Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Characterizing Evidence-Based Practice and Training Resource Barriers: A Needs Assessment

In the last two decades, evidence-based practices have become increasingly prioritized, and yet, adoption of evidence-based practices and principles is still limited. It is important then to characterize the contextual factors that facilitate or impede implementation and sustainment evidence-based practice. We conducted a needs assessment of diverse mental health providers (including clinical psychologists, social workers, and psychiatrists) to: (a) identify the most commonly perceived practical barriers to incorporating evidence-based practices into clinical care, (b) describe the most valuable features of existing resources that support evidence-based practice, and (c) offer suggestions for how those features can be leveraged to decrease challenges associated with integrating evidence-based principles into clinical practice. We present the results in this study of N = 476 clinical educators, practitioners, and trainees. Practicing in an evidence-based way was identified as a priority by most respondents and yet respondents noted time, cost, and access as barriers to training in, and ongoing engagement with, evidence-based practice. Assessing needs and desired resources helps create the roadmap toward sustainment of evidence-based care. Public Significance Statement Although effective treatments exist for a range of mental health concerns, adoption of evidence-based practices (EBPs) is still low. In this survey, mental health providers endorsed positive attitudes toward EBPs and yet many reported ongoing barriers, particularly lack of time, cost, and access. Our study suggests that sustainability of these practices may be enhanced by quality, accessible, and free resources for training and practice

Accelerating the rate of progress in reducing mental health burdens: Recommendations for training the next generation of clinical psychologists

Despite criticisms dating back to the 1950s, and minimal progress reducing mental health burdens, the dominant training model in clinical psychology has not changed. We argue that for clinical psychologists to reduce mental health burdens, they (collectively) need to devote a much larger proportion of their professional efforts to a broader range of activities, particularly prevention. We propose a highly flexible two-phase model for clinical psychology training. The initial Foundational Knowledge and Competency Phase focuses on foundational concepts in the science of clinical psychology and direct client care. During the Focused Competency Phase, students may continue training for traditional roles in providing direct client care or, alternatively, develop other roles for using psychological science to address mental health conditions.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm AML patients

We designed a prospective, observational study enrolling patients presenting for treatment of AML at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), function and geriatric health, in 6 groups: 1) the entire cohort, 2) ≥65 years old, 3) high comorbidity burden, 4) intermediate cytogenetic-risk, 5) adverse cytogenetic-risk, and 6) first complete remission with or without measurable residual disease. Patient health and preferences were assessed eight times across 2 years. Time-dependent regression models were used. Among 692 evaluable patients, 46% received HCT with 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality in the entire group and most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity-burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in all groups. While function, social life, performance status, and depressive symptoms were better for those selected for HCT compared to those who were not, these health advantages were lost after receiving HCT. Recipients and non-recipients of HCT similarly ranked and expected cure as main goal of therapy, while physicians expected more cure for the formers. Accounting for health impairments negate survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is due mostly to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT