Accuracy and cost-effectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable non-small cell lung cancer.
This retrospective study of patients who were referred for surgical resection of non-small cell lung cancer (NSCLC) assessed the accuracy and cost-effectiveness of positron emission tomography (PET) with radiolabeled [18F]-2-fluoro-deoxy-D-glucose (FDG) in staging mediastinal lymph nodes (MLNs). From January 2001 to September 2002, 90 patients with suspected or proven NSCLC who had been referred for curative resection were retrospectively reviewed. All patients were without evidence of metastatic disease. Sixty-nine of the 90 patients had undergone thoracic FDG-PET imaging as part of their evaluation and are the focus of this study. Sensitivity, specificity, accuracy, and positive and negative predictive values for metastasis to the MLN were calculated for CT scanning vs FDG-PET scanning. Four algorithms for staging MLN with mediastinoscopy and/or FDG-PET scan were compared. Sixty-nine patients underwent preoperative CT and FDG-PET scans, and 32 of 69 patients underwent mediastinoscopy. Fifty-seven patients underwent thoracotomy with complete mediastinal lymphadenectomy. Sensitivity, specificity, accuracy, and positive and negative predictive values for CT scans and FDG-PET scans were 46%, 86%, 78%, 43%, and 87%, and 62%, 98%, 91%, 89% and 92%, respectively. Mediastinoscopy was accurate in 32 of 32 patients (100%). Routine mediastinoscopy remains the most economically reasonable strategy with excellent sensitivity. Selective FDG-PET imaging improved the sensitivity of noninvasive staging for patients with normal MLNs on CT scans. Selective use of FDG-PET imaging improves staging accuracy compared to CT scanning alone and makes it a cost-effective adjunct to the preoperative staging of NSCLC. However, in patients with adenocarcinoma and MLNs of < 1 cm, FDG-PET scanning cannot yet replace mediastinoscopy.


[The effect of low doses of a synthetic analog of a quinoid radiotoxin on the viability of normal and gamma-irradiated animals].
The method for a production of synthetic quinoid radiotoxins in vitro has been developed and described. Synthetic quinoid radiotoxins like quinoid radiotoxins (qRT) which are being produced from irradiated tissues of the organisms have demonstrated high toxicity at relatively high qRT concentrations. However, when synthetic qRT is introduced into the organisms in ultra-small concentrations, one can observe the opposite action: the resistance of the organism increases and a number of essential functions are activated. Quinoid radiotoxins are assumed to take part in regulatory processes responsible for radiation hormesis.


Irreversible Blindness Following Periocular Autologous Platelet-Rich Plasma Skin Rejuvenation Treatment.
A 49-year-old woman developed acute visual loss in the right eye following bilateral cosmetic platelet-rich plasma injections to rhytids in the glabellar region. External exam showed skin necrosis in the region over the right rhytids and restricted right ocular motility. Dilated fundus exam was significant for ophthalmic artery occlusion. Imaging revealed right eye extraocular muscle ischemia and optic nerve infarction, along with right frontal, parietal, and occipital lobe infarction. Work-up for thromboembolic and vascular etiologies were negative. To our knowledge, this is the first case reported of extensive ischemia following autologous platelet-rich plasma therapy.


