Effect of an End-of-Life Planning Intervention on the completion of advance directives in homeless persons: a randomized trial.
Few interventions have focused on improving end-of-life care for underserved populations, such as homeless persons. To determine whether homeless persons will complete a counseling session on advance care planning and fill out a legal advance directive designed to assess care preferences and preserve the dignity of marginalized persons. Prospective, single-blind, randomized trial comparing self-guided completion of an advance directive with professionally assisted advance care planning. (ClinicalTrials.gov registration number: NCT00546884) 8 sites serving homeless persons in Minneapolis, Minnesota. 262 homeless persons recruited between November 2007 and August 2008. Minimal, self-guided intervention consisting of advance directive forms and written educational information versus a one-on-one advance planning intervention consisting of counseling and completing an advance directive with a social worker. Rate of advance directive completion, assessed by inspection of completed documents. The overall completion rate for advance directives was 26.7% (95% CI, 21.5% to 32.5%), with a higher rate in the counselor-guided group (37.9%) than in the self-guided group (12.8%) (CI of adjusted difference, 15.3 to 34.3 percentage points). This difference persisted across all sites and most subgroups. The advance directive's 4 clinical scenarios found a preference for surrogate decision making in 29% to 34% of written responses. Sampling was limited to a more stable subset of the homeless population in Minneapolis and may have been subject to selection bias. Modest compensation to complete the preintervention survey could have influenced participants to complete advance directives. Both a simple and complex intervention successfully engaged a diverse sample of homeless persons in advance care planning. One-on-one assistance significantly increased the completion rate. Homeless persons can respond to an intervention to plan for end-of-life care and can express specific preferences for care or a surrogate decision maker, but additional studies are needed to assess the effect of these directives on subsequent care. National Institute for Nursing Research and National Center on Minority Health and Health Disparities.


Secondary tracheal tumors: a systematic review.
Secondary tracheal tumors arise from mural invasion by primary tumors in adjacent organs, metastatic lymph nodes or blood-born metastasis from distant sites. This systematic review aims to assess the presentation, management options, and clinical outcomes of these uncommon non-tracheal malignancies. Electronic searches of the MEDLINE database were performed to identify case series and individual case reports of tracheal invasion by primary non-tracheal tumors or metastatic disease. All English-language studies with available abstracts or articles containing primary data were included. From 1978 to 2017, a total of 160 case reports or case series identified 2,242 patients with invasion of the trachea by tumors of adjacent organs (n=1,853) or by metastatic lymph nodes or hematogenous spread (n=389). Common primary sites of origin were thyroid, esophagus, and lung, and the most common presentation was metachronous (range of interval: 0 to 564 months) with dyspnea, neck mass, voice change and/or hemoptysis. A majority of patients in case reports (77.9%) and case series (66.0%) underwent resection and the most common reported operation was segmental tracheal resection. Fewer patients underwent bronchoscopic intervention (21.7%) and radiation was used in 32.2% of patients. Complications after bronchoscopic treatment included bleeding, granulation tissue, and retained secretions, while anastomotic leak, unplanned tracheostomy, and new recurrent laryngeal nerve paralysis were observed after surgical resection. The rate of 30-day mortality was low (0.01-1.80%). Median survival was higher in patients with thyroid malignancy and in patients who underwent surgical management. Follow-up time ranged from 0.03 to 183 months. Patients with tracheal invasion by metastatic or primary non-tracheal malignancies should be assessed for symptoms, tumor grade, tumor recurrence and concurrent metastases to decide on optimal surgical, bronchoscopic or noninterventional therapy. Clinical experience suggests that palliative endoscopic intervention for tracheal obstruction by metastasis-bearing lymph nodes is underreported.


Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT).
Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints. 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (-42.6 mm) and in celecoxib group (-39.5 mm) was significantly greater than the placebo group (-33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (-4.7) and celecoxib group (-4.6) was significantly greater than the placebo group (-3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles. A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.


Differential effects of non-informative vision and visual interference on haptic spatial processing.
The primary purpose of this study was to examine the effects of non-informative vision and visual interference upon haptic spatial processing, which supposedly derives from an interaction between an allocentric and egocentric reference frame. To this end, a haptic parallelity task served as baseline to determine the participant-dependent biasing influence of the egocentric reference frame. As expected, large systematic participant-dependent deviations from veridicality were observed. In the second experiment we probed the effect of non-informative vision on the egocentric bias. Moreover, orienting mechanisms (gazing directions) were studied with respect to the presentation of haptic information in a specific hemispace. Non-informative vision proved to have a beneficial effect on haptic spatial processing. No effect of gazing direction or hemispace was observed. In the third experiment we investigated the effect of simultaneously presented interfering visual information on the haptic bias. Interfering visual information parametrically influenced haptic performance. The interplay of reference frames that subserves haptic spatial processing was found to be related to both the effects of non-informative vision and visual interference. These results suggest that spatial representations are influenced by direct cross-modal interactions; inter-participant differences in the haptic modality resulted in differential effects of the visual modality.


Experiences of caregivers of people with Parkinson's disease in Singapore: a qualitative analysis.
To conduct an in-depth qualitative examination of the experiences of Singaporean people caring for those with Parkinson's disease (PD). The need to provide care for people with PD will increase with the extended life expectancy of Singaporeans. Caring for people with PD in their own homes for as long as possible is argued to provide psychosocial benefits as well as benefiting the community by delayed institutionalisation and reduced healthcare costs. This study reports the qualitative exploratory component of a large mixed method sequential explanatory design. Caregivers were selected through a purposive sampling technique and stratified based on the Hoehn and Yahr disease staging. Twenty-one semi-structured interviews were conducted in the home setting. Interviews were audio-taped and transcribed verbatim. The qualitative data were analysed using Ritchie and Spencer's framework method of qualitative analysis (1994, Analyzing Qualitative Data, Routledge, London). Seventeen (81%) caregivers were women, and their ages ranged from 31 years to more than 71 years. The length of the interview ranged from 42-106 minutes. The interview transcriptions produced 1731 free nodes, and after careful scrutiny for redundancy, 11 sub-themes were identified, which were organised into four key themes. These themes pertained to: (1) Coping and adaptation, (2) Challenges of caregiving, (3) Effects of caregiving on the caregivers and the (4) Need for better caregiver support. The results of this study have provided insights into the coping and well-being of caregivers of people with PD. The progressive nature of PD placed a significant burden on caregivers' emotional well-being. The findings of this study underscore the need for formal caregiver support and education to reduce strain in caregivers targeted at every stage of PD as there is no clear pattern of disease progression. This study has provided important findings that will inform the construction of interventional strategies to reduce caregiver burden and the provision of better support services for caregivers.


Biology, Epidemiology, Clinical Aspects of Hepatocellular Carcinoma and the Role of Sorafenib.
Sorafenib is a small molecular inhibitor of intracellular tyrosine and serine/threonine protein kinases (VEGFR, PDGFR, CRAF and BRAF), and is thought also to induce autophagy, a chief mechanism influencing tumor growth. Sorafenib shows efficacy in the management of non-resectable hepatocellular carcinoma (HCC), which is refractory to other chemotherapeutic drugs. HCC represents a major end point of chronic liver diseases and the third leading cause of cancer-related death. In HCC patients Sorafenib increases overall survival compared to placebo. The most common chronic liver disease affecting up to 30% of the population in Western countries is non-alcoholic fatty liver disease (NAFLD), an intra-hepatic amassing of triglycerides deemed as the hepatic manifestation of insulin resistance and obesity. NAFLD encompasses a range of disorders with grades of liver damage varying from steatosis to non-alcoholic steatohepatitis (NASH), hallmarked by hepatocellular injury/inflammation in the presence or not of fibrosis. NAFLD patients progress to NASH in 10% of cases, which may progress to cirrhosis and HCC. Recent exciting studies uncovered a potential therapeutic role for Sorafenib that goes beyond HCC, and extends to cirrhotic portal hypertensive syndrome during cirrhosis, and to selective anti-fibrotic effects mediated through direct inhibition of activated hepatic stellate cells (HSC), the cellular mediators of intra-hepatic matrix deposition. The aim of this review is to concisely summarize our current knowledge of the biology, epidemiology and clinical aspects of HCC, as well as the previously under-appreciated therapeutic efficacy of Sorafenib beyond HCC. The review therefore utilizes data along the spectrum of liver diseases, including from experimental via pre-clinical to clinical.


Finding the service you need: human centered design of a Digital Interactive Social Chart in DEMentia care (DEM-DISC).
Community dwelling people with dementia and their informal carers experience a lot of problems. In the course of the disease process people with dementia become more dependent on others and professional help is often necessary. Many informal carers and people with dementia experience unmet needs with regard to information on the disease and on the available care and welfare offer, therefore they tend not to utilize the broad spectrum of available care and welfare services. This can have very negative consequences like unsafe situations, social isolation of the person with dementia and overburden of informal carers with consequent increased risk of illness for them. The development of a DEMentia specific Digital Interactive Social Chart (DEM-DISC) may counteract these problems. DEM-DISC is a demand oriented website for people with dementia and their carers, which is easy, accessible and provides users with customized information on healthcare and welfare services. DEM-DISC is developed according to the human centered design principles, this means that people with dementia, informal carers and healthcare professionals were involved throughout the development process. This paper describes the development of DEM-DISC from four perspectives, a domain specific content perspective, an ICT perspective, a user perspective and an organizational perspective. The aims and most important results from each perspective will be discussed. It is concluded that the human centered design was a valuable method for the development of the DEM-DISC.


