Single motherhood is associated with increased psychosocial risks, affecting both mothers and their minor children. However, little is known about the specific psychosocial impact of maternal cancer in single mothers (SMs). This study compared psychological burden, quality of life, specific problems, and parental concerns between SMs and partnered mothers (PMs) affected by cancer and caring for minor children. Cross-sectional analysis of baseline data from a multicenter, non-randomized, controlled trial in Germany (Family-SCOUT). SMs and PMs affected by cancer were assessed for psychological burden (anxiety, depression, distress), quality of life, practical, family, emotional, spiritual/religious, and physical problems and parental concerns. A total of 54 SMs and 245 PMs were included. SMs reported more practical problems (p = 0.008, d = 0.44) and parental concerns than PMs (p = 0.011, d = 0.40). After controlling for demographic and clinical group differences, practical problems (p = 0.009, OR = 1.53) and parental concerns (p = 0.015, OR = 1.73) remained significantly associated with single motherhood. SMs and PMs did not differ in anxiety, depression, distress or quality of life. Overall, a large proportion of mothers reported clinically relevant elevated levels of anxiety (71.9

PURPOSE:This study aimed to assess the feasibility of a comprehensive psychosocial intervention for families coping with parental cancer. METHODS:A quasi-experimental trial with intervention and control group, employing a mixed-methods approach, was conducted. A total of 472 families affected by parental cancer participated. The feasibility of the intervention was evaluated based on study monitoring measures (on-site visits, team supervision meeting observations, case conference observations, best practice workshops, coordinating information exchange between intervention sites, and reviewing intervention documentation), process evaluation (semi-structured interviews, focus group discussion) and survey data. Data analysis involved thematic coding and descriptive statistics. RESULTS:The intervention was well-received by the participating families, with a high degree of acceptance observed. The feasibility of the intervention was found to be associated with specific dynamics within each family system and the motivation of the family members. The success of the intervention was described as dependent on the family-centered arrangement of the encounters, including factors such as frequency, duration, and mode, which greatly influenced its overall acceptability. CONCLUSION:The family-scout intervention demonstrates its feasibility as an effective intervention to reduce the burden experienced by families coping with parental cancer. Psychosocial oncology services should continue to develop and implement family-centered interventions to offer support to families during their cancer journey. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04186923. Retrospectively registered on 4 December 2019.

Background: Every year 37,000 parents with minor children receive a diagnosis of cancer. This leads to considerable distress and increased rates of psychological complications in all family members. Affected families are not adequately recognized, existing support structures do not adequately meet their specific needs, and are rarely used. Objectives: What are specific stressors and protective factors for families suffering from parental cancer? What care structures currently exist and what are the criteria for needs-based interventions for the family that can be implemented in standard care? Method: We provide a summary of the current state of knowledge (selective literature search), development of the new intervention “Family-SCOUT”, experiences, and first results of the effectiveness study. Results: Interventions need to address the complexity of the disease-related situation and the individual needs of all family members. In addition, they need to be conducted through active consultation and they should be family-centered, multisectoral, and comprehensive through all disease phases. Areas such as organizing everyday life, promoting open disease-related communication, and supporting emotional coping with the disease must be addressed. The successful implementation of such an intervention has been proven. The basis for inclusion in standard care is contractual regulations with health insurance companies. Conclusions: The prevention of health impairments in parents of underage children with cancer also includes support for all family members to cope with the disease. Oncologists and other physicians working with cancer patients should identify the affected parents, encourage transparent communication, and refer them to appropriate regional care services. These should become part of standard care.

Zusammenfassung Hintergrund Pro Jahr erfahren 37.000 Eltern mit minderjährigen Kindern, dass sie an Krebs erkrankt sind. Die Situation führt bei allen Familienmitgliedern zu erheblichen Belastungen und einer erhöhten Rate an psychischen Folgeerkrankungen. Betroffene Familien werden nicht adäquat wahrgenommen, bestehende Unterstützungsangebote treffen nicht ausreichend den spezifischen Bedarf und werden selten in Anspruch genommen. Fragestellung Was sind spezifische Belastungs- und Schutzfaktoren für Familien mit krebskrankem Elternteil? Welche Versorgungsangebote existieren aktuell und was sind Kriterien für bedarfsorientierte Interventionen, die in die Regelversorgung implementiert werden können? Methode Zusammenfassung aktueller Kenntnisstand (selektive Literaturrecherche), Entwicklung neue Versorgungsform „Familien-SCOUT“, Erfahrungen und erste Ergebnisse Wirsamkeitsstudie. Ergebnisse Passgenaue Interventionen sollten aufsuchend, familienzentriert, sektoren- und phasenübergreifend sein. Die Bereiche Organisation des Alltags, Förderung einer offenen krankheitsbezogenen Kommunikation und Unterstützung der emotionalen Krankheitsbewältigung müssen adressiert werden. Die erfolgreiche Implementierung einer solchen Intervention konnte nachgewiesen werden. Grundlage für die Übernahme in die Regelversorgung sind vertragliche Regelungen mit gesetzlichen Krankenversicherungen. Schlussfolgerungen Zur Prävention gesundheitlicher Beeinträchtigungen gehört bei krebskranken Eltern minderjähriger Kinder die Unterstützung aller Familienmitglieder bei der Krankheitsbewältigung. Onkologisch Tätige sollten die betroffenen Eltern identifizieren, sie zu offener Kommunikation in der Familie ermutigen und den entsprechenden regionalen Versorgungsangeboten zuführen. Diese sollten Teil der Regelversorgung werden.

