Transport of Protein Disulfide Isomerase from the Endoplasmic Reticulum to the Extracellular Space without Passage through the Golgi Complex.

Protein disulfide isomerase-A1 (PDIA1) is a master regulator of oxidative protein folding and proteostasis in the endoplasmic reticulum (ER). However, PDIA1 can reach the extracellular space, impacting thrombosis and other pathophysiological phenomena. Whether PDIA1 is externalized via passive release or active secretion is not known. To investigate how PDIA1 negotiates its export, we generated a tagged variant that undergoes N-glycosylation in the ER (Glyco-PDIA1). Addition of N- glycans does not alter its enzymatic functions. Upon either deletion of its KDEL ER-localization motif or silencing of KDEL receptors, Glyco-PDIA1 acquires complex glycans in the Golgi and is secreted. In control cells, however, Glyco-PDIA1 is released with endoglycosidase-H sensitive glycans, implying that it does not follow the classical ER-Golgi route, nor does it encounter glycanases in the cytosol. Extracellular Glyco-PDIA1 is more abundant than actin, lactate dehydrogenase or other proteins released by damaged or dead cells, suggesting active transport through a Golgi-independent route. The strategy we describe herein can be extended to dissect how select ER-residents reach the extracellular space.

Updates in the Treatment of Knee Osteoarthritis.

Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown considerably due to increased life expectancy and obesity, and its diagnosis relies on evaluation, medical examination, and confirmation by supplementary radiographic images. Knee OA is multifactorial and influenced by several local, systemic, and external aspects. In addition, its progress and therapeutic responses highly depend on the characteristics of each subject. The initial recommendation is drug treatment and alternative therapies to improve quality of life. However, if these treatments are unsuccessful, one must consider surgical treatment. Surgical options include arthroscopies, osteotomies, and partial and total arthroplasties, while non-surgical treatments include medications and alternative therapies such as infiltrations, acupuncture, and physical exercise. It is worth highlighting that biomarkers can be a significant strategy for early disease detection, assessment of disease activity, prediction of prognosis, and monitoring a better response to therapy. Nevertheless, this topic must be the focus of further research to confirm its findings.

Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension.

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension. We demonstrate that PDI contributes to the development of hypertension via enhanced transcriptional upregulation of Nox1 in vascular smooth muscle cells (VSMCs). We show for the first time that PDI sulfenylation by hydrogen peroxide contributes to EGFR activation in hypertension via increased shedding of epidermal growth factor-like ligands. PDI also increases intracellular calcium levels, and contractile responses induced by ANG II. PDI silencing or pharmacological inhibition in VSMCs significantly decreases EGFR activation and Nox1 transcription. Overexpression of PDI in VSMCs enhances ANG II-induced EGFR activation and ATF1 translocation to the nucleus. Mechanistically, PDI increases ATF1-induced Nox1 transcription and enhances the contractile responses to ANG II. Herein we show that ATF1 binding to Nox1 transcription putative regulatory regions is augmented by PDI. Altogether, we provide evidence that HB-EGF in SHR resistance vessels promotes the nuclear translocation of ATF1, under the control of PDI, and thereby induces Nox1 gene expression and increases vascular reactivity. Thus, PDI acts as a thiol redox-dependent enhancer of vascular dysfunction in hypertension and could represent a novel therapeutic target for the treatment of this disease.

Sex-associated differences in cardiac ageing: Clinical aspects and molecular mechanisms.

Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people aged 65 and over. Of all ageing-related diseases, CVD are responsible for almost one-third of deaths in the elderly, being above all cancers combined. Age is an independent and unavoidable risk factor contributing to the impairment of heart and blood vessels. As the average age of the population in industrialized countries has doubled in the last century, and almost a fifth of the world's population is predicted to be over 65 in the next decade, we can assume that the burden of CVD will fall primarily on the elderly. Evidence from basic and clinical science has shown that sex significantly influences the onset and severity of CVD. In women, CVD usually develop later than in men and with atypical symptomatology. After menopause, however, the incidence and severity of CVD increase in women, reaching equality in both sexes. Although intrinsic sexual dimorphism in cardiovascular ageing may contribute to the sex differences in CVD progression, the molecular mechanisms associated with cardiovascular ageing and their clinical value are not known in detail. In this review, we discuss the scientific knowledge available, focusing on structural, hormonal, genetic/epigenetic and inflammatory pathways, seeking to transfer these findings to the cardiovascular clinic in terms of prevention, diagnosis, prognosis and management of these pathologies and proposing possible validation of target specifics.

