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It is increasingly recognized that psychological stress is linked with type 2 diabetes mellitus and its late complications. Thus, the aim of the current study was to investigate the psychophysiological response to acute psychosocial stress in patients with type 2 diabetes. In total, 53 type 2 diabetes patients with complications, 16 type 2 diabetes patients without complications, and 47 age and gender matched non-diabetic participants underwent the Trier Social Stress Test. Subjective as well as biological parameters (i.e., blood levels of cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, methylglyoxal) were assessed repeatedly before and after stress induction. Data were analyzed by means of multilevel regression. Patients with type 2 diabetes showed an exaggerated cortisol response to acute stress as compared to age matched control participants (diabetes*T2 est. = 1.23, p < .001), while stress-induced alterations of ACTH and subjective parameters did not differ. Norepinephrine levels were lower among patients (diabetes est. = -4.36, p = .044) and tended to decrease earlier than in controls. The subjective reaction of type 2 diabetes patients with complications was stronger than that of patients without complications (complication*T2 est. = -1.83, p = .032), while their endocrine response to stress was similar. Stress had no effect on methylglyoxal level, and there were no group differences regarding methylglyoxal response. These results show that the cortisol reactivity of patients with type 2 diabetes to acute psychosocial stress is increased compared to a control group. Thus, alterations of the hypothalamus-pituitary-adrenal axis - especially regarding its dynamic regulation - are a plausible link between psychological stress and type 2 diabetes and its complications.
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Diabetes Mellitus Tipo 2 , Hidrocortisona , Hormônio Adrenocorticotrópico , Diabetes Mellitus Tipo 2/complicações , Humanos , Sistema Hipotálamo-Hipofisário , Norepinefrina/farmacologia , Sistema Hipófise-Suprarrenal , Aldeído Pirúvico/farmacologia , Saliva , Estresse PsicológicoRESUMO
BACKGROUND/OBJECTIVE: The COVID-19 pandemic and the accompanying preventive measures have shaped social life in unexpected ways. Because older persons with multiple chronic conditions have a high risk of a severe medical outcome, it has been strongly recommended that social contacts be curtailed in order to minimize risks of infection. While this appears to be alarming from a psychosocial point of view, it has been shown that older persons exhibit a high degree of equanimity and a good ability to cope with the crisis. The aim of the study was to describe the attitudes of multimorbid older people to the pandemic, their social contacts and their experiences with medical care. MATERIAL AND METHODS: This cross-sectional qualitative survey was based on 21 semi-structured short interviews of older patients with multiple chronic conditions during inpatient health care, at 4 different points in time: July 2020, September 2020, November 2020 and January 2021. The data were analyzed by qualitative content analysis. RESULTS: The statements of 21 participants (aged 58-88 years) were assessed. Over the course of the COVID-19 pandemic it became apparent that participants experienced the pandemic differently, both from an individual perspective and over time. While high infection rates were accompanied by serious concerns about health, periods of moderate infection risk were dominated by worry about social changes. In older persons there was a great sense of acceptance of the preventive measures. CONCLUSION: Our study exemplarily illustrates the attitudes and concerns of older persons who suffer from multiple chronic conditions over the course of the pandemic. Our data show that older persons reacted with equanimity to the novel medical and social circumstances.
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COVID-19 , Múltiplas Afecções Crônicas , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
BACKGROUND: Older patients with multiple morbidities are a particularly vulnerable population that is likely to face complex medical decisions at some time in their lives. A patient-centered medical care fosters the inclusion of the patients' perspectives, priorities, and complaints into clinical decision making. METHODS: This article presents a short and non-normative assessment tool to capture the priorities and problems of older patients. The so-called LAVA ("Life and Vitality Assessment") tool was developed for practical use in seniors in the general population and for residents in nursing homes in order to gain more knowledge about the patients themselves as well as to facilitate access to the patients. The LAVA tool conceptualizes well-being from the perspectives of older individuals themselves rather than from the perspectives of outside individuals. RESULTS: The LAVA tool is graphically presented and the assessment is explained in detail. Exemplarily, the outcomes of the assessments with the LAVA of three multimorbid older patients are presented and discussed. In each case, the assessment pointed out resources as well as at least one problem area, rated as very important by the patients themselves. CONCLUSIONS: The LAVA tool is a short, non-normative, and useful approach that encapsulates the perspectives of well-being of multimorbid patients and gives insights into their resources and problem areas.