HLA class I polymorphism, as characterised by PCR-SSOP, in a Brazilian exogamic population.
HLA-A, -B and -C genes were analysed in the population living in the metropolitan region of Curitiba, the main city of Parana State, southern Brazil, to provide data for studies and applications in HLA-related fields, and to contribute to the understanding of human microevolution. Heterozygosity is high (95-99%) for all three loci. Frequencies for most alleles and haplotypes of sub-Saharan African and of European ancestry presented a clear gradient between the White, Mulatto and Black subpopulations. Among Whites, the four most common haplotypes were A*01-Cw*07-B*0801, A*02-Cw*07-B*07, A*11-Cw*0401-B*35 and A*03-Cw*0401-B*35. Their frequencies ranged from 5.6% to 3.0%. In the Mulatto sub-population, six haplotypes presented very similar frequencies, close to 2.0-2.4%: A*02-Cw*03-B*15, A*02-Cw*0401-B*35, A*02-Cw*07-B*07, A*03-Cw*0401-B*35, A*30-Cw*17-B*4201, A*68-Cw*03-B*15. Haplotype A*30-Cw*17-B*4201 was found to be very common (6.6%) in the Black sub-population. Admixture estimate revealed the relative contributions of Europeans, sub-Saharan Africans and Amerindians to this populations which were, respectively, 94%, 3% and 3% for the White sub-population, 57%, 39% and 4% for the Mulatto sub-population, and 25%, 74% and 1% for the Black sub-population.


Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production.
Retrovirus vectors can be made in the absence of helper virus by using retrovirus packaging cell lines. Helper-free virus is critical for a variety of gene transfer studies. The most useful packaging cell lines contain helper virus DNA from which the signal required for packaging of the viral RNA genome into virions has been deleted. However, we showed that the ability to package virus is conferred at very low frequency to cells infected with virus from these packaging cell lines, presumably by low-frequency transmission of the deleted virus genome. In addition, these packaging cell lines can interact with some retroviral vectors to yield replication-competent virus. We constructed packaging cell lines containing helper virus DNA that had several alterations in addition to deletion of the packaging signal. The new packaging cells retained the useful features of previously available lines but did not yield helper virus after introduction of any of the vectors tested, and transfer of the packaging function was not detected.


Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study.
Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst(1,2,3)) and sst(5). Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 μg twice daily (bid), escalated to a maximum dose of 1200 μg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 μg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 μg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.


The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony.
Seals must manage their energy reserves carefully while they fast on land to ensure that they go to sea with sufficient fuel to sustain them until they find food. Glucocorticoids (GCs) have been implicated in the control of fuel metabolism and termination of fasting in pinnipeds. Here we tested the hypothesis that dexamethasone, an artificial GC, increases fat and protein catabolism, and induces departure from the breeding colony in wild, fasting grey seal pups. A single intramuscular dose of dexamethasone completely suppressed cortisol production for 24-72 h, demonstrating activation of GC receptors. In experiment 1, we compared the effects of a single dose of dexamethasone or saline administered 10 days after weaning on fasting mass and body composition changes, cortisol, blood urea nitrogen (BUN) and glucose levels, and timing of departure from the colony. In experiment 2, we investigated the effects of dexamethasone on short-term (5 days) changes in mass loss, body composition and BUN levels. In experiment 1, dexamethasone induced a short-lived increase in mass loss, but there was no difference in timing of departure between dexamethasone- and saline-treated pups (N=10). In experiment 2, dexamethasone increased protein and water loss and prevented a decrease in BUN levels (N=11). Our data suggest changes in cortisol contribute to regulation of protein catabolism in fasting seal pups, irrespective of the sex of the animal, but do not terminate fasting. By affecting the rate of protein depletion, lasting changes in cortisol levels could influence the amount of time seal pups have to find food, and thus may have important consequences for their survival.


Kelch-repeat proteins interacting with the Galpha protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast.
The cAMP-PKA pathway consists of an extracellular ligand-sensitive G protein-coupled receptor, a G protein signal transmitter, and the effector, adenylate cyclase, of which the product, cAMP, acts as an intracellular second messenger. cAMP activates PKA by dissociating the regulatory subunit from the catalytic subunit. Yeast cells (Saccharomyces cerevisiae) contain a glucose/sucrose-sensitive seven-transmembrane domain receptor, Gpr1, that was proposed to activate adenylate cyclase through the G(alpha) protein Gpa2. Consistently, we show here that adenylate cyclase binds only to active, GTP-bound Gpa2. Two related kelch-repeat proteins, Krh1/Gpb2 and Krh2/Gpb1, are associated with Gpa2 and were suggested to act as G(beta) mimics for Gpa2, based on their predicted seven-bladed beta-propeller structure. However, we find that although Krh1 associates with both GDP and GTP-bound Gpa2, it displays a preference for GTP-Gpa2. The strong down-regulation of PKA targets by Krh1 and Krh2 does not require Gpa2 but is strictly dependent on both the catalytic and the regulatory subunits of PKA. Krh1 directly interacts with PKA by means of the catalytic subunits, and Krh1/2 stimulate the association between the catalytic and regulatory subunits in vivo. Indeed, both a constitutively active GPA2 allele and deletion of KRH1/2 lower the cAMP requirement of PKA for growth. We propose that active Gpa2 relieves the inhibition imposed by the kelch-repeat proteins on PKA, thereby bypassing adenylate cyclase for direct regulation of PKA. Importantly, we show that Krh1/2 also enhance the association between mouse R and C subunits, suggesting that Krh control of PKA has been evolutionarily conserved.


Catch the moment: multisensory enhancement of rapid visual events by sound.
Repetition blindness (RB) is a visual deficit, wherein observers fail to perceive the second occurrence of a repeated item in a rapid serial visual presentation stream. Chen and Yeh (Psychon Bull Rev 15:404-408, 2008) recently observed a reduction of the RB effect when the repeated items were accompanied by two sounds. The current study further manipulated the pitch of the two sounds (same versus different) in order to examine whether this cross-modal facilitation effect is caused by the multisensory enhancement of the visual event by sound, or multisensory Gestalt (perceptual grouping) of a new representation formed by combining the visual and auditory inputs. The results showed robust facilitatory effects of sound on RB regardless of the pitch of the sounds (Experiment 1), despite an effort to further increase the difference in pitch (Experiment 2). Experiment 3 revealed a close link between participants' awareness of pitch and the effect of pitch on the RB effect. We conclude that the facilitatory effect of sound on RB results from multisensory enhancement of the perception of visual events by auditory signals.


Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review.
Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney. Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress. Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease. Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options.


Penguin lungs and air sacs: implications for baroprotection, oxygen stores and buoyancy.
The anatomy and volume of the penguin respiratory system contribute significantly to pulmonary baroprotection, the body O2 store, buoyancy and hence the overall diving physiology of penguins. Therefore, three-dimensional reconstructions from computerized tomographic (CT) scans of live penguins were utilized to measure lung volumes, air sac volumes, tracheobronchial volumes and total body volumes at different inflation pressures in three species with different dive capacities [Adélie (Pygoscelis adeliae), king (Aptenodytes patagonicus) and emperor (A. forsteri) penguins]. Lung volumes scaled to body mass according to published avian allometrics. Air sac volumes at 30 cm H2O (2.94 kPa) inflation pressure, the assumed maximum volume possible prior to deep dives, were two to three times allometric air sac predictions and also two to three times previously determined end-of-dive total air volumes. Although it is unknown whether penguins inhale to such high volumes prior to dives, these values were supported by (a) body density/buoyancy calculations, (b) prior air volume measurements in free-diving ducks and (c) previous suggestions that penguins may exhale air prior to the final portions of deep dives. Based upon air capillary volumes, parabronchial volumes and tracheobronchial volumes estimated from the measured lung/airway volumes and the only available morphometry study of a penguin lung, the presumed maximum air sac volumes resulted in air sac volume to air capillary/parabronchial/tracheobronchial volume ratios that were not large enough to prevent barotrauma to the non-collapsing, rigid air capillaries during the deepest dives of all three species, and during many routine dives of king and emperor penguins. We conclude that volume reduction of airways and lung air spaces, via compression, constriction or blood engorgement, must occur to provide pulmonary baroprotection at depth. It is also possible that relative air capillary and parabronchial volumes are smaller in these deeper-diving species than in the spheniscid penguin of the morphometry study. If penguins do inhale to this maximum air sac volume prior to their deepest dives, the magnitude and distribution of the body O2 store would change considerably. In emperor penguins, total body O2 would increase by 75%, and the respiratory fraction would increase from 33% to 61%. We emphasize that the maximum pre-dive respiratory air volume is still unknown in penguins. However, even lesser increases in air sac volume prior to a dive would still significantly increase the O2 store. More refined evaluations of the respiratory O2 store and baroprotective mechanisms in penguins await further investigation of species-specific lung morphometry, start-of-dive air volumes and body buoyancy, and the possibility of air exhalation during dives.


