Assessment of Daily Exposure to Organophosphate Esters through PM2.5 Inhalation, Dust Ingestion, and Dermal Contact.

Inhalation of airborne fine particulate matter (PM2.5), dust ingestion, and dermal contact with dust are important pathways for human exposure to different contaminants, such as organophosphate esters (OPE), compounds that are widely used as flame retardants and plasticizers. There are limited studies assessing the extent of the contamination of OPE in indoor airborne PM2.5. This study offers a novel approach by examining various indoor environments, such as homes, workplaces, and means of transport, where people typically spend their daily lives. The goal is to provide a comprehensive assessment of daily exposure to these pollutants. Both PM2.5 and dust samples were collected in order to determine the concentration levels of 17 different OPEs. Fifteen OPEs in PM2.5 and 16 in dust samples were detected. Concentration levels in indoor air ranged from 4.37 to 185 ng/m3 (median 24.4 ng/m3) and from 3.02 to 36.9 µg/g for the dust samples (median 10.2 µg/g). Estimated daily intakes (EDIs) of OPEs were calculated for adults, yielding median values of 3.97 ng/(kg bw × day) for EDIInhalation, 5.89 ng/(kg bw × day) for EDIDermal, and 1.75 ng/(kg bw × day) for EDIIngestion. Such levels lie below human health threshold risk limits, although in some cases they could be only 2 times below the threshold for carcinogenic risk, with a main contribution from tris(2-chloroethyl) phosphate (TCEP). Given this threshold proximity, additional exposure to these chemicals from other pathways, such as food ingestion, gas phase exposure, and/or inhalation of coarser particles (PM10-2.5), could therefore lead to health limit exceedances.

Aquiluscidin, a Cathelicidin from Crotalus aquilus, and the Vcn-23 Derivative Peptide, Have Anti-Microbial Activity against Gram-Negative and Gram-Positive Bacteria.

Anti-microbial peptides play a vital role in the defense mechanisms of various organisms performing functions that range from the elimination of microorganisms, through diverse mechanisms, to the modulation of the immune response, providing protection to the host. Among these peptides, cathelicidins, a well-studied family of anti-microbial peptides, are found in various animal species, including reptiles. Due to the rise in anti-microbial resistance, these compounds have been suggested as potential candidates for developing new drugs. In this study, we identified and characterized a cathelicidin-like peptide called Aquiluscidin (Aq-CATH) from transcripts obtained from the skin and oral mucosa of the Querétaro's dark rattlesnake, Crotalus aquilus. The cDNA was cloned, sequenced, and yielded a 566-base-pair sequence. Using bioinformatics, we predicted that the peptide precursor contains a signal peptide, a 101-amino-acid conserved cathelin domain, an anionic region, and a 34-amino-acid mature peptide in the C-terminal region. Aq-CATH and a derived 23-amino-acid peptide (Vcn-23) were synthesized, and their anti-microbial activity was evaluated against various species of bacteria in in vitro assays. The minimal inhibitory concentrations against bacteria ranged from 2 to 8 µg/mL for both peptides. Furthermore, at concentrations of up to 50 µM, they exhibited no significant hemolytic activity (<2.3% and <1.2% for Aquiluscidin and Vcn-23, respectively) against rat erythrocytes and displayed no significant cytotoxic activity at low concentrations (>65% cell viability at 25 µM). Finally, this study represents the first identification of an antimicrobial peptide in Crotalus aquilus, which belongs to the cathelicidin family and exhibits the characteristic features of these peptides. Both Aq-CATH and its derived molecule, Vcn-23, displayed remarkable inhibitory activity against all tested bacteria, highlighting their potential as promising candidates for further antimicrobial research.

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer's Disease.

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer's disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.

Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.

Human exposure to organophosphate esters in water and packed beverages.