Pérdida significativa como factor del alcoholismo / Perda significativa como fator de alcoolism / Significant loss as a factor in alcoholism

La relación de la pérdida significativa de un ser queridoy el alcoholismo ha minimizado las implicaciones sobremecanismos de afrontamientos para generar conductassaludables. Este artículo se basa en entrevistas semiestructuradasa profundidad en hombres de entre 30 y 70 años, conmás de 10 años en Alcohólicos Anónimos del Estado deTamaulipas, México. El objetivo fue reflexionar sobre lossignificados de la pérdida significativa de un ser querido yel alcoholismo. En la búsqueda del significado, se explicaque un factor que lleva al alcoholismo no es una sola pérdidasignificativa de personas queridas, sino un cúmulo tambiende pérdidas materiales y no materiales, se reflejaron recursoslimitados para afrontar las pérdidas, la relación entre lapérdida significativa con el alcoholismo fue mediado pordos principales aspectos, las creencias sobre los efectos queproduce el consumo de alcohol como formas de escapar de larealidad y las influencia de la familia al inicio del consumode alcohol. Por otra parte, la presencia de lo espiritual, laconciencia y las emociones que experimentan durante suproceso de duelo y alcoholismo, los llevó a identificar elproblema de la adicción, que permitió influir en el procesode rehabilitación.(AU)

A relação entre a perda significativa de um ente querido e oalcoolismo tem minimizado as implicações nos mecanismosde enfrentamento para gerar comportamentos saudáveis.Este artigo é baseado em entrevistas semiestruturadas emprofundidade com homens entre 30 e 70 anos, com mais de10 anos em Alcoólicos Anônimos no Estado de Tamaulipas,México. O objetivo foi refletir sobre os significados da perdasignificativa de um ente querido e do alcoolismo. Na buscade sentido, explica-se que um fator que leva ao alcoolismonão é uma única perda significativa de entes queridos, mastambém um acúmulo de perdas materiais e imateriais,recursos limitados foram refletidos para enfrentar as perdas,a relação entre a perda significativa com o alcoolismo foimediada por dois aspectos principais, as crenças sobre osefeitos que o consumo de álcool produz como formas defuga da realidade e a influência da família no início doconsumo de álcool. Por outro lado, a presença do espiritual,da consciência e das emoções que vivenciam durante oprocesso de luto e alcoolismo, levaram-nos a identificar oproblema da dependência, o que lhes permitiu influenciaro processo de reabilitação.(AU)

The relationship between the significant loss of a lovedone and alcoholism has minimized the implications oncoping mechanisms to generate healthy behaviors. Thisarticle is based on in-depth semi-structured interviews withmen between the ages of 30 and 70, with more than 10years in Alcoholics Anonymous in the State of Tamaulipas,Mexico. The objective was to reflect on the meanings of the significant loss of a loved one and alcoholism. In thesearch for meaning, it is explained that a factor that leadsto alcoholism is not a single significant loss of loved ones,but also an accumulation of material and non-materiallosses, limited resources were reflected to face the losses,the relationship between the loss significant with alcoholismwas mediated by two main aspects, beliefs about the effectsthat alcohol consumption produces as ways of escapingfrom reality and the influence of the family at the beginningof alcohol consumption. On the other hand, the presenceof the spiritual, the conscience and the emotions that theyexperience during their mourning process and alcoholism,led them to identify the problem of addiction, which allowedthem to influence the rehabilitation process.(AU)

Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

Resiliencia y consumo de alcohol o tabaco en adolescentes de la zona este de Tijuana / Resilience and use of alcohol or tobacco among adolescents from the eastern area of Tijuana

