Differences in traditional and emerging cardiovascular risk factors of subjects discordantly classified by metabolic syndrome definitions of the International Diabetes Federation and the National Cholesterol Education Program.
Several working definitions of metabolic syndrome have been proposed for clinical use. However, individuals can be discordantly classified as having or not having metabolic syndrome depending on the choice of one or another definition. This study compared the cardiovascular risk profile of subjects concordantly and discordantly diagnosed by the criteria of the National Cholesterol Education Program (NCEP) and the criteria of the International Diabetes Federation (IDF). Nine hundred and twenty-nine non-diabetic adult subjects belonging to a cross-sectional population-based study in Gran Canaria island (Spain) were assessed. Participants completed a questionnaire and underwent physical examination, fasting blood analyses, and a standardized oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5 (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol, triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1 (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in contrast to subjects meeting both criteria, those that fulfilled only the IDF criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose, glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly different from those observed in subjects without metabolic syndrome. The IDF definition identifies a surplus of individuals whose cardiovascular risk profile, particularly regarding to some non-traditional cardiovascular risk factors, is less adverse than that observed in subjects also diagnosed by the NCEP definition.


Pathogenicity of Salmonella enteritidis phage types 4, 8 and 23 in specific pathogen free chicks.
The pathogenicity of two isolates of Salmonella enterica serovar Enteritidis (SE) phage type (PT) 4, three of PT8 and one of PT23 was investigated in groups of 1-day-old specific pathogen free White Leghorn chicks. Two groups were crop gavaged with each culture but at two different doses. Two additional groups were given Salmonella enterica serovar Pullorum (SP) at similar doses and one further group served as uninoculated controls. Body weights were recorded at 14, 21, and 28 days postinoculation (d.p.i), and mortality was monitored throughout. In most treatment groups, the average body weights were significantly lower than the controls. Birds inoculated with SP had the highest mortality followed by those given SE PT4 of human or chicken origin. At 14 and 21 d.p.i., four chicks from each group were killed and examined for gross lesions. Selected tissues were collected for histopathology and cultured for bacteria. Dead birds had fibrinous exudate in the pericardium and also, in a few, on the liver capsule. They had enlarged livers, sometimes with congestion and white foci. At 7 d.p.i., several birds, especially those inoculated with SE PT4, had retained yolk sacs containing coagulated material. Microscopic lesions of pericarditis, myocarditis, hepatitis, splenitis, peritonitis and enteritis were present at 7 d.p.i. in most birds inoculated with SE, but was greatly variable at 14 d.p.i.. This study shows that 1-day-old SPF chicks are susceptible to various phage types of SE, with yolk-sac infection as the most prominent feature.


Characterization of neuronal intrinsic properties and synaptic transmission in layer I of anterior cingulate cortex from adult mice.
The neurons in neocortex layer I (LI) provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC), a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors), and inhibitory inputs (which were mediated by GABA(A) receptors). Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.


Power and Phase of Alpha Oscillations Reveal an Interaction between Spatial and Temporal Visual Attention.
Oscillatory brain rhythms can bias attention via phase and amplitude changes, which modulate sensory activity, biasing information to be processed or ignored. Alpha band (7-14 Hz) oscillations lateralize with spatial attention and rhythmically inhibit visual activity and awareness through pulses of inhibition. Here we show that human observers' awareness of spatially unattended targets is dependent on both alpha power and alpha phase at target onset. Following a predictive directional cue, alpha oscillations were entrained bilaterally using repetitive visual stimuli. Subsequently, we presented either spatially cued or uncued targets at SOAs either validly or invalidly predicted in time by the entrainers. Temporal validity maximally modulated perceptual performance outside the spatial focus of attention and was associated with both increased alpha power and increased neural entrainment of phase in the hemisphere processing spatially unattended information. The results demonstrate that alpha oscillations represent a pulsating inhibition, which impedes visual processing for unattended space.


The effects of high altitude trekking on body composition and resting metabolic rate.
Resting metabolic rate (RMR) and body composition were evaluated in 12 healthy volunteers before and after 16 days of high altitude trekking and climbing. RMR was measured by indirect calorimetry and body composition by electrical impedance. A 29% reduction in energy intake during high altitude exposure was observed. Fat mass loss averaged about 2.2 kg (p < 0.05) and lean body mass about 1.1 kg, which was almost significant (p = 0.07). As expected, estimated RMR at the end of the expedition--calculated by predictive formulae including body fat and lean body mass as covariates--was significantly reduced by 119 kcal/day as a consequence of the reduction in body weight. Measured RMR values, on the contrary, did not show any significant decline. In conclusion our study showed that high altitude trekking induced a weight loss due approximately 2/3rds to fat mass and 1/3rd to lean body mass. Decreased energy efficiency, which was still present several days after returning to sea level, may have helped contribute to weight loss due to reduced energy intake.


[3H]ouabain autoradiography of frog retina.
The kinetics and distribution of ouabain binding in retinas of Rana pipiens were examined quantitatively by scintillation counting and freeze-dry autoradiography. The time-course of binding at several concentrations was consistent with a bimolecular reaction. Estimated equilibrium binding levels gave a Michaelis-Menton relationship with a Km = 8.3 x 10(-8) M and a maximum binding level (Bmax) = 4.4 x 10(-8) mol/g protein. The distribution of binding sites measured autoradiographically varied considerably between layers. The photoreceptor, inner plexiform, and optic nerve fiber layers exhibited the heaviest binding. Within the photoreceptor layer, binding was nonuniform. Binding in the outer segment decreased distally, averaging approximately 4% of that in the proximal receptor layers (Bmax = 4.6 x 10(-6) M). The origin of the outer segment activity is uncertain at light microscope resolution, as it may be a result of inner segment calyceal processes. Binding within the proximal receptor layers was also nonuniform. Several peaks were observed, with those at the inner segment and synaptic layers being especially noticeable. Assuming an absence of glial cell binding in the proximal receptor layers, we calculated there to be 13 x 10(6) ouabain or Na+,K+ pump sites per rod receptor. Limited measurements suggest a Bmax of approximately 8 x 10(-6) M for the inner plexiform layer.


Quantification of plasminogen activator activity associated with herpesvirus-transformed cells.
Herpesvirus-transformed cell lines were examined for plasminogen activator (PA) activity using a quantitative assay. Previous results of cold fibrin overlay assays indicated that herpesvirus-transformed hamster cell lines produce fibrinolytic activity. Quantification of this activity involved the use of an 125I-fibrin lysis assay in which medium previously incubated with transformed or normal cells was tested for its ability to lyse 125I-fibrin polymers. This assay indicated an enhanced production of plasminogen-dependent fibrinolytic activity by transformed hamster cells compared to hamster embryo fibroblasts. The kinetics of secretion failed to reveal a significant difference in plasminogen activator activity in cells transformed by either herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); however, transformed cells exhibited a significant increase in activity over non-transformed cells. Further characterization of PA activity associated with cells transformed by HSV-1 or HSV-2 has revealed that the protease is secreted and can function extracellularly. Extracellular PA activity produced by HSV-transformed cells is detected more efficiently than the cell-associated enzyme. Extracellular PA can be induced in two different species of cells by infection with partially inactivated HSV-2. Lytic infection of human embryo lung cells by HSV-2 strain 333 did not enhance activity, but infection of these cells with virus inactivated by u.v. irradiation resulted in increased PA levels from the cells. Increased enzyme levels were also detected in hamster embryo fibroblasts infected with partially inactivated virus. Further investigation of this enzyme function may determine whether increased levels of protease will indicate oncogenic transformation in vitro by herpesviruses.


Comparative Genomics of Rhodococcus equi Virulence Plasmids Indicates Host-Driven Evolution of the vap Pathogenicity Island.
The conjugative virulence plasmid is a key component of the Rhodococcus equi accessory genome essential for pathogenesis. Three host-associated virulence plasmid types have been identified the equine pVAPA and porcine pVAPB circular variants, and the linear pVAPN found in bovine (ruminant) isolates. We recently characterized the R. equi pangenome (Anastasi E, et al. 2016. Pangenome and phylogenomic analysis of the pathogenic actinobacterium Rhodococcus equi. Genome Biol Evol. 8:3140-3148.) and we report here the comparative analysis of the virulence plasmid genomes. Plasmids within each host-associated type were highly similar despite their diverse origins. Variation was accounted for by scattered single nucleotide polymorphisms and short nucleotide indels, while larger indels-mostly in the plasticity region near the vap pathogencity island (PAI)-defined plasmid genomic subtypes. Only one of the plasmids analyzed, of pVAPN type, was exceptionally divergent due to accumulation of indels in the housekeeping backbone. Each host-associated plasmid type carried a unique PAI differing in vap gene complement, suggesting animal host-specific evolution of the vap multigene family. Complete conservation of the vap PAI was observed within each host-associated plasmid type. Both diversity of host-associated plasmid types and clonality of specific chromosomal-plasmid genomic type combinations were observed within the same R. equi phylogenomic subclade. Our data indicate that the overall strong conservation of the R. equi host-associated virulence plasmids is the combined result of host-driven selection, lateral transfer between strains, and geographical spread due to international livestock exchanges.