Drinks are an essential part of human diet, which makes them a source of human exposure to plasticizers such as organophosphate esters (OPEs). The current study provides new information about sixteen OPE levels in 75 different samples (tap water, packed water, cola drinks, juice, wine and hot drinks). Tap water mean levels (40.9 ng/L) were statistically higher than packed water mean levels (4.82 ng/L), mainly due to the contribution of tris(2-chloroisopropyl) phosphate (TCIPP) and tris(2-butoxyethyl) phosphate (TBOEP) that may come from PVC water pipes. Over 90% of samples presented at least one OPE, where regular cola drinks had the highest mean concentrations (2876 ng/L). There was a significantly higher presence of OPEs in added sugar beverages than sugar free drinks, especially for 2-ethylhexyl diphenyl phosphate (EHDPP), which might be related not only to packaging materials but to the added sugar content. Estimated daily intakes (EDIs) in normal and high-exposure scenarios were 2.52 ng/kg bw/day and 7.43 ng/kg bw/day, respectively. Human risk associated with beverages ingestion showed regular cola drinks, juice and tap water as the groups with the highest hazard quotients (HQs). Although OPE exposure was below to safety limits, it should be noted that EHDPP values for regular cola group must be cause of concern, and other routes of exposure such as food ingestion or air inhalation should be also considered.

Micro(nano)plastics in the atmosphere of the Atlantic Ocean.

The occurrence, long-range atmospheric transport and deposition of micro and nano plastics (MNPLs) remains un-quantified for the oceanic atmosphereopen ocean. Here we show the characterisation of MNPLs and the aerosol composition (PM10) in a north-south Atlantic transect from Vigo (Spain) to Punta Arenas (Chile). The analytical procedure to assess the composition of MNPLs consisted of a double suspect screening approach of the polymers and additives, the two constituents of plastics. Polymers were analysed by size exclusion chromatography coupled with high-resolution mass spectrometry using an atmospheric pressure photoionization source operated in positive and negative conditions (HPLC(SEC)-APPI(+/-)-HRMS). Plastic additives were screened with high-performance liquid chromatography coupled to high-resolution mass spectrometry using an electrospray ionisation source (HPLC-ESI(+/-)-HRMS). The most common polymers were polyethylene (PE), polypropylene (PP), polyisoprene (PI), and polystyrene (PS), with the highest polymer concentration being 51.7 ng·m-3 of PI. The air mass back trajectories showed the variable influence of oceanic and terrestrial air masses. These differences were reflected in the aerosol composition with different contributions of Saharan dust, sea spray aerosol, organic/elemental carbon, and MNPLs. Results showed that samples largely influenced by sea-spray and air masses originating from coastal South America and the north Atlantic subtropical gyre were more contaminated by MNPLs. Moreover, this information was complemented by the characterisation of the largest particles using scanning electron microscopy (SEM) and µ-Fourier Transform Infrared Spectroscopy (µ-FTIR). This work provides the first field evidence of the long-range transport of MNPLs in most of the Atlantic Ocean, as the result of dynamic coupling between the lower atmosphere and the surface ocean. Sea-spray formation arises as a key driver for the aerosolisation of MNPLs, and atmospheric transport followed by dry deposition may modulate the occurrence of MNPLs in large oceanic regions, issues that will require future research efforts.

Current Treatments and New, Tentative Therapies for Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson's disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.

Examining undergraduate student perceptions and engagement during the second year of the COVID-19 pandemic.

The objectives of this study were to understand undergraduate students' overall experiences with the transition to remote learning and understand students' level of involvement with online and in-person campus programs at the start of the COVID-19 pandemic. This paper presents the findings from a series of library focus groups conducted with undergraduate students in the summer 2021. Findings showed that students experienced parallel benefits and challenges to that of remote learning when attending online campus programs. Based on these findings this paper provides student-driven recommendations for library programming. Understanding the levels of student involvement across different types of engagement and different campus stakeholders allows for articulation of the greater implications for developing library student engagement efforts.

A new look at rubber recycling and recreational surfaces: The inorganic and OPE chemistry of vulcanised elastomers used in playgrounds and sports facilities.

