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Restrictive dermopathy (RD) is a lethal condition caused by biallelic loss-of-function mutations in ZMPSTE24, whereas mutations preserving residual enzymatic activity of the ZMPSTE24 protein lead to the milder mandibuloacral dysplasia with type B lipodystrophy (MADB) phenotype. Remarkably, we identified a homozygous, presumably loss-of-function mutation in ZMPSTE24 [c.28_29insA, p.(Leu10Tyrfs*37)] in two consanguineous Pakistani families segregating MADB. To clarify how lethal consequences are prevented in affected individuals, functional analysis was performed. Expression experiments supported utilization of two alternative translation initiation sites, preventing complete loss of protein function consistent with the relatively mild phenotypic outcome in affected patients. One of these alternative start codons is newly formed at the insertion site. Our findings indicate that the creation of new potential start codons through N-terminal mutations in other disease-associated genes should generally be taken into consideration in the variant interpretation process.
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Mutação da Fase de Leitura , Metaloendopeptidases , Humanos , Mutação da Fase de Leitura/genética , Códon de Iniciação/genética , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Mutação , Códon , Proteínas de Membrana/genéticaRESUMO
INTRODUCTION: Adolescence is regarded as a formative period for political development. One important developmental context is media. Negatively perceived political media content can foster populistic attitudes, which in turn decreases support of political institutions, such as the European Union (EU). As media valence effects are short-lived, this study examined intra-individual associations of media valence with European identity commitment and affect towards the EU, as well as indirect effects via populistic attitudes across 10 days. METHODS: We implemented a 10-day daily diary study with 371 adolescents from Germany (January to February 2022). Adolescents were on average 14.24 years old (SD = 0.55) and 60.4% were female. We estimated the hypothesized associations using multilevel structural equation models and dynamic structural equation models. RESULTS: We found significant associations between populistic attitudes and negative affect towards the EU on the same day and the next day. The lagged effect became nonsignificant, when including both same day and lagged effects into one model. Populistic attitudes were not significantly associated with European identity commitment within days or across days. Negative media content was associated with higher populistic attitudes on the same day and indirectly associated with negative affect towards the EU (b = -.01, 95% credible interval [-0.010, -0.004]). CONCLUSION: Negatively perceived political media content was associated with higher populistic attitudes and more negative affect towards the EU concurrently. Our results imply that media plays an important role for adolescents' development.
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Comportamento do Adolescente , Atitude , Humanos , Adolescente , Feminino , Masculino , União Europeia , Desenvolvimento do Adolescente , AlemanhaRESUMO
AIM OF THE STUDY: Involving potential end users in the development process of digital interventions makes it possible to ensure that these programs meet the needs, requirements and expectations of future users, which in turn has a positive impact on acceptance and adherence. This contribution presents a participatory development approach for the patient-centered design of the psycho-oncological online self-help epos, which aims to provide support in coping with cancer. METHODS: Patients were involved in the developmental process at two points. At an early stage of development, semi-standardized in-depth interviews were conducted with patients diagnosed by different types of cancer (N=10) and were qualitatively evaluated with regard to their view of (1) the cancer disease and (2) the design of an online self-help on the content, structural and design levels. At a later stage, a prototype of the online self-help was evaluated in a pilot phase. RESULTS: The qualitative analysis of the interviews with a total of N=742 codings resulted in five main content categories (changes in everyday life and future experience, changes in social relationships, processing mechanisms, loss of control, difficult emotions), which provide information about the central challenges and burdens of people with cancer. Participants showed particularly strong emotions around interpersonal concerns, so in addition to the emotion-based focus, the online self-help also included a focus on social relationships. Structural and design implications for development related primarily to clarity and user-friendliness. The pilot phase allowed evaluating whether the requirements for the online self-help that were described by cancer patients at an early stage of development were met. CONCLUSION: Patient participation in the development process of the digital online self-help epos provided information for the design at various levels. Involving potential end users in several development phases can ensure that the requirements and suggestions have been sufficiently considered not only from the perspective of the developers, but also from the perspective of future users. These findings confirm the importance of a patient-centered approach in the development of digital offerings.
