A small molecule accelerates neuronal differentiation in the adult rat

Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.     

N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta

We have identified a novel liver X receptor (LXR) agonist (2) that activates the LXRbeta subtype with selectivity over LXRalpha. LXRbeta selectivity was confirmed using macrophages derived from LXR mutant mice. Despite its selectivity and modest potency, the compound can induce APO-AI-dependent cholesterol efflux from macrophages with full efficacy. Our results indicate that it is possible to achieve significant LXRbeta selectivity in a small molecule while maintaining functional LXR activity.     

Teaching spiritual care – a grounded theory study among undergraduate nursing educators

Aims and objectives. To explore teachers’ understanding of spirituality and how they prepare undergraduate nursing students to recognise spiritual cues and learn to assess and provide spiritual care. Background. Nursing education addresses patient care in all domains of the person. Systematic teaching and supervision of students to prepare them to assist patients spiritually is an important part of holistic care. However, few role models for spiritual care are seen in clinical practice, and limited research addresses necessary student competencies or how teachers can best facilitate this process. Design. Grounded theory was used to identify teachers’ main concern and develop a substantive grounded theory. Methods. Data collected during semi‐structured interviews at three Norwegian University Colleges in five focus groups with 19 undergraduate nursing teachers were conducted from 2008 to 2009. Data were analysed through constant comparison of transcribed interviews until categories emerged and were saturated. Results. The participants’ main concern was ‘How to help students recognize cues and ways of providing spiritual care’. Participants resolved this by ‘Journeying with Students through their Maturation’. This basic social process has three iterative phases that develop throughout the nursing programme: ‘Raising Student awareness to Recognize the Essence of Spirituality’, ‘Assisting Students to Overcome Personal Barriers’, and ‘Mentoring Students’ Competency in Spiritual Care’. Conclusion. Nursing education should prepare students to recognise and act on spiritual cues. Making spiritual assessment and interventions more visible and explicit throughout nursing programmes, in both classroom and clinical settings, will facilitate student maturation as they learn to integrate theoretical thinking into clinical practice. Relevance to clinical practice. Nursing students need role models who demonstrate spiritual care in the fast‐paced hospital environment as well as in other clinical practice settings. To model spirituality as part of nursing care can assist students to overcome their vulnerability and to safeguard ethical issues and promote patient integrity.     

Utilization of serology for the diagnosis of suspected Lyme borreliosis in Denmark: Survey of patients seen in general practice

Background  

Serological testing for Lyme borreliosis (LB) is frequently requested by general practitioners for patients with a wide variety of symptoms.     

Depth-force patterns of periodontal probing

It was the purpose of this study to determine whether probing force had an influence on the amount of clinical attachment-gain assessed after treatment by scaling and rootplaning. A probing device was constructed which allowed simultaneous monitoring of probing force and probe penetration and which standardized the insertion pathway for repeated measurements. In 10 periodontal patients, 2 deep pockets were selected which were measured before and after periodontal treatment by scaling and root-planing. Depth-force plots were compared by superimposition. Depth values were determined at 5 different force levels (0.25, 0.50, 0.75, 1.00 and 1.25 N) on each plot and changes of clinical attachment levels were calculated. A significant relationship was seen between probing force and attachment level. The values obtained with 0.25 N were significantly different from the values obtained with higher forces (p less than 0.001). Slight, but non-significant differences were noted in the amount of attachment-gain obtained at the 5 force levels. At a probing force level of 0.25 N, there was 0.80 mm mean attachment gain. With 0.50 N, there was a gain of 0.70 mm; with 0.75 N the gain amounted to 0.67 mm in mean. At 1.00 N and at 1.25 N, a gain of 0.66 mm was recorded.     

Ki-67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications

Proliferative activity of tumour cells assessed by immunohistochemical Ki-67 expression is one of several prognostic indicators in breast cancer. The major objective of this study was to investigate the prognostic impact of Ki-67 proliferative activity in the axillary lymph node metastases and in the matched primary breast carcinoma from 194 patients. There was a statistically significant up-regulation of Ki-67 protein in the metastatic deposit compared to where the primary tumour was found (p = 0.001). A low Ki-67 index in both the primary and the metastatic tumours was a favorable prognostic factor. A high index in both primary and metastatic lesion and an up-regulation from a low index in the primary tumour to a high index in the metastatic deposit represented an unfavorable prognostic factor. Multivariate analysis showed that Ki-67 expression in the metastases was a superior independent prognostic factor of clinical outcomes compared to that in the primary tumours. Ki-67 expression in ≥10% of carcinoma cells in the primary tumours and ≥15% in the nodal metastases seems to be optimal cut-off levels. Ki-67 is of value as an independent prognostic factor in breast cancer.     

Sequestering of damage-associated molecular patterns (DAMPs): a possible mechanism affecting the immune-stimulating properties of aluminium adjuvants

Aluminium-based adjuvants (ABAs) have been used in human and veterinary vaccines for decades, and for a long time, the adjuvant properties were believed to be mediated by an antigen depot at the injection site, prolonging antigen exposure to the immune system. The depot hypothesis is today more or less abandoned, and instead replaced by the assumption that ABAs induce an inflammation at the injection site. Induction of an inflammatory response is consistent with immune activation initiated by recognition of molecular patterns associated with danger or damage (DAMPs), and the latter are derived from endogenous molecules that normally reside intracellularly. When extracellularly expressed, because of damage, stress or cell death, a sterile inflammation is induced. In this paper, we report the induction of DAMP release by viable cells after phagocytosis of aluminium-based adjuvants. Two of the most commonly used ABAs in pharmaceutical vaccine formulations, aluminium oxyhydroxide and aluminium hydroxyphosphate, induced a vigorous extracellular expression of the two DAMP molecules calreticulin and HMGB1. Concomitantly, extracellular adjuvant particles adsorbed the DAMP molecules released by the cells whereas IL-1β, a previously reported inflammatory mediator induced by ABAs, was not absorbed by the adjuvants. Induction of extracellular expression of the two DAMP molecules was more prominent using aluminium hydroxyphosphate compared to aluminium oxyhydroxide, whereas the extracellular adsorption of the DAMP molecules was more pronounced with the latter. Furthermore, it is hypothesised how induction of DAMP expression by ABAs and their concomitant adsorption by extracellular adjuvants may affect the inflammatory properties of ABAs.