We revisit current understanding of the chemical complexity of different kinds of particulate vulcanised elastomers widely used in playgrounds and sports fields, adding new data on trace element and organophosphate ester contents of used tyre and EDPM crumb rubber. Enrichments in elements such as Zn, S, Co, Bi and Nd relate to the vulcanised mixtures created during manufacture. Zinc concentrations vary across an order of magnitude, being highest in our used tyre particulate samples (up to 2.4 %). In contrast, other trace element variations are due to coloured pigments causing increases in Cu and Zr (blue), Cr (green), and Fe and Sn (red and yellow) concentrations. The use of pale fillers such as CaCO3 and clay minerals (rather than carbon black) strongly influences Ca and Al concentrations, which are much higher in the coloured EPDM than in black used tyre crumb rubber. Representatives from all three of the main organophosphate ester (OPE) groups, namely chlorinated (e.g. TCEP, TCIPP, TDCPP), alkyl (e.g. TEHP, TEP, TNBP, TBOEP) and aryl (e.g. TPHP, EHDPP, TCP) were identified, confirming how these chemicals are commonly used in modern rubber compounding as flame retardants and plasticisers. Elevated concentrations of TEHP (up to 117 µg/g) in coloured-coated used tyre turf infill crumb rubbers were traced to the coating rather than the crumb rubber itself. The presence and weathering behaviour of OPEs in recreational crumb rubber materials deserve closer investigation. The ecological "onehealth" impact of potentially toxic substances present in recreational crumb rubbers will depend on if and how they are released during play and sports activities, maintenance procedures, and natural weathering. We argue that detailed chemical data on these materials should be available to buyers, as manufacturers strive to reduce ecotoxin content as part of the quest towards sustainable use and recycling of vulcanised elastomers.

Poor Cognitive Agility Conservation in Obese Aging People.

Life expectancy has been boosted in recent decades at expenses of increasing the age-associated diseases. Dementia, for its incidence, stands out among the pathologies associated with aging. The exacerbated cognitive deterioration disables people from carrying out their daily lives autonomously and this incidence increases exponentially after 65 years of age. The etiology of dementia is a miscellaneous combination of risk factors that restrain the quality of life of our elderly. In this sense, it has been established that some metabolic pathologies such as obesity and diabetes act as a risk factor for dementia development. In contrast, a high educational level, as well as moderate physical activity, have been shown to be protective factors against cognitive impairment and the development of dementia. In the present study, we have evaluated the metabolic composition of a population between 60-90 years old, mentally healthy and with high academic degrees. After assessing agility in mental state, we have established relationships between their cognitive abilities and their body composition. Our data support that excess body fat is associated with poorer maintenance of cognition, while higher percentages of muscle mass are associated with the best results in the cognitive tests.

Cytotoxicity assessment and suspected screening of PLASTIC ADDITIVES in bioplastics of single-use household items.

Bioplastics made of renewable sources provide an excellent alternative to fossil-based materials. However, similar or greater quantities of plastic additives than fossil-based plastics are used in the formulations of bioplastics to improve their performance and barrier properties. Nowadays, there is an increasing concern about sources of chemical exposure. However, there is an important knowledge gap regarding complex additive mixtures, particularly in bio-based materials. In this study, we have characterised the presence of plastic additives in single-use materials (collected from retail shops in Spain), which are made of the most common bio-based biodegradable materials, poly(lactic acid) (PLA) and poly(hydroxybutyrate) (PHB), in contrast with a fossil-based plastic material that is extensively made from high-density polyethylene (HDPE). The approach consisted of the pulverization of material in the nano-micro range (100 nm-10 µm), with the materials being extracted using different solvents and ultrasonic-assisted solvent extraction (UASE). 100% of the additives in the material cannot be extracted, but since they were performed in the same condition for all materials can inform about the fingerprint of primary organics and the relative abundances between the different materials. The extracts were analysed by high-performance liquid chromatography coupled with high-resolution mass spectrometry equipped with a heated electrospray ionisation source operated in positive and negative ionisation conditions (HPLC-HESI(+/-)-HRMS), separately, using a suspect screening approach. A total number of 203 additives were tentatively identified (confidence level 2) in the bioplastics items of this study. An average of 123 plastic additives were found in PLA items and 121 in PHB items. Plasticisers were the most abundant additives; the phthalates group was the most commonly found, while 63 plastic additives were confirmed by standards and quantified. In parallel, the cytotoxicity of plastic particles in terms of cell viability and oxidative stress was studied using A549 alveolar basal epithelial cells, and the toxicity of the different extracts was also established using HepG2 adenocarcinoma cells. The main results of this study demonstrate that the plastic particles did not show a significant reduction in cell viability, but oxidative stress was significant, with PLA being the material that showed the highest effect. On the other hand, extracts of plastic particles did not show inhibition of cell viability except for HDPE extract, but the different extracts produced oxidative stress, with PLA showing the highest effect. Although the item showing the highest concentrations of additives was the extract of PLA material while also showing the most elevated oxidative stress, the low migration of toxicants from plastic materials ensures their safe use. However, this also supports the idea that bioplastics can contain many toxic substances in their formulations, some of which are unknown and should be studied in more depth.

Cyberbullying and Gambling Disorder: Associations with Emotion Regulation and Coping Strategies.

The presence of unsuitable coping and emotion regulation strategies in young populations with gambling disorder (GD) and in those who have experienced cyberbullying victimization has been suggested. However, this association has not been explored in depth. In this study, our aim was to analyze individual differences in emotion regulation, coping strategies, and substance abuse in a clinical sample of adolescents and young adult patients with GD (n = 31) and in a community sample (n = 250). Furthermore, we aimed to examine the association between cyberbullying and GD. Participants were evaluated using the Cyberbullying Questionnaire-Victimization, the Canadian Adolescent Gambling Inventory, the Coping Strategies Inventory, the Difficulties in Emotion Regulation Scale, the Alcohol Use Disorders Identification Test and the Drug Use Disorders Identification Test. Structural Equation Modeling was used to explore associations between these factors in a community sample and in a clinical group. In both groups, exposure to cyberbullying behaviors was positively associated with higher emotion dysregulation and the use of maladaptative coping styles. Our findings uphold that adolescents and young adults who were victims of cyberbullying show difficulties in emotion regulation and maladaptive coping strategies when trying to solve problems. The specific contribution of sex, age, gambling severity, emotion regulation, and coping strategies on cyberbullying severity is also discussed. Populations at vulnerable ages could potentially benefit from public prevention policies that target these risk factors.

e-Estesia: A Serious Game for Reducing Arousal, Improving Emotional Regulation and Increasing Wellbeing in Individuals with Gambling Disorder.

Gambling disorder (GD) is associated with deficits in emotion regulation and impulsivity-related personality traits. In recent years there has been an increase in the use of serious games (SG) to address these factors with positive results. The aim of this study was to analyze the efficacy of the intervention with a new SG (e-Estesia), as an adjunct to a CBT intervention for GD. The sample comprised two groups (experimental group (n = 40) and control group (n = 64)) of patients with GD diagnosis. Both groups received 16 weekly CBT sessions and, concurrently, only the experimental group received 15 additional sessions with e-Estesia. Pre-post treatment with e-Estesia administered in both groups were: DSM-5 Criteria, South Oaks Gambling Screen, Symptom Checklist-Revised and measure of relapses, dropout and compliance of treatment. As regards the experimental group were also administered: Difficulties in Emotion Regulation Scale, Emotion Regulation Questionnaire, and Impulsive Behavior Scale. No statistically significant differences in the general psychopathological state, emotion regulation or impulsivity were found when comparing the groups. However, patients enrolled in the e-Estesia intervention had significantly less relapses and better indicators of treatment compliance than the control group. Considering these results, the use of complementary tools such as SG are useful for addressing GD.

Methods for Elemental Analysis of Size-Resolved PM Samples Collected on Aluminium Foils: Results of an Intercomparison Exercise.