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Comportamentos Relacionados com a Saúde , Neoplasias , Adaptação Psicológica , Emoções , Alemanha , HumanosRESUMO
Renal ischemia reperfusion injury (IRI) adversely affects clinical outcomes following kidney transplantation. Understanding the cellular mechanisms and the changes in gene/protein expression following IRI may help to improve these outcomes. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein, is increased in the first week following kidney transplantation. We evaluated the casual relationship of elevated sFlt-1 levels with renal microvascular dysfunction following IRI in a longitudinal study of 93 kidney transplant recipients and in several animal models. Transplant recipients with higher sFlt-1 levels had higher odds of delayed graft function, graft rejection, impaired graft function, and death. In a subgroup of 25 participants who underwent kidney biopsy within 4 months of kidney transplantation, peritubular capillary area was lower in those with elevated serum sFtl-1 levels. The administration of recombinant sFlt-1 into rodents resulted in significant structural and functional changes of the renal microvasculature, including reduced peritubular capillary density and intracapillary blood volume, and lead to increased expression of inflammatory genes and increased fibrosis. In a murine model of IRI, the kidney was a site of sFlt-1 production, and systemic neutralization of sFlt-1 preserved peritubular capillary density and alleviated renal fibrosis. Our data indicate that high sFlt-1 levels after IRI play an important role in the pathogenesis of microvascular dysfunction, thereby contributing to adverse clinical outcomes following kidney transplantation.
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Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Traumatismo por Reperfusão/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Animais , Biópsia , Capilares/patologia , Linhagem Celular , Estudos de Coortes , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/mortalidade , Modelos Animais de Doenças , Feminino , Fibrose , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Rim/irrigação sanguínea , Rim/patologia , Falência Renal Crônica/mortalidade , Estudos Longitudinais , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/mortalidade , Resultado do Tratamento , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/administração & dosagemRESUMO
In predominately immigrant neighborhoods, the nuances of immigrant life in the ethnic enclave have important, yet underappreciated impact on community health. The complexities of immigrant experiences are essential to unpacking and addressing the impact of acculturative processes on observed racial, ethnic, and class-based health disparities in the United States. These insights because they are largely unexplored are best captured qualitatively through academic-community research partnership. We established the participatory mixed method Little Village participatory community health assessment (CHA) to explore community health in an ethnic enclave. In this paper, we share findings from our qualitative component exploring: how do Residents in a Predominately Immigrant Neighborhood Perceive Community Health Needs and Assets in Little Village. Three major themes emerged: rich, health promoting community assets inherent in the ethnic enclave; cumulative chronic stress impacting the mental health of families and intra-familial strain; and, work and occupation as important but underappreciated community health determinants in an immigrant neighborhood. These nuanced findings enhanced our community health assessment and contributed to the development of two additional tailored CHA methods, a community member-administered Community Health Survey, and an oral history component that provided deeper insight on the community's health needs and assets, and a focus for action on work as a social determinant of health at the community level. Conducting trusted community-driven health assessments that are adaptive and flexible to capture authentic needs and assets are critical, given health consequences of the new anti-immigrant rhetoric and growing socio-political tensions and fear in immigrant neighborhoods in the United States.
