Trends in Unplanned Admissions of Patients With Adult Congenital Heart Disease Based on the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination Study.
The prevalence of adult congenital heart disease (ACHD) is increasing rapidly and in particular, patients who underwent complicated surgeries are reaching their youth and middle age. Therefore, the need for ACHD treatment will increase, but the current medical situation is unknown. In this study we assessed trends in unplanned admissions in patients with ACHD in Japan.Methods and Results: From the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination, a nationwide claim-based database, we selected patients aged >15 years with CHD defined by the International Classification of Diseases, 10th Revision codes. We identified 39,676 admissions between April 2012 and March 2018; 10,444 (26.3%) were unplanned. Main diagnoses were categorized into 3 degrees of complexity (severe, moderate, and mild) and other. Among unplanned admissions, the proportion of the severe group increased with time. Patients in the mild group were significantly older than those in the moderate and severe groups (median age: 70.0, 39.0, and 32.0 years, respectively). There were 765 deaths during hospitalization (overall mortality rate, 7.3%). The odds ratio of death during admission was significantly higher in patients aged >50 years, especially in the moderate group. Patients with moderate or severe ACHD tended to experience unplanned admissions at a younger age. In anticipation of greater numbers of new, severe patients, we need to prepare for their increasing medical demands.


Total intravenous nutrition with peripherally inserted silicone elastomer central venous catheters.
Long-term indwelling central venous catheters inserted peripherally for total intravenous nutrition have been complicated by thrombophlebitis in most instances. However, experiences with silicone elastomer catheters used in this manner have not been previously reported. In this investigation a crank introducer unit has been developed that has allowed 61-cm silicone elastomer catheters to be placed in the superior vena cava with insertion in the basillic or cephalic vein. Thirty-five patients (36 catheter placements) received total intravenous nutrition exclusively via these silicone elastomer catheters. The mean time indwelling was 20.4 days (range, four to 56 days). Thirty of the 36 catheters were removed when total intravenous nutrition was discontinued. Only six catheters were removed for nonvenous and venous reactions. These results have shown the safety and efficacy of peripherally inserted silicone elastomer central venous catheters.


Gonadal effects of pinealectomy and immunization against N-acetylindolealkylamines in the hamster.
In order to determine whether circulating melatonin (MEL) is necessary for the gonadal regression seen in hamsters exposed to a short photoperiod, animals were immunized with N-acetylserotonin (NAS) conjugated to protein. Antibodies formed against this conjugate bind MEL and NAS equally. When exposed to a short photoperiod (L:D, 1:23), a dramatic regression was seen in gonadal weight with no effect on body, Harderian gland or adrenal weight. Plasma testosterone levels also dropped. Immunization against NAS did not modify these effects, suggesting that circulating MEL does not mediate the antigonadal effect of the short photoperiod.


Synergistic hemolytic activity of Staphylococcus lugdunensis is mediated by three peptides encoded by a non-agr genetic locus.
Some strains of the coagulase-negative Staphylococcus lugdunensis produce a synergistic hemolytic activity (SLUSH), phenotypically similar to the delta-hemolysin of S. aureus. Reverse-phase high-pressure liquid chromatography of supernatants from S. lugdunensis 307 yielded three late-eluting peaks of 3.5 kDa with synergistic hemolytic activity. A degenerate oligonucleotide probe was designed from partial amino acid sequences of the 23-amino-acid (aa) tryptic fragments from one of the three peaks and hybridized to a single 2.8-kb HindIII chromosomal fragment. The relevant portion of this fragment was cloned by PCR, and sequencing showed the presence of three related open reading frames (ORFs), SLUSH-A, SLUSH-B, and SLUSH-C, preceded by an unrelated short potentially coding sequence (ORF-X), cotranscribed on a polycistronic 838-nucleotide mRNA. The amino acid sequences of the peptides from the three peaks align perfectly with the predicted sequences from the three SLUSH ORFs (peak I = SLUSH-B; peak II = SLUSH-C; peak III = SLUSH-A). These three peptides are closely related (amino acid homology, >76%) and do not show significant homology to S. aureus delta-hemolysin but do resemble a Salmonella typhimurium invasin and the "gonococcal growth inhibitor," a bacteriocin secreted by Staphylococcus haemolyticus. The predicted ORF-X gene product is a 24-aa peptide with no homology to the SLUSH peptides.


Spatial audiometry: detection of spondaic words in noise.
It is important to select appropriate stimuli and test conditions for developing standardized spatial audiometric tests. In three experiments, binaural detection thresholds (BDTs) for a target signal, located at either 0, 45, 90, 135, 180, 225, 270, or 315 degrees azimuth, were measured in the presence of a masker positioned at one of these eight locations. Target signals included spondaic words from the CID W-1 list. The masker was speech spectrum noise (SSN) or multitalker noise (MTN) presented at a constant level (65 dBA). Bekesy tracking was used to measure BDTs in listeners with normal hearing. Results indicate that BDTs are significantly influenced by the (a) angular separation between the target and noise source and (b) choice of spondaic words used as target stimuli. BDTs for various spondaic words differed as much as 13 dB for a given angular separation. BDTs measured in SSN and MTN for otherwise identical test conditions differed less than 3 dB. A single spondaic word appears to be appropriate for spatial audiometric tests of detection. Nonsignificant differences between masked BDTs obtained for SSN and MTN noises indicate that for spatial detection, the masking effects of these noises are comparable. These results indicate that the development of a clinical test of spatial detection should include the use of SSN and a single spondaic word, with detection being measured for a set of four or five signal and noise source configurations.


A criterion measurement model for health behavior change.
Researchers in the field of health behavior change have traditionally relied on a univariate criterion measure to evaluate the efficacy of an intervention. Such measures have superficial face validity but suffer from a number of problems: (a) lack of precise definitions; (b) poor statistical power; and (c) a lack of meaningfulness for some aspects of the problem. As an alternative, a theoretical model is developed that attempts to define more appropriate multivariate sets of dependent variables for the study of health behavior change. The model involves three separate constructs: Positive Evaluation Strength, Negative Evaluation Strength, and Habit Strength. The pattern of change for each construct is described across four stages of change: Precontemplation, Contemplation, Action, and Maintenance. For each construct, two thresholds are proposed representing the ability of the environment to modify the construct. Four tests of the model are provided from existing data sets. First, a structural model analysis was used to test if the proposed measurement model adequately fits the data. Second, a dynamic typology approach produced profiles of change that are consistent with the model. Third, a time series analysis provided support for the assumed model. Fourth, longitudinal, five-wave panel design was employed to test if the relation between the two cognitive variables (Pros and Cons) and the behavioral measure (Habit Strength) was consistent with the model. Implications for alternative intervention strategies are discussed.


Effective Polarization in Pairwise Potentials at the Graphene-Electrolyte Interface.
At the graphene-electrolyte interface, the polarizability of both the surface and the solution plays a major role in defining the interfacial structure and dynamics of the ions. Current molecular models predict different ion adsorption behavior at the interface depending on whether surface or solution polarization is included in the model. Here, we propose a simple method to parametrize the ion-carbon interaction from density functional theory, implicitly modeling the solution using the conductor-like polarizable continuum model. The new model simultaneously takes into account the polarizability of both the graphene sheet and the solution without the need to use time-consuming polarizable potentials and can predict the ion adsorption trend so far only achievable using first-principles simulations. Simulations performed with 1 M electrolyte solutions of different ions show that cations are strongly adsorbed onto the graphene surface with a trend (Li+ < Na+ < K+) opposite to that predicted by the gas-phase calculations and different from that obtained from the single-ion simulations.


Generation of a novel HEK293 luciferase reporter cell line by CRISPR/Cas9-mediated site-specific integration in the genome to explore the transcriptional regulation of the PGRN gene.
Progranulin has multiple functions in several physiological and pathological processes, including embryonic development, wound repair, tumorigenesis, inflammation and neurodegeneration. To investigate the transcriptional regulation of the PGRN gene, a luciferase knock-in reporter system was established in HEK293 cells by integrating luciferase gene in the genome controlled by the endogenous PGRN promoter using CRISPR/Cas9. PCR results demonstrated the site-specific integration of the exogenous luciferase gene into the genome. To validate the novel luciferase knock-in system, a CRISPR/Cas9 transcription activation/repression system for the PGRN gene was constructed and applied to the knock-in system. In addition, phorbol ester (phorbol 12-myristate, 13-acetate), previously reported as activating the expression of PGRN, was applied to the system. The results indicated that luciferase activity was directly correlated with the activity of the PGRN endogenous promoter. This novel system will be a useful tool for investigating the transcriptional regulation of PGRN, and it has great potential in screening the drugs targeting PGRN.


Characteristics of Disaster-Related Suicide in Fukushima Prefecture After the Nuclear Accident.
Background: Suicide is a major concern after the 2011 earthquake and nuclear accident in Fukushima. Aims: This study delineates characteristics of the disaster-related suicides in Fukushima. Method: Data provided by the Fukushima Prefectural Police and data published by the Fukushima or Japanese Government were analyzed. Numbers of disaster-related suicides and evacuees were compared among the three prefectures affected. Age, sex, occupation, and means for disaster-related suicides in Fukushima were compared with overall suicides in Fukushima or Japan. History of medical treatment, changes in job and family structure after the disaster, and signs of contemplation were examined within the disaster-related suicides of Fukushima. Results: While other prefectures have experienced a drop in disaster-related suicides, Fukushima has not. Age-standardized disaster-related suicide rates were remarkably higher in men than in women. Moreover, disaster-related suicide rates in Fukushima were higher in women in their 50s and 80s as compared with overall suicide rates in Fukushima or Japan. Limitations: No detailed comparisons were made between disaster-related and non-disaster-related suicides. Conclusion: Disaster-related suicide rates were higher in men than in women. Also, it was found that the disaster-related suicide rates of elderly women were higher compared with overall suicide rates in Japan and Fukushima. In addition, many who died by suicide showed signs of contemplation before the attempt and had started psychiatric treatment. Improvement of suicide risk assessment skills for mental health professionals and gatekeeper training among residents will be essential to prevent disaster-related suicides.