Various human interferon alpha subclasses cross-react with common receptors: their binding affinities correlate with their specific biological activities.
Seven different human interferon (IFN) alpha subtypes were compared with regard to competitive inhibition of specific high-affinity binding of 125I-labeled IFN alpha-2 to human and bovine cells. All IFNs tested (alpha-1, -2, -4, -5, -6, -7, -8) competed for common binding sites. Marked differences in the binding affinities were observed between IFN alpha-1 and IFN alpha-2. The binding affinities of the various subtypes correlated with the respective specific biological activities determined in an antiviral assay. These observations suggest that at least some biological effects of IFNs are initiated by receptor activation and depend quantitatively on the degree of receptor saturation.


Development and Validation of a Turkish Hypnotic Suggestibility Scale.
To construct a scale for testing hypnotic suggestibility for Turkish-speaking adults that may be quick and convenient, and to test its reliability and validity. The study was conducted at the hypnotherapy outpatient clinics of Atatürk University Acupuncture and Complementary Medicine Application and Research Centre. Erzurum, Turkey, from June to August 2017, and comprised aged 18-60 years. As the first step in the preparation of the scale, a panel of 15 experts was founded. The draft was pilot-tested. Incomprehensible suggestion templates in the pilot study were abolished, and the templates were reduced to four which were put to test as the Tastan Suggestibility Scale. Stanford Hypnotic Clinic Scale was also used on the same subjects, and the results were analysed using SPSS. . Of the 61 subjects, 38(62.3%) were females and 23(37.7%) were males. The overall mean age was 34.21±9.9 years. Cronbach alpha internal reliability coefficient of the scale was calculated to be 0.53. Correlation between the Tastan Suggestibility Scale and Stanford Hypnotic Clinic Scale total scores was high (p<0.001). Mean duration of the application of the scale was 5.0±1.2 minutes. Tastan Suggestibility Scale was found to be a new, reliable, and rapidly applicable scale.


Central and peripheral correlates of eye movements in selected mood disorders.
Abnormalities and disturbances of saccadic and pursuit eye movements were studied in several mental disorders and diseases. Certain irregularities in the particular oculomotor behaviour have been proposed they may correspond with specific type of mental disorder. It was our aim to contribute to this question by analyzing the bioelectrical correlates of the visual-oculomotor integration in patients suffering from panic disorder and from depressive symptoms. The horizontal saccadic eye movements, optokinetic nystagmus, saccadic eye movement evoked potentials as well as saccadic eye movement related potentials we recorded in the groups of outpatients suffering from depressive symptoms and panic disorder respectively. Groups of healthy volunteers served as control. Saccadic eye movements were found to be significantly more inaccurate as compared to healthy subjects. The gain of the optokinetic nystagmus at middle and high velocities was significantly lower in panic patients. Preparation of motor plan for a saccade as well as the time of the maximal recruitment of the oculomotor muscle units was delayed in both groups of patients and their oculomotor event-related potentials were of the overall longer duration and higher variability as well. The changes in oculomotor behavior as well as in its EEG correlates in the groups of above mentioned patients can not be taken as specific for the given disorder. On the other hand, they may help to follow up the course of the complex therapy.


Impact of state anxiety on the jumping to conclusions delusion bias.
This is the first study to investigate the relationship between the level of state anxiety and the jumping to conclusions (JTC) reasoning bias in patients with first-episode psychosis using an experimental manipulation procedure. Thirty patients with psychotic delusions and 30 non-clinical controls, from Hong Kong, were randomized into an anxiety induction or an anxiety reduction imagery condition. Questionnaires were used to measure trait emotions, psychotic symptoms and delusional thinking at baseline. After the anxiety manipulation, participants completed two versions of an assessment of the JTC reasoning bias, the beads task. Both the patients and the non-clinical controls were responsive to the anxiety reduction imagery, but only the non-clinical controls responded to the anxiety induction imagery. The JTC reasoning bias was, as hypothesized, more common in patients than in controls, but was not significantly different between the anxiety manipulation conditions. Both patients and controls had higher rates of JTC than in previous studies. Patients with psychotic delusions have a marked JTC cognitive bias. This is the first JTC study in a Chinese sample, and the results suggest that the bias applies cross-culturally. The results indicate that state anxiety does not influence JTC. Limitations of the study include an inadequate anxiety state manipulation effect in psychotic patients using brief imagery, and unusually high rates of JTC in both patients and controls.


Cooperative inter- and intra-layer lattice dynamics of photoexcited multi-walled carbon nanotubes studied by ultrafast electron diffraction.
Optical tuning and probing ultrafast structural response of nanomaterials driven by electronic excitation constitute a challenging but promising approach for understanding microscopic mechanisms and applications in microelectromechanical systems and optoelectrical devices. Here we use pulsed electron diffraction in a transmission electron microscope to investigate laser-induced tubular lattice dynamics of multi-walled carbon nanotubes (MWCNTs) with varying laser fluence and initial specimen temperature. Our photoexcitation experiments demonstrate cooperative and inverse collective atomic motions in intralayer and interlayer directions, whose strengths and rates depend on pump fluence. The electron-driven and thermally driven structural responses with opposite amplitudes cause a crossover between intralayer and interlayer directions. Our ab initio calculations support these findings and reveal that electrons excited from π to π* orbitals in a carbon tube weaken the intralayer bonds while strengthening the interlayer bonds along the radial direction. Moreover, by probing the structural dynamics of MWCNTs at initial temperatures of 300 and 100 K, we uncover the concomitance of thermal and nonthermal dynamical processes and their mutual influence in MWCNTs. Our results illustrate the nature of electron-driven nonthermal process and electron-phonon thermalization in the MWCNTs, and bear implications for the intricate energy conversion and transfer in materials at the nanoscale.


Single scattering of light by circular cylinders.
We consider two topics pertaining to light scattering by circular cylinders. (A) Scattering properties of cylinders with increasing aspect ratio are studied. It is shown that the solution for finite cylinders does not converge to the solution for infinitely long cylinders if the aspect ratio increases. This is due to differences in the treatment of diffraction for finite and infinite cylinders. (B) Finite cylinders have sharp edges, so their scattering properties differ from those of spheroids having the same aspect ratio. To illustrate these differences we present scattering matrix elements of cylinders and spheroids for a large set of aspect ratios. To handle the large amount of data, the scattering matrix elements as functions of aspect ratio and scattering angle are presented in so-called three-dimensional figures.


Engineering Sugar Utilization and Microbial Tolerance toward Lignocellulose Conversion.
Production of fuels and chemicals through a fermentation-based manufacturing process that uses renewable feedstock such as lignocellulosic biomass is a desirable alternative to petrochemicals. Although it is still in its infancy, synthetic biology offers great potential to overcome the challenges associated with lignocellulose conversion. In this review, we will summarize the identification and optimization of synthetic biological parts used to enhance the utilization of lignocellulose-derived sugars and to increase the biocatalyst tolerance for lignocellulose-derived fermentation inhibitors. We will also discuss the ongoing efforts and future applications of synthetic integrated biological systems used to improve lignocellulose conversion.


[Surgical resection of recurrent pulmonary metastases].
The lung is a common site of metastasis. Resectability seems to be the only prognostic factor acknowledged in the literature. Other variables, such as time until tumoral reproduction, duration of the disease-free period, number of metastases and ganglia involvement are not grounds for ruling out surgery. Between February 1996 and January 1998 we operated on 45 patients with pulmonary metastasis, 16 of whom underwent surgery for the same reason more than once. The total number of chest operations in the study group was 42. Retrospectively, we studied all patients undergoing chest surgery more than once, with histologically confirmed resection of pulmonary metastases. One hundred twenty-five metastases (7.8 metastases/patient) were resected. We recorded 3 cases of persistent air leaks that stopped after aspiration through chest tubes was continued. No postoperative (1 to 30 days) mortality was observed. Repetition of pulmonary metastasis should not by itself be considered a reason for ruling out surgery.


Pharmaceutical Industry-Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries.
The association between industry payments to physicians and prescribing rates of the brand-name medications that are being promoted is controversial. In the United States, industry payment data and Medicare prescribing records recently became publicly available. To study the association between physicians' receipt of industry-sponsored meals, which account for roughly 80% of the total number of industry payments, and rates of prescribing the promoted drug to Medicare beneficiaries. Cross-sectional analysis of industry payment data from the federal Open Payments Program for August 1 through December 31, 2013, and prescribing data for individual physicians from Medicare Part D, for all of 2013. Participants were physicians who wrote Medicare prescriptions in any of 4 drug classes: statins, cardioselective β-blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACE inhibitors and ARBs), and selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs). We identified physicians who received industry-sponsored meals promoting the most-prescribed brand-name drug in each class (rosuvastatin, nebivolol, olmesartan, and desvenlafaxine, respectively). Data analysis was performed from August 20, 2015, to December 15, 2015. Receipt of an industry-sponsored meal promoting the drug of interest. Prescribing rates of promoted drugs compared with alternatives in the same class, after adjustment for physician prescribing volume, demographic characteristics, specialty, and practice setting. A total of 279 669 physicians received 63 524 payments associated with the 4 target drugs. Ninety-five percent of payments were meals, with a mean value of less than $20. Rosuvastatin represented 8.8% (SD, 9.9%) of statin prescriptions; nebivolol represented 3.3% (7.4%) of cardioselective β-blocker prescriptions; olmesartan represented 1.6% (3.9%) of ACE inhibitor and ARB prescriptions; and desvenlafaxine represented 0.6% (2.6%) of SSRI and SNRI prescriptions. Physicians who received a single meal promoting the drug of interest had higher rates of prescribing rosuvastatin over other statins (odds ratio [OR], 1.18; 95% CI, 1.17-1.18), nebivolol over other β-blockers (OR, 1.70; 95% CI, 1.69-1.72), olmesartan over other ACE inhibitors and ARBs (OR, 1.52; 95% CI, 1.51-1.53), and desvenlafaxine over other SSRIs and SNRIs (OR, 2.18; 95% CI, 2.13-2.23). Receipt of additional meals and receipt of meals costing more than $20 were associated with higher relative prescribing rates. Receipt of industry-sponsored meals was associated with an increased rate of prescribing the brand-name medication that was being promoted. The findings represent an association, not a cause-and-effect relationship.


Perylene-labeled silica nanoparticles: synthesis and characterization of three novel silica nanoparticle species for live-cell imaging.
The increasing exposure of humans to nanoscaled particles requires well-defined systems that enable the investigation of the toxicity of nanoparticles on the cellular level. To facilitate this, surface-labeled silica nanoparticles, nanoparticles with a labeled core and a silica shell, and a labeled nanoparticle network-all designed for live-cell imaging-are synthesized. The nanoparticles are functionalized with perylene derivatives. For this purpose, two different perylene species containing one or two reactive silica functionalities are prepared. The nanoparticles are studied by transmission electron microscopy, widefield and confocal fluorescence microscopy, as well as by fluorescence spectroscopy in combination with fluorescence anisotropy, in order to characterize the size and morphology of the nanoparticles and to prove the success and homogeneity of the labeling. Using spinning-disc confocal measurements, silica nanoparticles are demonstrated to be taken up by HeLa cells, and they are clearly detectable inside the cytoplasm of the cells.


Lipid and protein oxidation in female patients with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS. Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined. The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol. The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.


[Results of the Trail Making Test among patients suffering from depressive disorders and organic depressive disorders].
Coexistence of depression and dementia for many years has been widely studied for many years. According to the authors for clinical practice, both psychiatric and psychological, it is also important to effectively differentiate between these disease entities. The aim of this study is to compare the implementation of the Trail Making Test (TMT) in patients diagnosed with depressive disorders and those with organic depressive disorders. A sample of 150 persons aged 18-68 years participated in the study. Patients who took part in the investigation were divided into three groups: depressive disorders (DD, n=50), organic depressive disorders (ODD, n=50) and healthy controls (C, n=50). Cognitive functions were evaluated by the Trail Making Test. Relevant statistical differences among examined group were observed: in TMT part A: DD/ODD: p=0.006; DD/C: p<0.001; TMT part B: DD/ODD: p<0.001; DD/C: p<0.001. In both cases, patients with ZD group scored higher than patients from the OZD group, but lower than those in the control group. 1. Patients with organic depressive disorders achieved significantly lower results than patients with depressive disorders in TMT. 2. Subjects with depressive disorder compared to the healthy control group achieved significantly lower scores in TMT. 3. The authors determined the TMT performance indicators differentiating between groups: TMT part A: C=20-40 sec., DD>40 sec. - 90 sec.; ODD>90 sec.; TMT part B: C<60 sec.; DD>60 sec. - 180 sec.; ODD>180 sec.


Predicting survival after whole-brain irradiation for cerebral metastases from prostate cancer.
Prostate cancer patients represent a small minority of those presenting with cerebral metastases. Knowledge about overall survival (OS) contributes to individualization of treatment concepts. In this study an OS score was created for patients receiving whole-brain irradiation (WBI) for cerebral metastases from prostate cancer. Of six variables, four were significantly associated with OS: performance status, time from diagnosis of prostate cancer to WBI, number of cerebral lesions, extracranial metastases. Six-month OS rates of the four variables (in %, divided by 10) were added. The addition resulted in scores of 1 to 19 points. Six-month OS rates were 0% for <15 points and 100% for ≥ 15 points (p<0.001). An OS score was generated specifically for patients with cerebral lesions from prostate cancer. For patients with <15 points, a short WBI regimen (5x4 Gy) should be used, for patients with ≥ 15 points a longer regimen seems appropriate.


Comparison of Compass and Humphrey perimeters in detecting glaucomatous defects.
To compare the performance of Compass fundus automated perimetry (FAP) and Humphrey Field Analyzer (HFA) in glaucoma patients. A total of 120 patients with glaucoma underwent 1 FAP and 1 HFA perimetric test over the central 24° on one eye. The chosen eye and sequence were randomized and only reliable examinations were considered for analysis. Mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and the area of absolute scotoma were compared between perimeters. Glaucoma Staging System (GSS2) data were analyzed by means of k test. Mean sensitivity difference (FAP-HFA) was -1.0 ± 2.81 dB (p<0.001, 95% confidence interval [CI] -1.61, -0.60 dB), MD difference was +0.27 ± 2.84 dB (p = 0.36, 95% CI -5.30, 5.83 dB), PSD difference was +0.48 ± 1.95 dB (p = 0.0075, 95% CI -3.37, 4.33 dB), and VFI difference was +2.4% ± 8.4% (p = 0.003, 95% CI -14.0%, +18.8% dB). Weighted kappa for GSS2 was 0.87. Points with null sensitivities were 9.9 ± 10.2 with FAP and 8.2 ± 8.9 with HFA (difference: 1.7 ± 4.0 points, p = 0.013). Mean sensitivity with FAP is 1 dB lower than HFA, a finding due to different threshold strategies. Differences of global indices for FAP and HFA are small, which makes the 2 perimeters equivalent in the clinical setting. However, FAP seems more severe in evaluating glaucomatous damage, with absolute scotoma areas larger than with HFA. We raise the hypothesis that such difference may be the result of the active compensation of eye movements available with FAP.


[Regulation by tissue plasminogen activator of rewarding effects of drugs of abuse].
Drugs of abuse acutely modulate the activity of mesolimbic dopaminergic neurons, projecting from the ventral tegmental area of the midbrain to the nucleus accumbens (NAc). Tissue plasminogen activator (tPA) is a serine protease that catalyzes the conversion of plasminogen (plg) to plasmin. Here we show that this protease system participates in the rewarding effects of morphine, methamphetamine (METH) and nicotine. A single morphine treatment induces tPA mRNA and protein expression in the NAc. Morphine-induced conditioned place preference and hyperlocomotion are significantly reduced in tPA-deficient (tPA-/-) and plg-deficient (plg-/-) mice, being accompanied by a loss of morphine-induced dopamine release in the NAc. Repeated METH treatment also induces tPA mRNA expression in the NAc. METH-induced conditioned place preference and behavioral sensitization after repeated METH treatment are significantly reduced in tPA-/- mice compared with those in wild-type mice. Finally, we show that the tPA-plasmin system regulates nicotine-induced reward and dopamine release by activating protease activated receptor-1 (PAR1). Nicotine-induced dopamine release is markedly diminished in tPA-/- mice. Furthermore, plasmin activates PAR1 and nicotine-induced conditioned place preference and dopamine release are diminished in PAR1-deficient mice. Our findings suggest that targeting the tPA-plasmin-PAR1 system would provide new therapeutic approaches to the treatment of drug dependence.


The inequitable impact of health shocks on the uninsured in Namibia.
The AIDS pandemic in sub-Saharan Africa puts increasing pressure on the buffer capacity of low- and middle-income households without access to health insurance. This paper examines the relationship between health shocks, insurance status and health-seeking behaviour. It also investigates the possible mitigating effects of insurance on income loss and out-of-pocket health expenditure. The study uses a unique dataset based on a random sample of 1769 households and 7343 individuals living in the Greater Windhoek area in Namibia. The survey includes medical testing for HIV infection which allows for the explicit analysis of HIV-related health shocks. We find that the economic consequences of health shocks can be severe for uninsured households even in a country with a relatively well-developed public health care system such as Namibia. The uninsured resort to a variety of coping strategies to deal with the high medical expenses and reductions in income, such as selling assets, taking up credit or receiving financial support from relatives and friends. As HIV-infected individuals increasingly develop AIDS, this will put substantial pressure on the public health care system as well as social support networks. Evidence suggests that private insurance, currently unaffordable to the poor, protects households from the most severe consequences of health shocks.


Pathogenicity of an isolate of infectious bursal disease virus in local Nigerian ducks.
Three to six-week old local Nigerian ducks were inoculated orally and intraocularly with an isolate of infectious bursal disease virus (IBDV) serotype 1 which was pathogenic for chickens. Neither clinical signs nor gross or microscopic lesions were observed. IBDV antigen was not detected in the bursa by the agar gel diffusion precipitation test. Precipitins and neutralising antibodies to IBDV were also not detected in the serum samples and IBDV was not isolated from the bursa, spleen and liver of the ducks. The above observations suggest that the ducks might be resistant to IBDV infection.


Occupational self-coding and automatic recording (OSCAR): a novel web-based tool to collect and code lifetime job histories in large population-based studies.
Objectives The standard approach to the assessment of occupational exposures is through the manual collection and coding of job histories. This method is time-consuming and costly and makes it potentially unfeasible to perform high quality analyses on occupational exposures in large population-based studies. Our aim was to develop a novel, efficient web-based tool to collect and code lifetime job histories in the UK Biobank, a population-based cohort of over 500 000 participants. Methods We developed OSCAR (occupations self-coding automatic recording) based on the hierarchical structure of the UK Standard Occupational Classification (SOC) 2000, which allows individuals to collect and automatically code their lifetime job histories via a simple decision-tree model. Participants were asked to find each of their jobs by selecting appropriate job categories until they identified their job title, which was linked to a hidden 4-digit SOC code. For each occupation a job title in free text was also collected to estimate Cohen's kappa (κ) inter-rater agreement between SOC codes assigned by OSCAR and an expert manual coder. Results OSCAR was administered to 324 653 UK Biobank participants with an existing email address between June and September 2015. Complete 4-digit SOC-coded lifetime job histories were collected for 108 784 participants (response rate: 34%). Agreement between the 4-digit SOC codes assigned by OSCAR and the manual coder for a random sample of 400 job titles was moderately good [κ=0.45, 95% confidence interval (95% CI) 0.42-0.49], and improved when broader job categories were considered (κ=0.64, 95% CI 0.61-0.69 at a 1-digit SOC-code level). Conclusions OSCAR is a novel, efficient, and reasonably reliable web-based tool for collecting and automatically coding lifetime job histories in large population-based studies. Further application in other research projects for external validation purposes is warranted.


A schizophrenia-linked mutation in PIP5K2A fails to activate neuronal M channels.
Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing. Activation of KCNQ accordingly attenuates the central stimulating effects of dopamine, cocaine, methylphenidate, and phenylcyclidine. The aim of this study was to explore the functional relevance of PIP5K2A, which might influence schizophrenic behavior. Here, we study the effects of the neuronal PIP5K2A on KCNQ2, KCNQ5, KCNQ2/KCNQ3, and KCNQ3/KCNQ5 in the Xenopus expression system. We find that wild-type PIP5K2A but not the schizophrenia-associated mutant (N251S)-PIP5K2A activates heteromeric KCNQ2/KCNQ3 and KCNQ3/KCNQ5, the molecular correlate of neuronal M channels. Homomeric KCNQ2 and KCNQ5 channels were not activated by the kinase indicating that the presence of KCNQ3 in the channel complex is required for the kinase-mediated effects. Acute application of PI(4,5)P2 and a PIP2 scavenger indicates that the mutation N251S renders the kinase PIP5K2A inactive. Our results suggest that the schizophrenia-linked mutation of the kinase results in reduced KCNQ channel function and thereby might explain the loss of dopaminergic control in schizophrenic patients. Moreover, the addictive potential of dopaminergic drugs often observed in schizophrenic patients might be explained by this mechanism. At least, the insufficiency of (N251S)-PIP5K2A to stimulate neuronal M channels may contribute to the clinical phenotype of schizophrenia.


A review of multiple chemical sensitivity.
To review critically the scientific literature on multiple chemical sensitivity (MCS). Definitions of MCS vary but, for this review, a broad definition of MCS was adopted as symptoms in more than one organ system elicited by various unrelated chemicals at very low levels of exposure. A systematic literature search identified several hundred references from which key papers were selected. Two questions are considered, does MCS exist and what causes MCS. Despite extensive literature on the existence of MCS, there is no unequivocal epidemiological evidence; quantitative exposure data are singularly lacking; and qualitative exposure data are, at best, patchy. There is also some evidence to suggest that MCS is sometimes used as an indiscriminate diagnosis for undiagnosed disorders. Despite this, the collated evidence suggests that MCS does exist although its prevalence generally seems to be exaggerated. Many causal mechanisms have been proposed, some suggesting a physical origin--such as MCS reflecting an immunological overload (total body load)--others favouring a psychological basis--such as MCS symptoms being evoked as part of a conditioned response to previous trauma. The available evidence seems most strongly to support a physical mechanism involving sensitisation of part of the midbrain known as the limbic system. However, it is increasingly being recognised that the psychological milieu of a person can considerably influence physical illness, either through generating a predisposition to disease or in the subsequent prognosis. Work is needed to establish the prevalence of MCS and to confirm or refute selected causal mechanisms.


Plasmonics: merging photonics and electronics at nanoscale dimensions.
Electronic circuits provide us with the ability to control the transport and storage of electrons. However, the performance of electronic circuits is now becoming rather limited when digital information needs to be sent from one point to another. Photonics offers an effective solution to this problem by implementing optical communication systems based on optical fibers and photonic circuits. Unfortunately, the micrometer-scale bulky components of photonics have limited the integration of these components into electronic chips, which are now measured in nanometers. Surface plasmon-based circuits, which merge electronics and photonics at the nanoscale, may offer a solution to this size-compatibility problem. Here we review the current status and future prospects of plasmonics in various applications including plasmonic chips, light generation, and nanolithography.


Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats.
Hepatic fibrosis is a significant health problem that may progress to cirrhosis and cancer. It may be caused by viruses or chemicals such as dimethylnitrosamine, which is used as a preservative in processed meats and industrial products. The present study was designed to investigate the antifibrotic effect of hesperidin (100 or 200 mg/kg, a flavanone glycoside with potent anti-inflammatory and antioxidant activities) against liver fibrosis in rats compared to silymarin (100 mg/kg). Liver fibrosis was induced in rats using dimethylnitrosamine (10 mg/kg/day, i.p.) three times per week on alternating days for 4 weeks. After 28 days, tissue and blood samples were collected to assess the protective effect of hesperidin. Dimethylnitrosamine caused liver fibrosis as evidenced by the elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, as well as hepatic malondialdehyde content, gene expression of inducible nitric oxide synthase, α-smooth muscle actin and caspase-3. In addition, dimethylnitrosamine caused a reduction in serum total protein, albumin and hepatic glutathione content. Treatment with hesperidin (100 or 200 mg/kg) successfully ameliorated the deleterious effects of dimethylnitrosamine on all tested parameters. Our study indicates a novel protective effect of hesperidin against dimethylnitrosamine-induced liver fibrosis. Interestingly, the protection evoked by hesperidin (200 mg/kg) was superior to that of the standard silymarin.


Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II).
Squamous cell carcinoma of the oral (mobile) tongue (OTSCC) is increasingly regarded as a biologically different entity compared to cancer affecting other oral sites. It is more aggressive and generally associated with a higher rate of metastasis. This is the concluding part of our two-part article that examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this part, we continue our discussion of the histopathologic and molecular prognostic factors, and serum and salivary biomarkers in of OTSCC, and emphasize the need to regard OTSCC as a high risk variant of oral cancer. We conclude with future direction of prognostic studies of OTSCC.


Modelling the health benefits of smoking cessation in Japan.
In Japan, tobacco smoking is one of the main avoidable causes of disease and death. Although the benefits of smoking cessation for reducing disease risk and increasing longevity have been extensively documented, a relatively low proportion of Japanese smokers currently express a willingness to quit. This study attempted to quantify future reduction in the burden of smoking-attributable disease that could result from increases in smoking cessation. A simulation model was developed to project changes in mortality in Japan associated with increased quit attempts and use of nicotine replacement therapy (NRT) among smokers, incorporating data on smoking prevalence, cause-specific mortality rates, quitting behaviour and NRT use and effectiveness. Approximately 46 000 lung cancer deaths and 56 000 cardiovascular disease deaths could be avoided over 20 years if the proportion of smokers making a quit attempt per year gradually increased to current US levels over 20 years. If each of these quit attempts were aided by NRT, the estimates of avoidable deaths would increase to 64 000 for lung cancer and 78 000 for cardiovascular disease. In this model, negligible deaths were avoided due to decreased smoking initiation over the 20-year simulation. Smoking cessation can have measurable short-term impacts on the smoking-related mortality burden in Japan. However, to achieve these gains, tobacco control policies should focus both on increasing smokers' willingness to quit and providing the support and therapies to increase the likelihood that smoking cessation attempts will succeed.