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Emigrantes e Imigrantes , Americanos Mexicanos , Avaliação das Necessidades/organização & administração , Aculturação , Adolescente , Adulto , Chicago , Pesquisa Participativa Baseada na Comunidade/organização & administração , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos , Estresse Psicológico/etnologia , Confiança , Estados Unidos , Adulto JovemRESUMO
Predictions strongly influence perception. However, the neurophysiological processes that implement predictions remain underexplored. It has been proposed that high- and low-frequency neuronal oscillations act as carriers of sensory evidence and top-down predictions, respectively (von Stein and Sarnthein 2000; Bastos et al. 2012). However, evidence for the latter hypothesis remains scarce. In particular, it remains to be shown whether slow prestimulus alpha oscillations in task-relevant brain regions are stronger in the presence of predictions, whether they influence early categorization processes, and whether this interplay indeed boosts perception. Here, we directly address these questions by manipulating subjects' prior expectations about the identity of visually presented letters while collecting magnetoencephalographic recordings. We find that predictions lead to increased prestimulus alpha oscillations in a multisensory network representing grapheme/phoneme associations. Furthermore, alpha power interacts with stimulus degradation and top-down expectations to predict visibility ratings, and correlates with the amplitude of early sensory components (P1/N1m complex), suggesting a role in the selective amplification of predicted information. Our results thus indicate that low-frequency alpha oscillations can serve as a mechanism to carry and test sensory predictions about letters.
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Ritmo alfa/fisiologia , Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Leitura , Adolescente , Adulto , Piscadela , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Eletroculografia , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Limiar Sensorial/fisiologia , Adulto JovemRESUMO
Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.
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Insuficiência Cardíaca/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Microvasos/patologia , Ratos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: The COVID-19 pandemic has had unprecedented and deteriorating effects on the mental health of adolescents and young adults. Various studies have described changes regarding substance abuse, but findings are conflicting. STUDY DESIGN: We conducted a cross-sectional online survey on nicotine, alcohol, and illicit drug use. METHODS: From March to May 2023, 502 participants aged 14-24 from a community-based sample completed the questionnaire. RESULTS: We found a general trend of declining or stable substance use during the first 2 years of the pandemic; however, in the third year (i.e., 2022), substance use returned to pre-pandemic levels or exceeded it. Compared with young adults (age 19-24), adolescents' (age 14-18) use increased more clearly. Participants who scored above the cut-off on screening measures for problematic substance use showed a more pronounced increase in the use of cigarettes and illicit drugs but not of alcohol. Higher alcohol consumption during lockdowns was associated with increased likelihood of current problematic alcohol (odds ratio [OR]: 3.03) and cannabis use (OR: 2.60). Furthermore, individuals who reported increased usage of one psychotropic substance during lockdowns were more likely to have increased their use of other substances as well (OR: 2.66-4.87). CONCLUSIONS: Although not optimally generalizable due to the retrospective online format and convenience sampling, our results support the notion that special attention ought to be paid to certain subgroups such as younger people and those who already exhibit problematic substance use during the pandemic. Following up on post-pandemic trends in substance use is crucial for developing prevention measures and targeted interventions.
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BACKGROUND: Cancer-associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation. Several non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested for CAC treatment, yet no single medication has proven reliable. R-ketorolac (RK) is the R-enantiomer of a commonly used NSAID. The effect of RK on CAC has not yet been evaluated. METHODS: Ten- to 11-week-old mice were inoculated with C26 or CHX207 cancer cells or vehicle control (phosphate-buffered saline [PBS]). After cachexia onset, 2 mg/kg RK or PBS was administered daily by oral gavage. Body weight, food intake and tumour size were continuously measured. At study endpoints, blood was drawn, mice were sacrificed and tissues were excised. Immune cell abundance was analysed using a Cytek® Aurora spectral flow cytometer. Cyclooxygenase (COX) activity was determined in lung homogenates using a fluorometric kit. Muscle tissues were analysed for mRNA and protein expression by quantitative real-time PCR and western blotting analysis, respectively. Muscle fibre size was determined on histological slides after haematoxylin/eosin staining. RESULTS: Ten-day survival rate of C26-bearing animals was 10% while RK treatment resulted in a 100% survival rate (P = 0.0009). Chemotherapy resulted in a 10% survival rate 14 days after treatment initiation, but all mice survived upon co-medication with RK and cyclophosphamide (P = 0.0001). Increased survival was associated with a protection from body weight loss in C26 (-0.61 ± 1.82 vs. -4.48 ± 2.0 g, P = 0.0004) and CHX207 (-0.49 ± 0.33 vs. -2.49 ± 0.93 g, P = 0.0003) tumour-bearing mice treated with RK, compared with untreated mice. RK ameliorated musculus quadriceps (-1.7 ± 7.1% vs. -27.8 ± 8.3%, P = 0.0007) and gonadal white adipose tissue (-18.8 ± 49% vs. -69 ± 15.6%, P = 0.094) loss in tumour-bearing mice, compared with untreated mice. Mechanistically, RK reduced circulating interleukin-6 (IL-6) concentrations from 334 ± 151 to 164 ± 123 pg/mL (P = 0.047) in C26 and from 93 ± 39 to 35 ± 6 pg/mL (P = 0.0053) in CHX207 tumour-bearing mice. Moreover, RK protected mice from cancer-induced T-lymphopenia (+1.8 ± 42% vs. -49.2 ± 12.1% in treated vs. untreated mice, respectively). RK was ineffective in ameliorating CAC in thymus-deficient nude mice, indicating that the beneficial effect of RK depends on T-cells. CONCLUSIONS: RK improved T-lymphopenia and decreased systemic IL-6 concentrations, resulting in alleviation of cachexia and increased survival of cachexigenic tumour-bearing mice, even under chemotherapy and independent of COX inhibition. Considering its potential, we propose that the use of RK should be investigated in patients suffering from CAC.
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Linfopenia , Neoplasias , Humanos , Camundongos , Animais , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/metabolismo , Cetorolaco/metabolismo , Cetorolaco/farmacologia , Cetorolaco/uso terapêutico , Interleucina-6/metabolismo , Camundongos Nus , Qualidade de Vida , Músculo Esquelético/patologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Peso Corporal , Anti-Inflamatórios não Esteroides/uso terapêutico , Linfopenia/complicações , Linfopenia/tratamento farmacológico , Linfopenia/patologiaRESUMO
Background: Internet-based mental health interventions are considered effective in providing low-threshold support for people with mental health disorders. However, there is a lack of research investigating the transferability of such online programs into routine care settings. Low treatment adherence and problems with technical implementation often limit a successful transfer into clinical routines. This naturalistic study aims to identify influencing factors on program adherence in patients who participated in an online intervention during inpatient or day-clinic psychotherapeutic treatment. Methods and findings: In a naturalistic study, we investigated the transferability of the transdiagnostic psychodynamic online self-help program KEN-Online, which includes eight consecutive units. Between May 2017 and October 2018, patients who received inpatient or day-clinic psychotherapeutic treatment at the Department of Psychosomatic Medicine and Psychotherapy in the University Medical Center Mainz have been offered to use KEN-Online. Of the n = 749 patients who were admitted to the clinic, n = 239 patients (32%) registered for participation in KEN-Online. While 46.9% of the participants did not complete any unit (inactive participants), 53.1% completed at least the first unit (active participants). Age, number of diagnoses, and symptom severity were associated with (in)active participation. Adherence decreased over time resulting in only 17 participants (7.6%) who completed all units. None of the sociodemographic and medical characteristics proved to be significant predictors of adherence. Analyses of effectiveness showed a significant reduction of anxiety and depression in active participants in the course of participation, with higher improvements in participants that completed more than half of the units. Conclusion: Adherence to the online self-help program KEN-Online was lower in the naturalistic setting than in a previous clinical trial, but was still associated with greater program effectiveness. Adherence-promoting measures are crucial to increase the effectiveness of such interventions in clinical settings.
