A histone point mutation that switches on autophagy.

The multifaceted process of aging inevitably leads to disturbances in cellular metabolism and protein homeostasis. To meet this challenge, cells make use of autophagy, which is probably one of the most important pathways preserving cellular protection under stressful conditions. Thus, efficient autophagic flux is required for healthy aging in many if not all eukaryotic organisms.

Ruxolitinib.

Ruxolitinib, formerly known as INCB018424 or INC424, is a potent and selective oral inhibitor of JAK1 and JAK2. Ruxolitinib has been approved for the treatment of myelofibrosis, which is characterized, biologically, by the activation of the JAK-STAT pathway and, clinically, by bone marrow fibrosis, splenomegaly, abnormal blood counts, and poor quality-of-life through associated symptoms. Ruxolitinib treatment results in a meaningful reduction in spleen size and symptom burden in the majority of myelofibrosis patients, and it may also have a favorable effect on survival.

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats.

Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinson's disease (PD) cases refractory to medication. Cell transplantation is a tissue-restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival.

Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan.

Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast.

Musical chairs during mitophagy.

Mitophagy, or the autophagic degradation of mitochondria, is thought to be important in mitochondrial quality control, and hence in cellular physiology. Defects in mitophagy correlate with late onset pathologies and aging. Here, we discuss recent results that shed light on the interrelationship between mitophagy and mitochondrial dynamics, based on proteomic analyses of protein dynamics in wild-type and mutant cells.

Organization of the human fetal subpallium.

The subpallium comprises large parts of the basal ganglia including striatum and globus pallidus. Genes and factors involved in the development of the subpallium have been extensively studied in most vertebrates, including amphibians, birds, and rodents. However, our knowledge on patterning of the human subpallium remains insufficient.

Patient communication competence: development of a German questionnaire and correlates of competent patient behavior.

Objective: The aim of our study was to design and psychometrically test a patient questionnaire to capture patient communication competence in the context of patient-provider interaction (CoCo questionnaire). We also aimed to determine patient characteristics associated with competent patient behavior.

Methods: To assure content validity, we initially conducted 17 focus groups (n=97) made up of patients and providers.

Characterization of early autophagy signaling by quantitative phosphoproteomics.

Under conditions of nutrient shortage autophagy is the primary cellular mechanism ensuring availability of substrates for continuous biosynthesis. Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment.

Health education literacy in patients with chronic musculoskeletal diseases: development of a new questionnaire and sociodemographic predictors.

It was our aim to develop a questionnaire for patients with chronic musculoskeletal diseases to self-report their health education literacy, to analyse the psychometric properties of the instrument and to test hypotheses concerning sociodemographic predictors of health education literacy. A total of 577 patients with chronic back pain or osteoarthritis who underwent inpatient rehabilitation were surveyed. The resulting 'HELP questionnaire' (health education literacy of patients with chronic musculoskeletal diseases) consists of 18 items and three scales (comprehension of medical information, applying medical information, communicative competence in provider interactions).

Development and Psychometric Evaluation of a German Version of the PROMIS® Item Banks for Satisfaction With Participation.

The Patient Reported Outcomes Measurement Information System (PROMIS) initiative aims to provide reliable and precise item banks measuring patient-reported outcomes in different health domains. The aim of the present work was to provide a German translation of the PROMIS item banks for satisfaction with participation and to psychometrically test these German versions. Cognitive interviews followed a forward-backward translation.

The nephronophthisis gene product NPHP2/Inversin interacts with Aurora A and interferes with HDAC6-mediated cilia disassembly.

Background: Nephronophthisis (NPH) is a rare recessive disease caused by several different gene mutations. Most gene products localize to the cilium, and thus, the various NPH manifestations including kidney cysts and situs inversus have been linked to ciliary defects.

Results: Here, we describe that targeted knockdown of NPHP2 significantly reduced the number of cilia on polarized MDCK cells.

Participation and social functioning in patients with fibromyalgia: development and testing of a new questionnaire.

Background: While there are numerous instruments for capturing the symptoms of fibromyalgia syndrome (FMS) patients, there is a lack of questionnaires capable of measuring in detail FMS patients' participation and social functioning. It was our aim to develop and methodologically test a new patient questionnaire specific to FMS measuring these concepts (the "Fibromyalgia Participation Questionnaire" FPQ).

Methods: We first conducted a qualitative prestudy (focus groups, N = 38) to identify which impairments FMS patients experience in daily life because of their illness.

Validation of the Freiburg Comorbidity Index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome.

Background: The outcomes of MM patients vary considerably and depend on a variety of host- and disease-related risks. As yet, a comorbidity risk index in MM patients has neither been standardized nor validated.

Patients And Methods: We conducted an initial analysis in 127 MM patients and developed the FCI, validating it in an independent cohort of 466 MM patients.

Intraindividual comparison of histopathological diagnosis obtained by stereotactic serial biopsy to open surgical resection specimen in patients with intracranial tumours.