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Casas de Saúde , Assistência Centrada no Paciente , Humanos , Morbidade , MultimorbidadeRESUMO
BACKGROUND: Angina pectoris refractory to conventional medical treatment is a common phenomenon in patients with stable coronary artery disease (CAD). Many of these patients suffer from depression and generate substantial costs in the healthcare system. Therefore, the development of new therapeutic concepts is of particular importance. This study investigated whether professional, structured humor training has a positive effect on the symptoms of patients with treatment refractory angina pectoris. METHODS: Between 2013 and 2014 a total of 35 patients with stable CAD were included. Enrolment was possible if patients suffered from treatment refractory angina pectoris (Canadian Cardiovascular Society, CCS grades II-IV) despite optimal antianginal medication and exhaustion of options for myocardial revascularization. Previously, 25.8% of the patients had had a myocardial infarction. In this study, a professional humor coaching was conducted with a duration of 7 weeks. In order to evaluate the effects of the coaching, the following examinations were performed before and after the intervention: exercise stress test (treadmill), hair segment cortisol analysis, Beck Depression Inventory (BDI), the Trier Inventory for the Assessment of Chronic Stress (TICS) and the State-Trait-Cheerfulness Inventory (STCI). RESULTS: Out of the 35 initially recruited patients 31 completed the study. The mean age was 65.5 years and 94.5% were female. There was a significant improvement in cheerfulness (STCI, pre 23.3⯱ 5.4, post 27.5⯱ 5, pâ¯= 0,03). This effect was even stronger in a subgroup analysis in which only female patients were included (pre 23.6⯱ 5.5, post 27.7⯱ 4.6, pâ¯= 0.003). The results of the BDI showed a remarkable improvement in the pre-post analysis (pre 14.6⯱ 8.1, post 11.0⯱ 6.5, pâ¯= 0.064). Analyzing only the female patients, this difference became significant (pre 13.1⯱ 6.4, post 9.9⯱ 4.6 pâ¯= 0,037). The hair segment investigations showed that patients who had a higher cortisol level in the beginning (>25. percentile, nâ¯= 22) showed a significant reduction of the cortisol concentration (pre 6.54â¯pg/mg, 3.78-12.12â¯pg/mg, post 3.65â¯pg/mg, 2.82-7.68â¯pg/mg, pâ¯= 0.029). CONCLUSION: Patients with refractory angina pectoris and stable CAD benefit from a professional humor coaching. This effect was shown in a) a significant decrease in cortisol concentrations in the hair segment analysis, b) an improvement in cheerfulness in the STCI and c) a significant difference in the BDI between pre-post values.
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Doença da Artéria Coronariana , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/terapia , Canadá , Doença da Artéria Coronariana/complicações , Depressão/terapia , Feminino , Humanos , Masculino , Revascularização MiocárdicaRESUMO
OBJECTIVE: Patients' processing of psychotherapy between sessions ("inter-session process" (ISP)) has been repeatedly shown to be related to outcome. The aim of this study was to compare ISP characteristics of cognitive-behavioral vs. psychodynamic psychotherapy in the treatment of anorexia nervosa (AN) and their relation to outcome. METHODS: Data of 106 patients participating in a randomized-controlled trial who received either 40 sessions of enhanced cognitive-behavioral therapy (CBT-E) or focal psychodynamic therapy (FPT) were analyzed. The ISP was measured with the Inter-session Experience Questionnaire (IEQ). Three outcome classes were distinguished: full recovery, partial recovery, and still fulfilling all AN criteria. RESULTS: Patients receiving CBT-E reported more on "applying therapy" in the initial and the final treatment phase compared to FPT patients. In terms of process-outcome relations, higher levels of "recreating the therapeutic dialogue between sessions," "recreating the therapeutic dialogue with negative emotions" as well as "applying therapy with negative emotions" in the final phase of treatment predicted negative outcome in FPT, whereas overall higher levels of negative emotions predicted negative outcome in CBT-E. CONCLUSIONS: In outpatient treatment in AN, the processing of therapy as measured by the IEQ showed surprisingly few differences between CBT-E and FPT. However, different ISP patterns were predictive of outcome, pointing to different mechanisms of change.
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Anorexia Nervosa/terapia , Terapia Cognitivo-Comportamental/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Psicoterapia Psicodinâmica/métodos , Adulto , Feminino , HumanosRESUMO
BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾9825 and ⩾24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.