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BACKGROUND: Participant recruitment poses challenges in psycho-oncological intervention research, such as psycho-oncological web-based intervention studies. Strict consecutive recruitment in clinical settings provides important methodological benefits but is often associated with low response rates and reduced practicability and ecological validity. In addition to preexisting recruitment barriers, the protective measures owing to the COVID-19 pandemic restricted recruitment activities in the clinical setting since March 2020. OBJECTIVE: This study aims to outline the recruitment strategy for a randomized controlled trial evaluating the unguided emotion-based psycho-oncological online self-help (epos), which combined traditional and web-based recruitment. METHODS: We developed a combined recruitment strategy including traditional (eg, recruitment in clinics, medical practices, cancer counseling centers, and newspapers) and web-based recruitment (Instagram, Facebook, and web pages). Recruitment was conducted between May 2020 and September 2021. Eligible participants for this study were adult patients with any type of cancer who were currently receiving treatment or in posttreatment care. They were also required to have a good command of the German language and access to a device suitable for web-based interventions, such as a laptop or computer. RESULTS: We analyzed data from 304 participants who were enrolled in a 17-month recruitment period using various recruitment strategies. Web-based and traditional recruitment strategies led to comparable numbers of participants (151/304, 49.7% vs 153/304, 50.3%). However, web-based recruitment required much less effort. Regardless of the recruitment strategy, the total sample did not accurately represent patients with cancer currently undergoing treatment for major types of cancer in terms of various sociodemographic characteristics, including but not limited to sex and age. However, among the web-recruited study participants, the proportion of female participants was even higher (P<.001), the mean age was lower (P=.005), private internet use was higher (on weekdays: P=.007; on weekends: P=.02), and the number of those who were currently under treatment was higher (P=.048). Other demographic and medical characteristics revealed no significant differences between the groups. The majority of participants registered as self-referred (236/296, 79.7%) instead of having followed the recommendation of or study invitation from a health care professional. CONCLUSIONS: The combined recruitment strategy helped overcome general and COVID-19-specific recruitment barriers and provided the targeted participant number. Social media recruitment was the most efficient individual recruitment strategy for participant enrollment. Differences in some demographic and medical characteristics emerged, which should be considered in future analyses. Implications and recommendations for social media recruitment based on personal experiences are presented. TRIAL REGISTRATION: German Clinical Trials Register DRKS00021144; https://drks.de/search/en/trial/DRKS00021144. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.invent.2021.100410.
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OBJECTIVE: Self-harm is associated with alterations in the psychobiological stress response. Specifically, the reactivity of the autonomic nervous system (ANS) and the endocrine hypothalamic-pituitary-adrenal (HPA) axis may differ in individuals who engage in self-harm. However, evidence in this regard is inconsistent. BACKGROUND: We conducted a preregistered random-effects meta-analysis of sympathetic ANS, parasympathetic ANS, sympathetic-parasympathetic, i.e., mixed-influence ANS, and HPA axis reactivity following laboratory stress exposure in individuals who engage in self-harm and controls. Stress exposure consisted of paradigms using either social-evaluative (e.g., TSST), emotional (e.g., negatively valenced visual stimuli), or physical (e.g., cold pressor test) challenges. A total of 29 studies (self-harm: n = 954, controls: n = 1122, 74% females) were included in the analysis. RESULTS: Regarding ANS reactivity to stress, no differences emerged between the two groups. However, parasympathetic ANS activity was lower before stress (g = -0.30, CI -0.51 to -0.09) and after stressor cessation (g = 0.54, CI -1.07 to -0.01) in the self-harm group compared to controls. Regarding HPA axis reactivity, individuals who engage in self-harm showed significantly lower cortisol responses to stress than did controls (g = -0.26, CI -0.45 to -0.08). After stressor cessation (i.e., during stress recovery), cortisol was also lower in individuals who engage in self-harm compared to controls (g = -0.26, CI -0.43 to -0.08). CONCLUSIONS: Lower basal parasympathetic ANS activity and flattened cortisol responses indicate dysregulation of psychobiological stress systems in individuals who engage in self-harm. A better understanding of the psychobiological underpinnings of self-harm may allow for the establishment of biomarkers of risk stratification and treatment monitoring in affected individuals.