Two years of growth hormone (GH) treatment increase isometric and isokinetic muscle strength in GH-deficient adults.
GH deficiency in adults is associated with reduced muscle mass and muscle strength. The objective of this trial was to follow the effect of 2 yr of GH treatment in GH-deficient adults on muscle performance in relation to a reference population. Knee extensor and flexor strengths for isometric and isokinetic concentric muscle strength were measured using a Kin-Com dynamometer. Hand-grip strength was measured in both hands. The fatigue index was calculated as the percent reduction in peak torque at 50 repeated isokinetic knee extensions. Superimposed, single twitch electrical stimulation was performed. The GH-deficient subjects had lower isometric knee extensor, knee flexor, and hand-grip strength than the reference population. Two years of GH treatment increased and normalized the mean isometric knee extensor and flexor strengths. The concentric knee flexor and extensor strength at an angular velocity of pi rad/s increased, as did the concentric knee flexor strength at an angular velocity of pi/3 rad/s. The increase in muscle strength was more marked in younger patients and in patients with lower initial muscle strength than predicted. Quadriceps endurance decreased, whereas the effect of superimposing single twitches on isometric contraction and hand-grip strength was unaffected by the GH treatment. Two years of GH therapy in GH-deficient adults increased and normalized isokinetic and isometric muscle strength studied in proximal muscle groups. Hand-grip strength and the degree of lack of maximal motor unit activation on voluntary isometric knee extensor force did not change. The dynamic local muscle fatigue index decreased.


Patients with chronic hepatitis B infection: what is their quality of life?
Hepatitis B (HBV) is endemic in Singapore. This study aimed to determine the quality of life of patients with chronic HBV infection (HBV carriers) on conservative management. They were reviewed in primary care facilities and in a district hospital in Singapore. This cross-sectional survey utilised a validated Hepatitis Quality of Life questionnaire, which incorporated the SF-36 health survey, to assess a convenience sample of HBV carriers' quality of life in 14 domains. The mean scores in each domain were determined, with higher scores indicating better health. Wilcoxon-Mann-Whitney test was used in the data analysis to determine statistical significance (p-value is less than 0.05). The mean age of 108 participants was 44.1 (standard deviation 12.5) years. They were predominantly Chinese (90.7 percent), male (58.3 percent) and 50.7 percent of them had family members who were HBV-infected. The latter had higher scores in the hepatitis specific limitation (HLIM) domain. The majority did not have any impaired physical nor mental health. In comparison with the healthy peers in the local population, the Chinese HBV carriers scored significantly lower in the "social functioning" domain (p-value is less than 0.001), regardless of gender. The majority of HBV carriers had good physical and mental health. Physicians should recognise the impact of the chronic infection on the social aspects of daily living of the HBV carriers, and such issues should be addressed appropriately to provide better quality care.


Illinoian and Wisconsin (Farmdale) Drifts Recently Exposed at Rockford, Illinois.
New exposures in Rockford, Illinois, show fresh till overlying ferruginous gravel of marginal glacial origin. These, together with older sections, now slumped or no longer exposed, offer convincing evidence of two glaciations of the Rockford area, the first of Illinoian age and the second of early Wisconsin (Farmdale) age. The sections further suggest that the greater part of the drift fill in Ancient Rock River Valley is Illinoian, and that this is overlain by a relatively thin mantle of Farmdale drift.


Risk of second primary malignancy after esophagectomy for squamous cell carcinoma of the thoracic esophagus.
To assess the risk of subsequent malignancies after esophagectomy for squamous cell carcinoma of the thoracic esophagus for the establishment of an adequate follow-up program. We statistically analyzed clinical factors in 114 cases of second malignancy after esophagectomy that developed in 94 of 679 patients who underwent curative resection. The cancer incidence rates in the general population estimated by the Research Group for Population-Based Cancer Registration in Japan were used as standards for comparison. The 10-year cumulative risk of second malignancy was 34.5%, and the overall relative risk (RR) was 2.98 (95% CI, 2.41 to 3.65). The risk of head and neck cancer was markedly elevated (RR, 34.9; 95% CI, 24.3 to 48.6), followed by the risks of lung cancer (RR, 3.24; 95% CI, 1.89 to 5.19) and stomach cancer (RR, 2.00; 95% CI, 1.17 to 3.21). Multifactor analysis demonstrated that independent factors affecting the risk of subsequent malignancies were presence of other malignancies detected before esophagectomy and any of the following factors: masculine sex, alcohol consumption, and smoking. The 5-year survival rate after detection of subsequent malignancy was 45%. The outcome in patients with subsequent head and neck cancer was significantly less favorable as a result of difficulty in early detection. Patients had a remarkably high risk of subsequent cancer of the upper aerodigestive tract after esophagectomy, in particular, head and neck cancer. Minute postoperative surveillance is strongly recommended, especially in patients with a history of malignancies before esophagectomy. Early detection of second malignancies allowed less invasive treatment with favorable outcome.


Crohn's disease of the esophagus: Three cases and a literature review.
Three cases of esophageal Crohn's disease (CD) are described, each with dysphagia and/or odynophagia caused by esophageal ulceration. All three patients had associated ileocolitis. One patient followed for a prolonged period responded to treatment with sulfasalazine and prednisone. A computer search back to 1967 produced 72 additional cases of esophageal CD. Among these 75 patients (total), who were, on average, 34 years old, esophageal disease was the presenting disease symptom in 41 patients (55%). The diagnosis was difficult in 13 patients, in whom no distal bowel disease was detected at the time of initial esophageal presentation. The most common presentation was dysphagia associated with aphthous or deeper ulcerations (52 patients). In 11 of these patients, oral aphthous ulcerations were also present. Esophageal stenosis or fistulas to surrounding structures were present in 27 patients and led to surgery in 17 patients. Most of the unfavourable outcomes were in this group of 27 patients with esophageal complications, including five deaths. Fourteen additional patients required surgery for CD of other areas. Responses of uncomplicated ulcerative disease of the esophagus tended to be favourable if the medical regimen included prednisone. Clinical patterns of esophageal CD were divided into three categories: ulcerative, stenosing and asymptomatic (acute disease in children).


Prognostic implications of microvascular and macrovascular abnormalities in older adults: cardiovascular health study.
Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed. This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009). At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease. Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.


Gene expression during osteogenic differentiation in mandibular condyles in vitro.
The cartilagenous tissue of mandibular condyles of newborn mice contains progenitor cells as well as young and mature chondrogenic cells. During in vitro cultivation of the tissue, progenitor cells undergo osteogenic differentiation and form new bone (Silbermann, M., D. Lewinson, H. Gonen, M. A. Lizarbe, and K. von der Mark. 1983. Anat. Rec. 206:373-383). We have studied the expression of genes that typify osteogenic differentiation in mandibular condyles during in vitro cultivation. RNAs of the genes for collagen type I, osteonectin, alkaline phosphatase, and bone gla protein were sequentially expressed in progenitor cells and hypertrophic chondrocytes during culture. Osteopontin expression peaked in both the early and the late phase of the differentiation process. The data indicate a distinct sequence of expression of osteoblast-specific genes during osteogenic differentiation and new bone formation in mandibular condyles.


[Heart myxoma histogenesis in the light of its histological and ultrastructural features].
In 168 cases of heart myxoma histological and electron-microscopic examination have revealed signs of embryonal endothelium capable of vasoformation and glycoprotein and glycosaminoglycanes synthesis in myxoma cells. Neither differentiation of myxomas cells up to mature endotheliocytes no signs of malignant transformation was found. According to the authors, heart myxoma is a true benign dysontogenetic tumor originating from embryonal endothelium. The term myxoma does not reflect morphological entity of the tumor and the authors suggest to call it embryonal endocardial endothelioma.


The effect of dietary magnesium and caseinphosphopeptides on bone metabolism in rats.
The effect of dietary magnesium (Mg) or caseinphosphopeptides (CPPs) on bone metabolism has been reported. However, few studies have investigated the effects of simultaneous supplementation of Mg and CPPs. Sixty-three 3-week-old Sprague-Dawley male rats were divided into seven groups and fed a specified diet for 45 days. Body characteristics, bone physicochemical indicators, and bone metabolism indicators relative to bone metabolism were analyzed. We found that, first, a dietary Mg deficiency resulted in increased bone formation and decreased bone resorption. Second, dietary Mg or CPP supplementation promoted bone formation and prevented bone resorption. Third, dietary Mg supplementation with CPPs also functioned to enhance bone formation and prevent bone resorption. There were synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline of the HS-Mg-CPP group (0.2% Mg, 0.1% CPPs). The increase in the femur length of the HS-Mg-CPP group compared with the control group was 6% which was much higher than that of HS-Mg (1%) or CPPs (5%). The induction in serum parathyroid hormone content in the HS-Mg-CPP group was 33% compared with the control group which was higher than that of the induction of the HS-Mg (19%) or CPP (23%) group. The induction in the deoxypyridinoline content of the HS-Mg-CPP (43%) group compared with the control group was remarkably higher than that of HS-Mg (8%) or CPPs (16%). Overall our results demonstrated that high doses of Mg (0.2%) and CPPs (0.1%) in combination produced synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline in rats, which is important for a better understanding of the effect of Mg and CPPs on bone metabolism.