Improved sugar co-utilisation by encapsulation of a recombinant Saccharomyces cerevisiae strain in alginate-chitosan capsules.
Two major hurdles for successful production of second-generation bioethanol are the presence of inhibitory compounds in lignocellulosic media, and the fact that Saccharomyces cerevisiae cannot naturally utilise pentoses. There are recombinant yeast strains that address both of these issues, but co-utilisation of glucose and xylose is still an issue that needs to be resolved. A non-recombinant way to increase yeast tolerance to hydrolysates is by encapsulation of the yeast. This can be explained by concentration gradients occuring in the cell pellet inside the capsule. In the current study, we hypothesised that encapsulation might also lead to improved simultaneous utilisation of hexoses and pentoses because of such sugar concentration gradients. In silico simulations of encapsulated yeast showed that the presence of concentration gradients of inhibitors can explain the improved inhibitor tolerance of encapsulated yeast. Simulations also showed pronounced concentration gradients of sugars, which resulted in simultaneous xylose and glucose consumption and a steady state xylose consumption rate up to 220-fold higher than that found in suspension culture. To validate the results experimentally, a xylose-utilising S. cerevisiae strain, CEN.PK XXX, was constructed and encapsulated in semi-permeable alginate-chitosan liquid core gel capsules. In defined media, encapsulation not only increased the tolerance of the yeast to inhibitors, but also promoted simultaneous utilisation of glucose and xylose. Encapsulation of the yeast resulted in consumption of at least 50% more xylose compared with suspended cells over 96-hour fermentations in medium containing both sugars. The higher consumption of xylose led to final ethanol titres that were approximately 15% higher. In an inhibitory dilute acid spruce hydrolysate, freely suspended yeast cells consumed the sugars in a sequential manner after a long lag phase, whereas no lag phase was observed for the encapsulated yeast, and glucose, mannose, galactose and xylose were utilised in parallel from the beginning of the cultivation. Encapsulation of xylose-fermenting S. cerevisiae leads to improved simultaneous and efficient utilisation of several sugars, which are utilised sequentially by suspended cells. The greatest improvement is obtained in inhibitory media. These findings show that encapsulation is a promising option for production of second-generation bioethanol.


Long-term Comparative Effectiveness of Telemedicine in Providing Diabetic Retinopathy Screening Examinations: A Randomized Clinical Trial.
Minimal information exists regarding the long-term comparative effectiveness of telemedicine to provide diabetic retinopathy screening examinations. To compare telemedicine to traditional eye examinations in their ability to provide diabetic retinopathy screening examinations. From August 1, 2006, through September 31, 2009, 567 participants with diabetes were randomized and followed up to 5 years of follow-up (last date of patient follow-up occurred on August 6, 2012) as part of a multicenter randomized clinical trial with an intent to treat analysis. We assigned participants to telemedicine with a nonmydriatic camera in a primary care medical clinic (n = 296) or traditional surveillance with an eye care professional (n = 271). Two years after enrollment, we offered telemedicine to all participants. Percentage of participants receiving annual diabetic retinopathy screening examinations, percentage of eyes with worsening diabetic retinopathy during the follow-up period using a validated scale from stage 0 (none) to stage 4 (proliferative diabetic retinopathy), and percentage of telemedicine participants who would require referral to an eye care professional for follow-up care using a cutoff of moderate diabetic retinopathy or worse, the presence of macular edema, or an unable-to-determine result for retinopathy or macular edema. The telemedicine group was more likely to receive a diabetic retinopathy screening examination when compared with the traditional surveillance group during the 6-month or less (94.6% [280/296] vs 43.9% [119/271]; 95% CI, 46.6%-54.8%; P < .001) and greater than 6-month through 18-month (53.0% [157/296] vs 33.2% [90/271]; 95% CI, 16.5%-23.1%; P < .001) time bins. After we offered telemedicine to both groups, we could not identify a difference between the groups in the percentage of diabetic retinopathy screening examinations. Diabetic retinopathy worsened by 2 stages or more in 35 (8.6%) of 409 participants (95% CI, 5.8%-11.2%) and improved by 2 stages or more in 5 (1.2%) of 409 participants (95% CI, 0.1%-2.3%) during the 4-year period. The percent of telemedicine participants requiring referral ranged from 19.2% (52/271) to 27.9% (58/208). Telemedicine increased the percentage of diabetic retinopathy screening examinations, most participants did not require referral to an eye care professional, and diabetic retinopathy levels were generally stable during the study period. This finding suggests that primary care clinics can use telemedicine to screen for diabetic retinopathy and monitor for disease worsening over a long period. clinicaltrials.gov Identifier: NCT01364129.


Primary renal lymphoma. Case report and review of the literature.
Primary renal lymphoma is not well recognized, although secondary renal involvement from systemic lymphoma is common. A case of non-Hodgkin's B-cell-type malignant lymphoma in the kidney is reported, and a review of the literature on primary renal lymphoma is made.


Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA.
The advent of prostate specific antigen (PSA) testing in the United States of America (USA) has led to a dramatic increase in the incidence of prostate cancer in the United States as well as the number of men undergoing aggressive treatment with radical prostatectomy and radiation therapy. We compared patient characteristics and treatment selection between American men with screening-detected versus clinically diagnosed prostate cancers. We evaluated 3,173 men with prostate cancer in the USA. Surveys and medical records provided information on demographics, socioeconomic status, comorbidities, symptoms, tumor characteristics, and treatment. We classified men presenting with symptoms of advanced cancer - bone pain, weight loss, or hematuria - as "clinically diagnosed"; asymptomatic men and those with only lower urinary tract symptoms were considered "screening-detected." We used multivariate analyses to determine whether screening predicted receiving aggressive treatment for a clinically localized cancer. We classified 11% of cancers as being clinically diagnosed. Men with screening-detected cancers were more often non-Hispanic white (77% vs. 65%, P < 0.01), younger (36% < 65 years vs. 25%, P <or= 0.01), better educated (80% >or= high school vs. 67%, P < 0.01), healthier (18% excellent health vs. 10%, P < 0.01), and diagnosed with localized disease (90% vs. 75%, P < 0.01). Men with screening-detected localized cancers more often underwent aggressive treatment, 76% vs. 70%, P = 0.05. Most cancers were detected by screening in this American cohort. Appropriately, younger, healthier men were more likely to be diagnosed by screening. Minority status and lower socio-economic status appeared to be screening barriers. Screening detected earlier-stage cancers and was associated with receiving aggressive treatment.


Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors.
The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.


Predicting Alcohol-Impaired Driving among Spanish Youth with the Theory of Reasoned Action.
Alcohol consumption is a risk factor for motor vehicle accidents in young drivers. Crashes associated with alcohol consumption typically have greater severity. This study examines the prevalence of driving under the influence among Spanish youth and tests the theory of reasoned action as a model for predicting driving under the influence. Participants included 478 Spanish university students aged 17-26 years. Findings indicated that alcohol was the substance most associated with impaired driving, and was involved in more traffic crashes. Men engage in higher levels of alcohol and other drug use, and perceived less risk in drunk driving (p < .01). The study confirms that alcohol use and driving under the influence of alcohol are highly prevalent in Spanish young people, and some gender differences exist in these behaviors (p < .01). Furthermore, the study confirms the validity of theory of reasoned action as a predictive model of driving under the influence of alcohol among youth in Spain (p < .001) and can help in the design of prevention programs.


Pediatric lung transplantation.
Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not 'just small adults'. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a "one fits all approach", tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post-transplantation. However, chronic lung allograft dysfunction (CLAD) remains the major obstacle for improved long-term survival.


250 DPI at 1000 Hz acquisition rate S0 lamb wave digitizing pen.
This paper presents an active stylus (X, Y) flat digitizing tablet (AST). The tablet features an acquisition rate of 1000 pts/s with 0.1 mm resolution. The cordless stylus incorporates a 1-mA low-power pulse generator. Precision is limited by diffraction to about ±0.3 mm on a 57 x 57 mm region of a 71 x 71 x 1 mm digitizing plate. Selective generation and detection of the S(0) Lamb mode with a precessing tip is the key feature of this tablet. We first highlight the ultrasonic propagation inside the stylus tip and stability of Lamb wave generation when the stylus is inclined, rotated, and slid. Then, modeling of the limitations imposed by diffraction of a 1-MHz burst S(0) plane Lamb wave packet is carried out. The model takes into account high-order zero crossing detection as well as reflections and shear horizontal (SH) conversions of the S(0) Lamb mode at free edges of a glass plate. Reflection and transmission through an isotropic PZT bar are also calculated. Finally, localization precision by time difference of arrival (TDOA) is calculated and experimentally verified near the borders of the plate, taking into account the angular sensitivity of the precessing tip.


Quality of doctoral nursing education in the United Kingdom: exploring the views of doctoral students and staff based on a cross-sectional questionnaire survey.
To evaluate the quality of doctoral education in nursing in the United Kingdom. In recent decades, doctoral education programmes in nursing are increasing worldwide. There are many reasons for this and concerns have been raised regarding the quality of provision in and across countries. To date, the quality of doctoral education on a global level has not been reported in the literature. This United Kingdom study is part of a seven country investigation into the quality of doctoral education in nursing (Australia, Japan, Korea, South Africa, Thailand, United Kingdom and United States of America). A quantitative study using a cross-sectional comparative survey design. An online survey was administered to collect the views of doctoral students and staff members on four domains: programme, faculty/staff, resource and evaluation. The study was carried out between 2010-2012. In most cases, staff perceived these more positively than students and the differences in perception were often statistically significant. Interestingly, many students rated the quality of supervision as excellent, whereas no staff member rated supervision this highly. The crucial importance of resources was confirmed in the path analysis of the four Quality of Doctoral Nursing Education domains. This demonstrates that investment in resources is much more cost-effective than investment in the other domains in relation to improving the overall quality of doctoral education in nursing. This study has wide-ranging implications for how the quality of doctoral education is monitored and enhanced.


Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells.
Approximately 70% cases of breast cancers exhibit high expression and activity levels of estrogen receptor alpha (ERα), a transcription regulator that induces the expression of genes associated with cellular proliferation and survival. These nuclear functions of the receptor are associated with the development of breast cancer. However, ERα localization is not static, but rather, dynamic with continuous shuttling between the nucleus and the cytoplasm. Interestingly, both the nuclear import and export of ERα are modulated by several stimuli that include estradiol, antiestrogens, and growth factors. As ERα nuclear accumulation is critical to the regulation of gene expression, nuclear export of this receptor modulates the intensity and duration of its transcriptional activity. Thus, the subcellular spatial distribution of ERα ensures tight modulation of its concentration in cellular compartments, as well as of its nuclear and extranuclear functions. In this review, we will discuss current findings regarding the biological importance of molecular mechanisms of, and proteins responsible for, the nuclear import and export of ERα in breast cancer cells.


Multiple myopericytoma of the face and parotid gland.
Myopericytoma is a benign tumor that is composed of myoid-appearing oval to spindle-shaped cells with a concentric perivascular pattern of growth. The tumor is morphologically heterogeneous and can exhibit a broad histologic spectrum. We describe a case of multiple myopericytoma occurring in the head and neck skin region with involvement of the parotid gland where it is known to occur very rarely. A 40-year-old woman noticed multiple enlarging, painless, round-shaped masses on her left cheek. The patient had experienced a similar lesion of the same area 8 years earlier which was completely excised and the pathological diagnosis was spindle cell type myoepithelioma. On a computed tomographic image, one mass involved the superficial parotid gland and was well encapsulated. Excision of the facial masses and superficial parotidectomy with facial nerve preservation were performed. A diagnosis of myopericytoma was established in light of the immunohistochemical pattern with the histopathological findings. Over the 4-year follow-up period, there was no evidence of recurrence. As many perivascular myoid neoplasms share common morphologic features with myopericytoma, we should consider the differential diagnosis, and confirm the histological findings with appropriate immunohistochemical staining. After identifying myopericytoma, it should be treated with wide surgical excision to prevent local recurrence.


The self-referencing oxygen-selective microelectrode: detection of transmembrane oxygen flux from single cells.
A self-referencing, polarographic, oxygen-selective microelectrode was developed for measuring oxygen fluxes from single cells. This technique is based on the translational movement of the microelectrode at a known frequency through an oxygen gradient, between known points. The differential current of the electrode was converted into a directional measurement of flux using the Fick equation. Operational characteristics of the technique were determined using artificial gradients. Calculated oxygen flux values matched theoretical values derived from static measurements. A test preparation, an isolated neuron, yielded an oxygen flux of 11.46+/-1.43 pmol cm-2 s-1 (mean +/- s.e.m.), a value in agreement with those available in the literature for single cells. Microinjection of metabolic substrates or a metabolic uncoupler increased oxygen flux, whereas microinjection of KCN decreased oxygen flux. In the filamentous alga Spirogyra greveilina, the probe could easily differentiate a 16.6% difference in oxygen flux with respect to the position of the spiral chloroplast (13.3+/-0.4 pmol cm-2 s-1 at the chloroplast and 11.4+/-0.4 pmol cm-2 s-1 between chloroplasts), despite the fact that these positions averaged only 10.6+/-1.8 microm apart (means +/- s.e.m.). A light response experiment showed real-time changes in measured oxygen flux correlated with changes in lighting. Taken together, these results show that the self-referencing oxygen microelectrode technique can be used to detect local oxygen fluxes with a high level of sensitivity and spatial resolution in real time. The oxygen fluxes detected reliably correlated with the metabolic state of the cell.


The molecular pathogenesis of Trichilemmal carcinoma.
Trichilemmal carcinoma (TC) is an extremely rare hair follicle tumor. We aimed to explore the genetic abnormalities involved in TC to gain insight into its molecular pathogenesis. Data from patients diagnosed with TC within a 12-year period were retrospectively reviewed. Genomic DNA isolated from a formalin-fixed paraffin-embedded (FFPE) tumor tissue block was sequenced and explored for a panel of cancer genes. DNA was extracted from the FFPE tissue of four patients (50% female; mean age, 51.5 years) diagnosed with TC for analysis. The tumor was located in the head and neck of three patients and in the shoulder of one patient. TP53 mutations (p.Arg213*, p.Arg249Trp, and p.Arg248Gln) were found in three patients. Fusions previously identified in melanoma were detected in two patients (TACC3-FGFR3 and ROS1-GOPC fusions). Other mutations found included NF1-truncating mutation (Arg1362*), NRAS mutation (p.Gln61Lys), TOP1 amplification, and PTEN deletion. Overall, genetic changes found in TC resemble that of other skin cancers, suggesting similar pathogenesis. All patients with TP53 mutations had aggressive clinical course, two who died (OS 93 and 36 months), and one who experienced recurrent relapse. We reported the genomic variations found in TC, which may give insight into the molecular pathogenesis. Overall, genetic changes found in TC resembled that of other skin cancers, suggesting similar pathogenesis. TP53 mutations was were identified in patients who had an aggressive clinical course. Genetic alterations identified may further suggest the potential treatment options of TC.


Computerized radiation therapy data.
A computer data system by which data from radiation therapy records are stored, corrected, and up-dated continuously as information becomes available is described. Two main programs are involved. A data storage and retrieval system called TAXIR uses a high-level language similar to English and allows display of information in alphabetic or numerical fashion. The other program, MIDAS, is a statistical package designed to perform multiple statistical analyses on the data accumulated on the former program. Both of these programs utilize a logical syntax permitting easy identification and partition of a data set. In addition, several smaller program have been developed to advance survival information in a rapid and reliable way and to obtain information directly from computerized data available at the University of Michigan Cancer Follow-Up Unit. Programs to obtain life tables or graphs on survival or reactivation of neoplasms have been developed. Stress is placed on the development of a strategy to obtain the maximum accurate information with a minimum input. The development of suitable coding sheets including appropriate diagnoses and tumor classifications is discussed. The importance of keeping a continuous up-to-date flow of information is stressed.


Normal and Anomalous Diffusion: An Analytical Study Based on Quantum Collision Dynamics and Boltzmann Transport Theory.
Diffusion, an emergent nonequilibrium transport phenomenon, is a nontrivial manifestation of the correlation between the microscopic dynamics of individual molecules and their statistical behavior observed in experiments. We present a thorough investigation of this viewpoint using the mathematical tools of quantum scattering, within the framework of Boltzmann transport theory. In particular, we ask: (a) How and when does a normal diffusive transport become anomalous? (b) What physical attribute of the system is conceptually useful to faithfully rationalize large variations in the coefficient of normal diffusion, observed particularly within the dynamical environment of biological cells? To characterize the diffusive transport, we introduce, analogous to continuous phase transitions, the curvature of the mean square displacement as an order parameter and use the notion of quantum scattering length, which measures the effective interactions between the diffusing molecules and the surrounding, to define a tuning variable, η. We show that the curvature signature conveniently differentiates the normal diffusion regime from the superdiffusion and subdiffusion regimes and the critical point, η = ηc, unambiguously determines the coefficient of normal diffusion. To solve the Boltzmann equation analytically, we use a quantum mechanical expression for the scattering amplitude in the Boltzmann collision term and obtain a general expression for the effective linear collision operator, useful for a variety of transport studies. We also demonstrate that the scattering length is a useful dynamical characteristic to rationalize experimental observations on diffusive transport in complex systems. We assess the numerical accuracy of the present work with representative experimental results on diffusion processes in biological systems. Furthermore, we advance the idea of temperature-dependent effective voltage (of the order of 1 μV or less in a biological environment, for example) as a dynamical cause of the perpetual molecular movement, which eventually manifests as an ordered motion, called the diffusion.


Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network.
Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.


Marijuana Use Among Patients With Glaucoma in a City With Legalized Medical Marijuana Use.
Previous research has shown several limitations associated with the use of marijuana as a treatment for glaucoma. However, little is known regarding patients' perceptions toward using marijuana for glaucoma and their intentions to use this therapeutic alternative. To identify factors among patients with glaucoma that could lead to intentions to use marijuana for treatment. This cross-sectional survey study of 204 patients with glaucoma or suspected to have glaucoma was conducted at an academic-based glaucoma clinic in Washington, DC, between February 1 and July 31, 2013. Patients completed a self-administered survey assessing demographics, perceived severity of glaucoma, prior knowledge about marijuana use in glaucoma, past marijuana use, perceptions toward marijuana use (legality, systemic adverse effects, safety and effectiveness, and false beliefs), satisfaction with current glaucoma management, relevance of treatment costs, and intentions to use marijuana for glaucoma. Medical records were reviewed for disease severity. Data analysis was conducted from September 1, 2013, to September 30, 2015. The main outcome was patients' intentions to use marijuana for glaucoma. Multiple linear regression analysis was conducted to identify factors associated with patients' intentions to use marijuana for glaucoma. Of the 334 patients who were invited to participate in the study, 204 (61.1%) completed the survey. About half the participants were women (104 [51.0]%), and 82 (40.2%) were white. Regression analysis of 204 respondents indicated that perceptions of legality of marijuana use (β, 0.378; 95% CI, 0.205 to 0.444; P < .001), false beliefs regarding marijuana (β, 0.323; 95% CI, 0.236 to 0.504; P < .001), satisfaction with current glaucoma care (β, -0.222; 95% CI, -0.362 to -0.128; P < .001), and relevance of marijuana and glaucoma treatment costs (β, 0.127; 95% CI, 0.008 to 0.210; P = .04) were significantly associated with intentions to use marijuana for glaucoma treatment after controlling for demographic variables, disease severity, and previous marijuana use. This study's findings suggest a need for more education on this topic for ophthalmologists to be able to protect patients with glaucoma against the increased acceptability among the public of using marijuana based on false perceptions of its therapeutic value in glaucoma therapy. Considering the strong influence of perceptions of the legality of marijuana use on intentions to use this substance as a treatment for glaucoma, patient education might be particularly relevant in states in which marijuana use for glaucoma is legal, as in the case of the current study's setting.


