Increased lymph node yield in colorectal cancer is not necessarily associated with a greater number of lymph node positive cancers.
The presence of lymph node metastasis is a key prognostic factor in colorectal cancer and lymph node yield is an important parameter in assessing the quality of histopathology reporting of colorectal cancer excision specimens. This study assesses the trend in lymph node evaluation over time in a single institution and the relationship with the identification of lymph node positive tumours. It compares the lymph node yield of a contemporary dataset compiled from the histopathology reports of 2178 patients who underwent surgery for primary colorectal cancer between 2005 and 2012 with that of a historic dataset compiled from the histopathology reports of 1038 patients who underwent surgery for colorectal cancer at 5 yearly intervals from 1975 to 2000. The mean lymph node yield was 14.91 in 2005 rising to 21.38 in 2012. In 2012 92.9% of all cases had at least 12 lymph nodes examined. Comparison of the mean lymph node yield and proportion of Dukes C cases shows a significant increase (Pearson correlation = 0.927, p = 0.001) in lymph node yield while there is no corresponding significant trend in the proportion of Dukes C cases (Pearson correlation = -0.138, p = 0.745). This study shows that there is increasing yield of lymph nodes from colorectal cancer excision specimens. However, this is not necessarily associated with an increase number of lymph node positive cancers. Further risk stratifying of colorectal cancer requires consideration of other pathological parameters especially the presence of extramural venous invasion and relevant biomarkers.


Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines.
A dry, persistent cough is a well-described class effect of the angiotensin-converting enzyme (ACE) inhibitor medications. The mechanism of ACE inhibitor-induced cough remains unresolved, but likely involves the protussive mediators bradykinin and substance P, agents that are degraded by ACE and therefore accumulate in the upper respiratory tract or lung when the enzyme is inhibited, and prostaglandins, the production of which may be stimulated by bradykinin. Data for this review were obtained from a National Library of Medicine (PubMed) search, which was performed in May 2004, of the literature published in the English language from 1985 to 2004, using the search terms "angiotensin-converting enzyme," "angiotensin converting enzyme inhibitors," and "cough." The incidence of ACE inhibitor-induced cough has been reported to be in the range of 5 to 35% among patients treated with these agents. However, a much lower incidence has been described in studies of patients presenting for the evaluation of chronic cough. The onset of ACE inhibitor-induced cough ranges from within hours of the first dose to months after the initiation of therapy. Resolution typically occurs within 1 to 4 weeks after the cessation of therapy, but cough may linger for up to 3 months. The only uniformly effective treatment for ACE inhibitor-induced cough is the cessation of treatment with the offending agent. The incidence of cough associated with therapy with angiotensin-receptor blockers appears to be similar to that of the control drug. In a minority of patients, cough will not recur after the reintroduction of ACE inhibitor therapy. In a patient with chronic cough, ACE inhibitors should be considered as wholly or partially causative, regardless of the temporal relation between the initiation of ACE inhibitor therapy and the onset of cough. Although the cessation of therapy is the only uniformly effective treatment for ACE inhibitor-induced cough, some pharmacologic agents have been shown to attenuate the cough.


Hemagglutination by canine parvovirus: serologic studies and diagnostic applications.
Conditions for canine parvoviral hemagglutination (HA) and hemagglutination-inhibition (HI) reactions were defined. The HA phenomena were used to differentiate canine parvovirus (CPV) from feline panleukopenia virus (FPV), mink enteritis virus (MEV), and minute virus of canines. Serologic comparisons of the CPV, FPV, and MEV by HA-HI and serum-neutralization tests indicated that CPV, FPV, and MEV were antigenically similar but were different from minute virus of canines. Diagnostic application of HA tests to fecal samples from acute cases of enteritis was discussed. Combinating HA tests with HI tests on fecal samples provided a rapid and specific diagnostic method for CPV infection. Secular seroprevalence studies indicated the emergence of CPV infeciton in the United States dog population-at-large in 1978.


A model for the probability density function of downwelling irradiance under ocean waves.
We present a statistical model that analytically quantifies the probability density function (PDF) of the downwelling light irradiance under random ocean waves modeling the surface as independent and identically distributed flat facets. The model can incorporate the separate effects of surface short waves and volume light scattering. The theoretical model captures the characteristics of the PDF, from skewed to near-Gaussian shape as the depth increases from shallow to deep water. The model obtains a closed-form asymptotic for the probability that diminishes at a rate between exponential and Gaussian with increasing extreme values. The model is validated by comparisons with existing field measurements and Monte Carlo simulation.


Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe.
Plasmid-acquired carbapenemases in Enterobacteriaceae, which were first discovered in Europe in the 1990s, are now increasingly being identified at an alarming rate. Although their hydrolysis spectrum may vary, they hydrolyse most β-lactams, including carbapenems. They are mostly of the KPC, VIM, NDM and OXA-48 types. Their prevalence in Europe as reported in 2011 varies significantly from high (Greece and Italy) to low (Nordic countries). The types of carbapenemase vary among countries, partially depending on the cultural/population exchange relationship between the European countries and the possible reservoirs of each carbapenemase. Carbapenemase producers are mainly identified among Klebsiella pneumoniae and Escherichia coli, and still mostly in hospital settings and rarely in the community. Although important nosocomial outbreaks with carbapenemase-producing Enterobacteriaceae have been extensively reported, many new cases are still related to importation from a foreign country. Rapid identification of colonized or infected patients and screening of carriers is possible, and will probably be effective for prevention of a scenario of endemicity, as now reported for extended-spectrum β-lactamase (mainly CTX-M) producers in all European countries.


A Renal Olfactory Receptor Aids in Kidney Glucose Handling.
Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels. Consistent with this phenotype, Olfr1393 knockout mice have a significant decrease in luminal expression of Sglt1, a key renal glucose transporter, uncovering a novel regulatory pathway involving Olfr1393 and Sglt1. In addition, by utilizing a large scale screen of over 1400 chemicals we reveal the ligand profile of Olfr1393 for the first time, offering new insight into potential pathways of physiological regulation for this novel signaling pathway.


The Relationship Between Controlled Substances and Violence.
A causal relationship between controlled substances and firearm violence has been widely assumed in the United States, and federal law prohibits individuals who are "unlawful users of or addicted to any controlled substance" from purchasing or possessing firearms (68 FR 3750. 2003. Codified at 27 CFR §478.11). However, the law does a poor job of defining "unlawful users," resulting in recent calls for a revised, actionable definition. Such a definition should be informed by research evidence, but to date the epidemiologic research on the relationship between controlled substances and violence has not been comprehensively reviewed. The initial goal of this review was to summarize the best available evidence on the relationship between controlled substances and firearm violence, but only 1 study specific to firearm violence was identified. We therefore reviewed studies of this relationship using broader measures of interpersonal violence and suicide, all of which included but were not limited to firearm violence, and measures of illicit firearm carrying. Prospective longitudinal studies (n = 22) from 1990 to 2014 were identified by using searches of online databases and citation tracking. Information was extracted from each study by using a standardized protocol. Quality of evidence was independently assessed by 2 reviewers. Aggregate measures of controlled substance use were associated with increased interpersonal violence and suicide, but evidence regarding the relationship between specific substances and violence was mixed. Involvement in illegal drug sales was consistently associated with interpersonal violence. To effectively revise extant federal law and delineate appropriate prohibiting criteria, more research is needed to understand the relationship between controlled substances and firearm violence.


Regional intra-subject variability in abdominal adiposity limits usefulness of computed tomography.
Computed tomography (CT) and magnetic resonance imaging, the most accurate methods of abdominal fat measurement, have been applied using a number of protocols, ranging from single-slice area determination to multiple-slice volume calculation. The aim of this study was to assess the validity of single-slice CT for abdominal fat area measurement by estimating the intra-subject variability in abdominal fat areas and comparing the ranking of subjects across four contiguous abdominal levels. Nineteen premenopausal women (age, 35.3 +/- 1.4 years; mean +/- SE) were studied. CT was used to measure intra-abdominal fat (IAF) area, percentage of total intra-abdominal area (%IAF), subcutaneous abdominal fat (SAF) area, and IAF/SAF at four adjacent cross-sectional lumbar levels (L2-L4). Intra-subject variability (percentage) was defined as SD/mean x 100. Total body fat was measured by DXA, which was further analyzed for central abdominal fat. Mean body mass index was 24.9 +/- 1.0 kg/m(2). The average (range) intra-subject variability was 28% (8% to 61%) for IAF, 46% (19% to 124%) for %IAF, 26% (14% to 38%) for SAF area, and 19% (7% to 71%) for IAF/SAF. The pattern of this variability was not uniform between subjects, because their ranking by IAF area was markedly different at each CT level. We demonstrated significant intra-subject variability in CT-measured adipose tissue areas across four predetermined sites. This resulted in a difference in the ordering of subjects by IAF at each of the four imaging sites, suggesting that the usefulness of single-slice CT in the assessment of abdominal adiposity in premenopausal women may be limited, particularly when performed for the purpose of making comparisons between subjects based on abdominal fat area.


