Short-term exposure to stone minerals used in asphalt affect lung function and promote pulmonary inflammation among healthy adults

ObjectiveStone minerals are a partially ignored environmental challenge but a significant contributor to urban air pollution. We examined if short-term exposure to two stone minerals – quartz diorite and rhomb porphyry – commonly used in asphalt pavement would affect lung function, promote pulmonary inflammation, and affect bronchial reactivity differently.MethodsOur randomized crossover study included 24 healthy, non-smoking young adults exposed to the stone minerals quartz diorite, rhomb porphyry, and control dust (lactose). Exposure occurred in an exposure chamber, in three separate 4-hour exposure sessions. Fractional exhaled nitric oxide (FeNO) and lung function were monitored before exposure, then immediately following exposure, and 4 and 24 hours after exposure. In addition, methacholine was administered 4 hours following exposure, and exhaled breath condensate (EBC) was collected before exposure, then immediately and 4 hours after exposure. EBC was analyzed for pH, thiobarbituric acid reactive substances (TBARS), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), IL-10, P-Selectin, surfactant protein D (SP-D), and tumor necrosis factor-α (TNF-α).ResultsOur results showed significantly elevated concentrations of FeNO after exposure to quartz diorite compared to rhomb porphyry, suggesting that quartz diorite is more likely to trigger pulmonary inflammation after short-term exposure. Moreover, short-term exposure to rhomb porphyry was associated with a modest but statistically significant decline in forced vital capacity (FVC) compared to quartz diorite.ConclusionThese results emphasize that using stone material in asphalt road construction should be reconsidered as it may affect lung inflammation and lung function in exposed subjects.     

Development and validation in Ecuador of the EPD Questionnaire,a diabetes‐specific patient‐reported experience and outcome measure: A mixed‐methods study

IntroductionThe global prevalence of diabetes in 2019 in adults was estimated to be 9.3%. This study developed in Ecuador, for the first time, instruments to assess patient‐reported outcomes and experiences.MethodsThe Experiences of the Person with Diabetes (EPD) Questionnaire is a diabetes‐specific instrument. A mixed‐methods study was conducted. First, a qualitative item development phase that included four focus groups and six semi‐structured interviews with patients was conducted in different rural and urban areas of Ecuador to obtain information on culture, beliefs, demographics, diet and social perspectives. A second quantitative phase for psychometric validation was carried out in primary care settings of rural and urban areas of Ecuador.ResultsForty‐two and four hundred and eighty‐nine participants were included in each phase, respectively. The item development phase resulted in a questionnaire of 44 items (23 for perceived outcomes and 21 for experiences). In the validation study, most participants were women (58%) and from urban areas (57%). Exploratory factor analysis revealed three dimensions for each instrument. Outcomes instrument dimensions were symptoms and burnout, worries and fears and social limitations. Experiences instrument dimensions were information, patient‐centred care and care delivery. Cronbach''s α values of the total score and dimensions were high, ranging between .81 and .93 in both instruments. Confirmatory factor analysis showed an acceptable fit of the data.ConclusionThe EPD Questionnaire is probably the first instrument developed to assess patient‐reported experiences and perceived outcomes in a middle‐income country that included patients to capture all dimensions relevant for the intended population. Its psychometric properties are robust and could provide valuable information for clinicians and policymakers in the region.Patient or Public ContributionThe development of these instruments has taken into consideration patients and the public since their conception. A qualitative approach gathered relevant information related to the cultural, social and economic burden of different populations in Ecuador. Before validation, a pilot test was carried out with users of the National Health Services to obtain their perspectives and insights of the developed instrument. Finally, during the data analysis, we have given special consideration to social variables such as rural and urban populations.     

Evaluating denoising strategies in resting‐state functional magnetic resonance in traumatic brain injury (EpiBioS4Rx)

Resting‐state functional MRI is increasingly used in the clinical setting and is now included in some diagnostic guidelines for severe brain injury patients. However, to ensure high‐quality data, one should mitigate fMRI‐related noise typical of this population. Therefore, we aimed to evaluate the ability of different preprocessing strategies to mitigate noise‐related signal (i.e., in‐scanner movement and physiological noise) in functional connectivity (FC) of traumatic brain injury (TBI) patients. We applied nine commonly used denoising strategies, combined into 17 pipelines, to 88 TBI patients from the Epilepsy Bioinformatics Study for Anti‐epileptogenic Therapy clinical trial. Pipelines were evaluated by three quality control (QC) metrics across three exclusion regimes based on the participant''s head movement profile. While no pipeline eliminated noise effects on FC, some pipelines exhibited relatively high effectiveness depending on the exclusion regime. Once high‐motion participants were excluded, the choice of denoising pipeline becomes secondary ‐ although this strategy leads to substantial data loss. Pipelines combining spike regression with physiological regressors were the best performers, whereas pipelines that used automated data‐driven methods performed comparatively worse. In this study, we report the first large‐scale evaluation of denoising pipelines aimed at reducing noise‐related FC in a clinical population known to be highly susceptible to in‐scanner motion and significant anatomical abnormalities. If resting‐state functional magnetic resonance is to be a successful clinical technique, it is crucial that procedures mitigating the effect of noise be systematically evaluated in the most challenging populations, such as TBI datasets.     