Enoxaparin ameliorates post-traumatic brain injury edema and neurologic recovery, reducing cerebral leukocyte endothelial interactions and vessel permeability in vivo.
Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid administration. We hypothesized that enoxaparin (ENX) after TBI blunts in vivo leukocyte (LEU) mobilization to injured brain and cerebral edema, while improving neurologic recovery without increasing the size of the cerebral hemorrhagic contusion. CD1 male mice underwent either TBI by controlled cortical impact (CCI, 1-mm depth, 6 m/s) or sham craniotomy. ENX (1 mg/kg) or vehicle (VEH, 0.9% saline, 1 mL/kg) was administered at 2, 8, 14, 23, and 32 hours after TBI. At 48 hours, intravital microscopy was used to visualize live LEUs interacting with endothelium and microvascular leakage of fluorescein isothiocyanate-albumin. Neurologic function (Neurological Severity Score, NSS), activated clotting time, hemorrhagic contusion size, as well as brain and lung wet-to-dry ratios were evaluated post mortem. Analysis of variance with Bonferroni correction was used for statistical comparisons between groups. Compared with VEH, ENX significantly reduced in vivo LEU rolling on endothelium (72.7 ± 28.3 LEU/100 μm/min vs. 30.6 ± 18.3 LEU/100 μm/min, p = 0.02) and cerebrovascular albumin leakage (34.5% ± 8.1% vs. 23.8% ± 5.5%, p = 0.047). CCI significantly increased ipsilateral cerebral hemisphere edema, but ENX treatment reduced post-CCI edema to near control levels (81.5% ± 1.5% vs. 77.6% ± 0.6%, p < 0.01). Compared with VEH, ENX reduced body weight loss at 24 hours (8.7% ± 1.2% vs. 5.8% ± 1.1%, p < 0.01) and improved NSS at 24 hours (14.5 ± 0.5 vs. 16.2 ± 0.4, p < 0.01) and 48 hours (15.1 ± 0.4 vs. 16.7 ± 0.5, p < 0.01) after injury. There were no significant differences in activated clotting time, hemorrhagic contusion size, and lung water content between the groups. ENX reduces LEU recruitment to injured brain, diminishing visible microvascular permeability and edema. ENX may also accelerate neurologic recovery without increasing cerebral contusion size. Further study in humans is necessary to determine safety, appropriate dosage, and timing of ENX administration early after TBI.


Outcome of narrowing related side branches after high-speed rotational atherectomy.
High-speed rotational atherectomy (HSRA) is advocated for calcified and diffusely narrowed coronary arteries. There are often side branches involving these kinds of lesions. The presence of significant lesion-related side branches has been considered a relative contraindication to rotational atherectomy. This study was performed to determine the rate, predictors, and outcome of side branch occlusion after HSRA. The angiograms of 418 patients were examined with 320 side branches in 240 target vessels of > or = 1 mm in diameter being identified. Vessels were scored as either perfused (Thrombolysis In Myocardial Infarction 2 or 3 flow) or occluded (Thrombolysis In Myocardial Infarction 0 or 1 flow before and after the procedure. A detailed quantitative angiographic analysis was performed on a total of 108 side branches including all cases of branch occlusion. Clinical outcomes were determined in all cases with side branch loss. There were 24 occlusions in 21 patients after the procedure, giving a rate of branch loss of 7.5%. Follow-up angiography of > or = 24 hours was available for 13 of the occluded branches and 12 were found to be patent. In the 21 patients with branch occlusion, 6 sustained a myocardial infarct (of which 5 were non-Q-wave), 2 underwent coronary artery bypass grafting, and 2 died. There are frequently lesion-associated side branches in the types of vessels to undergo HSRA. These branches remained patent 92.5% of the time, with occlusion occurring infrequently and usually being transient. When occlusion did occur, there was a 29% incidence of myocardial infarction.


Investigation of Morphological, Optical, and Dielectric Properties of RF Sputtered WOx Thin Films for Optoelectronic Applications.
Tungsten oxide (WOx) thin films were synthesized through the RF magnetron sputtering method by varying the sputtering power from 30 W to 80 W. Different investigations have been conducted to evaluate the variation in different morphological, optical, and dielectric properties with the sputtering power and prove the possibility of using WOx in optoelectronic applications. An Energy Dispersive X-ray (EDX), stylus profilometer, and atomic force microscope (AFM) have been used to investigate the dependency of morphological properties on sputtering power. Transmittance, absorbance, and reflectance of the films, investigated by Ultraviolet-Visible (UV-Vis) spectroscopy, have allowed for further determination of some necessary parameters, such as absorption coefficient, penetration depth, optical band energy gap, refractive index, extinction coefficient, dielectric parameters, a few types of loss parameters, etc. Variations in these parameters with the incident light spectrum have been closely analyzed. Some important parameters such as transmittance (above 80%), optical band energy gap (~3.7 eV), and refractive index (~2) ensure that as-grown WOx films can be used in some optoelectronic applications, mainly in photovoltaic research. Furthermore, strong dependencies of all evaluated parameters on the sputtering power were found, which are to be of great use for developing the films with the required properties.


Iron-doped carbon nanotubes with magnetic enhanced Fe(VI) degradation of arsanilic acid and inorganic arsenic: Role of intermediate iron species and electron transfer.
Arsanilic acid (p-AsA), a prevalently used feed additive, is frequently detected in environment posing a great threat to humans. Potassium ferrate (Fe(VI)) was an efficient way to tackle arsenic contamination under acid and neutral conditions. However, Fe(VI) showed a noneffective removal of p-AsA under alkaline conditions due to its oxidation capacity attenuation. Herein, a magnetic iron-doped carbon nanotubes (F-CNT) was successfully prepared and further catalyzed Fe(VI) to remove p-AsA and total As species. The Fe(VI)/F-CNT system showed an excellent capability to oxidize p-AsA and adsorb total As species over an environment-related pH range of 6-9. The high-valent iron intermediates Fe(V)/Fe(IV) and the mediated electron-transfer played a significant part in the degradation of p-AsA according to the probes/scavengers experiments and galvanic oxidation process. Moreover, the situ formed iron hydroxide oxide and F-CNT significantly improved the adsorption capacity for total As species. The electron-donating groups (semiquinone and hydroquinone) and high graphitization of F-CNT were responsible for activating Fe(VI) based on the analysis of X-ray photoelectron spectroscopy (XPS). Density functional theory calculations and the detected degradation products both indicated that the amino group and the C-As bond of p-AsA were main reactive sites. Notably, Fe(VI)/F-CNT system was resistant to the interference from Cl-, SO42-, and HCO3-, and could effectively remove p-AsA and total As species even in the presence of complex water matrix. In summary, this work proposed an efficient method to use Fe(VI) for degrading pollutants under alkaline conditions and explore a new technology for livestock wastewater advanced treatment.


Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis.
To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis. Tertiary pediatric referral center. Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database. Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented. Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average. One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up. Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.


[Pulmonary edema in transcervical endometrial ablation: a case report].
The use of the transcervical resectoscope for endometrial ablation and/or resection of myomas is a relatively new technique in gynecologic surgery. Although complications are uncommon with this procedure, they can occasionally appear and lead to potential hazard. Here a patient presenting for endometrial ablation is described; 1.5% glycine was used as the irrigation solution to enhance visibility and to wash away blood and tissue particles. Unfortunately, a large amount of glycine was absorbed by the open vessels in the myometrium during operation, leading to pulmonary edema and dilutional hyponatremia. After administration of diuretics, sodium supplement and 100% oxygen, complications improved progressively. The patient was discharged on postoperative day 5 without any sequelae.


Identification of a human heavy chain antibody fragment directed against human platelet alloantigen 1a by phage display library.
The human platelet alloantigen HPA-1a (PlA1) is responsible for most cases of post-transfusion purpura and neonatal alloimmune thrombocytopenia in the Caucasian population. HPA-1a and HPA-1b are two allelic forms of the platelet membrane glycoprotein IIIa (GPIIIa) gene that differ by a single amino acid. In this report, we describe the development of a recombinant heavy chain antibody fragment capable of distinguishing between the homozygous forms of HPA-1a and HPA-1b. This antibody fragment was isolated from the lymphocytes of an immunized individual through the use of a phage display library system. The recombinant antibody fragment reacted with human platelet lysates from HPA-1a homozygous donors, the HPA-1a form of recombinant N-terminal GPIIIa and intact HPA-1a platelets, but did not react with platelet lysate from HPA-1b homozygous donors, reduced HPA-1a form of platelet GPIIIa or other platelet glycoproteins. This HPA-1a specific human antibody fragment works well in common laboratory assays such as ELISA and flow cytometry, which can assist in identifying HPA-1b homozygous individuals who are known to have a higher risk for developing neonatal alloimmmune thrombocytopenia and post-transfusion purpura. Thus, selection of recombinant antibody fragment using phage display offers a promising alternative to hybridoma technology for the production of human antibodies against human alloantigens and holds potential as a technique in therapeutic applications.


Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study.
Intravitreous bevacizumab (0.25 to 0.625 mg) is increasingly used to treat type 1 retinopathy of prematurity (ROP), but there remain concerns about systemic toxicity. A much lower dose may be effective while reducing systemic risk. To find a dose of intravitreous bevacizumab that was lower than previously used for severe ROP, was effective in this study, and could be tested in future larger studies. Between May 2015 and September 2016, 61 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, phase 1 dose de-escalation study. One eye of 10 to 14 infants received 0.25 mg of intravitreous bevacizumab. If successful, the dose was reduced for the next group of infants (to 0.125 mg, then 0.063 mg, and finally 0.031 mg). Diluted bevacizumab was delivered using 300 µL syringes with 5/16-inch, 30-gauge fixed needles. Bevacizumab injections at 0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg. Success was defined as improvement in preinjection plus disease or zone I stage 3 ROP by 5 days after injection or sooner, and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Fifty-eight of 61 enrolled infants had 4-week outcomes completed; mean birth weight was 709 g and mean gestational age was 24.9 weeks. Success was achieved in 11 of 11 eyes at 0.25 mg, 14 of 14 eyes at 0.125 mg, 21 of 24 eyes at 0.063 mg, and 9 of 9 eyes at 0.031 mg. A dose of bevacizumab as low as 0.031 mg was effective in 9 of 9 eyes in this phase 1 study and warrants further investigation. Identifying a lower effective dose of bevacizumab may reduce the risk for neurodevelopmental disability or detrimental effects on other organs.


Incorporating surrogate species and seascape connectivity to improve marine conservation outcomes.
Conservation focuses on maintaining biodiversity and ecosystem functioning, but gaps in our knowledge of species biology and ecological processes often impede progress. For this reason, focal species and habitats are used as surrogates for multispecies conservation, but species-based approaches are not widely adopted in marine ecosystems. Reserves in the Solomon Islands were designed on the basis of local ecological knowledge to conserve bumphead parrotfish (Bolbometopon muricatum) and to protect food security and ecosystem functioning. Bumphead parrotfish are an iconic threatened species and may be a useful surrogate for multispecies conservation. They move across tropical seascapes throughout their life history, in a pattern of habitat use that is shared with many other species. We examined their value as a conservation surrogate and assessed the importance of seascape connectivity (i.e., the physical connectedness of patches in the seascape) among reefs, mangroves, and seagrass to marine reserve performance. Reserves were designed for bumphead parrotfish, but also enhanced the abundance of other species. Integration of local ecological knowledge and seascape connectivity enhanced the abundance of 17 other harvested fish species in local reserves. This result has important implications for ecosystem functioning and local villagers because many of these species perform important ecological processes and provide the foundation for extensive subsistence fisheries. Our findings suggest greater success in maintaining and restoring marine ecosystems may be achieved when they are managed to conserve surrogate species and preserve functional seascape connections.


Seeking care as a system.
Kim, aged 3 years, lies asleep, waiting for a miracle. Outside her room, the nurses on the night shift pad softly through the half-lighted corridors, stopping to count breaths, take pulses, or check the intravenous pumps. In the morning, Kim will have her heart fixed. She will be medicated and wheeled into the operating suite. Machines will take on the functions of her body: breathing and circulating blood. The surgeons will place a small patch over a hole within her heart, closing off a shunt between her ventricles that would, if left open, slowly kill her. Kim will be fine if the decision to operate on her was correct; if the surgeon is competent; if that competent surgeon happens to be trained to deal with the particular anatomic wrinkle that is hidden inside Kim's heart; if the blood bank cross-matched her blood accurately and delivered it to the right place; if the blood gas analysis machine works properly and on time; if the suture does not snap; if the plastic tubing of the heart-lung machine does not suddenly spring loose; if the recovery room nurses know that she is allergic to penicillin; if the "oxygen" and "nitrogen" lines in the anesthesia machine have not been reversed by mistake; if the sterilizer temperature gauge is calibrated so that the instruments are in fact sterile; if the pharmacy does not mix up two labels; and if when the surgeon says urgently, "Clamp, right now," there is a clamp on the tray. If all goes well, if ten thousand "ifs" go well, then Kim may sing her grandchildren to sleep some day. If not, she will be dead by noon tomorrow. If Kim were an astronaut, strapped into her seat at the top of some throbbing rocket, the crowd assembled would hold their breath in the morning Florida sun. "How can it possibly work?" they would whisper. "How many parts are there in that machine? A million? What if one fails? My toaster fails. Please let it all work right." The machine would bellow smoke, the gantry fall away, and slowly the monster would rise, Kim on top. If it worked, they would cheer. "A miracle," they would shout, in awe that the millions of tiny lines of effort, the millions of tiny lines of cause and effect, from job shops in Ohio and laboratories in Pasadena, criss-crossing through time and space, could converge so magnificently in a massive, gleaming rocket launched exactly right. Perfect. If it failed, they would cry. So would the rocket's makers, who had done their very best. No one wanted it to end this way. Poor Kim. What was the trouble? What went wrong? Why? The lines of cause will converge around Kim in the morning as she wheels toward the operating room. Thousands upon thousands of elements weaving a basket to hold her safely, all hope. No crowd holds its breath tonight; but wouldn't they if they knew? From: Berwick DM. Controlling variation in health care: a consultation from Walter Shewhart. Medical Care 1991; 29: 1212-1225.


Importance of the heart vector origin point definition for an ECG analysis: The Atherosclerosis Risk in Communities (ARIC) study.
Our goal was to investigate the effect of a global XYZ median beat construction and the heart vector origin point definition on predictive accuracy of ECG biomarkers of sudden cardiac death (SCD). Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n = 15,768; 55% female, 73% white, mean age 54.2 ± 5.8 y). We developed an algorithm to automatically detect the heart vector origin point on a median beat. Three different approaches to construct a global XYZ beat and two methods to locate origin point were compared. Global electrical heterogeneity was measured by sum absolute QRST integral (SAI QRST), spatial QRS-T angle, and spatial ventricular gradient (SVG) magnitude, azimuth, and elevation. Adjudicated SCD served as the primary outcome. There was high intra-observer (kappa 0.972) and inter-observer (kappa 0.984) agreement in a heart vector origin definition between an automated algorithm and a human. QRS was wider in a median beat that was constructed using R-peak alignment than in time-coherent beat (88.1 ± 16.7 vs. 83.7 ± 15.9 ms; P < 0.0001), and on a median beat constructed using QRS-onset as a zeroed baseline, vs. isoelectric origin point (86.7 ± 15.9 vs. 83.7 ± 15.9 ms; P < 0.0001). ROC AUC was significantly larger for QRS, QT, peak QRS-T angle, SVG elevation, and SAI QRST if measured on a time-coherent median beat, and for SAI QRST and SVG magnitude if measured on a median beat using isoelectric origin point. Time-coherent global XYZ median beat with physiologically meaningful definition of the heart vector's origin point improved predictive accuracy of SCD biomarkers.


Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity.
Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic mice. Db/db mice were randomized to high sodium (HS 1.6% Na+, n = 6) or low sodium (LS 0.03% Na+, n = 8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n = 8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p < 0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p < 0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p < 0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p < 0.01). In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders.


Familial ROBO1 deletion associated with ectopic posterior pituitary, duplication of the pituitary stalk and anterior pituitary hypoplasia.
Background The genetic causes of abnormal pituitary development have been extensively studied in the last few years. ROBO1 is involved in neurogenesis and axon guidance. Loss-of-function variants in ROBO1 have been associated with pituitary stalk interruption syndrome (PSIS), suggesting that its haploinsufficiency could impair the guidance of hypothalamic axons to the pituitary gland leading to developmental abnormalities. Case presentation We report a 4.5-year-old girl with anterior pituitary hypoplasia and pituitary stalk duplication in the ventral-dorsal direction. Her father had a similar pituitary phenotype, characterized by anterior pituitary hypoplasia combined with ectopic posterior pituitary. Comparative genomic hybridization (CGH) microarray analysis identified a 343.7 kb deletion of 3p12.3 encompassing ROBO1 in both individuals. Conclusions We report the first familial ROBO1 deletion in two individuals with peculiar pituitary anomalies, including the rare pituitary stalk duplication in the ventral-dorsal direction. These findings widen the spectrum of the phenotypes associated with ROBO1 haploinsufficiency and support its role in human pituitary development.


