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1.
Cureus ; 16(8): e66247, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39238689

ABSTRACT

OBJECTIVE: The emergence of the coronavirus disease 2019 (COVID-19) pandemic severely compromised international travel and the practice of travel medicine. This study aimed to investigate the evolution of traveler behaviors and prophylactic prescriptions across the pandemic and post-pandemic periods. POPULATION AND METHODS: A retrospective study was conducted on travelers attending the International Vaccination Center in Vila Nova de Gaia, Portugal, from August 2019 to May 2023, where data were collected on travelers' demographics, destination, duration, reasons for traveling, and data regarding travel-related vaccines and malaria prophylaxis. Travelers' characteristics were compared between Period A (pre-pandemic), Period B (pandemic), and Period C (post-pandemic). RESULTS: The study included 1,711 travelers in the analysis. During the pandemic period, there were fewer travelers for tourism (5% decrease) and an increase in travelers for emigration and work (4.8% increase). There was also an increase in trips lasting less than two weeks among tourists, as well as trips lasting more than one month, primarily among travelers for work or emigration. During the pandemic, there was a significant decrease in Asia as a destination, with a shift toward African countries, which partially reverted in the post-pandemic period. Significant decreases in the prescriptions of vaccines were found during the pandemic and continued in the post-pandemic period. CONCLUSION: There was a change in travelers' characteristics due to the pandemic, with a shift to shorter trips for tourism, an avoidance of Asia, and a preference for sub-Saharan African countries as a main hub of destination. Some vaccine prescription practices remained low and even decreased during or after the pandemic.

2.
Plant Sci ; 348: 112231, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39154893

ABSTRACT

In angiosperms, ovules give rise to seeds upon fertilization. Thus, seed formation is dependent on both successful ovule development and tightly controlled communication between female and male gametophytes. During establishment of these interactions, cell walls play a pivotal role, especially arabinogalactan-proteins (AGPs). AGPs are highly glycosylated proteins decorated by arabinogalactan side chains, representing 90 % of the AGP molecule. AGP glycosylation is initiated by a reaction catalysed by hydroxyproline-O-galactosyltransferases (Hyp-GALTs), specifically eight of them (GALT2-9), which add the first galactose to Hyp residues. Five Hyp-GALTs (GALT2, 5, 7, 8 and 9) were previously described as essential for AGP functions in pollen and ovule development, pollen-pistil interactions, and seed morphology. In the present work, a higher order Hyp-GALT mutant (23456789) was studied, with a high degree of under-glycosylated AGPs, to gain deeper insight into the crucial roles of these eight enzymes in female reproductive tissues. Notably, the 23456789 mutant demonstrated a high quantity of unfertilized ovules, displaying abnormal callose accumulation both at the micropylar region and, sometimes, throughout the entire embryo sac. Additionally, this mutant displayed ovules with abnormal embryo sacs, had a disrupted spatiotemporal distribution of AGPs in female reproductive tissues, and showed abnormal seed and embryo development, concomitant with a reduction in AGP-GlcA levels. This study revealed that at least three more enzymes exhibit Hyp-O-GALT activity in Arabidopsis (GALT3, 4 and 6), and reinforces the crucial importance of AGP carbohydrates in carrying out the biological functions of AGPs during plant reproduction.


Subject(s)
Arabidopsis , Galactosyltransferases , Ovule , Arabidopsis/growth & development , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/enzymology , Galactosyltransferases/metabolism , Galactosyltransferases/genetics , Ovule/growth & development , Ovule/genetics , Seeds/growth & development , Seeds/genetics , Seeds/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Reproduction , Plant Proteins/metabolism , Plant Proteins/genetics , Mucoproteins/metabolism , Mucoproteins/genetics
3.
Rep Pract Oncol Radiother ; 29(2): 197-203, 2024.
Article in English | MEDLINE | ID: mdl-39143973