MxiN Differentially Regulates Monomeric and Oligomeric Species of the Shigella Type Three Secretion System ATPase Spa47.
Shigella rely entirely on the action of a single type three secretion system (T3SS) to support cellular invasion of colonic epithelial cells and to circumvent host immune responses. The ATPase Spa47 resides at the base of the Shigella needle-like type three secretion apparatus (T3SA), supporting protein secretion through the apparatus and providing a likely means for native virulence regulation by Shigella and a much needed target for non-antibiotic therapeutics to treat Shigella infections. Here, we show that MxiN is a differential regulator of Spa47 and that its regulatory impact is determined by the oligomeric state of the Spa47 ATPase, with which it interacts. In vitro and in vivo characterization shows that interaction of MxiN with Spa47 requires the six N-terminal residues of Spa47 that are also necessary for stable Spa47 oligomer formation and activation. This interaction with MxiN negatively influences the activity of Spa47 oligomers while upregulating the ATPase activity of monomeric Spa47. Detailed kinetic analyses of monomeric and oligomeric Spa47 in the presence and absence of MxiN uncover additional mechanistic insights into the regulation of Spa47 by MxiN, suggesting that the MxiN/Spa47 species resulting from interaction with monomeric and oligomeric Spa47 are functionally distinct and that both could be involved in Shigella T3SS regulation. Uncovering regulation of Spa47 by MxiN addresses an important gap in the current understanding of how Shigella controls T3SA activity and provides the first description of differential T3SS ATPase regulation by a native T3SS protein.


Immunization with cross-conserved H1N1 influenza CD4+ T-cell epitopes lowers viral burden in HLA DR3 transgenic mice.
The emergence of the pandemic H1N1 strain of influenza in 2009 was associated with a unique w-shaped age-related susceptibility curve, with higher incidence of morbidity and mortality among young persons and lower incidence among older persons, also observed during the 1918 influenza pandemic. Pre-existing H1N1 antibodies were not cross-reactive with the prior seasonal vaccine, forcing influenza experts to scramble to develop a new vaccine specific for the pandemic virus. We hypothesized that response to T-cell epitopes that are cross-conserved between pandemic H1N1 and the 2008 seasonal influenza vaccine strains might have contributed to partial protection from clinical illness among older adults, despite the lack of cross-reactive humoral immunity. Using immunoinformatics tools, we previously identified hemagglutinin and neuraminidase epitopes that were highly conserved between seasonal and pandemic H1N1. Here, we validated predicted CD4(+) T-cell epitopes for their ability to bind HLA and to stimulate interferon-γ production in peripheral blood mononuclear cells from a cohort of donors presenting with influenza-like illness during the 2009 pandemic and a separate cohort immunized with trivalent influenza vaccine in 2011. A limited-epitope heterologous DNA-prime/peptide-boost vaccine composed of these sequences stimulated immune responses and lowered lung viral loads in HLA DR3 transgenic mice challenged with pandemic 2009 H1N1 influenza. Cross-priming with conserved influenza T-cell epitopes such as these may be critically important to T cell-mediated protection against pandemic H1N1 in the absence of cross-protective antibodies.


Harmonising data on the correlates of physical activity and sedentary behaviour in young people: Methods and lessons learnt from the international Children's Accelerometry database (ICAD).
Large, heterogeneous datasets are required to enhance understanding of the multi-level influences on children's physical activity and sedentary behaviour. One route to achieving this is through the pooling and co-analysis of data from multiple studies. Where this approach is used, transparency of the methodology for data collation and harmonisation is essential to enable appropriate analysis and interpretation of the derived data. In this paper, we describe the acquisition, management and harmonisation of non-accelerometer data in a project to expand the International Children's Accelerometry Database (ICAD). Following a consultation process, ICAD partners were requested to share accelerometer data and information on selected behavioural, social, environmental and health-related constructs. All data were collated into a single repository for cataloguing and harmonisation. Harmonised variables were derived iteratively, with input from the ICAD investigators and a panel of invited experts. Extensive documentation, describing the source data and harmonisation procedure, was prepared and made available through the ICAD website. Work to expand ICAD has increased the number of studies with longitudinal accelerometer data, and expanded the breadth of behavioural, social and environmental characteristics that can be used as exposure variables. A set of core harmonised variables, including parent education, ethnicity, school travel mode/duration and car ownership, were derived for use by the research community. Guidance documents and facilities to enable the creation of new harmonised variables were also devised and made available to ICAD users. An expanded ICAD database was made available in May 2017. The project to expand ICAD further demonstrates the feasibility of pooling data on physical activity, sedentary behaviour and potential determinants from multiple studies. Key to this process is the rigorous conduct and reporting of retrospective data harmonisation, which is essential to the appropriate analysis and interpretation of derived data. These documents, made available through the ICAD website, may also serve as a guide to others undertaking similar projects.


Accumulation of aquaporin-1 during hemolysin-induced necrotic cell death.
Altered tissue water homeostasis may contribute to edema formation during various stresses including bacterial infection. We observed induction of aquaporin-1 (AQP1) during Staphylococcus aureus infection of cultured cells indicating a potential mechanism underlying altered water homeostasis during infection. To investigate mechanisms of AQP1 induction, we examined the effects of the S. aureus alpha-hemolysin on AQP1 abundance in Balb/c fibroblasts. Fibroblasts incubated with 30 microg/ml hemolysin exhibited a 5-10 fold increase in AQP1 protein within 4-6 hours of exposure. The use of multiple signaling cascade inhibitors failed to affect hemolysin-mediated accumulation of AQP1. However, immunoprecipitation revealed an initial accumulation of ubiquitinated AQP1 followed by a decrease to baseline levels after 4 hours. Immunofluorescence indicated that following hemolysin exposure, AQP1 was no longer on the plasma membrane, but was found in a population of submembrane vacuoles. AQP1 redistribution was further indicated by surface biotinylation experiments suggesting diminished AQP1 abundance on the plasma membrane as well as redistribution out of lipid raft fractions. Live cell confocal microscopy revealed that the pattern of cell volume change observed following hemolysin exposure was altered in cells in which AQP1 was silenced. We conclude that alpha-toxin alters proteasomal processing and leads to intracellular accumulation of AQP1, which may likely contribute to disrupted cell volume homeostasis in infection.


Evaluation of temocillin for phenotypic carbapenemase screening of Escherichia coli and Salmonella enterica isolates in relation to the presence of genes encoding ESBLs and carbapenemase production.
The expression of enzymes of the OXA-48 carbapenemase group is difficult to detect by phenotypic methods owing to frequent low levels of carbapenem resistance and negative results with some screening methods. Temocillin has been shown to be a good option for phenotypic screening as it is hydrolysed by the OXA-48-group enzymes, whereas ESBLs, AmpC and some other carbapenemases have a lower hydrolytic effect on this antimicrobial. However, no epidemiological cut-off for temocillin is available. To evaluate temocillin MICs in relation to the presence or absence of genes encoding ESBLs and carbapenemases in Escherichia coli and Salmonella enterica. In this study, 111 E. coli and 102 S. enterica isolates, including WT and well-characterized ESBL-, AmpC- or carbapenemase-producing isolates, were tested by three independent laboratories. MICs were determined according to the CLSI guidelines by agar dilution with the test range from 0.5 to 512 mg/L temocillin and WGS was performed and analysed with ResFinder. Some overlap was detected between temocillin MICs for WT and ESBL- or AmpC-producing isolates. However, isolates carrying genes encoding carbapenemases showed a broader range of MICs for both E. coli and S. enterica. Higher MICs were observed for the OXA-48 group, VIM and some NDM-producing isolates, whereas isolates harbouring KPC enzymes showed low MICs. The results indicate that temocillin MICs enable phenotypic distinction between strains producing OXA-48-group enzymes and both WT susceptible and ESBL/AmpC-carrying isolates, whereas the distinction from other carbapenemases likely requires genotypic testing.


Prevention and control of blood stream infection using the balanced scorecard approach.
to obtain formulation of an effective and efficient strategy to overcome blood stream infection (BSI). operational research design with qualitative and quantitative approach. The study was divided into two stages. Stage I was an operational research with problem solving approach using qualitative and quantitative method. Stage II was performed using quantitative method, a form of an interventional study on strategy implementation, which was previously established in stage I. The effective and efficient strategy for the prevention and control of infection in neonatal unit Cipto Mangunkusumo (CM) Hospital was established using Balanced Scorecard (BSC) approach, which involved several related processes. the BSC strategy was proven to be effective and efficient in substantially reducing BSI from 52.31°/oo to 1.36°/oo in neonates with birth weight (BW) 1000-1499 g (p=0.025), and from 29.96°/oo to 1.66°/oo in BW 1500-1999 g (p=0.05). Gram-negative bacteria still predominated as the main cause of BSI in CMH Neonatal Unit. So far, the sources of the microorganisms were thought to be from the environment of treatment unit (tap water filter and humidifying water in the incubator). Significant reduction was also found in neonatal mortality rate weighing 1000-1499 g at birth, length of stay, hospitalization costs, and improved customer satisfaction. effective and efficient infection prevention and control using BSC approach could significantly reduce the rate of BSI. This approach may be applied for adult patients in intensive care unit with a wide range of adjustment.