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Anorexia Nervosa/terapia , Terapia Cognitivo-Comportamental/métodos , Psicoterapia Psicodinâmica/métodos , Adulto , Assistência Ambulatorial/economia , Assistência Ambulatorial/métodos , Anorexia Nervosa/economia , Terapia Cognitivo-Comportamental/economia , Análise Custo-Benefício , Feminino , Alemanha , Hospitalização/economia , Humanos , Psicoterapia Psicodinâmica/economia , Adulto JovemRESUMO
BACKGROUND: Successful treatment in psychosomatic medicine requires intrinsic motivation of the patient and the belief that the chosen therapeutic option can help. Depression, somatization disorder and generalized anxiety disorder (GAD) are frequent mental disorders in the elderly population. Finding a suitable and successful treatment for elderly people with mental disorders is often difficult. Undertreatment and the utilization of inappropriate healthcare services are frequent. OBJECTIVE: Treatment preferences of elderly patients with mental disorders were ascertained in order to evaluate the motivation for psychotherapy or other therapeutic measures. MATERIAL AND METHODS: The data were derived from the 8-year follow-up of the epidemiological study on chances of prevention, early recognition and optimized therapy of chronic diseases in the elderly population (ESTHER), a population-based cohort study in Saarland, Germany. A total of 3124 patients aged 55-84 years were included in this analysis. The treatment preferences were documented using a questionnaire with 12 different answer categories. The occurrence of depression, somatization disorder and GAD was collated using the patient health questionnaire (PHQ-D). RESULTS: Physiotherapy and inpatient rehabilitation were the most frequently named treatment preferences in all three subgroups of patients with mental disorders. Psychotherapy was the preferred treatment for 18.3 % of depressive patients, for 15.0 % of somatization patients and for 15.7 % of GAD patients. CONCLUSION: Mentally ill elderly patients in Germany preferred physical treatment techniques, such as physiotherapy and inpatient rehabilitation over psychotherapy. Discussion is needed over the reasons for these findings and the clinical implications.
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Depressão/epidemiologia , Depressão/terapia , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Participação do Paciente/estatística & dados numéricos , Preferência do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Depressão/psicologia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Avaliação das Necessidades , Participação do Paciente/psicologia , Preferência do Paciente/psicologia , Modalidades de Fisioterapia/estatística & dados numéricos , Prevalência , Psicoterapia/estatística & dados numéricos , Reabilitação/estatística & dados numéricos , Estudos Retrospectivos , AutorrelatoRESUMO
Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests.
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Cerebelo/patologia , Riso , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia , Senso de Humor e Humor como Assunto , Adulto , Idoso , Depressão/diagnóstico , Depressão/etiologia , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Acidente Vascular Cerebral/complicações , Fatores de Tempo , Gravação em VídeoRESUMO
BACKGROUND: Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. METHODS: We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). RESULTS: At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. CONCLUSIONS: Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care.
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Medicina de Família e Comunidade , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Psicoterapia de Grupo/métodos , Qualidade de Vida , Transtornos Somatoformes/terapia , Adaptação Psicológica , Ansiedade/terapia , Análise por Conglomerados , Comportamento Cooperativo , Educação Médica Continuada , Feminino , Processos Grupais , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Psicoterapia de Grupo/educação , Índice de Gravidade de Doença , Transtornos Somatoformes/psicologia , Estresse Psicológico/terapiaRESUMO
Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.
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Riso/psicologia , Degenerações Espinocerebelares/psicologia , Adaptação Psicológica , Adulto , Idoso , Desenhos Animados como Assunto , Ataxia Cerebelar/psicologia , Depressão/psicologia , Expressão Facial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes de Personalidade , Escalas de Graduação Psiquiátrica , Desempenho Psicomotor/fisiologia , Degenerações Espinocerebelares/patologiaRESUMO
In recent years, a number of studies have been published on cerebral activation induced by funny stimuli. This article provides an overview on the structures involved and findings concerning the neuropsychological faculties necessary for joke comprehension, e.g., working memory and mental flexibility. On the other hand, there are also many aspects of humor, like joke production, that are not neuropsychologically well studied; an overview of current knowledge will be given. In addition, there is little research on the effect of aging on the different aspects of cerebral humor processing.
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Atitude , Encéfalo/fisiologia , Cognição/fisiologia , Memória/fisiologia , Temperamento/fisiologia , Senso de Humor e Humor como Assunto/psicologia , HumanosRESUMO
Individual nanometer-sized plasmonic antennas are excited resonantly with few-cycle laser pulses in the near infrared. Intense third-harmonic emission of visible light prevails for fundamental photon energies below 1.1 eV. Interband luminescence and second harmonic generation occur solely at higher driving frequencies. We attribute these findings to multiphoton resonances with the d-band transitions of gold. The strong third-order signal allows direct measurement of a subcycle plasmon dephasing time of 2 fs, highlighting the efficient radiation coupling and broadband response of the devices.
