Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.

Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

Prognostic Impact of Peripelvic Fat Invasion in pT3 Renal Pelvic Transitional Cell Carcinoma

Renal pelvic transitional cell carcinoma (TCC), which invades beyond muscularis into peripelvic fat or the renal parenchyma, is diagnosed as stage pT3 despite its structural complexity. We evaluated the prognostic impact of peripelvic fat invasion in pT3 renal pelvic TCC. Between 1986 and 2004, the medical records on 128 patients who were surgically treated for renal pelvic TCC were retrospectively reviewed. Sixty patients with pT3 disease were eligible for the main analysis. The prognostic impact of various clinicopathological factors was analyzed using univariate and multivariate analyses. On univariate analysis, sex, age, concomitant bladder tumors, concomitant ureter tumors, lymphadenectomy, adjuvant chemotherapy, tumor grade, multiplicity, renal parenchymal invasion, and carcinoma in situ did not influence the disease-specific survival (p>0.05). By contrast, peripelvic fat invasion, lymph node invasion, and lymphovascular invasion were each significantly associated with disease-specific survival (p<0.05). Multivariate analysis showed that peripelvic fat invasion (p=0.012) and lymph node invasion (p=0.004) were independent prognostic factors. In conclusion, peripelvic fat invasion is a strong prognostic factor in pT3 renal pelvic TCC. Thus, systemic adjuvant therapy should be considered in the presence of peripelvic fat invasion, even if the lymph nodes are not involved

EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series

<p>Abstract</p> <p>Background</p> <p>This paper presents a case study that demonstrates the evolution of a project entitled "Enhancing QUality-of-care In Psychosis" (EQUIP) that began approximately when the U.S. Department of Veterans Affairs' Quality Enhancement Research Initiative (QUERI), and implementation science were emerging. EQUIP developed methods and tools to implement chronic illness care principles in the treatment of schizophrenia, and evaluated this implementation using a small-scale controlled trial. The next iteration of the project, EQUIP-2, was further informed by implementation science and the use of QUERI tools.</p> <p>Methods</p> <p>This paper reports the background, development, results and implications of EQUIP, and also describes ongoing work in the second phase of the project (EQUIP-2). The EQUIP intervention uses implementation strategies and tools to increase the adoption and implementation of chronic illness care principles. In EQUIP-2, these strategies and tools are conceptually grounded in a stages-of-change model, and include clinical and delivery system interventions and adoption/implementation tools. Formative evaluation occurs in conjunction with the intervention, and includes developmental, progress-focused, implementation-focused, and interpretive evaluation.</p> <p>Results</p> <p>Evaluation of EQUIP provided an understanding of quality gaps <it>and </it>how to address related problems in schizophrenia. EQUIP showed that solutions to quality problems in schizophrenia differ by treatment domain and are exacerbated by a lack of awareness of evidence-based practices. EQUIP also showed that improving care requires creating resources for physicians to help them easily implement practice changes, plus intensive education as well as product champions who help physicians use these resources. Organizational changes, such as the addition of care managers and informatics systems, were shown to help physicians with identifying problems, making referrals, and monitoring follow-up. In EQUIP-2, which is currently in progress, these initial findings were used to develop a more comprehensive approach to implementing and evaluating the chronic illness care model.</p> <p>Discussion</p> <p>In QUERI, small-scale projects contribute to the development and enhancement of hands-on, action-oriented service-directed projects that are grounded in current implementation science. This project supports the concept that QUERI tools can be useful in implementing complex care models oriented toward evidence-based improvement of clinical care.</p

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Treatment Duration of Febrile Urinary Tract Infections

Although febrile urinary tract infections (UTIs) are relatively common in adults, data on optimal treatment duration are limited. Randomized controlled trials specifically addressing the elderly and patients with comorbidities have not been performed. This review highlights current available evidence. Premenopausal, non-pregnant women without comorbidities can be treated with a 5–7 day regimen of fluoroquinolones in countries with low levels of fluoroquinolone resistance, or, if proven susceptible, with 14 days of trimethoprim-sulfamethoxazole. Oral β-lactams are less effective compared with fluoroquinolones and trimethoprim-sulfamethoxazole. In men with mild to moderate febrile UTI, a 2-week regimen of an oral fluoroquinolone is likely sufficient. Although data are limited, this possibly holds even in the elderly patients with comorbidities or bacteremia

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women

Facebook's Mobile Career

At the end of its first decade, Facebook’s identity, popularity, and characteristics are shaped in important ways by its becoming a form of mobile media, as much as it as platform associated with Internet and social media. This paper seeks to explore and understand Facebook as the important force in mobile media and communication it now is. It draws upon and combines perspectives from technology production, design, and economy, as well as user adoption, consumption, practices, affect, emotion, and resistance. The paper discusses the beginnings of mobile Facebook, and the early adoption of mobile Facebook associated with the rise of smartphones. The second part of the paper explores Facebook’s integration with photography (with Instagram) and social games (such as Zynga’s Farmville). The paper argues that Facebook’s mobile career is an accomplishment that has distinctively melded evolving affordances, everyday use across a wide range of settings, as well as political economies, corporate strategy, and design.Australian Research Counci

Standardisation framework for the Maudsley staging method for treatment resistance in depression

Background: Treatment-resistant depression (TRD) is a serious and relatively common clinical condition. Lack of consensus on defining and staging TRD remains one of the main barriers to understanding TRD and approaches to intervention. The Maudsley Staging Method (MSM) is the first multidimensional model developed to define and stage treatment-resistance in “unipolar depression”. The model is being used increasingly in treatment and epidemiological studies of TRD and has the potential to support consensus. Yet, standardised methods for rating the MSM have not been described adequately. The aim of this report is to present standardised approaches for rating or completing the MSM. Method: Based on the initial development of the MSM and a narrative review of the literature, the developers of the MSM provide explicit guidance on how the three dimensions of the MSM–treatment failure, severity of depressive episode and duration of depressive episode– may be rated. Result: The core dimension of the MSM, treatment failure, may be assessed using the Maudsley Treatment Inventory (MTI), a new method developed for the purposes of completing the MSM. The MTI consists of a relatively comprehensive list of medications with options for rating doses and provisions treatment for multiple episodes. The second dimension, severity of symptoms, may be assessed using simple instruments such as the Clinical Global Impression, the Psychiatric Status Rating or checklist from a standard diagnostic checklist. The standardisation also provides a simple rating scale for scoring the third dimension, duration of depressive episode. Conclusion: The approaches provided should have clinical and research utility in staging TRD. However, in proposing this model, we are fully cognisant that until the pathophysiology of depression is better understood, staging methods can only be tentative approximations. Future developments should attempt to incorporate other biological/ pathophysiological dimensions for staging