Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea.
This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.


Importance of the green color, absorption gradient, and spectral absorption of chloroplasts for the radiative energy balance of leaves.
Terrestrial green plants absorb photosynthetically active radiation (PAR; 400-700 nm) but do not absorb photons evenly across the PAR waveband. The spectral absorbance of photosystems and chloroplasts is lowest for green light, which occurs within the highest irradiance waveband of direct solar radiation. We demonstrate a close relationship between this phenomenon and the safe and efficient utilization of direct solar radiation in simple biophysiological models. The effects of spectral absorptance on the photon and irradiance absorption processes are evaluated using the spectra of direct and diffuse solar radiation. The radiation absorption of a leaf arises as a consequence of the absorption of chloroplasts. The photon absorption of chloroplasts is strongly dependent on the distribution of pigment concentrations and their absorbance spectra. While chloroplast movements in response to light are important mechanisms controlling PAR absorption, they are not effective for green light because chloroplasts have the lowest spectral absorptance in the waveband. With the development of palisade tissue, the incident photons per total palisade cell surface area and the absorbed photons per chloroplast decrease. The spectral absorbance of carotenoids is effective in eliminating shortwave PAR (<520 nm), which contains much of the surplus energy that is not used for photosynthesis and is dissipated as heat. The PAR absorptance of a whole leaf shows no substantial difference based on the spectra of direct or diffuse solar radiation. However, most of the near infrared radiation is unabsorbed and heat stress is greatly reduced. The incident solar radiation is too strong to be utilized for photosynthesis under the current CO2 concentration in the terrestrial environment. Therefore, the photon absorption of a whole leaf is efficiently regulated by photosynthetic pigments with low spectral absorptance in the highest irradiance waveband and through a combination of pigment density distribution and leaf anatomical structures.


Influence of aging on thermal and vibratory thresholds of quantitative sensory testing.
Quantitative sensory testing has become a common approach to evaluate thermal and vibratory thresholds in various types of neuropathies. To understand the effect of aging on sensory perception, we measured warm, cold, and vibratory thresholds by performing quantitative sensory testing on a population of 484 normal subjects (175 males and 309 females), aged 48.61 +/- 14.10 (range 20-86) years. Sensory thresholds of the hand and foot were measured with two algorithms: the method of limits (Limits) and the method of level (Level). Thresholds measured by Limits are reaction-time-dependent, while those measured by Level are independent of reaction time. In addition, we explored (1) the correlations of thresholds between these two algorithms, (2) the effect of age on differences in thresholds between algorithms, and (3) differences in sensory thresholds between the two test sites. Age was consistently and significantly correlated with sensory thresholds of all tested modalities measured by both algorithms on multivariate regression analysis compared with other factors, including gender, body height, body weight, and body mass index. When thresholds were plotted against age, slopes differed between sensory thresholds of the hand and those of the foot: for the foot, slopes were steeper compared with those for the hand for each sensory modality. Sensory thresholds of both test sites measured by Level were highly correlated with those measured by Limits, and thresholds measured by Limits were higher than those measured by Level. Differences in sensory thresholds between the two algorithms were also correlated with age: thresholds of the foot were higher than those of the hand for each sensory modality. This difference in thresholds (measured with both Level and Limits) between the hand and foot was also correlated with age. These findings suggest that age is the most significant factor in determining sensory thresholds compared with the other factors of gender and anthropometric parameters, and this provides a foundation for investigating the neurobiologic significance of aging on the processing of sensory stimuli.


Roundtrip matrix method for calculating the leaky resonant modes of open nanophotonic structures.
We present a numerical method for calculating quasi-normal modes of open nanophotonic structures. The method is based on scattering matrices and a unity eigenvalue of the roundtrip matrix of an internal cavity, and we develop it in detail with electromagnetic fields expanded on Bloch modes of periodic structures. This procedure is simpler to implement numerically and more intuitive than previous scattering matrix methods, and any routine based on scattering matrices can benefit from the method. We demonstrate the calculation of quasi-normal modes for two-dimensional photonic crystals where cavities are side-coupled and in-line-coupled to an infinite W1 waveguide, and we show that the scattering spectrum of these types of cavities can be reconstructed from the complex quasi-normal mode frequency.


Study protocol: epidemiological and clinical characteristics of acute viral hepatitis in Brazilian health services.
Acute viral hepatitis is a disease of great clinical importance. This study proposes actions to better characterise cases of acute hepatitis in Brazil and to provide relevant information to institutionalised health policies within the Unified Health System. Available data on acute hepatitis in Brazil need to be re-evaluated regarding the different hepatotropic agent (hepatitis A to E virus) frequencies, as well as other agents that can cause similar clinical conditions, such as Herpes Simplex Virus 1 and 2(HSV1, HSV2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Herpes Virus 6 and 7 (HHV6, HHV7), arbovirus (yellow fever, dengue, chikungunya, Zika), parvovirus B19, adenovirus, parechovirus, enterovirus, HIV, leptospirosis, toxoplasmosis and syphilis, in addition to autoimmune hepatitis. In this context, the primary aim of this study is the clinical-epidemiological and molecular characterisation of acute viral hepatitis in Brazilian health services from all geographical regions of the country. The present article describes the study protocol. This study will evaluate 2280 patients with symptoms and/or signs suggestive of acute liver disease in Brazilian health institutions in all five geographic Brazilian regions. Demographic, epidemiological and clinical data will be collected, as well as blood samples to be analysed at Hospital Israelita Albert Einstein Clinical Laboratory. Ethics approval was obtained at the national research ethics committee (Conselho Nacional de Ética em Pesquisa- CONEP-CAAE 00952818.4.1001.0071) and at all participating sites. Results will be published in journals and presented at scientific meetings.


Selective angioembolisation for splenic salvage following blunt abdominal trauma.
Isolated high-grade splenic injury following blunt abdominal trauma is an uncommon finding. The selected use of catheter-directed angiography and angioembolisation for splenic salvage has been successful in haemodynamically stable patients.


Carbonyl and nitrogen dioxide emissions from gasoline- and diesel-powered motor vehicles.
Carbonyls can be toxic and highly reactive in the atmosphere. To quantify trends in carbonyl emissions from light-duty (LD) vehicles, measurements were made in a San Francisco Bay area highwaytunnel bore containing essentially all LD vehicles during the summers of 1999, 2001, and 2006. The LD vehicle emission factor for formaldehyde, the most abundant carbonyl, did not change between 1999 and 2001, then decreased by 61 +/- 7% between 2001 and 2006. This reduction was due to fleet turnover and the removal of MTBE from gasoline. Acetaldehyde emissions decreased by 19 +/- 2% between 1999 and 2001 and by the same amount between 2001 and 2006. Absent the increased use of ethanol in gasoline after 2003, acetaldehyde emissions would have further decreased by 2006. Carbonyl emission factors for medium- (MD) and heavy-duty (HD) diesel trucks were measured in 2006 in a separate mixed-traffic bore of the tunnel. Emission factors for diesel trucks were higher than those for LD vehicles for all reported carbonyls. Diesel engine exhaust dominates over gasoline engines as a direct source of carbonyl emissions in California. Carbonyl concentrations were also measured in liquid-gasoline samples and were found to be low (< 20 ppm). The gasoline brands that contained ethanol showed higher concentrations of acetaldehyde in unburned fuel versus gasoline that was formulated without ethanol. Measurements of NO2 showed a yearly rate of decrease for LD vehicle emissions similar to that of total NOx in this study. The observed NO2/NOx ratio was 1.2 +/- 0.3% and 3.7 +/- 0.3% for LD vehicles and diesel trucks, respectively.


PLASMA VOLUME EXPANSION BY RAPID INFUSION OF A LOW MOLECULAR WEIGHT DEXTRAN.
Large infusions of a 10% solution of dextran of molecular weight 40,000 were given to dogs during 3 min using a specially designed apparatus. The initial expansion of plasma volume was about twice the volume of solution injected. Plasma volume then fell rapidly (with a half life of about 2 hr), more rapidly than the fall in dextran concentration (half-life of about 4.5 hr). Fluctuations in plasma volume and protein concentration were repeatedly observed during the return towards normal values. At 5 to 6 hr renal excretion accounted for 40% of the infused dextran, about 20% was intravascular and the remaining 40% was presumably extravascular. No dextran was found in the cerebrospinal fluid.


Human genetics in dentistry: a summary of three national conferences.
By sanctioning these three annual conferences, the Society of Craniofacial Genetics hopes that the impact of human genetics in dental education and dental practice will be realized by the individual student and practitioner. Human genetics and dentistry will continue to have an impact on each other so that dentistry will meet the challenge with innovative educational programs, advances in dental research, and more importantly, interdisciplinary diagnostic and therapeutic concepts.


Fluorogenic Labeling Strategies for Biological Imaging.
The spatiotemporal fluorescence imaging of biological processes requires effective tools to label intracellular biomolecules in living systems. This review presents a brief overview of recent labeling strategies that permits one to make protein and RNA strongly fluorescent using synthetic fluorogenic probes. Genetically encoded tags selectively binding the exogenously applied molecules ensure high labeling selectivity, while high imaging contrast is achieved using fluorogenic chromophores that are fluorescent only when bound to their cognate tag, and are otherwise dark. Beyond avoiding the need for removal of unbound synthetic dyes, these approaches allow the development of sophisticated imaging assays, and open exciting prospects for advanced imaging, particularly for multiplexed imaging and super-resolution microscopy.


Degradation of song in a species using nesting holes: the Pied Flycatcher Ficedula hypoleuca.
The habitat, but also the nest hole of a hole-nesting species, will degrade the song during transmission. We investigated how the sounds degrade in a sound transmission experiment with the song of the Pied Flycatcher Ficedula hypoleuca (Muscicapidae). Ten different song elements were transmitted to microphones placed inside and outside a nest box. On average, song degradation was much greater inside than outside the nest boxes, especially with respect to excess attenuation and blurring of the song elements. Being inside a nest box therefore strongly reduces a Pied Flycatcher's possibility of detecting and recognizing songs or eavesdropping on singing interactions.


Neuroendocrine tumours of the pancreas: a clinicopathological study of nine cases including six insulinomas.
Pancreatic neuroendocrine tumours (pNET) are relatively uncommon, accounting for 1-2% of all pancreatic neoplasms. They are characterised by varying clinical presentation, tumour biology and prognosis. To provide an updated overview on clinicopathological features, treatment and outcome of pNET. In our retrospective study, we reviewed 9 cases of pNET that were diagnosed at the Pathology Department of Mongi Slim Hospital over an 11-year period (2003- 2013). Relevant clinical information and microscopic slides were available in all cases and were retrospectively reviewed. The latest WHO classification (2010) was adopted. Our study group included 3 men and 6 women (M/F ratio 0.5) with an age between 20 and 75 years (mean = 52 years). Pancreatic neuroendocrine tumours ranged in size from 0.5 to 10 cm (mean 4 cm). The sites of pNET were the head of the pancreas (n = 4), the body of the pancreas (n = 3) and the tail of the pancreas (n = 2). Enucleation of the tumour was performed in five cases, Three patients underwent distal pancreatectomy and splenectomy, whereas only one patient had central pancreatectomy. Histopathological examination of the surgical specimen coupled with immunohistochemical study established a diagnosis of pNET grade 1 (G1) in seven cases and grade 2 (G2) in two cases. Pancreatic neuroendocrine tumours are a heterogeneous group of neoplasms with distinct tumour genetics, biology and clinicopathological features. Accurate clinical and pathologic diagnosis is an important first step in developing an appropriate management plan.


Effect of age on parathyroid hormone and forskolin stimulated adenylate cyclase and protein kinase activity in the renal cortex.
The capacity of parathyroid hormone (PTH) to stimulate the renal production of 1,25-dihydroxyvitamin D declines with age. Since the action of PTH in the kidney is mediated by cAMP, we have examined the effect of PTH and forskolin on renal cortical adenylate cyclase in young (3 months), adult (13-15 months), and old (25-27 months) F344 rats. PTH-dependent adenylate cyclase, measured as cAMP accumulation in cortical slices, was reduced in adult and old rats compared to young rats over a PTH concentration range of 0.015-15 units/ml. There was no difference in PTH-dependent adenylate cyclase activity between adult and old rats. Renal plasma membrane preparations demonstrated similar changes in PTH-stimulated adenylate cyclase activity. There was no difference in calcitonin, forskolin, or guanyl-5-ylimidodiphosphate (Gpp(NH)p) stimulation of adenylate cyclase in plasma membranes from each age group, suggesting that the defect lies in the membrane receptor for PTH. The decreased adult sensitivity to PTH could be reversed by thyroparathyroidectomy. PTH stimulation of cytosolic protein kinase activity did not change with age. These results suggest that the decrease in PTH-dependent adenylate cyclase is due to the alterations at the level of PTH receptor. These alterations may be in response to the increase in serum PTH seen in these animals with increasing age.


Impact of CD31 mismatches on the outcome of hematopoeitic stem cell transplant of HLA-identical sibling.
Graft-versus host disease (GVHD) complicating allogeneic hematopoeitic stem cell transplantation (HSCT) is often attributed to mismatching of minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD (aGVHD), but reports disagree about its level of significance. Therefore, we examined the impact of CD31-matching on the outcome of HSCT in different hematological and immunological diseases. About 60 patients receiving HSC from their respective HLA-ABCDR and DQ-identical sibling were studied. DNA was used to study the CD31 allele polymorphism at the codon 125 (LL, LV or VV) in the patient-donor pairs using the principle of allele-specific PCR amplification. Four primer were used; two primers (forward and reverse) for the L allele and another two for the V allele. The CD31 identity was tested for correlation with HSCT outcome measures of aGVHD, chronic GVHD, and relapse. The gene frequency of CD31 alleles (LL, VV and LV) was 28.3, 20 and 51.7%, respectively. CD31 identity was found in 31 pairs (51.7%) versus 29 pairs (48.3%) for nonidentity. The CD31 noncompatibility showed statistical non-significant relation with aGVHD (G 0-I, and G II-IV) and chronic GVHD (De-novo and chronic on acute) (p = 0.59, p = 0.62, p = 036 and p = 0.83, respectively). The CD31 nonidentity had statistical significant relation with aGVHD versus no aGVHD (p = 0.008 and OR = 4.46). The CD31 nonidentity showed statistical significant relation with aGVHD (II-IV) versus no aGVHD (p = 0.012 and OR = 7.14) and also, aGVHD (0-I) versus the no aGVHD (p = 0.03, OR = 3.13, respectively). A statistical significant relation was found between CD31 nonidentity in patient-donor pairs and relapse (p = 0.014 and OR = 4.21). In conclusion, the donor-recipient CD31 nonidentity is a significant risk factor for aGVHD and relapse in HLA-identical sibling.


Palladium(II)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Nitrones to 3-Alkenoyl-1,3-oxazolidin-2-ones.
Chiral phosphinepalladium(II)-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to α,β-unsaturated carboxylic acid derivatives has been investigated. In the presence of a catalytic amount of [Pd(NCMe)2{(S)-tolbinap}](BF4)2 [TolBINAP = 2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl], the reaction of 3-alkenoyl-1,3-oxazolidin-2-ones as dipolarophiles and N-substituted N-benzylidenenitrones has been successfully performed to give isoxazolidine derivatives in high yields with high enantioselectivities. For example, 3-((2,5-dimethyl-3-phenylisoxazolidin-4-yl)carbonyl)-1,3-oxazolidin-2-one was obtained from the reaction of N-benzylidenemethylamine N-oxide and 3-crotonoyl-1,3-oxazolidin-2-one in 89% yield with 60% endo selectivity and 91% ee of the endo isomer. The cycloaddition of N-benzylidenebenzylamine N-oxide and 3-crotonoyl-1,3-oxazolidin-2-one afforded 3-((2-benzyl-5-methyl-3-phenylisoxazolidin-4-yl)carbonyl)-1,3-oxazolidin-2-one in 94% yield with 93% endo selectivity and 89% ee of the endo isomer. Remarkably, the endo/exo selectivity of the products depended on the N-substituent group of the nitrones. These selectivities were explained using molecular modeling.


N-acetylcysteine and celecoxib lessen cadmium cytotoxicity which is associated with cyclooxygenase-2 up-regulation in mouse neuronal cells.
In many neurodegenerative disorders, aggregates of ubiquitinated proteins are detected in neuronal inclusions, but their role in neurodegeneration remains to be defined. To identify intracellular mechanisms associated with the appearance of ubiquitin-protein aggregates, mouse neuronal HT4 cells were treated with cadmium. This heavy metal is a potent cell poison that mediates oxidative stress and disrupts the ubiquitin/proteasome pathway. In the current studies, the following intracellular events were found to be also induced by cadmium: (i) a specific rise in cyclooxygenase-2 (COX-2) gene expression but not COX-1; (ii) an increase in the extracellular levels of the proinflammatory prostaglandin E2, a product of COX-2; and (iii) production of 4-hydroxy-2-nonenal-protein adducts, which result from lipid peroxidation. In addition, cadmium treatment led to the accumulation of high molecular weight ubiquitin-COX-2 conjugates and perturbed COX-2 glycosylation. The thiol-reducing antioxidant N-acetylcysteine, and, to a lesser extent, the COX-2 inhibitor celecoxib, attenuated the loss of cell viability induced by cadmium demonstrating that oxidative stress and COX-2 activation contribute to cadmium cytotoxicity. These findings establish that disruption of the ubiquitin/proteasome pathway is not the only event triggered by cadmium. This oxidative stressor also activates COX-2 function. Both events could be triggered by formation of 4-hydroxy-2-nonenal as a result of cadmium-induced lipid peroxidation. Proinflammatory responses stimulated by oxidative stressors that mimic the cadmium effects may, therefore, be important initiators of the neurodegenerative process and exacerbate its progress.


Codling moth management and chemical ecology.
Lepidopteran insects use sex pheromones to communicate for mating. Olfactory communication and mate-finding can be prevented by permeating the atmosphere with synthetic pheromone. Pheromone-mediated mating disruption has become a commercially viable pest management technique and is used to control the codling moth, Cydia pomonella, a key insect pest of apple, on 160,000 ha worldwide. The codling moth sex pheromone, codlemone, is species specific and nontoxic. Orchard treatments with up to 100 grams of synthetic codlemone per hectare effectively control codling moth populations over the entire growing season. Practical implementation of the mating disruption technique has been realized at an opportune time, as codling moth has become resistant to many insecticides. We review codling moth chemical ecology and factors underlying the behavioral mechanisms and practical implementation of mating disruption. Area-wide programs are the result of collaborative efforts between academic research institutions, extension, chemical industries, and grower organizations, and they demonstrate the environmental and economic relevance of pheromone research.


A case of central nervous system lupus in succession to lupus peritonitis: a difficulty in the differential diagnosis between lupus psychosis and steroid-induced psychosis.
Abstract A 55-year-old woman with well-controlled systemic lupus erythematosus (SLE) suffered from the abrupt onset of massive intractable ascites, which did not respond to conventional diuretic therapy. While treatment with methylprednisolone pulse therapy ameliorated this lupus peritonitis, neuropsychiatric symptoms then appeared. After a diagnosis of the central nervous system (CNS) lupus, pulse therapy was continued and the patient recovered from the lupus psychosis. We discuss the differential diagnosis between CNS lupus and steroid-induced psychosis with particular references to recent diagnostic methods for CNS lupus.


The evaluation of tumour marker proteins in the diagnosis of primary hepatocellular carcinoma.
The sera of 122 patients with biopsy confirmed primary hepatocellular carcinoma (PHC) were examined for the presence of alphafoetoprotein (AFP), alpha 1antitrypsin 1 (AAT), alpha 1acidglycoprotein (AGP) 1, gammaglutamyl transpeptidase (GGT), carcinoemryonic antigen (Roche) (CEA) and the "Hepatoma-Liver antigen" H-L Ag). 83% of patients had elevation of AFP of more than 18 ng/ml 7.4% and 15.5% had levels between 19--100 ng/ml and 100-500 ng/ml respectively. Raised AAT, AGP, GGT, CEA and HL Ag were found in many patients with PHC. Grossly elevated AFP were usually diagnostic of PHC. The combination of AAT, AGP, CEA and HL Ag were useful in the diagnosis of AFP negative cases.


Thymectomy for myasthenia gravis: prognostic factors in 70 patients.
Thymectomy has become increasingly accepted as an efficacious procedure for myasthenia gravis, with high rates of complete clinical remission. Predictors of the response to thymectomy for myasthenia gravis vary in the literature. We retrospectively reviewed the clinical records of 70 patients (63% female; mean age, 38 years) diagnosed with myasthenia gravis from August 1993 to August 2004, to determine the factors predicting outcome. Complications occurred in 20%, but there was no hospital mortality. Complete clinical remission was obtained postoperatively in 47%. Our results indicate that patients with less than 1 year's duration of disease have a better prognosis, and Osserman stages I, IIa, and IIb are also associated with higher clinical remission rates. Female patients have a better prognosis than males, and the younger the patient the better the outcome. Thymectomy is indicated for myasthenia gravis as early as possible in the course of the disease.


Bereavement-related cognitive impairment in an oldest-old community-dwelling Brazilian sample.
As it is already known that depression can cause a demonstrable impact on cognition in elderly subjects, the objective of this study was to determine whether also the mourning process is associated with any cognitive impairment in this age range. A random and representative sample (a sample with 77 subjects/total county population of oldest-old with 219 subjects = 35%) aged 80 years or more was selected from the county of Veranópolis in the Brazilian rural southern region. Of this group, the cognitive function of subjects without grief and of subjects with the presence of grief were compared. Five neuropsychological tests (the Buschke-Fuld Selective Reminding Test, the word-list from the CERAD battery, the Verbal Fluency Test, and two subtests of the Wechsler memory scale), the Mini-Mental State Examination (MMSE) and two self-perceived memory impairment questionnaires were used. Presence of depressive symptomatology was identified by the Yesavage Geriatric Depression Scale (GDS). The prevalence rates of some psychiatric diagnoses (syndromic general anxiety disorder, major and minor depression) were compared between the bereaved group and the control group. There was not a statistically significant difference between the scores of controls and subjects with grief in the GDS. The frequency of affective disorders in both groups did not differ. However, the recently bereaved elderly subjects presented a mild cognitive impairment when evaluated with the MMSE, with the digit span test and with Word-list neuropsychological memory test. Likewise these bereaved octogenarian subjects presented more frequently a diagnosis of 'aging-associated cognitive decline' when compared with non-bereaved oldest-old. These results suggest that the normal sadness and/or the chronic stress of the grieving process, even without the presence of an identifiable syndromal-level depression, are associated with memory and cognitive differences among the bereaved oldest-old. Cause-effect relationships, however, cannot be established from this cross-sectional correlational study: Grief may influence cognitive functioning in the elderly, but mildly cognitively compromised elderly persons may be more likely to experience strong grief reactions after loss.


Effective Intense Pulsed Light Protocol in the Treatment of Moderate to Severe Acne Vulgaris of the Chest and Back.
Acne is defined as a chronic inflammatory disease of the pilosebaceous units, mainly affecting the face of young adults, but the chest and back can be involved as well. Oral antibiotics, topical retinoids, azelaic acid, benzoyl peroxide, and isotretinoin represent the most common treatment used for the treatment of acne, but several adverse effects and a lack of durable remission, with poor adherence by the patients, have been reported thus far. Lasers have been shown to be effective and safe to treat acne; intense pulsed light (IPL) demonstrates high efficacy rates, minimal discomfort, rapid recovery times, and excellent cosmetic and therapeutic outcomes. In this prospective study, we assessed the efficacy, safety, and reproducibility of a novel IPL protocol as a monotherapy in the treatment of acne of the chest and back. We included patients (N=50) aged 14 to 30 who presented with moderate papulopustular acne sited on the chest and back (Cook's Acne Grading Scale method 4-6, Pillsbury Scale III-IV). We performed four IPL sessions at two-week intervals on each patient. An excellent outcome was achieved in 50 percent of the patients and a good outcome in the 35 percent of the patients. Patients experienced light erythema and mild burning as the most common side effects, which spontaneously resolved within 24 to 96 hours. Consistent with previous reports, our study demonstrated IPL to be a safe and effective treatment for severe cases of acne on the chest and back, providing excellent aesthetic and therapeutic results in 85 percent of treated patients.


Fall TIPS: strategies to promote adoption and use of a fall prevention toolkit.
Patient falls are serious problems in hospitals. Risk factors for falls are well understood and nurses routinely assess for fall risk on all hospitalized patients. However, the link from nursing assessment of fall risk, to identification and communication of tailored interventions to prevent falls is yet to be established. The Fall TIPS (Tailoring Interventions for Patient Safety) Toolkit was developed to leverage existing practices and workflows and to employ information technology to improve fall prevention practices. The purpose of this paper is to describe the Fall TIPS Toolkit and to report on strategies used to drive adoption of the Toolkit in four acute care hospitals. Using the IHI "Framework for Spread" as a conceptual model, the research team describes the "spread" of the Fall TIPS Toolkit as means to integrate effective fall prevention practices into the workflow of interdisciplinary caregivers, patients and family members.


Only half right: species with female-biased sexual size dimorphism consistently break Rensch's rule.
Most animal species display Sexual Size Dimorphism (SSD): males and females consistently attain different sizes, most frequently with females being larger than males. However the selective mechanisms driving patterns of SSD remain controversial. 'Rensch's rule' proposes a general scaling phenomenon for all taxa, whereby SSD increases with average body size when males are larger than females, and decreases with body size when females are larger than males. Rensch's rule appears to be general in the former case, but there is little evidence for the rule when females are larger then males. Using comprehensive data for 1291 species of birds across 30 families, we find strong support for Rensch's rule in families where males are typically larger than females, but no overall support for the rule in families with female-biased SSD. Reviewing previous studies of a broad range of taxa (arthropods, reptiles, fish and birds) showing predominantly female-biased SSD, we conclude that Rensch's conjecture is the exception rather than the rule in such species. The absence of consistent scaling of SSD in taxa with female-biased SSD, the most prevalent direction of dimorphism, calls into question previous general evolutionary explanations for Rensch's rule. We propose that, unlike several other ecological scaling relationships, Rensch's rule does not exist as an independent scaling phenomenon.


Web-based delivery of medical multimedia contents using an MPEG-4 system.
Moving picture expert group compression standard version 4 (MPEG-4) is a standard for video coding aimed at multimedia applications. MPEG-4 was developed to enable high compression rate in a low bitrate transmission via the Internet or mobile telecommunications. Although these characteristics of MPEG-4 are suitable for telemedicine, little is known about the possibility of using this technology in the field of telemedicine. We evaluated the quality of MPEG-4-encoded medical video streams and compared them with original analogue videos and audio-video-interleave (AVI) files. Although MPEG-4 video streams have the advantage of small file size, they were found to be inferior to original videos and AVI files in terms of smoothness of motion pictures, sharpness of images and clearness of sound. Illegibility of characters was a major problem in MPEG-4 files. The score for total impression of MPEG-4 files was significantly lower than those for AVI files. The results of this study suggest that the quality of MPEG-4-encoded video streams is not adequate for telemedicine.


