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PURPOSE: Intimate partner violence is a global public health problem that mainly affects women rather than men. It has been associated with negative physical and mental health outcomes, including experiences of revictimization. This systematic review describes the risk and protective factors associated with revictimization in female victims of intimate partner violence. METHODS: We searched for articles published between 1995 and 2024 in the Scopus, Web of Science, and PsycINFO databases. In total, 925 studies that met the inclusion criteria were reviewed, of which 38 were evaluated as eligible, and 12 were finally included in the review. RESULTS: Among the risk factors were mental health problems, some demographic characteristics of the victims, previous experiences of violence, and coping and attachment styles. Economic independence, empowerment, and restraining orders were protective factors. CONCLUSIONS: Based on the results, we present some practical implications for health and public policy as well as recommendations for directing future research into revictimization.
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Sierra Nevada (southern Iberian Peninsula) harbours a great biodiversity and the studies on some aquatic insect groups have been and continue to be numerous there. This database brings together information on Plecoptera, Trichoptera and Coleoptera inhabiting running waters of this mountain system above 800 m of altitude. It includes data on the number, life stage and sex of individuals as well as the available information on abiotic characteristics of their habitats. The dataset is composed of 1,718 sampling events carried out between 1901 and 2022 in approximately 60 different water bodies, 15,347 occurrences pertaining to more than 203,000 individuals, and 10,173 records of associated measurements (23 physico-chemical parameters). The dataset is the result of a comprehensive review of scientific literature and of integrating data from recent research projects and the Sierra Nevada Global-Change Observatory's long-term monitoring data. This information is valuable for those studying past distributions and abundances of the species in the dataset, for building predictive models or just studying temporal trends in the current context of climate change.
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Escarabajos , Ecosistema , Animales , España , Insectos , Biodiversidad , Cambio ClimáticoRESUMEN
Chagas disease (CD), caused by Trypanosoma cruzi and endemic in Latin America, has become an emergent health problem in non-endemic countries due to human migration. The United States (US) is the non-Latin American country with the highest CD burden and cannot be considered as non-endemic, since triatomine vectors and reservoir animals have been found. Populations of T. cruzi are divided into genetic subdivisions, which are known as discrete typing units (DTUs): TcI to TcVI and TcBat. Autochthonous human T. cruzi infection in the US is sporadic, but it may change due to environmental factors affecting the geographic distribution of triatomines. We aimed to perform a literature review of the genetic diversity of T. cruzi in triatomine vectors and mammalian hosts, including human cases, in the US. The 34 analyzed studies revealed the presence of T. cruzi in 18 states, which was mainly concentrated in Texas, Louisiana and New Mexico. TcI and TcIV were the principal DTUs identified, being TcI the most genotyped (42.4%; 917/2164). This study represents a first attempt to compile the molecular epidemiology of T. cruzi in the US, which is fundamental for predicting the progression of the infection in the country and could be of great help in its future management.
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BACKGROUND: some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible. AIMS: to assess the management of antiTNF-IP in IBD, and its impact in both diseases. METHODS: patients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks. RESULTS: 234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse. CONCLUSION: skin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies.
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BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.
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Toxoplasma gondii is a ubiquitous zoonotic protozoan parasite that infects a wide variety range of warm-blooded animals. This study describes the epidemiological scenario of T. gondii in an indigenous community that relies on subsistence hunting in a well-conserved and isolated area of the Peruvian Amazon. The high seropositivity against T. gondii in humans (83.3% IgG and 6.1% IgM), wild mammals (30.45%, 17 species), peri-domestic rodents (10.0% Rattus sp.), and domestic animals (94.1% dogs and 100% cats) indicates the existence of a sylvatic cycle in the community under study. Individual age was found to be positively associated with IgG detection against T. gondii but not with IgM. It is estimated that each family consumed 5.67 infected animals per year with terrestrial species having higher infective rates than arboreal species. The main risk factors included improper handling and cooking of wild meat, poor hygiene practices, and feeding uncooked offal to domestic animals. This scenario results in a continuous process of infection and reinfection within the indigenous community with cats, dogs, and peri-domestic animals becoming infected through the ingestion of infected raw viscera. Our results emphasize the need to promote safe food handling practices and disposal of waste materials from hunted animals in such communities.