Long-term administration of intranasal oxytocin is a safe and promising therapy for early adolescent boys with autism spectrum disorders.
Oxytocin (OT) has been a candidate for the treatment of autism spectrum disorders (ASD), and the impact of intranasally delivered OT on ASD has been investigated. However, most previous studies were conducted by single-dose administration to adults; and, therefore, the long-term effect of nasal OT on ASD patients and its effect on children remain to be clarified. We conducted a singled-armed, open-label study in which OT was administered intranasally over the long term to eight male youth with ASD (10-14 years of age; intelligence quotient [IQ] 20-101). The OT administration was performed in a stepwise increased dosage manner every 2 months (8, 16, 24 IU/dose). A placebo period (1-2 weeks) was inserted before each step. The outcome measures were autism diagnostic observation schedule--generic (ADOS-G), child behavior checklist (CBCL), and the aberrant behavior checklist (ABC). In addition, side effects were monitored by measuring blood pressure and examining urine and blood samples. Six of the eight participants showed improved scores on the communication and social interaction domains of the ADOS-G. However, regarding the T-scores of the CBCL and the scores of the ABC, we could not find any statistically significant improvement, although several subcategories showed a mild tendency for improvement. Caregivers of five of the eight participants reported certain positive effects of the OT therapy, especially on the quality of reciprocal communication. All participants showed excellent compliance and no side effects. Although our results on the efficacy of long-term nasal OT therapy still remain controversial, to the best of our knowledge, this is the first report documenting the safety of long-term nasal OT therapy for children with ASD. Even though our data are too preliminary to draw any definite conclusions about efficacy, they do suggest this therapy to be safe, promising, and worthy of a large-scale, double-blind placebo-controlled study.


Construction and evaluation of yeast expression networks by database-guided predictions.
DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We performed microarray experiments to elucidate the transcriptional networks, which are up- or down-regulated in response to the expression of toxic polyglutamine proteins in yeast. Such experiments initially generate hit lists containing differentially expressed genes. To look into transcriptional responses, we constructed networks from these genes. We therefore developed an algorithm, which is capable of dealing with very small numbers of microarrays by clustering the hits based on co-regulatory relationships obtained from the SPELL database. Here, we evaluate this algorithm according to several criteria and further develop its statistical capabilities. Initially, we define how the number of SPELL-derived co-regulated genes and the number of input hits influences the quality of the networks. We then show the ability of our networks to accurately predict further differentially expressed genes. Including these predicted genes into the networks improves the network quality and allows quantifying the predictive strength of the networks based on a newly implemented scoring method. We find that this approach is useful for our own experimental data sets and also for many other data sets which we tested from the SPELL microarray database. Furthermore, the clusters obtained by the described algorithm greatly improve the assignment to biological processes and transcription factors for the individual clusters. Thus, the described clustering approach, which will be available through the ClusterEx web interface, and the evaluation parameters derived from it represent valuable tools for the fast and informative analysis of yeast microarray data.


Physiological basis of limb-impedance modulation during free and constrained movements.
Arm stiffness is a critical factor underlying stable interactions with the environment. When the hand moves freely through space, a stiff limb would most effectively maintain the hand on the desired path in the face of external perturbations. Conversely, when constrained by a rigid surface, a compliant limb would allow the surface to guide the hand while minimizing variations in contact forces. We aimed to identify the physiological basis of stiffness adaptation for these two classes of movement. Stiffness can be regulated by two mechanisms: coactivation of antagonistic muscles and modulation of reflex gains. We hypothesized that subjects would select high stiffness (high coactivation and/or reflex gains) in free space and high compliance (low coactivation and reflex gains) for constrained movements. We measured EMG and the H-reflex during constrained and unconstrained movement of the wrist. As predicted, subjects coactivated antagonist muscles more when performing the unconstrained movement. Contrary to our hypothesis, however, H-reflex amplitude was higher for the constrained movement despite the a priori preference for lower reflex gains in this situation. In addition, the H-reflex depended on the task and the net force exerted by the limb on the environment, rather than showing a simple dependence on the level of muscle activation. Thus stiffness seems to increase in free space compared with constrained motion through the use of coactivation, whereas spinal loop gains are adjusted to better regulate the influence of afferences on the ongoing movement. These observations support the hypothesis of movement programming in terms of impedance.