Objetivo: describir las características de la resiliencia y su asociación con el consumo de alcohol y tabaco en adolescentes residentes en la zona este de Tijuana, frontera norte de México. Método: estudio descriptivo transversal cuya población fueron 7.611 adolescentes de 11 a 16 años escolarizados de la ciudad de Tijuana, Baja California. Se estimó una muestra de 663 participantes seleccionados mediante muestreo por conglomerados. Se recogieron variables sociodemográficas, de historia de consumo de tabaco y alcohol y la resiliencia (ER-14) (mín. 14 a máx. 98 p; muy baja, baja, normal, alta o muy alta). Se realizó estadística descriptiva, bivariante y modelos de regresión logística ajustados por sexo para la variable “consumo de alcohol o tabaco”. Resultados: participaron 710 adolescentes (50,7% mujeres). El 46% había consumido alcohol o tabaco en algún momento de su vida y el 27,1% en el último año (mujeres 31,5%; hombres 23,3%; p= 0,005). El 29% mostró alta resiliencia y el 25,5% muy alta resiliencia. Se obtuvo con más frecuencia alta puntuación en las afirmaciones: soy alguien en quien se puede confiar en emergencias (42,5%), siento orgullo de mis logros (41,3%), la vida tiene sentido (33,1%). Se encontró un efecto negativo de la resiliencia sobre el consumo de alcohol o tabaco alguna vez en la vida (ORa= 0,984; IC95% [0,978-0,990]) y en el último año (ORa= 0,987; IC95% [0,981-0,994]). Conclusión: a mayor resiliencia menor fue la probabilidad de consumo de alcohol o tabaco alguna vez en la vida y en el último año. Intervenciones futuras deben considerar estos resultados.(AU)

Objective: to describe the characteristics of resilience and its association with the use of alcohol and tobacco among adolescents living in Eastern Tijuana, in the Northern border of Mexico. Method: a descriptive cross-sectional study on a population of 7,611 adolescents from 11 to 16 years old, attending school in the city of Tijuana, Baja California. The sample was estimated in 633 participants, selected through cluster sampling. Sociodemographic variables were collected, their history of use of tobacco and alcohol, as well as resilience (RS-14) (minimum 14 to maximum 98 scores; very low, low, normal, high or very high). Descriptive bivariate statistics were used, as well as logistical regression models adjusted by gender for the “use of alcohol of tobacco” variable. Results: the study included 710 adolescents (50.7% were female); 46% of them had used alcohol or tobacco at some point in their lives, and 27.1% during the past year (31.5% female; 23.3% male; p= 0.005); 29% showed high resilience and 25.5% showed very high resilience. The most frequently obtained high scores were for the statements: I am someone who can be trusted in emergencies (42.5%), I feel proud of my achievements (41.3%), and Life makes sense (33.1%). A negative effect of resilience was found on alcohol and tobacco use at some point in life (ORa= 0.984; CI95% [0.978-0.990]) and during the past year (ORa= 0.987; CI95% [0.981-0.994]). Conclusion: the higher the resilience, the lower the likelihood of using alcohol or tobacco at some point in life and during the last year. Future interventions should consider these results.(AU)

DNAJB12 and DNJB14 are non-redundant Hsp40 redox chaperones involved in endoplasmic reticulum protein reflux.

BACKGROUND: The endoplasmic reticulum (ER) transmembrane chaperones DNAJB12(B12) and DNAJB14(B14) are cofactors that cooperate with cytosolic Heat Shock-70 protein (HSC70) facilitating folding/degradation of nascent membrane proteins and supporting the ER-membrane penetration of viral particles. Here, we assessed structural/functional features of B12/B14 with respect to their regulation by ER stress and their involvement in ER stress-mediated protein reflux. METHODS: We investigated the effect of Unfolded Protein Response(UPR)-eliciting drugs on the expression/regulation of B12-B14 and their roles in ER-to-cytosol translocation of Protein Disulfide Isomerase-A1(PDI). RESULTS: We show that B12 and B14 are similar but do not seem redundant. They share predicted structural features and show high homology of their cytosolic J-domains, while their ER-lumen DUF1977 domains are quite dissimilar. Interactome analysis suggested that B12/B14 associate with different biological processes. UPR activation did not significantly impact on B12 gene expression, while B14 transcripts were up-regulated. Meanwhile, B12 and B14 (33.4 kDa isoform) protein levels were degraded by the proteasome upon acute reductive challenge. Also, B12 degradation was impaired upon sulfenic-acid trapping by dimedone. We originally report that knockdown of B12/B14 and their cytosolic partner SGTA in ER-stressed cells significantly impaired the amount of the ER redox-chaperone PDI in a cytosolic-enriched fraction. Additionally, B12 but not B14 overexpression increased PDI relocalization in non-stressed cells. CONCLUSIONS AND GENERAL SIGNIFICANCE: Our findings reveal that B12/B14 regulation involves thiol redox processes that may impact on their stability and possibly on physiological effects. Furthermore, we provide novel evidence that these proteins are involved in UPR-induced ER protein reflux.

