bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fgf22 regulated by Fgf3/Fgf8 signaling is required for zebrafish midbrain development
Authors: Miyake Ayumi , Itoh Nobuyuki 
Published: April 2013

Summary
Fibroblast growth factor (Fgf) signaling plays important roles in various developmental processes including brain development. Here, we identified zebrafish fgf22 predominantly expressed in the posterior midbrain and anterior midbrain–hindbrain boundary (MHB) primordia during early embryonic brain development. To examine roles of Fgf22 in midbrain development, we analyzed fgf22 knockdown embryos. The fgf22 morphants were defective in proper formation of the MHB constriction and the midbrain. The knockdown of fgf22 caused decreased cell proliferation in the midbrain, expanded expression of roof plate and tegmental marker genes, and decreased expression of tectal marker genes, indicating that Fgf22 is required for cell proliferation, roof plate formation, and tectum specification in the midbrain. Fgf receptor 2b (Fgfr2b), a potential receptor for Fgf22, was also required, indicating that Fgf22 signaling is mediated through Fgfr2b. The floor plate and the MHB are crucial for the dorsoventral patterning of the midbrain through Hedgehog (Hh) and Fgf signaling, respectively. The fgf3/fgf8 double morphant phenotype was essentially similar to that of fgf22 morphants, whereas the phenotype caused by inhibition of Hh signaling was not. fgf3 and fgf8 were expressed earlier than fgf22 in the MHB primordium and Fgf3/Fgf8 signaling was required for fgf22 expression in the posterior midbrain. Furthermore, fgf22 partially rescued the fgf3/fgf8 double morphant phenotype. The present results indicate Fgf22 to be involved in midbrain development downstream of Fgf3 and Fgf8 in the MHB but not of Hh in the floor plate.
Inter-channel scaffolding of presynaptic CaV2.2 via the C terminal PDZ ligand domain
Authors: Gardezi Sabiha R. , Li Qi , Stanley Elise F. 
Published: April 2013

Summary
Calcium entry through CaV2.2 calcium channels clustered at the active zone (AZ) of the presynaptic nerve terminal gates synaptic vesicle (SV) fusion and the discharge of neurotransmitters, but the mechanism of channel scaffolding remains poorly understood. Recent studies have implicated the binding of a PDZ ligand domain (PDZ-LD) at the tip of the channel C terminal to a partner PDZ domain on RIM1/2, a synaptic vesicle-associated protein. To explore CaV2.2 scaffolding, we created intracellular region fusion proteins and used these to test for binding by ‘fishing’ for native CaV2.2 channels from cell lysates. Fusion proteins mimicking the distal half of the channel C terminal (C3strep) reliably captured CaV2.2 from whole brain crude membrane or purified synaptosome membrane lysates, whereas channel I–II loop or the distal half of the II–III loop proteins were negative. This capture could be replicated in a non-synaptic environment using CaV2.2 expressed in a cell line. The distal tip PDZ-LD, DDWC-COOH, was confirmed as the critical binding site by block of pull-down with mimetic peptides. Pull-down experiments using brain crude membrane lysates confirmed that RIM1/2 can bind to the DDWC PDZ-LD. However, robust CaV2.2 capture was observed from synaptosome membrane or in the cell line expression system with little or no RIM1/2 co-capture. Thus, we conclude that CaV2.2 channels can scaffold to each other via an interaction that involves the PDZ-LD by an inter-channel linkage bridged by an unknown protein.
Sonic hedgehog promotes autophagy in hippocampal neurons
Authors: Petralia Ronald S. , Schwartz Catherine M. , Wang Ya-Xian , Kawamoto Elisa M. , Mattson Mark P. , Yao Pamela J. 
Published: April 2013

Summary
The Sonic hedgehog (Shh) signaling pathway is well known in patterning of the neural tube during embryonic development, but its emerging role in differentiated neurons is less understood. Here we report that Shh enhances autophagy in cultured hippocampal neurons. Microarray analysis reveals the upregulation of multiple autophagy-related genes in neurons in response to Shh application. Through analysis of the autophagy-marker LC3 by immunoblot analysis and immunocytochemistry, we confirm activation of the autophagy pathway in Shh-exposed neurons. Using electron microscopy, we find autophagosomes and associated structures with a wide range of morphologies in synaptic terminals of Shh-exposed neurons. Moreover, we show that Shh-triggered autophagy depends on class III Phosphatidylinositol 3-kinase complexes (PtdIns3K). These results identify a link between Shh and autophagy pathways and, importantly, provide a lead for further understanding the physiology of Shh signaling activity in neurons.
What is the role of a full physical examination in the management of asymptomatic patients with late syphilis?
Authors: Dabis R , Radcliffe K 
Published: April 2013

According to the British Association for Sexual Health and HIV guidelines, a full physical examination is recommended in patients with possible late syphilis. The aim of this audit was to review all cases of late syphilis diagnosed at our centre since 1994 to see if a full cardiovascular and neurological examination was documented and also to see what a full examination contributed to the management of asymptomatic patients. Of the 480 medical notes audited, 295 patients were asymptomatic of whom 288 (98%) had normal physical examinations; the rest were either not documented, declined or defaulted follow-up. Seven asymptomatic patients had positive clinical findings but these did not lead to a diagnosis of cardiovascular or neurological syphilis. This audit has shown that performing a physical examination in asymptomatic patients added no benefit in diagnosing complications of late syphilis; it would appear that the physical examination did not alter the management.
Patients’ experiences of health and social care in long-term neurological conditions in England: A cross-sectional survey
Authors: Peters Michele , Fitzpatrick Ray , Doll Helen , Playford E Diane , Jenkinson Crispin 
Published: April 2013

Objectives: To investigate patients’ experiences of health and social care services in long-term neurological conditions in England. Method: Cross-sectional survey of 5209 patient members of the Motor Neurone Disease Association (MND, n = 890), Multiple Sclerosis Society (MS, n = 2345) or Parkinson's UK (PD, n = 1974). A questionnaire on patient experiences of health and social care was completed by 2563 (49%) (505 MND, 1157 MS and 901 PD). Results: A mixed picture of experiences of health and social care in MND, MS or PD was found with few problems reported for some aspects of services such as obtaining information about medication (n = 117, 6.1%). In contrast, problems with planning and integration of care were reported frequently, with 78.0% of patients not having a care plan and 61.9% reporting that services do not collaborate well in planning care. Other problems included delays with diagnosis, information about medication side effects, and management of conditions whilst in hospital. Significant differences between the three conditions were found for most aspects of care, with MND patients generally reporting fewer problems. The findings highlight which areas of health and social care need to be improved and monitored. While a larger sample size was obtained than in other studies, possible limitations include the sampling frame and the 49% response rate. Conclusion: Planning and integration of care are key areas that require improvement.
Impact of cost of medicines for chronic conditions on low income households in Australia
Authors: Kemp Anna , Preen David B , Glover John , Semmens James , Roughead Elizabeth E 
Published: April 2013

Objectives: To determine the cost of medicines for selected chronic illnesses and the proportion of discretionary income this would potentially displace for households with different pharmaceutical subsidy entitlements and incomes. Methods: We analysed household income and expenditure data for 9,774 households participating in two Australian surveys in 2009-10. The amount of ‘discretionary’ income available to households after basic living and health care expenditure was modelled for households with high pharmaceutical subsidies: pensioner and non-pensioner concessional (social security entitlements); and households with general pharmaceutical subsidies and low, middle or high incomes. We calculated the proportion of discretionary income that would be needed for medicines if one household member had diabetes or acute coronary syndrome, or if one member also had two co-existing illnesses (gastro-oesophageal reflux disease and depression, or asthma and osteoarthritis). Results: Pensioner and low income households had little discretionary income after basic living and health care expenditure (AUD$92 and $164/week, respectively). Medicines for the specified illnesses ranged from $11-$42/month for high subsidy households and $34-$186/month for low subsidy households. Costs reduced substantially once patients reached the annual pharmaceutical cap (safety net), prior to which medicine costs would displace the equivalent of 1%-10% of discretionary income for most household types. However, low income households would have to forego the equivalent of between 5%-26% of their discretionary income for between 7 and 9 months of the year before receiving additional subsidies. Conclusions: Prescription medicines for chronic conditions pose a substantial financial burden to many households, particularly those with low incomes and general pharmaceutical subsidies. Policies are needed to minimize the cost burden of prescription medicines, particularly for low-income working households.
Contrasting Beliefs About Screening for Mental Disorders Among Uk Military Personnel Returning from Deployment to Afghanistan
Authors: Keeling M , Knight T , Sharp D , Fertout M , Greenberg N , Chesnokov M , Rona R J 
Published: April 2013

