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Introduction: Nitrous oxide, commonly known as laughing gas, is used medically as an analgesic and anaesthetic. It has been used recreationally for its brief euphoric effects for over 200 years, however, in the last decade, there has been a large increase in its recreational use and, more recently, an increase in reported serious health and social harms in some countries. The situation in seven European countries has been analyzed, including epidemiology, health and social harms, policy responses, and lessons learned. This can be used to inform relevant stakeholders on how to respond to nitrous. Methods: Case studies on the situation with nitrous oxide in Denmark, France, Ireland, Lithuania, the Netherlands, and Portugal were developed based on the information collected by the national Early Warning Systems within their networks and literature. For the case study of the United Kingdom, open-source data were used. In addition, relevant information was retrieved from PubMed and Web of Science. Results: Easy availability, low price, short-lived effects, and perception as a safe and socially acceptable drug might explain growing popularity of nitrous oxide. The market has expanded in recent years with a range of specialised internet shops, partly offering it under the disguise of ‘party accessories’, but also openly when the legal situation permits. Social media is also used to promote and sell it. In some cases, the supply has moved from shops to social media following measures to restrict its supply. Of special concern is that most use of nitrous is by young people, including teenagers inexperienced with drug use. The current situation has led to an increase in frequent and heavy use and an increase in poisonings reported to poison centres. According to the French Addictovigilance networ, the number of notifications linked to nitrous increased from 10 in 2018 to 358 in 2021. Harms include frostbites, barotrauma, serious neurological toxicity (such as myeloneuropathy), cardiovascular consequences (such as thrombo-embolic events), psychiatric disorders, and driving under the influence. More recently, harms are fuelled by a switch from small canisters to large cylinders. Conclusions: Poison centres and the French Addictovigilance system played a key role in detecting, monitoring, and responding to the issue of nitrous oxide. Its growing recreational use is a public health concern requiring an integrated multi-sectoral approach to reduce demand, availability, and risks. The responses might include prevention, monitoring, treatment, and legislative actions. Data sharing at EU level to monitor this issue is needed.

O ecossistema midiático se transformou de forma expressiva após a pandemia da covid-19, vivida entre 2020 e 2022. Dentro dessas transformações, destaca-se um importante segmento econômico: o turismo. Tal transformação foi provocada pelas limitações de mobilidade ocorridas em todo o planeta. Diante disso, a sociedade passou a viver novas experiências “turísticas” em ambientes virtuais, o que nos levou a realizar este projeto, que teve como proposta metodológica a realização do procedimento Ágil Scrum, comumente adotado pelas engenharias, além da observação participante e da pesquisa bibliográfica. O resultado foi a conclusão de uma pesquisa aplicada, que envolve procedimentos teóricos e práticos que ressignificam a fotografia de viagem na nova ecologia dos meios.

Bisphenol A (BPA) is one of the most produced synthetic monomers in the world and is widespread in the environment. BPA was replaced by bisphenol analogues (BP) because of its adverse effects on life. Bacteria can degrade BPA and other bisphenol analogues (BP), diminishing their environmental concentrations. This study aimed to summarize the knowledge and contribute to future studies. In this review, we surveyed papers on bacterial degradation of twelve different bisphenol analogues published between 1987 and June 2022. A total of 102 original papers from PubMed and Google Scholar were selected for this review. Most of the studies (94.1%, n = 96) on bacterial degradation of bisphenol analogues focused on BPA, and then on bisphenol F (BPF), and bisphenol S (BPS). The number of studies on bacterial degradation of bisphenol analogues increased more than six times from 2000 (n = 2) to 2021 (n = 13). Indigenous microorganisms and the genera Sphingomonas, Sphingobium, and Cupriavidus could degrade several BP. However, few studies focussed on Cupriavidus. The acknowledgement of various aspects of BP bacterial biodegradation is vital for choosing the most suitable microorganisms for the bioremediation of a single BP or a mixture of BP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of α1(V) and α2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naïve patients with SSc-related fibrosis and four healthy controls. Our data showed increased α1(V) and α2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the α1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 ± 1.34 vs. 66.84 ± 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the α1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the α2(V) chain was overexpressed in the small vessels (63.18 ± 3.56 vs. 12.16 ± 0.81; p < 0.0001) and capillaries (60.88 ± 5.82 vs. 15.11 ± 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased α1(V) chain expression. These results highlight an intense decrease in the α1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the α1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.