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Leishmaniases are zoonotic diseases caused by protozoa of the genus Leishmania. In Bolivia, leishmaniasis occurs mainly in the cutaneous form (CL) followed by the mucosal or mucocutaneous form (ML or MCL), grouped as tegumentary leishmaniosis (TL), while cases of visceral leishmaniasis (VL) are rare. The cases of TL are routinely diagnosed by parasitological methods: Direct Parasitological Exam (DPE) and axenic culture, the latter being performed only by specialized laboratories. The aim of the present study was to optimize the parasitological diagnosis of TL in Bolivia, using two sampling methods. Samples from 117 patients with suspected TL, obtained by aspiration (n = 121) and scraping (n = 121) of the edge of the lesion were tested by: direct parasitological exam, culture in TSTB medium, and miniculture and microculture in Schneider's medium. A positive laboratory result by any of the four techniques evaluated using either of the two sampling methods was considered the gold standard. Of the 117 suspected patients included, TL was confirmed in 96 (82 %), corresponding 79 of the confirmed cases (82.3 %) to CL and 16 (16.7 %) to ML. Parasitological techniques specificity was 100 % and their analytical sensitivity was greater with scraping samples in TSTB culture (98 %). Scraping samples in TSTB and miniculture correlated well with the reference (Cohen's kappa coefficient=0.88) and showed good reliability (Cronbach's alpha coefficient ≥0.91). Microculture provided positive results earlier than the other culture methods (mean day 4.5). By day 14, 98 % of positive cultures had been detected. Scraping sampling and miniculture were associated with higher culture contamination (6 % and 17 %, respectively). Bacterial contamination predominated, regardless of the sampling and culture method, while filamentous fungi and mixed contamination were more frequently observed in cultures from scraping samples. In conclusion: (i) scraping samples proved more suitable for the diagnosis of TL as they increased analytical sensitivity, are less traumatic for the patient and are safer for laboratory personnel than aspirates; (ii) culture, mainly in TSBT medium, should be used for the diagnosis of TL due to its high sensitivity (doubling the number of cases diagnosed by DPE) and its low cost compared to other culture media.
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Leishmania , Leishmaniasis Cutánea , Leishmaniasis Visceral , Leishmaniasis , Humanos , Bolivia , Reproducibilidad de los Resultados , Leishmaniasis/diagnóstico , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/parasitología , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitologíaRESUMEN
El artículo aborda el trabajo remunerado en la vejez como fenómeno complejo, para enriquecer la discusión de la Terapia Ocupacional y los estudios sobre la ocupación acerca del tema. Se detiene en la relevancia del trabajo como ocupación y reflexiona sobre las desigualdades que se construyen en torno al trabajo de las personas mayores. Al proponer un diálogo interdisciplinario con la perspectiva del curso de la vida, destaca la relación entre las trayectorias laborales y los contextos históricos en los que estas se insertan. El texto resalta la importancia del tema para la Terapia Ocupacional, la necesidad de comprender el trabajo en la vejez y de cuestionar la mirada individualizadora que tienden a usar los estudios disciplinares sobre el asunto. Esto implica dinamizar las teorías clásicas de la Terapia Ocupacional, de manera que trasciendan los enfoques clínicos centrados en la prevención y el tratamiento de las enfermedades de las personas mayores, y se interroguen por los sistemas políticos, económicos y sociales en los que se enmarca el trabajo de esta población.
The article addresses work in old age as a complex phenomenon, looking to enrich the conversation about this subject in Occupational Therapy and studies on occupation. It focuses on the importance of work as an occupation and reflects on the inequalities that are constructed around work in older people. Proposing an interdisciplinary dialogue with the life course perspective, the relationship between work trajectories and the historical contexts in which these are embedded are highlighted. The text emphasizes the importance of the topic for Occupational Therapy, the need to understand work in old age, and to question the individualizing gaze that the disciplinary studies tend to use. This implies revitalizing the classic theories of Occupational Therapy so that they transcend the clinical approaches centered on the prevention and treatment of diseases in elderly people and question themselves about the political, economic and social systems in which the work of this population is framed.
