Scaling Up and Out HIV Prevention and Behavioral Health Services to Latino Sexual Minority Men in South Florida: Multi-Level Implementation Barriers, Facilitators, and Strategies.
Latino sexual minority men (LSMM) are disproportionately affected by HIV in the United States. Concurrently, behavioral health disparities, including mental health and substance use concerns, worsen HIV disparities affecting LSMM. Yet, evidence-based HIV prevention and behavioral health services are insufficiently scaled up and out to this population, perpetuating health disparities, thwarting efforts to control the HIV epidemic, and highlighting the need for culturally relevant evidence-based implementation strategies that address these disparities. Participants included 28 LSMM with varying degrees of engagement in HIV prevention and behavioral health services, and 10 stakeholders with experience delivering HIV prevention and behavioral health services to LSMM in South Florida, an HIV epicenter in general and in particular for LSMM. Participants completed semistructured interviews (English/Spanish) regarding LSMM's barriers and facilitators to engaging in HIV prevention and behavioral health services. Interviews were audio recorded and analyzed using thematic analysis. The 16 themes that emerged from the qualitative analysis were consistent with the consolidated framework for implementation research, an implementation research framework that articulates barriers and facilitators to implementing clinical interventions. Findings suggested the need for implementation strategies that simplify and reduce costs of HIV prevention and behavioral health services, address syndemic challenges impacting service use among LSMM, reduce stigma about service utilization, leverage peer networks, increase provider and community knowledge about services, and build LSMM's readiness and motivation to engage in services. Such strategies may ultimately address HIV and behavioral health disparities among LSMM and facilitate achievement of ending the HIV epidemic goals in this disproportionally affected population.


LTBP2-related "Marfan-like" phenotype in two Roma/Gypsy subjects with the LTBP2 homozygous p.R299X variant.
Recessive variants in LTBP2 are associated with eye-restricted phenotypes including (a) primary congenital glaucoma and (b) microspherophakia/megalocornea and ectopia lentis with/without secondary glaucoma. Nosology of LTBP2 pathology in humans is apparently in contrast with the consolidated evidence of a wide expression of this gene in the developing embryo. Accordingly, in previously published patients with LTBP2-related eye disease, additional extraocular findings have been occasionally reported and include, among others, high-arched palate, tall stature, and variable cardiac involvement. Anyway, no emphasis was put on such systemic manifestations. Here, we report two unrelated Roma/Gypsy patients first ascertained for a multisystem disorder mainly characterized by primary congenital glaucoma, complex congenital heart defect, tall stature, long fingers, skin striae and dystrophic scarring, and resembling Marfan syndrome. Heart involvement was severe with polyvalvular heart dysplasia in one, and transposition of great arteries, thoracic arterial tortuosity, polyvalvular heart dysplasia, and neo-aortic root dilatation in the other. Both patients were homozygous for the recurrent c.895C>T[p.(R299X)] variant, typically found in individuals of Roma/Gypsy descent with an eye-restricted phenotype. Our findings point out LTBP2 as responsible of a systemic phenotype coherent with the community of syndromes related to anomalies in genes involved in the TGFβ-pathway. Among these disorders, LTBP2-related systemic disease emerges as a distinct condition with expanding prognostic implications and autosomal recessive inheritance.


Lagrangian modelling of oil concentrations at sea: A sensitivity analysis to the grid resolution and number of Lagrangian elements.
This paper presents a novel method to select the optimal combination of grid resolution and number of Lagrangian elements (LEs) required in numerical modelling of oil concentrations at sea. A sensitivity analysis in terms of grid resolution and the number of LEs, was carried out to understand the uncertainty that these user-dependent parameters introduce in the numerical results. A dataset of 211,200 simulations performed under 400 metocean patterns, 6 initial volumes, 11 grid resolutions, and different numbers of LEs (100 to 500,000), was used to analyze the sensitivity of the model along different Thresholds of Concern. Results show the importance of a correct selection of the number of LEs and the grid resolution in Lagrangian modelling of surface oil concentrations. The method proposed will allow selecting the optimal combination of these parameters to find an optimal balance between the accuracy and the computational cost of the simulation.


Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature.
Anabolic androgenic steroids (AAS) are used illicitly at high doses by bodybuilders. The misuse of these drugs is associated with serious adverse effects to the liver, including cellular adenomas and adenocarcinomas. We report two very different cases of adult male bodybuilders who developed hepatocellular adenomas following AAS abuse. The first patient was asymptomatic but had two large liver lesions which were detected by ultrasound studies after routine medical examination. The second patient was admitted to our hospital with acute renal failure and ultrasound (US) studies showed mild hepatomegaly with several very close hyperecogenic nodules in liver, concordant with adenomas at first diagnosis. In both cases the patients have evolved favourably and the tumours have shown a tendency to regress after the withdrawal of AAS. The cases presented here are rare but may well be suggestive of the natural course of AAS induced hepatocellular adenomas. In conclusion, sportsmen taking AAS should be considered as a group at risk of developing hepatic sex hormone related tumours. Consequently, they should be carefully and periodically monitored with US studies. In any case, despite the size of the tumours detected in these two cases, the possibility of spontaneous tumour regression must also be taken in account.


Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker.
The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P = 0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment.


Sr(II)-UPRM-5 titanium silicate framework thermally induced contraction: in situ high temperature XRD and 29Si MAS NMR.
The thermally induced contraction process of a titanosilicate prepared with tetraethylammonium hydroxide and ion exchanged with Sr(II) (Sr-UPRM-5) after detemplation has been characterized via in situ high temperature X-ray diffraction (XRD) and (29)Si magic angle spinning nuclear magnetic resonance (MAS NMR). The as-synthesized material was prepared via conventional and microwave-assisted hydrothermal methods, the latter resulting in a reaction time an order of magnitude shorter than the former case. In situ high temperature XRD tests performed on Sr-UPRM-5 indicate that at 120 °C, water coordinated to the structure is released initiating the collapse of the framework. At much higher temperatures, the material eventually becomes an amorphous phase. Indexing of the XRD patterns indicates that lattice constant a was more affected by the heat treatment, probably related to the material's pore system, while the unit cell volume experienced a 44% reduction. (29)Si MAS NMR analyses for as-synthesized UPRM-5 confirmed two different silicon environments: Si(2Si, 2Ti(octa)) and Si(3Si, 1Ti(semi-octa)), which are similar to those exhibited by titanosilicate ETS-4. On the other hand, in situ high temperature (29)Si MAS NMR analyses for Sr-UPRM-5 demonstrated that changes in the silicon environment due to the presence of titanium centers possessing additional multiple coordination states, which arise from elimination of framework coordinated water molecules, are responsible for the structure collapsing. In general, these results underline the importance of avoiding complete removal of tenacious water molecules in order to preserve the Sr-UPRM-5 properties suitable for adsorption and catalysis applications.


Leveling the Maxillary Occlusal Plane Without Orthodontic Appliances in Patients With Hemifacial Microsomia Using Unilateral Vertical Mandibular Distraction Osteogenesis.
To assess maxillary occlusal plane correction in patients with hemifacial microsomia (HFM) after vertical vector mandibular distraction osteogenesis (vMDO) without orthodontic appliances. A retrospective study was performed on consecutive patients with HFM and Kaban-Pruzansky type-II mandibular deformities who underwent unilateral vMDO by a single surgeon over an 18-month period. Patients with 12-months minimum clinical follow-up and postero-anterior (PA) cephalograms taken preoperatively and at a minimum of 3 months post-consolidation were included. Five patients met inclusion criteria, 3 were female, median age was 13 years, median distraction length was 21.3 mm. Median radiographic follow-up was 5 months (range 3-38) post-consolidation. Median correction of the ramus height differential (difference between non-diseased and diseased side) was 97.3%. Median maxillary height differential correction was 72.2%. Median maxillary occlusal plane angle correction (towards zero) was 84.2%. Relative and absolute maxillary bone growth was greater on the diseased side (median 7.4%, 3.5 mm versus 2.8%, 1.4 mm). Dentoalveolar height decreased bilaterally in 4 of the 5 patients. Median chin point correction (towards midline) was 31.4%. Unilateral vMDO without orthodontic appliances effectively corrected mandibular ramus height, leveled the maxillary occlusal plane, and preferentially increased maxillary bone growth on the diseased side in patients with HFM.


More behavioral recommendations produce more change: A meta-analysis of efficacy of multibehavior recommendations to reduce nonmedical substance use.
Death and morbidity associated with substance use have risen continuously over the last few decades, increasing the need for rigorous examination of promising programs. Interventions attempting to change multiple behaviors have been designed to address interconnected problems such as use of both alcohol and drugs. This meta-analysis aimed to examine the efficacy of multibehavior interventions to curb nonmedical substance use in relation to the theoretical relation among different substance use behaviors. Specifically, our synthesis aimed to estimate the optimal number of recommendations for intervention efficacy and evaluate the impact of different combinations of recommendations on intervention efficacy. A synthesis of multibehavior interventions addressing nonmedical substance use was conducted to measure behavioral changes between the pretest and the follow-up. These changes were then compared across different numbers of recommendations. Sixty-nine reports and 233 effect sizes (k of conditions = 155, n = 28,295) were included. A positive linear relation was found between the number of targeted behaviors and intervention efficacy, which was stronger for drug use than alcohol use. Furthermore, recommendations on drug use worked better when paired with recommendations targeting other behaviors, whereas recommendations on alcohol use worked more independently. Lastly, multibehavior interventions were especially efficacious when delivered by experts. Overall, our synthesis indicated that targeting multiple substances is beneficial for changing drug use outcomes, but less so for alcohol use outcomes. Therefore, in the current substance use epidemic, innovative multibehavior programs appear to hold promise, especially to combat nonmedical drug use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


NEU Screen Shows High Accuracy in Detecting Cognitive Impairment in Older Persons Living With HIV.
The NEUrocognitive (NEU) Screen is a practical tool proposed to screen for HIV-associated cognitive impairment in the clinical setting. This is a pencil-and-paper method that can be applied rapidly (≤10 minutes for administration) and has no copyright limitations. In this study, we aimed at investigating its diagnostic accuracy in an older population of persons living with HIV (PLWH), with cutoffs set at 30, 40, 50, and 60 years. Data were collected from a sample of 368 PLWH who underwent a comprehensive neuropsychological tests battery (gold standard). Results of statistical tests showed that accuracy of the NEU Screen increased with age of the participants. The highest degree of precision, with a sensitivity of 91% and specificity of 92%, was obtained for people ages 60 years or older (correct classification: 91%). These optimal results point to the great potential of the NEU Screen as a tool for detecting cognitive disorders in older PLWH.


Edible Bird's nest extract as a chondro-protective agent for human chondrocytes isolated from osteoarthritic knee: in vitro study.
Osteoarthritis (OA) is a degenerative joint disease that results in the destruction of cartilage. Edible Bird's Nest (EBN) extract contains important components, which can reduce the progression of osteoarthritis and helps in the regeneration of the cartilage. The present study aimed to investigate the effect of EBN extract on the catabolic and anabolic activities of the human articular chondrocytes (HACs) isolated from the knee joint of patients with OA. A single batch of EBN extract was prepared with hot-water extraction and coded as HMG. HACs were isolated from the knee joint cartilage removed during surgery. The optimum concentration of HMG for HAC cultures was determined using MTT assay. The effect of HMG on the catabolic and anabolic genes' expression in HACs was measured by real-time PCR. The total amount of prostaglandin E2 (PGE2) production was determined by ELISA method, and the total sulphated glycosaminoglycan (GAGs) production was quantified by 1,9-dimethylmethylene blue (DMMB) assay. MTT assay showed 0.50% - 1.00% HMG supplementation promoted HACs proliferation. HMG supplementation was able to reduce the catabolic genes' expression in cultured HACs such as matrix metalloproteinases (MMP1 & MMP3), Interleukin 1, 6 and 8 (IL-1, IL-6 & IL-8), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Prostaglandin E2 (PGE2) production was significantly reduced in HAC cultures supplemented with HMG. With regard to anabolic activity assessment, type II collagen, Aggrecan and SOX-9 gene expression as well as sGAG production was increased in the HMG supplemented groups. Edible Bird's Nest extract coded as HMG demonstrated chondro-protection ability on human articular chondrocytes in vitro. It reduced catabolic activities and increased cartilage extracellular matrix synthesis. It is concluded that HMG is a potential agent in the treatment of osteoarthritis.


Sexually-transmitted disease risk in a Micronesian atoll population.
The potential health threat of AIDS to the native island-based populations in the Pacific is now widely appreciated by those working in the public-health sector throughout the region. Although several countries in the region are yet to identify any cases of AIDS or HIV seropositivity, there is reason to suspect that heterosexual contact may emerge as a predominant mode of spread of HIV infection into native Pacific island populations. Sexual networks and their relationship to potentially 'risky behaviours' are described for a single native Micronesian atoll community on the basis of ethnographic observation and interviewing. This description is combined with the investigation of historic-demographic dimensions of the epidemiology of sexually-transmitted diseases in the same population to draw some conclusions about the opportunities for HIV transmission and acquisition among the sexually-active portions of this community. Although sexually-transmitted diseases have not had an appreciable epidemiological or demographic impact on the population in the past, the sexual networks within the community and beyond provide ample opportunity for the introduction and spread of sexually transmitted diseases, including HIV and its sequel AIDS.


Proanthocyanidin from grape seed extracts protects indomethacin-induced small intestinal mucosal injury.
Proanthocyanidin (grape seed proanthocyanidin extracts, GSPEs) is an antioxidant and scavenges free radicals. Excessive oxidative stress and free radical production are major components in the pathogenesis of NSAID-induced small intestinal injury. We investigated the effect of GSPEs on indomethacin-induced intestinal mucosal injury in the rat. Rats were allocated into four groups: the null control group, the indomethacin control group, the low-dose GSPEs group, and the high-dose GSPEs group. GSPEs were administered for 4 days. Then indomethacin and GSPEs were coadministered for the following 2 days by oral route. The dose of indomethacin was 200 mg/Kg. The doses of GSPEs were 100 mg/Kg for low-dose group and 300 mg/Kg for high-dose group. Luminal bleeding was solely observed in one of 5 rats from indomethacin control group. The number of ulcer count was reduced to 0.1 ± 0.3 per rat in GSPEs treated group compared to 1.4 ± 0.5 per rat in indomethacin control group. Submucosal inflammatory cell infiltration was also reduced to 50% in GSPEs treated group. The tissue level of prostaglandin E2 was not affected by GSPEs treatment. GSPEs attenuated the indomethacin-induced small intestinal injury irrespective of the tissue PGE2 depletion and glutathione consumption.


Serum and secretory antibody responses to Neisseria gonorrhoeae in patients with gonococcal infections.
The present study was conducted to characterize the nature and pattern of serum and secretory antibody responses to N. gonorrhoeae by haemagglutination inhibition, opsonization, and immunofluorescence techniques in male and female patients with different clinical manifestations of gonorrhoea. Most male patients with acute gonococcal infection developed serum IgG and, less frequently, IgM antibodies against pilated gonococci within 2 weeks of infection and these antibodies declined to normal levels 1 to 2 months after treatment. This response was not noticeably different from the responses developed in male patients with subacute infection and female patients with chronic infection. Immunological analyses of the seminal plasmas and cervical fluids from these patients showed that antibodies reactive with both pilated and non-pilated N. gonorrhoeae are present in some of the cases. A small percentage of male patients who recovered from subacute gonococcal infection but not from acute infection possessed low levels of IgG and, less frequently, IgA antibodies to gonococcal antigens in their seminal plasmas. In contrast, more than half of the females with gonorrhoea had IgG antigonococcal antibodies in the cervical fluid. However, a small number of samples also showed the presence of IgA and IgM antibodies. IgA antibody in most of these IgA-positive samples was of the secretory type. The presence of secretory IgA (SIgA) in secretions and the lack of correlation between the antibody titres in serum and in secretions of these patients suggest that infection with N. gonorrhoeae may independently stimulate both a systemic and a local humoral immune response.


Biomarkers in cardiovascular medicine: towards precision medicine.
Biomarkers are noninvasive, inexpensive, highly reproducible tools that allow clinicians to quantify pathophysiological processes relevant to a specific disease. Although the concept of biomarker-guided precision medicine is still in its infancy once a specific cardiovascular diagnosis is established, biomarker guidance has become the standard of care in the early diagnosis of acute cardiovascular disease in patients presenting to the emergency department with common symptoms such as acute chest pain or acute dyspnoea. This review highlights recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers, namely high-sensitivity cardiac troponin and natriuretic peptides in established indications such as the early diagnosis of acute myocardial infarction and heart failure. In addition, we address emerging indications such as the screening for perioperative myocardial infarction.


Demonstrating the value of antimicrobial stewardship programs to hospital administrators.
The movement away from fee-for-service models to those that emphasize quality of care and patient outcomes affords a unique opportunity for antimicrobial stewardship programs to expand their value for hospital administration. Antimicrobial stewardship participants must collaborate with administrators and key stakeholders to position themselves to improve economic, process, and outcomes measures. This will allow the establishment of antimicrobial stewardship programs as essential components of the present and future healthcare quality journey.