Bayesian pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging: validation and application.
Tracer-kinetic analysis of dynamic contrast-enhanced magnetic resonance imaging data is commonly performed with the well-known Tofts model and nonlinear least squares (NLLS) regression. This approach yields point estimates of model parameters, uncertainty of these estimates can be assessed e.g. by an additional bootstrapping analysis. Here, we present a Bayesian probabilistic modeling approach for tracer-kinetic analysis with a Tofts model, which yields posterior probability distributions of perfusion parameters and therefore promises a robust and information-enriched alternative based on a framework of probability distributions. In this manuscript, we use the quantitative imaging biomarkers alliance (QIBA) Tofts phantom to evaluate the Bayesian tofts model (BTM) against a bootstrapped NLLS approach. Furthermore, we demonstrate how Bayesian posterior probability distributions can be employed to assess treatment response in a breast cancer DCE-MRI dataset using Cohen's d. Accuracy and precision of the BTM posterior distributions were validated and found to be in good agreement with the NLLS approaches, and assessment of therapy response with respect to uncertainty in parameter estimates was found to be excellent. In conclusion, the Bayesian modeling approach provides an elegant means to determine uncertainty via posterior distributions within a single step and provides honest information about changes in parameter estimates.


[Multiple lipomatosis and Recklinghausen's neurofibromatosis (author's transl)].
On the occasion of two separate observations of multiple lipomatosis on a 48 years old female patient and a neurofibromatosis on a 49 years old male patient, the differential diagnosis of these diseases was compiled with regard to the cutaneous and subcutaneous symptoms and to the relations to the nervous system and the inner organs. The differential diagnostical plan requires a series of clinical examinations for the clarification of these pathological conditions, which often comprise more than one disease or one syndrome.


Unlocking the health system barriers to maximise the uptake and utilisation of molecular diagnostics in low-income and middle-income country setting.
Early access to diagnosis is crucial for effective management of any disease including tuberculosis (TB). We investigated the barriers and opportunities to maximise uptake and utilisation of molecular diagnostics in routine healthcare settings. Using the implementation of WHO approved TB diagnostics, Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) and Line Probe Assay (LPA) as a benchmark, we evaluated the barriers and how they could be unlocked to maximise uptake and utilisation of molecular diagnostics. Health officers representing 190 districts/counties participated in the survey across Kenya, Tanzania and Uganda. The survey findings were corroborated by 145 healthcare facility (HCF) audits and 11 policy-maker engagement workshops. Xpert MTB/RIF coverage was 66%, falling behind microscopy and clinical diagnosis by 33% and 1%, respectively. Stratified by HCF type, Xpert MTB/RIF implementation was 56%, 96% and 95% at district, regional and national referral hospital levels. LPA coverage was 4%, 3% below culture across the three countries. Out of 111 HCFs with Xpert MTB/RIF, 37 (33%) used it to full capacity, performing ≥8 tests per day of which 51% of these were level five (zonal consultant and national referral) HCFs. Likewise, 75% of LPA was available at level five HCFs. Underutilisation of Xpert MTB/RIF and LPA was mainly attributed to inadequate-utilities, 26% and human resource, 22%. Underfinancing was the main reason underlying failure to acquire molecular diagnostics. Second to underfinancing was lack of awareness with 33% healthcare administrators and 49% practitioners were unaware of LPA as TB diagnostic. Creation of a national health tax and decentralising its management was proposed by policy-makers as a booster of domestic financing needed to increase access to diagnostics. Our findings suggest higher uptake and utilisation of molecular diagnostics at tertiary level HCFs contrary to the WHO recommendation. Country-led solutions are crucial for unlocking barriers to increase access to diagnostics.