O artigo aborda o trabalho remunerado na velhice como um fenômeno complexo, visando enriquecer a discussão sobre o assunto na Terapia Ocupacional e nos estudos sobre ocupação. Explora-se a relevância do trabalho como ocupação e reflete-se sobre as desigualdades no trabalho para as pessoas idosas. No diálogo interdisciplinar com a perspectiva do curso de vida proposto, destaca-se a relação entre as trajetórias laborais e os contextos históricos nos quais elas estão inseridas. O texto destaca a importância do tema para a Terapia Ocupacional, realçando a necessidade de compreender o trabalho na velhice e de questionar a abordagem individualizadora do assunto, comum nos estudos disciplinares. Isso leva à revitalização das teorias clássicas da Terapia Ocupacional, transcendendo os enfoques clínicos centrados na prevenção e tratamento de doenças nas pessoas idosas, bem como ao questionamento dos sistemas políticos, econômicos e sociais, nos quais o trabalho dessa população está inserido.
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EnvejecimientoRESUMEN
(1) Background: Spirituality is a factor that plays a role in decisions related to health and illness. When a woman becomes a mother, she undergoes physical, psychological, and social changes for which healthcare professionals must provide the necessary care. However, women may feel misunderstood and stigmatized when they carry out their religious practices and express their spirituality related to motherhood. The aim of this study was to describe the experiences of women with Muslim and Christian religious ideologies on the influence of spirituality and religious beliefs in motherhood and child-rearing. (2) Methods: A descriptive phenomenological qualitative study with two groups of women of Islamic and Christian ideology, respectively. Three focus groups and in-depth interviews were conducted, recorded, transcribed, and analyzed with ATLAS.ti 7.0. An inductive analysis was carried out according to the Moustakas model. (3) Results: Three themes were identified: religious and cultural aspects that determine child-rearing, the influence of spirituality and family on the mother's role, and the support received from healthcare personnel. (4) Conclusions: Spirituality and religious beliefs are manifested during motherhood and child-rearing in the form of infant feeding, the need for their protection, or the need for support from mothers. Healthcare personnel must be able to offer culturally competent and spiritually respectful care. Patients should not be judged based on their spirituality.
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Nerve injuries cause permanent neurological disability due to limited axonal regeneration. Injury-dependent and -independent mechanisms have provided important insight into neuronal regeneration, however, common denominators underpinning regeneration remain elusive. A comparative analysis of transcriptomic datasets associated with neuronal regenerative ability revealed circadian rhythms as the most significantly enriched pathway. Subsequently, we demonstrated that sensory neurons possess an endogenous clock and that their regenerative ability displays diurnal oscillations in a murine model of sciatic nerve injury. Consistently, transcriptomic analysis showed a time-of-day-dependent enrichment for processes associated with axonal regeneration and the circadian clock. Conditional deletion experiments demonstrated that Bmal1 is required for neuronal intrinsic circadian regeneration and target re-innervation. Lastly, lithium enhanced nerve regeneration in wild-type but not in clock-deficient mice. Together, these findings demonstrate that the molecular clock fine-tunes the regenerative ability of sensory neurons and propose compounds affecting clock pathways as a novel approach to nerve repair.
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Relojes Circadianos , Ratones , Animales , Relojes Circadianos/genética , Ritmo Circadiano , Regeneración Nerviosa/fisiología , Células Receptoras Sensoriales , Factores de Transcripción ARNTL/genéticaRESUMEN
Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models. Drugs targeting COPI have poor pharmacological properties, but we find that N-myristoyltransferase inhibitors (NMTi) phenocopy COPI inhibition and are potent senolytics. NMTi selectively eliminated senescent cells and improved outcomes in models of cancer and non-alcoholic steatohepatitis. Our results suggest that senescent cells rely on a hyperactive secretory apparatus and that inhibiting trafficking kills senescent cells with the potential to treat various senescence-associated diseases.