Teoría de rango medio: Estímulos y Afrontamiento a la Marihuana en Universitarios / Middle Range Theory: Stimuli and Coping with Marijuana Among College Students

En el presente artículo se expone un ejemplo de estrategia de substracción conceptual-teórico-empírica (C-T-E), obteniendo como resultado una propuesta de Teoría de Rango Medio (TRM) que explique los elementos que influyen en el consumo de marihuana en estudiantes universitarios. Esta propuesta se desarrolla a partir de la revisión de la literatura sobre el tema y de la aplicación del Modelo de Adaptación de Roy (MAR), prestando especial atención al papel que desempeñan la Espiritualidad, el Rasgo de Atención Plena (RAP). Esta TRM ofrece al profesional de enfermería una alternativa para entender un fenómeno actual, cuya prevalencia se ha venido agravando en los últimos años en México de manera alarmante. Por ello, se ofrece una estrategia útil que permita la identificación de factores de riesgo y preventivos para continuar con investigaciones que favorezcan la prevención del consumo de marihuana.(AU)

This article presents an example of a conceptual-theoretical-empirical subtraction strategy (C-T-E), which leads to the development of a Middle-Range Theory (MRT) aimed at explaining the factors that influence marijuana consumption among college students. This proposal is constructed through a comprehensive literature review and the application of Roy's Adaptation Model (RAM), with special emphasis on the roles of Spirituality, the Trait of Mindfulness (TOM). By offering nursing professionals an alternative to understanding a current phenomenon, whose prevalence has been alarmingly increasing in Mexico in recent years. Therefore, a useful strategy is provided to identify risk and protective factors, allowing for further research that promotes the prevention of marijuana consumption.(AU)

Benthic microbial biogeographic trends in the North Sea are shaped by an interplay of environmental drivers and bottom trawling effort.

Microbial composition and diversity in marine sediments are shaped by environmental, biological, and anthropogenic processes operating at different scales. However, our understanding of benthic microbial biogeography remains limited. Here, we used 16S rDNA amplicon sequencing to characterize benthic microbiota in the North Sea from the top centimeter of 339 sediment samples. We utilized spatially explicit statistical models, to disentangle the effects of the different predictors, including bottom trawling intensity, a prevalent industrial fishing practice which heavily impacts benthic ecosystems. Fitted models demonstrate how the geographic interplay of different environmental and anthropogenic drivers shapes the diversity, structure and potential metabolism of benthic microbial communities. Sediment properties were the primary determinants, with diversity increasing with sediment permeability but also with mud content, highlighting different underlying processes. Additionally, diversity and structure varied with total organic matter content, temperature, bottom shear stress and bottom trawling. Changes in diversity associated with bottom trawling intensity were accompanied by shifts in predicted energy metabolism. Specifically, with increasing trawling intensity, we observed a transition toward more aerobic heterotrophic and less denitrifying predicted metabolism. Our findings provide first insights into benthic microbial biogeographic patterns on a large spatial scale and illustrate how anthropogenic activity such as bottom trawling may influence the distribution and abundances of microbes and potential metabolism at macroecological scales.

Leishmanicidal and healing effects of 3ß,6ß,16ß-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo.

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.

Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection.