Peripheral nerve injuries are cause of sensory disturbances and in functional abilities, and are associated personal and social costs. Strategies that maximize nerve regeneration and functional recovery are necessary, the exercise is an option. This study evaluated the effects of forced swimming exercise on neuromuscular histomorphometry and on functional recovery in a median nerve crush model. Sixteen Wistar rats underwent median nerve crush and were divided into control group (CG) and swimming group (SG). The forced swimming protocol started one week after the injury and was performed for 1 hr a day, 5 days per week, for 2 weeks. The rats swam with an overload of 5% and 10% of body weight in the first and second week, respectively. The functional recovery was assessed in three moments using the grasping test. On day 21, fragments of the median nerve and of the forearm flexors muscles were removed for histomorphometric analysis. The SG had functional recovery impaired ( P <0.001) and presented lower myelinated fibers number, fiber and axon minimal diameter, myelin thickness and g-ratio in the proximal e distal segments of the median nerve ( P <0.005) and area muscle fiber ( P <0.005) than CG. Also, the SG presented a number of capillaries in the proximal segments of the median nerve greater than CG ( P <0.005). The exercise protocol used in this study impaired the regeneration of the median nerve and negatively influenced the functional recovery., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2022 Korean Society of Exercise Rehabilitation.)

Background: The transmission patterns and genetic diversity of dengue virus (DENV) circulating in Africa remain poorly understood. Circulation of the DENV serotype 1 (DENV1) in Angola was detected in 2013, while DENV serotype 2 (DENV2) was detected in 2018. Here, we report results from molecular and genomic investigations conducted at the Ministry of Health national reference laboratory (INIS) in Angola on suspected dengue cases detected between January 2017 and February 2019., Methods: A total of 401 serum samples from dengue suspected cases were collected in 13 of the 18 provinces in Angola. Of those, 351 samples had complete data for demographic and epidemiological analysis, including age, gender, province, type of residence, clinical symptoms, as well as dates of onset of symptoms and sample collection. RNA was extracted from residual samples and tested for DENV-RNA using two distinct real time RT-PCR protocols. On-site whole genome nanopore sequencing was performed on RT-PCR+ samples. Bayesian coalescent models were used to estimate date and origin of outbreak emergence, as well as population growth rates., Results: Molecular screening showed that 66 out of 351 (19%) suspected cases were DENV-RNA positive across 5 provinces in Angola. DENV RT-PCR+ cases were detected more frequently in urban sites compared to rural sites. Of the DENV RT-PCR+ cases most were collected within 6 days of symptom onset. 93% of infections were confirmed by serotype-specific RT-PCR as DENV2 and 1 case (1.4%) was confirmed as DENV1. Six CHIKV RT-PCR+ cases were also detected during the study period, including 1 co-infection of CHIKV with DENV1. Most cases (87%) were detected in Luanda during the rainy season between April and October. Symptoms associated with severe dengue were observed in 11 patients, including 2 with a fatal outcome. On-site nanopore genome sequencing followed by genetic analysis revealed an introduction of DENV2 Cosmopolitan genotype (also known as DENV2-II genotype) possibly from India in or around October 2015, at least 1 year before its detection in the country. Coalescent models suggest relatively moderately rapid epidemic growth rates and doubling times, and a moderate expansion of DENV2 in Angola during the studied period., Conclusion: This study describes genomic, epidemiological and demographic characteristic of predominately urban transmission of DENV2 in Angola. We also find co-circulation of DENV2 with DENV1 and CHIKV and report several RT-PCR confirmed severe dengue cases in the country. Increasing dengue awareness in healthcare professional, expanding the monitorization of arboviral epidemics across the country, identifying most common mosquito breeding sites in urban settings, implementing innovative vector control interventions and dengue vaccination campaigns could help to reduce vector presence and DENV transmission in Angola., Competing Interests: The authors declare no conflict of interest.