RESUMO
BACKGROUND: Little is known specifically about the association between generalized anxiety symptoms or panic and health care costs in older age. The aim of this study was to examine the association between generalized anxiety symptoms, panic and health care costs in people aged 65 and over. METHODS: Cross-sectional data from the 8-year follow-up of a large, prospective cohort study, the ESTHER study, was used. Individuals aged 65 and over, who participated in the study's home assessment, were included in this analysis (nâ¯=â¯2348). Total and sectoral costs were analyzed as a function of either anxiety symptoms, probable panic disorder, or a panic attack, while controlling for selected covariates, using Two Part and Generalized Linear Models. Covariates were chosen based on Andersen's Behavioral Model of Health Care Use. RESULTS: There was no significant association between either of the anxiety or panic measures and total health care costs. Stratified by health care sectors, only the occurrence of a panic attack was significantly associated with incurring costs for outpatient non-physician services (OR: 1.99; 95% CI: 1.15-3.45) and inpatient services (OR: 2.14; 95% CI: 1.07-4.28). Other illness-related factors, such as comorbidities and depressive symptoms, were associated with health care costs in several models. LIMITATIONS: This was a cross-sectional study relying on self-reported data. CONCLUSION: This study points to an association between a panic attack and sector-specific health care costs in people aged 65 and over. Further research, especially using longitudinal data, is needed.
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Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Transtorno de Pânico/epidemiologia , Idoso , Assistência Ambulatorial/economia , Estudos de Coortes , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Feminino , Alemanha/epidemiologia , Hospitalização/economia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos ProspectivosRESUMO
Anorexia nervosa differs distinctly from other psychogenic eating disorders. Well known for the past 300 years, anorexia occurs consistently and is one of the most serious illnesses to be found for a certain age group. Three-quarters of the patients are healed or improve their condition long-term; one-quarter has a chronic course frequently including somatic complications and death. Because of the long healing process as well as the extensive chronification and complication rate, an individual treatment plan should be set up at the beginning of therapy to allow for a long-term structure of the course of therapy. Depending on the severity, phase and co-morbidity, inpatient and ambulant therapies are indicated. Depending on the duration of therapy, adequate weight (BMI > 15 kg/m2), good motivation, and lack of complications, an ambulant therapy is justified. Inpatient treatment is multimodal corresponding to the multifactorial etiology of anorexia nervosa. Weight gain is an important primary goal of therapy and a prerequisite for a conflict oriented, ambulant psychotherapy to be carried on after inpatient treatment. Ambivalent psychotherapy motivation and the necessity of symptom orientation demand technical modification both for inpatient as well as ambulant psychotherapy.
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Anorexia Nervosa/diagnóstico , Anorexia Nervosa/terapia , Anorexia/diagnóstico , Anorexia/terapia , Medição de Risco/métodos , Anorexia/epidemiologia , Anorexia Nervosa/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Prevalência , Fatores de RiscoRESUMO
OBJECTIVES: To bring to the attention of East African practitioners, the characteristics of Hb Stanleyville II, its interaction with HbS, and the resemblance of the double heterozygote to sickle cell-haemoglobin C (SC) disease. DATA SOURCES: A prospective study of 100 patients with Sickle Cell (SS) disease in the steady state attending the sickle cell Clinic at Mulago Hospital, Kampala, Uganda. STUDY SELECTION: Out of 100 patients with SS disease, two were also heterozygous for an alpha chain variant identified as Hb Stanleyville II. CONCLUSIONS: In association with HbS, Hb Stanleyville II produces a hybrid haemoglobin band which on alkaline haemoglobin electrophoresis, travels in the position of HbC. Such cases may cause confusion with sickle cell-haemoglobin C (SC) disease. The index cases in both families had associated alpha thalassaemia but from this small group, no conclusions may be drawn on the haematological or clinical significance of the interaction of Hb Stanleyville II with SS disease.
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Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Hemoglobina Falciforme/análise , Hemoglobinas Anormais/análise , Adulto , Anemia Falciforme/genética , Eletroforese das Proteínas Sanguíneas , Diagnóstico Diferencial , Feminino , Doença da Hemoglobina SC/sangue , Doença da Hemoglobina SC/diagnóstico , Doença da Hemoglobina SC/genética , Humanos , Masculino , Linhagem , Estudos Prospectivos , UgandaRESUMO
Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2 ) in blood samples order to enable screening and diagnosis of carriers of ß-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.