Effectiveness of Surgeon-Performed Paravertebral Block Analgesia for Minimally Invasive Thoracic Surgery: A Randomized Clinical Trial.
In minimally invasive thoracic surgery, paravertebral block (PVB) using ultrasound (US)-guided technique is an efficient postoperative analgesia. However, it is an operator-dependent process depending on experience and local resources. Because pain-control failure is highly detrimental, surgeons may consider other locoregional analgesic options. To demonstrate the noninferiority of PVB performed by surgeons under video-assisted thoracoscopic surgery (VATS), hereafter referred to as PVB-VATS, as the experimental group compared with PVB performed by anesthesiologists using US-guided technique (PVB-US) as the control group. In this single-center, noninferiority, patient-blinded, randomized clinical trial conducted from September 8, 2020, to December 8, 2021, patients older than 18 years who were undergoing a scheduled minimally invasive thoracic surgery with lung resection including video-assisted or robotic approaches were included. Exclusion criteria included scheduled open surgery, any antalgic World Health Organization level greater than 2 before surgery, or a medical history of homolateral thoracic surgery. Patients were randomly assigned (1:1) to an intervention group after general anesthesia. They received single-injection PVB before the first incision was made in the control group (PVB-US) or after 1 incision was made under thoracoscopic vision in the experimental group (PVB-VATS). PVB-VATS or PVB-US. The primary end point was mean 48-hour post-PVB opioid consumption considering a noninferiority range of less than 7.5 mg of opioid consumption between groups. Secondary outcomes included time of anesthesia, surgery, and operating room occupancy; 48-hour pain visual analog scale score at rest and while coughing; and 30-day postoperative complications. A total of 196 patients were randomly assigned to intervention groups: 98 in the PVB-VATS group (mean [SD] age, 64.6 [9.5] years; 53 female [54.1%]) and 98 in the PVB-US group (mean [SD] age, 65.8 [11.5] years; 62 male [63.3%]). The mean (SD) of 48-hour opioid consumption in the PVB-VATS group (33.9 [19.8] mg; 95% CI, 30.0-37.9 mg) was noninferior to that measured in the PVB-US group (28.5 [18.2] mg; 95% CI, 24.8-32.2 mg; difference: -5.4 mg; 95% CI, -∞ to -0.93; noninferiority Welsh test, P ≤ .001). Pain score at rest and while coughing after surgery, overall time, and postoperative complications did not differ between groups. PVB placed by a surgeon during thoracoscopy was noninferior to PVB placed by an anesthesiologist using ultrasonography before incision in terms of opioid consumption during the first 48 hours. ClinicalTrials.gov Identifier: NCT04579276.


The solar magnetic activity band interaction and instabilities that shape quasi-periodic variability.
Solar magnetism displays a host of variational timescales of which the enigmatic 11-year sunspot cycle is most prominent. Recent work has demonstrated that the sunspot cycle can be explained in terms of the intra- and extra-hemispheric interaction between the overlapping activity bands of the 22-year magnetic polarity cycle. Those activity bands appear to be driven by the rotation of the Sun's deep interior. Here we deduce that activity band interaction can qualitatively explain the 'Gnevyshev Gap'—a well-established feature of flare and sunspot occurrence. Strong quasi-annual variability in the number of flares, coronal mass ejections, the radiative and particulate environment of the heliosphere is also observed. We infer that this secondary variability is driven by surges of magnetism from the activity bands. Understanding the formation, interaction and instability of these activity bands will considerably improve forecast capability in space weather and solar activity over a range of timescales.


Solid-phase enzyme immunoassay for determination of antibodies to cytomegalovirus.
A solid-phase enzyme immunoassay for the determination of immunoglobulin H (IgG) and IgM antibodies to cytomegalovirus is described. The enzyme immunoassay gave reliable and consistent results which were in concordance with those obtained by the complement fixation test and the indirect immunofluorescence test. Antibodies to herpes simplex and varicella-zoster viruses did not interfere in the enzyme immunoassay for cytomegalovirus IgM antibodies. In a few patients with IgM antibodies to Epstein-Barr virus, cytomegalovirus IgM antibodies were also detected. False-positive cytomegalovirus IgM antibody results were observed in sera containing both the rheumatoid factor and cytomegalovirus IgG antibodies. This rheumatoid factor interference was overcome by the absorption of sera with polymerized human gamma globulin. The absorption did not affect true cytomegalovirus IgM antibody titers. Also described is a simple enzyme immunoassay that makes possible a more sensitive detection of the rheumatoid factor than the latex agglutination test.


Semisupervised category learning facilitates the development of automaticity.
In the human category of learning, learning is studied in a supervised, an unsupervised, or a semisupervised way. The rare human semisupervised category of learning studies all focus on early learning. However, the impact of the semisupervised category learning late in learning, when automaticity develops, is unknown. Therefore, in Experiment 1, all participants were first trained on the information-integration category structure for 2 days until they reached an expert level. Afterwards, half of the participants learned in a supervised way and the other half in a semisupervised way over two successive days. Both groups received an equal number of feedback trials. Finally, all participants took part in a test day where they were asked to respond as quickly as possible. Participants were significantly faster on this test in the semisupervised group than in the supervised group. This difference was not found on day 2, implying that the no-feedback trials in the semisupervised condition facilitated automaticity. Experiment 2 was designed to test whether the higher number of trials in the semisupervised condition of Experiment 1 caused the faster response times. We therefore created an almost supervised condition where participants almost always received feedback (95%) and an almost unsupervised condition where participants almost never received feedback (5%). All conditions now contained an equal number of trials to the semisupervised condition of Experiment 1. The results show that receiving feedback almost always or almost never led to slower response times than the semisupervised condition of Experiment 1. This confirms the advantage of semisupervised learning late in learning.


Endoscopic ultrasound-guided transluminal drainage for peripancreatic fluid collections: where are we now?
Endoscopic drainage for pancreatic and peripancreatic fluid collections (PFCs) has been increasingly used as a minimally invasive alternative to surgical or percutaneous drainage. Recently, endoscopic ultrasound-guided transluminal drainage (EUS-TD) has become the standard of care and a safe procedure for nonsurgical PFC treatment. EUS-TD ensures a safe puncture, avoiding intervening blood vessels. Single or multiple plastic stents (combined with a nasocystic catheter) were used for the treatment of PFCs for EUS-TD. More recently, the use of covered self-expandable metallic stents (CSEMSs) has provided a safer and more efficient approach route for internal drainage. We focused our review on the best approach and stent to use in endoscopic drainage for PFCs. We reviewed studies of EUS-TD for PFCs based on the original Atlanta Classification, including case reports, case series, and previous review articles. Data on clinical outcomes and adverse events were collected retrospectively. A total of 93 patients underwent EUS-TD of pancreatic pseudocysts using CSEMSs. The treatment success and adverse event rates were 94.6% and 21.1%, respectively. The majority of complications were of mild severity and resolved with conservative therapy. A total of 56 patients underwent EUS-TD using CSEMSs for pancreatic abscesses or infected walled-off necroses. The treatment success and adverse event rates were 87.8% and 9.5%, respectively. EUS-TD can be performed safely and efficiently for PFC treatment. Larger diameter CSEMSs without additional fistula tract dilation for the passage of a standard scope are needed to access and drain for PFCs with solid debris.


Clonality, recombination, and hybridization in the plumbing-inhabiting human pathogen Fusarium keratoplasticum inferred from multilocus sequence typing.
Recent work has shown that Fusarium species and genotypes most commonly associated with human infections, particularly of the cornea (mycotic keratitis), are the same as those most commonly isolated from plumbing systems. The species most dominant in plumbing biofilms is Fusarium keratoplasticum, a cosmopolitan fungus known almost exclusively from animal infections and biofilms. To better understand its diversity and population dynamics, we developed and utilized a nine-locus sequence-based typing system to make inferences about clonality, recombination, population structure, species boundaries and hybridization. High levels of genetic diversity and evidence for recombination and clonality were detected among 75 clinical and 156 environmental isolates of Fusarium keratoplasticum. The multilocus sequence typing system (MLST) resolved 111 unique nine-locus sequence types (STs). The single locus bifactorial determinants of mating compatibility (mating types MAT1-1 and MAT1-2), were found in a ratio of 70:30. All but one of the 49 isolates of the most common ST (FSSC 2d-2) came from human infections, mostly of the cornea, and from biofilms associated with contact lenses and plumbing surfaces. Significant levels of phylogenetic incongruence were found among loci. Putative clonal relationships among genotypes were estimated, showing a mixture of large clonal complexes and unrelated singletons. Discordance between the nuclear ribosomal rRNA and other gene genealogies is consistent with introgression of ribosomal RNA alleles of phylogenetic species FSSC 9 into F. keratoplasticum. No significant population subdivision based on clinical versus non-clinical sources was found. Incongruent phylogenetic trees and the presence of both mating types within otherwise identical STs were observed, providing evidence for sexuality in F. keratoplasticum. Cryptic speciation suggested in a published three-locus MLST system was not supported with the addition of new loci, but evidence of introgression of ribosomal RNA genes from another strongly supported phylogenetic species (FSSC 9), also known from plumbing systems and human infections, was detected in two isolates. Overall, F. keratoplasticum is a diverse and geographically unstructured species with a mixed clonal and recombinant life history.