[En bloc resection for apical invading lung cancer under anterior transcervical approach and assisted thoracoscopic procedure].
A 64-year-old male admitted for dry cough and fever was diagnosed with apical invading squamous cell carcinoma of left lung, and underwent operation. Anterior transcervical incision and removal of the sternoclavicular joint ensured vast and safe exposure of the thoracic inlet, and removal of the chest wall including the involved anterior 1st and 2nd ribs was underwent in safe by additional assisted thoracoscopic procedure in the supine position. After converting position, en bloc resection of the left upper lobe and chest wall, and lymph node dissection was performed under posterolateral thoracotomy. Anterior transcervical approach was useful to exposure of the thoracic inlet and the structures.


Peripheral T cell activation in long-term renal transplant patients: concordant upregulation of adhesion molecules and cytokine gene transcription.
In renal transplant, patients, the number of T cells expressing high levels of LFA-1 (LFA-1-bright) and of T cells expressing CD57 increases in response to viral infection, even if the latter is asymptomatic. Their role in long-term renal transplant patients with cytomegalovirus (CMV) antigenemia and concomitant transplant dysfunction was investigated. For this purpose, this study used triple-color flow cytometry, fluorescence-activated cell sorting of peripheral blood T cells (CD3+/LFA-1-dim or -bright and CD8+/CD57+ or CD57- subsets), and subsequent semiquantitative reverse transcription-polymerase chain reaction. Cytokine mRNA levels for interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, tumor necrosis factor alpha, and interferon-gamma, as well as Granzyme A and IL-2R p55 and p75 transcripts were determined and compared in peripheral blood mononuclear cells and in separated T cell subsets. Although in patients with CMV infection and/or rejection, cytokine transcripts were readily detected and the levels in the CD3+/LFA-1-bright subsets were, by orders of magnitudes, higher than in the LFA-1-dim subset, hardly any cytokine message was found in patients without CMV infection or rejection episodes or in control subjects. The expression of Granzyme A, which is involved in cytotoxic T lymphocyte-mediated cytotoxicity, was not upregulated in LFA-1-bright T cells, which is in discordance with cytokine levels. Differences between CD57+ and CD57- T cells were limited to the IL-2R p55 mRNA, of which the former expressed significantly less than the latter. It is concluded that upon virus-induced activation of peripheral blood T cells, an effector type that is marked by high inflammatory but small cytotoxic potential is produced. The results of this study propose that these cells represent a correlate of persistent immune activation and are liable to produce graft dysfunction, although they are unable to clear the organism from virus infection because of their lack of cytotoxic potential.


Predictors of clinical recurrence after successful electrical cardioversion of chronic persistent atrial fibrillation: clinical and electrophysiological observations.
Recurrence of atrial fibrillation (AF) after electrical cardioversion of chronic AF is not uncommon. However, it remains unclear which parameter(s) predict clinical recurrence. To assess the potential predictors of clinical recurrence after successful electrical cardioversion, we analyzed clinical, echocardiographic and electrophysiologic parameters in 36 patients (age 63 +/- 11 years; 26 males, 10 females) with chronic persistent AF lasting more than 3 months. The dimensions of the left atrium and left ventricular end diastole and end systole were measured by echocardiography. The P wave characteristics from the surface 12-lead electrocardiogram (ECG) were studied in sinus rhythm. Atrial local activations were studied by biatrial basket electrode mapping in AF. With a mean of 7 +/- 2 months of follow-up, 17 (47%) patients had AF recurrence despite multiple antiarrhythmic drug therapy. None of the clinical or echocardiographic parameters were relevant to the recurrence. However, among the surface ECG and intraatrial electrophysiological parameters, the mean P wave duration was the only independent predictor of the risk of clinical recurrence after successful electrical cardioversion. The sensitivity and predictive accuracy of recurrence were 82 and 70%, respectively, when the mean P wave duration was more than 125 ms.


Dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.
Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.


Worse than measurement error: Consequences of inappropriate latent variable measurement models.
Previous research and methodological advice has focused on the importance of accounting for measurement error in psychological data. That perspective assumes that psychological variables conform to a common factor model. We explore what happens when data that are not generated from a common factor model are nonetheless modeled as reflecting a common factor. Through a series of hypothetical examples and an empirical reanalysis, we show that when a common factor model is misused, structural parameter estimates that indicate the relations among psychological constructs can be severely biased. Moreover, this bias can arise even when model fit is perfect. In some situations, composite models perform better than common factor models. These demonstrations point to a need for models to be justified on substantive, theoretical bases in addition to statistical ones. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Forodesine Enhances Immune Responses through Guanosine-Mediated TLR7 Activation while Preventing Graft-versus-Host Disease.
Recent evidence indicates that specific types of nuclear acids, including guanosine and its derivatives, act as natural ligands for TLR7. This led us to hypothesize that purine nucleoside phosphorylase inhibitors not only can induce apoptosis of T cells but also can lead to TLR7 activation by accumulation of guanine nucleosides, in particular under systemic inflammation, where damaged tissues release a large amount of nucleotides. We demonstrate in the present study that a purine nucleoside phosphorylase inhibitor, forodesine, can reduce the disease severity and prolong the survival in a xenogeneic mouse model of graft-versus-host disease (GVHD). Guanine nucleosides were undetectable in mice during GVHD but increased significantly following forodesine treatment. Our in vitro experiments showed that forodesine enhanced guanosine-mediated cytokine production from APCs, including alveolar macrophages and plasmacytoid dendritic cells, through TLR7 signaling. Forodesine also enhanced Ag-presenting capacity, as demonstrated by increased CD8+ T cell proliferation and higher secretion of IFN-γ and IL-12p40 in an MLR with plasmacytoid dendritic cells. Furthermore, forodesine stimulated IFN-γ production from activated T cells in the presence of a low concentration of guanosine while inhibiting their proliferation and inducing apoptotic cell death. Although forodesine ameliorated GVHD severity, mice treated with forodesine showed significantly higher levels of multiple proinflammatory cytokines and chemokines in plasma, suggesting in vivo upregulation of TLR7 signaling. Our study suggests that forodesine may activate a wide range of immune cells, including T cells, through TLR7 stimulation while inhibiting GVHD by inducing apoptosis of T cells, after allogeneic hematopoietic stem cell transplant.


Hippocampal long-lasting potentiation produced by pairing single volleys and brief conditioning tetani evoked in separate afferents.
Cooperative effects between afferents on the induction of long-lasting potentiation (LLP) of synaptic transmission were examined in the CA1 region of the hippocampal slice preparation. Synaptic activity was recorded extracellularly in the dendritic layer (stratum radiatum) as a field EPSP, and the amount of LLP produced was measured from the change in slope of the rising phase of this potential. Experiments were performed with the GABA antagonist picrotoxin in the bath solution in order to facilitate the induction of LLP. It is shown that under these conditions a test input evoked by single volleys (at 0.2 Hz) is potentiated when paired with brief tetani (2-15 impulses at 50 Hz) to a separate population of fibers in the stratum radiatum. For this potentiation to appear, the test input had to occur during the train or precede it by less than 40 msec. Maximal effects were observed with the test volley positioned in the early part of the tetanus, and were largely independent of train duration. The potentiation obtained in this manner reached a peak level after some 20 conjunction events, and its magnitude measured 10 min after conjunction was about half that which could be induced by homosynaptic tetanization. Prior homosynaptic potentiation occluded the potentiation induced by conjunction, suggesting an identity of their underlying mechanisms. A test input to the apical dendritic layer was potentiated also by inputs to the basal dendritic layer, although greater effects were observed with both inputs in the same dendritic layer. It is suggested that the conditioning effect is related to the postsynaptic depolarization created by the tetanus.(ABSTRACT TRUNCATED AT 250 WORDS)


Blended payment methods in physician organizations under managed care.
Independent practice associations (IPAs) are developing new methods of physician reimbursement to balance the objectives of encouraging individual productivity and clinical cooperation. The economic literature on payment incentives, derived from nonhealth industries, predicts that methods blending elements of fee-for-service and capitation will outperform exclusive reliance on either form of payment. To identify emerging payment methods within IPA physician groups that contract with managed care organizations. Case studies of 7 large IPAs in the San Francisco, Calif, metropolitan region that served 826000 health maintenance organization (HMO) patients during the summer and fall of 1998. Payment methods of IPAs for primary care physicians, specialists, and physicians grouped by specialty department within the overall IPA structure. All the IPAs contracted with multiple HMOs for the full range of primary and specialty care physicians' services but paid member physicians using methods that blended elements of fee-for-service and subcapitation. For primary care, most IPAs used monthly capitation adjusted for patient age, sex, and selected diagnoses, supplemented with fee-for-service payment for a wide range of visits and procedures, including patient visits in subacute, skilled nursing facility, emergency department, or home settings; for preventive care services; for office procedures requiring expensive supplies; and, most importantly, for borderline primary care procedures that either could be performed directly or referred to specialty care. All the IPAs paid specialty departments on a capitated basis and delegated to the departments responsibility for allocating the budget among individuals. Allocation mechanisms for individual specialists included adjusted fee-for-service, referral-based capitation, and blends of both. Our results and case studies indicate that IPAs are developing payment methods that blend elements of fee-for-service and capitation in innovative ways for primary care and specialty physicians.