[Body mass index cut-offs for overweight and obesity in Chinese children and adolescents aged 2 - 18 years].
To study the body cut-offs of mass index (BMI) for the purpose of screening overweight and obesity for Chinese children and adolescents aged 2 - 18 years. Based on the BMI growth reference values for Chinese children aged 0 - 18, using the common methods to establish the BMI cut-offs for screening overweight and obesity. These methods were having the same empirical percentile or Z scores and the BMI value at 18 years consistent with adults. Three sets of BMI cut-offs, including (BMI₂₄, BMI₂₈), (P₈₅, P₉₅) and (Z₁, Z₂), were initially identified. Differences were compared on different cut-off points and prevalence rates of overweight and obesity with different BMI reference, different values and "prevalence" of overweight and obesity based on "2004 Beijing Child and Adolescent Metabolic Syndrome Study". Cut-offs standards which recommended by the Chinese Working Group on Obesity for Children (WGOC) and by the International Obesity Task Force (IOTF) were also used. Finally the appropriate cut-offs were defined. Three sets of BMI cut-offs for screening overweight and obesity for Chinese children and adolescents aged 2 - 18 years were obtained according to the above mentioned methods for selection. The prevalence rates of overweight and obesity defined by those cut-offs appeared not to be significantly different. Compared with the WGOC, the BMI cut-off points for screening overweight and obesity for both boys and girls from our study were very close to the WGOC', but cut-off points for screening overweight for girls aged 8.5 - 15.5 y was 0.3 - 1.0 kg/m² lower than the WGOC'. Going through the database on screening of "2004 Beijing Children's Metabolic Syndrome Survey", the prevalence of overweight for girls was about 3.4% higher than using the cut-offs of WGOC. Results from this study suggested that the BMI cut-offs passed through the cut-off point of BMI₂₄ and BMI₂₈ at 18 years was appropriate for screening overweight and obesity in Chinese children from 2 to 18 years, and achieved the continuity in age and consistency in screening standard when using the BMI indicator in children and adolescents.


Magnetic Motor Evoked Potential Recording in Horses Using Intramuscular Needle Electrodes and Surface Electrodes.
To date, motor evoked potential (MEP) recording in animals is often performed using intramuscular monopolar needle electrodes. Their placement and use has several disadvantages. Adhesive surface electrodes appear to be attractive because they are painless and easy to place. Because these are not used in horses, a scouting study is performed to (1) explore the applicability of surface electrodes in horses (2) determine the repeatability of motor latency times (MLTs) and amplitude measurements, and (3) to investigate if MLTs and amplitude values of surface electrode recordings were similar to intramuscular needle electrode recordings. Transcranial MEP recordings were performed by both coated needle and surface electrodes on ten sedated warmblood horses. Mean MLTs for the thoracic limbs were 20.8 ± 1.5 ms for needle and 21.2 ± 1.4 ms for surface electrode recording and 39.4 ± 3.8 ms and 39.2 ± 3.8 ms for the pelvic limbs, respectively. Mean amplitude values were 8.3 ± 4.1 and 7.2 ± 4.7 mV for the thoracic limbs and 4.2 ± 3.1 and 3.8 ± 2.4 mV for the pelvic limbs, respectively. A good agreement and repeatability for MLTs but insufficient agreement and repeatability for amplitude between both recording types were determined by Bland-Altman plots and Passing-Bablok regression and coefficients of variation calculation. In conclusion, this preliminary study shows that surface electrode recording of MEP is possible and well tolerated in horses. Surface recordings were repeatable and look similar to the intramuscular recordings when regarding MLTs, but overshadowing effects of large test-to-test variations precluded a conclusion concerning amplitude.


THE IMPACT OF VENTILATION RATE ON RADON CONCENTRATION INSIDE HIGH-RISE APARTMENT BUILDINGS.
Radon is the main pollutant of indoor air, being considered a primary cause of lung cancer, especially in non-smokers. In 2013, European legislation required the standardization of regulations on radon exposure in member states using EC Directive 59/2013 EURATOM. The directive establishes basic safety rules for protection against the dangers represented by the exposure to ionizing radiation. Directive 59/2013 mandates each European country to establish a national action plan to reduce the risks of lung cancer attributed to radon in the general population and exposed workers. Romania is a European country with almost 20 million citizens, with over half of population living in urban locations. Most urban buildings in Romania are high-rise structures (4-10 floors), having many residential units. In this paper, we present results of season-dependent measurements of radon concentration and ventilation rates in high-rise apartment buildings and show the influence of ventilation on indoor radon levels. Indoor radon concentrations varied between 70 and 168 Bq m-3 in winter and 17-30 Bq m-3 in summer, being higher than the respective outdoor concentrations by 2-5 times in winter and 1-4 times in summer. Ventilation rates varied with season and were influenced by meteorological conditions at the time of measurements. Findings indicate that levels of indoor radon concentration depend on ventilation rates of the unit, but also on building materials, wind speed around building, time of day (higher around noon) and season of the year (higher in the cold season when ventilation rate is lower).


The Relationship of Built Environment to Health-Related Behaviors and Health Outcomes in Elderly Community Residents in a Middle Income Country.
Few studies have examined the impact of the built environment (BE) on health behaviours and health outcomes in middle income countries. This study examines associations between self-assessed characteristics of the home and neighbourhood environment and health-related behaviours and health outcomes in an elderly population in Brazil. In a community sample of 6963 community dwellers 60 years old and older living in the state of Rio Grande do Sul, Brazil, associations between self-reported BE conditions and health behaviours and health outcomes were assessed using a structured questionnaire. Multivariate analysis was conducted to investigate these associations while accounting for other relevant characteristics. We found significant positive associations between adverse BE conditions and pulmonary, urinary conditions, gastrointestinal, problems, headache and depression. There were mixed associations between adverse BE conditions and musculoskeletal and sensory conditions, inverse associations with metabolic disorders. and no associations with dermatologic problems and cancer. After accounting for health related behaviours, results suggest a modest association between adverse BE conditions and hypertension, with no significant associations with other indicators of cardiovascular conditions (heart problems, stroke, varicose veins). The findings in this study suggest links between adverse conditions in the BE and health related behaviours in the hypothesized direction. Associations with the health conditions examined here are mixed. We find the strongest evidence for effects of adverse BE conditions for pulmonary and infectious conditions. Significant associations between the adverse BE indicators and health outcomes persist after accounting for health related behaviours, suggesting that BE conditions are linked to health pathways above and beyond the health related behaviours assessed in this study. Significance for public healthThe health outcomes for which we found most consistent evidence of associations with the built environment index (BEI) included respiratory conditions (bronchitis, pneumonia), urinary and renal conditions, gastrointestinal problems, headache, visual impairment and stroke. These health outcomes in the elderly may reflect exposures in the household environment associated with inadequate housing, such as mold, dust and damp. They may also be influenced by poor sanitary conditions, reflected in the absence of indoor plumbing and inadequate waste disposal facilities. Poor vision, headache and depression may all be associated with chronic exposure to poverty and stress, for which the measures of the household and neighborhood environmental conditions used in the BEI may be indicators. Assuring that the elderly in Brazil have access to adequate housing located in neighborhoods with access to basic sanitary conditions, water and lighting, will be increasingly important as the average age of Brazilians continues to increase, and increasing proportions of the population experience the adverse health effects associated with these conditions.


Effects of anxiety disorder on impairment and recovery from stroke.
The effect of anxiety disorder on recovery from impairment following stroke was examined in 142 patients with acute stroke who had follow-up evaluations. Anxiety disorder significantly interacted with depression to influence the severity and course of depression, outcome of activities of daily living, and social functioning. Anxiety disorder, however, did not affect cognitive impairment, which was influenced only by major depression. These data suggest that the existence of anxiety disorders plays an important role in the prognosis of patients with poststroke depression. These data also suggest that depression and anxiety disorder may have different mechanisms.


1,3-Bis[(1H-benzotriazol-1-yl)meth-yl]-2,3-dihydro-1H-benzimidazole.
In the title compound, C(21)H(18)N(8), the two (benzotriazol-1-yl)methyl groups are located in an anti position with respect to the benzimidazoline moiety. The dihedral angles between the benzotriazole ring systems and the central benzimidazoline moiety are 57.03 (4) and 81.01 (3)°. The crystal packing is stabilized by two C-H⋯π inter-actions.


Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions.
The MAT alpha 2 homeodomain regulates the expression of cell type-specific genes in yeast. We have determined the 2.7 A resolution crystal structure of the alpha 2 homeodomain bound to a biologically relevant DNA sequence. The DNA in this complex is contacted primarily by the third of three alpha-helices, with additional contacts coming from an N-terminal arm. Comparison of the yeast alpha 2 and the Drosophila engrailed homeodomain-DNA complexes shows that the protein fold is highly conserved, despite a 3-residue insertion in alpha 2 and only 27% sequence identity between the two homeodomains. Moreover, the orientation of the recognition helix on the DNA is also conserved. This docking arrangement is maintained by side chain contacts with the DNA--primarily the sugar-phosphate backbone--that are identical in alpha 2 and engrailed. Since these residues are conserved among all homeodomains, we propose that the contacts with the DNA are also conserved and suggest a general model for homeodomain-DNA interactions.


Identification of the chemokine CX3CL1 as a new regulator of malignant cell proliferation in epithelial ovarian cancer.
Little is known about the molecules that contribute to the growth of epithelial ovarian carcinomas (EOC), which remain the most lethal gynecological cancer in women. The chemokine Fractalkine/CX(3)CL1 has been widely reported to play a biologically relevant role in tumor growth and spread. We report here the first investigation of the expression and role of CX(3)CL1 in EOC. Epithelial cells from the surface of the ovary and the Fallopian tubes and from benign, borderline and malignant tumors all stained positive for CX(3)CL1. In tumor specimens from 54 women who underwent surgical treatment for EOC diagnosis, CX(3)CL1 immunoreactivity was unevenly distributed in epithelial tumor cells, and ranged from strong (33%) to absent (17%). This uneven distribution of CX(3)CL1 did not reflect the morphological heterogeneity of EOC. It was positively correlated with the proliferation index Ki-67 and with GILZ (glucocorticoid-induced leucine zipper), previously identified as an activator of the proliferation of malignant EOC cells. Hierarchical clustering analysis, including age at diagnosis, tumor grade, FIGO stage, Ki-67 index, CX(3)CL1, SDF-1/CXCL12 and GILZ immunostaining scores, distinguished two major clusters corresponding to low and high levels of proliferation and differing in terms of GILZ and CX(3)CL1 expression. GILZ overexpression in the carcinoma-derived BG1 cell line resulted in parallel changes in CX(3)CL1 products. Conversely, CX(3)CL1 promoted through its binding to CX(3)CR1 AKT activation and proliferation in BG1 cells. In a mouse subcutaneous xenograft model, the overexpression of GILZ was associated with higher expression of CX(3)CL1 and faster tumor growth. Our findings highlight the previously unappreciated constitutive expression of CX(3)CL1 preceding tumorigenesis in ovarian epithelial cells. Together with GILZ, this chemokine emerges as a regulator of cell proliferation, which may be of potential clinical relevance for the selection of the most appropriate treatment for EOC patients.


