Relationship of health literacy and adherence to oral anticoagulation therapy in patients with atrial fibrillation: a cross‐sectional study

Journal of Thrombosis and Thrombolysis - Oral anticoagulant therapy (OAT) has increased substantially due to the aging population and prevalence rise of atrial fibrillation (AF). Medication...     

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Adult stem cells are believed to be maintained by a specialized microenvironment, the niche, which provides short-range signals that either instruct stem cells to self-renew or inhibit execution of preprogrammed differentiation pathways. In Drosophila testes, somatic cyst stem cells (CySCs) and the apical hub form the niche for neighboring germline stem cells (GSCs), with CySCs as the proposed source of instructive self-renewal signals [Leatherman JL, Dinardo S (2010) Nat Cell Biol 12(8):806–811]. In contrast to this model, we show that early germ cells with GSC characteristics can be maintained over time after ablation of CySCs and their cyst cell progeny. Without CySCs and cyst cells, early germ cells away from the hub failed to initiate differentiation. Our results suggest that CySCs do not have a necessary instructive role in specifying GSC self-renewal and that the differentiated progeny of CySCs provide an environment necessary to trigger GSC differentiation. This work highlights the complex interaction between different stem cell populations in the same niche and how the state of one stem cell population can influence the fate of the other.The ability of a stem cell niche to maintain a population of stem cells ensures the continued availability of adult stem cells to replenish and repair specific tissues throughout the lifetime of an organism (1, 2). Failure of a niche to maintain its appropriate stem cell population may lead to degeneration, aging, or an inability to repair tissue damage (3). Conversely, failure of a niche to properly regulate differentiation versus proliferation may contribute to the genesis of cancer in adult stem cell lineages (4). A comprehensive understanding of how the local microenvironment of the stem cell niche functions suggests strategies for expansion of adult stem cell populations in vitro, facilitates design of artificial niches for transplantation, and provides ideas for increasing maintenance and functionality of endogenous adult stem cell populations used for regenerative medicine.The Drosophila testis stem cell niche, a key model for understanding how the microenvironment regulates stem cell behavior (5–7), supports two distinct adult stem cell populations—germline stem cells (GSCs) and cyst stem cells (CySCs)—both of which attach to a cluster of postmitotic somatic cells that form the apical hub (Fig. 1A). GSCs and CySCs normally divide with oriented spindles to produce daughters that remain next to the hub and self-renew and daughters displaced away from the hub that initiate differentiation (8, 9). GSCs give rise to gonialblasts (Gb) and CySCs give rise to postmitotic cyst cells (10), a pair of which encapsulates each Gb to form a cyst. The encapsulated Gb undergoes four rounds of synchronous transit-amplifying (TA) divisions before entering meiosis and terminal differentiation (Fig. 1A).Open in a separate windowFig. 1.Early germ cells can be maintained after ablation of CySCs and cyst cells. (A) Diagram of Drosophila spermatogenesis at the apical tip of the testis. (Red) fusomes; (green) Bam protein expression. (B–G) Immunofluorescence images of c587Gal4; UAS Grim; tubGal80^ts testes stained with anti-FasIII (white, hub), anti-Vasa (red, germ cells), and anti-Tj (green) nuclei of hub, CySCs, and cyst cells). (B) Newly eclosed flies before shift to 30 °C. (Arrowheads) CySCs; (arrows) cyst cells. (C) Flies shifted to 30 °C for 1 d. (D) Flies shifted to 30 °C for 1 d and back to 18 °C for 7 d. (E) Flies shifted to 30 °C for 1 d and back to 18 °C for 7 d. (F) Flies shifted to 30 °C for 1 d and back to 18 °C for 14 d. (G) Flies shifted to 30 °C for 1 d and back to 18 °C for 21 d. (H) Bar graph depicting phenotype distribution at different time points. (Blue bar) Testes with CySCs and/or cyst cells (incomplete ablation); (red bar) testes with early germ cells but lacked CySCs or cyst cells; (green bar) testes lacking early germ cells, CySCs, and cyst cells. No significant difference in phenotype distribution was observed among the 7-, 14-, and 21-d time points. (Scale bar: B–G, 10 μm.)Both the apical hub and the CySCs influence the GSC state. A cytokine-like signal from the hub activates the JAK-STAT signaling pathway in both GSCs and CySCs (11, 12). Although JAK-STAT signaling is required cell autonomously for CySC maintenance, it is not necessary to retain GSCs in their stem cell state. Rather, activity of Stat in the germline is essential for continued attachment of GSCs to the hub and retains GSCs in their niche (13). Several lines of evidence suggest that CySCs provide a niche for maintenance of GSCs (13–15). Consistent with this model, it has been proposed that self-renewal of GSCs is specified by instructive signal(s) from the CySCs, with a likely candidate being TGF-β signaling (13).Here we show that early germ cells can be maintained next to the hub in testes in which CySCs and cyst cells had been permanently ablated. We further show that the progeny of GSC-like cells displaced from the hub failed to initiate the TA program in the absence of CySCs and cyst cells, and instead continued to proliferate as undifferentiated cells. Our findings suggest that CySCs do not play a required instructive role in GSC self-renewal and that cyst cells, the differentiated progeny of CySCs, are required for proper onset of the germline differentiation.     