Aluminium is the most common substrate in studies using impactors for the measurement of the number or the weight of size-segregated atmospheric particulate matter (PM), as its characteristics perfectly fit impactor requirements. However, its use is not recommended by manufacturers when one of the purposes of the study is the determination of the metal content in the sample. The aim of this work was to develop an efficient analytical procedure for the removal and acid digestion of PM samples collected on aluminium foils by a cascade impactor to perform the determination of metals. The possibility of performing the trace metal analysis of PM samples collected using aluminium foils is of great importance, as it allows the determination of an accurate size distribution and the elemental composition of the PM collected on each impactor stage. Two procedures were optimised by using different digestion and analysis techniques. Both procedures were then applied to the two halves of several Dekati low-pressure impactor (DLPI) samples, and the results were critically compared. The two procedures proved to be effective in the determination of extremely low concentrations of a large suite of analytes in different size fractions of PM emitted by a brake system.

Inherited myopathies in patients from Sub-Saharan Africa: Results from a retrospective cohort.

The clinical epidemiology of inherited myopathies in sub-Saharan Africa (SSA) is unknown but likely underdiagnosed due to problems of scientific research and social issues. We report a case series of patients born in SSA, evacuated to Portugal through an international health protocol and seen at a single neuromuscular disorders centre, between January/2004 and August/2021. We identified 9 patients (5 males), 35.6 ± 19.3 years-old (10-64), from Cape Verde (n = 4), Angola (n = 2), Sao Tome and Principe (n = 2) and Guinea-Bissau (n = 1), with a delay in diagnosis of 19.7 ± 14.3 years. Seven patients (77.8 %) had positive family history. Most patients had significant morbidity, requiring wheelchair (55.6 %), and nocturnal non-invasive ventilation (55.6 %). The diagnosis included Bethlem myopathy (n = 2), Duchenne muscular dystrophy (n = 2), Emery-Dreifuss muscular dystrophy (n = 1), LGMDR1 (n = 2), LGMDR2 (n = 1), and type-1 myotonic dystrophy (n = 1). Genetic testing was remarkable for 3 mutations previously not described. Despite the small sample, the spectrum of hereditary myopathies in our cohort is like western studies. Further studies are needed to better understand the epidemiology of muscle diseases in SSA.

Cognitive Behavioral Therapy Plus a Serious Game as a Complementary Tool for a Patient With Parkinson Disease and Impulse Control Disorder: Case Report.

BACKGROUND: Impulse control disorders (ICDs) are commonly developed among patients who take dopamine agonist drugs as a treatment for Parkinson disease (PD). Gambling disorder and hypersexuality are more frequent in male patients with PD, with a prevalence over 4% in dopamine agonists users. Although impulsive-compulsive behaviors are related to antiparkinsonian medication, and even though ICD symptomatology, such as hypersexuality, often subsides when the dopaminergic dose is reduced, sometimes ICD persists in spite of drug adjustment. Consequently, a multidisciplinary approach should be considered to address these comorbidities and to explore new forms of complementary interventions, such as serious games or therapies adapted to PD. OBJECTIVE: The aim of this study is to present the case of a patient with ICD (ie, hypersexuality) triggered by dopaminergic medication for PD. A combined intervention was carried out using cognitive behavioral therapy (CBT) for ICD adapted to PD, plus an intervention using a serious game-e-Estesia-whose objective is to improve emotion regulation and impulsivity. The aim of the combination of these interventions was to reduce the harm of the disease. METHODS: After 20 CBT sessions, the patient received the e-Estesia intervention over 15 sessions. Repeated measures, before and after the combined intervention, were administered to assess emotion regulation, general psychopathology, and emotional distress and impulsivity. RESULTS: After the intervention with CBT techniques and e-Estesia, the patient presented fewer difficulties to regulate emotion, less emotional distress, and lower levels of impulsivity in comparison to before the treatment. Moreover, the frequency and severity of the relapses also decreased. CONCLUSIONS: The combined intervention-CBT and a serious game-showed positive results in terms of treatment outcomes.

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives.

Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-ß, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aß pathology and tau pathology, and which include γ-secretase inhibitors, ß-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aß clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease. Therefore, the aim of this review was to analyze and describe current treatments and possible future alternatives in the therapeutic approach to AD.