Inhibition of TGF-β signaling enables human corneal endothelial cell expansion in vitro for use in regenerative medicine.
Corneal endothelial dysfunctions occurring in patients with Fuchs' endothelial corneal dystrophy, pseudoexfoliation syndrome, corneal endotheliitis, and surgically induced corneal endothelial damage cause blindness due to the loss of endothelial function that maintains corneal transparency. Transplantation of cultivated corneal endothelial cells (CECs) has been researched to repair endothelial dysfunction in animal models, though the in vitro expansion of human CECs (HCECs) is a pivotal practical issue. In this study we established an optimum condition for the cultivation of HCECs. When exposed to culture conditions, both primate and human CECs showed two distinct phenotypes: contact-inhibited polygonal monolayer and fibroblastic phenotypes. The use of SB431542, a selective inhibitor of the transforming growth factor-beta (TGF-β) receptor, counteracted the fibroblastic phenotypes to the normal contact-inhibited monolayer, and these polygonal cells maintained endothelial physiological functions. Expression of ZO-1 and Na(+)/K(+)-ATPase maintained their subcellular localization at the plasma membrane. Furthermore, expression of type I collagen and fibronectin was greatly reduced. This present study may prove to be the substantial protocol to provide the efficient in vitro expansion of HCECs with an inhibitor to the TGF-β receptor, and may ultimately provide clinicians with a new therapeutic modality in regenerative medicine for the treatment of corneal endothelial dysfunctions.


Combination of physical activity and screen time on life satisfaction in adults: A cross-sectional survey.
Sufficient physical activity (PA) and limited screen time (ST) have been shown to be positively associated with a variety of mental health outcomes. It has been known that PA and ST are independently associated with life satisfaction. Whereas, little is known about the association between combinations of PA and ST with life satisfaction in adults. This study aimed to explore the associations between PA and ST (in insolation or combination) and life satisfaction in adults. Data from the 2014 European Social Survey (ESS) round 7 consisting of 22 countries were analyzed in this study. In total, self-reported data from 40,185 adults were included in the final analysis. The self-administered method was used to collect demographic information, PA, ST, and life satisfaction. The prevalence of meeting PA guidelines (at least 150 min per week) and ST guidelines (no more than 3 h per day) was calculated according to Canadian 24-h Movement Guidelines for Adults. Adults who were engaged in sufficient PA and limited ST were more likely to report a higher level of life satisfaction. Meeting PA or ST guidelines was more likely to report higher life satisfaction scores [odds ratio (OR) = 1.31, 95% CI: 1.16-1.47]. Compared with not meeting any guidelines, those who met both PA and ST guidelines had a higher OR (OR = 1.55, 95% CI: 1.37-1.76). This study found that participating PA while limiting ST concurrently was linked with better life satisfaction. Creating an active lifestyle is important to population's well-being.


Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.
The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem.


Arabidopsis GOLDEN2-LIKE (GLK) transcription factors activate jasmonic acid (JA)-dependent disease susceptibility to the biotrophic pathogen Hyaloperonospora arabidopsidis, as well as JA-independent plant immunity against the necrotrophic pathogen Botrytis cinerea.
Arabidopsis thaliana GOLDEN2-LIKE (GLK1 and 2) transcription factors regulate chloroplast development in a redundant manner. Overexpression of AtGLK1 (35S:AtGLK1) in Arabidopsis also confers resistance to the cereal pathogen Fusarium graminearum. To further elucidate the role of GLK transcription factors in plant defence, the Arabidopsis glk1 glk2 double-mutant and 35S:AtGLK1 plants were challenged with the virulent oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) Noco2. Compared with Col-0, glk1 glk2 plants were highly resistant to Hpa Noco2, whereas 35S:AtGLK1 plants showed enhanced susceptibility to this pathogen. Genetic studies suggested that AtGLK-mediated plant defence to Hpa Noco2 was partially dependent on salicylic acid (SA) accumulation, but independent of the SA signalling protein NONEXPRESSOR OF PATHOGENESIS-RELATED 1 (NPR1). Pretreatment with jasmonic acid (JA) dramatically reversed Hpa Noco2 resistance in the glk1 glk2 double mutant, but only marginally affected the 35S:AtGLK1 plants. In addition, overexpression of AtGLK1 in the JA signalling mutant coi1-16 did not increase susceptibility to Hpa Noco2. Together, our GLK gain-of-function and loss-of-function experiments suggest that GLK acts upstream of JA signalling in disease susceptibility to Hpa Noco2. In contrast, glk1 glk2 plants were more susceptible to the necrotrophic fungal pathogen Botrytis cinerea, whereas 35S:AtGLK1 plants exhibited heightened resistance which could be maintained in the absence of JA signalling. Together, the data reveal that AtGLK1 is involved in JA-dependent susceptibility to the biotrophic pathogen Hpa Noco2 and in JA-independent resistance to the necrotrophic pathogen B. cinerea.


Chemical Mapping of Excitons in Halide Double Perovskites.
Halide double perovskites comprise an emerging class of semiconductors with tremendous chemical and electronic diversity. While their band structure features can be understood from frontier-orbital models, chemical intuition for optical excitations remains incomplete. Here, we use ab initio many-body perturbation theory within the GW and the Bethe-Salpeter equation approach to calculate excited-state properties of a representative range of Cs2BB'Cl6 double perovskites. Our calculations reveal that double perovskites with different combinations of B and B' cations display a broad variety of electronic band structures and dielectric properties and form excitons with binding energies ranging over several orders of magnitude. We correlate these properties with the orbital-induced anisotropy of charge-carrier effective masses and the long-range behavior of the dielectric function by comparing them with the canonical conditions of the Wannier-Mott model. Furthermore, we derive chemically intuitive rules for predicting the nature of excitons in halide double perovskites using computationally inexpensive density functional theory calculations.


Using MutPred derived mtDNA load scores to evaluate mtDNA variation in hypertension and diabetes in a two-population cohort: The SABPA study.
Mitochondrial DNA (mtDNA) variation has been implicated in many common complex diseases, but inconsistent and contradicting results are common. Here we introduce a novel mutational load hypothesis, which also considers the collective effect of mainly rare variants, utilising the MutPred Program. We apply this new methodology to investigate the possible role of mtDNA in two cardiovascular disease (CVD) phenotypes (hypertension and hyperglycaemia), within a two-population cohort (n = 363; mean age 45 ± 9 yrs). Very few studies have looked at African mtDNA variation in the context of complex disease, and none using complete sequence data in a well-phenotyped cohort. As such, our study will also extend our knowledge of African mtDNA variation, with complete sequences of Southern Africans being especially under-represented. The cohort showed prevalence rates for hypertension (58.6%) and prediabetes (44.8%). We could not identify a statistically significant role for mtDNA variation in association with hypertension or hyperglycaemia in our cohort. However, we are of the opinion that the method described will find wide application in the field, being especially useful for cohorts from multiple locations or with a variety of mtDNA lineages, where the traditional haplogroup association method has been particularly likely to generate spurious results in the context of association with common complex disease.


Choosing to write the paper format thesis.
Graduate students today may be faced with the option of writing either a traditional format thesis or a paper format thesis. In contrast to the traditional format in which the text body consists of four or five chapters, the body of the paper format thesis can be comprised of an introductory chapter, two or more papers written as publishable manuscripts, and a conclusion. In this article, an overview of the paper format thesis is presented and contrasted with the traditional format thesis. The description of the paper format thesis is followed by its advantages and disadvantages for writers and readers. It is by weighing all possible pros and cons, as well as considering one's individual situation, that the graduate student will be able to decide which format of thesis to write.


Serial study of C reactive protein in neonatal septicaemia.
Serial C reactive protein concentrations were assayed by electroimmunoassay in 41 infants. Values in most of the non-infected infants were below 0.3 mg/dl, the lower limit of detection of C reactive protein by electroimmunoassay. Eleven of 12 infants with proved sepsis (positive blood cultures) had significantly raised concentrations and one infant with recurrent pseudomonas chest infection had a raised C reactive protein concentration. High C reactive protein concentrations were also found in infants with suspected infection. Successful treatment was followed by a decrease in the C reactive protein concentration. Total white blood cell count was not as appropriate as C reactive protein determination in the early identification of bacterial infection in the newborn.