Specific subtypes of GABAA receptors mediate phasic and tonic forms of inhibition in hippocampal pyramidal neurons.
The main inhibitory neurotransmitter in the mammalian brain, GABA, mediates multiple forms of inhibitory signals, such as fast and slow inhibitory postsynaptic currents and tonic inhibition, by activating a diverse family of ionotropic GABA(A) receptors (GABA(A)Rs). Here, we studied whether distinct GABA(A)R subtypes mediate these various forms of inhibition using as approach mice carrying a point mutation in the alpha-subunit rendering individual GABA(A)R subtypes insensitive to diazepam without altering their GABA sensitivity and expression of receptors. Whole cell patch-clamp recordings were performed in hippocampal pyramidal cells from single, double, and triple mutant mice. Comparing diazepam effects in knock-in and wild-type mice allowed determining the contribution of alpha1, alpha2, alpha3, and alpha5 subunits containing GABA(A)Rs to phasic and tonic forms of inhibition. Fast phasic currents were mediated by synaptic alpha2-GABA(A)Rs on the soma and by synaptic alpha1-GABA(A)Rs on the dendrites. No contribution of alpha3- or alpha5-GABA(A)Rs was detectable. Slow phasic currents were produced by both synaptic and perisynaptic GABA(A)Rs, judged by their strong sensitivity to blockade of GABA reuptake. In the CA1 area, but not in the subiculum, perisynaptic alpha5-GABA(A)Rs contributed to slow phasic currents. In the CA1 area, the diazepam-sensitive component of tonic inhibition also involved activation of alpha5-GABA(A)Rs and slow phasic and tonic signals shared overlapping pools of receptors. These results show that the major forms of inhibitory neurotransmission in hippocampal pyramidal cells are mediated by distinct GABA(A)Rs subtypes.


Stability of locking and non-locking plates in an osteoporotic calcaneal fracture model.
The aim of this biomechanical cadaver study of calcaneal fractures was to investigate whether a locking calcaneal plate provides more stiffness in osteoporotic bone compared to a non-locking plate. Sixteen fresh frozen bone mineral density (BMD)-matched cadaver feet were tested in a four-part model of a Sanders Type IIB calcaneal fracture. The fractures were fixed either with a non-locking AO (Sanders) plate or an interlocking AO plate (Synthes, Paoli, PA) to the lateral calcaneal wall with six screws. Specimens were subjected to cyclic loading which was increased stepwise to full body weight. Displacement of the posterior facet fragment was measured with an optical tracking system in the sagittal and transverse planes. No statistically significant differences were observed between the non-locking and the locking plates with respect to number of cycles to failure or 1-mm displacement of the posterior facet. The initial stiffness was significantly higher for non-locking plates. In osteoporotic bone, the greater stiffness of the screw-locking-plate construct was offset by the smaller diameter of the screw threads and the lower friction between the plate and bone when a locking plate was used. In clinical practice, the plate should first be compressed to osteoporotic bone with cancellous screws and at least two screws should be placed in the anterior process and in the tuberosity of the calcaneus.


Zfx mutation results in small animal size and reduced germ cell number in male and female mice.
The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y chromosomes, have been speculated to function in sex differentiation, spermatogenesis, and Turner syndrome. We derived Zfx mutant mice by targeted mutagenesis. Mutant mice (both males and females) were smaller, less viable, and had fewer germ cells than wild-type mice, features also found in human females with an XO karyotype (Turner syndrome). Mutant XY animals were fully masculinized, with testes and male genitalia, and were fertile, but sperm counts were reduced by one half. Homozygous mutant XX animals were fully feminized, with ovaries and female genitalia, but showed a shortage of oocytes resulting in diminished fertility and shortened reproductive lifespan, as in premature ovarian failure in humans. The number of primordial germ cells was reduced in both XX and XY mutant animals at embryonic day 11.5, prior to gonadal sex differentiation. Zfx mutant animals exhibited a growth deficit evident at embryonic day 12.5, which persisted throughout postnatal life and was not complemented by the Zfy genes. These phenotypes provide the first direct evidence for a role of Zfx in growth and reproductive development.


Discovery of Novel ncRNA Sequences in Multiple Genome Alignments on the Basis of Conserved and Stable Secondary Structures.
Recently, non-coding RNAs (ncRNAs) have been discovered with novel functions, and it has been appreciated that there is pervasive transcription of genomes. Moreover, many novel ncRNAs are not conserved on the primary sequence level. Therefore, de novo computational ncRNA detection that is accurate and efficient is desirable. The purpose of this study is to develop a ncRNA detection method based on conservation of structure in more than two genomes. A new method called Multifind, using Multilign, was developed. Multilign predicts the common secondary structure for multiple input sequences. Multifind then uses measures of structure conservation to estimate the probability that the input sequences are a conserved ncRNA using a classification support vector machine. Multilign is based on Dynalign, which folds and aligns two sequences simultaneously using a scoring scheme that does not include sequence identity; its structure prediction quality is therefore not affected by input sequence diversity. Additionally, ensemble defect was introduced to Multifind as an additional discriminating feature that quantifies the compactness of the folding space for a sequence. Benchmarks showed Multifind performs better than RNAz and LocARNATE+RNAz, a method that uses RNAz on structure alignments generated by LocARNATE, on testing sequences extracted from the Rfam database. For de novo ncRNA discovery in three genomes, Multifind and LocARNATE+RNAz had an advantage over RNAz in low similarity regions of genome alignments. Additionally, Multifind and LocARNATE+RNAz found different subsets of known ncRNA sequences, suggesting the two approaches are complementary.


Skin, thermal and umbilical cord care practices for neonates in southern, rural Zambia: a qualitative study.
In Choma District, southern Zambia, the neonatal mortality rate is approximately 40 per 1000 live births and, although the rate is decreasing, many deliveries take place outside of formal facilities. Understanding local practices during the postnatal period is essential for optimizing newborn care programs. We conducted 36 in-depth interviews, five focus groups and eight observational sessions with recently-delivered women, traditional birth attendants, and clinic and hospital staff from three sites, focusing on skin, thermal and cord care practices for newborns in the home. Newborns were generally kept warm by application of hats and layers of clothing. While thermal protection is provided for preterm and small newborns, the practice of nighttime bathing with cold water was common. The vernix was considered important for the preterm newborn but dangerous for HIV-exposed infants. Mothers applied various substances to the skin and umbilical cord, with special practices for preterm infants. Applied substances included petroleum jelly, commercial baby lotion, cooking oil and breastmilk. The most common substances applied to the umbilical cord were powders made of roots, burnt gourds or ash. To ward off malevolent spirits, similar powders were reportedly placed directly into dermal incisions, especially in ill children. Thermal care for newborns is commonly practiced but co-exists with harmful practices. Locally appropriate behavior change interventions should aim to promote chlorhexidine in place of commonly-reported application of harmful substances to the skin and umbilical cord, reduce bathing of newborns at night, and address the immediate bathing of HIV-infected newborns.


Structural studies of Saccharomyces cerevesiae mitochondrial NADP-dependent isocitrate dehydrogenase in different enzymatic states reveal substantial conformational changes during the catalytic reaction.
Isocitrate dehydrogenases (IDHs) catalyze oxidative decarboxylation of isocitrate (ICT) into alpha-ketoglutarate (AKG). We report here the crystal structures of Saccharomyces cerevesiae mitochondrial NADP-IDH Idp1p in binary complexes with coenzyme NADP, or substrate ICT, or product AKG, and in a quaternary complex with NADPH, AKG, and Ca(2+), which represent different enzymatic states during the catalytic reaction. Analyses of these structures identify key residues involved in the binding of these ligands. Comparisons among these structures and with the previously reported structures of other NADP-IDHs reveal that eukaryotic NADP-IDHs undergo substantial conformational changes during the catalytic reaction. Binding or release of the ligands can cause significant conformational changes of the structural elements composing the active site, leading to rotation of the large domain relative to the small and clasp domains along two hinge regions (residues 118-124 and residues 284-287) while maintaining the integrity of its secondary structural elements, and thus, formation of at least three distinct overall conformations. Specifically, the enzyme adopts an open conformation when bound to NADP, a quasi-closed conformation when bound to ICT or AKG, and a fully closed conformation when bound to NADP, ICT, and Ca(2+) in the pseudo-Michaelis complex or with NADPH, AKG, and Ca(2+) in the product state. The conformational changes of eukaryotic NADP-IDHs are quite different from those of Escherichia coli NADP-IDH, for which significant conformational changes are observed only between two forms of the apo enzyme, suggesting that the catalytic mechanism of eukaryotic NADP-IDHs is more complex than that of EcIDH, and involves more fine-tuned conformational changes.


KNDC1 Is a Predictive Marker of Malignant Transformation in Borderline Ovarian Tumors.
Few screening markers for malignant transformation in borderline ovarian tumors (BOT) have been clearly established. The kinase noncatalytic C-lobe domain containing 1 (KNDC1), a brain-specific Ras guanine nucleotide exchange factor, negatively regulates dendrite growth. However, the biological role and underlying mechanism of KNDC1 in human cancers, including ovarian cancer (OC), remain unknown. Gene chip screening was used to detect the expression of KNDC1 mRNA in normal ovarian tissues, BOT tissues, and OC tissues. And results were further validated by RT-qPCR, Western blotting and immunohistochemistry. KNDC1 overexpression and knockdown ovarian cancer cells were established to study the possible pathways that KNDC1 was involved. The effects of KNDC1 on the malignant behaviors of ovarian tumors were also investigated both in vitro and in vivo. We observed that the expression of KNDC1 mRNA and KNDC1 protein in OC was significantly downregulated compared with BOT. Subsequent investigation revealed that knockdown of KNDC1 enhanced the proliferation of ovarian cancer cells in vitro via induction of ERK1/2 phosphorylation, whereas reinforcing the expression of KNDC1 attenuated the ERK1/2 activity. Similarly, knockdown of KNDC1 also promoted cell proliferation in vivo. Survival analysis showed that lower KNDC1 predicted a poor progression-free survival (PFS) for patients. Collectively, we conclude that KNDC1 might function as a tumor suppressor in ovarian tumors, inhibiting the proliferation of ovarian cells by suppressing ERK1/2 activity and hindering the malignant transformation of BOT.