Selective modification of variable loops alters tropism and enhances immunogenicity of human immunodeficiency virus type 1 envelope.
Although the B clade of human immunodeficiency virus type 1 (HIV-1) envelopes (Env) includes five highly variable regions, each of these domains contains a subset of sequences that remain conserved. The V3 loop has been much studied for its ability to elicit neutralizing antibodies, which are often restricted to a limited number of closely related strains, likely because a large number of antigenic structures are generated from the diverse amino acid sequences in this region. Despite these strain-specific determinants, subregions of V3 are highly conserved, and the effects of different portions of the V3 loop on Env tropism and immunogenicity have not been well delineated. For this report, selective deletions in V3 were introduced by shortening of the stem of the V3 loop. These mutations were explored in combination with deletions of selected V regions. Progressive shortening of the stem of V3 abolished the immunogenicity as well as the functional activity of HIV Env; however, two small deletions on both arms of the V3 stem altered the tropism of the dualtropic 89.6P viral strain so that it infected only CXCR4(+) cells. When this smaller deletion was combined with removal of the V1 and V2 loops and used as an immunogen in guinea pigs, the antisera were able to neutralize multiple independent clade B isolates with a higher potency. These findings suggest that highly conserved subregions within V3 may be relevant targets for eliciting neutralizing antibody responses, affecting HIV tropism, and increasing the immunogenicity of AIDS vaccines.


IFEL TOUR: A Description of the Introduction to FUN Electrophysiology Labs Workshop at Bowdoin College, July 27-30, and the Resultant Faculty Learning Community.
The workshop "Introduction to FUN Electrophysiology Labs" was organized by Patsy Dickinson (Bowdoin College), Steve Hauptman (Bowdoin College), Bruce Johnson (Cornell University), and Carol Ann Paul (Wellesley College). It took place July 27-30 2006 at Bowdoin College. There were fifteen participants, most of whom were junior faculty at college and universities around the country. This article describes the workshop content, the incorporation of lab exercises at home institutions, and the faculty learning community that has resulted from the workshop.


[Experimental study of combination of ciprofloxacin and oxytocin on formation of biofilms by opportunistic bacteria].
To study in vitro and in vivo effect of oxytocin and ciprofloxacin combination on formation of biofilms by agents of surgical infections. Microorganisms of different species isolated by conventional methods from patients with purulent soft tissue infections were used in experiments. Ciprofloxacin manufactured by "Dr. Reddys" (India) and oxytocin manufactured by "Gedeon Richter" (Hungary) were used. For in vitro experiments one-half of minimal inhibitory concentrations of drugs were used. Oxytocin-placebo ("Gedeon Richter", Hungary) was used for control tests. Formation of biofilms was assessed using method proposed by G. O'Toole (2000). For in vivo experiments septic wounds in 1st phase of wound process were modeled according to method proposed by E.M. Danilova (1992). Wounds were infected with Staphylococcus aureus strain 104, which has strong ability to form biofilms. Efficacy of treatment was assessed on signs of inflammatory process and microscopy of touch smears for detection of bacterial biofilms. In experiments in vivo addition of oxytocin to nutrient medium resulted in suppression of biofilm formation by studied microorganisms. Obtained data were confirmed by in vivo experiments which demonstrated higher efficacy of local application of ciprofloxacin and oxytocin combination for treatment of septic wounds compared to separate use of ciprofloxacin or oxytocin. Studies performed in vitro and in vivo showed efficacy of oxytocin and ciprofloxacin combination, which is determined not only by enhancement of antimicrobial effect of the drug against pathogen but also by suppression of biofilm formation in the wound during infection.