ABSTRACT

Background: Esthesioneuroblastoma (ENB) is an uncommon malignant sinonasal tumor. There are few data regarding ENB management, namely its treatment. We review our institute's experience in the treatment of ENB and evaluate survival outcomes. Materials and methods: Retrospective study of patients with ENB treated between 1984-2022. A total of 20 patients were identified, 13 men and 7 women, aged between 20 and 76 years. Results: Eleven patients were stage C of the modified Kadish staging system at initial presentation, 7 stage B, 1 stage A and 1 stage D. Seventeen patients underwent surgery alone or combined with adjuvant treatment (radiotherapy or chemoradiotherapy). The majority of the patients (71.4%) treated with surgery alone were stage B, whereas most of the patients (63.6%) that underwent surgery combined with adjuvant treatment were stage C. Five of the 7 patients treated with surgery alone had a locoregional recurrence. Two of the 10 patients treated with surgery followed by adjuvant treatment had relapsed, locoregionally and at a distance, respectively. One patient was treated with chemotherapy and 2 patients were treated with chemoradiotherapy and neoadjuvant chemotherapy followed by chemoradiotherapy, respectively. The recurrence and persistence rates were 35% and 15%, respectively. The median time from the end of the first treatment to recurrence was 20.9 months. Two- and 5-year overall survival rates were 83.9% and 77.9%; while progression-free survival rates were 76.7% and 61.0%, respectively. Conclusions: Sixty percent of patients were treated with a multimodal approach, which appeared to be a favorable strategy for the majority of patients.

4.
Elife ; 122024 Jul 19.
Article in English | MEDLINE | ID: mdl-39027984

ABSTRACT

Amyloid ß (Aß) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aß42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aß42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events. We conducted kinetic analyses of γ-secretase activity in cell-free systems in the presence of Aß, as well as cell-based and ex vivo assays in neuronal cell lines, neurons, and brain synaptosomes to assess the impact of Aß on γ-secretases. We show that human Aß42 peptides, but neither murine Aß42 nor human Aß17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75, and pan-cadherin. Moreover, Aß42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems. Our findings raise the possibility that pathological elevations in Aß42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aß toxicity in the context of γ-secretase-dependent homeostatic signaling.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Amyloid beta-Peptides , Neurons , Signal Transduction , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Humans , Alzheimer Disease/metabolism , Animals , Neurons/metabolism , Neurons/drug effects , Mice , Feedback, Physiological , Peptide Fragments/metabolism , Cell Line
5.
Pediatr Rep ; 16(2): 461-481, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38921705

ABSTRACT

BACKGROUND: Investigations have shown the different impacts that ACEs have on an individual's adult life, on both physical and mental health, but they have not yet shown the issue of the influence of ACEs on adults and young adults. Objective/Participants and Setting: This systematic review, performed according to the PRISMA norms and guidelines, intended to understand the most frequent outcomes of adverse childhood experiences in the life of young adults and adults. METHODS: Studies were identified through multiple literature search databases at EBSCOhost, Web of Science, and PubMed April 2023, and a total of 279 studies, published between 1999 and 2002, were excluded, 256 because of multiple factors: being duplicates, showing statistical analysis with correlations only, being systematic reviews or case studies, comprising individuals under the age of 18, and not meeting the intended theme; ultimately, we selected for the review a total of 23 studies. RESULTS AND CONCLUSIONS: The impacts of the various articles are subdivided into three main themes: antisocial and criminal behaviour; sexual Behaviour and intimate partner violence; and attachment, quality of life, and therapeutic alliance.

6.
BMC Prim Care ; 25(1): 107, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580901

ABSTRACT

BACKGROUND: Domestic violence (DV) is a serious and prevalent public health problem with devastating consequences for the victims and their families. Whilst the number of cases reported to the authorities has risen in recent years, many victims still chose not to present a complaint. In Portugal, to address this, DV became a public crime. As victims of DV present multiple health problems and frequently seek professional help, family doctors are in a privileged position to detect and report cases of DV to the authorities. However, little is known about what motivates these professionals to report or not the DV cases they encounter in their practice to the authorities. METHODS: We conducted semi-structured interviews with family doctors from all regional health administrations of continental Portugal. Interviews occurred between July 2020 and September 2022, were conducted in person or remotely, audio recorded, transcribed, and analysed using thematic analysis. Content analysis was conducted to assess the agreement or disagreement regarding mandatory reporting in each of the themes and subthemes. RESULTS: Fifty-four family doctors took part in this study (n = 39 women, n = 15 men). The main themes that arose from the analysis were: "Barriers related to the physician's activity," "Barriers related to the victim or aggressor," "Facilitators related to the physician's activity," "Facilitators related to the victim or aggressor." Although different barriers were described, most doctors agreed with the mandatory reporting of DV cases. CONCLUSIONS: Family doctors encounter multiple barriers and facilitators when considering reporting a DV case to the authorities. The results of this study can help develop new interventions to address the barriers described by the doctors, increasing their compliance with mandatory reporting, the protection of victims and the just persecution of the aggressor.


Subject(s)
Domestic Violence , Male , Humans , Female , Portugal/epidemiology , Domestic Violence/prevention & control , Qualitative Research , Physicians, Family , Interpersonal Relations
7.
Article in English | MEDLINE | ID: mdl-38541345

ABSTRACT

Over the last century, there has been a growing interest in researching pathological gambling, particularly in industrialized nations. Historically, gambling was widely perceived as morally questionable, condemned by religious groups. However, contemporary concerns have shifted towards the health repercussions of gambling disorders and broader societal impacts like increased crime and money laundering. Governments, aiming to mitigate social harm, often regulate or directly oversee gambling activities. The global surge in legal gambling has resulted in a substantial rise in its prevalence, popularity, and accessibility in the last two decades. This paper provides a comprehensive overview of global research on interventions for pathological gambling. Through a systematic search on platforms such as EBSCO, PubMed, and Web of Science, 13 relevant records were identified. The revised findings indicate a heightened occurrence of behavioral addictions, linking them to the early onset of gambling issues and their severe consequences. The research emphasizes the active role that clients play in the process of self-directed change and therapy. Therapists recognizing clients as both catalysts for change and potential obstacles can enhance their effectiveness. A common source of resistance arises when clients and therapists are in different stages of the change process, underlining the importance of therapists aligning with clients' readiness for change. Recognizing the urgent need for a better understanding of this problem in adolescents, this study emphasizes the necessity to tailor prevention and treatment plans based on gender and age-specific requirements.


Subject(s)
Gambling , Gambling/therapy , Gambling/psychology , Humans , Behavior, Addictive/therapy , Behavior, Addictive/psychology
8.
Behav Sci (Basel) ; 14(2)2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38392468

ABSTRACT

Childhood maltreatment is the strongest predictor of psychopathology and personality disorders across the lifespan and is strongly associated with a variety of psychological problems, namely, mood and anxiety disorders, behavioral and personality disorders, substance abuse, aggression, and self-harm. In this study, we aim to provide a comprehensive picture of the interplay between different traits of psychopathy and distinct dimensions of childhood maltreatment, emotion regulation, and aggression. Using a cross-sectional design, we employed correlational network analysis to explore the nomological network of psychopathy and provide a sample-based estimate of the population parameters reflecting the direction, strength, and patterns of relationships between variables. The sample consisted of 846 adults (71% females) who completed questionnaires measuring psychopathy, childhood maltreatment, emotion regulation, and aggression. The results highlight that disinhibition traits of psychopathy are the closest attributes of early experiences of abuse (but not neglect) in childhood and correlate with all dimensions of emotion regulation difficulties, being specifically associated with reactive aggression. Neglect was a unique attribute in the nomological network of meanness, with widespread correlations with emotion regulation difficulties but also an increased ability to engage in goal-directed behavior. Physical abuse was the only dimension of childhood adversity that was found to be intercorrelated with boldness and increased emotional regulation was found in this psychopathic trait. No significant associations were found between boldness, meanness, and aggression once shared variance with disinhibition was controlled. These results are discussed in terms of their implication for research and clinical practice.

9.
Plant Reprod ; 37(3): 341-353, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38294499

ABSTRACT

KEY MESSAGE: GPI anchor addition is important for JAGGER localization and in vivo function. Loss of correct GPI anchor addition in JAGGER, negatively affects its localization and function. In flowering plants, successful double fertilization requires the correct delivery of two sperm cells to the female gametophyte inside the ovule. The delivery of a single pair of sperm cells is achieved by the entrance of a single pollen tube into one female gametophyte. To prevent polyspermy, Arabidopsis ovules avoid the attraction of multiple pollen tubes to one ovule-polytubey block. In Arabidopsis jagger mutants, a significant number of ovules attract more than one pollen tube to an ovule due to an impairment in synergid degeneration. JAGGER encodes a putative arabinogalactan protein which is predicted to be anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Here, we show that JAGGER fused to citrine yellow fluorescent protein (JAGGER-cYFP) is functional and localizes mostly to the periphery of ovule integuments and transmitting tract cells. We further investigated the importance of GPI-anchor addition domains for JAGGER localization and function. Different JAGGER proteins with deletions in predicted ω-site regions and GPI attachment signal domain, expected to compromise the addition of the GPI anchor, led to disruption of JAGGER localization in the cell periphery. All JAGGER proteins with disrupted localization were also not able to rescue the polytubey phenotype, pointing to the importance of GPI-anchor addition to in vivo function of the JAGGER protein.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Glycosylphosphatidylinositols , Ovule , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis/physiology , Glycosylphosphatidylinositols/metabolism , Ovule/metabolism , Ovule/genetics , Ovule/physiology , Plant Proteins/metabolism , Plant Proteins/genetics , Mucoproteins/metabolism , Mucoproteins/genetics , Pollen Tube/metabolism , Pollen Tube/genetics
10.
Aggress Behav ; 50(1): e22116, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37769036

ABSTRACT

Previous studies have established relationships between the Dark Tetrad traits and sexual violence and its acceptance through myths about this type of violence. Sexual violence is positively associated with machismo, with sexist beliefs having been found to be linked with the Dark Tetrad and with the acceptance of sexual violence. Using a community sample comprising 362 adults between the ages of 18 and 70 (M = 35.6, SD = 14.3) and three self-report measures, this cross-sectional study aimed to explore the mediating role of sexual machismo in the relationship between each of the Dark Tetrad traits and the acceptance of sexual violence, both in the overall sample and by gender, as well as whether a significant variance in this acceptance is explained by the "dark" traits, sexual machismo, and gender. In the regression, sexual machismo (the male) gender, and only Machiavellianism were uniquely associated with the acceptance of sexual violence, and sexual machismo partially mediated the associations between the Dark Tetrad and the acceptance of sexual violence. These findings indicate that being male and higher in sexism is more closely linked with the acceptance of sexual violence than most Dark Tetrad traits. Moreover, the associations between the Dark Tetrad, sexual machismo, and the acceptance of sexual violence were stronger in men, consistent with the notion that these traits facilitate a "male" exploitive mating strategy, which likely also extends to victim-blaming and positive attitudes about sexual violence more broadly. Lastly, the results emphasize the pervasiveness of beliefs about male superiority over women and its relationship with victim-blaming even in women.


Subject(s)
Sex Offenses , Sexual Behavior , Adult , Humans , Male , Female , Adolescent , Young Adult , Middle Aged , Aged , Cross-Sectional Studies , Gender Identity , Machiavellianism
11.
Plant Physiol Biochem ; 206: 108270, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38091934

ABSTRACT

Abiotic stress combinations, such as high temperatures and soil/water salinization, severely threaten crop productivity worldwide. In this work, an integrative insight into the photosynthetic metabolism of tomato plants subjected to salt (100 mM NaCl) and/or heat (42 °C; 4 h/day) was performed. After three weeks, the stress combination led to more severe consequences on growth and photosynthetic pigments than the individual stresses. Regarding the photochemical efficiency, transcript accumulation and protein content of major actors (CP47 and D1) were depleted in all stressed plants, although the overall photochemical yield was not negatively affected under the co-exposure. Gas-exchange studies revealed to be mostly affected by salt (single or combined), which harshly compromised carbon assimilation. Additionally, transcript levels of stress-responsive genes (e.g., HsfA1 and NHX2) were differentially modulated by the single and combined treatments, suggesting the activation of stress-signature responses. Overall, by gathering an insightful overview of the main regulatory hub of photosynthesis, we show that the impacts on the carbon metabolism coming from the combination of heat and salinity, two major conditioners of crop yields, were not harsher than those of single stresses, indicating that the growth impairment might be attributed to a proficient distribution of resources towards defense mechanisms.


Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Hot Temperature , Salinity , Photosynthesis/physiology , Stress, Physiological , Sodium Chloride , Chlorophyll/metabolism
12.
Psychol Trauma ; 16(3): 462-469, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37053406

ABSTRACT

OBJECTIVE: This study aimed to analyze the experiences of victims of violence in intimate relationships (VIRs) who remain in, return to, or abandon the abusive relationship, as well as examine the type of violence suffered, the existing symptoms, and the motivation to change as explained by the Transtheoretical Model of Change. METHOD: The participants were 38 victims, three males and 35 females, who completed an online questionnaire comprising a section on sociodemographic data, and three instruments, the Self-Reporting Questionnaire 20 (SRQ-20), Marital Violence Inventory (MVI), and the University of Rhode Island Change Assessment (URICA). RESULTS: Data analysis has shown that psychological violence was the type of violence most frequently experienced followed by physical and verbal violence, the house of the victims was the local where the violence mostly took place, the help-seeking behaviors were mostly directed to the family and attempts to leave from the abusive relationship is related to the experience of family violence in childhood. Participants were all in the action stage of the change, but aggressor's expectation/promise to change, the existence of children and maintaining the family or marriage, as well as economic difficulties are the main factors that contribute to both remaining in, or returning to, the abusive relationship. CONCLUSION: We will reflect on the social, clinical, and legal implications for the future of research with victims of VIR. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Crime Victims , Domestic Violence , Intimate Partner Violence , Male , Female , Child , Humans , Motivation , Crime Victims/psychology , Sexual Partners , Surveys and Questionnaires
13.
Cell Surf ; 10: 100117, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38076635