Reliability of iCare ic100 Rebound Tonometry and Agreement With Goldmann Applanation Tonometry in Healthy and Post-myopic LASIK Patients.
Rebound tonometry offers excellent reliability for obtaining intraocular pressure (IOP) measurements in healthy and post-myopic laser-assisted in situ keratomileusis (LASIK) patients regardless of corneal parameters and axial length and regardless of the instillation of ocular topical anesthesia. The purpose of this study was to assess the reliability of rebound tonometry, its agreement with Goldmann applanation tonometry (GAT) and its concordance after topical anesthesia in a group of nonoperated healthy patients and a group of post-myopic LASIK patients. Fifty-four patients were included in this prospective observational, case-control study. Patients were divided into 2 groups: control (n=32, 26.7±6.1 y) and LASIK (n=22, 35.8±7.6 y). Measurements of IOP were carried out using the iCare ic100 tonometer and GAT. The repeatability, intersession and interobserver reproducibility, GAT interchangeability and concordance after topical anesthesia of the iCare ic100 tonometer were assessed. Clinical reliability of the iCare ic100 was excellent in terms of repeatability [intraclass correlation coefficient (ICC)=0.909 and 0.951 in control and ICC=0.938 and 0.961 in LASIK] as well as interobserver reproducibility (ICC=0.896 in control and 0.916 in LASIK) and concordance after anesthesia (ICC=0.910 in control and 0.972 in LASIK) in both groups. Intersession reproducibility was clinically good in nonoperated patients (ICC=0.758 and 0.849) and excellent in LASIK patients (ICC=0.878 and 0.904), although statistically significant differences were obtained in the control group for both examiners (P=0.003 for examiner 1 and P=0.04 for examiner 2). Agreement with GAT was good in both groups (ICC=0.805 in control and 0.790 in LASIK), although statistically different (P<0.001 and P=0.02, respectively). Finally, the iCare ic100 reliability was independent of corneal parameters and axial length in both groups (P>0.05 for all parameters). Rebound tonometry offers good or excellent clinical reliability in both healthy and post-myopic LASIK patients. This article highlights the efficacy of iCare ic100 rebound tonometry as a reliable tool for the measurement of IOP and the management of glaucoma in healthy patients and patients undergoing myopic LASIK surgery.


Divergent evolution in metabotropic glutamate receptors. A new receptor activated by an endogenous ligand different from glutamate in insects.
The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors involved in the regulation of glutamatergic synapses. Surprisingly, the evolution-arily distant Drosophila mGluR shares a very similar pharmacological profile with its mammalian orthologues (mGlu2R and mGlu3R). Such a conservation in ligand recognition indicates a strong selective pressure during evolution to maintain the ligand recognition selectivity of mGluRs and suggests that structural constraints within the ligand binding pocket (LBP) would hinder divergent evolution. Here we report the identification of a new receptor homologous to mGluRs found in Anopheles gambiae, Apis mellifera, and Drosophila melanogaster genomes and called AmXR, HBmXR, and DmXR, respectively (the mXRs group). Sequence comparison associated with three-dimensional modeling of the LBP revealed that the residues contacting the amino acid moiety of glutamate (the alpha-COO(-) and NH(3)(+) groups) were conserved in mXRs, whereas the residues interacting with the gamma-carboxylic group were not. This suggested that the mXRs evolved to recognize an amino acid different from glutamate. The Drosophila cDNA encoding DmXR was isolated and found to be insensitive to glutamate or any other standard amino acid. However, a chimeric receptor with the heptahelical and intracellular domains of DmXR coupled to G-protein. We found that the DmX receptor was activated by a ligand containing an amino group, which was extracted from Drosophila head and from other insects (Anopheles and Schistocerca). No orthologue of mXR could be detected in Caenorhabditis elegans or human genomes. These data indicate that the LBP of the mGluRs has diverged in insects to recognize a new ligand.


Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal.
To identify the emotional and motivational processes that reinstate palatable food intake following removal of high-fat diet (HFD) and associated neuroadaptations tied to neurochemical and behavioural changes underlying dopaminergic function. Adult male C57Bl6 mice were placed on a HFD (58% kcal fat) or ingredient-matched, low-fat diet (LFD; 11% kcal fat) for 6 weeks. At the end of diet-regimen mice were either maintained on their respective diets, or HFD and LFD were replaced with normal chow (withdrawal). Effort-based operant responding for sucrose and high-fat food rewards was measured along with basal and stress-induced corticosterone levels and anxiety (elevated-plus maze). Protein levels for tyrosine hydroxylase (TH), corticosterone releasing factor type 1 receptor (CRF-R1), brain-derived neurotrophic factor (BDNF), phospho-CREB (pCREB) and ΔFosB (truncated splice variant of FosB) were assessed in the amygdala, nucleus accumbens (NAc) and ventral tegmental area (VTA) via western immunoblotting. Six weeks of HFD resulting in significant weight gain elicited sucrose anhedonia, anxiety-like behaviour and hypothalamic-pituitary-adrenocortical axis (HPA) hypersensitivity to stress. Withdrawal from HFD but not LFD-potentiated anxiety and basal corticosterone levels and enhanced motivation for sucrose and high-fat food rewards. Chronic high-fat feeding reduced CRF-R1 and increased BDNF and pCREB protein levels in the amygdala and reduced TH and increased ΔFosB protein in NAc and VTA. Heightened palatable food reward in mice withdrawn from HFD coincided with increased BDNF protein levels in NAc and decreased TH and pCREB expression in the amygdala. Anhedonia, anxiety and sensitivity to stressors develops during the course of HFD and may have a key role in a vicious cycle that perpetuates high-fat feeding and the development of obesity. Removal of HFD enhances stress responses and heightens vulnerability for palatable foods by increasing food-motivated behaviour. Lasting changes in dopamine and plasticity-related signals in reward circuitry may promote negative emotional states, overeating and palatable food relapse.


Predictors of physical activity in older adults 65 years and older: findings in health survey of the Valencian Community.
Physical activity is part of a healthy lifestyle in the older adult and is related to multiple variables that promote this behavior. To identify the relationship and predictive power of sociodemographic variables, multimorbidity, severity index, risk of poor mental health, social support, affective support and confidential support with the time devoted to physical activity in the population over 65 years of age in the Valencian Community. Cross-sectional descriptive analytical study of the data collected in the Health Survey of the Valencian Community on a total of 3,199 people over 65 years of age. The study variables were age, sex, educational level, marital status, social class, multimorbidity, severity index collected with the EQ-5D-5L tool, risk of poor mental health collected with the Goldberg general health questionnaire (GHQ-12), and perceived social, affective and confidential support collected with the Duke-Unc social support scale (Duke-UNC-11). All variables, except affective support, are significantly related to the time of physical activity performed by people older than 65 years. The severity index has a predictive capacity of 13.7% of physical activity performed and age is able to predict 1.2% of this variable. Sex, age, education, social class, marital status, multimorbidity, risk of poor mental health or social support and confidentiality are related to the physical activity time of the Valencian population over 65 years of age. On the other hand, the variables severity index and age have been identified as variables capable of predicting up to 14.8% of the variance of the physical activity time variable in our study population.


Contrasting patterns of diversification between Amazonian and Atlantic forest clades of Neotropical lianas (Amphilophium, Bignonieae) inferred from plastid genomic data.
The mechanisms and processes underlying patterns of species distributions have intrigued ecologists and biogeographers for a long time. The Neotropics is the most species-rich region in the World, representing an excellent model for studying the drivers of diversification. In this study, we used a phylogenomic approach to infer relationships and examine the role of major geological and climatic events in shaping biogeographic patterns within Amphilophium (Bignonieae, Bignoniaceae), a genus of Neotropical lianas. Even though Amphilophium is broadly distributed across the Neotropics, it is centered in Amazonia and the Atlantic rainforest. We generated nearly-complete plastome sequences for 32 species of Amphilophium, representing 70% of the species diversity in the genus. The final dataset included 78 plastid-coding regions and was analyzed under Maximum Likelihood and Bayesian approaches to reconstruct the phylogeny of Amphilophium. We also used this dataset to estimate divergence times using a Bayesian relaxed-clock approach. We further inferred ancestral ranges, migration events, and shifts in diversification rates using a branch-specific diversification model and the Dispersal-Extinction-Cladogenesis (DEC) model implemented in a Bayesian phylogenetic framework. Overall, we obtained a well-resolved and strongly supported phylogeny for Amphilophium, with five main clades that are well characterized by morphological features. Amphilophium originated in the Early Oligocene, and started to diversify in the Late Oligocene. The first diversification event involved a split between Amazonian and Atlantic forest clades. These two clades showed very different diversification scenarios. Divergence within the Atlantic forest clade began in the Mid-Oligocene, while the Amazonian clade underwent rapid diversification starting in the Late Miocene. In-situ speciation characterized the Amazonian clade, whereas allopatric speciation driven by migration events into other Neotropical biomes were mostly inferred within the Atlantic forest clade. The diversification of Amphilophium in the Neotropics was triggered by major geological events and changes in landscape that occurred during the Late Paleogene and Neogene, with little influence of the climatic changes of the Pleistocene ice ages. The divergence times and range inferences support the role of the Western Amazonian "megawetlands" and the formation of the South American "dry diagonal" as key climatic and geological barriers that separated the Atlantic forest from the Amazonian lowlands. Timing of migration events agrees with a Mid-Miocene closure of the Central American Seaway.


The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer.
The mitogen-activated protein kinase (MAPK) family is an important bridge in the transduction of extracellular and intracellular signals in different responses at the cellular level. Within this MAPK family, the p38 kinases can be found altered in various diseases, including cancer, where these kinases play a fundamental role, sometimes with antagonistic mechanisms of action, depending on several factors. In fact, this family has an immense number of functionalities, many of them yet to be discovered in terms of regulation and action in different types of cancer, being directly involved in the response to cancer therapies. To date, three main groups of MAPKs have been identified in mammals: the extracellular signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), and the different isoforms of p38 (α, β, γ, δ). In this review, we highlight the mechanism of action of these kinases, taking into account their extensive regulation at the cellular level through various modifications and modulations, including a wide variety of microRNAs. We also analyze the importance of the different isoforms expressed in the different tissues and their possible role as biomarkers and molecular targets. In addition, we include the latest preclinical and clinical trials with different p38-related drugs that are ongoing with hopeful expectations in the present/future of developing precision medicine in cancer.


Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis.
Mucosal epithelial cells are uniquely equipped to maintain barrier function even under adverse conditions. Previous studies have implicated hypoxia in mucosal tissue damage resulting from both acute and chronic inflammation. Given the importance of the transcriptional regulator hypoxia-inducible factor-1 (HIF-1) for adaptive hypoxia responses, we hypothesized that HIF-1 may serve as a barrier-protective element during mucosal inflammation. Initial studies of hapten-based murine colitis revealed extensive mucosal hypoxia and concomitant HIF-1 activation during colitis. To study this in more detail, we generated 2 mouse lines with intestinal epithelium-targeted expression of either mutant Hif1a (inability to form HIF-1) or mutant von Hippel-Lindau gene (Vhlh; constitutively active HIF-1). Studies of colitis in these mice revealed that decreased HIF-1 expression correlated with more severe clinical symptoms (mortality, weight loss, colon length), while increased HIF levels were protective in these parameters. Furthermore, colons with constitutive activation of HIF displayed increased expression levels of HIF-1-regulated barrier-protective genes (multidrug resistance gene-1, intestinal trefoil factor, CD73), resulting in attenuated loss of barrier during colitis in vivo. Taken together, these studies provide insight into tissue microenvironmental changes during model inflammatory bowel disease and identify HIF-1 as a critical factor for barrier protection during mucosal insult.


Importance of correlations between phagocytic activity and superoxide production of neutrophils under conditions of voluntary exercise and stress.
The importance of the neutrophil function to host defense and tissue damage has been widely recognized. However, the usefulness of the correlation analysis between phagocytic activity and superoxide production of neutrophils is unknown. We investigated the relationship by histochemical NBT assay using rats and mice exposed to voluntary exercises and stresses. The following conclusions were shown from the results in this report and from our previously published findings. The results of voluntary exercise showed significant positive correlations between phagocytic activity and superoxide production of neutrophils after the continuation of the exercise for 8 months, but no relationship after only 3 or 4 months. However, when Salmonella was injected into the same group after 4 months, significant positive correlations were observed immediately following and on the 6th and 14th days after injection. In contrast, negative correlations emerged after psychological stress and severe-crowding stress, suggesting that appropriate expression of neutrophil function was disturbed by the reverse effects, such as by suppression of oxygen-dependent killing capacity or over-production of toxic free radicals subsequent to these stress. These results suggest that the correlations of phagocytic activity and superoxide production of neutrophils reflect whether a neutrophil functional state is appropriate or not.


Monitoring ATP hydrolysis and ATPase inhibitor screening using (1)H NMR.
We present a versatile method to characterize ATPase and kinase activities and discover new inhibitors of these proteins. The proton NMR-based assay directly monitors ATP turnover and is easy to implement, requires no additional reagents and can potentially be applied to GTP. We validated the method's accuracy, applied it to the monitoring of ATP turnover by actin and to the screening of ATPase inhibitors, and showed that it is also applicable for the monitoring of GTP hydrolysis.


Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology.
Bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases whose antigenic target is located at the basement membrane zone. Mucous membrane pemphigoid and epidermolysis bullosa acquisita can evolve with cicatricial mucosal involvement, leading to respiratory, ocular and/or digestive sequelae with important morbidity. For each of these dermatoses, a literature review covering all therapeutic options was performed. A flowchart, based on the experience and joint discussion among the authors of this consensus, was constructed to provide treatment orientation for these diseases in Brazil. In summary, in the localized, low-risk or non-severe forms, drugs that have immunomodulatory action such as dapsone, doxycycline among others may be a therapeutic option. Topical treatment with corticosteroids or immunomodulators may also be used. Systemic corticosteroid therapy continues to be the treatment of choice for severe forms, especially those involving ocular, laryngeal-pharyngeal and/or esophageal mucosal involvement, as may occur in mucous membrane pemphigoid and epidermolysis bullosa acquisita. Several immunosuppressants are used as adjuvant alternatives. In severe and recalcitrant cases, intravenous immunoglobulin is an alternative that, while expensive, may be used. Immunobiological drugs such as rituximab are promising drugs in this area. Omalizumab has been used in bullous pemphigoid.


Road Environment Semantic Segmentation with Deep Learning from MLS Point Cloud Data.
In the near future, the communication between autonomous cars will produce a network of sensors that will allow us to know the state of the roads in real time. Lidar technology, upon which most autonomous cars are based, allows the acquisition of 3D geometric information of the environment. The objective of this work is to use point clouds acquired by Mobile Laser Scanning (MLS) to segment the main elements of road environment (road surface, ditches, guardrails, fences, embankments, and borders) through the use of PointNet. Previously, the point cloud was automatically divided into sections in order for semantic segmentation to be scalable to different case studies, regardless of their shape or length. An overall accuracy of 92.5% has been obtained, but with large variations between classes. Elements with a greater number of points have been segmented more effectively than the other elements. In comparison with other point-by-point extraction and ANN-based classification techniques, the same success rates have been obtained for road surfaces and fences, and better results have been obtained for guardrails. Semantic segmentation with PointNet is suitable when segmenting the scene as a whole, however, if certain classes have more interest, there are other alternatives that do not need a high training cost.


Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor.
The concept of "design space" plays an integral part in implementation of quality by design for pharmaceutical products. ICH Q8 defines design space as "the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post-approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval." Computational fluid dynamics (CFD) is increasingly being used as a tool for modeling of hydrodynamics and mass transfer. In this study, a laboratory-scale aerated bioreactor is modeled using CFD. Eulerian-Eulerian multiphase model is used along with dispersed k-ε turbulent model. Population balance model is incorporated to account for bubble breakage and coalescence. Multiple reference frame model is used for the rotating region. We demonstrate the usefulness of CFD modeling for evaluating the effects of typical process parameters like impeller speed, gas flow rate, and liquid height on the mass transfer coefficient (k(L)a). Design of experiments is utilized to establish a design space for the above mentioned parameters for a given permissible range of k(L)a.


Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.
Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype-related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular "commuting" enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole-genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non-regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c-Jun N-terminal kinase 2 (JNK2) is linked to impaired lung function in early childhood.