Objective The objective of the study was to elicit beliefs and experiences of the value of a screening programme for mental illness among UK military personnel. Method Three months after returning from Afghanistan 21 army personnel participated in a qualitative study about mental health screening. One-to-one interviews were conducted and recorded. Data-driven thematic analysis was used. Researchers identified master themes represented by extracts of text from the 21 complete transcripts. Results Participants made positive remarks on the advantages of screening. Noted barriers to seeking help included: unwillingness to receive advice, a wish to deal with any problems themselves and a belief that military personnel should be strong enough to cope with any difficulties. Participants believed that overcoming barriers to participating in screening and seeking help would be best achieved by making screening compulsory. Conclusions Although respondents were positive about a screening programme for mental illness, the barriers to seeking help for mental illness appear deep rooted and reinforced by the value ascribed to hardiness.
Interval Cancers in Nasopharyngeal Carcinoma Screening: Comparing Two Screening Intervals after a Negative Initial Screening Result
Authors: Chen Feng , Huang Qi-Hong , Fang Fang , Liu Zhi-Wei , Liu Ke , Xie Shang-Hang , Liu Qing , Hong Ming-Huang , Liao Zhen-Er , Ye Wei-Min , Zeng Yi-Xin , Cao Su-Mei 
Published: April 2013

Objectives To examine the optimal screening interval among the individuals who received a negative Epstein-Barr virus immunoglobulin A antibodies against viral capsid antigen (VCA-IgA) serum test result and who comprised the majority of the population screened for nasopharyngeal carcinoma (NPC). Methods Screening was performed in Sihui, Guangdong, China, offering a repeated screening for participants with an initial negative test either after 4-5 years in one centre (short interval centre), or 9-10 years in another (long interval centre). The characteristics and incidence rates (IRs) of interval NPCs (defined as cases diagnosed outside the screening protocol while within the screening interval) were compared between these two centres. Standard incidence ratios (SIRs) were also calculated using the general Sihui population as the reference. Results Seven interval NPCs were detected in the short interval centre (IR: 17.8/10 5 person-years) and 20 in the long interval centre (IR: 20.8/10 5 person-years during the first four years and 43.5/10 5 person-years during the remaining years). The SIR in the short interval centre was 0.43 (95% confidence interval [CI]: 0.17-0.89); SIR in the long interval centre was 0.47 (95% CI: 0.17-1.02) during the first four years and 0.90 (95% CI: 0.49-1.51) during the remaining years. No aggressive interval NPC was observed in the short interval centre; four were identified in the long interval centre. Conclusions The incidence of NPC, especially aggressive NPC, was low during the first few years after a negative screening; the incidence increased to the general population level afterwards. A screening interval of 4-5 years may therefore be more suitable than 9–10 years after a negative VCA-IgA test in NPC screening.
Cervical Screening Uptake, Political Interest and Voter Turnout: A Population-Based Survey of Women in England
Authors: Macedo Ana , Waller Jo , Patnick Julietta , Marlow Laura 
Published: April 2013