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Neoplasias , Senoterapéuticos , Ratones , Animales , Aparato de Golgi/metabolismo , Senescencia Celular , Neoplasias/metabolismo , FibrosisRESUMEN
BACKGROUND: Hypoxic burden (HB) has emerged as a strong predictor of cardiovascular risk in obstructive sleep apnoea (OSA). We aimed to assess the potential of HB to predict the cardiovascular benefit of treating OSA with continuous positive airway pressure (CPAP). METHODS: This was a post hoc analysis of the ISAACC trial (ClinicalTrials.gov: NCT01335087) including non-sleepy patients with acute coronary syndrome (ACS) diagnosed with OSA (apnoea-hypopnoea index ≥15â events·h-1) by respiratory polygraphy. Patients were randomised to CPAP or usual care and followed for a minimum of 1â year. HB was calculated as the total area under all automatically identified desaturations divided by total sleep time. Patients were categorised as having high or low baseline HB according to the median value (73.1%min·h-1). Multivariable Cox regression models were used to assess whether the effect of CPAP on the incidence of cardiovascular outcomes was dependent on the baseline HB level. RESULTS: The population (362 patients assigned to CPAP and 365 patients assigned to usual care) was middle-aged (mean age 59.7â years), overweight/obese and mostly male (84.5%). A significant interaction was found between the treatment arm and the HB categories. In the high HB group, CPAP treatment was associated with a significant reduction in the incidence of cardiovascular events (HR 0.57, 95% CI 0.34-0.96). In the low HB group, CPAP-treated patients exhibited a trend toward a higher risk of cardiovascular outcomes than those receiving usual care (HR 1.33, 95% CI 0.79-2.25). The differential effect of the treatment depending on the baseline HB level followed a dose-response relationship. CONCLUSION: In non-sleepy ACS patients with OSA, high HB levels were associated with a long-term protective effect of CPAP on cardiovascular prognosis.
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Síndrome Coronario Agudo , Apnea Obstructiva del Sueño , Persona de Mediana Edad , Humanos , Masculino , Femenino , Presión de las Vías Aéreas Positiva Contínua , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , Modelos de Riesgos Proporcionales , Síndrome Coronario Agudo/complicaciones , Hipoxia/complicacionesRESUMEN
The one-pot reaction of a chiral aldehyde, p-methoxyaniline or p-fluoroaniline, and triethylborane produces the corresponding alkylated chiral amine with high yields and diastereoisomeric ratios. Stereocontrol is induced by the presence of a heteroatom in the α-position to the aldehyde. In the case of alkylation of imines derived from chiral aliphatic amines, good yields and moderate to high diastereoselectivity are obtained: yields are significantly better when the preformed imine is used in the reaction with triethyl borane, and diastereoselectivity of the reactions largely depends on the structure of the chiral aliphatic amine. The methodology is successfully applied to the synthesis of romneine, a natural benzylisoquinoline.
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Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a proteomic technique with proven efficiency in the identification of microorganisms, such as bacteria, fungi, and parasites. The present study aimed to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia using hsp70 gene sequencing as a reference technique. 55 Leishmania strains that were isolated from patients with tegumentary leishmaniasis were analyzed. MALDI-TOF MS identified two species of the L. braziliensis complex (L. braziliensis, n = 26; L. braziliensis outlier, n = 18), one species of the L. guyanensis complex (L. guyanensis, n = 1), one species of the L. lainsoni complex (L. lainsoni, n = 2), and two species of the L. mexicana complex (L. amazonensis, n = 5; and L. garnhami, n = 3). All of the strains were correctly identified at the subgenus, genus, and complex level, but 10 of them (18%) were misidentified as other species within the same complex by the hsp70 gene sequencing, with 7 of these corresponding to possible hybrids. Thus, one L. braziliensis corresponded to L. peruviana, two L. braziliensis corresponded to L. braziliensis/L. peruviana possible hybrids, two L. amazonensis corresponded to L. mexicana, and three L. garnhami and two L. amazonensis corresponded to L. mexicana/L. amazonensis possible hybrids. Accordingly, MALDI-TOF MS could be used as an alternative to molecular techniques for the identification of Leishmania spp., as it is low cost, simple to apply, and able to quickly produce results. In Bolivia, its application would allow for the improvement of the management of patient follow-ups, the updating of the epidemiological data of the Leishmania species, and a contribution to the control of tegumentary leishmaniasis. IMPORTANCE The objective of the study was to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia, in comparison with the sequencing of the hsp70 gene. In our study, all of the isolates could be identified, and no misidentifications were observed at the complex level. Although the equipment implies a high initial investment in our context, MALDI-TOF MS can be used in different areas of microbiology and significantly reduces the cost of testing. Once the parasite culture is obtained, the technique quickly yields information by accessing a free database that is available online. This would allow for the improvement of the management of patients and follow-ups, the updating of the epidemiological data of the species, and a contribution to the control of tegumentary leishmaniasis in Bolivia. Likewise, it can be used to determine a specific treatment to be given, according to the causal species of Leishmania, when there are protocols in this regard in the area.