Test-Retest Reliability of a Modified Visual Analog Scale Assessment Tool for Determining Incidence and Severity of Gastrointestinal Symptoms in Response to Exercise Stress.
Considering the recent growth of exercise gastroenterology research focusing on exercise-induced gastrointestinal syndrome mechanisms, response magnitude, prevention and management strategies, the standardized assessment of gastrointestinal symptoms (GIS) is warranted. The current methodological study aimed to test the reliability of a modified visual analog scale for assessing GIS during exercise, in response to a variety of exertional-stress scenarios, with and without dietary intervention. Recreational endurance runners (n = 31) performed one of the three exercise protocols, which included: 2-hr running at 70% V˙O2max in temperate (24.7 °C) ambient conditions, with fluid restriction; 2-hr running at 60% V˙O2max in hot (35.1 °C) ambient conditions, while consuming chilled water immediately before and every 15 min during exercise; and 2-hr running at 60% V˙O2max in temperate (23.0 °C) ambient conditions, while consuming 30 g/20 min carbohydrate (2∶1 glucose∶fructose, 10% temperate w/v), followed by a 1-hr distance test. GIS was monitored pre-exercise, periodically during exercise, and immediately postexercise. After wash out, participants were retested in mirrored conditions. No significant differences (p > .05) were identified between test-retest using Wilcoxon signed-rank test for all GIS (specific and categorized), within each exercise protocol and the combined protocols. Strong correlations were observed for gut discomfort, total GIS, upper GIS, and nausea (rs = .566 to rs = .686; p < .001), but not for lower GIS (rs = .204; p = .232). Cohen's magnitude of difference was minimal for all GIS (specific δ < 0.14 and categorized δ < 0.08). The modified visual analog scale for assessing GIS during exercise appears to be a reliable tool for identifying incidence and severity of GIS in cohort populations and is sensitive enough to detect exertional and intervention differences.


[Autoimmune reactions in patients with various tumor localizations].
Autoantibody levels in patients with malignancies of the oral cavity and lung and autoimmune disorders have been assayed. It was found that tumors initiated polymorphous autoimmune reactions to various tissue antigens. Autoantibody production rates in tumor patients were comparable with those in autoimmune disorders. The role of autoimmune reactions in cancer pathogenesis is discussed.


[Bifocal contact lenses as a correction method in presbyopia].
A study aimed at assessing the efficiency of presbyopia correction by bifocal contact lenses (BCL) was undertaken; it envisaged a comprehensive evaluation of subjective data provided by patients and measurements of a number of functional parameters of the visual quality for far and near, including mono- and binocular measurements with BCL of different constructions versus a maximal sphero-cylindrical spectacle correction for far and for near. Soft Acuvue Bifocal BCL as well as soft and rigid BCL manufactured in the optical-and-mechanical laboratory of the Research Institute for Eye Disease of the Russian Academy of Medical Sciences and Russian-made and imported bifocal soft and rigid lenses, respectively, were made use of in the study. A reduced contrast sensitivity (mainly in high frequencies) to 7% with Russian-made BCL, to 12.5% with Acuvue Bifocal BCL, to 8.7% with monofocal BCL and to 13.4% with the "mono-vision" system was registered. A decreased visual working ability to 13% with soft bifocal Russian-made BCL, to 17.3% with Acuvue Bifocal BCL and to 20.7% with the "mono-vision" system was detected versus the spectacle correction. A reduction by 25% was noted in the stereoscopic vision indices with the "mono-vision" system. A study of sensitivity to dazzling did not show any statistically reliable differences between various correction types.


Small Molecule Inhibitors Confirm Ubiquitin-Dependent Removal of TOP2-DNA Covalent Complexes.
DNA topoisomerase II (TOP2) is required for the unwinding and decatenation of DNA through the induction of an enzyme-linked double-strand break (DSB) in one DNA molecule and passage of another intact DNA duplex through the break. Anticancer drugs targeting TOP2 (TOP2 poisons) prevent religation of the DSB and stabilize a normally transient intermediate of the TOP2 reaction mechanism called the TOP2-DNA covalent complex. Subsequently, TOP2 remains covalently bound to each end of the enzyme-bridged DSB, which cannot be repaired until TOP2 is removed from the DNA. One removal mechanism involves the proteasomal degradation of the TOP2 protein, leading to the liberation of a protein-free DSB. Proteasomal degradation is often regulated by protein ubiquitination, and here we show that inhibition of ubiquitin-activating enzymes reduces the processing of TOP2A- and TOP2B-DNA complexes. Depletion or inhibition of ubiquitin-activating enzymes indicated that ubiquitination was required for the liberation of etoposide-induced protein-free DSBs and is therefore an important layer of regulation in the repair of TOP2 poison-induced DNA damage. TOP2-DNA complexes stabilized by etoposide were shown to be conjugated to ubiquitin, and this was reduced by inhibition or depletion of ubiquitin-activating enzymes. SIGNIFICANCE STATEMENT: There is currently great clinical interest in the ubiquitin-proteasome system and ongoing development of specific inhibitors. The results in this paper show that the therapeutic cytotoxicity of DNA topoisomerase II (TOP2) poisons can be enhanced through combination therapy with ubiquitin-activating enzyme inhibitors or by specific inhibition of the BMI/RING1A ubiquitin ligase, which would lead to increased cellular accumulation or persistence of TOP2-DNA complexes.


Preoperative radiotherapy for colorectal cancer.
In a prospective randomized trial, 700 patients with a confirmed histological diagnosis of adenocarcinoma of the rectum or rectosigmoid were randomized to receive radiotherapy prior to operation (2000 to 2500 rads in two weeks) or surgery alone. Five year observed survival in the 453 patients on whom "curative" resection was possible was 48.5% in the X-ray treated group compared with 38.8% in controls, while in the 305 having low lying lesions requiring abdominoperineal resection, survival in the treated group was 46.9% compared with 34.3% in controls. Although suggestive of a treatment benefit, neither is considered statistically significant. Histologically positive lymph nodes were found in 41.2% of the control group and in only 27.8% of the patients receiving radiotherapy. Reveiw of all patients who died during the study shows a consistently lower death rate from cancer in the radiotherapy group. Although this study suggests a treatment benefit from preoperative radiotherapy, further studies now in progress by this group and others are necessary to determine the optimal dose regimen.


The Strongest Risk Factor for Operative Mortality in Acute Type A Aortic Dissection is Acidosis: Validation of Risk Model.
Multiple risk factors for operative mortality in the setting of acute type A aortic dissection (ATAAD) have been described. Recently, the combination of severe acidosis and malperfusion was found to significantly impact operative mortality following surgery for ATAAD and a treatment algorithm was proposed. The purpose of this study is to validate these findings in our institution. A retrospective chart review was performed for patients who underwent ATAAD repair between Feb 1997 and Jan 2018. Preoperative nadir pH, bicarbonate, base deficit, organ malperfusion, and other relevant parameters were collected. Multivariable logistic regression was performed to evaluate operative mortality. A total of 298 patients underwent ATAAD repair. The highest operative mortality (18/49; 37%) was noted in patients with severe acidosis (base deficit ≤ -10). There were 96 patients (32%) with malperfusion. In patients with abdominal malperfusion, this trend is even more pronounced. Multivariable logistic regression showed that severe acidosis is associated with higher operative mortality, odds ratio of 13.9 (P = 0.001). The presence of diabetes and advanced age were also associated with higher operative mortality. These findings validate the previously reported findings that severe acidosis is a strong predictor of operative mortality, and risk increases with associated organ malperfusion. This supports the suggestion that base deficit, which is easily performed at the bedside, should be used clinically to predict operative mortality and should be collected in aortic dissection databases.


Prevalence of prematurely lost primary teeth in 5-10-year-old children in Thamar city, Yemen: A cross-sectional study.
The premature loss of primary teeth is a potential risk factor for poor arch length development. Adequate arch length is important to the progression of the permanent teeth. Poor arch length can lead to crowding, ectopic eruption, or impaction of these teeth. This study is designed to assess the prevalence of premature loss of primary teeth in the 5-10-year-old age group. The study group included 185 children, that is, 91 boys and 94 girls. The dental examination was conducted by an experienced examiner under sufficient artificial light. Data including patient age and missing teeth were collected. Descriptive statistics were applied for data analysis, and from the results, Chi-square tests were used at a level of significance of 5% (P < 0.05). We observed a 40.54% prevalence of premature loss of primary teeth with no statistically significant difference between genders. The lower left primary second molar was the most commonly absent tooth in the dental arch (13.5%). The status of premature loss of primary teeth was high in the study group. Implementation of efficient educational and preventive programs to promote oral health would help children maintain a healthy primary dentition and eventually prevent the disturbances in the future development of normal occlusion. Early detection and management of the space problems associated with the early loss of primary teeth would help in reducing malocclusion problems.