Stratigraphy of the wisconsin range, horlick mountains, antarctica.
The Wisconsin Range consists of a basement complex of granitic and metamorphic rocks unconformably overlain by about 550 meters of Upper Paleozoic sedimentary rocks. The base of the Upper Paleozoic succession is composed of the Buckeye formation, a tillite, which varies in thickness from 80 to more than 140 meters. Overlying the Buckeye formation are the Weaver and Queen Maud formations, with a combined thickness of about 455 meters, characterized by a prolific Glossopteris flora, indicative of a Permian age.


A Unique Case of Bilateral Microphthalmia That May Be Related to 14q32.33.
A 2-day-old Hispanic boy was transferred to us with concerns of a small left eye. The pregnancy was uncomplicated, and both parents are healthy. Examination showed a left orbit that appeared to be empty with conjunctival tissue. The right eye had a 7 mm clear cornea, and retinal exam showed areas of thin or absent tissue and no visible optic nerve. MRI revealed a hypoplastic left orbit with an orbital cyst. The anterior-posterior diameter of the right globe was 14 mm and the left globe was 4 mm. Genetic microanalysis showed genetic abnormalities (845 kb gain) on chromosome 14 at q32.33. A diagnosis of bilateral microphthalmia with an orbital cyst was made. This is an isolated case of bilateral microphthalmia possibly associated with 14q32-33.


Systemic inflammation in young adults is associated with abnormal lung function in middle age.
Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain. We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV(1)) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV(1) (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30-1.75) for fibrinogen and 1.35 (95% CI: 1.14-1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV(1). A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08-2.16). Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke. ClinicalTrials.gov NCT00005130.


In situ calcium signaling: no calcium sparks detected in rat myometrium.
Controlled uterine smooth muscle activity is essential for our reproductive health. While we understand reasonably well the steps that produce contraction following a rise in intracellular [Ca], the mechanism controlling excitability and thus the rise of Ca, is less well understood. Here we examine the role of the internal Ca sore, the sarcoplasmic reticulum (SR), and its relation to surface membrane ion channels. We show that despite having a well-developed SR, the rat uterus does not produce the elemental and local Ca signals, known as Ca sparks. This in turn has consequences for excitability, as the negative feedback loop between these Ca signals and Ca-activated K (BK) channels on the surface membrane is lost. This may be important for producing the powerful long-lasting contractions of the uterus required during labor.


Silencing of CrNPR1 and CrNPR3 Alters Plant Susceptibility to Periwinkle Leaf Yellowing Phytoplasma.
Phytoplasmas are prokaryotic plant pathogens that cause considerable loss in many economically important crops, and an increasing number of phytoplasma diseases are being reported on new hosts. Knowledge of plant defense mechanisms against such pathogens should help to improve strategies for controlling these diseases. Salicylic acid (SA)-mediated defense may play an important role in defense against phytoplasmas. Here, we report that SA accumulated in Madagascar periwinkle (Catharanthus roseus) infected with periwinkle leaf yellowing (PLY) phytoplasma. CrPR1a expression was induced in both symptomatic and non-symptomatic tissues of plants exhibiting PLY. NPR1 plays a central role in SA signaling, and two NPR1 homologs, CrNPR1 and CrNPR3, were identified from a periwinkle transcriptome database. Similar to CrPR1a, CrNPR1 expression was also induced in both symptomatic and non-symptomatic tissues of plants exhibiting PLY. Silencing of CrNPR1, but not CrNPR3, significantly repressed CrPR1a induction in Tobacco rattle virus-infected periwinkle plants. In addition, symptoms of PLY progressed fastest in CrNPR1-silenced plants and slowest in CrNPR3-silenced plants. Consistently, expression of CrNPR1, but not CrNPR3, was induced by phytoplasma infection as well as SA treatment. This study highlights the importance of NPR1- and SA-mediated defense against phytoplasma in periwinkle and offers insight into plant-phytoplasma interactions to improve disease control strategies.


[Clinico-neuropsychological syndromes involving the human gyrus cinguli].
There was performed clinical and neurophysiological observation of 41 patients with arteriovenous malformations (AVM) of gyrus cinguli. Disorders of memory appeared to be the main manifestations before the operation in 38 patients, moreover they had the features of Korsakov's syndrome in 5 patients. Autonomic and epileptic-like fits weren't quite characteristic. Memory impairment was observed in 23 from 38 patients after operation, however there weren't found any qualitatively new disorders. The first appearance of Korsakov's syndrome after operation was found in 3 patients. The degree of the increase of memory impairment correlated with the degree of the destruction of the gyrus cinguli as well as with the massivity of AVM passing into corpus callosum. Qualitative analysis of amnestic syndromes revealed that practically all the patients had the alteration of the selectivity of the memory traces, inability to keep in mind the meaning of the tale. It was accompanied by an absence of criticism toward patients' own defects. Similar signs of disorders had close resemblance with amnestic defects of the patients with frontal damages. That testified the significance of both damages of frontal lobes and their connections in formation of clinical pattern in human.


Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing.
Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas. Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations. Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells. IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.


The role of m6A demethylases in lung cancer: diagnostic and therapeutic implications.
m6A is the most prevalent internal modification of eukaryotic mRNA, and plays a crucial role in tumorigenesis and various other biological processes. Lung cancer is a common primary malignant tumor of the lungs, which involves multiple factors in its occurrence and progression. Currently, only the demethylases FTO and ALKBH5 have been identified as associated with m6A modification. These demethylases play a crucial role in regulating the growth and invasion of lung cancer cells by removing methyl groups, thereby influencing stability and translation efficiency of mRNA. Furthermore, they participate in essential biological signaling pathways, making them potential targets for intervention in lung cancer treatment. Here we provides an overview of the involvement of m6A demethylase in lung cancer, as well as their potential application in the diagnosis, prognosis and treatment of the disease.


Plasmodiophora brassicae affects host gene expression by secreting the transcription factor-type effector PbZFE1.
The protist pathogen Plasmodiophora brassicae hijacks the metabolism and development of host cruciferous plants and induces clubroot formation, but little is known about its regulatory mechanisms. Previously, the Pnit2int2 sequence, a sequence around the second intron of the nitrilase gene (BrNIT2) involved in auxin biosynthesis in Brassica rapa, was identified as a specific promoter activated during clubroot formation. In this study, we hypothesized that analysis of the transcriptional regulation of Pnit2int2 could reveal how P. brassicae affects the host gene regulatory system during clubroot development. By yeast one-hybrid screening, the pathogen zinc-finger protein PbZFE1 was determined to specifically bind to Pnit2int2. Specific binding of PbZFE1 to Pnit2int2 was also confirmed by electrophoretic mobility shift assay. The binding site of PbZFE1 is essential for promoter activity of Pnit2int2 in clubbed roots of transgenic Arabidopsis thaliana (Pnit2int2-2::GUS), suggesting that PbZFE1 is indeed secreted from P. brassicae and functions within plant cells. Ectopic expression of PbZEF1 in A. thaliana delayed growth and flowering time, suggesting that PbZFE1 has significant impacts on host development and metabolic systems. Thus, P. brassicae appears to secrete PbZFE1 into host cells as a transcription factor-type effector during pathogenesis.


Local Health Department Values and Organizational Authorities Guiding Cross-Sector Work During COVID-19.
The COVID-19 pandemic highlighted the role that local health departments (LHDs) have in cross sector can address alone, including the work of value alignment and the strategic use of organizational authorities. The practices by which LHDs used their authorities to conduct cross-sector work during the pandemic need exploration. We conducted semi-structured interviews with 19 public health leaders from metropolitan LHDs across the United States. Our interview guide assessed the values that LHD leadership prioritized in their cross-sector work as well as the range of organizational authorities they leveraged to influence external decision-making in other sectors. We found that LHDs approached cross-sector work by leaning on diverse values and authorities, each with unique implications for their work. The LHDs emphasized their approach to value alignment on a sector-by-sector basis, strategically using diverse organizational authorities-economic, political, moral, scientific, and logistical. While each authority and value we assessed was present across all interviewees, how each shaped action varied. Internally, LHDs emphasized certain authorities more than others to the degree that they more closely aligned with prioritized core values. Our findings highlight the ongoing need for LHD leadership to improve their ability to effectively communicate public health values and the unique authorities by which health-supporting work can be facilitated, including how this message must be adapted, depending on the specific sectors with which the LHD needs to partner and the governance arrangement in which the LHD is situated.


