Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo.

Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process.This is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.15252/embj.201387500/abstract

Focus on vulnerable populations and promoting equity in health service utilization ––an analysis of visitor characteristics and service utilization of the Chinese community health service

Background Community health service in China is designed to provide a convenient and affordable primary health service for the city residents, and to promote health equity. Based on data from a large national study of 35 cities across China, we examined the characteristics of the patients and the utilization of community health institutions (CHIs), and assessed the role of community health service in promoting equity in health service utilization for community residents. Methods Multistage sampling method was applied to select 35 cities in China. Four CHIs were randomly chosen in every district of the 35 cities. A total of 88,482 visitors to the selected CHIs were investigated by using intercept survey method at the exit of the CHIs in 2008, 2009, 2010, and 2011. Descriptive analyses were used to analyze the main characteristics (gender, age, and income) of the CHI visitors, and the results were compared with that from the National Health Services Survey (NHSS, including CHIs and higher levels of hospitals). We also analyzed the service utilization and the satisfactions of the CHI visitors. Results The proportions of the children (2.4%) and the elderly (about 22.7%) were lower in our survey than those in NHSS (9.8% and 38.8% respectively). The proportion of the low-income group (26.4%) was apparently higher than that in NHSS (12.5%). The children group had the lowest satisfaction with the CHIs than other age groups. The satisfaction of the low-income visitors was slightly higher than that of the higher-income visitors. The utilization rate of public health services was low in CHIs. Conclusions The CHIs in China appears to fulfill the public health target of uptake by vulnerable populations, and may play an important role in promoting equity in health service utilization. However, services for children and the elderly should be strengthened

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

Factors influencing the opinion of individuals in determining tumour spread after biopsy

<p>Abstract</p> <p>Background</p> <p>People often have concerns regarding tumour spread after biopsy which leads to a delay in seeking expert medical advice. The data regarding this perception is scanty. Therefore, we conducted this cross sectional study to explore the beliefs and perceptions of individuals regarding tumour spread after biopsy and the basis of those beliefs.</p> <p>Methods</p> <p>The survey was conducted in outpatient areas of two different tertiary care hospitals of Karachi namely Aga Khan University Hospital Karachi (AKUH) and Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). We interviewed 600 individuals and documented their responses on a questionnaire. There were 400 responders from Aga Khan's Consulting Clinic and 100 each from Aga Khan's Oncology Clinic and KIRAN.</p> <p>Results</p> <p>Only 50% of the respondents chose biopsy as the best test for diagnosis of cancer. The level of education was statistically significant in making this choice of answer (<it>p </it>= 0.02) only in univariate analysis. Those individuals who were involved in the work up of cancer patients irrespective of their educational status gave more intelligent answers (<it>p </it>= 0.003). The tumour disturbance after biopsy was regarded as a major factor among 127 respondents (53%) who believed that biopsy could lead to spread of tumour.</p> <p>Conclusions</p> <p>Our study revealed that awareness regarding cancer diagnosis and biopsy is lacking among general public and it does not co-relate well with the level of formal education. These misconception and taboos need to be addressed in public seminars and in the media in order to increase the awareness which could facilitate prompt diagnosis.</p

Physician Perception of Blood Pressure Control and Treatment Behavior in High-Risk Hypertensive Patients: A Cross-Sectional Study

Objective: We examined physician perception of blood pressure control and treatment behavior in patients with previous cardiovascular disease and uncontrolled hypertension as defined by European Guidelines. Methods: A cross-sectional study was conducted in which 321 primary care physicians throughout Spain consecutively studied 1,614 patients aged ≥18 years who had been diagnosed and treated for hypertension (blood pressure ≥140/90 mmHg), and had suffered a documented cardiovascular event. The mean value of three blood pressure measurements taken using standardized procedures was used for statistical analysis. Results: Mean blood pressure was 143.4/84.9 mmHg, and only 11.6% of these cardiovascular patients were controlled according to 2007 European Guidelines for Hypertension Management target of <130/80 mmHg. In 702 (49.2%) of the 1426 uncontrolled patients, antihypertensive medication was not changed, and in 480 (68.4%) of these cases this was due to the physicianś judgment that blood pressure was adequately controlled. In 320 (66.7%) of the latter patients, blood pressure was 130-139/80-89 mmHg. Blood pressure level was the main factor associated (inversely) with no change in treatment due to physician perception of adequate control, irrespective of sociodemographic and clinical factors. Conclusions: Physicians do not change antihypertensive treatment in many uncontrolled cardiovascular patients because they considered it unnecessary, especially when the BP values are only slightly above the guideline target. It is possible that the guidelines may be correct, but there is also the possibility that the care by the physicians is appropriate since BP <130/80 mmHg is hard to achieve, and recent reviews suggest there is insufficient evidence to support such a low BP targetFunding for this study was obtained from RECORDATI ESPAÑA, S.L through an unrestricted grant. Krista Lundelin has a ‘‘Rio Hortega’’ research training contract (Expediente CM10/00327) from the Ministry of Science and Innovation (Instituto de Salud Carlos III), Spain Governmen

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study

Predictors of well child care adherence over time in a cohort of urban Medicaid-eligible infants