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Leishmania , Leishmaniasis , Humanos , Bolivia/epidemiología , Proteómica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Rayos LáserRESUMEN
BACKGROUND: Childhood cancer is a "stressful experience" for parents in their role as caregivers. The aim of this study is to analyze the needs of a group of parents who have children diagnosed with cancer. The assessment looks at all areas of their daily life using a qualitative content analysis approach. METHODS: This study uses open questions designed to investigate the main problems faced by the parents of children with cancer. All the answers were analyzed using MAXQDA 20 software. The study was conducted according to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: The content analysis of the answers from 13 mothers and 7 fathers is presented. The main themes as priority areas of need were: "informal social support", "coping", "stressors/imbalances" and "health problems". Dissatisfaction with the support provided from the informal network was detected. Although the participants expressed active coping, they also exhibited helplessness, as well as concerns regarding possible sequelae and the impact of this situation on the family's economic/work context. Conciliation problems were a source of stress. All this is consistent with the participants suffering from a variety of health issues. CONCLUSIONS: the results show the effect of childhood cancer on different aspects of family life. They provide essential information for designing psychosocial interventions.
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RESUMEN Objetivo: Se presentan los resultados de un estudio con enfoque psicosocial cuyo objetivo es investigar la autonomía de las personas con sufrimiento psíquico atendidas en centros de atención psicosocial desde la perspectiva del trabajo, a partir de las percepciones de los usuarios y sus familias, usando el marco de rehabilitación psicosocial y la teoría de la vida cotidiana de Agnes Heller. Métodos: Se seleccionaron 4 centros de atención psicosocial y colaboraron con la investi gación 40 personas mediante entrevistas semiestructuradas, analizadas con la técnica del discurso del sujeto colectivo. Resultados: Aunque los usuarios deseaban tener un trabajo, no esbozaban iniciativa, ya que existen impedimentos para llevar a cabo actividades laborales por los efectos secunda rios de la medicación y los impedimentos planteados por terceros ante la preocupación por la pérdida de beneficios sociales. El prejuicio fue visto como un mecanismo que inter fiere negativamente con las relaciones sociales y el empoderamiento para la autonomía. Las expectativas de reanudar los estudios y la participación en actividades voluntarias, especialmente religiosas, fueron frecuentes en el discurso de los usuarios. Conclusiones: Existe una necesidad urgente de expandir los espacios territoriales para que los usuarios de los servicios de salud mental puedan ser protagonistas de su propia autonomía y, así, realizar sus ocupaciones en el área de la productividad con mayor apropiación.
ABSTRACT Objective: To present the results of a study with a psychosocial approach that aimed to examine the autonomy of people with mental suffering cared for at psychosocial care centres from the perspective of work, based on the perceptions of the users and their families, and using the psychosocial rehabilitation framework and Agnes Heller's theory of everyday life. Methods: Four psychosocial care centres were selected, and 40 people collaborated with the research through semi-structured interviews analysed with the Collective Subject Discourse technique. Results: Although the users wanted to have a job, they showed no initiative, as there are impediments to carrying out work activities due to the side effects of the medication and the obstacles posed by third parties concerned about the loss of social benefits. Prejudice was seen as a mechanism that negatively interferes with social relations and empowerment for autonomy. Expectations of resuming studies and participation in voluntary activities, especially religious ones, were frequent in the users' discourse. Conclusions: There is an urgent need to expand territorial spaces so that the users of mental health services can be protagonists of their own autonomy and carry out their occupations in the area of productivity with greater ownership.