How Could POCT be a Useful Tool for Migrant and Refugee Health?
Point of care testing (POCT) represents an important step forward in the clinical management of patients. POC assays are easy to use and do not require skilled personnel; therefore they are particularly useful in low resource settings where diagnostics laboratories equipped with complex instruments that require well trained technicians are not available. Samples can be processed immediately overcoming the problems related to the stability of the sample, storage and shipping to a centralized laboratory hospital based. Furthermore, results are delivered in real-time, usually less than 1 hr; thus, a clinical decision can be taken earlier. A prompt diagnosis is crucial in the case of contagious diseases allowing a rapid isolation of the infected patient and treatment; thus, reducing the risk of transmission of the pathogen. In this report, we address the use of POC assays in the diagnosis of infectious pathogens including hepatitis B and C viruses, human immunodeficiency virus-type 1, human papillomavirus, chlamydia trachomatis, neisseria gonorrhea, trichomonas vaginalis, mycobacterium tuberculosis and the parasite plasmodium. These pathogens are commonly detected among vulnerable people such as refugees and migrants. The described POC assays are based on nuclei acid amplification technology (NAAT) that is generally characterized by a high sensitivity and specificity.


Tattoo removal--state of the art.
Tattooing has been around since the early beginnings of modern civilization. The discovery of selective photothermolysis at last has made it possible to remove tattoos without leaving a scar. Q-switched neodymium: yttrium-aluminum-garnet, alexandrite, and ruby lasers with pulse durations in the nanosecond domain fulfill this need. Argon or cw-CO(2) lasers as well as intense pulsed light sources should not be used since they often produce significant scarring. This article provides an overview of current laser systems. Developments leading to new tattoo inks, feedback systems to detect the absorbance characteristics of tattoo inks, dermal clearing agents, and perhaps even lasers with shorter pulse-durations might improve the results in the future.


Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance.
Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol-ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0-160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined.


Change in BMI after radioactive iodine ablation for graves disease.
We aimed to determine the extent of post-treatment weight gain that occurs in pediatric patients in the first year following radioactive iodine (RAI) therapy for Graves disease (GD) and its relationship to clinical characteristics. A retrospective chart review of patients receiving RAI therapy for GD between 1998-2015 was performed. Change in BMI SDS (∆BMI SDS) from baseline to one year after treatment was determined. We also investigated whether individual clinical and/or biochemical factors were associated with the weight trajectory in these patients. One hundred fifty seven patients aged 12.7 ± 3 years (80% girls) were included in the analysis. Average ∆BMI SDS was 0.70 ± 0.71 (p < 0.001) at 1 year. Patients with weight loss at presentation had a greater ∆BMI SDS than those without (0.92 vs 0.56, p = 0.005), whereas no association was seen with gender, pubertal status, use of antithyroid drugs, history of ADHD, or Down syndrome. Baseline BMI SDS was negatively correlated with ∆BMI SDS, with a stronger correlation in males. From baseline to 1 year, the proportion of overweight and obese patients increased from 9.6% to 18.5% and from 6.4% to 21%, respectively. In a subset of 81 patients, a positive correlation was noted between time to euthyroidism and ∆BMI SDS, particularly in boys. The number of our patients in the overweight category doubled and the number in the obese category more than tripled in the first year following RAI treatment for GD. Anticipatory guidance regarding this important issue is badly needed.


The functions and roles of C2H2 zinc finger proteins in hepatocellular carcinoma.
C2H2 zinc finger (C2H2-ZF) proteins are the majority group of human transcription factors and they have many different molecular functions through different combinations of zinc finger domains. Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors and the main reason for cancer-related deaths worldwide. More and more findings support the abnormal expression of C2H2-ZF protein in the onset and progression of HCC. The C2H2-ZF proteins are involved in various biological functions in HCC, such as EMT, stemness maintenance, metabolic reprogramming, cell proliferation and growth, apoptosis, and genomic integrity. The study of anti-tumor drug resistance also highlights the pivotal roles of C2H2-ZF proteins at the intersection of biological functions (EMT, stemness maintenance, autophagy)and chemoresistance in HCC. The involvement of C2H2-ZF protein found recently in regulating different molecules, signal pathways and pathophysiological activities indicate these proteins as the possible therapeutic targets, and diagnostic or prognostic biomarkers for HCC.


Cross-cultural patterns in college student drinking and its consequences--a comparison between the USA and Sweden.
The aim of the study was to compare alcohol use, consequences and common risk factors between American and Swedish college students. A secondary comparative analysis from one American and two Swedish studies in college settings. Swedish freshmen report higher alcohol use than US freshmen students. Swedish residence hall students report higher alcohol use than US residence hall students, but lower than American fraternity/sorority members. US students were less likely to be drinkers. Controlling for age, country moderated the relationship between family history and harmful drinking scores for women (stronger in the USA), and between expectancies and harmful drinking scores for men (stronger in Sweden), though in both cases this represented a small effect and patterns were similar overall. Swedish students are at higher risk for alcohol use than US students, but similar patterns between aetiological predictors and outcomes in both countries suggest that research from the USA is generalizable to Swedish students and vice versa. More research is needed to better understand unique relationships associated with age and family history.


A new approach to vital root resection.
This report deals with ten cases in which periodontal surgery was performed followed by immediate resection of one of the vital buccal roots on maxillary molars. The resultant pulpal opening was treated with calcium hydroxide, zinc oxide and eugenol then sealed with an amalgam alloy. Two additional cases were treated in reverse order by first resecting the vital root followed by immediate periodontal surgery. All cases were evaluated over a 1 to 3 year period. The results indicate that vital root resection at the same time as periodontal surgery compares favorably with cases treated in which periodontal surgery was completed at a prior appointment.


Patterns of exposure to smoked tobacco advertisements among youths in India and its association with smoked tobacco use: a Latent Class Analysis.
Youths are exposed to multiple sources of tobacco advertisements. We sought to examine patterns of exposure to smoked tobacco advertisements through various modes among Indian youths and its association with smoked tobacco use. Cross-sectional survey design. We utilised data from the national Global Adult Tobacco Survey 2016-17 in India, which covered adults >15 years of age. Latent Class Analysis (LCA) was used to examine patterns of exposure to tobacco advertisements through various modes (television, radio, cinema, internet, posters, billboards, public transportation, public walls, stores, newspaper) among youths. Classes were compared across sociodemographic and tobacco use-related characteristics. Various model-fit statistics (Akaike, Bayesian and sample size-adjusted Bayesian Information Criteria, likelihood-ratio tests and, Entropy) and meaningfulness of the classes were used to select the number of latent classes. Three distinct latent classes were identified in terms of exposure to smoked tobacco products advertisements: "Multimodal exposure" (n = 448, 4.0%), "low exposure" (n = 9584, 86.0%), and "Television and stores" (n = 1116, 10.0%). There were significant differences between classes emerged on sociodemographics (age, sex, residence, education, wealth quintile, region). The "Multimodal exposure" class was associated with current tobacco smoking (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 1.4-3.0, P-value <0.001) and cigarette use (OR: 1.9, 95% CI: 1.3-3.4, P-value <0.001) compared to the "low exposure" class. Youths could be grouped into three classes based on their exposure to smoked tobacco product advertisements. The "Multimodal exposure" class with a distinct profile was significantly associated with smoked tobacco use among youths. This evidence supports complete ban on all forms of tobacco advertisements.


A Qualitative Study of a Maintenance Support Program for Women at Risk of Homelessness: Part 3: Societal Factors.
Homelessness is a collective societal problem, and people who are homeless are often treated as society's underclass, stigmatised and excluded. These issues are often exacerbated among homeless people from countries other than the one in which they are currently living. In this article we report findings from a qualitative study of homeless women, case managers and health professionals from a Maintenance Support Program and their personal accounts and insights into their experiences of the program. This article presents the third and last sub-theme "societal factors" of the study where the overarching theme was "A life-changing event: I have the power to change." This sub-theme is supported by three categories including gender, race and ethnicity, and environment. The findings highlight the impact of the societal factors that linked women's experiences with domestic violence and abuse. Further cultural views regarding the role of women in society hinder their capacity to recognise that they should not be treated differently and that they should be supported to access health and social services to improve their lives in a safe and supportive environment.


Unexpected laboratory diagnosis of latent urogenital coccidioidomycosis in a nonendemic area.
Dissemination of coccidioidomycosis beyond the respiratory tract is not uncommon, but involvement of the urogenital tract is rarely observed. Most, if not all, reported cases of urogenital infections caused by Coccidioides immitis have been diagnosed in areas considered endemic for the fungus, where suspicion of this illness and its extrapulmonary manifestations is high. In nonendemic regions, however, C immitis is not likely to be considered as a possible cause of genitourinary tract infections unless the organism is fortuitously identified by histologic, cultural, or serologic studies. We report the unexpected isolation of C immitis from routine bacterial cultures of a draining urethral-scrotal fistula from a patient residing in a nonendemic area of the United States. We also discuss the difficulties and potential hazards encountered during the laboratory evaluation of this case.