Objectives To examine the relationship between cervical screening uptake and political engagement, and to test whether political engagement and voting behaviour mediate the association between age and cervical screening uptake Setting A population-based survey of women in England in 2010. Methods Women aged 26-64 took part in home-based computer-assisted interviews ( n = 890). Women were classified as ‘up to date’ or ‘overdue/never been screened’ for cervical screening. Results Most women (81%) were up-to-date with screening; 19% were overdue. Age and marital status were associated with screening status. Women who were not registered to vote, had not voted in previous general elections, and those who showed less interest in elections and lower intention to engage in political activities were more likely to be overdue for screening. In multivariate analyses (adjusting for all significant measures) ‘being on the electoral register’ was the only significant independent predictor of screening status. ‘Being on the electoral register’ was also the only measure of voting behaviour that mediated the association between age and screening status. Conclusion We found limited evidence for the hypothesis that falling attendance for cervical screening could be associated with a broader phenomenon of disillusionment as indexed by reported voting behaviour and other measures of political engagement. Alternative explanations should be considered in order to better understand falling cervical screening uptake, particularly among younger women.
The Jade Goody Effect: Whose Cervical Screening Decisions Were Influenced by Her Story?
Authors: Marlow Laura Av , Sangha Amrit , Patnick Julietta , Waller Jo 
Published: April 2013

Objectives In 2009 more women attended cervical screening in England and Wales than in the previous year. Described as the ‘Jade Goody Effect’ this was attributed to the death from cervical cancer of a UK celebrity. The present study aimed to establish which sociodemographic characteristics were associated with being influenced by Jade Goody's story. Methods Data were collected as part of a Taylor Nelson Sofres (TNS) omnibus survey using random location sampling. Women in England aged 26-64 years were asked to report whether they felt Jade Goody's story had influenced their decisions about cervical screening over the 18 months between her death and the time of the survey. Results Data from 890 participants was included in analysis. Over a third of women felt Goody's story had influenced their decisions about cervical screening (40%). Younger women (aged 26-35 years) were more likely to have been influenced by Goody's story than older women (56-64 year olds). There was also evidence of socioeconomic variation with women from lower socioeconomic class groups and those with fewer educational qualifications more likely to say they had been influenced by Goody's story. Conclusions The ‘Jade Goody Effect’, as acknowledged by women themselves, was more pronounced among young women and influenced screening decisions more markedly among those from lower socioeconomic backgrounds. Narrative communication may be an effective way to encourage attendance at cervical cancer screening and reach groups of the population that are difficult to reach using traditional intervention methods.
A Review of the Use of Angiotensin Receptor Blockers for the Prevention of Cardiovascular Events in Patients with Essential Hypertension Without Compelling Indications
Authors: Zaiken Kathy , Hudd Timothy R , Cheng Judy WM 
Published: April 2013

OBJECTIVE To review the role of angiotensin receptor blockers (ARBs) for the prevention of cardiovascular events in patients with essential hypertension without other compelling indications. DATA SOURCES Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE and Current Content database (both 1966-November 15, 2012) using the search terms angiotensin receptor blockers (ARBs), azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, hypertension, myocardial infarction, stroke, heart failure, and cardiovascular outcomes. Results were limited to human trials published in English. Citations from articles were also reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION The focus was on clinical trials evaluating cardiovascular end points of ARBs used in patients with essential hypertension without compelling indications. DATA SYNTHESIS Data supporting the use of ARBs for reducing cardiovascular events in patients with essential hypertension without compelling indications are inconsistent. To date, only candesartan and losartan have shown a significant reduction in cardiovascular morbidity within this sizable subgroup of patients. In the Study on Cognition and Prognosis in the Elderly (SCOPE) trial, candesartan showed a 27.8% reduction in nonfatal stroke versus placebo (95% CI 1.3–47.2; p = 0.04). Moreover, losartan demonstrated a decrease in all cardiovascular events compared to atenolol in the Cardiovascular Morbidity and Mortality in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study (RR 0.87; 95% CI 0.77–0.98; p = 0.021). CONCLUSIONS Data supporting the use of ARBs for reducing cardiovascular events in patients with essential hypertension without compelling indications are limited and inconclusive. More studies are needed before ARBs can be routinely recommended as first-line therapy for hypertension management in patients without other compelling indications.
Azilsartan Medoxomil/Chlorthalidone: A New Fixed-Dose Combination Antihypertensive
Authors: Pierini Danielle , Anderson Katherine Vogel 
Published: April 2013

