Quality of the caregiving relationship and quality of life in mild Alzheimer's dementia.

BACKGROUND: The present study aims to investigate the quality of the dyadic relationship between mild Alzheimer patients and their caregivers. The main objective is to evaluate the consistency, agreement and validity of the German version of the Scale for Quality of the Current Relationship in Caregiving (SQCRC). The secondary objective was to examine the association of relationship quality with quality of life (QOL) in patients with mild Alzheimer's disease (AD) and their caregivers. METHODS: In this study, a sample of 50 patients diagnosed with mild AD and their primary caregivers were included. Participants underwent a full neuropsychological evaluation. The quality of the relationship between persons with AD and their caregivers was assessed using the SQCRC. Furthermore, other scales of relationship quality, well-being of the person with AD, and well-being of the caregiver were used. RESULTS: The results showed that the SQCRC has a good internal consistency and high validity. Also, relationship quality as rated by the AD patients (r = 0.37, P < 0.1) and their caregivers (r = 0.51, P < 0.1) was significantly correlated with QOL. CONCLUSIONS: The findings suggest that many persons with mild AD can rate their relationship quality and that the patient's self-rated relationship quality is a substantial predictor of their QOL.

Telephone-Administered Cognitive Behavioral Therapy for Body Dysmorphic Disorder: Case Series.

Cognitive behavioral therapy is an effective treatment for body dysmorphic disorder (BDD), but many patients do not receive appropriate treatment due to several treatment barriers and psychosocial care structures. Low-threshold interventions, including those from the field of e-mental health, could improve access to psychotherapy. In addition to internet-administered therapy, telephone-administered therapy may reduce treatment barriers, especially during the COVID-19 pandemic. This article presents four case reports of the same treatment (12 weeks of telephone-administered cognitive behavioral therapy accompanied by a workbook) applied to patients with body dysmorphic disorder during the summer of 2020. Three patients who completed the treatment had clinically relevant reductions in body dysmorphic and depressive symptoms and improved insight. One patient did not complete the telephone-administered therapy because her symptoms worsened, and she needed a more intensive form of treatment. These findings encourage future studies on the efficacy and effectiveness of telephone-administered treatment for BDD and its role in stepped-care models.

A Tailored Gender-Sensitive mHealth Weight Loss Intervention (I-GENDO): Development and Process Evaluation.

BACKGROUND: Given the increase in the prevalence of overweight and obesity worldwide, the number of digital weight loss interventions has also risen. However, these interventions often lack theoretical background and data on long-term effectiveness. The consideration of individual and gender differences in weight-related psychological parameters might enhance the efficacy and sustainability of mobile-based weight loss interventions. OBJECTIVE: This paper presented an introduction to and the process evaluation of a 12-week gender-sensitive mobile health (mHealth) weight loss intervention (I-GENDO) combining computer-based and self-tailoring features. METHODS: Between August 2020 and August 2021, individuals with overweight (BMI 25.0-29.9 kg/m²), those with obesity class I (BMI 30.0-34.9 kg/m²), and those with obesity class II (BMI 35.0-39.9 kg/m²) were recruited to the I-GENDO project, a multicenter study in Germany. The mHealth intervention aimed at targeting individual psychological factors associated with the development and persistence of overweight and obesity (eg, emotional eating) using computer-based tailoring. Moreover, the intervention took a gender-sensitive approach by implementing self-tailoring of gender-targeted module versions. The computer-based assignment of the main modules, self-selection of gender-targeted module versions, and use patterns were evaluated while considering gender. Moreover, gender differences in the usability assessment were analyzed. RESULTS: Data from the intervention arm of the study were processed. A total of 116 individuals with overweight and obesity (77/116, 66.4% women; age mean 47.28, SD 11.66 years; BMI mean 33.58, SD 3.79 kg/m2) were included in the analyses. Overall, the compliance (90/109, 82.6%) and satisfaction with the app (mean 86% approval) were high and comparable with those of other mobile weight loss interventions. The usability of the intervention was rated with 71% (5.0/7.0 points) satisfaction. More women obtained the main module that focused on emotion regulation skills. Most men and women selected women-targeted versions of the main modules. Women used the app more frequently and longer than men. However, women and men did not differ in the progress of use patterns throughout the intervention. CONCLUSIONS: We developed a tailored gender-sensitive mHealth weight loss intervention. The usability of and engagement with the intervention were satisfactory, and the overall satisfaction with the intervention was also high. Gender differences must be considered in the evaluation of the effectiveness and sustainability of the intervention.