BACKGROUND AND AIMS: Redox signaling is involved in the pathophysiology of aortic aneurysm/dissection. Protein Disulfide Isomerases and its prototype PDIA1 are thiol redox chaperones mainly from endoplasmic reticulum (ER), while PDIA1 cell surface pool redox-regulates thrombosis, cytoskeleton remodeling and integrin activation, which are mechanisms involved in aortic disease. Here we investigate the roles of PDIA1 in aortic dissection. METHODS: Initially, we assessed the outcome of aortic aneurysm/dissection in transgenic PDIA1-overexpressing FVB mice using a model of 28-day exposure to lysyl oxidase inhibitor BAPN plus angiotensin-II infusion. In a second protocol, we assessed the effects of PDIA1 inhibitor isoquercetin (IQ) against aortic dissection in C57BL/6 mice exposed to BAPN for 28 days. RESULTS: Transgenic PDIA1 overexpression associated with ca. 50% (p = 0.022) decrease (vs.wild-type) in mortality due to abdominal aortic rupture and protected against elastic fiber breaks in thoracic aorta. Conversely, exposure of mice to IQ increased thoracic aorta dissection-related mortality rates, from ca. 18%-50% within 28-days (p = 0.019); elastic fiber disruption and collagen deposition were also enhanced. The structurally-related compound diosmetin, which does not inhibit PDI, had negligible effects. In parallel, stretch-tension curves indicated that IQ amplified a ductile-type of biomechanical failure vs. control or BAPN-exposed mice aortas. IQ-induced effects seemed unassociated with nonspecific antioxidant effects or ER stress. In both models, echocardiographic analysis of surviving mice suggested that aortic rupture was dissociated from progressive dilatation. CONCLUSIONS: Our data indicate a protective role of PDIA1 against aortic dissection/rupture and potentially uncovers a novel integrative mechanism coupling redox and biomechanical homeostasis in vascular remodeling.

Tendência da mortalidade por Paracoccidioidomicose no Brasil ­ 1996 a 2020 / Mortality trends due to Paracoccidioidomycosis in Brazil ­ 1996 to 2020

Objetivo: Analisar a tendência da mortalidade por paracoccidioidomicose (PCM) e caracterizar o perfil sociodemográfico no Brasil e suas regiões geográficas numa série temporal de 25 anos. Métodos: Trata-se de estudo ecológico de séries temporais. Considerou-se como participantes do estudo a população brasileira dividida em faixas etárias, que tiveram como causa básica do óbito a PCM. Para calcular a variação percentual anual (VPA) dos coeficientes, na análise de tendência, foi utilizada a regressão de Prais-Winsten. Os coeficientes de mortalidade foram calculados a nível nacional, segundo as regiões geográficas, sexo e faixa etária e proporcional para as demais variáveis. Resultados: De acordo com os resultados deste estudo, ocorreram 2.101 óbitos por PCM no Brasil. A tendência ao longo dos 25 anos evidenciou um comportamento estável nas regiões Norte e Nordeste. Já no Sul, Sudeste e Centro-Oeste houve uma tendêndia de queda. A mortalidade média no Brasil foi de 84,04/100 mil hab., VPA -3,29 (IC 95% -2,43; -4,14). Levando em consideração a análise dos aspectos sociodemográficos, houve um predomínio de escolaridade ignorada (764; 36%), raça/ cor da pele branca (1.109; 53%), estado civil misto: casado (942; 45%) e solteiro (640; 30%), local de ocorrência do óbito predominantemente no âmbito hospitalar (1.852; 88%). Conclusão: Tanto no Brasil como nas regiões geográficas Sudeste, Sul e Centro-Oeste a mortalidade por PCM apresentou-se com tendência temporal decrescente. Já nas regiões Nordeste e Norte a tendência foi estacionária. O perfil sociodemográfico dos pacientes que foram a óbito apontou para sexo masculino, adultos, de baixa escolaridade, brancos e casados.

Objective: To analyze the trend in mortality from paracoccidioidomycosis (PCM) and characterize the sociodemographic profile in Brazil and its geographic regions in a 25-year time series. Methods: This is an ecological time series study. The study participants were the Brazilian population divided into age groups whose underlying cause of death was PCM. To calculate the annual percentage change (VPA) of the coefficients in the trend analysis, the Prais-Winsten regression was used. National mortality coefficients were calculated according to geographic regions, sex and age group and proportional to the other variables. Results: According to this study, there were 2,101 deaths from PCM in Brazil. The trend over the 25 years showed stable behavior in the North and Northeast regions. In the South, Southeast, and Midwest, there was a downward trend. The average mortality in Brazil was 84.04/100,000 inhab., VPA -3.29 (95% CI -2.43; -4.14). According to the analysis of sociodemographic aspects, there was a predominance of ignored schooling (764 deaths; 36%), white race/skin color (1,109; 53%), mixed marital status: married (942; 45%) and single (640; 30%), and place of death predominantly in the hospital environment (1,852; 88%). Conclusion: In Brazil and in the Southeast, South, andMidwest geographic regions, mortality from PCM showed a decreasing temporal trend. In the Northeast and North regions, the trend was stationary. The sociodemographic profile of the dying patients indicated males, adults, with low education, white, and married.

Estilos de crianza parental y consumo de tabaco y alcohol en adolescentes y jóvenes escolarizados / Parenting styles and use of tobacco and alcohol in adolescents and young persons enrolled in school

Objetivo: describir la asociación de los estilos de crianza parental con el consumo de tabaco y alcohol en adolescentes y jóvenes del norte del estado de Nuevo León, México.Método: estudio descriptivo transversal. Población formada por estudiantes de 15 a 23 años de preparatoria y universitarios (N= 1.562) seleccionados por muestreo estratificado. Se midieron variables demográficas y de consumo de sustancias, así como el estilo de crianza percibido en padre y madre mediante la Escala de Steinberg (democrático, indulgente, autoritario, negligente). Se realizó estadística descriptiva y modelos de regresión lineal.Resultados: participaron 448 estudiantes. El 49,6% había consumido tabaco y el 76,6% alcohol alguna vez. Se encontraron diferencias estadísticamente significativas en el consumo de alcohol en función del estilo de crianza maternal, más frecuente en caso de estilo negligente (87%). A nivel multivariante, el estilo de crianza negligente del padre (β= 0,15) y mayor edad (β= 0,30) se asociaron a mayor cantidad de cigarros fumados en un día normal (R2= 0,08; p < 0,001). El estilo de crianza democrático de la madre (β= -0,16) y ser hombre (β= -0,25) explicaron una menor cantidad de copas consumidas en un día típico (R2= 0,08; p < 0,001).Conclusiones: la mitad de las personas participantes había consumido alguna vez tabaco y tres cuartas partes alcohol. Percibir al padre con estilo de crianza negligente aumentó la cantidad de tabaco consumido en un día típico. El estilo de crianza democrático de la madre se asoció a menor cantidad de alcohol consumido en un día típico.(AU)

Objective: to describe the association between parental styles and use of tobacco and alcohol in adolescents and young persons from the northern Nuevo León state, Mexico.Method: a descriptive cross-sectional study. The population was formed by 15-to-23-year-old high school and university students (N= 1.562) selected through stratified sampling. Demographic variables and use of substances were measured, as well as the parenting style perceived in their father and mother through the Steinberg Scale (democratic, indulgent, authoritative, neglectful). Descriptive statistics and linear regression models were conducted.Results: in total, 448 students participated in the study; 49.6% of them had smoked and 76.6% had used alcohol at some point. Statistically significant differences were found in the use of alcohol according to the parenting style by their mother, more frequent in the case of neglectful style (87%). At multivariate level, the neglectful parenting style by the father (β= 0.15) and older age (β= 0.30) were associated with a higher number of cigars smoked in a typical day (R2= 0.08; p < 0.001). The democratic parenting style by the mother (β= -0.16) and being male (β= -0.25) explained a lower number of drinks taken during a typical day (R2= 0.08; p < 0.001).Conclusions: half of the participants had smoked at some time, and three fourths of them had drank alcohol. Perceiving a neglectful parenting style in the father increased the amount of tobacco used in a typical day. The democratic parenting style of the mother was associated with a lower volume of alcohol taken in a typical day.(AU)

Percepción de riesgo y religiosidad en el consumo de marihuana en adolescentes de zonas marginales / Perception of risk and religiosity in the consumption of marijuana in adolescents from marginal áreas

Resumen Objetivo: Describir el efecto de la percepción de riesgo y la religiosidad sobre el consumo de marihuana en adolescentes de zonas marginales del Estado de Chihuahua, Chihuahua. Materiales y métodos: Estudio descriptivo correlacional. El muestreo fue probabilístico aleatorio simple. La muestra final fue de 248 adolescentes de 12 a 17 años de zonas marginales de Chihuahua. Se utilizó una cédula de datos personales, inventario de religiosidad y la escala de percepción de riesgo. Resultados: El 59.3% de los adolescentes entrevistados fueron hombres, 59.7% católico y 23% cristiano. El 16.1% indicó consumo de marihuana alguna vez en la vida y 6.5% en el último año. El modelo de regresión logística de las variables de religiosidad y percepción de riesgo mostró una varianza explicada del 19% para el consumo de marihuana alguna vez en la vida, destacando que a mayor percepción de riesgo (β=-0.032, p<0.001) y mayor índice de religiosidad (β=-0.023, p<0.001) menor es la probabilidad del consumo de marihuana. Conclusiones: La percepción de riesgo y la religiosidad en adolescentes de zonas marginales muestran ser factores protectores para el consumo de marihuana. Estos resultados deben ser considerados en programas de prevención para el consumo de drogas en poblaciones marginales.