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OBJECTIVE: To present the results of a study with a psychosocial approach that aimed to examine the autonomy of people with mental suffering cared for at psychosocial care centres from the perspective of work, based on the perceptions of the users and their families, and using the psychosocial rehabilitation framework and Agnes Heller's theory of everyday life. METHODS: Four psychosocial care centres were selected, and 40 people collaborated with the research through semi-structured interviews analysed with the Collective Subject Discourse technique. RESULTS: Although the users wanted to have a job, they showed no initiative, as there are impediments to carrying out work activities due to the side effects of the medication and the obstacles posed by third parties concerned about the loss of social benefits. Prejudice was seen as a mechanism that negatively interferes with social relations and empowerment for autonomy. Expectations of resuming studies and participation in voluntary activities, especially religious ones, were frequent in the users' discourse. CONCLUSIONS: There is an urgent need to expand territorial spaces so that the users of mental health services can be protagonists of their own autonomy and carry out their occupations in the area of productivity with greater ownership.
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Servicios de Salud Mental , Humanos , AnsiedadRESUMEN
Trypanosoma cruzi infection has expanded globally through human migration. In Spain, the mother-to-child route is the mode of transmission contributing to autochthonous Chagas disease (CD); however, most people acquired the infection in their country of origin and were diagnosed in the chronic phase (imported chronic CD). In this context, we assessed the quantitative potential of the Loopamp Trypanosoma cruzi detection kit (Sat-TcLAMP) based on satellite DNA (Sat-DNA) to determine parasitemia levels compared to those detected by real-time quantitative PCRs (qPCRs) targeting Sat-DNA (Sat-qPCR) and kinetoplast DNA minicircles (kDNA-qPCR). This study included 173 specimens from 39 autochthonous congenital and 116 imported chronic CD cases diagnosed in Spain. kDNA-qPCR showed higher sensitivity than Sat-qPCR and Sat-TcLAMP. According to all quantitative approaches, parasitemia levels were significantly higher in congenital infection than in chronic CD (1 × 10-1 to 5 × 105 versus >1 × 10-1 to 6 × 103 parasite equivalents/mL, respectively [P < 0.001]). Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR results were equivalent at high levels of parasitemia (P = 0.381). Discrepancies were significant for low levels of parasitemia and older individuals. Differences between Sat-TcLAMP and Sat-qPCR were not qualitatively significant, but estimations of parasitemia using Sat-TcLAMP were closer to those by kDNA-qPCR. Parasitemia changes were assessed in 6 individual cases in follow-up, in which trends showed similar patterns by all quantitative approaches. At high levels of parasitemia, Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR worked similarly, but significant differences were found for the low levels characteristic of late chronic CD. A suitable harmonization strategy needs to be developed for low-level parasitemia detection using Sat-DNA- and kDNA-based tests. IMPORTANCE Currently, molecular equipment has been introduced into many health care centers, even in low-income countries. PCR, qPCR, and loop-mediated isothermal amplification (LAMP) are becoming more accessible for the diagnosis of neglected infectious diseases. Chagas disease (CD) is spreading worldwide, and in countries where the disease is not endemic, such as Spain, the parasite Trypanosoma cruzi is transmitted from mother to child (congenital CD). Here, we explore why LAMP, aimed at detecting T. cruzi parasite DNA, is a reliable option for the diagnosis of congenital CD and the early detection of reactivation in chronic infection. When the parasite load is high, LAMP is equivalent to any qPCR. In addition, the estimations of T. cruzi parasitemia in patients living in Spain, a country where the disease is not endemic, resemble natural evolution in areas of endemicity. If molecular tests are introduced into the diagnostic algorithm for congenital infection, early diagnosis and timely treatment would be accomplished, so the interruption of vertical transmission can be an achievable goal.