Evaluation of Zearalenones and Their Metabolites in Chicken,Pig and Lamb Liver Samples

Zearalenone (ZON), zearalanone (ZAN) and their phase I metabolites: α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), α-zearalalanol (α-ZAL) and β-zearalalanol (β-ZAL) are compounds with estrogenic activity that are metabolized and distributed by the circulatory system in animals and can access the food chain through meat products from livestock. Furthermore, biomonitoring of zearalenones in biological matrices can provide useful information to directly assess mycotoxin exposure; therefore, their metabolites may be suitable biomarkers. The aim of this study was to determine the presence of ZON, ZAN and their metabolites in alternative biological matrices, such as liver, from three different animals: chicken, pig and lamb, in order to evaluate their exposure. A solid–liquid extraction procedure coupled to a GC-MS/MS analysis was performed. The results showed that 69% of the samples were contaminated with at least one mycotoxin or metabolite at varying levels. The highest value (max. 152.62 ng/g of β-ZOL) observed, and the most contaminated livers (42%), were the chicken liver samples. However, pig liver samples presented a high incidence of ZAN (33%) and lamb liver samples presented a high incidence of α-ZOL (40%). The values indicate that there is exposure to these mycotoxins and, although the values are low (ranged to 0.11–152.6 ng/g for α-ZOL and β-ZOL, respectively), analysis and continuous monitoring are necessary to avoid exceeding the regulatory limits and to control the presence of these mycotoxins in order to protect animal and human health.     

Gut–Kidney Axis Investigations in Animal Models of Chronic Kidney Disease

Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut–kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut–kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota.     

Is present pharmacy education adapted to needs? Survey results from young practitioner views regarding pharmacy education outcome towards a national reform in Hungary

BackgroundThe pharmacist career is constantly adapting to societal and health care needs. The past decade has seen a growing demand for curricular development to align graduation outcome with workforce competencies.ObjectiveThis study aims to identify expectations for both didactic and experiential components of a new curriculum based on young pharmacist practitioner views.MethodsAn online survey questionnaire was used in 2019–2020 to evaluate the pharmacy curriculum to detect indicators or key areas which require comprehensive reform.ResultsThe predominant majority of the 205 study participants recommended reduction in credit hours for Natural Sciences (78.54%) and a similar increase in the Theoretical and Practical Expertise Module (77.9%). Pharmaceutical care, clinical therapeutics and clinical pharmacy competencies should also be more highlighted in the program. Findings indicate the current training does not prepare for problem-solving and daily workplace challenges (72.7%) or for extended pharmacist skills and competencies (71.71%). Results show inconsistency in practical training experience, as all respondents participated in practical training for drug manufacturing and analysis but 61.0% reported no hands-on skills training in a hospital-clinical simulation setting. Indications for practitioner involvement into the natural sciences and biomedical subjects (86.3%) confirm the obvious need for more practice-oriented education.ConclusionsEducational reforms seem to be inevitable to achieve measurable improvement in professional practice and skills competency. The country specific demand for a needs-based pharmacy education reflects global trends but may also provide useful insights for individual transitions to transform education through practice and improve practice through education.     

Effects of cyanamide on body weight and brain monoamines and metabolites in rats

Cyanamide, a disulfiram-like drug used in the treatment of alcoholism, decreased in a dose-dependent manner (2-25 mg/kg) the body weight gain curve in rats, which resulted in a marked decrease of body weight (10-35%). Long-term administration of cyanamide also decreased food intake (6-34%) in a dose-dependent manner (2-25 mg/kg). Both effects of cyanamide were reversible. After the acute and long-term administration (1-12 months) of cyanamide (8-35 mg/kg) the brain concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MOPEG-SO4) was also significantly increased (26-46%). Cyanamide, however, had no effects on the brain concentration of noradrenaline, dopamine, 5-hydroxytryptamine, tryptophan and 5-hydroxyindolacetic acid. It is suggested that the loss of weight, the decrease in food intake and the increase in brain MOPEG-SO4 induced by cyanamide reflect possible anorectic properties of the drug.     

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.