Genetic divergence and signatures of natural selection in marginal populations of a keystone, long-lived conifer, Eastern White Pine (Pinus strobus) from Northern Ontario.
Marginal populations are expected to provide the frontiers for adaptation, evolution and range shifts of plant species under the anticipated climate change conditions. Marginal populations are predicted to show genetic divergence from central populations due to their isolation, and divergent natural selection and genetic drift operating therein. Marginal populations are also expected to have lower genetic diversity and effective population size (Ne) and higher genetic differentiation than central populations. We tested these hypotheses using eastern white pine (Pinus strobus) as a model for keystone, long-lived widely-distributed plants. All 614 eastern white pine trees, in a complete census of two populations each of marginal old-growth, central old-growth, and central second-growth, were genotyped at 11 microsatellite loci. The central populations had significantly higher allelic and genotypic diversity, latent genetic potential (LGP) and Ne than the marginal populations. However, heterozygosity and fixation index were similar between them. The marginal populations were genetically diverged from the central populations. Model testing suggested predominant north to south gene flow in the study area with curtailed gene flow to northern marginal populations. Signatures of natural selection were detected at three loci in the marginal populations; two showing divergent selection with directional change in allele frequencies, and one balancing selection. Contrary to the general belief, no significant differences were observed in genetic diversity, differentiation, LGP, and Ne between old-growth and second-growth populations. Our study provides information on the dynamics of migration, genetic drift and selection in central versus marginal populations of a keystone long-lived plant species and has broad evolutionary, conservation and adaptation significance.


A new design strategy to access zwitterionic metal-organic frameworks from anionic viologen derivates.
Two isostructural microporous zwitterionic metal-organic frameworks (ZW MOFs), {[M(bdcbpy)(OH2)4]·4H2O}n with M = Mn (1) and Ni (2), were synthesized by the rational design of the flexible anionic viologen derivate, 1,1'-bis(3,5-dicarboxybenzyl)-4,4'-bipyridinium dibromide dihydrate solvate (H4bdcbpyBr2·2H2O), and its self-assembly with metal(II) acetates in an aqueous medium. Single-crystal structure analyses revealed that both compounds exhibit three-dimensional hydrogen-bonded supramolecular frameworks with one-dimensional channel pores. Significantly, the pore surfaces are lined with charge gradients employed by the ZW ligand bdcbpy(2-) leading to the adsorption of hydrogen attributed to polarization effects. The thermostabilty and activation conditions were systematically investigated by thermogravimetric analysis, differential scanning calorimetry, and powder X-ray diffraction experiments. Furthermore, repeating cycles of reversible color changes are observed in air upon irradiation with UV light attributed to the formation of viologen radicals via an intermolecular electron transfer. This work also contains an in-depth literature analysis on ZW MOFs, which shows the need for the development of alternative routes for the rational design of new porous ZW MOFs.


A device for the cutaneous exteriorization of chronic intravascular catheters.
A device has been designed which permits the cutaneous exteriorization of chronically implanted intravascular catheters. From one to three catheters may be exteriorized for withdrawing blood samples or for connecting to a pressure transducer. The device is uniquely suited for studying animals in a conscious and unrestrained state such as during exercise.


Academic monitoring and support of undergraduate nursing education programme: A middle-range theory.
Globally, there is consensus on the need for student support to address high student attrition and low throughputs, especially in nursing and midwifery programmes. This study analysed the implementation of academic monitoring and support (AMS) in an undergraduate nursing programme to generate a context-informed academic monitoring and support middle-range theory. An ethnographic design and grounded theory approach were adopted in this study. Data sources included individual and focus group interviews, observations, reflective conversations and document analysis. Ethical clearance was obtained from the University Research Ethics Board, and ethical principles were maintained throughout the study. The country's contextual conditions emerged as conditions that necessitated a comprehensive approach to student support to increase throughput in a nursing programme that attracted students from diverse backgrounds. A shared common vision, supportive leadership, collaboration and investing resources in a student support programme that uses a comprehensive and holistic approach emerged as key to an AMS model that will yield the desired outcomes. Major concepts in an AMS middle-ranged theory generated included education for social justice, visionary leadership, comprehensive, holistic and intentional student support, AMS pillars, AMS threats and process and goal-oriented consequences. Academic monitoring and support is a tool used to facilitate access of all deserving students to an undergraduate nursing programme and to ensure that they all have an equal chance to succeed academically, resulting in improved throughput rates. Strengthening support in clinical settings is recommended and further research to improve effectiveness of AMS programmes is suggested.


Smartphone applications: potential tools for use in preparing for CCRN certification examinations.
Recent advances in smartphone technology now allow clinicians to use commercially produced applications when studying for nursing certification examinations. The quality of currently available CCRN review applications varies in this first generation of products. Most are limited to multiple-choice practice questions, although a few have additional elements such as study guides and reference charts. Weaknesses found in the applications evaluated include poorly written and edited content, questions limited to rote memorization rather than application and analysis of knowledge, and content too basic or outside the scope of experienced critical care nursing practice. A list of important factors for consumers to consider before purchase is provided.


Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.
To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.


Barriers to Telehealth Uptake in Rural, Regional, Remote Australia: What Can Be Done to Expand Telehealth Access in Remote Areas?
Telehealth using high quality satellite internet has been shown to improve health service delivery in three very remote Aboriginal communities, however, further expansion of telehealth in this and other areas of the Northern Territory (NT) is limited by the lack of adequate internet. Despite the growing evidence of the benefits of telehealth there remains limited uptake in the NT in the primary health care sector. A national survey through Broadband for the Bush Alliance (B4BA) and its member organisations into consumers' experiences of telecommunications and telehealth services was done. The survey was supported by detailed case studies based on semi-structured interviews. It was found there were a number of barriers to telehealth uptake at the national level: Lack of adequate internet; consumers not being aware of, or knowing how, to access telehealth; lack of access to clinicians providing telehealth services; lack of Medicare item numbers for telehealth and the lack of resourcing at the patient end. The research indicated there needs to be investment into telecommunications infrastructure, public education about telehealth, an increase in Medicare telehealth item numbers and resourcing for primary health care services to support telehealth expansion particularly in rural, regional and remote areas.


Performance of rapid tests for canine visceral leishmaniasis diagnosis in Argentina.
To diagnose dogs infected by Leishmania infantum rK39 rapid diagnosis test is widely used in the Americas, while dual path platform (DPP) was recently adopted by Brazil. In this study we assessed the performance of rK39-RDT and DPP tests in recent urban transmission scenarios of Argentina. The sensitivity and specificity were evaluated with a sera panel and field samples, taken as true infected those from parasitological and/or PCR positive tests. Since none of these tests can be taken as a gold standard, the performance was also evaluated using Latent Class Analysis, a statistical modeling technique which allows to estimating sensitivity and specificity defining a latent class variable as the reference standard. The sensitivity of both tests in the panel was around 92% (symptomatic dogs 96%, asymptomatic 83%), while the sensitivity in field samples of rK39-RDT was 77%, and DPP 98% (mean in symptomatic dogs 89%, asymptomatic 82%). The specificity was similar for both tests and samples, around 98%. Therefore, these tests are acceptable for program dog population-based studies, as spatial stratification, focus intervention and follow up, and they could be used for individual screening and confirmation of clinical presumptive diagnosis in polysymptomatic dogs. The inability to discriminate between immunity and actual infectiousness suggest that a combination with other non-immunological based tests will be required for highly sensitive/specific diagnosis in order to targeting control measures in individual reservoirs from public health perspective, as for individual management from animal health perspective.


The Finding My Way UK Clinical Trial: Adaptation Report and Protocol for a Replication Randomized Controlled Efficacy Trial of a Web-Based Psychological Program to Support Cancer Survivors.
Cancer survivors frequently report a range of unmet psychological and supportive care needs; these often continue after treatment has finished and are predictive of psychological distress and poor health-related quality of life. Web-based interventions demonstrate good efficacy in addressing these concerns and are more accessible than face-to-face interventions. Finding My Way (FMW) is a web-based, psycho-educational, and cognitive behavioral therapy intervention for cancer survivors developed in Australia. Previous trials have demonstrated that FMW is acceptable, highly adhered to, and effective in reducing the impact of distress on quality of life while leading to cost savings through health resource use reduction. This study aims to adapt the Australian FMW website for a UK cancer care context and then undertake a single-blinded, randomized controlled trial of FMW UK against a treatment-as-usual waitlist control. To an extent, our trial design replicates the existing Australian randomized controlled trial of FMW. Following a comprehensive adaptation of the web resource, we will recruit 294 participants (147 per study arm) from across clinical sites in North West England and North Wales. Participants will have been diagnosed with cancer of any type in the last 6 months, have received anticancer treatment with curative intent, be aged ≥16 years, be proficient in English, and have access to the internet and an active email address. Participants will be identified and recruited through the National Institute for Health Research clinical research network. Measures of distress, quality of life, and health economic outcomes will be collected using a self-report web-based questionnaire at baseline, midtreatment, posttreatment, and both 3- and 6-month follow-up. Quantitative data will be analyzed using intention-to-treat mixed model repeated measures analysis. Embedded semistructured qualitative interviews will probe engagement with, and experiences of using, FMW UK and suggestions for future improvements. The website adaptation work was completed in January 2021. A panel of cancer survivors and health care professionals provided feedback on the test version of FMW UK. Feedback was positive overall, although minor updates were made to website navigation, inclusivity, terminology, and the wording of the Improving Communication and Sexuality and Intimacy content. Recruitment for the clinical trial commenced in April 2021. We aim to report on findings from mid-2023. Replication studies are an important aspect of the scientific process, particularly in psychological and clinical trial literature, especially in different geographical settings. Before replicating the FMW trial in the UK setting, content updating was required. If FMW UK now replicates Australian findings, we will have identified a novel and cost-effective method of psychosocial care delivery for cancer survivors in the United Kingdom. International Standard Randomized Controlled Trial Number (ISRCTN) 14317248; https://www.isrctn.com/ISRCTN14317248. DERR1-10.2196/31976.