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Sistema Hipotálamo-Hipofisário , Comportamento Autodestrutivo , Feminino , Humanos , Masculino , Sistema Hipotálamo-Hipofisário/fisiologia , Hidrocortisona , Estresse Psicológico , Sistema Hipófise-Suprarrenal/fisiologia , Estresse Fisiológico , SalivaRESUMO
BACKGROUND: Few have examined factors associated with community advisory board (CAB) sustainability from the perspective of members. OBJECTIVES: We aimed to provide insight into the formation of a CAB and attributes and challenges to sustaining it in addressing Latino health disparities in Chicago. METHODS: The Little Village CAB was formed in 2009 with members representing a wide range of local organizations, including churches, nonprofit organizations, and health centers. We analyzed annual survey results sent to members over a 10-year period. Likert-type questions assessed five domains: mission, commitment, communication, respect/trust, and teamwork/balance of power. We also analyzed free-text responses to determine prevalent themes. Ten years of CAB monthly meeting minutes were used to form word clouds which were assessed for changes across years. RESULTS: Survey questions demonstrated high averages across all years for each domain with minimal variation. Free-text responses indicated that members initially joined the CAB owing to request or interest in community health. CAB attributes included mission, community focus, openness/respect, teamwork, and leadership. Areas for improvement included broadening membership, clarifying goals periodically, and meeting structure. Meeting minutes demonstrated a progression from program creation to maintenance across the years. CONCLUSIONS: The CAB rated openness/respect, community focus, and commitment to mission high across all 10 years. Areas for improvement included broadening membership and clarifying goals periodically. In forming a CAB to address health disparities in a Latino community, researchers must be aware of factors that motivated members to join and remain engaged with an academic team using an iterative evaluative process.
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Participação da Comunidade , Pesquisa Participativa Baseada na Comunidade , Humanos , Pesquisa Participativa Baseada na Comunidade/métodos , Participação da Comunidade/métodos , Saúde Pública , Pesquisadores , ConfiançaRESUMO
Healthy mitochondria and their epigenetic control are essential to maintaining health, extending life expectancy, and improving cardiovascular performance. Strategies to maintain functional mitochondria during aging include training; cardiovascular exercise has been suggested as the best method, but strength training has also been identified as essential to health and healthy aging. We therefore investigated the effects of concurrent exercise training and dietary habits on epigenetic mechanisms involved in mitochondrial (mt) functions and biogenesis. We analyzed epigenetic biomarkers that directly target the key regulator of mitochondrial biogenesis, PGC-1α, and mtDNA content. Thirty-six healthy, sedentary participants completed a 12-week concurrent training program. Before and after the intervention, dried blood spot samples and data on eating habits, lifestyle, and body composition were collected. MiR-23a, miR-30e expression, and mtDNA content were analyzed using real-time quantitative polymerase chain reaction (qPCR) analysis. PGC-1α methylation was analyzed using bisulfite pyrosequencing. MiR-23a, miR-30e expression, and PGC-1α methylation decreased after the intervention (p < 0.05). PGC-1α methylation increased with the consumption of red and processed meat, and mtDNA content increased with the ingestion of cruciferous vegetables (p < 0.05). Our results indicate that concurrent training could improve mitochondrial biogenesis and functions by altering the epigenetic regulation. These alterations can also be detected outside of the skeletal muscle and could potentially affect athletic performance.