PEX19 Coordinates Neutral Lipid Storage in Cells in a Peroxisome-Independent Fashion.

Cellular lipid metabolism is tightly regulated and requires a sophisticated interplay of multiple subcellular organelles to adapt to changing nutrient supply. PEX19 was originally described as an essential peroxisome biogenesis factor that selectively targets membrane proteins to peroxisomes. Metabolic aberrations that were associated with compromised PEX19 functions, were solely attributed to the absence of peroxisomes, which is also considered the underlying cause for Zellweger Spectrum Disorders. More recently, however, it was shown that PEX19 also mediates the targeting of the VCP/P97-recuitment factor UBXD8 to the ER from where it partitions to lipid droplets (LDs) but the physiological consequences remained elusive. Here, we addressed the intriguing possibility that PEX19 coordinates the functions of the major cellular sites of lipid metabolism. We exploited the farnesylation of PEX19 and deciphered the organelle-specific functions of PEX19 using systems level approaches. Non-farnesylated PEX19 is sufficient to fully restore the metabolic activity of peroxisomes, while farnesylated PEX19 controls lipid metabolism by a peroxisome-independent mechanism that can be attributed to sorting a specific protein subset to LDs. In the absence of this PEX19-dependent LD proteome, cells accumulate excess triacylglycerols and fail to fully deplete their neutral lipid stores under catabolic conditions, highlighting a hitherto unrecognized function of PEX19 in controlling neutral lipid storage and LD dynamics.

A p38-p65 transcription complex induced by endothelin-1 mediates signal transduction in cancer cells.

Endothelin-1 is a powerful mitogen for various tumor and non-tumor cells. Its signaling cascade induces the inflammatory NF-kappaB complex, leading to expression of a number of target genes. In this context, MAPK p38 has been regarded as a potential phosphate donor for the p65 subunit of NF-kappaB. In the present study in HeLa cells, we have found that ET-1 induced signalling activates the NF-kappaB transcription complex (TC) in the nucleus at 6 h specifically via ET-A - but not ET-B receptor. The TC contains p65, p38 (alpha and beta) - binding to the NLS of p65 in the cytoplasm - as well as p50, but no IkappaBalpha. Specific p38 inhibition by SB203580 or by siRNA interferes markedly with gene expression of several target genes. Complex formation occurs in the cytoplasm, and both transcription factors transmigrate as a complex in the nucleus. Overexpression of p38, treatment with Chrysin, MG132, or dimethylformamide shows dependence of TC on p38 as partner. In other tumor cells lines studied, ET-1 activates TC, with p38 as an important complex partner of p65. TC-induction by ET-1 contains about twice the amount of p38 than by TNFalpha. Thus, p38 may be an additional therapeutic target to control inflammatory gene expression in tumor cells.

Endothelin-1 induces NF-kappaB via two independent pathways in human renal tubular epithelial cells.

BACKGROUND: Endothelin-1 (ET-1) is a major transcriptional activator of renal proximal tubule cells acting in an autocrine and paracrine manner. In animal studies, ET-1 has been implicated in progressive renal interstitial fibrosis by promoting gene expression, possibly via the inflammatory NF-kappaB signal pathway. While ET-1-dependent mechanisms of signal transduction have been studied mainly in tumor cell lines, we analyzed the mechanism of ET-1-induced, NF-kappaB-mediated target gene activation in proximal tubule cells. METHODS: Human renal proximal tubule cells were stimulated with ET-1 and gene expression analyzed by protein microarray, Western blot, non-radioactive electromobility shift assay, and quantitative real-time polymerase chain reaction. RESULTS: Activation of NF-kappaB occurs only via an ET-1-specific type A receptor (not type B as in animals). Induction can be blocked by bosentan, and endothelin-A but not endothelin-B receptor-specific antagonists. Protein microarray screening shows activation of two independent cascades (via the endothelin-A receptor, or via diacylglycerol) leading to NF-kappaB induction. The independent induction is also reflected by target gene expression such as the vascular cell adhesion molecule-1, interleukin-6, and fractalkine at different time points. CONCLUSION: Thus prohibiting ET-1-mediated gene transcription necessitates blocking of NF-kappaB and diacylglycerol signal transduction in proximal tubule cells.

