The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation.

Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation.

Pain Interventions for people with dementia: a quasi-experimental study.

Background: Due to the complexity of the provision of care for people with dementia, pain assessment and management is still considered to be lacking. An optimal way to support frontline staff in providing pain assessment and management for people with dementia living in nursing homes has not yet been identified. The success of supporting interventions seems dependent on contextual factors in the nursing homes.

Trophic factor BDNF inhibits GABAergic signaling by facilitating dendritic enrichment of SUMO E3 ligase PIAS3 and altering gephyrin scaffold.

Posttranslational addition of a small ubiquitin-like modifier (SUMO) moiety (SUMOylation) has been implicated in pathologies such as brain ischemia, diabetic peripheral neuropathy, and neurodegeneration. However, nuclear enrichment of SUMO pathway proteins has made it difficult to ascertain how ion channels, proteins that are typically localized to and function at the plasma membrane, and mitochondria are SUMOylated. Here, we report that the trophic factor, brain-derived neurotrophic factor (BDNF) regulates SUMO proteins both spatially and temporally in neurons.

Medical end-of-life decisions in the oldest old in Switzerland.

Aims Of The Study: To analyse medical end-of-life decision making among the oldest old (80+ years) in Switzerland, focusing not only on treatments withheld or withdrawn but also on those continued until death.

Methods: This was a retrospective follow-up study of deaths registered in Switzerland between August 2013 and January 2014 using a standardised questionnaire completed by the attending physician. All individuals aged 65 years and older who did not die suddenly and completely unexpectedly, and who had met the responding physician prior to death were included (n = 2842).

Continuing, Withdrawing, and Withholding Medical Treatment at the End of Life and Associated Characteristics: a Mortality Follow-back Study.

Background: Studies on forgoing treatment often ignore treatments that are continued until death.

Objective: To investigate how often specific treatments are withdrawn or withheld before death and to describe the associated patient, physician, and care characteristics.

Design: National mortality follow-back study in Switzerland in 2013/2014 using a standardized survey to collect information on the patient's end of life and demographics on the physician.

Physician-related determinants of medical end-of-life decisions - A mortality follow-back study in Switzerland.

Background: Medical end-of-life decisions (MELD) and shared decision-making are increasingly important issues for a majority of persons at the end of life. Little is known, however, about the impact of physician characteristics on these practices. We aimed at investigating whether MELDs depend on physician characteristics when controlling for patient characteristics and place of death.

The catalytic function of the gephyrin-binding protein IQSEC3 regulates neurotransmitter-specific matching of pre- and post-synaptic structures in primary hippocampal cultures.

In dissociated neuronal cultures the absence of spatial and temporal cues causes the emergence of mismatched synapses, where post-synaptic proteins of GABAergic synapses are in part apposed to glutamatergic pre-synaptic terminals and vice versa. This mismatch offers an opportunity to study the mechanisms that regulate correct apposition of pre- and post-synaptic elements. We report here that the IQ motif and Sec7 domain-containing protein 3 (IQSEC3; BRAG3; synArfGEF) specifically regulates the mislocalization of GABAergic post-synaptic density (PSD) proteins.

Continuous deep sedation until death in patients admitted to palliative care specialists and internists: a focus group study on conceptual understanding and administration in German-speaking Switzerland.

Background: Continuous deep sedation until death is increasingly used to treat intolerable suffering of terminally ill patients. One of the highest incidences and strongest increases has been observed in Switzerland. Variation in prevalence estimates indicates a potential effect of differences in sedation practice between care settings and professionals.

Continuous Deep Sedation Until Death-a Swiss Death Certificate Study.

Background: In the last decade, the number of patients continuously deeply sedated until death increased up to fourfold. The reasons for this increase remain unclear.

Objective: To identify socio-demographic and clinical characteristics of sedated patients, and concurrent possibly life-shortening medical end-of-life decisions.

Pain Intervention for people with Dementia in nursing homes (PID): study protocol for a quasi-experimental nurse intervention.

Background: It is estimated that 19 to 83% of people with dementia suffer from pain that is inadequately treated in the last months of life. A large number of healthcare workers who care for these people in nursing homes lack appropriate expertise and may therefore not always recognise, assess and treat pain in those with dementia who have complex problems on time, properly and efficiently. The aim of this intervention trial is to identify care needs of people with dementia suffering from pain living in a nursing home.

Relocation experiences with unplanned admission to a nursing home: a qualitative study.

Background: In many countries, people over 85 years of age are relocated involuntarily or unplanned to a nursing home. In Switzerland, 43% of elderly over 85 years are admitted to nursing homes after hospital discharge. This percentage is higher than in the USA with 32.

Medical end-of-life decisions in Switzerland 2001 and 2013: Who is involved and how does the decision-making capacity of the patient impact?

Questions Under Study: In Switzerland, the prevalence of medical end-of-life practices had been assessed on a population level only once - in 2001 - until in 2013/14 an identical study was conducted. We aimed to compare the results of the 2001 and 2013 studies with a special focus on shared decision-making and patients' decision-making capacity.

Methods: Our study encompassed a 21.

Decision-making in caring for people with dementia at the end of life in nursing homes.

Background: Alleviating symptoms, fulfilling psychosocial needs, and the inclusion of family are among the criteria that determine care quality in palliative treatment. The care quality is especially inadequate for people with dementia (PwD) at the end of life. To improve this, it is necessary to understand the process of nurses' clinical decision-making in symptom management in the terminal phase of PwD.

Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects.

The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure.

Type and course of symptoms demonstrated in the terminal and dying phases by people with dementia in nursing homes.

Background: In all, 39 % of people living in Swiss nursing homes suffer from dementia. Detailed data about type and course of symptoms displayed by these patients in their terminal phase are lacking.

Methods: This descriptive, retrospective study analysed 65 nursing documents from deceased people with dementia in four nursing homes in the canton of Zurich, Switzerland.

Chemotherapy near the end of life: a retrospective single-centre analysis of patients' charts.

Background: Chemotherapy near the end of life is an issue frequently discussed nowadays. The concern is that chemotherapy could cause more harm than good in a palliative situation; this is even truer as the patient nears death. The objective of our study is to evaluate the aggressiveness of patient care near the end of life by determining how many cancer patients receive chemotherapy during their final weeks.

Breast cancer in women 80 years of age and older: a comprehensive analysis of an underreported entity.

Background: Approximately 10% of breast cancer (BC) patients are over the age of 80. We present the first comprehensive review on this particular group of patients.

Patients And Methods: The treatments and disease courses of an unselected cohort of patients, whose age at first diagnosis was ≥ 80 years (n = 151), were compared to those of a group of women, who were aged 56-66 years (n = 372).

A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome.

Background: Aggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) (intermediate BL/DLBCL) but deviating with respect to one or more characteristics are increasingly recognized. The limited knowledge about these biologically heterogeneous lymphomas hampers their assignment to a known entity, raising incertitude about optimal treatment approaches. We therefore searched for discriminative, prognostic, and predictive factors for their better characterization.