Rationale: The effort to make fake documents look real leads to the use of crickets and beverages to produce artificially aged papers, as land titles, based on yellowing caused by the use of these methods. An old practice in Brazil, called "cricketing", has led to the misappropriation of Brazilian land using these documents. We propose a rapid, simple, instantaneous and non-destructive method to identify artificially aged papers by easy ambient sonic-spray ionization mass spectrometry (EASI-MS) analysis., Methods: Three typical aging procedures were used to obtain artificially aged papers using coffee, cola drink, and crickets, with the papers being analyzed by EASI-MS. Multivariate statistical analyses were performed on the data to find the sample groups and to study the most relevant ions of each ageing procedure. High-resolution MS (HRMS) was used to obtain the exact masses and attribute formulae to relevant ions present in the samples., Results: The combination of EASI-MS and multivariate statistical analyses allowed us to identify the most relevant ions to classify the adulteration of documents and HRMS identified most of these relevant ions. TMS fingerprinting in combination with multivariate analysis also demonstrated that this approach can qualitatively differentiate all the examined paper samples., Conclusions: We developed a cheap, fast and easy method that can help to elucidate counterfeit documents that have been artificially aged, helping to identify chemical additives and one that can be used in forensic laboratories., (© 2021 John Wiley & Sons Ltd.)

Etonitazene and related 2-benzylbenzimidazoles are potent analgetics invented in the research laboratories of the Swiss pharmaceutical giant CIBA in the late 1950s. Though the unprecedented structure distinguishes this class of compounds from poppy-derived and other synthetic analgetics, a range of studies indicate that these drugs are selective μ opioid receptor agonists possessing morphine-like pharmacotoxicological properties in animals as well as humans. Several unscheduled members of this synthetically readily accessible class of opioids that are not controlled under the international and national drug control systems have recently emerged on the illicit drug market. Among them, isotonitazene has been implicated in at least 200 fatalities in Europe and North America. None of the 2-benzylbenzimidazole derivatives have been developed into medicines, but etonitazene and some of its derivatives have been used as receptor probes and in addiction behavior studies in animals. The unique structure has inspired research on such benzimidazoles and related benzimidazolones of which "brorphine" made its debut as one of the newest psychoactive substance to emerge on the illicit opioid drug market in mid-2019. This in-depth review provides a historical introduction, an overview on the chemistry, pharmacological profiles, adverse effects, addiction liability, regulatory status, and the impact on chemical neuroscience of the 2-benzylbenzimidazoles. Structurally related benzimidazoles with opioid and/or analgesic properties are also discussed briefly.

Progress in understanding the complexity of a devastating disease such as cancer has underscored the need for developing comprehensive panels of molecular markers for early disease detection and precision medicine applications. The present study was conducted to assess whether a cohesive biological context can be assigned to protein markers derived from public data mining, and whether mass spectrometry can be utilized to screen for the co-expression of functionally related biomarkers to be recommended for further exploration in clinical context. Cell cycle arrest/release experiments of MCF7/SKBR3 breast cancer and MCF10 non-tumorigenic cells were used as a surrogate to support the production of proteins relevant to aberrant cell proliferation. Information downloaded from the scientific public domain was queried with bioinformatics tools to generate an initial list of 1038 cancer-associated proteins. Mass spectrometric analysis of cell extracts identified 352 proteins that could be matched to the public list. Differential expression, enrichment, and protein-protein interaction analysis of the proteomic data revealed several functionally-related clusters of relevance to cancer. The results demonstrate that public data derived from independent experiments can be used to inform biological research and support the development of molecular assays for probing the characteristics of a disease.

Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment.