Cognitive behavioural treatment for mild Alzheimer's patients and their caregivers (CBTAC): study protocol for a randomized controlled trial.

BACKGROUND: About 90 % of all persons with mild Alzheimer's disease experience neuropsychiatric symptoms, most frequently apathy, depression, anxiety and irritability. These symptoms are associated with greater morbidity, a reduced quality of life for the patient, an increased burden and depression for the caregiver, and higher costs of care and nursing home placement. Psychosocial interventions based on behaviour therapy represent the most efficacious treatment of neuropsychiatric symptoms. However, there is no study, to our knowledge, that has evaluated a multicomponent treatment programme based on comprehensive, cognitive behavioural therapy (CBT). This randomized controlled trial aims to evaluate a CBT-based treatment programme consisting of 8 modules and 25 sessions. METHODS/DESIGN: Fifty patients with mild Alzheimer's disease alone or with mild mixed dementia (Alzheimer's disease and vascular dementia) who have any neuropsychiatric symptom will be included. A caregiver must be available. The patients and their caregivers will be randomized to either the CBT-based intervention group or to the control condition group, which receives treatment as usual. The primary outcome measure is depression in the patient with Alzheimer's disease. The secondary outcome measures for a person with Alzheimer's disease are other neuropsychiatric symptoms, quality of life and coping strategies. The secondary outcome measures for a caregiver are caregiver's burden, depression, anxiety, anger, quality of life and coping strategies. Neuropsychological testing includes tests of cognitive function and activities of daily living and a global clinical assessment of severity. Participants in both groups will be assessed before and after the treatment phase (lasting approximately 9 months). Follow-up assessments will take place 6 and 12 months after treatment. All assessments will be conducted by blinded assessors. DISCUSSION: This trial has the potential to establish an empirically based psychological treatment for non-cognitive symptoms that reduce the quality of life of a person with dementia and a caregiver. This treatment approach focuses not only on the person with dementia, but also on the caregiver and on the dyad. The treatment manual will be published and training workshops will be offered, so that the information can be widely spread among healthcare professionals. TRIAL REGISTRATION: ClinicalTrials.gov NCT01273272.

A novel evaluation method for paraffinized human renal biopsies using quantitative analysis of microdissected glomeruli and VCAM-1 as marker of inflammatory mesangial cell activation.

BACKGROUND: In the glomerular mesangium, immunologic and/or infectious activation of the inflammatory, NF-kappaB-mediated signal pathway can induce a progression of already existing mesangial lesions in non-immunologic and immunologic glomerular disease. This progression is preceded by upregulated mesangial gene expression of which the vascular cell adhesion molecule-1, VCAM-1 (vascular cell adhesion molecule-1), is a well-established marker. Its evaluation on minimal tissue such as routinely paraffinized needle core biopsies is not established and needs the development of a novel evaluation method more meaningful than common immunohistology. METHODS: By laser-microdissection, 10 glomeruli/case were isolated from 5 micro m thick tissue slices in a total of 15 cases of mesangial proliferation with different renal diseases (IgA nephropathy, lupus nephritis and mesangial proliferative lesions of unknown aetiology) vs transplant biopsies as negative and TNF alpha-treated cultured human mesangial cells as positive controls. After reverse transcription of isolated RNA, cDNA aliquots were quantified for VCAM-1 expression by real-time PCR using the threshold cycle (C(t)) method, normalized for the housekeeping gene beta-actin, and compared with qualitative RT-PCR results. RESULTS: Unsuspected VCAM-1 transcript steady-state levels could be detected by real-time PCR in agreement with qualitative PCR, while morphologic and immunohistologic analyses were unrevealing. As yields of RNA extraction in femtogram quantities cannot be measured spectrophotometrically, a C(t)-ratio was formed between beta-actin and VCAM-1 per case showing high VCAM-1 expression in lupus nephritis (1.39), and moderate expression in IgA nephropathy (1.08-1.23) vs TNF alpha-treated mesangial cells (0.97-1.23) and negative control cases (0.66-0.68). CONCLUSIONS: This is the first reported gene expression analysis method for routinely paraffininzed human renal biopsies, demonstrating the power of combined laser-microdissection and PCR quantification as novel methods for the evaluation of minimal tissue beyond purely descriptive morphologic analysis.