Are Blacks and Hispanics Disproportionately Incarcerated Relative to Their Arrests? Racial and Ethnic Disproportionality Between Arrest and Incarceration.
Do large racial and ethnic disparities in prison populations reflect systematic racial and policy discrimination in the criminal justice system, or do they reflect disproportionate involvement of blacks and Hispanics in "serious" or street crime? Our investigation of this question keys off the approach initiated by Alfred Blumstein is his pioneering studies on the topic. While yielding important findings, there are, however, substantial gaps in the empirical literature on the racial disproportionality issue. We attempt to fill those gaps by (1) using both data on prison admission as well as in-stock prison populations, (2) presenting more recent racially and ethnically disaggregated arrest and incarceration data from Pennsylvania for 2003-2007, and (3) including Hispanic offenders in our racial and ethnic disproportionality comparisons. Our results indicate, first, that the representation of blacks, whites, and Hispanics among offenders admitted to state prison and in the prison population corresponds closely to their representation in arrest statistics. Second, using arrests as a marker of violent offending, the overrepresentation of blacks among offenders admitted to state prisons occurs because they commit a disproportionate number of frequently imprisoned (i.e., violent) crimes. Third, for those offenses where there is a within-race difference between arrest and incarceration representation, Hispanics experience the greatest disadvantage. Fourth, failing to account for Hispanics in white and black estimates tends to inflate white proportions and deflate black proportions of arrests, admissions, and prison population estimates, masking the "true" black and white racial disproportionality. We conclude that while there is a need for continued concern with possible racial discrimination in justice system processing, this concern should not distract attention from what arguably is the more important matter-ameliorating the social environmental conditions that foster disproportionate minority (especially black) involvement in violent crime.


[Mandibular function after a condylectomy for unilateral condylar hyperplasia].
Unilateral condylar hyperplasia is a rare growth disorder originating in the growth centre of the mandibular condyles and resulting in facial asymmetry. Primary treatment consists of condylectomy. In this cross-sectional research, limitations in mandibular function and oral health related quality of life were measured with the Mandibular Function Impairment Questionnaire and the Oral Health Impact Profile (NL49). The study included 17 patients who underwent treatment for unilateral condylar hyperplasia with a condylectomy in the University Medical Center Groningen between 1997 and 2012. The median (IQR) scores of the Mandibular Function Impairment Questionnaire (8,0 [1,0; 15,0]) and the Oral Health Impact Profile (25,0 [3,0; 53,0] were low compared to other conditions involving the mandible. A higher age was associated with increased limitations in mandibular function (rs = 0,588 (p = 0,013)). After a condylectomy for unilateral condylar hyperplasia the functional impairment of the mandible and the decrease in oral health related quality of life are low.


Self-sorting of foreign proteins in a bacterial nanocompartment.
Nature uses bottom-up approaches for the controlled assembly of highly ordered hierarchical structures with defined functionality, such as organelles, molecular motors, and transmembrane pumps. The field of bionanotechnology draws inspiration from nature by utilizing biomolecular building blocks such as DNA, proteins, and lipids, for the (self-) assembly of new structures for applications in biomedicine, optics, or electronics. Among the toolbox of available building blocks, proteins that form cage-like structures, such as viruses and virus-like particles, have been of particular interest since they form highly symmetrical assemblies and can be readily modified genetically or chemically both on the outer or inner surface. Bacterial encapsulins are a class of nonviral protein cages that self-assemble in vivo into stable icosahedral structures. Using teal fluorescent proteins (TFP) engineered with a specific native C-terminal docking sequence, we report the molecular self-sorting and selective packaging of TFP cargo into bacterial encapsulins during in vivo assembly. Using native mass spectrometry techniques, we show that loading of either monomeric or dimeric TFP cargo occurs with unprecedented high fidelity and exceptional loading accuracy. Such self-assembling systems equipped with self-sorting capabilities would open up exciting opportunities in nanotechnology, for example, as artificial (molecular storage or detoxification) organelles or as artificial cell factories for in situ biocatalysis.


Eimeria tenella: further studies on the development of the oocyst.
The present study investigated the processes of macrogametogenesis and oocyst formation of Eimeria tenella (Xiamen strain), including the formation of wall-forming body1 (WFB1) and wall-forming body 2 (WFB2), the club-shape body and the origin of the residual body during the transformation from a macrogamete to an oocyst. Transmission electron microscopy was used to follow ultrastructural changes of the organelles during parasite development. Frozen section techniques and special staining were used to determine the chemical composition of the club-shape body. Electron lighter WFB1 appeared earlier than the electron denser WFB2 during the process of cyst wall formation. WFB2 appeared to play a key role in cyst wall formation, whereas WFB1 may have a limited role in the wall-forming process. When two last generation merozoites entered the same host cell simultaneously, one of them grew well, but the other one was developmentally retarded, and became a residual body. Our study indicates that the content of the club-shape body are lipoidal in nature, not amyolpectin as suggested previously, because they stained black by Sudan black-B. During of macrogametogenesis and oocyst formation of E. tenella (Xiamen strain), WFB2 plays a major role in cyst wall formation. The residual bodies come from the undeveloped macrogametes. The club-body is lipoid; and lipometabolism is important energy resource in E. tenella development.


Between-group competition, intra-group cooperation and relative performance.
We report the results of a new public goods experiment with an intra-group cooperation dilemma and inter-group competition. In our design subjects receive information about their relative individual and group performance after each round with non-incentivized and then incentivized group competition. We found that, on average, individuals with low relative performance reduce their contributions to the public good, but groups with low performance increase theirs. With incentivized competition, where the relative ranking of the group increases individual payoffs, the reaction to relative performance is larger with individuals contributing more to the group; further, we observe that the variance of strategies decreases as individual and group rankings increase. These results offer new insights on how social comparison shapes similar reactions in games with different incentives for group performance and how competition and cooperation can influence each other.


Evidence Collection and Evaluation for the Development of Dietary Guidelines and Public Policy on Nutrition.
Dietary guidelines and recommendations, usually developed by government bodies or large authoritative organizations, have major downstream effects on public policy. A growing body of evidence supports the notion that there are serious deficiencies in the methods used to develop dietary guidelines. Such deficiencies include the failure to access or conduct comprehensive systematic reviews, a lack of systematic or rigorous evaluation of the quality of the evidence, a failure to acknowledge the limitations of the evidence base underlying recommendations, and insufficiently stringent management of conflicts of interest. These issues may be addressed by adhering to international standards for guideline development, including adopting systematic review methodology and using rigorous systems to evaluate the certainty of the evidence and to move from evidence to recommendations, of which the GRADE approach (Grading of Recommendations Assessment,Development and Evaluation) is the most rigorous and fully developed. Improving the methods by which dietary guidelines are produced has considerable potential to substantially improve public policy decision-making.


Further evolution of a strain of Staphylococcus aureus in vivo: evidence for significant inactivation of flucloxacillin by penicillinase.
A strain of Staphylococcus aureus (no. FAR4) has been isolated at intervals, for 32 months, from the sputum of a patient with cystic fibrosis of the lung. Changes in the properties of isolates of this strain over the first 18 months have been reported previously (Lacey et al., 1973 and 1974). During the last 14 months (May 1973 to July 1974), further evolution has occurred to produce a total of 31 distinct phenotypes. Recent changes are as follows. 1. The ability of isolates to produce penicillinase in vitro was closely correlated with flucloxacillin therapy. Inactivation of flucloxacillin by penicillinase was demonstrated by diffusion testing (but not MIC determination) in vitro and may have occurred to a significant extent in vivo. 2. Lincomycin-resistant mutants slowly disappeared from the sputum after the termination of clindamycin therapy. 3. All of the recent isolates were resistant to erythromycin, possibly because of the linkage of the genes coding for erythromycin resistance with those coding for the production of delta-haemolysin; delta-haemolysin may be an important "virulence factor".


Motivation for palatable food despite consequences in an animal model of binge eating.
Binge eating involves an abnormal motivation for highly palatable food in that these foods are repeatedly consumed despite their binge-triggering effects and life-affecting consequences associated with binge eating. We determined if rats identified as binge-eating prone (BEP) similarly display abnormal motivation for palatable food. Food-sated BEP and binge-eating resistant (BER) rats were given voluntary access to palatable food paired with increasing intensity of footshock. Later, they were exposed to a period of cyclic caloric restriction-refeeding. BEPs consumed significantly more and tolerated higher levels of footshock for palatable food than BERs. Cyclic restriction-refeeding increased BERs' tolerance of shock for palatable food. Previously observed parallels of the rat BEP model to human binge eating can now be extended to include an abnormal motivation for palatable food. This model should prove useful in identifying specific genes that interact with the nutritional environment to mediate binge eating and may point to novel physiological targets to treat compulsive overeating.


Chemonucleolysis versus open discectomy. A ten-year follow-up study.
Retrospectively 156 patients with an average follow-up period of 10.3 years were classified in two groups. Group I, 85 patients, chose chymopapain as their primary treatment. Group II, 71 patients, elected to have a laminectomy with discectomy. Overall, 98% of patients responded to follow-up investigations. Based on several well-accepted pain outcome measures there were no significant differences between the two groups at ten years. Recurrence rates, however, were greater following open discectomy at one- and ten-year follow-up examination. The question of when to return a patient to work yielded interesting results. Those patients returning to work before feeling completely recovered from symptoms had a poorer outcome at final follow-up examination.