The plantaris longus tendon (PLT) in bullfrog develops a fibrocartilage-like tissue in the area that is functionally subject to compressive forces. The aim of this study was to analyze the modifications of the pressure-bearing region in bullfrog PLT with different ages (7, 180, and 1,080 days after the end of metamorphosis) using histomorphometric, ultrastructural and biochemical methods. Weak basophilia and cells with a fibroblastic phenotype were observed in the compression region at 7 days of age. On the other hand, a large area of intense tissue basophilia associated with a chondroblast-like cell population was noted at the other ages. Collagen fibers exhibited a three-dimensional network-like arrangement at all ages. The number of connective tissue cells increased between 7 and 180 days of age and was reduced in older animals. The 180-day-old animals presented a well-developed pericellular matrix rich in proteoglycans. The mean diameter of collagen fibrils increased from 7 to 180 days and was the same at 1,080 days. Glycosaminoglycan content was higher in 7-day-old animals. A higher amount of hydroxyproline was observed at 180 and 1,080 days. The swelling test showed a significant increase of wet weight in 7-day-old animals. In conclusion, the alterations that occur in the pressure-bearing of bullfrog PLT are the result of physiological alterations of the animal with the maturation and aging., (© 2014 Wiley Periodicals, Inc.)

Objective: The physiological and mechanical properties of the skin, the primary tissue affected by systemic sclerosis, depend on the assembly of collagen types I, III and V, which form heterotypic fibers. Collagen V (COLV) regulates heterotypic fiber diameter, and the maintenance of its properties is important for maintaining normal tissue architecture and function. Based on a COLV-induced experimental SSc model, in which overexpression of abnormal COLV was a prominent feature, we assumed that this abnormality could be present in SSc patients and could be correlated to disease duration, skin thickening and disease activity., Methods: Skin biopsies from 18 patients (6 early-stage and 12 late-stage) and 10 healthy controls were studied. Skin thickening assessment was performed with the Modified Rodnan Skin Score (MRSS), and activity was calculated using the Valentini Disease Activity Index. Morphology, morphometry of COLV deposition in dermis, as well as, quantitative RT-PCR and 3D-reconstruction of the dermal fibroblast culture were performed., Results: Structurally abnormal COLV was overexpressed in SSc skin, mainly in the early stages of the disease, when compared to normal controls and late-stage. A positive correlation between COLV expression and MRSS and disease activity was observed. Collagen V alpha-1 and alpha-2 mRNA expression levels were higher in SSc. Tridimensional reconstruction of SSc dermal heterotypic fibers confirmed the presence of atypical COLV., Conclusion: Increased synthesis of abnormal COLV and its correlation with disease stage, activity and MRSS suggest that this collagen can be a possible trigger involved in the pathogenesis of SSc., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Collagen V shows promise as an inducer of interstitial lung fibrosis in experimental systemic sclerosis (SSc)., Materials and Methods: Remodelling of the pulmonary interstitium was evaluated based on the clinical data and open lung biopsies from 15 patients with SSc. Normal lung tissues obtained from eight individuals who died of traumatic injuries were used as control group. Immunofluorescence, immunohistochemistry, morphometry, tri-dimensional reconstruction and a real-time polymerase chain reaction were used to evaluate the quantity, structure and molecular chains of collagen V. The impact of these markers was tested on clinical data., Results: The main difference in collagen V content between SSc patients and the control group was an increased, abnormal and distorted fibre deposition in the alveolar septa and the pre-acinar artery wall. The lungs from SSc patients presented [alpha1(V)] and [alpha2(V)] mRNA chain expression increased, but [alpha2(V)] was proportionally increased compared with the control group. High levels of collagen V were inversely associated with vital capacity (r = -0.72; P = 0.002), forced vital capacity (r = -0.76; P < 0.001), forced expiratory volume in 1-s (r = -0.89; P < 0.001) and diffusing capacity for carbon monoxide (r = -0.62; P = 0.04)., Conclusions: Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [alpha2(V)] gene of unknown origin.