A novel serpin expressed by blood-borne microfilariae of the parasitic nematode Brugia malayi inhibits human neutrophil serine proteinases.
Serine proteinase inhibitors (serpins) play a vital regulatory role in a wide range of biological processes, and serpins from viruses have been implicated in pathogen evasion of the host defence system. For the first time, we report a functional serpin gene from nematodes that may function in this manner. This gene, named Bm-spn-2, has been isolated from the filarial nematode Brugia malayi, a causative agent of human lymphatic filariasis. Polymerase chain reaction (PCR) and Western blot experiments indicate that Bm-spn-2 is expressed only by microfilariae (Mf), which are the long-lived blood-dwelling larval stage. A survey of the greater than 14,000 expressed sequence tags (ESTs) from B malayi deposited in dbEST shows that greater than 2% of the ESTs sequenced from Mf cDNA libraries correspond to Bm-spn-2. Despite its abundance in the microfilarial stage, Bm-spn-2 has not been found in any other point in the life cycle. The predicted protein encoded by Bm-spn-2 contains 428 amino acids with a putative signal peptide. Antibodies to recombinant Bm-SPN-2 protein react specifically with a 47.5-kD native protein in Mf extract. Bm-SPN-2 is one of the largest of the 93 known serpins, due to a 22 amino acid carboxy-terminal extension, and contains the conserved serpin signature sequence. Outside these regions, levels of homology are low, and only a distant relationship can been seen to a Caenorhabditis elegans serpin. The Bm-spn-2 gene contains 6 introns, 2 of which appear to be shared by both nematode species. The B malayi introns have an extended and conserved 3' splice site and are relatively large compared with C elegans. A panel of mammalian serine proteinases were screened and Bm-SPN-2 protein was found to specifically inhibit enzymatic activity of human neutrophil cathepsin G and human neutrophil elastase, but not a range of other serine proteinases. It is possible that Bm-SPN-2 could function as a stage-specific serpin in the blood environment of the microfilarial parasite in protection from human immunity and thus may be a good candidate for protective vaccine.


Red Beetroot and Betalains as Cancer Chemopreventative Agents.
Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review, we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water-soluble betalains extracted from the plant.


Noble gas dimers confined inside C70.
The potential energy surfaces for the interior rotation of a series of pairs of noble gas atoms encapsulated in the C70 cavity have been explored. He2@C70, Ne2@C70, Ar2@C70, HeNe@C70, HeAr@C70 and NeAr@C70 were chosen as case studies. Our calculations suggest stable minima with the two noble gas atoms lying along the symmetry axis of the fullerene. Transition states for the rotations are expected to occur when the two atoms are located in the symmetry plane perpendicular to the C5 axis. The energy barriers for the rotations are predicted to be in the 5-64 kcal mol-1 range, significantly increasing with the size of the noble gas atoms inside C70. These energy barriers lead to a wide range of rate constants, including those characteristic of very fast internal rotations, of the order of k = 2.40 × 109 s-1 for He2@C70, and those describing very slow rotations, of the order of k = 1.80 × 10-33 s-1 for Ar2@C70. It is mandatory to correct for the basis set superposition error to calculate accurate binding energies.


Enhancing teacher collaboration in higher education: the potential of activity-oriented design for professional development.
Professional development programs for teachers in higher education are often characterized by top-down approaches, which fail to make appreciable differences in teaching practices. This study uses a qualitative approach to explore activity-oriented design (AOD) as an instrument for collaborative learning in higher education teacher professional development. We examine Teknosofikum, an ongoing project developed in Denmark along three iterations, involving a total of 64 course participants (42 in the hybrid format; 22 online). The study applies the methodology of design-based research: data was collected via 15 semi-structured group interviews, online forums, and field notes/recordings from online meetings and onsite workshops. Data analysis follows the methodology of grounded theory and evidence is given significance inductively, based on contextual data. Four activities were selected to assess the potential of AOD methods in enhancing teacher collaboration, with different aims reflection, discussion, theory-practice alignment, and participation. Our analysis revolved around three main categories: trust, deep interaction, and shared beliefs/values. The results show how collaborative group work activities have improved trust and knowledge-sharing among participants and have contributed to creating a safe learning environment. The paper concludes that AOD methods could better assist educational designers in promoting professional development courses that aim at enhancing teacher collaboration in higher education.


Comparative evaluation of susceptibility to motion artifact in different wearable systems for monitoring respiratory rate.
The purpose of this study is to comparatively evaluate the performance of different wearable systems based on indirect breathing monitoring in terms of susceptibility to motion artifacts. These performances are compared with direct respiratory measurements using a spirometer, which is accurate, reliable, and less sensitive to movement artifacts, but cannot be integrated into truly wearable form. Experiments were carried out on four indirect methods implemented into wearable systems, inductive plethysmography, impedance plethysmography, piezoresistive pneumography, and piezoelectric pneumography, to ascertain the performance of each of them in terms of noise due to movement artifacts, as well as to study the effects of different movements or gestures during each test. A group of volunteers was asked to wear all of the breath monitoring systems simultaneously along with the face mask of the spirometer while carrying out four physical exercises in a gym under controlled conditions. Data are analyzed in the time and frequency domain to estimate the frequency respiration from each wearable system and compare it with those of the spirometer. Results confirmed that all the wearable systems are somehow affected by movement artifacts, but statistical investigation showed that for most of the physical exercises, three out of four, piezoelectric pneumography provided best performance in terms of robustness and reduced susceptibility to movement artifacts.


Changes in soil microbial community structure influenced by agricultural management practices in a mediterranean agro-ecosystem.
Agricultural practices have proven to be unsuitable in many cases, causing considerable reductions in soil quality. Land management practices can provide solutions to this problem and contribute to get a sustainable agriculture model. The main objective of this work was to assess the effect of different agricultural management practices on soil microbial community structure (evaluated as abundance of phospholipid fatty acids, PLFA). Five different treatments were selected, based on the most common practices used by farmers in the study area (eastern Spain): residual herbicides, tillage, tillage with oats and oats straw mulching; these agricultural practices were evaluated against an abandoned land after farming and an adjacent long term wild forest coverage. The results showed a substantial level of differentiation in the microbial community structure, in terms of management practices, which was highly associated with soil organic matter content. Addition of oats straw led to a microbial community structure closer to wild forest coverage soil, associated with increases in organic carbon, microbial biomass and fungal abundances. The microbial community composition of the abandoned agricultural soil was characterised by increases in both fungal abundances and the metabolic quotient (soil respiration per unit of microbial biomass), suggesting an increase in the stability of organic carbon. The ratio of bacteria:fungi was higher in wild forest coverage and land abandoned systems, as well as in the soil treated with oat straw. The most intensively managed soils showed higher abundances of bacteria and actinobacteria. Thus, the application of organic matter, such as oats straw, appears to be a sustainable management practice that enhances organic carbon, microbial biomass and activity and fungal abundances, thereby changing the microbial community structure to one more similar to those observed in soils under wild forest coverage.


Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial.
Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. US President's Emergency Plan for AIDS Relief.


Security enhancement of color image cryptosystem by optical interference principle and spiral phase encoding.
A color information cryptosystem based on optical interference principle and spiral phase encoding is proposed. A spiral phase mask (SPM) is used instead of a conventional random phase mask because it contains multiple storing keys in a single phase mask. The color image is decomposed into RGB channels. The decomposed three RGB channels can avoid the interference of crosstalks efficiently. Each channel is encoded into an SPM and analytically generates two spiral phase-only masks (SPOMs). The two SPOMs are then phase-truncated to get two encrypted images and amplitude-truncated to produce two asymmetric phase keys. The two SPOMs and the two asymmetric phase keys can be allocated to four different authorized users. The order, the wavelength, the focal length, and the radius are construction parameters of the SPM (or third SPOM) that can also be assigned to the four other different authorized users. The proposed technique can be used for a highly secure verification system, so an unauthorized user cannot retrieve the original image if only one key out of eight keys is missing. The proposed method does not require iterative encoding or postprocessing of SPOMs to overcome inherent silhouette problems, and its optical setup alleviates stringent alignment of SOPMs. The validity and feasibility of the proposed method are supported by numerical simulation results.


Looking the World in the Face: The Benefits and Challenges of Facial Transplantation for Blind Patients
Total bilateral blindness in the setting of facial transplantation is a controversial matter. Some transplant teams exclude these candidates, while others accept them onto their facial transplant waiting list. Using 3 cases, the clinical and ethical complexity of total bilateral blindness is explored. Guidance (medical, psychological, and social) for total bilateral blindness as both an inclusion and exclusion criterion is provided, with the stipulation that total bilateral blindness should not be an automatic exclusion criterion for facial transplantation. Additionally, guidance for corneal transplant in facial transplant candidates is discussed. Suggestions for posttransplant disability assistance for patients with total bilateral blindness are also provided.