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BACKGROUND: Dementia in people with intellectual disability (ID) is frequent but hard to recognise. Evidence-based recommendations for suitable instruments are lacking. AIMS: The present study set out to evaluate informant-based dementia assessment instruments and to provide evidence-based recommendations for instruments most suitable in clinical practice and research. METHOD AND PROCEDURES: A systematic review was conducted across ten international electronic databases. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, including a risk of bias assessment, was applied to extract information and to evaluate measurement properties and the quality of available evidence. OUTCOMES AND RESULTS: In total, 42 studies evaluating 18 informant-based assessment instruments were analysed. For screening purposes, we recommend the Behavioral and Psychological Symptoms of Dementia in Down Syndrome Scale (BPSD-DS), the Cognitive Scale for Down Syndrome (CS-DS), and the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). For a more thorough dementia assessment, we recommend the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). CONCLUSIONS AND IMPLICATIONS: Our study informs clinicians and researchers about adequate, well-evaluated dementia assessment instruments for people with ID, and highlights the need for high quality studies, especially regarding content validity.
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Demência , Síndrome de Down , Deficiência Intelectual , Idoso , Viés , Demência/diagnóstico , Síndrome de Down/diagnóstico , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/epidemiologia , Programas de RastreamentoRESUMO
BACKGROUND AND PURPOSE: Dipeptidyl peptidase 4 (DPP-4) inhibitors are a class of oral glucose-lowering drugs used in the treatment of type 2 diabetes. In a pilot study using human kidney biopsies, we observed high DPP-4 expression in early crescent formation. This glomerular lesion occurs in different kidney diseases and is a hallmark in the pathogenesis of renal dysfunction. Therefore, we investigated the potential involvement of DPP-4 in the pathogenesis of nephritis induced by anti-glomerular basement membrane (GBM) antibody in rats. EXPERIMENTAL APPROACH: Linagliptin and vehicle were used to treat anti-GBM nephritis in a 2- and 8-week regimen, that is either preventive or therapeutic (treatment started 7 days or 4 weeks after disease induction). Kidney function, morphologic changes, inflammation and fibrosis were monitored. KEY RESULTS: In the long-term experiment, linagliptin preventive treatment in anti-GBM nephritic rats significantly reduced the number of crescents, glomerulosclerosis, tubular injury and renal fibrosis, compared with those in untreated nephritic rats. Both linagliptin regimes significantly lowered the number of Pax8+ cells on the glomerular tuft in anti-GBM nephritis, indicating accelerated resolution of the cellular crescents. The linagliptin treatment did not change the podocyte stress in both therapeutic groups. Therapeutic intervention with linagliptin resulted in weaker amelioration of renal disease on Week 8 than did preventive intervention. CONCLUSION AND IMPLICATIONS: DPP-4 inhibition with linagliptin ameliorates renal injury in a rat model of anti-GBM, indicating that linagliptin not only is a secure therapy in diabetes but also can improve resolution of glomerular injury and healing in non-diabetic renal disease.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Nefrite , Animais , Dipeptidil Peptidase 4 , Rim , Linagliptina , Projetos Piloto , RatosRESUMO
BACKGROUND: A cancer diagnosis can cause severe emotional distress and affect quality of life as well as social relationships. The transition from inpatient to outpatient treatment is burdened by stressful uncertainties and a gap of psycho-oncological care. In addition, further barriers, such as information deficits or fear of stigmatization, might hinder cancer patients to use psycho-oncological face-to-face interventions. Online interventions can be a low-threshold adjunct to existing face-to-face services. This study aims to evaluate the effect of the online self-help program epos (emotion-based psycho-oncological online self-help) on improving symptoms of anxiety and depression in German-speaking cancer patients. METHODS: A randomized controlled trial (RCT) is carried out in a parallel group design. N = 325 patients will be enrolled in the trial, randomly assigned to an intervention and a control group. While the intervention group has access to nine modules of epos, the control group gets access to an informational website. Participants will complete online questionnaires at baseline (T0), after the intervention (T1) and three-month follow-up (T2). Primary outcome is a combined measure of depression and anxiety. Secondary outcomes include psychological distress, anxiety, depression, quality of life, emotional control, posttraumatic growth, and satisfaction with epos. Participants are at least 18 years old, have a cancer diagnosis, currently receive cancer treatment or aftercare, have sufficient German language competence, and have access to the Internet. Exclusion criteria are severe mental comorbidities (i.e. severe depression, suicidality) or somatic comorbidities (i.e. visual disabilities). DISCUSSION: The results of this study will provide information about acceptability, feasibility, and efficacy of epos in improving symptoms of depression and anxiety in cancer patients and thus contribute to the research on web-based interventions. If found efficacious, epos will improve psycho-oncological care in cancer patients in transition from inpatient to outpatient care and in those who struggle to find adequate psycho-oncological support due to other (perceived) barriers.
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In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialysis approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), is required for aggression in female rats. Accordingly, increased activity of putative OXT receptor-positive neurons in the vLS, and decreased activity of putative AVP receptor-positive neurons in the dLS, are likely to underly aggression in female rats. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data suggest a model showing that septal release of OXT and AVP differentially affects aggression in females by modulating the inhibitory tone within LS sub-networks.
Assuntos
Agressão/fisiologia , Arginina Vasopressina/metabolismo , Ocitocina/metabolismo , Núcleos Septais/metabolismo , Isolamento Social/psicologia , Agressão/efeitos dos fármacos , Animais , Arginina Vasopressina/farmacologia , Feminino , Microdiálise , Neurônios/metabolismo , Ocitocina/farmacologia , Ratos Wistar , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Núcleos Septais/citologia , Núcleos Septais/efeitos dos fármacosRESUMO
The "Sniffin' Sticks" test kit is a validated and commonly used tool for assessment of olfactory function in subjects with normal sense of smell and in individuals with smell loss. That test incorporates subtests for odor threshold, discrimination, and identification. To gain higher subtest reproducibility, tests on odor discrimination and odor identification were extended using 32 instead of the usually applied 16 single trials each. In developing the extended Sniffin' Sticks test, a number of preliminary experiments were performed in 46 healthy, normosmic individuals 1) to evaluate intensity and familiarity of the additionally selected odors, 2) to select distractors for the discrimination and identification test, and 3) to evaluate the test-retest reliability of each subtest. Furthermore, the extended test was applied to 126 patients with olfactory loss and 71 normosmic individuals. Follow-up investigation could be performed in 69 controls within an average interval of 4 days. Results revealed significant differences between patients and healthy subjects. Estimated intensity and familiarity of the newly selected 16 items of the discrimination test did not differ significantly from the 16 standard items. Test-retest reliability was found to be r = 0.80 (odor discrimination), r = 0.88 (odor identification), and r = 0.92 (odor threshold). In conclusion, the extended test kit allows a precise evaluation of olfactory function, especially when different olfactory tasks are assessed using individual subtests. Furthermore, the high test-retest reliability of both the 16 and the 32-item tests allows the evaluation of even relatively small changes of olfactory function over time by means of either test.
Assuntos
Técnicas e Procedimentos Diagnósticos , Transtornos do Olfato/diagnóstico , Olfato , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
UNLABELLED: Chronic rhinosinusitis affects 1-4% of the adult population. The aetiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE type) immune response. AIM: If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. METHODS: To check on this assumption, the authors conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; one group of them (group A, 14 randomly selected patients) was treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group (group B, 16 randomly selected patients) received a nasal spray lacking amphotericin B. The results were evaluated with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which evaluates changes in the symptoms), the life-quality test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and one year postoperatively. RESULTS: The CT scores of the group A patients exhibited wide scattering without signs of recovery one year after the operation. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant in relation to group A. Both the SNAQ-11 test and the life-quality test revealed a significant improvement in each group, but the degrees of change in these tests did not significantly differ between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. CONCLUSION: These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in CT scores, clinical symptoms, or quality of life. The more favourable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study the authors discuss the available data on the fungal theory. They critically analyse the contradictory observations of 7 recent clinical studies.