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Automação Laboratorial , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Hemoglobina A2/química , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Eletroforese Capilar/instrumentação , Eletroforese Capilar/métodos , Eletroforese Capilar/normas , Hemoglobina A2/genética , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
Rhabdomyosarcoma (RMS), a neoplasm characterised by undifferentiated myoblasts, is the most common soft tissue tumour of childhood. Although aggressive treatment of RMS could provide long-term benefit, resistance to current therapies is an ongoing problem. We report here that insulin-like growth factor 2-binding protein 1 (IGF2BP1), an oncofetal protein, is expressed in RMS patient-derived cell lines and in primary tumours where it drives translation of the cellular inhibitor of apoptosis 1 (cIAP1), a key regulator of the nuclear factor-κB signalling pathway and of caspase-8-mediated cell death. We demonstrate that reducing the levels of cIAP1 in RMS, either by IGF2BP1 knockdown or by IAP antagonists, sensitises these cells to tumour necrosis factor-α-mediated cell death. Finally, we show that targeting cIAP1 by IAP antagonists delays RMS tumour growth and improve survival in mice. Our results identify IGF2BP1 as a critical translational regulator of cIAP1-mediated apoptotic resistance in RMS and advocate for the combined use of IAP antagonists and tumour necrosis factor-α as a therapeutic approach for this type of cancer.
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Resistencia a Medicamentos Antineoplásicos , Proteínas Inibidoras de Apoptose/genética , Proteínas de Ligação a RNA/metabolismo , Rabdomiossarcoma/metabolismo , Alcinos/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Biossíntese de Proteínas , Proteínas de Ligação a RNA/antagonistas & inibidores , Rabdomiossarcoma/tratamento farmacológico , Transdução de Sinais , Tiazóis/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína LigasesRESUMO
Conditional probability judgments of rare events are often inflated. Early accounts assumed a general deficit in using statistical base rates. More recent approaches predict improvement when problems are presented in frequency format or refer to natural categories. The present theory focuses on sampling processes. Experiment 1 showed that a seeming advantage of frequency over probability formats is due to a confounded factor, the need to mentally transform stimulus samples. An information search paradigm was used in Experiment 2. When sampling by the predictor, the probability to be estimated, p(criterion/predictor), was conserved in the samples and judgments were quite accurate. However, when sampling by the criterion, the low base-rate event was strongly overrepresented, accounting for the entire bias. Judgments were quite sensitive to the sampled data, but failed to take sampling constraints into account, as shown in Experiments 3 and 4.
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Formação de Conceito , Julgamento , Variações Dependentes do Observador , Probabilidade , Padrões de Referência , Adulto , Feminino , Humanos , Masculino , Modelos Psicológicos , Modelos EstatísticosRESUMO
Slowness of goal-directed movements is a frequent symptom following cerebellar lesions. So far it has not been demonstrated whether this slowness represents compensation for impaired braking which is a feature of cerebellar dysfunction with the consequence of hypermetria, or whether it is an independent part of cerebellar movement disorder. To resolve this question we tested 18 cerebellar patients in a paradigm where they not only had to perform fast goal-directed wrist flexion movements (amplitudes 5 degrees and 30 degrees) but also wrist flexion movements as fast and large as possible without particular target. In normals antagonist activity is minimal in large movements without target. Although subjects were clinically only mildly affected they regularly showed a 'slowness of movement' resulting from a reduction of peak acceleration. This in turn was due to the reduced generation of agonist activity. Peak velocity was not significantly decreased because the acceleration phase was adequately prolonged. Since these changes were most pronounced in the 'fast' movements without target the compensation hypothesis should be discarded. The reduction of acceleration must at least partially be due to a genuine cerebellar deficiency in the fast generation of agonist activity.
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Cerebelo/lesões , Transtornos dos Movimentos/fisiopatologia , Punho/fisiopatologia , Adolescente , Adulto , Idoso , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
1. Transcranial Magnetic Stimulation (TMS) is suggested to be an effective tool in the treatment of depression. However, the methodology most suitable for clinical application remains unclear. 2. The effect of TMS was tested in a double-blind and placebo-controlled setting on 18 healthy subjects. At the same time an established learned helplessness paradigm was applied to induce dysphoria, which consisted of unsolvable anagrams. 3. Sixty 0.5 Hz stimuli were administered at an intensity of 130% of the subject's motor threshold after the subjects were exposed to the learned helplessness situation. Using a vertically positioned coil, the stimuli were applied to the right or to the left frontal cortex, or on the occipital cortex as a placebo condition. 4. Although dysphoria was successfully induced by unsolvable anagrams, TMS on either of the two frontal locations did not influence mood. This lack of effect may be due to the stimulation characteristics employed here (low TMS intensity, and low frequency). On the other hand, the findings may reflect the neurobiological difference between experimentally induced sad mood and clinical depression.