Evolution of Massachusetts physician attitudes, knowledge, and experience regarding the use of antiretrovirals for HIV prevention

The Center for the AIDS Programme of Research in South Africa (CAPRISA) 004 and Pre-exposure Prophylaxis Initiative (iPrEx) studies demonstrated that topical or oral chemoprophylaxis could decrease HIV transmission. Yet to have an appreciable public health impact, physicians will need to be educated about these new HIV prevention modalities. Massachusetts physicians were recruited via e-mail to complete an online survey of their knowledge and use of HIV prevention interventions. Data were collected before (July-December, 2010) (n=178) and after (December, 2010-April, 2011) (n=115) the release of iPrEx data. Over the two time intervals, knowledge of oral PrEP significantly increased (79% to 92%, p<0.01), whereas knowledge about topical microbicides was already high (89% pre-iPrEx). Post-iPrEx, specialists were more knowledgeable about oral PrEP (p<0.01) and topical microbicides (p<0.001) than generalists. The majority of the respondents would prefer to prescribe topical microbicides (75%) than oral PrEP (25%; p<0.001), primarily because they perceived fewer side effects (95%). Respondents indicated that PrEP should be available if it were a highly effective, daily pill; however, ongoing concerns included: potential drug resistance (93%), decreased funds for other forms of HIV prevention (88%), medication side effects (83%), and limited data regarding PrEP's clinical efficacy (75%). Participants indicated that formal CDC guidelines would have the greatest impact on their willingness to prescribe PrEP (96%). Among Massachusetts physicians sampled, chemoprophylaxis knowledge was high, but current experience was limited. Although topical gel was preferred, responses suggest a willingness to adapt practices pending additional efficacy data and further guidance from normative bodies. Educational programs aimed at incorporating antiretroviral chemoprophylaxis into physicians' HIV prevention practices are warranted.     

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

Background  

Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease.     

Nuances of Whitefly Vector–Crinivirus Interactions Revealed in the Foregut Retention and Transmission of Lettuce Chlorosis Virus by Two Bemisia tabaci Cryptic Species

Lettuce infectious yellows virus is the first crinivirus for which the retention of purified virions ingested into the whitefly (Bemisia tabaci New World (NW)) vector’s foregut, has been demonstrated to be a requisite for successful virus transmission. This key finding supports the hypothesis that the determinant of foregut retention and transmission is present on the virion itself. However, whether this is also true for other criniviruses has not been established. Here, we provide evidence that lettuce chlorosis virus (LCV) acquired from plants is retained in the foreguts of both the B. tabaci NW and Middle East–Asia Minor 1 (MEAM1) vector species and transmitted upon inoculation feeding. An association between foregut retention and transmission by NW vectors is also observed following the acquisition and inoculation feeding of LCV virions purified using a standard procedure involving 2% or 4% (v/v) Triton™ X-100 (TX-100). However, while virions purified with 2% or 4% TX-100 are also retained in the foreguts of MEAM1 vectors, transmission is observed with the 4% TX-100-purified virions or when more vectors are used for acquisition and inoculation feeding. These results suggest that an intrinsic difference exists between NW and MEAM1 vectors in their interactions with, and transmission of, LCV virions.