Abstract Objective: To describe the effect of the perception of risk and religiosity on the consumption of marijuana in adolescents from marginal areas of the State of Chihuahua, Chihuahua. Materials and methods: Study descriptive correlational design. The sampling was simple random probabilistic. The final sample consisted of 248 adolescents between the ages of 12 and 17 from marginal areas of Chihuahua. A personal data card, religiosity inventory and the risk perception scale were used. Results: 59.3% of the adolescents interviewed were men, of whom 59.7% said they were Catholic and 23% Christian. 16.1% indicated marijuana use at some time in their life, and 6.5% in the last year. The logistic regression model of the religiosity and risk perception variables showed an explained variance of 19% for marijuana use at some time in life, highlighting that the higher the risk perception (β=-0.032, p<.001) and a higher religiosity index (β=-0.023, p<0.001), the lower the probability of marijuana use. Conclusions: Risk perception and religiosity in adolescents from marginal areas show to be protective factors for marijuana use. These results should be analyzed in greater depth to be considered in prevention programs for drug use in marginal populations.

Raman mapping for determination of TiO2 in different solid food samples by multivariate curve resolution with alternating least squares.

Titanium dioxide is a food additive commonly used as a white food coloring (E171). Its wide use by the food industry associated with the nanometric size distribution of the particles of this pigment has shown high genotoxicity associated with recurrent exposure by ingestion. Therefore, the use of E171 in food products has already been banned by some industries and in the European Union. Such banishment should soon be extended to other countries around the world, making it important to establish techniques for the efficient determination of TiO2 in different food products. The association between hyperspectral images and chemometric tools can be useful in this sense, aiming to enable the use of a single method for sample preparation and analysis of different types of food. Thus, the present work aims to evaluate the use of Raman mapping associated with the resolution of multivariate curves with alternating least squares (MCR-ALS) for the determination of titanium dioxide in solid food samples with different compositions, without the need to introduce specific sample preparation. The proposed method allowed for the first-time quantification of TiO2 in different food matrices without specific sample preparation, with a simple, rapid, accurate (93% of recovery), low detection limits (0.0111% m/m) and quantification (0.0370% m/m) and adequate linearity (r = 0.9990) and precise (standard deviation around 0.020-0.030% w/w) methodology. Such results highlight the potential use of Raman mapping associated with the MCR-ALS for quantification of the nano-TiO2 in commercial samples.

Marine heatwaves and upwelling shape stress responses in a keystone predator.

Climate change increases the frequency and intensifies the magnitude and duration of extreme events in the sea, particularly so in coastal habitats. However, the interplay of multiple extremes and the consequences for species and ecosystems remain unknown. We experimentally tested the impacts of summer heatwaves of differing intensities and durations, and a subsequent upwelling event on a temperate keystone predator, the starfish Asterias rubens. We recorded mussel consumption throughout the experiment and assessed activity and growth at strategically chosen time points. The upwelling event overall impaired starfish feeding and activity, likely driven by the acidification and low oxygen concentrations in the upwelled seawater. Prior exposure to a present-day heatwave (+5°C above climatology) alleviated upwelling-induced stress, indicating cross-stress tolerance. Heatwaves of present-day intensity decreased starfish feeding and growth. While the imposed heatwaves of limited duration (9 days) caused slight impacts but allowed for recovery, the prolonged (13 days) heatwave impaired overall growth. Projected future heatwaves (+8°C above climatology) caused 100% mortality of starfish. Our findings indicate a positive ecological memory imposed by successive stress events. Yet, starfish populations may still suffer extensive mortality during intensified end-of-century heatwave conditions.

Contributions towards the hazard evaluation of two widely used cytostatic drugs.