OBJECTIVE To evaluate the efficacy, safety, and clinical utility of the combination product azilsartan medoxomil/chlorthalidone for the treatment of hypertension. DATA SOURCES Articles indexed in PubMed through December 2012 were identified using the MeSH terms azilsartan and chlorthalidone, Edarbyclor, TAK-490, and Edarbi. Additional information was gathered from references cited in the identified publications, the package insert, and from a review of the ClinicalTrials.gov registry. STUDY SELECTION AND DATA EXTRACTION English-language articles, including clinical trials and reviews involving azilsartan medoxomil/chlorthalidone or each component individually for the treatment of hypertension were reviewed. DATA SYNTHESIS The antihypertensive combination tablet azilsartan medoxomil/chlorthalidone is the first to combine an inhibitor of the renin-angiotensin-aldosterone system with chlorthalidone, a thiazide-type diuretic. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide. Reductions in 24-hour ambulatory BP and clinic BP were observed, and a greater proportion of patients achieved BP targets while receiving azilsartan medoxomil/chlorthalidone. Azilsartan medoxomil/chlorthalidone was generally well tolerated, with minor, transient increases in serum creatinine and without a significant effect on potassium homeostasis. No studies have directly examined cardiovascular morbidity and mortality benefits associated with this combination. CONCLUSIONS The combination of azilsartan medoxomil/chlorthalidone has demonstrated safety and efficacy in lowering BP in hypertensive patients to a greater degree than olmesartan medoxomil/hydrochlorothiazide and azilsartan medoxomil/hydrochlorothiazide. As a fixed-dose combination tablet, it offers several clinical advantages.
Impact of Medication Therapy Management on Underserved, Primarily Hispanic Patients with Diabetes
Authors: Congdon Heather B , Dowling Thomas C , Cheng Iliana , Truong Hoai-An 
Published: April 2013

BACKGROUND Diabetes-related complications are more pronounced in Hispanic patients versus patients of other ethnicities. It is documented that medication therapy management (MTM) can improve diabetes outcomes; however, data regarding Hispanic patients are limited. OBJECTIVE To evaluate the impact of MTM on hemoglobin A1c (A1C), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) in underserved, primarily Hispanic patients who use a safety-net clinic as their medical home. METHODS A retrospective, observational study of uninsured, primarily Hispanic patients with diabetes who received MTM from October 2009 through March 2011. Patients were stratified into 2 cohorts: A1C less than 9% and A1C greater than or equal to 9%. Patients were also stratified by frequency of MTM visits and insulin use, regardless of A1C. A chart review was conducted to evaluate diabetes-related outcomes pre- and postimplementation of MTM. The primary study outcome was reduction of A1C. Secondary outcomes included reduction of BP and LDL-C and reduction of A1C based on MTM visit frequency or insulin use. RESULTS Sixty-four patients with at least 1 MTM visit and pre- and postimplementation A1C data were included. In the cohort with A1C greater than or equal to 9%, mean (SD) A1C values decreased from 10.9% (1.4%) to 8.8% (1.5%) versus the cohort with A1C less than 9%, whose A1C changed minimally, from 7.2% (0.9%) to 7.4% (1.4%). Regardless of their A1C, patients who were using insulin at baseline had a change in A1C of −0.8% (1.5%) versus −0.1% (1.6%) in those who were not using insulin at baseline (p = 0.04); patients who participated in multiple MTM visits had a significant reduction in A1C, from 9% to 8.3% (95% CI −1.26 to −0.03; p = 0.02) compared with patients participating in only 1 MTM visit. CONCLUSIONS Pharmacist-provided MTM can significantly improve diabetes control in uninsured, primarily Hispanic patients with poorly controlled diabetes and in those who are using insulin. Multiple MTM visits also yielded significant A1C reductions.