Disinfectant Treatments That Reduce Transmission of Stagonosporopsis citrulli During Cucurbit Grafting.
Gummy stem blight can develop in greenhouses on cucurbit seedlings grown as scions and rootstocks for grafting. When diseased seedlings are cut during grafting, Stagonosporopsis spp., the fungal pathogens causing gummy stem blight, may be transferred to healthy seedlings. The objective of this study was to evaluate efficacy of disinfectant treatments to prevent or reduce transmission during cutting and grafting. A blade contaminated with mycelium and spores from a culture of S. citrulli transferred the pathogen to 72%, 73%, and 55% of the second, third, and fourth seedlings, respectively, cut in sequence when 100% of the first seedlings cut were infected. Kleengro (didecyl dimethyl ammonium chloride), Physan 20 (dimethyl benzyl ammonium chloride), and Virkon S (potassium peroxymonosulfate) were ineffective when sprayed onto watermelon seedlings before or after cutting hypocotyls with a contaminated blade. Dipping a contaminated blade in 0.3% sodium hypochlorite, 0.4% Physan 20, or 70% or 95% ethanol before cutting watermelon hypocotyls significantly (P = 0.01) reduced incidence of gummy stem blight compared with water but did not prevent transmission. Soaking a contaminated blade for 3 s in 95% ethanol, 30 s in 0.8% sodium hypochlorite, or flaming the blade after dipping in 95% ethanol, prevented transmission. In a grafting experiment, both the watermelon scion and the interspecific hybrid squash rootstock were cut with contaminated or contaminated and treated blades before grafting. Sterilizing a contaminated blade by flaming significantly (P = 0.01) reduced incidence of gummy stem when compared with a 1-s dip in ethanol, a 1-s dip in Physan 20, or water. Disease incidences in these treatments were 11%, 45%, 100%, and 100%, respectively. Using heat, ethanol, or sodium hypochlorite to disinfest cutting tools may reduce transmission of S. citrulli during cucurbit grafting.


Meta-analysis of interventions to increase physical activity among cardiac subjects.
Extensive primary research has tested interventions to increase physical activity (PA) among adults with cardiovascular disease. This meta-analysis integrates the extant research about how to increase PA in cardiac samples. Extensive literature searching located published and unpublished intervention studies that measured PA outcomes. Results were coded from primary studies. Fixed- and random-effects meta-analytic procedures included moderator analyses. Data were synthesized across 11,877 subjects from 79 eligible research reports. The overall mean PA effect size for 2-group comparisons was 0.35 (higher mean for treatment than control), which is consistent with a difference of 1984 kcal/week for treatment subjects versus 1615 for control subjects. The fitness effect size for 2-group comparisons was .17. Other statistically significantly positive 2-group effect sizes were .24 for quality of life and .23 for subsequent cardiac events. Effect sizes for anthropometric measures and blood pressure did not differ significantly from 0. Exploratory moderator analyses found large effect sizes for PA among studies that had (1) an exclusive focus on PA versus diverse health behaviors, (2) more contact between interventionists and subjects, (3) supervised exercise sessions, (4) fitness testing, (5) face-to-face encounters versus mediated intervention delivery, and (6) more minutes of activity per week. Effect sizes were unrelated to funding status, dissemination vehicle, gender distribution, or attrition rate. These findings document that interventions can be effective in increasing PA among patients with cardiovascular diseases. Primary research should compare interventions in randomized trials to confirm causal relationships.


Toxicity and possible mechanisms of action of honokiol from Magnolia denudata seeds against four mosquito species.
This study was performed to determine the toxicity and possible mechanism of the larvicidal action of honokiol, extracted from Magnolia denudata seeds, and its 10 related compounds against third-instar larvae of insecticide-susceptible Culex pipiens pallens, Aedes aegypti, and Aedes albopictus and Anopheles sinensis resistant to deltamethrin and temephos. Honokiol (LC50, 6.13-7.37 mg/L) was highly effective against larvae of all of the four mosquito species, although the toxicity of the compound was lower than that of the synthetic larvicide temephos. Structure-activity relationship analyses indicated that electron donor and/or bulky groups at the ortho or para positions of the phenol were required for toxicity. Honokiol moderately inhibited acetylcholinesterase and caused a considerable increase in cyclic AMP levels, indicating that it might act on both acetylcholinesterase and octopaminergic receptors. Microscopy analysis clearly indicated that honokiol was mainly targeted to the midgut epithelium and anal gills, resulting in variably dramatic degenerative responses of the midgut through sequential epithelial disorganization. Honokiol did not affect the AeCS1 mRNA expression level in Ae. aegypti larvae, but did enhance expression of the genes encoding vacuolar-type H+-ATPase and aquaporin 4, indicating that it may disturb the Na+, Cl- and K+ co-transport systems. These results demonstrate that honokiol merits further study as a potential larvicide, with a specific target site, and as a lead molecule for the control of mosquito populations.


Effect on gastric mucus of the proton pump inhibitor leminoprazole and its cytoprotective action against ethanol-induced gastric injury in rats.
The effect of leminoprazole ((+-)-2-[[2-(isobutyl-methylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, CAS 104340-86-5), a new compound being developed as an inhibitor of the gastric mucosal proton pump (H+,K(+)-ATPase), on gastric mucus secretion was studied by a biochemical method measuring the gastric mucin content in rats. Oral administration of leminoprazole (30 mg/kg) strongly inhibited the hemorrhagic lesions induced by 60% ethanol containing 0.15 mol/l HCl (acid-ethanol) administered 1 h later. Leminoprazole significantly inhibited the acid-ethanol-induced reduction of the mucin content in the surface mucosa including the mucus gel layer, but no significant effect could be obtained on the reduction of mucin present in the deep layer of the corpus and antral mucosa. Leminoprazole given to rats not treated with acid ethanol accelerated the secretion of deep mucosal mucus and increased significantly the content of soluble mucus which was recovered from the gastric luminal contents to about 200% of control, but failed to produce any significant change in the mucus content present in the surface mucosal and the mucus gel layers. The effect of leminoprazole on gastric mucus secretion might contribute to healing the peptic ulcer diseases and may be involved in the cytoprotective mechanism of this drug.


Modified cable equation incorporating transverse polarization of neuronal membranes for accurate coupling of electric fields.
We present a theory and computational methods to incorporate transverse polarization of neuronal membranes into the cable equation to account for the secondary electric field generated by the membrane in response to transverse electric fields. The effect of transverse polarization on nonlinear neuronal activation thresholds is quantified and discussed in the context of previous studies using linear membrane models. The response of neuronal membranes to applied electric fields is derived under two time scales and a unified solution of transverse polarization is given for spherical and cylindrical cell geometries. The solution is incorporated into the cable equation re-derived using an asymptotic model that separates the longitudinal and transverse dimensions. Two numerical methods are proposed to implement the modified cable equation. Several common neural stimulation scenarios are tested using two nonlinear membrane models to compare thresholds of the conventional and modified cable equations. The implementations of the modified cable equation incorporating transverse polarization are validated against previous results in the literature. The test cases show that transverse polarization has limited effect on activation thresholds. The transverse field only affects thresholds of unmyelinated axons for short pulses and in low-gradient field distributions, whereas myelinated axons are mostly unaffected. The modified cable equation captures the membrane's behavior on different time scales and models more accurately the coupling between electric fields and neurons. It addresses the limitations of the conventional cable equation and allows sound theoretical interpretations. The implementation provides simple methods that are compatible with current simulation approaches to study the effect of transverse polarization on nonlinear membranes. The minimal influence by transverse polarization on axonal activation thresholds for the nonlinear membrane models indicates that predictions of stronger effects in linear membrane models with a fixed activation threshold are inaccurate. Thus, the conventional cable equation works well for most neuroengineering applications, and the presented modeling approach is well suited to address the exceptions.


Unusual light-reflecting pigment cells appear in the Xenopus neural tube culture system in the presence of guanosine.
Isolation and culture of Xenopus laevis neural tubes resulted in differentiation of melanophores and iridophores from neural crest cells; the differentiated melanophores and iridophores were then maintained in culture for more than 6 months. Guanosine has been reported to promote reflecting platelet formation in melanin-producing pigment cells; however, the process of pigment organellogenesis is still unclear. In the present study, unusual light-reflecting pigment cells were observed upon addition of guanosine to the neural tube culture system, which contained melanosomes specific to melanophores, and reflecting platelets specific to iridophores. Ultrastructural studies suggested that irregularly shaped reflecting platelets were formed from stage II melanosomes (the early stage of melanosome formation) in these unusual pigment cells.


Ethanol facilitates glutamatergic transmission to dopamine neurons in the ventral tegmental area.
The cellular mechanisms underlying alcohol addiction are poorly understood. In several brain areas, ethanol depresses glutamatergic excitatory transmission, but how it affects excitatory synapses on dopamine neurons of the ventral tegmental area (VTA), a crucial site for the development of drug addiction, is not known. We report here that in midbrain slices from rats, clinically relevant concentrations of ethanol (10-80 mM) increase the amplitude of evoked EPSCs and reduce their paired-pulse ratio in dopamine neurons in the VTA. The EPSCs were mediated by glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In addition, ethanol increases the frequency but not the amplitude of spontaneous EPSCs. Furthermore, ethanol increases extracellular glutamate levels in the VTA of midbrain slices. The effects of ethanol are mimicked by SKF 38393, a dopamine D(1) receptor agonist, and by GBR 12935, a dopamine reuptake inhibitor, and they are blocked by SKF 83566, a D(1) antagonist, or by reserpine, which depletes dopamine stores. The enhancement of sEPSC frequency reaches a peak with 40 mM ethanol and declines with concentrations >or=80 mM ethanol, which is quite likely a result of D(2) receptor activation as raclopride, a D(2) receptor blocker, significantly enhanced 80 mM ethanol-induced enhancement of sEPSCs. Finally, 6, 7-dinitroquinoxaline-2, 3-dione (DNQX), an AMPA receptor antagonist, attenuates ethanol-induced excitation of VTA DA neurons. We therefore conclude that, acting via presynaptic D(1) receptors, ethanol at low concentrations increases glutamate release in the VTA, thus raising somatodendritic dopamine release, which further activates the presynaptic D(1) receptors. Enhancement of this positive feedback loop may significantly contribute to the development of alcohol addiction.