Star-shaped poly(2-methyl-2-oxazoline)-based films: rapid preparation and effects of polymer architecture on antifouling properties.
Development of surfaces with antifouling properties is of great interest in biomedical applications. In this paper, the research was aimed at rapid preparation of poly(2-methyl-2-oxazoline)-based antifouling coating. We designed and synthesized a set of well-defined multiarm star copolymers hyperbranched poly(ethylenimine)-graft-poly(2-methyl-2-oxazoline) (PEI-g-PMOXA) with different PMOXA grafting ratios and chain lengths. The cytotoxicity of the polymer was tested and the PMOXA-based films were successfully deposited rapidly onto substrates via a simple one-step dopamine-assisted codeposition method. The effect of polymer architecture (linear PMOXA with different molecular weights, star PMOXA with different PMOXA grafting ratios and arm lengths) on deposited films with respect to their deposition kinetics, surface composition, wettability, morphology, cytotoxicity, and antifouling properties was investigated systematically. The antifouling properties of PMOXA-based films were found to be dependent on the surface PMOXA chain densities, which were controlled by the PMOXA grafting ratios and chain lengths. Moreover, the star PMOXA structures gave the surfaces with higher PMOXA chain densities and enhanced antifouling properties compared to the linear ones. Among the star copolymers, PEI-g(70)-PMOXA(5K)/polydopamine and PEI-g(70)-PMOXA(7K)/polydopamine deposited films showed the highest resistance to protein adsorption (96-99% relative to the bare gold surface) and cell attachment (97-99% relative to the bare glass surface), as well as complete inhibition against platelet adhesion. At last, the stability test results showed that the PMOXA-based film exhibited superior stability in long-term applications than the poly(ethylene glycol)-based film.


A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways.
Deregulated c-Myc occurs in approximately 30% of human cancers. Similarly, hypoxia-inducible factor (HIF) is commonly overexpressed in a variety of human malignancies. Under physiologic conditions, HIF inhibits c-Myc activity; however, when deregulated oncogenic c-Myc collaborates with HIF in inducing the expression of VEGF, PDK1 and hexokinase 2. Most of the knowledge of HIF derives from studies investigating a role of HIF under hypoxic conditions, however, HIF-1alpha stabilization is also found in normoxic conditions. Specifically, under hypoxic conditions HIF-1-mediated regulation of oncogenic c-Myc plays a pivotal role in conferring metabolic advantages to tumor cells as well as adaptation to the tumorigenic micromilieu. In addition, our own results show that under normoxic conditions oncogenic c-Myc is required for constitutive high HIF-1 protein levels and activity in Multiple Myeloma (MM) cells, thereby influencing VEGF secretion and angiogenic activity within the bone marrow microenvironment. Further studies are needed to delineate the functional relevance of HIF, MYC, and the HIF-MYC collaboration in MM and other malignancies, also integrating the tumor microenvironment and the cellular context. Importantly, early studies already demonstrate promising preclinical of novel agents, predominantly small molecules, which target c-Myc, HIF or both.


High mobility group box 1 protein (HMGB1) as biomarker in hypoxia-induced persistent pulmonary hypertension of the newborn: a clinical and in vivo pilot study.
Background: Inflammation plays an important role in neonatal hypoxia-induced organ damage. Newborns with perinatal asphyxia often develop persistent pulmonary hypertension of the newborn (PPHN). The objective of this study was to explore changes in the pro-inflammatory high mobility group box-l (HMGB1) protein during hypoxia-induced PPHN clinically and in vivo. Methods: Serum samples were collected from full-term newborns at PPHN onset and remission. As controls, blood serum samples were collected from the umbilical arteries of healthy full-term newborns born in our hospital during the same period. Clinical data for neonates were collected and serum levels of HMGB1, IL-6, and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). An animal study compared a PPHN Sprague-Dawley rat model to healthy newborn control rats. Histopathology was used to evaluate changes in the pulmonary artery wall. ELISA and western blot analyses were used to examine HMGB1 levels in the serum and lungs. Results: Serum HMGB1 levels were significantly elevated in newborns with PPHN, compared to those in healthy controls, and decreased dramatically after PPHN resolution. HMGB1 changes were positively correlated with serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Histopathological analysis demonstrated that the median wall thickness of pulmonary arterioles accounting for the percentage of pulmonary arteriole diameter (MT%) was not significantly different between PPHN and control groups 3 d after PPHN, although thickness of the small pulmonary arterial wall middle membrane and stenosis of the small pulmonary arteries. ELISA and western blot analyses showed similar trends between serum HMGB1 levels and HMGB1 protein expression in the lungs. Serum and lung HMGB1 levels were significantly elevated soon after PPHN onset, peaked after 24 h, and then decreased after 3 d, although they remained elevated compared to those in the control group. Conclusions: This study indicates that HMGB1 is related to hypoxia-induced PPHN pathogenesis. HMGB1 changes might thus be used as an early indicator to diagnose hypoxia-induced PPHN and evaluate its improvement. We also provide important evidence for the involvement of inflammation in the progression of hypoxia-induced PPHN.


The Canadian Otolaryngology-Head and Neck Surgery Workforce in the Urban-Rural Continuum: Longitudinal Data from 2002 to 2013.
Objectives To evaluate the proportion of otolaryngology-head and neck surgery (OHNS) providers who are rural versus urban based from 2002 to 2013. Secondary objective was to present perspectives of rural primary care providers on unmet needs for OHNS services. Study Design Mixed methods database analysis and prospective survey. Setting National administrative database. Subjects and Methods The Canadian Medical Association OHNS provider Masterfile and the Statistics Canada postal code file were used to determine provincial, urban, rural, and Aboriginal group care coverage. The Society of Rural Physicians of Canada was surveyed to explore care delivery and unmet needs for OHNS and audiology. Descriptive statistics and linear regression were used to describe results. Results Ontario and Quebec had the largest annual OHNS physician growth (6.38 providers/year; r2 = 0.94) versus stagnant growth in the territories. The clear majority of OHNS providers are in urban centers, and rural OHNS coverage is decreasing annually (-0.33 providers/year, r2 = 0.28). There are no OHNS providers in 485 population centers where Aboriginal groups are located. A survey of 40 rural primary care providers reported that OHNS care is most commonly delivered through seasonal visits to a local facility, with otology (hearing loss, chronic ear disease) and rhinology (nonmalignant nasal or sinus conditions) as the most frequently reported unmet needs. Conclusion From 2002 to 2013, OHNS coverage showed a trend for urban consolidation. Most Aboriginal groups may have decreased access to care, as there are no OHNS providers in 485 population centers where reserves are located. There is an unmet need for specialized OHNS services reported by rural primary care physicians, especially otology and rhinology.


Observations on the "cascade" of Na-K-ATPase inhibitory and digoxin-like immunoreactive material in human urine: possible relevance to essential hypertension.
Previous investigations have demonstrated an increased amount of a sodium pump inhibitor (N.H.) in plasma from humans with essential hypertension and from animals with various forms of experimental hypertension. The present study has employed Sephadex column and C18 reverse phase separation of urines from patients with essential hypertension and normal controls to distinguish "high", "intermediate" and "low" molecular weight forms of N.H., measured through properties of Na-K-ATPase inhibition and digoxin-like immunoreactivity. The major difference between hypertensive and normotensive urines was a highly significant increase in the "intermediate" molecular weight form of N.H., as measured by Na-K-ATPase inhibition. In contrast, digoxin-like immunoreactivity was significantly decreased in urine from hypertensive patients. The results are compatible with an hypothesis that the defect in some forms of essential hypertension may be partial inhibition of enzymatic conversion of intermediate to final form of N.H., with the increased sodium pump inhibition primarily related to the precursor.


Disinhibition of rostral raphe pallidus neurons increases cardiac sympathetic nerve activity and heart rate.
We determined the cardiovascular effects of microinjecting the GABA(A) receptor antagonist, bicuculline, into the rostral raphe pallidus (RPa) on arterial pressure (AP), heart rate (HR) and cardiac sympathetic nerve activity (CSNA) in urethane-chloralose anesthetized, artificially-ventilated rats. In 26 animals, microinjection of the GABA(A) receptor antagonist, bicuculline (2 mM, 30 nl), into RPa increased CSNA (+234+/-64% of control), HR (+91+/-10 bpm) and mean AP (+16+/-3 mmHg). A similar tachycardia was evoked after removal of both adrenal glands, but was absent after beta-adrenergic receptor blockade with atenolol. Equivalent percentage increases in CSNA and HR were evoked by disinhibition of the rostral RPa neurons after inhibition of cardiovascular sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) with bilateral microinjections of the GABA(A) receptor agonist, muscimol (6 mM, 50 nl) which markedly lowered CSNA, HR and AP. These results indicate that RPa contains a population of neurons, possibly sympathetic premotor neurons with direct projections to spinal cardiac sympathetic preganglionic neurons, that receive a tonic, GABAergic inhibition and thus do not contribute markedly to resting levels of CSNA and HR, but when disinhibited, they can produce large increases in CSNA and HR comparable to those seen during certain stress responses.


Radiographic assessment of the alveolar bone height in children and adolescents with familial dysautonomia.
Familial dysautonomia (FD) is a progressive neuropathy, characterized by somatic and skeletal abnormalities, and by a variety of oral and diet disturbances. The purpose of the study was to assess the alveolar bone height at the molar areas of children and adolescents with FD. The distance from the cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured on routine diagnostic bitewing radiographs of nine males and seven females with FD (mean age = 122 months) and in those of two matching groups (C1 = 119 months; C2 = 122 months). The mean values for the maxilla were significantly larger than those in the mandible. A positive significant correlation was found between the CEJ-ABC measurements of the primary and the permanent teeth, and between the CEJ-ABC measurements and age. The mean values per patient for the CEJ-ABC distances of the FD group were smaller than the control groups, but the difference was not statistically significant. The CEJ-ABC measurements in the primary and the permanent molars were smaller in the FD group, and in the premolars and permanent cuspids they were larger than those in the two control groups. These differences were not statistically significant. No differences were found between the FD and the control groups in the primary cuspids. The alveolar bone height of children and adolescent with familial dysautonomia does not differ from that of healthy controls.