Effects of dried and ensiled apple pomace from puree making on performance of finishing lambs.
This experiment was conducted to study the effect of ensiled and dried Apple Pomace (AP) obtained from puree making on finishing performance of lambs. Digestibilities of both ensiled and dried AP were determined using 4 mature sheep. In finishing experiment, 18 Sanjabi male lambs were used (9 per treatment) in a 120 day finishing experiment which was divided into two periods (60 day each). In the first period the ensiled AP and in the second period the dried AP were fed in an iso caloric, iso nitrogenous total mix ration. The Dry Matter (DM), crude protein and neutral detergent fiber of ensiled and dried AP were 247.1, 63.85, 386.4 g kg(-1) DM and 888.4, 51.2, 385.6 g kg(-1) DM, respectively. No significant difference was observed in the apparent digestibility of ensiled and dried AP. The apparent DM digestibilities of ensiled and dried AP were 704.3 and 668.2 g kg(-1) DM, respectively. Feeding ensiled AP significantly increased Dry Matter Intake (0.938 vs. 0.803 kg day(-1)), Average Daily Gain (ADG) (199.8 vs. 155.56 g) and Feed Conversion Ratio (FCR) (4.69 vs. 5.16). Use of dried AP had no significant effect on DMI (1.030 vs. 0.932 kg day(-1)) but significantly improved the ADG (192.3 vs. 123.82 g) and FCR (5.36 vs. 7.52). Apple pomace increased carcass dressing percentage but had no effect on the percentage of different cuts. Results of this study suggest that AP, in both ensiled and dried forms, can improve the performance of finishing lambs.


Biological Effects of Indole-3-Propionic Acid, a Gut Microbiota-Derived Metabolite, and Its Precursor Tryptophan in Mammals' Health and Disease.
Actions of symbiotic gut microbiota are in dynamic balance with the host's organism to maintain homeostasis. Many different factors have an impact on this relationship, including bacterial metabolites. Several substrates for their synthesis have been established, including tryptophan, an exogenous amino acid. Many biological processes are influenced by the action of tryptophan and its endogenous metabolites, serotonin, and melatonin. Recent research findings also provide evidence that gut bacteria-derived metabolites of tryptophan share the biological effects of their precursor. Thus, this review aims to investigate the biological actions of indole-3-propionic acid (IPA), a gut microbiota-derived metabolite of tryptophan. We searched PUBMED and Google Scholar databases to identify pre-clinical and clinical studies evaluating the impact of IPA on the health and pathophysiology of the immune, nervous, gastrointestinal and cardiovascular system in mammals. IPA exhibits a similar impact on the energetic balance and cardiovascular system to its precursor, tryptophan. Additionally, IPA has a positive impact on a cellular level, by preventing oxidative stress injury, lipoperoxidation and inhibiting synthesis of proinflammatory cytokines. Its synthesis can be diminished in the presence of different risk factors of atherosclerosis. On the other hand, protective factors, such as the introduction of a Mediterranean diet, tend to increase its plasma concentration. IPA seems to be a promising new target, linking gut health with the cardiovascular system.


Clinical efficacy and safety of Naprelan versus Naprosyn in the treatment of rheumatoid arthritis.
A double-blind, randomized study compared the efficacy and safety of a controlled-release naproxen sodium formulation (Naprelan, Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) 1,000 mg once daily; a conventional naproxen formulation (Naprosyn, Syntex Laboratories, Inc., Palo Alto, California) 500 mg BID; and placebo given for 12 weeks to 348 patients with rheumatoid arthritis (RA). This was followed by an open-label study to evaluate the safety of naprelan 1,000 mg once daily for an additional 9 months. In the double-blind phase of this study, the safety and efficacy of Naprelan 1,000 mg once daily were compared with those of Naprosyn 500 mg twice daily and placebo in 348 patients with RA. At the end of 12 weeks of treatment, Naprelan and Naprosyn were numerically superior to placebo in 3 of the 4 primary efficacy variables--physician's global assessment, patient's global assessment, and number of painful joints. Differences between Naprelan and placebo reached statistical significance for the patient's global assessment at Week 12 (Visit 7). Significantly more Naprosyn- than placebo-treated patients had at least 1 severe digestive system adverse event (AE); 1 drug-related AE; or 1 drug-related, digestive-system AE. There was no statistically significant difference in the number of AEs experienced by Naprelan-treated patients compared with those who received placebo. A total of 240 patients enrolled in the Naprelan open-label phase. As would be expected, patients initially treated with placebo showed significant improvement after starting Naprelan. Those initially receiving Naprelan or Naprosyn also maintained their improvement. The AE profile with Naprelan was similar to that reported in the double-blind phase. It was concluded that Naprelan 1,000 mg once daily was as effective as Naprosyn 500 mg BID in the treatment of RA and was particularly effective in relieving pain later in the day. The controlled-release formulation may also offer safety benefits.


3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.
3H-(+/-)-4-Bromo-2,5-dimethoxyphenylisopropylamine (3H-DOB), a putative agonist radioligand, was synthesized and used to label 5-HT2 receptors in a particulate fraction prepared from rat frontal cortex tissue homogenates. The specific binding (defined by the difference in 3H-DOB binding in the presence and absence of 10(-6) M cinanserin, a potent and specific 5-HT2 antagonist) displayed high affinity (KD = 4.1 X 10(-10) M) and saturability with a Bmax of 17.9 fmol/mg of protein. The distribution of specific 3H-DOB binding in nine brain regions correlated closely with the distribution of 3H-ketanserin (an antagonist radioligand)-labeled 5-HT2 receptors. Competition studies in frontal cortex homogenates using a variety of compounds revealed a distinct 5-HT2 receptor pharmacology. A series of 5-HT2 antagonists exhibited high affinities in competition studies for specific 3H-DOB binding. The absolute potencies of these antagonists as well as their order of potencies closely correlated with their potencies in competing for 3H-ketanserin-labeled brain 5-HT2 receptors. A series of 5-HT2 agonists also exhibited high affinities in competition studies for specific 3H-DOB binding. Although the order of potencies of these agonists was similar to their order in competing for 3H-ketanserin-labeled brain 5-HT2 receptors, the agonists displayed 10-100-fold higher affinities for the 3H-DOB-labeled sites than for the 3H-ketanserin-labeled sites. The level of specific 3H-DOB binding in the frontal cortex homogenates was approximately 5% of the levels of 3H-ketanserin-labeled 5-HT2 receptors (358 fmol/mg of protein). Taken together, these results indicate that 3H-DOB labels a subset of brain 5-HT2 receptors that has high affinity for agonists as well as antagonists); 3H-ketanserin appears to label both subsets of brain 5-HT2 receptors. Antagonists apparently do not discriminate between these two subsets of 5-HT2 receptors. 3H-DOB specific binding to 5-HT2 receptors was potently inhibited by guanosine 5'-(beta, gamma-imido)triphosphate and guanosine 5'-O-(3-thio)triphosphate (nonhydrolyzable derivatives of GTP) with IC50 values of 42 and 21 nM, respectively, whereas adenosine 5'-(beta, gamma-imido)triphosphate and adenosine 5'-O-(3-thio)triphosphate (nonhydrolyzable derivatives of ATP) had no effect. In summary, 3H-DOB specific binding displays the pharmacological characteristics of a 5-HT2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)


Reliability of proxy respondents for patients with stroke: a systematic review.
Proxy respondents are an important aspect of stroke medicine and research. We performed a systematic review of studies evaluating the reliability of proxy respondents for stroke patients. Studies were identified by searches of MEDLINE, Google, and the Cochrane Library between January 1969 and June 2008. All were prospective or cross-sectional studies reporting the reliability of proxy respondents for patients with a history of previous stroke or transient ischemic attack. One author abstracted data. For each study, intraclass correlation (ICC) or the k-statistic was categorized as poor (<or=0.40), moderate (0.41-0.60), substantial (0.61-0.80), or excellent (>0.80). Thirteen studies, with a total of 2618 participants, met our inclusion criteria. Most studies recruited patients >3 months after their stroke. Of these studies, 5 (360 participants; 5 scales) evaluated reliability of proxy respondents for activities of daily living (ADL), and 9 (2334 participants; 9 scales) evaluated reliability of proxy respondents for quality of life (QoL). One study evaluated both. In studies, the ICC/k for scales ranged from 0.61 to 0.91 for ADL and from 0.41 to 0.8 for QoL. Most studies reported that proxy respondents overestimated impairments compared with patient self-reports. Stroke severity and objective nature of questions were the most consistent determinants of disagreement between stroke patient and proxy respondent. Our data indicate that beyond the acute stroke period, the reliability of proxy respondents for validated scales of ADL was substantial to excellent, while that of scales for QoL was moderate to substantial.


The Diagnostic, Prognostic, and Therapeutic Utility of Molecular Testing in a Patient with Waldenstrom's Macroglobulinemia.
The application of molecular genomics and our understanding of its clinical implications in the diagnosis, prognostication and treatment of lymphoproliferative disorders has rapidly evolved over the past few years. Of particular importance are indolent B-cell malignancies where tumour cell survival and proliferation are commonly driven by mutations involving the B-cell receptor and downstream signalling pathways. In addition, the increasing number of novel therapies and targeted agents have provided clinicians with new therapeutic options with the aim of exploiting such mutations. In this case report, we highlight one such success story involving the diagnostic impact of the MYD88L265P mutation in Waldenstrom's macroglobulinemia (WM), its prognostic implications and effect on choice of therapy in the era of novel therapies.