Recovery from monocular deprivation using binocular deprivation.
Ocular dominance (OD) plasticity is a robust paradigm for examining the functional consequences of synaptic plasticity. Previous experimental and theoretical results have shown that OD plasticity can be accounted for by known synaptic plasticity mechanisms, using the assumption that deprivation by lid suture eliminates spatial structure in the deprived channel. Here we show that in the mouse, recovery from monocular lid suture can be obtained by subsequent binocular lid suture but not by dark rearing. This poses a significant challenge to previous theoretical results. We therefore performed simulations with a natural input environment appropriate for mouse visual cortex. In contrast to previous work, we assume that lid suture causes degradation but not elimination of spatial structure, whereas dark rearing produces elimination of spatial structure. We present experimental evidence that supports this assumption, measuring responses through sutured lids in the mouse. The change in assumptions about the input environment is sufficient to account for new experimental observations, while still accounting for previous experimental results.


Adaptation to infectious disease exposure in indigenous Southern African populations.
Genetic analyses can provide information about human evolutionary history that cannot always be gleaned from other sources. We evaluated evidence of selective pressure due to introduced infectious diseases in the genomes of two indigenous southern African San groups-the ‡Khomani who had abundant contact with other people migrating into the region and the more isolated Ju|'hoansi. We used a dual approach to test for increased selection on immune genes compared with the rest of the genome in these groups. First, we calculated summary values of statistics that measure genomic signatures of adaptation to contrast selection signatures in immune genes and all genes. Second, we located regions of the genome with extreme values of three selection statistics and examined these regions for enrichment of immune genes. We found stronger and more abundant signals of selection in immune genes in the ‡Khomani than in the Ju|'hoansi. We confirm this finding within each population to avoid effects of different demographic histories of the two populations. We identified eight immune genes that have potentially been targets of strong selection in the ‡Khomani, whereas in the Ju|'hoansi, no immune genes were found in the genomic regions with the strongest signals of selection. We suggest that the more abundant signatures of selection at immune genes in the ‡Khomani could be explained by their more frequent contact with immigrant groups, which likely led to increased exposure and adaptation to introduced infectious diseases.


Behavioural effects of electrical stimulation of the hypothalamus of the goldfish (Carassius auratus).
Food-satiated goldfish were stimulated in tanks containing food on the surface of the water and on the bottom of the tank. Various components of the feeding response were seen, and complete feeding was observed, which was elicited from sites in the postero-medial hypothalamus. Evidence is put forward to support the supposition that the full response was due to a change in feeding motivation, rather than to changes in sensory or motor factors. Other types of behaviour, such as fin movements and swimming, could not be identified as part of any normal ethological sequence. However, vertical movements and gas-spitting responses indicated a possible hypothalamic control of buoyancy. None of the behaviours observed was seen to change in a social context.


Daily social and affective lives of homeless youth: What is the role of teacher and peer social support?
Youth spend a significant amount of time in school surrounded by and interacting with teachers and peers. For doubled-up homeless youth (i.e., youth who share housing with a series of friends and/or extended family members), in-school relationships may be important for their emotional functioning. The current study captured dynamic processes by which in-school teacher and peer social support (i.e., baseline assessments of prior support and daily early-day reports of school day support) influence homeless youth's daily emotional well-being, as assessed by positive and negative affect later in the day. Specifically, a baseline survey was used in combination with a 10-day twice-a-day diary design to examine the competing influences of prior (i.e., between-person) and daily (i.e., within-person) social support from teachers and peers during the school day. Baseline teacher support and early-day peer support were associated with higher later-day positive affect. In contrast, baseline peer support was associated with lower later-day negative affect. Baseline peer support moderated the association between early-day peer support and later-day positive affect, in that there was a significant effect of early-day peer support and later-day positive affect for youth who reported medium and high levels of baseline peer support. However, the later-day positive affect of youth who reported low baseline levels of social support did not appear to benefit from early-day peer support. Results suggest that the source of support (i.e., teacher and peer) differently influences daily affect and that receiving daily in-school support can promote daily positive affect while mitigating negative affect for doubled-up homeless youth. Overall, study findings suggest that providing peer and teacher social support is a promising prevention and intervention approach for fostering resilience among doubled-up homeless youth.


Re-thinking global health sector efforts for HIV and tuberculosis epidemic control: promoting integration of programme activities within a strengthened health system.
The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis control programme activities within a strengthened health system. HIV and tuberculosis share many similarities in terms of their disease burden and the recommended stratagems for their control. HIV and tuberculosis programmes implement similar sorts of control activities, e.g. case finding and treatment, which depend for success on generic health system issues, including vital registration, drug procurement and supply, laboratory network, human resources, and financing. However, the current health system approach to HIV and tuberculosis control often involves separate specialised services. Despite some recent progress, collaboration between the programmes remains inadequate, progress in obtaining synergies has been slow, and results remain far below those needed to achieve universal access to key interventions. A fundamental re-think of the current strategic approach involves promoting integrated delivery of HIV and tuberculosis programme activities as part of strengthened general health services: epidemiological surveillance, programme monitoring and evaluation, community awareness of health-seeking behavior, risk behaviour modification, infection control, treatment scale-up (first-line treatment regimens), drug-resistance surveillance, containing and countering drug-resistance (second-line treatment regimens), research and development, global advocacy and global partnership. Health agencies should review policies and progress in HIV and tuberculosis epidemic control, learn mutual lessons for policy development and scaling up interventions, and identify ways of joint planning and joint funding of integrated delivery as part of strengthened health systems. As both a danger and an opportunity, the global financial crisis may entail disaster or recovery for global health sector efforts for HIV and tuberculosis epidemic control. Review of policies and progress in control paves the way for identification of synergies between the two programmes, within strengthened health services. The silver lining in the global economic crisis could be better control of the HIV and tuberculosis epidemics, better overall health system performance and outcomes, and better value for money.


Acceptance and Commitment Therapy preceded by an experimental Attention Bias Modification procedure in recurrent depression: study protocol for a randomized controlled trial.
This project studies the effect of group-based Acceptance and Commitment Therapy (ACT) following Attention Bias Modification (ABM) on residual symptoms in recurrent depression. ACT is a cognitive-behavioral intervention combining acceptance and mindfulness processes with commitment and behavior-change processes. ACT enjoys modest empirical support in treating depression and has also shown promising results in secondary prevention of depression. The experimental cognitive bias modification (ABM) procedure has been shown to reduce surrogate markers of depression vulnerability in patients in remission from depression. The aim of the current project is to investigate if the effect of group-based ACT on reducing residual depressive symptoms can be enhanced by preceding it with ABM. Also, assessment of the relationship between conceptually relevant therapeutic processes and outcome will be investigated. An invitation to participate in this project was extended to 120 individuals within a larger sample who had just completed a separate randomized, multisite, clinical trial (referred to hereafter as Phase 1) in which they received either ABM (n = 60) or a control condition without bias modification (n = 60). This larger Phase-1 sample consisted of 220 persons with a history of at least two episodes of major depression who were currently in remission or not fulfilling the criteria of major depression. After its inclusion, Phase-1 participants from the Sørlandet site (n = 120) were also recruited for this study in which they received an 8-week group-based ACT intervention. Measures will be taken immediately after Phase 1, 1 month, 2 months, 6 months, and 1 year after the conclusion of Phase 1. This study sequentially combines acceptable, nondrug interventions from neuropsychology and cognitive-behavioral psychology in treating residual symptoms in depression. The results will provide information about the effectiveness of treatment and on mechanisms and processes of change that may be valuable in understanding and further developing ABM and ACT, combined and alone. ClinicalTrials.gov, Identifier: NCT02648165 . Registered on 6 January 2016.


Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat.
Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36.


Topoisomerase I inhibitors in the combined-modality therapy of lung cancer.
Locally advanced non-small-cell lung cancer represents 30% to 40% of all pulmonary malignancies. Most patients will die of the disease after aggressive contemporary treatments. Therefore, significant improvement in therapeutic methods must be implemented to improve overall survival rates. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar) and topotecan (Hycamtin)--offers the hope of significant advances in the treatment of lung cancer. Irinotecan and topotecan are camptothecin derivatives that inhibit topoisomerase I enzyme. It is believed that topoisomerase I inhibitors stabilize a DNA/topoisomerase I complex and interact with replication machinery to cause cell death. A significant amount of data demonstrates that these topoisomerase I inhibitors also act as radiosensitizers. With the increasing data that support concurrent chemoradiation treatment for malignancies, including lung cancer and head and neck cancers, there is an impetus to pursue the additional drugs that may potentially improve local control and survival. Irinotecan is undergoing early clinical trials in the combined-modality setting in several different disease sites. This paper will review the data on the role of camptothecin derivatives as a radiosensitizer and as a component of combined-modality therapy for lung cancer. It is hoped that newer treatment strategies, like the combination of radiation and topoisomerase I inhibitors, will have a significant impact on cure rates in the future.


