Developing a mobile data collection tool to manage a dispersed mental health workforce.

CONTEXT: The Rural Adversity Mental Health Program (RAMHP) connects people who need mental health assistance in rural and remote New South Wales (NSW), Australia with appropriate services and resources. In 2016, RAMHP underwent a comprehensive reorientation to meet new state and federal priorities. A full assessment of program data collection methods for management, monitoring and evaluation was undertaken. Reliable data were needed to ensure program fidelity and to assess program performance. ISSUES: The review indicated that existing data collection methods provided limited and unreliable information, were inconvenient for RAMHP coordinators to use and unsuited to their itinerant role. A mobile collection tool (app) was developed to address RAMHP activity data needs. A design and implementation process was followed to optimise data collection and to ensure the successful use of the app by coordinators. LESSONS LEARNED: The early planning investment was worthwhile, the app was successfully adopted by the coordinators and a much improved data collection capability was achieved. Moreover, data capture increased, while errors decreased. Data are more reliable, specific, timely and informative and are used for strategic and operational planning and to demonstrate program performance.

Reorientation of the Rural Adversity Mental Health Program: the value of a program logic model.

CONTEXT: The Rural Adversity Mental Health Program (RAMHP) was founded in 2007 with the specific focus of responding to drought-related mental health needs among farmers in rural and remote New South Wales (NSW), Australia. Successive re-funding enabled the program to evolve strategically and increase its reach. Over a decade, the program's focus has expanded to include all people in rural and remote NSW in need of mental health assistance, and not just in times of adversity such as drought. ISSUE: The program's longest re-funding period, 2016-2020, provided the opportunity for a comprehensive review and longer term planning. Several priorities influencing program renewal were evident at this time: the need to improve data collection and evaluation methods, a reassessment of the program's primary focus and the need to align with significant government mental health reforms. A program logic model (PLM) was developed, in collaboration with frontline RAMHP coordinators, to steer reorientation, clarify objectives, activities and outcomes, and improve data collection. A PLM is a graphic depiction of a program, showing the rationale of how inputs and activities lead to outcomes. LESSONS LEARNED: Four key lessons were identified. (1) The development of the PLM in collaboration with the RAMHP coordinators (frontline staff) was found to be an important vehicle for ensuring their acceptance and adoption of strategic changes. (2) The collaborative development process also provided the opportunity to decide upon consistent terminology to describe the program, facilitating communication of the value of RAMHP to external stakeholders. (3) The PLM enabled a clear but flexible program structure that aligned with changes in the mental health system to be described. (4) The PLM provided the foundation for the development of an evaluation framework, including a mobile app, to aid data collection to underpin accountability. Investing in the development of a PLM early in program reorientation provided many benefits for RAMHP, including improved role clarity and communication, staff commitment to program changes and a foundation for comprehensive program evaluation that integrates with program planning. The PLM proved a key foundational tool to reorient RAMHP by producing a clear program structure that was agreed upon by all staff.

Regulation of the divalent metal ion transporter via membrane budding.

The release of extracellular vesicles (EVs) is important for both normal physiology and disease. However, a basic understanding of the targeting of EV cargoes, composition and mechanism of release is lacking. Here we present evidence that the divalent metal ion transporter (DMT1) is unexpectedly regulated through release in EVs. This process involves the Nedd4-2 ubiquitin ligase, and the adaptor proteins Arrdc1 and Arrdc4 via different budding mechanisms. We show that mouse gut explants release endogenous DMT1 in EVs. Although we observed no change in the relative amount of DMT1 released in EVs from gut explants in Arrdc1 or Arrdc4 deficient mice, the extent of EVs released was significantly reduced indicating an adaptor role in biogenesis. Furthermore, using Arrdc1 or Arrdc4 knockout mouse embryonic fibroblasts, we show that both Arrdc1 and Arrdc4 are non-redundant positive regulators of EV release. Our results suggest that DMT1 release from the plasma membrane into EVs may represent a novel mechanism for the maintenance of iron homeostasis, which may also be important for the regulation of other membrane proteins.

Medical graduates becoming rural doctors: rural background versus extended rural placement.

OBJECTIVES: To determine whether recruitment of rural students and uptake of extended rural placements are associated with students' expressed intentions to undertake rural internships and students' acceptance of rural internships after finishing medical school, and to compare any associations. DESIGN, SETTING AND PARTICIPANTS: Longitudinal study of three successive cohorts (commencing 2005, 2006, 2007) of medical students in the Sydney Medical Program (SMP), University of Sydney, New South Wales, using responses to self-administered questionnaires upon entry to and exit from the Sydney Medical School and data recorded in rolls. MAIN OUTCOME MEASURES: Students' expressed intentions to undertake rural internships, and their acceptance of rural internships after finishing medical school. RESULTS: Data from 448 students were included. The proportion of students preferring a rural career dropped from 20.7% (79/382) to 12.5% (54/433) between entry into and exit from the SMP. A total of 98 students took extended rural placements. Ultimately, 8.1% (35/434) accepted a rural internship, although 14.5% (60/415) had indicated a first preference for a rural post. Students who had undertaken an extended rural placement were more than three times as likely as those with rural backgrounds to express a first preference for a rural internship (23.9% v 7.7%; χ(2) = 7.04; P = 0.008) and more than twice as likely to accept a rural internship (21.3% v 9.9%; χ(2) = 3.85; P = 0.05). CONCLUSION: For the three cohorts studied, rural clinical training through extended placements in rural clinical schools had a stronger association than rural background with a preference for, and acceptance of, rural internship.

Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis.

The divalent metal ion transporter DMT1 is critical for nonheme iron import. We have previously shown that DMT1 is regulated in vitro by ubiquitination that is facilitated by the adaptor proteins Ndfip1 and Ndfip2. Here we report that in Ndfip1(-/-) mice fed a low- iron diet, DMT1 expression and activity in duodenal enterocytes are significant higher than in the wild-type animals. This correlates with an increase in serum iron levels and transferrin saturation. Liver and spleen iron stores were also increased in Ndfip1(-/-) mice fed a normal diet. Counterintuitive to the increase in iron uptake, Ndfip1(-/-) mice fed a low iron diet develop severe microcytic, hypochromic anemia. We demonstrate that this is due to a combination of iron deficiency and inflammatory disease in Ndfip1(-/-) mice, because Ndfip1(-/-)/Rag1(-/-) immunodeficient mice fed a low iron diet did not develop anemia and showed an iron overload phenotype. These data demonstrate that Ndfip1 is a critical mediator of DMT1 regulation in vivo, particularly under iron restricted conditions.

Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2.

Many ion channels and transporters are regulated by ubiquitination mediated by the Nedd4 family of HECT-type ubiquitin ligases (E3s). These E3s commonly interact with substrates via their WW domains that bind to specific motifs in target proteins. However, not all potential targets of these E3s contain WW-binding motifs. Therefore, accessory proteins may mediate the interaction between Nedd4 family members and their targets. Here we report that the divalent metal ion transporter DMT1, the primary nonheme iron transporter in mammals, is regulated by ubiquitination mediated by the Nedd4 family member WWP2. DMT1 interacts with 2 WW domain-interacting proteins, Ndfip1 and Ndfip2, previously proposed to have roles in protein trafficking. This promotes DMT1 ubiquitination and degradation by WWP2. Consistent with these observations, Ndfip1(-/-) mice show increased DMT1 activity and a concomitant increase in hepatic iron deposition, indicating an essential function of Ndfip1 in iron homeostasis. This novel mechanism of regulating iron homeostasis suggests that Ndfips and WWP2 may contribute to diseases involving aberrant iron transport.

Regulation of functional diversity within the Nedd4 family by accessory and adaptor proteins.

Ubiquitination is essential in mediating diverse cellular functions including protein degradation and trafficking. Ubiquitin-protein (E3) ligases determine the substrate specificity of the ubiquitination process. The Nedd4 family of E3 ligases is an evolutionarily conserved family of proteins required for the ubiquitination of a large number of cellular targets. As a result, this family regulates a wide variety of cellular processes including transcription, stability and trafficking of plasma membrane proteins, and the degradation of misfolded proteins. The modular architecture of the proteins, comprising a C2 domain, multiple WW domains and a catalytic domain, enables diverse intermolecular interactions and recruitment to various subcellular locations. The WW domains commonly mediate interaction with substrate proteins; however, an increasing number of Nedd4 targets do not contain obvious WW domain-interaction motifs suggesting the involvement of accessory proteins. This review discusses recent insights into how accessory and adaptor proteins modulate the activities of Nedd4 family members, including recruitment of novel substrates, alteration of subcellular localisation and effects on ubiquitination.

Citron kinase is an essential effector of the Pbl-activated Rho signalling pathway in Drosophila melanogaster.

Pebble (Pbl)-activated RhoA signalling is essential for cytokinesis in Drosophila melanogaster. Here we report that the Drosophila citron gene encodes an essential effector kinase of Pbl-RhoA signalling in vivo. Drosophila citron is expressed in proliferating tissues but is downregulated in differentiating tissues. We find that Citron can bind RhoA and that localisation of Citron to the contractile ring is dependent on the cytokinesis-specific Pbl-RhoA signalling. Phenotypic analysis of mutants showed that citron is required for cytokinesis in every tissue examined, with mutant cells exhibiting multinucleate and hyperploid phenotypes. Strong genetic interactions were observed between citron and pbl alleles and constructs. Vertebrate studies implicate at least two Rho effector kinases, Citron and Rok, in cytokinesis. By contrast, we failed to find evidence for a role for the Drosophila ortholog of Rok in cell division. We conclude that Citron plays an essential, non-redundant role in the Rho signalling pathway during Drosophila cytokinesis.