Zusammenfassung Ziel der Studie Familien mit einem onkologisch erkrankten Elternteil sind besonderen emotionalen und organisatorischen Belastungen ausgesetzt, unter denen v. a. minderjährige Kinder leiden. Um die Belastung der Familienmitglieder zu reduzieren und einen koordinierten Zugang zu sozialen und logistischen Unterstützungsmöglichkeiten zu schaffen, wurde das Modellprojekt Brückenschlag initiiert. Ziel des vorliegenden Beitrags ist, die Einführung dieses Projektes in Anlehnung an das Inanspruchnahme-Modell von Andersen bezüglich Akzeptanz und Inanspruchnahme zu evaluieren. Methodik In einer querschnittlich angelegten Beobachtungsstudie im Mixed-Methods-Ansatz wurden semi-strukturierte schriftliche Expertenbefragungen (n=10) und die Sekundäranalyse von Routinedaten des Versorgungsmodells (n=171 Familien) kombiniert. Ergebnisse Quantitative Sekundäranalyse: Die teilnehmenden Familien haben 1–7 Kinder (Median (M) 2, Spannweite (S) 6). In 66% der Fälle ist die Mutter erkrankt, in 20% ist das erkrankte Elternteil alleinerziehend. Die familiären Kommunikationsstrukturen werden als „mittelmäßig“ bis „ziemlich offen“ eingeschätzt. Von den insgesamt 171 Kontaktaufnahmen (Studienzeitraum 9/14 bis 11/17), wurde Brückenschlag von 133 Familien in Anspruch genommen. 59,2% der Kontakte entstanden über die Psychoonkologie und den Sozialdienst. Kam der Kontakt auf Initiative des Patienten selbst oder durch die Psychoonkologie zustande, so wird signifikant häufiger (p=0,047) eine Begleitung etabliert als bei anderen Kontaktpersonen. Qualitative Analyse: Es zeigt sich ein Mangel in der Bekanntschaft und Koordination vorhandener Unterstützungsangebote und an familiären Ressourcen, vorhandene Unterstützungsangebote in Anspruch zu nehmen. Sowohl von den Familien gewünschte als auch im Verlauf etablierte Unterstützung fallen vor allem in den Bereich organisatorischer Unterstützung. Brückenschlag erleichtert dabei die Netzwerkarbeit und übernimmt eine Lotsenfunktion für die Familien. Schlussfolgerung Die gesammelten Daten deuten darauf hin, dass Familien, die in ihren soziodemographischen Merkmalen dem deutschen Durchschnitt entsprechen, tatsächlich einen großen Bedarf an organisatorischer Unterstützung entwickeln, sobald ein Elternteil an Krebs erkrankt. Das Modellprojekt Brückenschlag schafft einen Zugang zu Unterstützungsleistungen für Familien mit einem krebserkrankten Elternteil.

Background Every year 37,000 parents with minor children receive a diagnosis of cancer. This leads to considerable distress and increased rates of psychological complications in all family members. Affected families are not adequately recognized, existing support structures do not adequately meet their specific needs, and are rarely used. Objectives What are specific stressors and protective factors for families suffering from parental cancer? What care structures currently exist and what are the criteria for needs-based interventions for the family that can be implemented in standard care? Method We provide a summary of the current state of knowledge (selective literature search), development of the new intervention "Family-SCOUT", experiences, and first results of the effectiveness study. Results Interventions need to address the complexity of the disease-related situation and the individual needs of all family members. In addition, they need to be conducted through active consultation and they should be family-centered, multisectoral, and comprehensive through all disease phases. Areas such as organizing everyday life, promoting open disease-related communication, and supporting emotional coping with the disease must be addressed. The successful implementation of such an intervention has been proven. The basis for inclusion in standard care is contractual regulations with health insurance companies. Conclusions The prevention of health impairments in parents of underage children with cancer also includes support for all family members to cope with the disease. Oncologists and other physicians working with cancer patients should identify the affected parents, encourage transparent communication, and refer them to appropriate regional care services. These should become part of standard care.