<p>Abstract</p> <p>Background</p> <p>Changes in well child care (WCC) adherence over time have not previously been examined. Our objective is to describe adherence rates to WCC over time in a low-income urban population of infants 0-24 months of age, and to identify predictors of WCC adherence in this population.</p> <p>Methods</p> <p>This is a secondary analysis of a cohort of Medicaid-eligible children followed from birth to 2 years between 2005 and 2008 with structured telephone surveys to assess maternal well-being, social support, and household and demographic information. For the 260 children attending 4 urban pediatric practices, WCC adherence was assessed based on visit data abstracted from electronic medical records. A random-intercept mixed effects logit model clustered on subject was used.</p> <p>Results</p> <p>92% of the mothers were African-American, 27% had not finished high school, 87% were single, and 43% earned < $500/month; mean age was 23. WCC adherence decreased from 88% at 6 months to 47% (12 mo), 44% (18 mo), and 67% (24 mo). The difference across time periods was statistically significant (p < 0.001). Married (OR 1.71, p = 0.02) and primiparous (OR 1.89, p < 0.001) mothers had significantly greater odds of adherence, along with women who reported having been adherent to prenatal care visits (OR 1.49, p = 0.03) and those with the lowest household income (OR 1.40, p = 0.03).</p> <p>Conclusions</p> <p>Maternal education efforts should emphasize the importance of establishing WCC, especially for mothers of more than one child. Further studies using larger, more broadly defined populations are needed to confirm our findings that efforts to increase WCC adherence should be intensified after 6 months of age, particularly for children at higher risk.</p

Barriers to implementation of a computerized decision support system for depression: an observational report on lessons learned in "real world" clinical settings

<p>Abstract</p> <p>Background</p> <p>Despite wide promotion, clinical practice guidelines have had limited effect in changing physician behavior. Effective implementation strategies to date have included: multifaceted interventions involving audit and feedback, local consensus processes, marketing; reminder systems, either manual or computerized; and interactive educational meetings. In addition, there is now growing evidence that contextual factors affecting implementation must be addressed such as organizational support (leadership procedures and resources) for the change and strategies to implement and maintain new systems.</p> <p>Methods</p> <p>To examine the feasibility and effectiveness of implementation of a computerized decision support system for depression (CDSS-D) in routine public mental health care in Texas, fifteen study clinicians (thirteen physicians and two advanced nurse practitioners) participated across five sites, accruing over 300 outpatient visits on 168 patients.</p> <p>Results</p> <p>Issues regarding computer literacy and hardware/software requirements were identified as initial barriers. Clinicians also reported concerns about negative impact on workflow and the potential need for duplication during the transition from paper to electronic systems of medical record keeping.</p> <p>Conclusion</p> <p>The following narrative report based on observations obtained during the initial testing and use of a CDSS-D in clinical settings further emphasizes the importance of taking into account organizational factors when planning implementation of evidence-based guidelines or decision support within a system.</p

Perceived Discrimination and Adherence to Medical Care in a Racially Integrated Community

BACKGROUND: Past research indicates that access to health care and utilization of services varies by sociodemographic characteristics, but little is known about racial differences in health care utilization within racially integrated communities. OBJECTIVE: To determine whether perceived discrimination was associated with delays in seeking medical care and adherence to medical care recommendations among African Americans and whites living in a socioeconomically homogenous and racially integrated community. DESIGN: A cross-sectional analysis from the Exploring Health Disparities in Integrated Communities Study. PARTICIPANTS: Study participants include 1,408 African-American (59.3%) and white (40.7%) adults (≥18 years) in Baltimore, Md. MEASUREMENTS: An interviewer-administered questionnaire was used to assess the associations of perceived discrimination with help-seeking behavior for and adherence to medical care. RESULTS: For both African Americans and whites, a report of 1–2 and >2 discrimination experiences in one’s lifetime were associated with more medical care delays and nonadherence compared to those with no experiences after adjustment for need, enabling, and predisposing factors (odds ratio [OR] = 1.8, 2.6; OR = 2.2, 3.3, respectively; all P < .05). Results were similar for perceived discrimination occurring in the past year. CONCLUSIONS: Experiences with discrimination were associated with delays in seeking medical care and poor adherence to medical care recommendations INDEPENDENT OF NEED, ENABLING, AND PREDISPOSING FACTORS, INCLUDING MEDICAL MISTRUST; however, a prospective study is needed. Further research in this area should include exploration of other potential mechanisms for the association between perceived discrimination and health service utilization

Body fatness and physical activity at young ages and the risk of breast cancer in premenopausal women

We examined the relationship between body fatness, sports participation and breast cancer risk in 1560 premenopausal cases and 1548 controls, from three related population-based case–control studies in the UK. Half of the women with breast cancer were aged less than 36 years at diagnosis. Women who perceived themselves as plump at age 10 years had a relative risk of 0.83 (95% confidence interval 0.69–0.99, P=0.03) as compared with those who perceived themselves as thin. Self-reported obesity compared with leanness at diagnosis was associated with a relative risk of 0.78 (95% confidence interval 0.56–1.06, P=0.11). Women who reported having been plump at age 10 years and overweight or obese at diagnosis had a relative risk of 0.75 (95% confidence interval 0.56–1.01, P=0.06) as compared with those who reported being thin at age 10 years and at diagnosis. Findings for three related measures of body fatness suggested that obesity is associated with a reduced risk of premenopausal breast cancer. There was no association between sports participation and breast cancer risk in these premenopausal women. The relative risk for spending an average of more than 1 h per week in sports compared with less from ages 12 to 30 years was 1.00 (95% CI 0.86–1.16, P=0.98)