Pericardial effusions with tamponade and visceral constriction in patients with rheumatoid arthritis on tumour necrosis factor (TNF)-inhibitor therapy.
Tumour necrosis factor-inhibitor (TNF-inhibitor) therapy is increasingly used for the treatment of rheumatoid arthritis. While it is effective for the articular manifestations of rheumatoid arthritis we have reason to believe that it is less effective for extra-articular disease. We present two cases of life-threatening cardiac tamponade in two patients with well-controlled rheumatoid arthritis on adalimumab. An extensive literature search was carried out and three other patients were found. We believe that these cases highlight the need for rheumatologists to be vigilant for extra-articular manifestations of rheumatoid arthritis even in the presence of quiescent joint disease while on TNF-inhibitors.


Molecular genetic findings in suicidal behavior: what is beyond the serotonergic system?
Various studies provide consistent evidence for a genetic component in suicidal behavior. First molecular genetic studies concentrated on genes of the serotonergic system based on the biochemical evidence that serotonergic neurotransmission is implicated in this behavior. Furthermore, genes of the dopaminergic and noradrenergic neurotransmitter systems have also been the subjects of investigations in this context. Some epidemical and clinical studies showed that low serum cholesterol levels are associated with suicidal behavior and genes involved in these pathways have been investigated. Microarray experiments provide the possibility of genome-wide gene expression analysis and help to investigate associated molecular mechanisms. The aim of this article is to review molecular genetic studies in suicidal behavior and to emphasize findings on new genes.


Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase.
Purpose: Recent epidemiological and clinical studies have suggested the benefit of aspirin for patients with cancer, which inspired increasing efforts to demonstrate the anticancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anticancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anticancer of aspirin.Experimental Design: A homogeneous time-resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay, and molecular docking were performed to identify heparanase as an aspirin-binding protein. Transwell, rat aortic rings, and chicken chorioallantoic membrane model were used to evaluate the antimetastasis and anti-angiogenesis effects of aspirin, and these phenotypes were tested in a B16F10 metastatic model, MDA-MB-231 metastatic model, and MDA-MB-435 xenograft model.Results: This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis, and growth in heparanase-dependent manner.Conclusions: In summary, this study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anticancer effects, and offers a direction for the development of small-molecule inhibitors of heparanase. Clin Cancer Res; 23(20); 6267-78. ©2017 AACR.


Cross-talk of alloimmune response and autoimmunity: role in pathogenesis of chronic rejection.
Chronic rejection following organ transplantation continues to be a major problem in the long-term survival of the engraftment. Recent literature points to role of both the humoral and cellular alloimmune responses in the pathogenesis of chronic rejection. Our recent studies have provided evidence for alloimmune-response-induced de novo development of immune responses to self-antigens in the post-transplant period in the pathogenesis of chronic rejection following lung, heart, and kidney transplantation. This review details our current understanding of two distinct yet inter-dependent immune processes in the immunopathogenesis of chronic rejection.


Whole genome association studies in complex diseases: where do we stand?
Hundreds of genome-wide association studies have been performed in recent years in order to try to identify common variants that associate with complex disease. These have met with varying success. Some of the strongest effects of common variants have been found in late-onset diseases and in drug response. The major histocompatibility complex has also shown very strong association with a variety of disorders. Although there have been some notable success stories in neuropsychiatric genetics, on the whole, common variation has explained little of the high heritability of these traits. In contrast, early studies of rare copy number variants have led rapidly to a number of genes and loci that strongly associate with neuropsychiatric disorders. It is likely that the use of whole-genome sequencing to extend the study of rare variation in neuropsychiatry will greatly advance our understanding of neuropsychiatric genetics.


Mismatch repair deficient mice show susceptibility to oxidative stress-induced intestinal carcinogenesis.
We have previously established an experimental system for oxidative DNA damage-induced tumorigenesis in the small intestine of mice. To elucidate the roles of mismatch repair genes in the tumor suppression, we performed oxidative DNA damage-induced tumorigenesis experiments using Msh2-deficient mice. Oral administration of 0.2% Potassium Bromate, KBrO3, effectively induced epithelial tumors in the small intestines of Msh2-deficient mice. We observed a 22.5-fold increase in tumor formation in the small intestines of Msh2-deficient mice compared with the wild type mice. These results indicate that mismatch repair is involved in the suppression of oxidative stress-induced intestinal tumorigenesis in mice. A mutation analysis of the Ctnnb1 gene of the tumors revealed predominant occurrences of G:C to A:T transitions. The TUNEL analysis showed a decreased number of TUNEL-positive cells in the crypts of small intestines from the Msh2-deficient mice compared with the wild type mice after treatment of KBrO3. These results suggest that the mismatch repair system may simultaneously function in both avoiding mutagenesis and inducing cell death to suppress the tumorigenesis induced by oxidative stress in the small intestine of mice.


Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction.
Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate "off-the-shelf" delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction.In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at -80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells.Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.


Implantable Cardioverter Defibrillators The state of the art.
Implantable devices are now being routinely used for the treatment of patients with malignant ventricular tachyarrhythmias. This technology became an approved clinical therapy in the United States in 1985. The prototype implantable cardioverterdefibrillator ICD was developed in the 1970s and investigated in the 1980s. Since its approval in 1985 for general clinical application, ICDs are being increasingly used in patients with life-threatening ventricular tachyarrhythmias based upon a number of clinical trials undertaken in North America and western Europe.


Intravascular device infections: epidemiology, diagnosis, and management.
Intravascular devices such as pacemakers, implantable cardioverter-defibrillators (ICDs), left ventricular assist devices (LVADs), and prosthetic vascular grafts are life-saving therapies for patients with malignant arrhythmias, heart failure, and various vascular diseases. As indications for their use have increased, so has the prevalence of infectious complications associated with these devices. We present a review of the clinical literature on the epidemiology, diagnosis, and management of infectious complications of these intravascular devices. Most intravascular device infections are thought to result from skin flora contamination during implantation. Infection of the subcutaneous portion of the device can subsequently track to deeper intravascular tissues. Infection that involves the intravascular or intracardiac portion of these devices carries a high morbidity and mortality. Despite appropriate antibiotic therapy, cure of infection is frequently possible only with device removal. Well-designed placebo-controlled, randomized studies evaluating antimicrobial therapy for treatment of intravascular device infections are lacking. In the absence of better information, authorities recommend antibiotics targeted toward cultured organisms for approximately 4 to 6 weeks and device removal.


Quantum-randomized polarization of laser pulses derived from zero-point diamond motion.
Intrinsic randomness in quantum systems is a vital resource for cryptography and other quantum information protocols. To date, randomizing macroscopic polarization states requires randomness from an external source, which is then used to modulate the polarization e.g. for quantum key-distribution protocols. Here, we present a Raman-based device for directly generating laser pulses with quantum-randomized polarizations. We show that crystals of diamond lattice symmetry provide a unique operating point for which the Raman gain is isotropic, so that the spontaneous symmetry breaking initiated by the quantum-random zero-point motion determines the output polarization. Experimentally measured polarizations are demonstrated to be consistent with an independent and identical uniform distribution with an estimated quantum entropy rate of 3.8 bits/pulse.


How Regrouping Alerts in Computerized Physician Order Entry Layout Influences Physicians' Prescription Behavior: Results of a Crossover Randomized Trial.
As demonstrated in several publications, low positive predictive value alerts in computerized physician order entry (CPOE) induce fatigue and may interrupt physicians unnecessarily during prescription of medication. Although it is difficult to increase the consideration of medical alerts by physician through an improvement of their predictive value, another approach consists to act on the way they are presented. The interruption management model inspired us to propose an alternative alert display strategy of regrouping the alerts in the screen layout, as a possible solution for reducing the interruption in physicians' workflow. In this study, we compared 2 CPOE designs based on a particular alert presentation strategy: one design involved regrouping the alerts in a single place on the screen, and in the other, the alerts were located next to the triggering information. Our objective was to evaluate experimentally whether the new design led to fewer interruptions in workflow and if it affected alert handling. The 2 CPOE designs were compared in a controlled crossover randomized trial. All interactions with the system and eye movements were stored for quantitative analysis. The study involved a group of 22 users consisting of physicians and medical students who solved medical scenarios containing prescription tasks. Scenario completion time was shorter when the alerts were regrouped (mean 117.29 seconds, SD 36.68) than when disseminated on the screen (mean 145.58 seconds, SD 75.07; P=.045). Eye tracking revealed that physicians fixated longer on alerts in the classic design (mean 119.71 seconds, SD 76.77) than in the centralized alert design (mean 70.58 seconds, SD 33.53; P=.001). Visual switches between prescription and alert areas, indicating interruption, were reduced with centralized alerts (mean 41.29, SD 21.26) compared with the classic design (mean 57.81, SD 35.97; P=.04). Prescription behavior (ie, prescription changes after alerting), however, did not change significantly between the 2 strategies of display. The After-Scenario Questionnaire (ASQ) that was filled out after each scenario showed that overall satisfaction was significantly rated lower when alerts were regrouped (mean 4.37, SD 1.23) than when displayed next to the triggering information (mean 5.32, SD 0.94; P=.02). Centralization of alerts in a table might be a way to motivate physicians to manage alerts more actively, in a meaningful way, rather than just being interrupted by them. Our study could not provide clear recommendations yet, but provides objective data through a cognitive psychological approach. Future tests should work on standardized scenarios that would enable to not only measure physicians' behavior (visual fixations and handling of alerts) but also validate those actions using clinical criteria.