Abstract Background: Families with minor children affected by parental cancer are at risk of considerable emotional and organizational stress that can severely burden all family members. So far, there has been a lack of comprehensive support services for affected families. The aim of this project is to implement and evaluate a complex psychosocial intervention for these families by providing advice, information and care on an emotional, psycho-social and communicative level during and after the cancer experience and across healthcare sectors.Methods: Family-SCOUT is a project supported by the German Innovation Fund (https://innovationsfonds.g-ba.de/). The evaluation is based on a mixed method quasi-experimental design with intervention and control group. A standardized postal survey at three measurement points (T0: study enrollment; T1: 3 months follow-up; T2: 9 months follow-up), secondary data from the participating health insurance funds, and semi-structured qualitative interviews are used for summative and formative evaluation. Study aim is to include n=560 families. Data will be analyzed according to the intention-to-treat principle. The primary analysis is the comparison of the Hospital Anxiety and Depression Scale (HADS) response rates (minimal important difference (MID) ≥ 1.6 in at least one of the two parents) at T2 between the intervention and control group using Fisher’s exact test. The conduct of the study as well as the development and implementation of the intervention will be accompanied by comprehensive study monitoring following the principles of an effectiveness-implementation hybrid study. Discussion: Results will allow to test the effectiveness and efficiency of the intervention for the target group. First experience with the implementation of the intervention in model regions will be available. The evaluation results will serve as basis to assess the need of including the intervention in the catalogue of services of the statutory health insurance funds in Germany. Trial registration: ClinicalTrials.gov, NCT04186923. Retrospectively registered on 4 December 2019.

The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.

The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.

Abstract Introduction Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown. Methods The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4) to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1 (placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examinations including cardiological signs. The primary outcome is the change in the Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the up-regulation of the frataxin protein level, safety and survival/death. Perspective The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide treatment in patients with Friedreich ataxia. Trial registration EudraCT-No.: 2017-002163-17, ClinicalTrials.gov NCT03761511.

AMPK is an energy-sensing kinase and is required for the induction and progression of the autophagy process. In this chapter, we describe experimental approaches to study the steady state and flux of autophagy in response to AMPK activation. For this purpose, we provide detailed protocols for the measurement of general as well as AMPK-specific autophagy markers by immunoblot and immunofluorescence analysis.

Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway. The E102Q mutation in one such candidate gene, the endoplasmic reticulum (ER) chaperone Sigma receptor-1 (SigR1), has been reported to cause juvenile ALS. Although loss of SigR1 protein contributes to neurodegeneration in several ways, the molecular mechanisms underlying E102Q-SigR1-mediated neurodegeneration are still unclear. In the present study, we showed that the E102Q-SigR1 protein rapidly aggregates and accumulates in the ER and associated compartments in transfected cells, leading to structural alterations of the ER, nuclear envelope and mitochondria and to subsequent defects in proteasomal degradation and calcium homeostasis. ER defects and proteotoxic stress generated by E102Q-SigR1 aggregates further induce autophagy impairment, accumulation of stress granules and cytoplasmic aggregation of the ALS-linked RNA-binding proteins (RBPs) matrin-3, FUS, and TDP-43. Similar ultrastructural abnormalities as well as altered protein degradation and misregulated RBP homeostasis were observed in primary lymphoblastoid cells (PLCs) derived from E102Q-SigR1 fALS patients. Consistent with these findings, lumbar α-MNs of both sALS as well as fALS patients showed cytoplasmic matrin-3 aggregates which were not co-localized with pTDP-43 aggregates. Taken together, our results support the notion that E102Q-SigR1-mediated ALS pathogenesis comprises a synergistic mechanism of both toxic gain and loss of function involving a vicious circle of altered ER function, impaired protein homeostasis and defective RBPs.

For quantitative determinations of orcokinin, an indirect, noncompetitive sandwich ELISA was developed. This ELISA is highly specific for orcokinin and the detection limit is 1 fmol. In three astacidean species (Orconectes limosus, Homarus americanus, and Astacus astacus) orcokinin immunoreactivity (OK-IR) was measurable in all parts of the nervous system. Upon normalization to the protein content of the tissue (pmol/mg protein), concentrations were shown to be in the same range in all three species. The distribution of OK-IR in the nervous system is also very similar in the three species. In Orconectes limosus the following values were obtained (in pmol/mg protein): cerebral ganglion 215, optic ganglia in the eyestalk 38, subesophageal ganglion 182. The thoracic ganglia have lower concentrations (35-72) and the abdominal ganglia (AG) 1-5 even lower ones (11-17). In the AG 6 of Orconectes, from which the innervation of the hindgut arises, concentrations are approximately five times higher than in the other AG. In hindgut tissue, relatively high concentrations of 22 pmol/mg were measured, which is in agreement with the demonstrated function of orcokinin as a hindgut excitatory substance. Markedly elevated levels of orcokinin were observed in the AG 6 of Astacus, but not in Homarus. Orcokinin could also be measured consistently and reliably in the hemolymph, where its concentration is approximately 1 X 10(-11) M. These results show that orcokinin may be released into the hemolymph and may act as a hormone, in addition to its role as a locally acting neurotransmitter/modulator.