Risk of Recurrence of Low Back Pain: A Systematic Review.
Study Design Systematic review. Background While most people with acute low back pain (LBP) recover quickly, recurrences are believed to be common. To our knowledge, no published high-quality systematic review has assessed the risk of recurrent LBP or the factors that would predict LBP recurrence. Objectives The aim of this study was to investigate the risk of, and prognostic factors for, a recurrence of LBP in patients who have recovered from a previous episode of LBP within the last year. Methods Systematic searches were conducted in the MEDLINE, Embase, and CINAHL databases. We included longitudinal studies of adults who had recovered from a previous episode of LBP within 12 months. The primary outcome was a new episode of LBP. Secondary outcomes were other types of recurrence (eg, episodes causing care seeking). Results Eight studies were included in the review: 7 observational studies and 1 randomized trial (2 publications). Six studies reported recurrence proportions for the primary outcome of an episode of LBP. Meta-analysis was not conducted due to the low quality and heterogeneity of studies. Only 1 study was considered an inception cohort study; it reported a 1-year recurrence proportion of 33%. A history of previous episodes of LBP prior to the most recent episode was the only factor that consistently predicted recurrence of LBP. Conclusion The available research does not provide robust estimates of the risk of LBP recurrence and provides little information about factors that predict recurrence in people recently recovered from an episode of LBP. Level of Evidence Prognosis, 1a-. Prospectively registered in PROSPERO on February 9, 2016 (CRD42016030220). J Orthop Sports Phys Ther 2017;47(5):305-313. Epub 29 Mar 2017. doi:10.2519/jospt.2017.7415.


The use of colposcopy for triage in HPV-positive women aged 65 years and older.
Persistent high-risk HPV infection is associated with an elevated risk for prevalent CIN II + despite normal cytology (NILM). Our study aims to evaluate the clinical relevance of a persistent high-risk HPV infection without cytologic changes in women aged ≥ 65 and to determine the role of colposcopy for triage in these cases. 211 patients aged ≥ 65 with persistent HPV infection and normal cytology (NILM) who presented for colposcopy at five certified centers between January 2021 and April 2022 were included in the study. Colposcopic findings, HPV subtypes, when available, histology and p16/Ki67 staining were assessed as well as individual risk factors such as smoking and previous HPV-related surgery. 87.7% (185/211) of the included women had a type 3 transformation zone. In 83.4% (176/211), a biopsy was taken [thereof 163 endocervical curettages (ECC)]. In 35/211 women (16.6%), sampling was not possible during colposcopy due to an inaccessible cervix, pain during examination or obliteration of the cervical canal. Out of these, 6 women received a diagnostic excision. CIN II + was detected in 10.6% of all histologies (excisional or biopsy) (20/182). 50% of the women with a CIN II + where HPV 16 positive. Taking only the women diagnosed with CIN III or AIS into account, (n = 12) 75% were HPV 16 positive. Interestingly, 80% of the women with CIN II + had an abnormal cytology when repeatedly taken during colposcopy, vice versa an endocervical lesion was diagnosed in 53% of women with abnormal repeat cytology (27/51). The prevalence of CIN II + in women is ≥ 65 with persistent hr HPV infection but NILM cytology is similar to that in younger women. However, more than 85% of the women have a type 3 transformation zone. Colposcopy is, therefore, not helpful to diagnose the women who need treatment in this age group.


The COP II adaptor protein TMED7 is required to initiate and mediate the delivery of TLR4 to the plasma membrane.
Toll-like receptor 4 (TLR4), the receptor for the bacterial product endotoxin, is subject to multiple points of regulation at the levels of signaling, biogenesis, and trafficking. Dysregulation of TLR4 signaling can cause serious inflammatory diseases, such as sepsis. We found that the p24 family protein TMED7 (transmembrane emp24 protein transport domain containing 7) is required for the trafficking of TLR4 from the endoplasmic reticulum to the cell surface through the Golgi. TMED7 formed a stable complex with the ectodomain of TLR4, an interaction that required the coiled-coil and Golgi dynamics (GOLD) domains, but not the cytosolic, coat protein complex II (COP II) sorting motif, of TMED7. Depletion of TMED7 reduced TLR4 signaling mediated by the adaptor protein MyD88 (myeloid differentiation marker 88), but not that mediated by the adaptor proteins TRIF [Toll-interleukin-1 receptor (TIR) domain-containing adaptor protein inducing interferon-β] and TRAM (TRIF-related adaptor molecule). Truncated forms of TMED7 lacking the COP II sorting motif or the transmembrane domain were mislocalized and resulted in ligand-independent signaling that probably arises from receptors accumulated intracellularly. Together, these results support the hypothesis that p24 proteins perform a quality control step by recognizing correctly folded anterograde cargo, such as TLR4, in early secretory compartments and facilitating the translocation of this cargo to the cell surface.


Renin-aldosterone axis in ethanol intoxication during sodium and fluid repletion versus depletion.
Renin-aldosterone axis in acute moderate ethanol intoxication was studied in four healthy males during sodium depletion and during sodium and volume repletion. Ethanol (1.2 g/kg body wt) was taken orally in supine position at a steady rate for 90 min. In sodium-depleted subjects starting levels of plasma renin activity (PRA) and plasma aldosterone were increased as expected. During ethanol intoxication PRA rose further (p less than 0.001), whereas aldosterone showed a decreasing trend, albeit not significant. Thus, a dissociation between PRA and plasma aldosterone was noticed. Increased serum NA+/K+ ratio (p less than 0.02), or an inhibitory action of ethanol on aldosterone secretion, may explain the broken renin-aldosterone nexus. In the second experiment, the subjects were sodium replete. During ethanol intoxication, 1350-1420 ml isotonic NaCl was infused intravenously to compensate for fluid loss due to alcohol diuresis. In that experiment neither PRA nor plasma aldosterone showed significant changes. Thus, dehydration due to alcohol diuresis appears to be the main reason for increased PRA during ethanol intoxication. As in previous studies increased serum Na+/K+ ratio along with rising blood alcohol concentration was observed, independently of sodium and fluid balance.


Abnormal distribution of CD45 isoforms expressed by CD4+ and CD8+ T cells in rheumatoid arthritis.
CD45RO+ T cells are referred to as memory or helper-inducer while CD45RA+ T cells are regarded as naive or suppressor-inducer T cells. The former population predominates in the peripheral blood and even more in the synovial fluid of patients with rheumatoid arthritis, to the expense of the latter population. Within the CD45RB+ compartment, there appears to be more of the fully-differentiated than of the early-differentiated CD4+ T cells. In spite of the fact that these lymphocytes are close to undergoing apoptosis, this programmed cell death is inhibited in the rheumatoid synovium.


[Clinical reasoning and decision-making in practice. A man with hip pain and fever].
A 42-year-old man was admitted to the hospital because of pain in the left hip. On examination he was febrile at 38 degrees C and he walked with a limp. The chest, abdomen and extremities were normal. Laboratory tests showed an elevated ESR and CRP. The ANA test was positive. CT-scan of the abdomen revealed a mass in the psoas region and some dilatation of the left renal pelvis. Following the histological results of the first and second diagnostic percutaneous biopsies, the clinicians suspected idiopathic retroperitoneal fibrosis. They treated the patient with corticosteroids for a period of 4 weeks. After a short interval of improvement this treatment failed and a third biopsy was taken. Subsequently, the diagnosis of anaplastic large cell lymphoma (ALCL) was made. The patient was successfully treated with combination chemotherapy. Usually, in practice, clinical reasoning and decision-making is carried out in accordance with Bayes' theorem. But when the a priori probability of disease is unknown and the likelihood ratio of a diagnostic test unavailable, one has to combine the available 'evidence' with critical thinking, interdisciplinary communication, judgement, intuition and common sense.


Expectation Learning for Stimulus Prediction Across Modalities Improves Unisensory Classification.
Expectation learning is a unsupervised learning process which uses multisensory bindings to enhance unisensory perception. For instance, as humans, we learn to associate a barking sound with the visual appearance of a dog, and we continuously fine-tune this association over time, as we learn, e.g., to associate high-pitched barking with small dogs. In this work, we address the problem of developing a computational model that addresses important properties of expectation learning, in particular focusing on the lack of explicit external supervision other than temporal co-occurrence. To this end, we present a novel hybrid neural model based on audio-visual autoencoders and a recurrent self-organizing network for multisensory bindings that facilitate stimulus reconstructions across different sensory modalities. We refer to this mechanism as stimulus prediction across modalities and demonstrate that the proposed model is capable of learning concept bindings by evaluating it on unisensory classification tasks for audio-visual stimuli using the 43,500 Youtube videos from the animal subset of the AudioSet corpus.