Background: There are concerns in the literature about the accuracy of histopathological diagnosis obtained by stereotactic biopsy in patients with brain tumours. The aim of this study was to analyse intraindividually the histopathological accuracy of stereotactic biopsies of intracerebral lesions in comparison to open surgical resection.

Materials And Methods: Between 2007 and 2011 a total of 635 patients underwent stereotactic serial biopsy in our department.

Rat model for dominant dystrophic epidermolysis bullosa: glycine substitution reduces collagen VII stability and shows gene-dosage effect.

Dystrophic epidermolysis bullosa, a severely disabling hereditary skin fragility disorder, is caused by mutations in the gene coding for collagen VII, a specialized adhesion component of the dermal-epidermal junction zone. Both recessive and dominant forms are known; the latter account for about 40% of cases. Patients with dominant dystrophic epidermolysis bullosa exhibit a spectrum of symptoms ranging from mild localized to generalized skin manifestations.

Transplantation of human fetal tissue for neurodegenerative diseases: validation of a new protocol for microbiological analysis and bacterial decontamination.

Restorative cell therapy concepts in neurodegenerative diseases are aimed at replacing lost neurons. Despite advances in research on pluripotent stem cells, fetal tissue from routine elective abortions is still regarded as the only safe cell source. Progenitor cells isolated from distinct first-trimester fetal CNS regions have already been used in clinical trials and will be used again in a new multicenter trial funded by the European Union (TRANSEURO).

Illness beliefs and treatment beliefs as predictors of short-term and medium-term outcome in chronic back pain.

Objective: Patients' illness beliefs were shown to be more relevant than other psychosocial factors of influence for predicting outcome in back pain in primary care. The aim of this study was to determine whether illness beliefs and beliefs about rehabilitation are predictors of functioning, pain intensity, and coping with pain after rehabilitation in a population with longstanding chronic back pain.

Design And Patients: The study included 110 patients with longstanding chronic back pain in a longitudinal study design with 3 measurement points (before rehabilitation, end of rehabilitation, and 6 months follow-up).

Cell- and protein-based therapy approaches for epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin fragility disorder characterized by mechanically induced mucocutaneous blistering. On the molecular level DEB is caused by mutations leading to deficiency in collagen VII (CVII), a large extracellular protein building anchoring fibrils that attach the epidermis to the dermis. Severely affected patients suffer from wounds, which heal with excessive scarring causing mutilating deformities of hands and feet.

Induction of contact hypersensitivity in the mouse model.

Contact hypersensitivity (CHS) in the mouse model is a standard method to assess delayed type hypersensitivity (DTH) responses in the skin induced by low molecular weight chemicals that in humans cause contact dermatitis. These responses are clinically important and present as eczematous skin reactions. Here, this chapter describes the standard protocol for T cell-mediated CHS and a variation thereof, which allows to address more specific questions regarding immunologic pathomechanisms.

Self-efficacy for coping with cancer in melanoma patients: its association with physical fatigue and depression.

Objective: The purpose of this study was to explore the impact of self-efficacy for coping with cancer (SECC) on physical fatigue and depressive symptoms in melanoma patients, in comparison with objective factors, such as treatment with interferon-alpha (IFN-α) and medical and sociodemographic variables. Current literature shows that psychological distress in melanoma patients is generally moderate, that they experience high quality of life, and that symptoms of depression and fatigue have been mostly associated with adjuvant IFN-α treatment

Methods: A total of 175 melanoma patients, stages Ib-IIIc with and without low-dose IFN-α therapy, completed surveys on SECC, depression, and fatigue. Two hierarchical regression analyses were conducted to explore the predictive role of objective factors (first step: tumor stage, time since diagnosis, and current IFN-α treatment; second step: age and gender) in conjunction with the subjective factor of SECC (third step) on physical fatigue and depression.

Resistance to hypoxia-induced, BNIP3-mediated cell death contributes to an increase in a CD133-positive cell population in human glioblastomas in vitro.

In addition to intrinsic regulatory mechanisms, brain tumor stemlike cells (BTSCs), a small subpopulation of malignant glial tumor-derived cells, are influenced by environmental factors. Previous reports showed that lowering oxygen tension induced an increase of BTSCs expressing CD133 and other stem cell-related genes and more pronounced clonogenic capacity in vitro. We investigated the mechanisms responsible for hypoxia-dependent induction of CD133-positive BTSCs in glioblastomas.

The comprehensibility of health education programs: questionnaire development and results in patients with chronic musculoskeletal diseases.

Objective: The objective was to develop a comprehensive questionnaire for measuring the patient-perceived comprehensibility of health education programs (COHEP questionnaire). According to a conceptual model outlined in the article, comprehensibility is considered a context factor of patient health literacy.

Methods: A questionnaire study was carried out on N=577 patients with chronic musculoskeletal diseases.