ABSTRACT

Arabinogalactan-proteins (AGPs) are a family of hyperglycosylated hydroxyproline-rich cell wall proteins found throughout the plant kingdom. To date, eight Hydroxyproline-galactosyltransferases (Hyp-GALTs), named GALT2-GALT9, are known to catalyze the addition of the first galactose sugar to Hyp residues in AGP protein cores. The generation and characterization of galt23456789 octuple mutants using CRISPR-Cas9 gene editing technology, provided strong reverse genetic evidence that AG glycans are essential for normal vegetative and reproductive growth, as these mutants demonstrated stunted growth, greatly delayed flowering and significant defects in floral organ development and morphogenesis. Compared to the lower seed set of galt25789 quintuple mutants being more so contributed by female gametophytic defects, dramatically low seed-set of octuple mutants was largely due to impaired male reproductive function, specifically due to shorter filaments, delayed anther dehiscence, and large decreases in pollen quantity and viability. Octuple mutant pollen had severely distorted reticulate exine, tectum patterning and intine thickness. Reduced amounts of galactose and arabinose in overall lower amounts of ß-Yariv precipitated AGPs illustrated how biological functions of AGPs are affected by abnormal glycosylation.

14.
Article in English | MEDLINE | ID: mdl-37754645

ABSTRACT

OBJECTIVE: Conduct a systematic review concerning the literature that reflects whether the callous and unemotional traits present in childhood and/or adolescence are precursors in the development of female psychopathy in adulthood. MATERIALS AND METHODS: A systematic review involved consulting three databases-EBSCO, the Web of Science, and PubMed-for peer-reviewed and quantitative studies within the period 2000-2023. Nine articles with quality of three and above were included. RESULTS: The presence of callous and unemotional traits designates a group of youth that show characteristics associated with psychopathy, specifically when predicting a more severe and chronic pattern of antisocial behaviour. Children with high rates of callous and unemotional traits, who show symptoms of attention deficit hyperactivity disorder in combination with severe conduct problems, are most likely to show features associated with psychopathy. The multidimensional psychopathy construct is considered a better predictor of future and stable antisocial behaviour than the callous and unemotional traits alone model. CONCLUSIONS: According to the studies selected, the callous and unemotional traits in childhood seem to be precursors of female psychopathy in adulthood, but only because of the way they seem to enhance conduct problems, disruptive behaviour disorders, and, as a possible outcome, delinquency and antisocial traits, which may be precursors of future psychopathy.


Subject(s)
Antisocial Personality Disorder , Problem Behavior , Adolescent , Child , Female , Humans , Databases, Factual , Phenotype , PubMed
15.
Immunology ; 170(4): 510-526, 2023 12.
Article in English | MEDLINE | ID: mdl-37635289

ABSTRACT

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Animals , Mice , Leishmaniasis, Visceral/drug therapy , Adaptive Immunity , CD8-Positive T-Lymphocytes , Lipids , Mice, Inbred BALB C , Mammals
16.
bioRxiv ; 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37577527

ABSTRACT

Amyloid ß (Aß) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aß42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aß42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events. We show that human Aß42 peptides, but neither murine Aß42 nor human Aß17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75 and pan-cadherin. Moreover, Aß42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems. Our findings raise the possibility that pathological elevations in Aß42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aß toxicity in the context of γ-secretase-dependent homeostatic signaling.

17.
Sci Data ; 10(1): 432, 2023 07 06.
Article in English | MEDLINE | ID: mdl-37414779

ABSTRACT

The discovery of surrogate biomarkers reflecting neuronal dysfunction in neurodegenerative diseases (NDDs) remains an active area of research. To boost these efforts, we demonstrate the utility of publicly available datasets for probing the pathogenic relevance of candidate markers in NDDs. As a starting point, we introduce the readers to several open access resources, which contain gene expression profiles and proteomics datasets from patient studies in common NDDs, including proteomics analyses of cerebrospinal fluid (CSF). Then, we illustrate the method for curated gene expression analyses across select brain regions from four cohorts of Parkinson disease patients (and from one study in common NDDs), probing glutathione biogenesis, calcium signaling and autophagy. These data are complemented by findings of select markers in CSF-based studies in NDDs. Additionally, we enclose several annotated microarray studies, and summarize reports on CSF proteomics across the NDDs, which the readers can utilize for translational purposes. We anticipate that this "beginner's guide" will benefit the research community in NDDs, and would serve as a useful educational tool.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , Access to Information , Biomarkers , Gene Expression Profiling , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Parkinson Disease/genetics , Datasets as Topic
18.
BMC Health Serv Res ; 23(1): 571, 2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37268919