Hippo Deficiency Leads to Cardiac Dysfunction Accompanied by Cardiomyocyte Dedifferentiation During Pressure Overload.
The Hippo pathway plays an important role in determining organ size through regulation of cell proliferation and apoptosis. Hippo inactivation and consequent activation of YAP (Yes-associated protein), a transcription cofactor, have been proposed as a strategy to promote myocardial regeneration after myocardial infarction. However, the long-term effects of Hippo deficiency on cardiac function under stress remain unknown. We investigated the long-term effect of Hippo deficiency on cardiac function in the presence of pressure overload (PO). We used mice with cardiac-specific homozygous knockout of WW45 (WW45cKO), in which activation of Mst1 (Mammalian sterile 20-like 1) and Lats2 (large tumor suppressor kinase 2), the upstream kinases of the Hippo pathway, is effectively suppressed because of the absence of the scaffolding protein. We used male mice at 3 to 4 month of age in all animal experiments. We subjected WW45cKO mice to transverse aortic constriction for up to 12 weeks. WW45cKO mice exhibited higher levels of nuclear YAP in cardiomyocytes during PO. Unexpectedly, the progression of cardiac dysfunction induced by PO was exacerbated in WW45cKO mice, despite decreased apoptosis and activated cardiomyocyte cell cycle reentry. WW45cKO mice exhibited cardiomyocyte sarcomere disarray and upregulation of TEAD1 (transcriptional enhancer factor) target genes involved in cardiomyocyte dedifferentiation during PO. Genetic and pharmacological inactivation of the YAP-TEAD1 pathway reduced the PO-induced cardiac dysfunction in WW45cKO mice and attenuated cardiomyocyte dedifferentiation. Furthermore, the YAP-TEAD1 pathway upregulated OSM (oncostatin M) and OSM receptors, which played an essential role in mediating cardiomyocyte dedifferentiation. OSM also upregulated YAP and TEAD1 and promoted cardiomyocyte dedifferentiation, indicating the existence of a positive feedback mechanism consisting of YAP, TEAD1, and OSM. Although activation of YAP promotes cardiomyocyte regeneration after cardiac injury, it induces cardiomyocyte dedifferentiation and heart failure in the long-term in the presence of PO through activation of the YAP-TEAD1-OSM positive feedback mechanism.


Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India.
This study aimed to evaluate the prevalence of resistance mutations in the protease gene of HIV-1 strains isolated from north Indian antiretroviral (ARV) treatment-naive patients and to assess the phylogenetic relatedness of these strains with known HIV-1 strains. Fifty-four HIV-1 strains isolated from treatment-naive patients (n = 54) were included in this study. Resistance genotyping for the protease gene was performed using semi-nested PCR and DNA sequencing. The sequences were aligned (ClustalW) and a phylogenetic tree was built (MEGA 4 software). Drug resistance (DR) pattern was analyzed using the Stanford HIV-DR database and the IAS-USA mutation list. For subtyping purposes, all the nucleotide sequences were submitted to the REGA HIV-1 subtyping tool version 2.0l. All the strains (100%) were found to belong to the C subtype and to harbor at least two secondary mutations in the protease gene. The most frequent mutations were H69K and I93L (52 of 52 strains), followed by I15V (80.7%), L19I (69.2%), M36I (67.3%), R41K (94.2%), L63P (61.5%), and L89M (82.7%). This study confirms that HIV-1 subtype C predominates in northern India. Protease secondary mutations associated with drug resistance to protease inhibitors (PIs) were present with high frequency in the HIV-1 C subtype strains isolated from north Indian ARV treatment-naive patients, but no primary resistance mutations were found in this region. We suggest that resistance testing in HIV-1 infected patients should ideally be performed before the initiation of therapy to tailor the treatment for the individual to achieve the optimal therapeutic outcome.


Effect of Hemoporfin-mediated photodynamic therapy in the treatment of facial port-wine stains on intraocular pressure.
Photodynamic therapy (PDT) is a potential treatment for port-wine stains (PWS), but its effects on intraocular pressure (IOP) have not been reported. This study evaluated the efficacy of PDT for facial PWS and analyzed the changes in IOP before and after treatment. Data from 32 patients with facial PWS who underwent single PDT treatment at our department were collected. The patients were divided into three groups based on the location of the PWS. Group A (15 cases) involved the eyelid of the eye being measured; Group B (10 cases) was located near the eyes but did not involve the measured eyelid; and Group C (7 cases) was situated on the face but not near the eyes. IOP measurements were taken before and after treatment, and the efficacy and changes in IOP were analyzed. The overall efficacy rates of single PDT were 84.37 %, demonstrating superior efficacy for the pink type, age < 6 years, and skin lesions < 10 cm2 (P < 0.05). The higher IOP was observed on the side with eyelid involvement of PWS (P < 0.001). The IOP of the affected side in Group A decreased by 2.13 ± 2.10 mmHg on average after treatment, which was statistically significant compared with the other two groups (P<0.05). Eyelid involvement in PWS increases the risk of elevated IOP. Hemoporfin-mediated PDT can reduce the IOP in patients with PWS involving the eyelid within a safe range. PDT for facial PWS is considered to be safe and effective.


Rapid HIV Testing on the College Campus: Comparing Traditional and Outreach Models.
The purpose of this study was to compare rapid HIV testing services on a college campus between a clinic-based testing group and an outreach-based testing group. Study participants were 1,233 individuals who underwent HIV counseling and testing. Questionnaires assessed demographics and HIV transmission risk behaviors. Results indicate that outreach-based testers were more likely to be younger, female, and African American relative to clinic-based testers. Overall, 100% of clinic-based testers and 99.5% of outreach-based testers receiving their test results. All individuals with positive rapid test results received confirmatory blood testing and entered medical care within one week of preliminary diagnosis. College campuses may provide a unique setting to deliver HIV testing and may help increase the percentage of young people who are aware of their serostatus, particularly younger, female, and African American students who may be less likely to undergo testing in traditional clinic settings.


Novel excitatory Conus peptides define a new conotoxin superfamily.
A new class of Conus peptides, the I-superfamily of conotoxins, has been characterized using biochemical, electrophysiological and molecular genetic methods. Peptides in this superfamily have a novel pattern of eight Cys residues. Five peptides that elicited excitatory symptomatology, r11a, r11b, r11c, r11d and r11e, were purified from Conus radiatus venom; four were tested on amphibian peripheral axons and shown to elicit repetitive action potentials, consistent with being members of the 'lightning-strike cabal' of toxins that effect instant immobilization of fish prey. A parallel analysis of Conus cDNA clones revealed a new class of conotoxin genes that was particularly enriched (with 18 identified paralogues) in a Conus radiatus venom duct library; several C. radiatus clones encoded the excitatory peptides directly characterized from venom. The remarkable diversity of related I-superfamily peptides within a single Conus species is unprecedented. When combined with the excitatory effects observed on peripheral circuitry, this unexpected diversity suggests a corresponding molecular complexity of the targeted signaling components in peripheral axons; the I-conotoxin superfamily should provide a rich lode of pharmacological tools for dissecting and understanding these. Thus, the I-superfamily conotoxins promise to provide a significant new technology platform for dissecting the molecular components of axons.


Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders.
Schizophrenia, a psychological disorder with enormous societal impact, is a result of abnormalities in gene expression and dysregulation of the immune response in the brain. Few studies have been conducted to understand its etiology, however, the exact molecular mechanism largely remains unknown, though some poorly understood theories abound. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis. We retrieved genome-wide mRNA expression data and clinico-pathological information from five independent studies of schizophrenic patients from Gene Expression Omnibus database. We continued further with three studies having common platform. Our result showed a total of 527 differentially expressed genes of which 314 are up regulated and 213 are down regulated. After adjusting the sources of variation, we carried out pathway and gene ontology analysis, and observed alteration of 14-3-3-mediated signaling, γ-aminobutyric acid receptor signaling, role of nuclear factor of activated T-cells in regulation of the immune response, G beta gamma signaling, dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 feedback in cAMP signaling, complement system, axonal guidance signaling, dendritic cell maturation, cAMP response element-binding protein signaling in neurons and interleukin-1 signaling pathways and networks. Conclusively, our global gene expression pathway and gene set enrichment analysis studies suggest disruption of many common pathways and processes, which links schizophrenia to immune and central nervous system. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis.


Identification of mRNAs associated with programmed cell death in immature thymocytes.
Programmed cell death is an essential cellular process that occurs in epithelial turnover, neural development, and regulation of cell populations of the immune system. Thymocytes undergo programmed cell death in response to several inductive stimuli, including exposure to glucocorticoids or radiation. This program can be blocked by inhibitors of RNA or protein synthesis; this implies that new proteins are required to execute the death programs. To search for possible death-associated mRNAs, we directionally cloned cDNA representing mRNA from control and dexamethasone-treated thymocytes. These libraries were used to produce ample amounts of DNA and RNA used in subtractive hybridization for the removal of sequences present in both control and induced cells. The remaining unhybridized sequences were selectively amplified by polymerase chain reaction and cloned to produce a library enriched for sequences expressed in death-induced cells. From this library we isolated cDNAs of death-associated mRNAs. One of these mRNAs, RP-8, appears within 1 h after exposure to gamma radiation, and a second mRNA, RP-2, is observed within 2 h. Both of these mRNAs accumulate during a period when a reference mRNA, actin, is declining. RP-2 and RP-8 are no longer detectable after 6 h postinduction, when apoptosis and mRNA degradation are evident in the culture. Sequence analysis of RP-8 cDNA indicates the presence of a zinc finger domain suggestive of a possible DNA regulatory role for the RP-8 protein. cDNA sequence results on RP-2 classify the corresponding protein as an integral membrane protein. We conclude that RP-2 and RP-8 are death-associated mRNAs that should be functionally evaluated in the context of the death process. As previously suggested, it may be that a family of "death genes" is activated by various stimuli depending on the type of cell, in a manner somewhat analogous to the induction of heat shock (stress) protein genes.


[Chemical speciation and pollution characteristics of soil mercury in mercury deposit area of Western Hunan-Eastern Guizhou province].
By the BCR extraction procedures and HG-ICP-AES technique, the chemical speciation and pollution characteristics of soil mercury in typical mercury deposit areas of Western Hunan-Eastern Guizhou province were studied. It was found that the concentrations of mercury in soils are dominated by residual form, followed by organic-sulfide form. Fe-Mn oxides and acid-exchangeable form are rather low. The percent of the four mercury species in soils are 85.77%, 12.44%, 0.93% and 0:86%, respectively. The total concentrations and each species of mercury in soils show positive relationship with the concentration of sands, and negative relationship with the concentration of clays in soils. They also increase with the soil pH value. Mercury concentration in soils has spatial changes. In general, the concentrations in the surface soil are higher than those of sub-surface soils. Furthermore, the concentrations rapidly decrease with the distance from the pollution source increased and vary among different soil samples from different location and land use type. The results indicated that exogenous mercury pollution caused by human activities provides significant influence on environmental toxicity and pollution characteristics of mercury in soils of mercury deposit area.


Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease.
Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future. To compare the efficacy and safety of adjuvant ropinirole therapy with bromocriptine in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications. Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with SmithKline Beecham. Randomised controlled trials of ropinirole versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. No significant differences between ropinirole and bromocriptine were found in off time reduction, dyskinesia as an adverse event, motor impairment and disability, or levodopa dose reduction. Withdrawal rates and adverse event frequency were similar with the two agents apart from significantly less nausea with ropinirole (odds ratio 0.50; 0.29, 0. 84 95% CI; p =0.01). Ropinirole is at least as good as bromocriptine in patients with Parkinson's disease with motor complications in terms of improving off time and reducing levodopa dose, without increasing adverse events including dyskinesia. However, these comparitor studies may have been underpowered to detect clinically meaningful differences between the agonists. Further, much larger, phase IV studies are required to examine the efficacy, effectiveness, and safety of all of the dopamine agonists as adjuvant therapy in Parkinson's disease.


Automated black-box boundary value detection.
Software systems typically have an input domain that can be subdivided into sub-domains, each of which generates similar or related outputs. Testing it on the boundaries between these sub-domains is critical to ensure high-quality software. Therefore, boundary value analysis and testing have been a fundamental part of the software testing toolbox for a long time and are typically taught early to software engineering students. Despite its many argued benefits, boundary value analysis for a given software specification or application is typically described in abstract terms. This allows for variation in how testers apply it and in the benefits they see. Additionally, its adoption has been limited since it requires a specification or model to be analysed. We propose an automated black-box boundary value detection method to support software testers in performing systematic boundary value analysis. This dynamic method can be utilized even without a specification or model. The proposed method is based on a metric referred to as the program derivative, which quantifies the level of boundariness of test inputs. By combining this metric with search algorithms, we can identify and rank pairs of inputs as good boundary candidates, i.e., inputs that are in close proximity to each other but with outputs that are far apart. We have implemented the AutoBVA approach and evaluated it on a curated dataset of example programs. Furthermore, we have applied the approach broadly to a sample of 613 functions from the base library of the Julia programming language. The approach could identify boundary candidates that highlight diverse boundary behaviours in over 70% of investigated systems under test. The results demonstrate that even a simple variant of the program derivative, combined with broad sampling and search over the input space, can identify interesting boundary candidates for a significant portion of the functions under investigation. In conclusion, we also discuss the future extension of the approach to encompass more complex systems under test cases and datatypes.


A novel approach to flea control on cats, using pyriproxyfen.
Pyriproxyfen is a new insect growth regulator with potent activity against developing stages of the cat flea, Ctenocephalides felis. To determine its duration of action after application as a spot-on topical treatment, 20 cats were allocated to two groups. One group acted as untreated controls, and each cat in the other was given a single dose of 1 mg/kg pyriproxyfen. Each cat was infected with fleas at weekly intervals and caged. Eggs were collected and their viability determined as a measure of the effect of the agent on adult fleas. The effect of the transfer of pyriproxyfen from each cat to its immediate surroundings was monitored by observing the development of fertile flea eggs placed on samples of blanket taken from each cage. Results from untreated control cats showed that the experimental conditions were favourable for the lifecycle of the flea. Flea reproduction on treated cats was inhibited completely for seven weeks and substantially for at least a further two weeks. Blankets used by cats treated up to two weeks previously prevented flea development entirely and substantial control was still achieved up to four weeks after treatment.


Stability of fronts in the Kuramoto-Sivashinsky equation advected by a Poiseuille flow.
We study reaction fronts described by the Kuramoto-Sivashinsky equation subject to a Poiseuille flow. The fronts propagate with or against the flow located inside a two-dimensional slab. Steady front profiles can be flat, axisymmetric, or nonaxisymmetric, depending on the gap between the plates and the average flow speed. We first obtain the steady front solutions, later executing a linear stability analysis to determine the stability of the fronts. Applying fluid flow can turn initially unstable fronts into stable fronts. Stable steady fronts propagating in the adverse direction of the Poiseuille flow are axisymmetric for slow fluid flows. However, for higher speeds an adverse flow can lead to stable nonaxisymmetric fronts. We also show regions of bistability where stable nonaxisymmetric and axisymmetric fronts can coexist.


2-Phenylpyridine- and 2-(benzo[b]thiophen-2-yl)pyridine-based o-carboranyl compounds: impact of the structural formation of aromatic rings on photophysical properties.
2-Phenylpyridine- and 2-(benzo[b]thiophen-2-yl)pyridine-based (ppy- and btp-based) o-carboranyl (Car1 and Car2) and their B(CH3)2-C∧N-chelated (Car1B and Car2B) compounds were prepared and fully characterised by multinuclear NMR spectroscopy and elemental analysis. The solid-state structure of Car2B was determined by single-crystal X-ray diffraction, which revealed a four-coordinated dimethylboryl centre. All compounds displayed major absorption bands that were assigned to π-π* transitions involving the ppy and btp moieties, as well as weak intramolecular charge-transfer (ICT) transitions between the o-carboranes and their aryl groups. Furthermore, the chelated compounds exhibited dominant low-energy absorption bands (λabs = 333 nm for Car1B and 383 nm for Car2B) resulting from the reinforcement of ICT transitions that correspond to the o-carborane moieties through the restriction of aromatic-ring free rotation. While Car1 and Car2 did not exhibit photoluminescence emissions in toluene at 298 K, Car1B and Car2B showed intense emissions, which are assignable to π-π* transitions associated with each chelated aryl group. However, Car1 and Car2 evidently emitted at around 450 nm in solution at 77 K, invoked by radiative ICT transitions between the carborane and the ppy or btp moiety, indicating that ICT-based radiative decay is only invigorated in the rigid state in the absence of structural variations, such as C-C bond fluctuations in the carborane cage and aromatic-ring free rotation. Interestingly, while Car1 in the film state exhibited a weak ICT-based emission spectrum, and Car1B and Car2B showed intense emissions originating from π-π* transitions associated with each chelated aryl group, Car2 showed significantly enhanced emissions in the same energy region as that exhibited in solution at 77 K, resulting in a much larger quantum efficiency over that in solution. DFT-optimised structures of Car1 and Car2 in their ground and the first-excited states clearly reveal that the enhanced emissive features of Car2 in the film state are strongly associated with the retained planarity of the btp moiety in both the ground and excited states. The photophysical results for these o-carboranyl compounds definitively reveal that the planarities of the aryl groups appended to the o-carborane decisively affect the efficiency of radiative decay based on ICT involving the o-carborane.


Symptom scores and medication treatment patterns in children with ADHD versus autism.
Most children with autism have ADHD, and children with ADHD-Combined and children with autism have high rates of irritable, oppositional, and aggressive behavior. Despite similar symptoms, prescribing practices may differ between autism and ADHD, which has not been examined in a single study. 1407 children with autism and 1036 with ADHD without autism, 2-17 years, were compared with 186 typical peers. Symptom scores were maternal Pediatric Behavior Scale ratings in eight areas (ADHD, oppositional/aggressive, irritable/angry, anxious, depressed, and social, writing, and learning problems). Psychotropics were prescribed to 38.0% with ADHD-Combined, 33.3% with autism, and 20.2% with ADHD-Inattentive, most often an ADHD medication (22.1% stimulant, 2.3% atomoxetine), antipsychotic (7.8%), SSRI (5.5%), and alpha agonist (4.9%). ADHD medications were more often prescribed than other medications in all diagnostic groups. Compared to autism, children with ADHD-Combined were more likely to be prescribed an ADHD medication, whereas antipsychotics and SSRIs were more likely to be prescribed in autism than in ADHD-Combined. Children with ADHD-Inattentive were least impaired and least likely to be medicated. More severely impaired children were more often medicated regardless of diagnosis. Symptom scores were far worse for treated and untreated children with ADHD and with autism than for typical peers.


Kv1 channels and neural processing in vestibular calyx afferents.
Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K(+) channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K(+) channels could help alleviate vestibular dysfunction on earth and in space.


Correlation between plant cell wall stiffening and root extension arrest phenotype in the combined abiotic stress of Fe and Al.
The plasticity and growth of plant cell walls (CWs) remain poorly understood at the molecular level. In this work, we used atomic force microscopy (AFM) to observe elastic responses of the root transition zone of 4-day-old Arabidopsis thaliana wild-type and almt1-mutant seedlings grown under Fe or Al stresses. Elastic parameters were deduced from force-distance curve measurements using the trimechanic-3PCS framework. The presence of single metal species Fe2+ or Al3+ at 10 µM exerts no noticeable effect on the root growth compared with the control conditions. On the contrary, a mix of both the metal ions produced a strong root-extension arrest concomitant with significant increase of CW stiffness. Raising the concentration of either Fe2+ or Al3+ to 20 µM, no root-extension arrest was observed; nevertheless, an increase in root stiffness occurred. In the presence of both the metal ions at 10 µM, root-extension arrest was not observed in the almt1 mutant, which substantially abolishes the ability to exude malate. Our results indicate that the combination of Fe2+ and Al3+ with exuded malate is crucial for both CW stiffening and root-extension arrest. However, stiffness increase induced by single Fe2+ or Al3+ is not sufficient for arresting root growth in our experimental conditions.


