The mental health safety improvement programme: a national quality improvement collaborative to reduce restrictive practice in England

In 2018, 38 mental health inpatient wards belonging to NHS trusts across England took part in the national reducing restrictive practice collaborative project, which aimed to reduce the use of rapid tranquillisation, restraint and seclusion of patients by 33%. Teams were supported to use quality improvement tools by skilled coaches as part of a national collaborative learning system. At the end of the programme, the overall use of restrictive practice had reduced by 15%. Of the teams that achieved improvements, the average reduction in restrictive practice was 61%. Across the collaborative there were improvements in the mean monthly use of restraints and rapid tranquillisation, and in the total use of all three measures of restrictive practice combined. Support from quality improvement coaches allowed ideas to be tested across the collaborative, enabling the creation of a theory of change for reducing restrictive practice based on areas with a high degree of belief to inform future improvement work in this area

Regulation of PTP1D mRNA by Peptide Growth Factors in the Human Endometrial Cell Line HEC-1-A

Objective: To assess, in the human endometrial cell line HEC-1-A, the presence of protein tyrosine phosphatase 1D (PTDP1D) and the possible regulation of its mRNA expression by mitogens such as forskolin (an agent that increases intracellular cyclic adenosine monophosphate [cAMP] levels), epidermal growth factor (EGF), and insulin-like growth factor-I (IGF-I). Methods: Cells were grown to confluence and maintained in serum-free media for 24 hours before treatment. Cells were exposed to forskolin, EGF, and IGF-I for increasing time periods (0, 1, 3, 6, and 24 hours), and PTP1D mRNA expression was determined by Northern blot analysis. In addition, cells were incubated with increasing doses of forskolin (final concentrations: 1, 5, 10, 20, and 30 μmol/L0 for 6 hours. Results: When treated with the various mitogens, cells increased their stimulation of PTP1D mRNA expression in a time- and dose-dependent fashion. Specifically, forskolin, EGF, and IGF-I induced maximal mRNA expression at 6, 3, and 6 hours, respectively. Expression induced by forskolin, EGF, and IGF-I was five, three, and six times control levels, respectively. At a dose of 10 μmol/L, forskolin induced PTP1D mRNA expression almost two times higher than control values. Conclusion: These data suggest that in human endometrial carcinomas, cAMP, EGF, and IGF-I may regulate the expression of PTP1D mRNA, which may, in turn, play a role in uncontrolled cell proliferation and neoplastic transformation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68928/2/10.1177_107155769700400608.pd

Phosphoproteomics-Based Modeling Defines the Regulatory Mechanism Underlying Aberrant EGFR Signaling

BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR) results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992), one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling

Chromosomal location of human genes encoding major heat-shock protein HSP70

The HSP70 family of heat-shock proteins constitutes the major proteins synthesized in response to elevated temperatures and other forms of stress. In eukaryotes members of the HSP70 family also include a protein similar if not identical to bovine brain uncoating ATPase and glucose-regulated proteins. An intriguing relation has been established between expression of heat-shock proteins and transformation in mammalian cells. Elevated levels of HSP70 are found in some transformed cell lines, and viral and cellular gene products that are capable of transforming cells in vitro can also stimulate transcription of HSP70 genes. To determine the organization of this complex multigene family in the human genome, we used complementary approaches: Southern analysis and protein gels of Chinese hamster-human somatic cell hybrids, and in situ hybridization to human chromosomes. We demonstrate that functional genes encoding HSP70 proteins map to human chromosomes 6, 14, 21, and at least one other chromosome .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45535/1/11188_2005_Article_BF01534692.pd

The Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinases MK2 and MK3 Cooperate in Stimulation of Tumor Necrosis Factor Biosynthesis and Stabilization of p38 MAPK

MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels