pseudomonas serology at all stages of infection and disease severity and to study the impact of short- and long-term therapeutic interventions.

[A CASE OF A GIRL WITH ANAPHYLAXIS INDUCED BY INHALATION OF SOYBEAN DUST].

The patient was a 3-year-old girl whose father was employed sorting and washing soybeans. She exhibited transient respiratory distress and loss of activity on the same day or the next day after her father came home wearing work clothes with soybean dust on them. One day, she developed anaphylaxis after being lifted into her father's arms while he was wearing his work clothes. Although a blood test was positive for soybean and Gly m 4-specific IgE antibodies, the girl was able to consume soy products (not including soy milk, which she had never consumed) without any issues. The father was instructed to change clothes before leaving work and bathe immediately upon returning home, and the girl has not had any further episodes of respiratory distress, loss of activity, or anaphylaxis. Though reports of anaphylaxis from soybean antigen inhalation are extremely rare, it is very likely that inhalation of soybean dust from the father's work clothes induced anaphylaxis in this case.

[A ssociations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index: A family-based study].

OBJECTIVE: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). METHODS: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. RESULTS: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 µg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 µg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. CONCLUSION: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Rapid in vitro activity of telavancin against Bacillus anthracis and in vivo protection against inhalation anthrax infection in the rabbit model.

Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 µg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.

Investigating the impact of inhaled paraquat: A comprehensive evaluation protocol.

This paper provides a complete protocol for studying the effects of inhaled paraquat (PQ), a toxic herbicide that has negative effects systemically and on the lungs. The protocol aims to evaluate the effects of aerosolized PQ exposure on lung and systemic injury in an animal model, which will provide significant information for therapeutic interventions for PQ-induced pulmonary and systemic damage. The protocol involves the following key components: 1. Study groups: By including control, non-treated aerosolized PQ-exposed, and treated PQ-exposed animals with various agent groups in the experiment, lung and systemic injury in each group could be evaluated, and different measured parameters could be compared among groups. 2. PQ exposure: Animals in the PQ-exposed groups are subjected to PQ aerosol inhalation, simulating occupational or accidental exposure in farmers working with this herbicide. 3. Assessment measures: To determine the degree of lung and systemic injury and its physiological effects, several assessments, such as biochemical markers, histopathological analysis, and functional tests, are used. The protocol offers reliable and accurate results by using standardized methods and data collection. The effect of PQ exposure on lung and systemic injury could be evaluated by statistical analysis of the collected data, which also makes it easier to identify possible protective agents or interventions. This comprehensive evaluation protocol provides an essential basis for studying the mechanisms behind PQ-induced lung and systemic injury and assessing the effectiveness of preventative or therapeutic strategies in minimizing its adverse effects.