ABSTRACT

BACKGROUND: Domestic violence leads to multiple health problems in victims and their families. Family doctors are in a particularly privileged position to detect, follow up, refer and report cases of domestic violence. However, little is known about the perception of these physicians regarding their role in managing domestic violence cases. METHODS: We conducted semi-structured interviews with family doctors from all regional health administrations of continental Portugal. Interviews were audio recorded, transcribed, and analysed using thematic analysis. RESULTS: Fifty-four family doctors participated in this study (n = 39 women, n = 15 men). The themes and subthemes that emerged from the data analysis translated doctors' broad responsibilities when approaching victims and aggressors. These included: "Implement preventive measures", "Empower the victim leading them to recognize the violent situation", "Detect domestic violence cases", "Treat health problems related to violence", "Provide emotional support", "Refer victims to specialized services", "Register the episode on the victims and/or aggressor clinical records", "Incentivize the victim to report", "Report the case to the authorities", "Intervene with the aggressor", "Protect other individuals" and "Follow up the patient and the process". CONCLUSIONS: The results of this study provide an overview of the current practical approaches being adopted by physicians and may provide a base for developing new interventions to support physicians to manage cases of domestic violence.


Subject(s)
Domestic Violence , Female , Humans , Male , Aggression , Domestic Violence/prevention & control , Domestic Violence/psychology , Physicians, Family , Portugal , Qualitative Research
19.
Front Psychiatry ; 14: 935755, 2023.
Article in English | MEDLINE | ID: mdl-36873220

ABSTRACT

The association between substance use and crime is very common, but complex. Several countries have found strategies to face drug abuse and criminality that may exist associated to it, seeking to reduce overcrowded prisons and to promote the reductions of criminal recidivism and/or substance use. Through the guidelines of PRISMA, a systematic review was conducted with the aim to explore the different criminal reactions to individuals who use substances and are involved in the criminal justice system, namely the role of treatment and/or punishment in the reduction of crime recidivism and/or drug (ab)use. After gathering the following criteria of inclusion (individuals who use substances and are involved in the criminal justice system, between 18 and 65 years old, regardless of gender; consumers of licit/illicit psychoactive substances; without psychopathology not related with use/abuse of drugs; treatment programs; judicial interventions) the database found 155 articles between 1971 and 2022 from which 110 were selected for analysis (57 are from Academic Search Complete, 28 from PsycInfo, 10 from Academic Search Ultimate, seven from Sociology Source Ultimate, four from Business Source Complete, two from Criminal Justice Abstracts, and two from PsycArticles); additional records were included trough manual search. From these studies, 23 articles were included, as they answered the research question, and therefore, constitute the final sample of this revision. The results indicate treatment as an effective response of the criminal justice system in the reduction of criminal recidivism and/or drug use, addressing the criminogenic effect of reclusion/imprisonment. Therefore, interventions that privilege treatment should be chosen, although there are still gaps in terms of evaluation, monitoring and scientific publications regarding the effectiveness of treatment in this population.

20.
J Gambl Stud ; 39(2): 483-511, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36884150

ABSTRACT

Gambling disorder is a common and problematic behavioral disorder associated with depression, substance abuse, domestic violence, bankruptcy, and high suicide rates. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), pathological gambling was renamed "gambling disorder" and moved to the Substance-Related and Addiction Disorders chapter to acknowledge that research suggests that pathological gambling and alcohol and drug addiction are related. Therefore, this paper provides a systematic review of risk factors for gambling disorder. Systematic searches of EBSCO, PubMed, and Web of Science identified 33 records that met study inclusion criteria. A revised study acknowledges as risk factors for developing/maintaining a gambling disorder being a single young male, or married for less than 5 years, living alone, having a poor education, and struggling financially.


Subject(s)
Behavior, Addictive , Gambling , Substance-Related Disorders , Humans , Male , Gambling/psychology , Comorbidity , Substance-Related Disorders/epidemiology , Behavior, Addictive/epidemiology , Behavior, Addictive/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Risk Factors
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