Preference of diagnostic tools, medications, and devices for asthma management: A survey of doctors in Algeria.
This study aimed to evaluate the doctors' perspectives in using tools for diagnosis, prescribing medications, and devices for the treatment of asthma in Algeria. Data were collected from randomly selected physicians, pediatricians, allergists, and pulmonologists through a questionnaire-based survey in 12 cities and 60 rural locations across Algeria. Of the 213 doctors who responded to the survey, >90% doctors attended an average of 20 asthma patients daily. Peak flow meter was used by 69% doctors for diagnosis and by 93% for monitoring of asthma. Spirometer was used by 76% doctors for diagnosis of asthma. Budesonide (86%), fluticasone (46%), and beclomethasone (40%) were the most prescribed inhaled corticosteroid (ICS) by doctors. Formoterol/budesonide was the most preferred ICS/long-acting β2-agonist (LABA) (72%), followed by salmeterol/fluticasone (57%) for asthma treatment. Salbutamol was preferred by 93% doctors as reliever medication. ICS was the preferred controller in mild asthma (76%), and ICS/LABA combination in moderate (74%) and severe asthma (80%). Most doctors (94%) preferred pressurized metered-dose inhalers (pMDIs) with (46%) or without spacer (48%) for their asthma patients. About 83% doctors believed that pMDI with spacer would show a better outcome in asthma, over pMDI alone. Continuous exposure to allergens/smoking (73%) and incorrect inhaler technique (66%) were the most common reasons for uncontrolled asthma. The use of diagnostic tools in asthma was found to be adequate among the doctors in Algeria. Most of the doctors managed asthma in accordance with the global initiative for asthma guidelines. Spacers were found to be less prescribed in regular treatment, despite having good awareness about its better outcomes.


[Genetic alterations in preneoplastic and neoplastic injuries of the gallbladder].
This article aims to review the most relevant morphological and molecular aspects involved in gallbladder (GB) cancer. In Chile, gallbladder cancer is the main cause of death due to cancer, among women older than 40 years. However, there is almost none information about the morphological changes and the genetic alterations involved in the beginning and development of this neoplasia. Two carcinogenic ways have been described. The sequence adenoma-carcinoma is accepted to be less frequent and important. The most important is the sequence where a metaplasia evolves to displasia that progresses to carcinoma in situ and finally it becomes invasive. This progress requires 10 to 15 years approximately. During this time, a continue progression of injuries have been described. Molecular research studies show genetic anomalies in some genes which are temporary events in preneoplastic injuries of the gallbladder. Some of them even exist before the first morphological changes, while the expression of tumor suppressor genes like p53, adhesion molecules and oncogenes, among others, can be related to late GB carcinogenesis. The K-ras gene seems to play a role in this neoplasia, mainly in those that present an abnormal biliopancreatic union. The microsatelital instability has been found in a small subset of preneoplastic and neoplastic lesions. The existence of methylation in the promotor gene areas has been related to the cellular proliferation, invasion and metastasis and also in cases of chronic cholecystitis, suggesting that this epigenetic phenomenon represents a crucial early event in GB carcinogenesis.


Mitotic rate in melanoma: a reexamination.
We reexamined the relationship between mitotic rate and overall survival in more than 1,200 cases of cutaneous melanoma with long-term follow-up. Like others, we found that mitotic rate was significantly associated with survival (P < 4 x 10(-8)) and more prognostic than tumor ulceration but was not an independent prognosticator because it was significantly associated with tumor thickness and ulceration. Thus, all 3 histologic variables are interrelated; among these, tumor thickness is the most important. Although mitotic rate can be effectively categorized in 3 groups (1/mm2, 1/mm2(-4)/mm2, and > 4/mm2), the optimal way to use mitotic rate remains unclear, and even this simplification requires determining the raw number per square millimeter. Because the collective information provided by tumor thickness, mitotic rate, ulceration, patient age, and site of tumor about hard outcomes such as 5-year fatality is limited and because measuring mitotic rate requires extra time, we recommend that mitotic rate need not be part of routine reports on cutaneous melanoma. Nevertheless, mitotic rate should continued to be measured in academic centers and other sites that maintain large prospective databases on melanoma, and it should be included in further studies of prognosis and adjuvant therapies for cutaneous melanoma.


Sorption process of municipal solid waste biochar-montmorillonite composite for ciprofloxacin removal in aqueous media.
This study evaluates a novel adsorbent for ciprofloxacin (CPX) removal from water using a composite derived from municipal solid waste biochar (MSW-BC) and montmorillonite (MMT). The composite adsorbent and pristine materials were characterized using powder X-Ray Diffraction (PXRD), Fourier-Transform Infrared (FTIR) spectroscopy, and Scanning Electron Microscope (SEM) before and after the adsorption. Batch experiments were conducted to study the mechanisms involved in the adsorption process. Ciprofloxacin sorption mechanisms were interpreted in terms of its pH-dependency and the distribution coefficients. The SEM images confirmed the successful binding of MMT onto the MSW-BC through flaky structure along with a porous morphology. Encapsulation of MMT onto MSW-BC was exhibited through changes in the basal spacing of MMT via PXRD analysis. Results from FTIR spectra indicated the presence of functional groups for both pristine materials and the composite that were involved in the adsorption reaction. The Hill isotherm model and pseudo-second-order and Elovich kinetic models fitted the batch sorption data, which explained the surface heterogeneity of the composite and cooperative adsorption mechanisms. Changes made to the MSW-BC through the introduction of MMT, enhanced the active sites on the composite adsorbent, thereby improving its interaction with ionizable CPX molecules giving high sorption efficiency.


Modified inferior vena caval anastomosis to reduce tricuspid valve regurgitation after heart transplantation.
Postoperative tricuspid valve regurgitation is moderate to severe in 15% to 20% of heart transplant recipients despite use of the bicaval surgical technique. We hypothesized that the regurgitation might be partly due to increased tension on the donor right atrium. To study the right atrial distortion, we modified the standard bicaval anastomosis. Our technique involves augmenting the donor right atrial anterior wall with a flap of the recipient's right atrium, which is left attached in continuity with the anterior aspect of the inferior vena cava along 65% of its circumference. We measured tricuspid regurgitation, right atrial area, and right atrioventricular diameter in 7 consecutive patients who underwent orthotopic heart transplantation with the modified anastomosis. Tricuspid regurgitation was graded as follows: 1 = trace, <10%; 2 = mild, 10%-24%; 3 = moderate, 25%-50%; and 4 = severe, >50%. All patients were weaned from inotropic support within 1 week after transplantation with excellent ventricular function, no heart block, and 100% survival at 30 days. The median follow-up time was 173 days (44-358 days). Other median measurements included tricuspid valve regurgitation jet area, 0.30 cm(2) (0-1.90 cm(2)); right atrial area, 15.90 cm(2) (14.47-18.00 cm(2)); atrioventricular diameter, 2.70 cm (2.63-3.09 cm); and tricuspid regurgitation, 1.67% (0-12.42%). Mild regurgitation occurred in 1 recipient; in all others, it was trace. The modified inferior vena caval anastomosis is simple and safe. It eliminates moderate and severe tricuspid valve regurgitation without routine annuloplasty after orthotopic heart transplantation via the bicaval technique.


Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice.
Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against beta cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than beta cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.


In the wake of the Supreme Court decision, many stakeholders still support the Affordable Care Act.
In the aftermath of the Supreme Court decision largely upholding the constitutionality of the Affordable Care Act, many stakeholders have renewed their commitment to health care reform. In fact, a new political economy of health care has emerged that is characterized by three dynamics. One is the "log-rolling" dynamic of distributive politics, as evident in mutually supportive efforts for maintenance and expansion of subsidies and other opportunities to advance the interests of stakeholders. A second is the cut-throat zero-sum politics of interest-group conflict, as evident in the intense competition among stakeholders for limited resources and authority. The third dynamic is the result of the emotional and ideological conflicts of resource redistribution. These new dynamics may make repeal of reform more daunting than expected.


Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate.
In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.


Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.
Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.


Sex/gender bias in the management of chest pain in ambulatory care.
Cardiovascular diseases (CVD) are the main cause of death worldwide and despite a higher prevalence in men, mortality from CVD is higher among women. Few studies have assessed sex differences in chest pain management in ambulatory care. The objective of this post hoc analysis of data from a prospective cohort study was to assess sex differences in the management of chest pain in ambulatory care. We used data from the Thoracic Pain in Community cohort study that was realized in 58 primary care practices and one university ambulatory clinic in Switzerland. In total, 672 consecutive patients aged over 16 years attending a primary care practice or ambulatory care clinic with a complaint of chest pain were included between February and June 2001. Their mean age was 55.2 years and 52.5% were women. The main outcome was the proportion of patients referred to a cardiologist at 12 months follow-up. A panel of primary care physicians assessed the final diagnosis retained for chest pain at 12 months. The prevalence of chest pain of cardiovascular origin (n = 108, 16.1%) was similar for men and women (17.5% vs 14.8%, respectively, p = 0.4). Men with chest pain were 2.5 times more likely to be referred to a cardiologist than women (16.6% vs 7.4%, odds ratio: 2.49, 95% confidence interval: 1.52-4.09). After adjustment for the patients' age and cardiovascular disease risk factors, the estimates did not significantly change (odds ratio: 2.30, 95% confidence interval: 1.30-3.78). Although the same proportion of women and men present with a chest pain of cardiovascular origin in ambulatory care, there is a strong sex bias in their management. These data suggest that effort must be made to assure equity between men and women in medical care.


Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy.
Systemic chemotherapy is used increasingly prior to resection of hepatic colorectal metastases. Previous reports have indicated an increased risk of perioperative complications associated with the use of systemic chemotherapy prior to resection. The purpose of this study was to investigate perioperative complications in patients receiving neoadjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and leucovorin (LV) with or without CPT-11 within 6 months of major liver resection. A retrospective review of 108 patients undergoing major liver resection for colorectal metastases with curative intent from 1997 to 2002 was performed. Patient and tumor characteristics, perioperative parameters, and morbidity and mortality were measured. Forty-seven patients (44%) received no chemotherapy, 27 patients (25%) received systemic 5-FU/LV, and 34 (31%) received systemic 5-FU/LV/CPT-11. A significantly higher number of patients in the group treated with preoperative 5-FU/LV plus CPT-11 had multiple tumors. Patients in this group also tended to have smaller tumors, fewer complications, and a higher R0 margin resection rate, but these findings were not statistically significant. Median blood loss and length of hospital stay were also not significantly different. There were no perioperative deaths. We conclude that the use of fluoropyrimidine-based chemotherapy and CPT-11 prior to major liver resection is not associated with increased morbidity or mortality. It may therefore provide a better therapeutic option, particularly in patients with multiple colorectal metastases.


Effect of hypothermia in patients undergoing simultaneous carotid endarterectomy and coronary artery bypass graft surgery.
We sought to determine whether hypothermia provided any benefit in patients undergoing simultaneous coronary artery bypass graft surgery (CABG) and carotid endarterectomy (CEA) using one of two different surgical strategies. Group 1 patients (n = 34, 88.2% male, mean age 65.94 ± 6.67 years) underwent CEA under moderate hypothermia before cross clamping the aorta, whereas group 2 patients (n = 23, 69.6% male, mean age 65.78 ± 9.29 years) underwent CEA under normothermic conditions before initiating cardiopulmonary bypass (CPB). Primary outcome of interest was the occurrence of any new neurological event. The two groups were similar in terms of baseline characteristics. Permanent impairment occurred in one patient (2.9%) in group 1. One patient from each group (2.9 and 4.37%) had transient neurological events and they recovered completely on the sixth and 11th postoperative days, respectively. Overall, there was no statistically significant difference between the two groups with regard to occurrence of early neurological outcomes (n = 2, 5.8 % vs n = 1, 4.3 %, p = 0.12). This study could not provide evidence regarding benefit of hypothermia in simultaneous operations for carotid and coronary artery disease because of the low occurrence rate of adverse outcomes. The single-stage operation is safe and completion of the CEA before CPB may be considered when short duration of CPB is required.


Decidualization of intranodal endometriosis in a postmenopausal woman.
Here we describe an unusual case of decidualized endometriosis detected in pelvic lymph nodes. The presence of intranodal ectopic decidua in pregnant women has been described. A few cases of decidualization of endometriotic foci in the pelvic or para-aortic lymph nodes have also been associated with pregnancy. However, decidualized intranodal endometriosis occurring in a postmenopausal woman has not been described. A 52-year-old woman presented with a very large adnexal mass. Menopause occurred at the age of 47, and she had been treated with hormone replacement therapy. She received a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic and para-aortic lymphadenectomy for clear cell carcinoma of the right ovary. Histological examination revealed the presence of ectopic decidua in several pelvic lymph nodes. The deciduas consisted of sheets of loosely cohesive, large, uniform, round cells with abundant eosinophilic cytoplasm. Typical of decidualization of intranodal endometriosis, a few irregularly shaped, inactive endometrial glands lined by single layers of columnar to cuboidal epithelium were present within the decidua. An immunohistochemical study revealed that the decidual cells were positive for CD10, vimentin, estrogen receptor and progesterone receptor, which indicated that progestin-induced decidualization had occurred in the intranodal endometriotic stroma. To the best of our knowledge, this case represents the first report of decidualized intranodal endometriosis occurring in association with hormone replacement therapy in a postmenopausal woman. Misdiagnosis of this condition as a metastatic tumor can be avoided by an awareness of these benign inclusions, supported by immunohistochemical staining results.


Surface passivation and self-regulated shell growth in selective area-grown GaN-(Al,Ga)N core-shell nanowires.
The large surface-to-volume ratio of GaN nanowires implicates sensitivity of the optical and electrical properties of the nanowires to their surroundings. The implementation of an (Al,Ga)N shell with a larger band gap around the GaN nanowire core is a promising geometry to seal the GaN surface. We investigate the luminescence and structural properties of selective area-grown GaN-(Al,Ga)N core-shell nanowires grown on Si and diamond substrates. While the (Al,Ga)N shell allows a suppression of yellow defect luminescence from the GaN core, an overall intensity loss due to Si-related defects at the GaN/(Al,Ga)N interface has been observed in the case of Si substrates. Scanning transmission electron microscopy measurements indicate a superior crystal quality of the (Al,Ga)N shell along the nanowire side facets compared to the (Al,Ga)N cap at the top facet. A nucleation study of the (Al,Ga)N shell reveals a pronounced bowing of the nanowires along the c-direction after a short deposition time which disappears for longer growth times. This is assigned to an initially inhomogeneous shell nucleation. A detailed study of the proceeding shell growth allows the formulation of a strain-driven self-regulating (Al,Ga)N shell nucleation model.


Genetic and anatomic determinants of enzootic Venezuelan equine encephalitis virus infection of Culex (Melanoconion) taeniopus.
Venezuelan equine encephalitis (VEE) is a re-emerging, mosquito-borne viral disease with the potential to cause fatal encephalitis in both humans and equids. Recently, detection of endemic VEE caused by enzootic strains has escalated in Mexico, Peru, Bolivia, Colombia and Ecuador, emphasizing the importance of understanding the enzootic transmission cycle of the etiologic agent, VEE virus (VEEV). The majority of work examining the viral determinants of vector infection has been performed in the epizootic mosquito vector, Aedes (Ochlerotatus) taeniorhynchus. Based on the fundamental differences between the epizootic and enzootic cycles, we hypothesized that the virus-vector interaction of the enzootic cycle is fundamentally different from that of the epizootic model. We therefore examined the determinants for VEEV IE infection in the enzootic vector, Culex (Melanoconion) taeniopus, and determined the number and susceptibility of midgut epithelial cells initially infected and their distribution compared to the epizootic virus-vector interaction. Using chimeric viruses, we demonstrated that the determinants of infection for the enzootic vector are different than those observed for the epizootic vector. Similarly, we showed that, unlike A. taeniorhynchus infection with subtype IC VEEV, C. taeniopus does not have a limited subpopulation of midgut cells susceptible to subtype IE VEEV. These findings support the hypothesis that the enzootic VEEV relationship with C. taeniopus differs from the epizootic virus-vector interaction in that the determinants appear to be found in both the nonstructural and structural regions, and initial midgut infection is not limited to a small population of susceptible cells.


The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era.
Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era. Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted. A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42-1.01), or long-term mortality (RR 0.79; 95% CI, 0.47-1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25-0.67). In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.


Omental grafting: a cell-based therapy for blood vessel repair.
Clinicians regularly transplant omental pedicles to repair a wide variety of injured tissues, but the basic mechanism underlying this efficacious procedure is not understood. One possibility that has not been addressed is the ability of omentum to directly contribute regenerative cells to injured tissues. We hypothesized that if omental progenitor cells could be mobilized to incorporate into damaged tissue, the power of this therapy would be greatly expanded. Labelled omental grafts were transplanted into a murine carotid artery injury model. Selected grafts were treated with thymosin β4 (Tβ4) prior to transplantation to investigate the effects of chemical potentiation on healing. We found treatment of grafts with Tβ4-induced progenitor cells to fully integrate into the wall of injured vessels and differentiate into vascular smooth muscle. Myographic studies determined that arteries receiving Tβ4-stimulated grafts were functionally indistinguishable from uninjured controls. Concurrent in vitro analyses showed that Tβ4 promoted proliferation, migration and trans-differentiation of cells via AKT signalling. This study is the first to demonstrate that omentum can provide progenitor cells for repair, thus revealing a novel and naturally occurring source of vascular smooth muscle for use in cell-based therapies. Furthermore, our data show that this system can be optimized with inducing factors, highlighting a more powerful therapeutic potential than that of its current clinical application. This is a paradigm-setting concept that lays the foundation for the use of chemical genetics to enhance therapeutic outcomes in a myriad of fields.


Mucosal leishmaniasis and abnormalities on computed tomographic scans of paranasal sinuses.
Studies evaluating radiologic aspects, local complications, and structural alterations of the paranasal sinus in patients with mucosal leishmaniasis (ML) are lacking. The aim of this study was to analyze alterations of the paranasal sinuses in patients with ML by using computed tomography (CT) scans. This prospective study evaluated 26 patients in Brazil with ML from December 2008 through June 2009. All patients underwent CT scans of the paranasal sinuses. Paranasal thickening was observed in 25 patients (96%). Nasal perforation was observed in 17 patients (65%). Those patients who received re-treatment showed more abnormalities on CT scan than cured patients (P < 0.05). Complications of ML are not limited to the nasal mucosa but extend to the paranasal sinuses. Mucosal thickening, opacified air cells, bony remodeling, and bony thickening caused by inflammatory osteitis of the sinus cavity walls are CT findings suggestive of chronic sinusitis.


WE-E-213CD-07: Deformable Registration Between CT and Truncated CBCT for Adaptive Therapy Dose Calculation.
Deformable image registration (DIR) is a crucial step in adaptive radiation therapy (ART) to deform the planning CT to the current CBCT for dose calculation and for contour propagation. CBCT images are sometimes truncated in the axial plane due to limited field of view (FOV). DIR between CT and truncated CBCT often leads to unphysical results, especially in and near missing regions, which may result in significant errors in dose calculation afterwards. The purpose of this work is to develop and evaluate a method to improve existing DIR algorithms to solve the truncation problem. The radius of FOV of CBCT is first estimated. A recently developed robust CT-CBCT DIR algorithm, called Deformation with Intensity Simultaneously Corrected (DISC), is used for deformation field calculation. At each iteration of DISC, the calculated deformation vector field outside the FOV is replaced by a smooth propagation of the deformation field inside the FOV. Six head-and-neck cancer cases and two prostate cancer cases are used for evaluation. Dose calculation is performed to test the impacts on the resulting dose distribution. In terms of DIR accuracy, it is found that the average normalized mutual information (NMI), normalized cross correlation (NCC) and feature similarity index (FSIM) increase from 0.638, 0.948 and 0.917, to 0.641, 0.951 and 0.919, respectively, when compared with DISC without propagation. In terms of dose distribution, the relative L2 distance of dose (inside the FOV) between the ground truth and that calculated on deformed CT with propagation reduces from 9.25%to 1.41%, compared with those without propagation. We have developed a deformation field propagation method for DIR to register the planning CT and the CBCT image with small FOV. Tests on head-and-neck and prostate cancer cases have demonstrated that our algorithm can generate more accurate registration results for dose calculation. This work is supported in part by the University of California Lab Fees Research Program, the Master Research Agreement from Varian Medical Systems, Inc., and the grants from the National Natural Science Foundation of China (No.30970866).


CLAHRCs in practice: combined knowledge transfer and exchange strategies, cultural change, and experimentation.
The nine NIHR CLAHRCs are collaborations between universities and local NHS organizations that seek to improve patient outcomes through the conduct and application of applied health research. The theoretical and practical context within which the CLAHRCs were set up was characterized by a considerable degree of uncertainty, and the CLAHRCs were established as a natural experiment. We adopted a formative and emergent evaluation approach. Drawing on in-depth, multi-method case studies of two CLAHRCs we explored how they pursued their remit by supporting efforts to increase the relevance and use of health research, and building relationships. Both CLAHRCs: strengthened local networks and relationships; built capacity in their local academic and NHS communities to undertake and use research that meets the needs of the service; developed research and implementation methodologies; and added to understanding of the complex relation between research and implementation. There was evidence of impact of CLAHRC projects on health and social care services. Informed by the literature on implementing collaborative research initiatives, knowledge transfer and exchange and cultural change, some key lessons can be drawn. The CLAHRCs pursued a strategy that can be categorized as one of flexible comprehensiveness; i.e. their programmes have been flexible and responsive and they have used a range of approaches that seek to match the diverse aspects of the complex issues they face. Key features include their work on combining a range of knowledge transfer and exchange strategies, their efforts to promote cultural change, and the freedom to experiment, learn and adapt. Although the CLAHRCs do not, by themselves, have the remit or resources to bring about wholesale service improvement in health care, they do have features that would allow them to play a key role in some of the wider initiatives that encourage innovation.


Surgeon and nonsurgeon personalities at different career points.
Previous studies have demonstrated correlations between personality traits and job performance and satisfaction. Evidence suggests that personality differences exist between surgeons and nonsurgeons, some of which may develop during medical training. Understanding these personality differences may help optimize job performance and satisfaction among surgical trainees and be used to identify individuals at risk of burnout. This study aims to identify personality traits of surgeons and nonsurgeons at different career points. We used The Big Five Inventory, a 44-item measure of the five factor model. Personality data and demographics were collected from responses to an electronic survey sent to all faculty and house staff in the Departments of Surgery, Medicine, and Family Medicine at The Ohio State University College of Medicine. Data were analyzed to identify differences in personality traits between surgical and nonsurgical specialties according to level of training and to compare surgeons to the general population. One hundred ninety-two house staff and faculty in surgery and medicine completed the survey. Surgeons scored significantly higher on conscientiousness and extraversion but lower on agreeableness compared to nonsurgeons (all P < 0.05). Surgery faculty scored lower in agreeableness compared with that of surgery house staff (P = 0.001), whereas nonsurgeon faculty scored higher on extraversion compared with that of nonsurgeon house staff (P = 0.04). There appears to be inherent personality differences between surgical and nonsurgical specialties. The use of personality testing may be a useful adjunct in the residency selection process for applicants deciding between surgical and nonsurgical specialties. It may also facilitate early intervention for individuals at high risk for burnout and job dissatisfaction.


Macaque monkey retrosplenial cortex: II. Cortical afferents.
We investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (approximately 78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (approximately 67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long-term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions.


Near-neighbor interactions of the membrane-embedded subunits of the mitochondrial ATP synthase of a chlorophycean alga.
Mitochondrial F1FO-ATP synthase of the chlorophycean algae Polytomella sp. can be isolated as a highly stable dimeric complex of 1600kDa. It is composed of eight highly conserved orthodox subunits (α, β, γ, δ, ε, OSCP, a, and c) and nine subunits (Asa1-9) that are exclusive of chlorophycean algae. The Asa subunits replace those that build up the peripheral stalk and the dimerization domains of the ATP synthase in other organisms. Little is known about the disposition of subunits Asa6, Asa8 and Asa9, that are predicted to have transmembrane stretches and that along with subunit a and a ring of c-subunits, seem to constitute the membrane-embedded Fo domain of the algal ATP synthase. Here, we over-expressed and purified the three Asa hydrophobic subunits and explored their interactions in vitro using a combination of immunochemical techniques, affinity chromatography, and an in vivo yeast-two hybrid assays. The results obtained suggest the following interactions Asa6-Asa6, Asa6-Asa8, Asa6-Asa9, Asa8-Asa8 and Asa8-Asa9. Cross-linking experiments carried out with the intact enzyme corroborated some of these interactions. Based on these results, we propose a model of the disposition of these hydrophobic subunits in the membrane-embedded sector of the algal ATP synthase. We also propose based on sequence analysis and hydrophobicity plots, that the algal subunit a is atypical in as much it lacks the first transmembrane stretch, exhibiting only four hydrophobic, tilted alpha helices.


Syndrome of inappropriate secretion of antidiuretic hormone in traumatic brain injury: when tolvaptan becomes a life saving drug.
To outline the role of a new drug, tolvaptan, in treating severe and chronic hyponatraemia. Tolvaptan decreases aquaporin expression in renal collecting ducts, by inhibiting antidiuretic hormone (ADH)-V2 receptors, to promote free water clearance. Given its mechanism of action, this drug seems the ideal treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) when the osmotic imbalance leads to life threatening complications. A case is described of severe hyponatraemia deriving from SIADH secondary to meningoencephalitis in a patient admitted to hospital for traumatic brain injury. Clinical, laboratory and radiological data at presentation and for a 1 year of follow-up were analysed. Tolvaptan ameliorated hyponatraemia, brain oedema and consciousness, and drug withdrawal led to recurrence of hyponatraemia and coma. In patients with SIADH, which is not self-limited, and is associated with severe cognitive impairment, the use Tolvaptan may prove life saving and should be rigorously evaluated.


Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group.
Rocky Mountain spotted fever and other related diseases are systemic infections caused by rickettsiae. These obligatory intracellular bacteria target the endothelium, offering an appealing model to study the interactions between endothelial cells and T lymphocytes. We investigated the mRNA expression of chemokines known to target CD8+ T cells and CD4(+) T-helper 1 cells in the lungs of C3H/HeN mice infected with Rickettsia conorii with the purpose of identifying evidence for a role of chemokines in the immune clearance of rickettsiae from the vasculature. The expression of the CXCR3 ligands CXCL9 and CXCL10 was significantly higher than the other chemokines investigated. We validated the relevance of these results in the animal model through the analysis of tissues from humans with Rocky Mountain spotted fever. We then characterized the kinetics and localization of expression of CXCL9 and CXCL10 in lungs, brain, and liver of mice infected with lethal or sublethal doses of R. conorii by a combination of quantitative real-time polymerase chain reaction and immunohistochemistry. Interestingly, the peak of expression of these chemokines occurred 4 days before CD8+ T cells infiltrated the infected tissues. Our results suggest that CXCL9 and CXCL10 may play a role early during the immune response against rickettsial infections.


How much the eye tells the brain.
In the classic "What the frog's eye tells the frog's brain," Lettvin and colleagues showed that different types of retinal ganglion cell send specific kinds of information. For example, one type responds best to a dark, convex form moving centripetally (a fly). Here we consider a complementary question: how much information does the retina send and how is it apportioned among different cell types? Recording from guinea pig retina on a multi-electrode array and presenting various types of motion in natural scenes, we measured information rates for seven types of ganglion cell. Mean rates varied across cell types (6-13 bits . s(-1)) more than across stimuli. Sluggish cells transmitted information at lower rates than brisk cells, but because of trade-offs between noise and temporal correlation, all types had the same coding efficiency. Calculating the proportions of each cell type from receptive field size and coverage factor, we conclude (assuming independence) that the approximately 10(5) ganglion cells transmit on the order of 875,000 bits . s(-1). Because sluggish cells are equally efficient but more numerous, they account for most of the information. With approximately 10(6) ganglion cells, the human retina would transmit data at roughly the rate of an Ethernet connection.


Effects of 4-wk training using Vmax/Tmax on VO2max and performance in athletes.
The aim of this study was to determine the effects of a 4-wk individualized training program using Vmax as the exercise intensity and utilizing between 60 and 75% of a subject's Tmax as the exercise duration. Five male, middle-distance, trained subjects with the following characteristics (mean +/- SD): age, 22.8 +/- 4.5 yr; height, 181 +/- 4.7 cm; weight, 74.1 +/- 3.2 kg; skinfolds based on five areas, 35.9 +/- 3.9; and VO2max, 61.5 +/- 6.1 mL O2 x kg min(-1) volunteered to participate in this study. Before the training program, the subjects completed a 3000-m time trial, and three each of VO2max/Vmax and Tmax tests. Subjects then completed a 4-wk training program on the treadmill and were then retested on the VO2max/Vmax and Tmax tests. Pretraining versus posttraining results showed significant (P < 0.05) increases in average Vmax (20.5 km x h(-1) vs 21.3 km x h(-1) posttraining), Tmax (225.5 s vs 300.9 s posttraining), and VO2max (61.5 mL O2 x kg x min(-1) vs 64.5 mL O2 x kg x min(-1)). The 3000-m time trial decreased significantly from a pretraining value of 616.6 s to a posttraining value of 599.6 s (P < 0.05). The results of this study indicate that by utilizing between 60 and 75% of Tmax as an exercise duration and using Vmax as an exercise intensity that these two parameters can be extremely valuable in the prescription of exercise programs for athletes.


Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation.
Formation of the Drosophila embryo's dorsal-ventral pattern requires the maternal product of the Toll gene. DNA sequence and genetic analyses together suggested that the Toll gene product is a transmembrane protein which communicates information from an extracytoplasmic compartment to the cytoplasm. Using antibodies as probes, we show that the Toll protein is a 135 x 10(3) Mr glycoprotein which is tightly associated with embryonic membranes. During the syncytial stage when dorsal-ventral polarity is established, the maternal Toll protein is associated with the plasma membrane around the entire embryo. During later embryonic stages, the Toll protein is expressed zygotically on many cell surfaces, possibly to promote cell adhesion. The plasma membrane localization of the Toll protein in the syncytial embryo suggests that transmembrane signaling from the extracellular perivitelline space to the cytoplasm is required for establishment of the embryonic dorsal-ventral pattern.


FAS activation induces dephosphorylation of SR proteins; dependence on the de novo generation of ceramide and activation of protein phosphatase 1.
The search for potential targets for ceramide action led to the identification of ceramide-activated protein phosphatases (CAPP). To date, two serine/threonine protein phosphatases, protein phosphatase 2A (PP2A) and protein phosphatase 1 (PP1), have been demonstrated to function as ceramide-activated protein phosphatases. In this study, we show that treatment with either anti-FAS IgM (CH-11) (150 ng/ml) or exogenous d-(e)-C(6-)ceramide (20 microm) induces the dephosphorylation of the PP1 substrates, serine/arginine-rich (SR) proteins, in Jurkat acute leukemia T-cells. The serine/threonine protein phosphatase inhibitor, calyculin A, but not the PP2A-specific inhibitor, okadaic acid, inhibited both FAS- and ceramide-induced dephosphorylation of SR proteins. Anti-FAS IgM treatment of Jurkat cells led to a significant increase in levels of endogenous ceramide beginning at 2 h with a maximal increase of 10-fold after 7 h. A 2-h pretreatment of Jurkat cells with fumonisin B(1) (100 microm), a specific inhibitor of CoA-dependent ceramide synthase, blocked 80% of the ceramide generated and completely inhibited the dephosphorylation of SR proteins in response to anti-FAS IgM. Moreover, pretreatment of Jurkat cells with myriocin, a specific inhibitor of serine-palmitoyl transferase (the first step in de novo synthesis of ceramide), also blocked FAS-induced SR protein dephosphorylation, thus demonstrating a role for de novo ceramide. These results were further supported using A549 lung adenocarcinoma cells treated with d-(e)-C(6-)ceramide. Dephosphorylation of SR proteins was inhibited by fumonisin B(1) and by overexpression of glucosylceramide synthase; again implicating endogenous ceramide generated de novo in regulating the dephosphorylation of SR proteins in response to FAS activation. These results establish a specific intracellular pathway involving both de novo ceramide generation and activation of PP1 to mediate the effects of FAS activation on SR proteins.


Synthesis of dihydronaphthalene analogues inspired by combretastatin A-4 and their biological evaluation as anticancer agents.
The natural products colchicine and combretastatin A-4 (CA4) have provided inspiration for the discovery and development of a wide array of derivatives and analogues that inhibit tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. A water-soluble phosphate prodrug salt of CA4 (referred to as CA4P) has demonstrated the ability to selectively damage tumor-associated vasculature and ushered in a new class of developmental anticancer agents known as vascular disrupting agents (VDAs). Through a long-term program of structure activity relationship (SAR) driven inquiry, we discovered that the dihydronaphthalene molecular scaffold provided access to small-molecule inhibitors of tubulin polymerization. In particular, a dihydronaphthalene analogue bearing a pendant trimethoxy aryl ring (referred to as KGP03) and a similar aroyl ring (referred to as KGP413) were potent inhibitors of tubulin polymerization (IC50 = 1.0 and 1.2 μM, respectively) and displayed low nM cytotoxicity against human cancer cell lines. In order to enhance water-solubility for in vivo evaluation, the corresponding phosphate prodrug salts (KGP04 and KGP152, respectively) were synthesized. In a preliminary in vivo study in a SCID-BALB/c mouse model bearing the human breast tumor MDA-MB-231-luc, a 99% reduction in signal was observed with bioluminescence imaging (BLI) 4 h after IP administration of KGP152 (200 mg kg-1) indicating reduced tumor blood flow. In a separate study, disruption of tumor-associated blood flow in a Fischer rat bearing an A549-luc human lung tumor was observed by color Doppler ultrasound following administration of KGP04 (15 mg kg-1).


Influence and adjustment of carrier lifetimes in InGaAs/InAlAs photoconductive pulsed terahertz detectors: 6 THz bandwidth and 90dB dynamic range.
We investigate the influence of Beryllium (Be) doping on the performance of photoconductive THz detectors based on molecular beam epitaxy (MBE) of low temperature (LT) grown In(0.53)Ga(0.47)As/In(0.52)Al(0.48)As multilayer heterostructures (MLHS). We show how the optical excitation power affects carrier lifetime, detector signal, dynamic range and bandwidth in THz time domain spectroscopy (TDS) in dependence on Be-doping concentration. For optimal doping we measured a THz bandwidth in excess of 6 THz and a dynamic range of up to 90 dB.


Intranasal delivery of Thyroid hormones in MCT8 deficiency.
Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3'-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present a paradoxical state of peripheral hyperthyroidism and brain hypothyroidism, this last one most likely arising from impaired thyroid hormone transport across the brain barriers. The administration of thyroid hormones by delivery pathways that bypass the brain barriers, such as the intranasal delivery route, offers the possibility to improve the neurological defects of MCT8-deficient patients. In this study, the thyroid hormones T4 and T3 were administrated intranasally in different mouse models of MCT8 deficiency. We have found that, under the present formulation, intranasal administration of thyroid hormones does not increase the content of thyroid hormones in the brain and further raises the peripheral thyroid hormone levels. Our data suggests intranasal delivery of thyroid hormones is not a suitable therapeutic strategy for MCT8 deficiency, although alternative formulations could be considered in the future to improve the nose-to-brain transport.


Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry.
The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry. Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions </=35%. The median age of the 9580 Registry patients was 66 years, 26% were women, the median ejection fraction was 27%, and the primary aetiology of left ventricular dysfunction was ischaemic (63%). Eighty percent of patients were receiving ACE inhibitors. The most common reason for non-use of ACE inhibitors was intolerance (9%). The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction. The contemporary use of ACE inhibitors (80%) appears to be higher than previously reported and the main reason for non-use is perceived intolerance (9%).


The course of arterial pressure and the effect of Sar1-Thr8-angiotensin II in a new model of two-kidney hypertension in conscious dogs.
1. We describe a new method of producing two-kidney hypertension in dogs by a two-step procedure with complete occlusion of a renal artery 2 weeks after it was partially constricted. 2. Control mean arterial pressure (96 +/- 3 mmHg) of nine conscious, trained dogs rose to 107 +/- 3 mmHg 2 weeks after partial constriction of a renal artery, and it stabilized at a sustained hypertensive plateau (124 +/- 7 mmHg) 3 weeks after complete occlusion. 3. Intravenous infusion of an angiotensin II antagonist (Sar1-Thr8-angiotensin II) caused arterial pressure to fall during the acute but not the chronic phase of renal hypertension. In this latter phase plasma renin activity had returned to control values. 4. We conclude that the renin-angiotensin system appears not to be directly involved in the chronic phase of two-kidney hypertension in the dog.


The Impact of Collagenase Clostridium histolyticum Introduction on Dupuytren Treatment Patterns in the United States.
The U.S. Food and Drug Administration approved the use of collagenase Clostridium histolyticum (CCH) in the United States in February 2010. This study addresses the impact of that approval on the number of Dupuytren contracture (DC) encounters and treatment patterns in the United States. Using the Intercontinental Marketing Services Health Office-Based Medical Claims database, we identified the monthly number of DC encounters and DC procedures between January 2007 and December 2013. Collagenase Clostridium histolyticum usage data from March 2010 to December 2013 was derived from the U.S. CCH manufacturer's data warehouse. Using the combined data, the yearly increasing trends in DC encounters and treatment volume were compared before and after the introduction of CCH. Time trends in the relative procedure frequencies were then examined. Finally, the presence of seasonal variation was tested for in each treatment type. Dupuytren contracture encounters increased on average by 19,015 per year between 2007 and 2009, whereas between 2011 and 2013, DC encounters increased on average by 34,940 per year. In terms of absolute procedure counts, the surgery trend line began decreasing in 2010 with the release of CCH. Meanwhile, CCH continuously increased between 2010 and 2013, and needle aponeurotomy (NA) remained relatively stable. By the year 2013, minimally invasive techniques (NA and CCH) comprised 39% of all treatment, compared with only 14% in 2007. Lastly, there was a statistically significant seasonal increase in the number of surgical procedures during the wintertime but no seasonal variation in NA or CCH. After the introduction of CCH, the number of Dupuytren encounters increased at a greater annual rate. The introduction and growth of CCH coincided with a decrease in surgery. The number of NA procedures remained steady throughout the study period. The number of open surgery cases followed a predictable seasonal variation with more procedures during the winter months, but this seasonal variation was not seen with less invasive techniques. Economic/Decision Analysis II.


Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA-1) Interactome in Human Dendritic Cells.
The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) plays an important role in the migration, adhesion and intercellular communication of dendritic cells (DCs). During the differentiation of human DCs from monocyte precursors, LFA-1 ligand binding capacity is completely lost, even though its expression levels were remained constant. Yet LFA-1-mediated adhesive capacity on DCs can be regained by exposing DCs to the chemokine CCL21, suggesting a high degree of regulation of LFA-1 activity during the course of DC differentiation. The molecular mechanisms underlying this regulation of LFA-1 function in DCs, however, remain elusive. To get more insight we attempted to identify specific LFA-1 binding partners that may play a role in regulating LFA-1 activity in DCs. We used highly sensitive label free quantitative mass-spectrometry to identify proteins co-immunoprecipitated (co-IP) with LFA-1 from ex vivo generated DCs. Among the potential binding partners we identified not only established components of integrin signalling pathways and cytoskeletal proteins, but also several novel LFA-1 binding partners including CD13, galectin-3, thrombospondin-1 and CD44. Further comparison to the LFA-1 interaction partners in monocytes indicated that DC differentiation was accompanied by an overall increase in LFA-1 associated proteins, in particular cytoskeletal, signalling and plasma membrane (PM) proteins. The here presented LFA-1 interactome composed of 78 proteins thus represents a valuable resource of potential regulators of LFA-1 function during the DC lifecycle.


Measurement of serum haptoglobin as an indicator of the efficacy of malaria intervention trials.
Serum haptoglobin levels were measured by an enzyme-linked immunosorbent assay in Gambian children who participated in 3 malaria intervention trials with untreated or impregnated bed nets. In one study, in which a significant effect on clinical malaria was observed, the mean serum haptoglobin level was significantly higher in the intervention than in the control group. In the other 2 studies, in which no significant protection was observed, mean haptoglobin levels were similar in intervention and control groups. Measurement of serum haptoglobin may provide a useful indirect measure of the effectiveness of malaria control programmes.


Conformational dynamics of the frameshift stimulatory structure in HIV-1.
Programmed ribosomal frameshifting (PRF) in HIV-1 is thought to be stimulated by a hairpin in the mRNA, although a pseudoknot-like triplex has also been proposed. Because the conformational dynamics of the stimulatory structure under tension applied by the ribosomal helicase during translation may play an important role in PRF, we used optical tweezers to apply tension to the HIV stimulatory structure and monitor its unfolding and refolding dynamics. The folding and unfolding kinetics and energy landscape of the hairpin were measured by ramping the force on the hairpin up and down, providing a detailed biophysical characterization. Unexpectedly, whereas unfolding reflected the simple two-state behavior typical of many hairpins, refolding was more complex, displaying significant heterogeneity. Evidence was found for multiple refolding pathways as well as previously unsuspected, partially folded intermediates. Measuring a variant mRNA containing only the sequence required to form the proposed triplex, it behaved largely in the same way. Nonetheless, very rarely, high-force unfolding events characteristic of pseudoknot-like structures were observed. The rare occurrence of the triplex suggests that the hairpin is the functional stimulatory structure. The unusual heterogeneity of the hairpin dynamics under tension suggests a possible functional role in PRF similar to the dynamics of other stimulatory structures.


Major depression in community-dwelling middle-aged and older adults: prevalence and 2- and 4-year follow-up symptoms.
Although major depression is a common condition across the age range, there is some evidence from clinical studies that it may be more persistent and disabling in older adults. This study examined the demographic, socio-economic and clinical factors associated with major depression and with persistence of depressive symptoms at 2- and 4-year follow-ups in a large population sample of middle-aged and older adults. In a sample of 9747 participants aged over 50 in the 1996 wave of the US Health and Retirement Study, the authors assessed the 12-month prevalence of major depression using the Composite International Diagnostic Interview-Short Form (CIDI-SF). Significant depressive symptoms at the time of 1996, 1998 and 2000 interviews were assessed using a short form of the Center for Epidemiological Studies Depression Scale (CES-D). The 12-month prevalence of CIDI-SF major depression was 6.6%. With age, prevalence declined, but the likelihood of significant depressive symptoms at follow-ups increased. Both prevalence and persistence of significant depressive symptoms at follow-ups were associated with socio-economic disadvantage and physical illness. Persistence of depressive symptoms at follow-ups was also associated with symptoms of anhedonia, feelings of worthlessness, and thoughts of death at baseline. Sociodemographic, physical health and a specific profile of depressive symptoms are associated with a poorer course of major depression in the middle-aged and older adults. These indicators may identify a subgroup of patients in need of more careful follow-up and intensive treatment.