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Enfermedad de Chagas , Trypanosoma cruzi , Femenino , Humanos , ADN de Cinetoplasto/genética , Parasitemia/diagnóstico , Parasitemia/epidemiología , Parasitemia/genética , ADN Satélite , España/epidemiología , ADN Protozoario/genética , ADN Protozoario/análisis , Transmisión Vertical de Enfermedad Infecciosa , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/genética , Trypanosoma cruzi/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
Objetivos: Los objetivos son: identificar variables de eficacia empleadas en fármacos para enfermedades de depósito lisosomal (EDL), evaluar la calidad de esta evidencia, y conocer la efectividad y seguridad de estos tratamientos.Material y métodosEstudio observacional retrospectivo que incluyó pacientes con EDL tratados con terapia de sustitución enzimática (TSE) o de reducción de sustrato (TRS). Se revisaron los ensayos clínicos (EC) publicados y guías de tratamiento de EDL para seleccionar las variables de eficacia. Se obtuvieron los datos para medirlas (y efectos adversos) de la historia clínica.ResultadosNo se encontraron EC en los que se evalúe la eficacia con variables finales, todas fueron subrogadas. Se incluyeron 22 pacientes: 8 con enfermedad de Gaucher, 6 con enfermedad de Niemann-Pick tipo C, 2 con enfermedad de Hunter, uno con enfermedad de Morquio-A y 5 con enfermedad de Pompe. Ocho pacientes respondieron a TSE y uno a TRS. La TSE no se relacionó con efectos adversos. Miglustat produjo problemas de tolerancia que requirieron cambio de tratamiento en un paciente.ConclusionesLa efectividad fue variable según la enfermedad. Respecto a seguridad, se asociaron reacciones adversas a TRS manejables con ajustes posológicos. (AU)
Objectives: Identify the efficacy variables collected in the literature for therapies used in lysosomal storage diseases (LDS), evaluate the quality of this evidence, and know the effectiveness and safety of these treatments.Material and methodsRetrospective observational study that included patients with LDS treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Published clinical trials (CT) and LDS treatment guidelines were reviewed to select efficacy variables. Data to measure them (and adverse effects) were obtained from the medical history.ResultsNo CTs have been found in which efficacy is evaluated with final variables, all have been surrogated. Twenty-two patients were included: eight with Gaucher disease, six with NiemannPickC disease, two with Hunter disease, one with Morquio-A disease, and five with Pompe disease. Eight patients have responded to ERT and one to SRT with eliglustat. ERT has not been associated with adverse effects. Miglustat has produced tolerance problems, requiring a change in a patient.ConclusionsThe effectiveness was variable according to the pathology. Regarding safety, manageable adverse reactions to SRT were associated with dosage adjustments. (AU)
Asunto(s)
Humanos , Terapia de Reemplazo Enzimático , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad del Almacenamiento de Glucógeno Tipo II , Lisosomas , Estudios RetrospectivosRESUMEN
OBJECTIVES: Identify the efficacy variables collected in the literature for therapies used in lysosomal storage diseases (LDS), evaluate the quality of this evidence, and know the effectiveness and safety of these treatments. MATERIAL AND METHODS: Retrospective observational study that included patients with LDS treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Published clinical trials (CT) and LDS treatment guidelines were reviewed to select efficacy variables. Data to measure them (and adverse effects) were obtained from the medical history. RESULTS: No CTs have been found in which efficacy is evaluated with final variables, all have been surrogated. Twenty-two patients were included: eight with Gaucher disease, six with Niemann-PickC disease, two with Hunter disease, one with Morquio-A disease, and five with Pompe disease. Eight patients have responded to ERT and one to SRT with eliglustat. ERT has not been associated with adverse effects. Miglustat has produced tolerance problems, requiring a change in a patient. CONCLUSIONS: The effectiveness was variable according to the pathology. Regarding safety, manageable adverse reactions to SRT were associated with dosage adjustments.