Antimicrobial Susceptibility and SOS-Dependent Increase in Mutation Frequency Are Impacted by Escherichia coli Topoisomerase I C-Terminal Point Mutation.
Topoisomerase functions are required in all organisms for many vital cellular processes, including transcription elongation. The C terminus domains (CTD) of Escherichia coli topoisomerase I interact directly with RNA polymerase to remove transcription-driven negative supercoiling behind the RNA polymerase complex. This interaction prevents inhibition of transcription elongation from hypernegative supercoiling and R-loop accumulation. The physiological function of bacterial topoisomerase I in transcription is especially important for a rapid network response to an antibiotic challenge. In this study, Escherichia coli with a topA66 single nucleotide deletion mutation, which results in a frameshift in the TopA CTD, was shown to exhibit increased sensitivity to trimethoprim and quinolone antimicrobials. The topoisomerase I-RNA polymerase interaction and the SOS response to the antimicrobial agents were found to be significantly reduced by this topA66 mutation. Consequently, the mutation frequency measured by rifampin selection following SOS induction was diminished in the topA66 mutant. The increased antibiotic sensitivity for the topA66 mutant can be reversed by the expression of recombinant E. coli topoisomerase I but not by the expression of recombinant Mycobacterium tuberculosis topoisomerase I that has a nonhomologous CTD even though the recombinant M. tuberculosis topoisomerase I can restore most of the plasmid DNA linking number deficiency caused by the topA66 mutation. Direct interactions of E. coli topoisomerase I as part of transcription complexes are likely to be required for the rapid network response to an antibiotic challenge. Inhibitors of bacterial topoisomerase I functions and interactions may sensitize pathogens to antibiotic treatment and limit the mutagenic response.


Frequencies and spatial distributions of Cryptosporidium in livestock animals and children in the Ismailia province of Egypt.
Faecal samples from 804 cattle and buffaloes and 165 diarrhoeal children of Ismailia province were investigated by an immunochromatographic screening test and PCR to determine prevalences and distributions of Cryptosporidium spp. Results were analysed statistically for clustering of animal and human cases. Cryptosporidium herd prevalence was 73·3% and individual animal prevalence 32·3%. C. parvum was the dominant species in animals (65·7%). Young calves watered with canal or underground water were at particular risk of infection. Detection rates were higher when calves showed diarrhoea, fever and dehydration. Human Cryptosporidium prevalence was 49·1%. C. hominis dominated in humans (60·5%), followed by C. parvum (38·3%). Living in villages, drinking underground water and having contact with animals were risk factors. Cluster analysis revealed differences in the distribution of infections between animals and humans and suggests different transmission dynamics.


Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131.
Two hundred thirty-one cats treated with radioactive iodine at the Texas Veterinary Medical Teaching Hospital were followed for a median of 25 months by means of an ambidirectional (prospective, retrospective) cohort study design. Cox proportional hazards models were used to determine predictors of survival based on data at the time of hyperthyroid diagnosis (collected retrospectively) and found that only age at diagnosis and sex of the cat were predictors of survival. Increasing age (for each year of age, relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1-1.3) and being male (RR = 0.68, 95% CI = 0.5-0.9) increased likelihood of death. Tables predicting survival after diagnosis and treatment of hyperthyroidism for various age and sex combinations were created. In addition, Cox proportional hazard models were run with all data available at the end of the study (collected retrospectively and prospectively) including number and type of major health problems reported at the time of death or censoring. In this model, significant factors were age at diagnosis, sex, and either type of major health problem or number of health problems. Cats with renal disease or cancer were more likely not to survive and increasing from none to 2 health problems also decreased survival. Renal problems and cancer were the most common health problems at the time of death or censoring. This study provides estimates of duration of survival for cats successfully treated for hyperthyroidism with radioactive iodine, which can be useful in assisting with client treatment decisions.


Self-management programmes in temporomandibular disorders: results from an international Delphi process.
Self-management (SM) programmes are commonly used for initial treatment of patients with temporomandibular disorders (TMD). The programmes described in the literature, however, vary widely with no consistency in terminology used, components of care or their definitions. The aims of this study were therefore to construct an operationalised definition of self-management appropriate for the treatment of patients with TMD, identify the components of that self-management currently being used and create sufficiently clear and non-overlapping standardised definitions for each of those components. A four-round Delphi process with eleven international experts in the field of TMD was conducted to achieve these aims. In the first round, the participants agreed upon six principal concepts of self-management. In the remaining three rounds, consensus was achieved upon the definition and the six components of self-management. The main components identified and agreed upon by the participants to constitute the core of a SM programme for TMD were as follows: education; jaw exercises; massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. This Delphi process has established the principal concepts of self-management, and a standardised definition has been agreed with the following components for use in clinical practice: education; self-exercise; self-massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. The consensus-derived concepts, definitions and components of SM offer a starting point for further research to advance the evidence base for, and clinical utility of, TMD SM.


Larger pupil dilation to nonsocial sounds in infants with subsequent autism diagnosis.
Studies of infants with an elevated likelihood of autism spectrum disorder can identify basic developmental processes that are associated with subsequently emerging clinical symptoms. Atypical responsiveness to sounds in infancy is such a potential early marker of autism. Here, we used pupillometry to quantify reactivity to social and nonsocial sounds in infants with a subsequent diagnosis. Previous research suggest that pupil dilation reflects attentional alerting, and link it to the locus coeruleus norepinephrine system. We measured pupil dilation responses to child-directed speech and the sound of running water; sounds infants often hear in their everyday life. The final sample consisted of 99 ten-month-old infants (52 girls), of whom 68 had an elevated likelihood of autism and 31 were typically developing low-likelihood infants. At follow-up (36 months of age), 18 children in the elevated-likelihood group were diagnosed with autism. Compared to infants without diagnosis, the infants who were subsequently diagnosed with autism had larger pupil dilation when listening to nonsocial sounds, while reactivity to speech was strikingly similar between groups. In the total sample, more pupil dilation to the nonsocial sound was associated with higher levels of autistic symptoms. We also found that on a trial-by-trial basis, across all conditions and groups, more pupil dilation was associated with making fewer gaze shifts. This study did not find evidence of atypical pupillary reactivity to child-directed speech early in life in autism. Instead, the results suggest that certain nonsocial sounds elicit atypically strong alerting responses in infants with a subsequent autism diagnosis. These findings may have important theoretical and clinical implications.


Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants.
Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization in children less than 1 year of age worldwide. It is usually a mild disease, but some children may develop severe symptoms, requiring hospital admission and ventilatory support in the ICU. Infants with pre-existing risk factors (prematurity, bronchopulmonary dysplasia, congenital heart diseases and immunodeficiency) may be predisposed to a severe form of the disease. Clinical diagnosis of bronchiolitis is manly based on medical history and physical examination (rhinorrhea, cough, crackles, wheezing and signs of respiratory distress). Etiological diagnosis, with antigen or genome detection to identify viruses involved, may have a role in reducing hospital transmission of the infection. Criteria for hospitalization include low oxygen saturation (<90-92%), moderate-to-severe respiratory distress, dehydration and presence of apnea. Children with pre-existing risk factors should be carefully assessed.To date, there is no specific treatment for viral bronchiolitis, and the mainstay of therapy is supportive care. This consists of nasal suctioning and nebulized 3% hypertonic saline, assisted feeding and hydration, humidified O2 delivery. The possible role of any pharmacological approach is still debated, and till now there is no evidence to support the use of bronchodilators, corticosteroids, chest physiotherapy, antibiotics or antivirals. Nebulized adrenaline may be sometimes useful in the emergency room. Nebulized adrenaline can be useful in the hospital setting for treatment as needed. Lacking a specific etiological treatment, prophylaxis and prevention, especially in children at high risk of severe infection, have a fundamental role. Environmental preventive measures minimize viral transmission in hospital, in the outpatient setting and at home. Pharmacological prophylaxis with palivizumab for RSV bronchiolitis is indicated in specific categories of children at risk during the epidemic period. Viral bronchiolitis, especially in the case of severe form, may correlate with an increased incidence of recurrent wheezing in pre-schooled children and with asthma at school age.The aim of this document is to provide a multidisciplinary update on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications, identify gaps in knowledge and drive future research.


Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins.
This review will highlight the significance of three critical pathways in developmental biology and our emerging understanding of their roles in regulating tumor metastasis: Bone morphogenic protein (BMP), Notch and Sonic hedgehog (SHH). We will discuss parallels between their known roles in development and how these processes can be used by tumor cells to create microenvironments that enhance tumor metastasis. That tumor cells usurp pathways critical to the developing embryo is not surprising, as many of the normal developmental programs include processes that are also seen during tumor progression to a metastatic phenotype, including epithelial to mesenchymal transition (EMT), tissue specific morphogenesis, cellular motility and invasion. BMPs are involved in EMT, contribute to tissue specific morphogenesis, and are expressed in highly-metastatic tumor cells. BMPs have also been hypothesized to have a role in the establishment of a pre-neoplastic niche. Notch and SHH facilitate neovascularization, angiogenesis, EMT and can contribute to the maintenance of highly-metastatic tumor stem cells.