Light-folded projection three-dimensional display.
A light-folded projection three-dimensional (3D) display system with a single projection lens and a rectangular light tunnel which is composed of four folding mirrors on its inside walls is proposed. It is theoretically shown through the Wigner distribution function analysis that the proposed system can generate the same light field effectively as that of the conventional projection-type multiview 3D display system with plural projection lenses. Multiview 3D imaging of the proposed system configuration is experimentally demonstrated.


Encephalitozoon hellem in a patient with CD4+ T-cell prolymphocytic leukemia: case report and genomic identification.
Five cases of microsporidioses among leukemic patients, 4 in myeloid-leukemic patients and 1 in a chronic lymphocytic leukemia, have been described until now. We report a case of microsporidiosis and the genomic identification of Encephalitozoon hellem in a patient with CD4(+) T-cell prolymphocytic leukemia.


Regulation of Elg1 activity by phosphorylation.
ELG1 is a conserved gene with important roles in the maintenance of genome stability. Elg1's activity prevents gross chromosomal rearrangements, maintains proper telomere length regulation, helps repairing DNA damage created by a number of genotoxins and participates in sister chromatid cohesion. Elg1 is evolutionarily conserved, and its Fanconi Anemia-related mammalian ortholog (also known as ATAD5) is embryonic lethal when lost in mice and acts as a tumor suppressor in mice and humans. Elg1 encodes a protein that forms an RFC-like complex that unloads the replicative clamp, PCNA, from DNA, mainly in its SUMOylated form. We have identified 2 different regions in yeast Elg1 that undergo phosphorylation. Phosphorylation of one of them, S112, is dependent on the ATR yeast ortholog, Mec1, and probably is a direct target of this kinase. We show that phosphorylation of Elg1 is important for its role at telomeres. Mutants unable to undergo phosphorylation suppress the DNA damage sensitivity of Δrad5 mutants, defective for an error-free post-replicational bypass pathway. This indicates a role of phosphorylation in the regulation of DNA repair. Our results open the way to investigate the mechanisms by which the activity of Elg1 is regulated during DNA replication and in response to DNA damage.


Impacts of an HIA on inter-agency and inter-sectoral partnerships and community participation: lessons from a local level HIA in the Republic of Ireland.
This study evaluates the impacts of a locally based health impact assessment (HIA) on community participation, inter-sectoral and inter-agency partnership in local decision and policy-making processes. The methods comprised a series of semi-structured interviews with key informants followed by thematic analysis of transcribed responses. The study revealed a number of positive impacts among both community and service providers. A particularly advantageous impact was the facilitation of community learning through a local action group formed as a recommendation of the HIA that provided community development and HIA training. During the HIA process all participants increased their knowledge of health determinants and recognized a broader range of evidence sources for local decision-making. Participants also developed a greater understanding of each other's roles and perspectives. Additionally, the study revealed a number of barriers to HIA. Differing views on the role of HIA were evident whereby community members tended to regard HIA as an advocacy tool for local issues impacting on health in their locality, while service providers perceived its role more in terms of networking and collaboration. A key area remaining to be tackled in terms of partnership working is the approach of service agencies to enabling meaningful community participation in local decision-making processes. In this respect, attention to the cultural dimension of inter-sectoral working, and the need for training for both service agency staff and community members prior to or at the initial stages of HIA are required. Such changes could facilitate more meaningful community inclusion and help to address the current power imbalance between these two sectors.


Histomorphometrical analysis of bone formed after maxillary sinus floor augmentation by grafting with a combination of autogenous bone and demineralized freeze-dried bone allograft or hydroxyapatite.
Maxillary sinus floor augmentation procedures are currently the treatment of choice when the alveolar crest of the posterior maxilla is insufficient for dental implant anchorage. This procedure aims to obtain enough bone with biomaterial association with the autogenous bone graft to create volume and allow osteoconduction. The objective of this study was to histologically and histometrically evaluate the bone formed after maxillary sinus floor augmentation by grafting with a combination of autogenous bone, from the symphyseal area mixed with DFDBA or hydroxyapatite. Ten biopsies were taken from 10 patients 10 months after sinus floor augmentation using a combination of 50% autogenous bone plus 50% demineralized freeze-dried bone allograft (DFDBA group) or 50% autogenous bone plus 50% hydroxyapatite (HA group). Routine histological processing and staining with hematoxylin and eosin and Masson's trichrome were performed. The histomorphometrical analysis indicated good regenerative results in both groups for the bone tissue mean in the grafted area (50.46+/-16.29% for the DFDBA group and 46.79+/-8.56% for the HA group). Histological evaluation revealed the presence of mature bone with compact and cancellous areas in both groups. The inflammatory infiltrate was on average nonsignificant and of mononuclear prevalence. Some biopsies showed blocks of the biomaterial in the medullary spaces close to the bone wall, with absence of osteogenic activity. The results indicated that both DFDBA and HA associated with an autogenous bone graft were biocompatible and promoted osteoconduction, acting as a matrix for bone formation. However, both materials were still present after 10 months.


Computed tomographic findings in dogs and cats with temporomandibular joint disorders: 58 cases (2006-2011).
To describe CT findings in dogs and cats with temporomandibular joint (TMJ) disorders. Retrospective case series. 41 dogs and 17 cats. Medical records and CT images of the skull were reviewed for dogs and cats that were examined at a dentistry and oral surgery specialty practice between 2006 and 2011. Of 142 dogs and 42 cats evaluated, 41 dogs and 17 cats had CT findings consistent with a TMJ disorder. In dogs, the most common TMJ disorder was osteoarthritis; however, in most cases, there were other TMJ disorders present in addition to osteoarthritis. Osteoarthritis was more frequently identified at the medial aspect rather than the lateral aspect of the TMJ, whereas the frequency of osteoarthritic involvement of the dorsal and ventral compartments did not differ significantly. In cats, fractures were the most common TMJ disorder, followed by osteoarthritis. Clinical signs were observed in all dogs and cats with TMJ fractures, dysplasia, ankylosis, luxation, and tumors; however, only 4 of 15 dogs and 2 of 4 cats with osteoarthritis alone had clinical signs. Results indicated that TMJ disorders were frequently present in combination. Osteoarthritis was the most common TMJ disorder in dogs and the second most common TMJ disorder in cats. Computed tomography should be considered as a tool for the diagnosis of TMJ disorders in dogs and cats with suspected orofacial disorders and signs of pain. (J Am Vet Med Assoc 2013;242:69-75).


Food allergy.
Food allergies affect up to 6% of young children and 3%-4% of adults. They encompass a range of disorders that may be IgE and/or non-IgE mediated, including anaphylaxis, pollen food syndrome, food-protein-induced enterocolitis syndrome, food-induced proctocolitis, eosinophilic gastroenteropathies, and atopic dermatitis. Many complex host factors and properties of foods are involved in the development of food allergy. With recent advances in the understanding of how these factors interact, the development of several novel diagnostic and therapeutic strategies is underway and showing promise.


A qualitative study of barriers to and facilitators of optimal engagement in care among PLWH and substance use/misuse.
Persons living with HIV (PLWH) and substance use/misuse experience significant barriers to engagement in HIV care at every step of the HIV care continuum including: (1) HIV testing and diagnosis (2) linkage to clinical care (3) retention in care pre-antiretroviral therapy (ART) (4) ART initiation and adherence (5) viral suppression. We qualitatively explored the facilitators of and barriers to participation in the HIV care continuum among PLWH with substance use/misuse. We performed semi-structured in-depth interviews with 34 PLWH in care with recent substance use. The transcripts were analyzed in an iterative process using an editing style analysis. Interviews were conducted until thematic saturation was achieved. Participants attributed an escalation in drug use at the time of diagnosis to denial of their disease and the belief that their death was inevitable and cited this as a barrier to treatment entry. In contrast, participants reported that experiencing adverse physical effects of uncontrolled HIV infection motivated them to enroll in care. Reported barriers to retention and adherence to care included forgetting medications and appointments because of drug use, prioritizing drug use over HIV treatment and side effects associated with medications. Participants described that progression of illness, development of a medication taking ritual and a positive provider-patient relationship all facilitated engagement and reengagement in care. PLWH with substance use engaged in care describe barriers to and facilitators of optimal engagement related to and distinct from substance use. Greater understanding of the biologic, psychological and social factors that promote and impair engagement in care can inform interventions and reduce the increased morbidity and mortality experienced by PLWH with substance use.