Cardiac MR assessment of aortic regurgitation: holodiastolic flow reversal in the descending aorta helps stratify severity.
To assess the utility of holodiastolic flow reversal (HDR) in the descending aorta on velocity-encoded cardiac magnetic resonance (MR) images in the stratification of aortic regurgitation (AR) severity. This study was approved by the institutional review board, with waiver of informed consent. A total of 80 patients (overall mean age, 49 years ± 18 [standard deviation]; 22 women and 58 men) with clinical indication for cardiac MR imaging of the aorta were analyzed retrospectively. Velocity-encoded MR imaging was used to quantify AR and assess for HDR at the level of the middescending aorta. These indexes were compared with a qualitative integrated echocardiographic evaluation of AR severity. Sensitivity and specificity for HDR in the prediction of substantial AR were determined, and logistic regression analysis (with associated odds ratios and C statistics) was performed, with HDR and regurgitant fraction as independent predictors. An additional 42 patients (overall mean age, 48 years ± 21; 12 female and 30 male) were then prospectively evaluated in similar fashion to evaluate a decision model derived from analysis of the first group. HDR predicted severe AR (echo grade, 4) with high sensitivity (100%) and specificity (93%). HDR was highly specific (100%) but had lower sensitivity (61%) for moderate to severe AR (echo grade, 3-4). Integration of HDR and direct AR quantification into a combined stratification model based on analysis of the primary group showed good predictive results in the validation group, with a C statistic of 0.94 for moderate to severe AR and 0.93 for severe AR. HDR in the middescending thoracic aorta observed at cardiac MR is indicative of severe AR and can be used in conjunction with quantified regurgitant values obtained from velocity-encoded MR imaging to stratify AR severity.


Comparison of Turkish Injury Scale (TIS) with the Abbreviated Injury Scale (AIS).
According to the Turkish Penal Code, Section 456, an assailant is punished in a correlation to the severity of the victim's injury. In this study, the injury scale used in Turkey in the basis code 456 is compared with Abbreviated Injury Scale (AIS). For this aim, a total of 984 cases out of the total amount reported at the Traumatology Section of the Turkish Council for Forensic Medicine were randomly selected and evaluated retrospectively. In all, 40.7% of injuries were caused by blunt trauma, whereas 59.3% were caused by a penetrating trauma. According to the Turkish Injury Scale (TIS), 40.3% of the cases were scored to be of a first degree of injury, 15.6% as second degree and 44.1% as third degree. When compared, the score points 3, 4 and 5 in the AIS were seen to be nearly equivalent to the TIS of third degree. From this point of view, in the modified AIS 91.1% of first degree of injury, 51.2% of second degree and 97.2% of third degree of injury are harmonious with TIS. Generally, 83.2% of the cases are harmonious with the AIS system. The purpose of this study is to determine what was the source of differences and to focus on particular traumatic lesions in order to determine a possible rearrangement of the Turkish Injury Scale.


[Clinical and immunological studies in borderline mental disorders: problems and solutions].
The study demonstrated that patients having an acute response to stress and those with adaptative disorders with prevailing short-term depressive disorders had certain immunological disorders. Therapy with tranquilizers indicated that they produced an inhibitory effect on T- and B-cell immunity, antibody formation and lymphokine production. Among the immunomodulating peptides myelopid, licopid, and Tactivin, the former was found to be the most effective against anxiety and fear while licopid was the most effective agent in the treatment of psychoasthenic disorders. The findings suggest that therapy with psychotropic peptides will open new vistas in treating mental disorders.


International collaborative project to compare and track the nutritional composition of fast foods.
Chronic diseases are the leading cause of premature death and disability in the world with over-nutrition a primary cause of diet-related ill health. Excess quantities of energy, saturated fat, sugar and salt derived from fast foods contribute importantly to this disease burden. Our objective is to collate and compare nutrient composition data for fast foods as a means of supporting improvements in product formulation. Surveys of fast foods will be done in each participating country each year. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from fast food companies, in-store materials or from company websites. Foods will be categorized into major groups for the primary analyses which will compare mean levels of saturated fat, sugar, sodium, energy and serving size at baseline and over time. Countries currently involved include Australia, New Zealand, France, UK, USA, India, Spain, China and Canada, with more anticipated to follow. This collaborative approach to the collation and sharing of data will enable low-cost tracking of fast food composition around the world. This project represents a significant step forward in the objective and transparent monitoring of industry and government commitments to improve the quality of fast foods.


The diagnostic/prognostic potential and molecular functions of long non-coding RNAs in the exosomes derived from the bile of human cholangiocarcinoma.
Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it's difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.


The experiences and understandings of obesity: families' decisions to attend a childhood obesity intervention.
This study investigated the families' experiences of a childhood obesity intervention and sought to understand factors that influence attendance and lifestyle behaviours. Eleven semi-structured interviews were conducted and analysed using Interpretative Phenomenological Analysis. Four themes emerged highlighting the differences and similarities between attendees and non-attendees perceptions of childhood obesity, perceptions of the intervention, practical barriers and overcoming hurdles to attending and, availability and suitability of local facilities. The findings relate to identity and health communication. For some families attending an obesity intervention may challenge social and individual identities, which may have an impact on subsequent behavioural decisions. Those who attend the obesity intervention may experience a shift in identity, which may or may not initially be perceived as a positive outcome. Public Health and those involved in treatment interventions should aim to bridge the gap between people's in-group identities and those associated with particular lifestyle behaviours. In order to be effective, services must meet the needs of their clients and address any preconceived negative perceptions by carefully considering how health information is presented, how it is understood and most importantly how identity may affect motivation to engage in, and sustain, new behaviours.


Training and disillusion in counselling psychology: a psychoanalytic perspective.
In this paper, I argue that Counselling Psychology's professional identification with pluralism poses significant emotional problems for trainees. An important factor in such problems may be the trainee's sense of disappointment and disillusion that the route to professional and personal self-transformation will not be achieved via a set of universal theoretical principles and established clinical 'rules'. I draw on recent psychoanalytic theory to suggest that the task facing trainees involves balancing pluralism, characterized as an 'external' third position, with an 'internal' third space indexing an awareness of subjectivity and intersubjectivity. Maintaining a dialogical-dialectical perspective on these two positions allows for a creative space in which the trainee may be transformed from lay helper into professional counselling psychologist via a personal engagement with theoretical, clinical and academic material presented during training.


Development of a Congenital Heart Surgery Composite Quality Metric: Part 1-Conceptual Framework.
Current pediatric and congenital heart surgery quality measures focus on operative mortality, and numerous stakeholders are interested in more comprehensive measures. This report describes the background, rationale, and conceptual framework related to the development of the first composite quality metric in the field. A multidisciplinary panel reviewed methodology and framework related to quality measurement and several composite quality measures across adult cardiac surgery and other fields. The panel subsequently developed methodology and selected measures for a congenital heart surgery composite measure and reviewed potential advantages and limitations. Individual measures considered for potential inclusion in the composite were reviewed within the context of Donabedian's triad and the Institute of Medicine quality domains. Decisions were made through group consensus. The final composite measure selected is comprised of two domains: (1) a mortality domain (operative mortality) and (2) a morbidity domain (the 6 major complications endorsed by The Society of Thoracic Surgeons and Congenital Heart Surgeons Society plus cardiac arrest, and postoperative length of stay). Potential advantages include the more comprehensive view of quality compared with mortality alone and improvements in discrimination of hospital performance through increasing the number of end points. Potential limitations include the lack of longer term outcomes and challenges related to case-mix adjustment. We have applied and adapted conceptual framework and methodology related to composite quality measures across other fields to congenital heart surgery. The composite quality metric created is inclusive of both morbidity and mortality, and expands our view of quality in this patient population.