Cytostatic drugs are one of the most important therapeutic options for cancer, a disease that is expected to affect 29 million individuals by 2040. After being excreted, cytostatics reach wastewater treatment plants (WWTPs), which are unable to efficiently remove them, and consequently, they will be released into the aquatic environment. Due to the highly toxic properties of cytostatics, it is particularly relevant to evaluate their potential ecological risk. Yet, cytostatics toxicity data is still not available for various species. In this work, the ecotoxicity of two widely consumed cytostatics, cyclophosphamide (CYP-as a model cytostatic) and mycophenolic acid (MPA-as a priority cytostatic), was evaluated on three freshwater species-Raphidocelis subcapitata, Brachionus calyciflorus, and Danio rerio, and the risk quotient (RQ) was assessed. Both drugs significantly affected the yield and growth inhibition of the microalgae, while for rotifers, the least sensitive species, only significant effects were registered for CYP. These drugs also caused significant effects on the mortality and morphological abnormalities on zebrafish. The estimation of the RQ discloses that CYP seems to pose a low risk to aquatic biota while MPA poses a very high risk. Altogether, these results emphasize the need for more complete environmental risk assessments, to properly prioritize and rank cytostatics according to their potentially toxic effects on the environment and aquatic biota.

A função da mancha no caso Hans: da falta à presença do objeto / La función de la mancha en el Juanito: de la falta a la presencia del objeto / The function of the stain in little Hans: from lack to presence of the object / La fonction de la tache dans le petit Hans: du manque à la présence de l'objet

O artigo desenvolve a hipótese de que o trabalho de releitura do caso Hans, realizado por Lacan no Seminário 4, A relação de objeto (1956-1957), antecipa a formulação do conceito de objeto a em seu ensino. Dois pontos cruciais em relação ao objeto são destacados em um trabalho de leitura próxima e atenta ao texto do Seminário. Nesse percurso, a introdução da falta de objeto, modulada pelas operações de privação, frustração e castração, se contrapõe à noção de uma certa presença do objeto. O artigo propõe que em sua teorização sobre a angústia do pequeno Hans, Lacan introduz a função da mancha operando como objeto a, situando-a como um resíduo impossível de ser simbolizado, a coisa preta na boca do cavalo, objeto da fobia de Hans

El artículo desarrolla la hipótesis de que la relectura del caso Juanito realizada por Lacan en el Seminario 4, La relación de objeto (1956-1957) presenta una primera versión del concepto de objeto a en su enseñanza. Del trabajo de lectura cercana del texto del Seminario se destacan dos puntos cruciales con relación al objeto. En este recorrido, la introducción de la falta de objeto, modulada por las operaciones de privación, frustración y castración, admite la noción paradójica de una cierta presencia del objeto. El artículo propone que, a partir del desarrollo de su teorización sobre la angustia del Juanito, Lacan introduce la función de la mancha operando como objeto a, ubicándola como un residuo imposible de simbolizar, la cosa negra en la boca del caballo, objeto de la fobia de Juanito

The article develops the hypothesis that the re-reading of little Hans, carried out by Lacan in Seminar 4, The Object Relation (1956-1957), presents a primary version of the objet petit a in his teaching. In this course, two crucial points concerning the object are emphasized in a close reading of the Seminar's text. The introduction of the notion of lack of object, modulated by the operations of deprivation, frustration and castration, is then opposed to the notion of a certain presence of the object. The article proposes that with the development of a theorization on little Hans' anxiety, Lacan introduces the function of the stain working as na object a, a residue impossible to be symbolized, located in the black spot in the horse's mouth, object of Hans' phobia

L'article développe l'hypothèse qui la relecture du cas le petit Hans effectuée par Lacan dans le Séminaire 4, La relation d'objet(1956-1957) anticipe la formulation du concept d'objet (a) dans son enseignement. Deux points cruciaux par rapport à l'objet sont mis en évidence dans un travail de lecture attentive du texte du Séminaire. Dans ce parcours, l'introduction de la notion de manque d'objet, modulée par les opérations de privation, frustration et castration, s'oppose à la notion d'une certaine présence de l'objet. L'article soutient qui depuis sa théorisation sur l'angoisse du petit Hans, Lacan introduit la fonction de la tache comme un résidu impossible à symboliser, la chose noire dans la bouche du cheval, objet de la phobie de Hans. Et comme tel, la tache noire opère la fonction d'(a)