Co-digestion of by-products and agricultural residues: A bioeconomy perspective for a Mediterranean feedstock mixture.
This study focused on applying batch and continuous co-digestion approaches to investigate the effects of a feedstock mixture (FM) constituted by ten Mediterranean feedstocks highly available in the Mediterranean area (i.e., olive pomace, olive mill wastewater, citrus pulp, poultry litter, poultry and cattle manure, whey and cereal straw) on methane production for bioenergy generation. For the same feedstock mixture (FM), two different anaerobic digestion (AD) tests were carried out to evaluate the possible inhibitory effects of some biomasses on the biological process. The first AD test showed a methane yield equal to 229 Nm3CH4/tVS (27% lower than that measured during the batch test). During the second AD test, the specific production was 272 m3CH4/tVS. Both tests showed a similar methane content of methane in the biogas, equal to about 57%. The first AD test showed an inhibition effect of the process: total conversion of the organic matter into biogas was not ended. The second batch test demonstrated that the selected FM could be viable to carry out the co-digestion and could provide a flexible solution to generate advanced biofuels in biogas plants located in the Mediterranean area.


Structural modification of a base disaccharide alters antiadhesion properties towards Yersinia pestis.
Incubation in the presence of structurally modified disaccharides altered the in vitro attachment of Yersinia pestis GB to three human respiratory epithelial cell lines. Each disaccharide resulted in decreased attachment to the alveolar epithelial (A549) cell line. The best inhibitor of attachment for each cell line was the benzylated derivative of Galbeta1-4GalNAc. Highly negatively charged saccharides were efficient inhibitors, particularly for the bronchial epithelial (BEAS2-B) cell line. The data indicate that targeted modification of receptor ligands could offer a novel therapeutic preventing Y. pestis attachment to host cells.


Graphene based flexible electrochromic devices.
Graphene emerges as a viable material for optoelectronics because of its broad optical response and gate-tunable properties. For practical applications, however, single layer graphene has performance limits due to its small optical absorption defined by fundamental constants. Here, we demonstrated a new class of flexible electrochromic devices using multilayer graphene (MLG) which simultaneously offers all key requirements for practical applications; high-contrast optical modulation over a broad spectrum, good electrical conductivity and mechanical flexibility. Our method relies on electro-modulation of interband transition of MLG via intercalation of ions into the graphene layers. The electrical and optical characterizations reveal the key features of the intercalation process which yields broadband optical modulation up to 55 per cent in the visible and near-infrared. We illustrate the promises of the method by fabricating reflective/transmissive electrochromic devices and multi-pixel display devices. Simplicity of the device architecture and its compatibility with the roll-to-roll fabrication processes, would find wide range of applications including smart windows and display devices. We anticipate that this work provides a significant step in realization of graphene based optoelectronics.


Susceptibility to Fear of Heights in Bilateral Vestibulopathy and Other Disorders of Vertigo and Balance.
Aims: To determine the susceptibility to visual height intolerance (vHI) in patients with acquired bilateral vestibulopathy (BVP). The question was whether postural instability in BVP, which is partially compensated for by visual substitution of the impaired vestibular control of balance, leads to an increased susceptibility. This is of particular importance since fear of heights is dependent on body posture, and visual control of balance at heights can no longer substitute vestibular input. For comparison susceptibility to vHI was determined in patients with other vestibular or functional disorders. Methods: A total of 150 patients aged 18 or above who had been referred to the German Center for Vertigo and Balance Disorders and diagnosed to have BVP were surveyed with a standardized questionnaire by specifically trained neurological professionals. Further, 481 patients with other vestibular or functional disorders were included. Results: Susceptibility to vHI was reported by 29% (32 % in females, 25% in males) of the patients with BVP. Patients with vHI were slightly younger (67 vs. 71 years). Seventy percent of those with vHI reported avoidance of climbing, hiking, stairs, darkness, cycling or swimming (84% of those without vHI). Mean age for onset of vHI was 40 years. Susceptibility to vHI was higher in patients with other vertigo disorders than in those with BVP: 64% in those with phobic postural vertigo, 61% in vestibular migraine, 56% in vestibular paroxysmia, 54% in benign paroxysmal positional vertigo, 49% in unilateral vestibulopathy and 48% in Menière's disease. Conclusions: The susceptibility to vHI in BVP was not higher than that of the general population (28%).This allows two explanations that need not be alternatives but contribute to each other: (1) Patients with a bilateral peripheral vestibular deficit largely avoid exposure to heights because of their postural instability. (2) The irrational anxiety to fall from heights triggers increased susceptibility to vHI, not the objective postural instability. However, patients with BVP do not exhibit increased comorbid anxiety disorders. This view is supported by the significantly increased susceptibility to vHI in other vestibular syndromes, which are characterized by an increased comorbidity of anxiety disorders.


Human T-cell lymphotropic virus infection among blood donors in south Florida. The Transfusion Safety Study Group.
Knowledge of the epidemiologic pattern of human T-lymphotropic virus (HTLV) in the United States is being enlarged by blood donor screening. We tested stored sera from 29,937 donations made in South Florida in 1984-1985. Twenty-three donors were confirmed as seropositive, a prevalence of 0.8 per 1,000 donations. Specificity was supported by serologic retesting and virus culture of 11 donors located for follow-up. Sex- and age-specific prevalences did not differ significantly; blacks, however, accounted for 65% of seropositive donations. Within South Florida, one section of Miami had a prevalence of 4.5 per 1,000 donations, significantly above the 0.1 to 1.1 per 1,000 rates for other parts. An epidemiologic association with known HTLV-I endemic areas could account for most infections; all seven typed isolates were characterized as HTLV-I. Exposures, however, were diverse, sometimes multiple, and had no necessary relationship to personal lifestyle. This finding suggests that sources of infection were varied. Seropositive family members emphasize familial clustering of HTLV-I infection.


Treating immigrant patients in psychiatric emergency rooms.
We examine whether patient variables (geographic origin, gender, Spanish language proficiency) and subjective clinician aspects in emergency department psychiatric encounters (diagnostic certainty, clinician's comfort level with patient) are associated with diagnosis and the use of coercive measures. Using a descriptive cross-sectional design, we recorded 467 visits (400 foreign-born and 67 native-born patients) in hospital psychiatry emergency rooms (ERs) in Barcelona between 2007 and 2015. We first assessed the association of patient variables and subjective clinician aspects of psychiatric encounters with service use outcomes and with mental illness diagnosis. Fitted logistic models predicted the likelihood of service use outcomes and estimated the propensity of receiving each diagnosis. The null model evaluated the role of patient's geographical origin, while the full model evaluated the additional roles of patient's gender and language, the clinician's assessment of the influence of culture in diagnosis, and clinician comfort with two outcomes: patient's diagnosis and use of coercive measures in the ER. Women were less likely to receive coercive measures or intramuscular medications compared to men. Significant ethnic/racial and gender differences were found in receiving certain diagnoses. Additionally, a patient's lower Spanish proficiency was correlated with a higher probability of receiving a psychosis diagnosis. The clinician's level of diagnostic certainty was also positively correlated with increasing clinician-reported comfort with patient. Overall, ethnic factors and the subjective aspects of psychiatric encounters were found to influence diagnosis and the use of coercive measures. Cultural competency programs and interpreter services within psychiatric ER settings should thus be required.


Photopic and scotopic flicker sensitivity of a rod monochromat.
The sensitivity to sine-wave flicker of a rod monochromat was compared with that of a normal subject at photopic and scotopic levels of luminance. The sensitivity of the rod monochromat in the low-frequency region (below 3 Hz at scotopic levels and below 12 to 14 Hz at photopic levels) was found to be superior to that of the control. This superiority was most pronounced at photopic levels, where the rod monochromat frequently showed a two-peak sensitivity curve.


DNA breakage in human lung carcinoma cells and nuclei that are naturally sensitive or resistant to etoposide and teniposide.
Evidence suggests that the anticancer agents etoposide (VP16-213) and teniposide (VM26) produce DNA breaks and cytotoxicity by interaction with type II topoisomerase. Therefore, levels of type II topoisomerase may influence sensitivity to VP16-213 and VM26. We have characterized four lung carcinoma-derived cell lines for natural sensitivity or resistance to VP16-213 and VM26. Included in this study were two small cell lung carcinoma lines (SW900 and SW1271), an adenocarcinoma line (A549), and a large cell carcinoma (H157). SW1271 was the most sensitive line with a median inhibitory concentration for cell proliferation of 0.5 microM for VM26 and 2.7 microM for VP16-213, and SW900 was the most resistant with median inhibitory concentration values of 2.0 and 16 microM, respectively. A549 and H157 cells were intermediate in sensitivity to these drugs. Alkaline elution techniques were used to study in vivo formation and repair of single and double strand DNA breaks. Single strand DNA breaks were observed in SW1271 cells exposed to as little as 10 nM VM26 or 100 nM VP16-213 for 1 h, whereas SW900 cells required exposure to 10-fold higher concentrations of VM26 or VP16-213 to produce similar results. Single strand DNA breaks predominated only in SW1271 and A549 cells and then, only at low drug concentrations, whereas the ratios between single and double strand DNA breaks decreased at higher drug concentrations. Plots of cytotoxicity versus single and double strand DNA breakage revealed that cytotoxicity produced by both drugs was more closely related to double strand DNA break formation in all four cell lines. DNA breaks appeared rapidly upon addition of drug, reaching plateaus in DNA breaks within 30 min, and repair of both single and double strand DNA breaks occurred rapidly with time to repair one-half of the DNA breaks of 20 to 60 min in all four cell lines upon removal of drug, arguing against repair as a mechanism for drug resistance. DNA breakage was also observed in nuclei isolated from SW900 and SW1271 cells in similar magnitude to that observed in the respective cells. Results indicate that DNA breakage plateaus may reflect a steady-state equilibrium established between the drug and its nuclear target, possibly type II topoisomerase, and suggest that natural resistance to VP16-213 and VM26 may be due to different enzyme levels in sensitive and naturally resistant cells.