A dielectric metasurface optical chip for the generation of cold atoms.
Compact and robust cold atom sources are increasingly important for quantum research, especially for transferring cutting-edge quantum science into practical applications. In this study, we report on a novel scheme that uses a metasurface optical chip to replace the conventional bulky optical elements used to produce a cold atomic ensemble with a single incident laser beam, which is split by the metasurface into multiple beams of the desired polarization states. Atom numbers ~107 and temperatures (about 35 μK) of relevance to quantum sensing are achieved in a compact and robust fashion. Our work highlights the substantial progress toward fully integrated cold atom quantum devices by exploiting metasurface optical chips, which may have great potential in quantum sensing, quantum computing, and other areas.


Is unilateral tonsillar enlargement alone an indication for tonsillectomy?
Unilateral tonsillar enlargement is often seen in the out-patient setting. Frequently, these patients are listed for tonsillectomy for the purpose of ruling out malignant histology. This study aims to determine the necessity for tonsillectomy. This retrospective case-note review looks at all the tonsillectomies performed for histological examination at our institution over a five year period, and analyses the histological findings in those with unilateral tonsillar enlargement (UTE) alone, and those with UTE with other clinical features (history of chronic pain, dysphagia, the presence of tonsillar or peritonsillar mucosal abnormality, those with cervical lymphadenopathy). All patients who underwent tonsillectomy for the purpose of histological examination from 1 June 1998 to 30 May 2003 were identified and their notes reviewed. Exclusion criteria included cases where there were no pre-operative out-patient notes, those patients where the specimens had been sent from other hospitals, those patients who had malignancy already diagnosed, and those cases where tonsillectomy had been performed by other surgical specialties (e.g. maxillofacial, plastics). There were 1475 tonsillectomies, of which 181 performed over this period were sent for histological analysis. After excluding those patients that did not meet our criteria, we were left with 53 patients who had UTE. The primary outcome measure was the rate of malignancy in the two groups. Of these, 33 had UTE alone, 20 had associated clinical features. In the former group, none of the patients were found to have malignancy. In the latter, nine (45 per cent) had a malignancy. Fisher's exact test was used to test for differences between the UTE alone group versus the UTE plus other features group (p<0.001). The prevalence of malignancy in tonsils which exhibit asymmetry with no other clinical features is very low; in our study it was zero. However, other studies have found a small percentage representing underlying malignancy. In view of this, we feel that a 'watch and wait' policy is initially more appropriate, and if symptoms or signs are progressive, tonsillectomy should then be advised.


Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels.
The aim of the present study was to investigate the role of GABAergic and nitriergic modulation in the antianxiety effect of thymoquinone, a major constituent of Nigella sativa, in mice under unstressed and stressed conditions. Thymoquinone (10 and 20 mg/kg), methylene blue (1 mg/kg) and diazepam (2 mg/kg) were administered followed by behavioral testing using an elevated plus maze, the light/dark test and the social interaction test in both unstressed and stressed mice (mice subjected to 6 h immobilization). The effects of the above-mentioned drugs on plasma nitrite, a stable metabolite of nitric oxide (NO) and brain GABA content were also studied. Diazepam (2 mg/kg) produced significant anxiolytic-like effects only in unstressed mice. However, diazepam significantly increased the GABA content in both unstressed and stressed mice as compared with their respective control groups. Thymoquinone (10 and 20 mg/kg) produced significant antianxiety effects in unstressed mice without altering nitrite levels, but only the higher dose (20 mg/kg) of thymoquinone increased the GABA content in unstressed mice. In stressed mice, thymoquinone (20 mg/kg) showed anxiolytic effects, with a significant decrease in plasma nitrite and reversal of the decreased brain GABA content. Pre-treatment with methylene blue enhanced the antianxiety effect of thymoquinone in both unstressed and stressed mice. Therefore, the present study suggests an involvement of NO-cGMP and GABAergic pathways in the anxiolytic-like activity of thymoquinone.


FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics.
The transcription factor DeltaFosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) between controls and alcoholics using semiquantitative immunoblotting. In both structures, we detected three forms of FOSB, one of which was DeltaFOSB, but in neither case did their immunoreactivities differ between the groups. Our results indicate that the DeltaFOSB immunoreactivity in the human brain is very low, and that it is not accumulated in the OFC and DLPFC of human alcoholics, suggesting that it may not be directly involved in addiction maintenance, at least not in ethanol dependence.


Pseudomonas aeruginosa infection in mice after treatment with cyclophosphamide.
This study attempted to determine if the antineoplastic alkylating agent, cyclophosphamide (Cytoxan), altered the host response to Pseudomonas aeruginosa infection in mice. The effect of cyclophosphamide was evaluated by an increased mortality or enhanced bacterial growth in the liver, lungs, spleen, and kidneys. The mice that were treated with either single or multiple doses of 25 mg/kg cyclophosphamide showed no increase in mortality, nor did they exhibit an enhanced localization of P aeruginosa in any of the organs studied. Higher dose levels of cyclophosphamide produced a statistically significant increase in mortality and greater distribution of bacteria in the mouse organs, but there appeared to be no organ that was particularly susceptible to infection.


Imaging assessment of bioresorbable vascular scaffolds.
Vascular reparative therapy has become a reality with bioresorbable scaffolds (BRSs). To assess acute and long-term performance of the device, multimodality imaging would be essential. Radiopacity of metal hinders the imaging assessment, whereas radiolucent polymeric scaffolds allow for a precise imaging assessment with either invasive or non-invasive modality at baseline and at follow-up, which is one of the advantages of polymeric BRSs. Recent large trials evaluating clinical results of the first-generation BRS technology raised concerns about the safety and efficacy of these devices, namely, scaffold thrombosis. Intensive research with multimodality imaging in the field is being conducted to have in-depth understanding of the issues, which will facilitate the improvement of implantation techniques and the development of the next-generation BRSs. The current review focuses on the clinical application of the imaging modalities to assess the short- and long-term performance of the Absorb BVS.


Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in vivo.
Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. A549 cells were treated with 10~320 μg/ml Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) . Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at 20 μg/ml, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.


Pre-orchiectomy tumor marker levels should not be used for International Germ Cell Consensus Classification (IGCCCG) risk group assignment.
To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT). Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen's kappa. Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen's kappa of 0.888 (p < 0.001). Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended.


Ultrasound elastography in thyroid disease.
Thyroid elastography has become, lately, one of the main focuses in thyroid imaging. With more than one hundred papers published on this subject, the core of accumulated knowledge justifies the need for a comprehensive review on the topic. The paper presents the various elastographic techniques used for thyroid assessment. Both strain and shear wave elastography, with all their variants, are discussed. Thereafter the paper proceeds to a detailed description of the technical peculiarities, diagnostic value, limitations and pitfalls for each technique. Although the main accent is placed on thyroid nodules, the applications of elastography in other thyroid disease, diffuse or focal, are also presented. The results of the available metaanalyses are reviewed and the proven value of the technique is highlighted. Still unanswered questions and directions for future research are emphasized, whenever appropriate.


The Retention of Older Employees and Core Work Activities: Evidence From Denmark.
Retention of older employees in the labor market is crucial to cope with aging populations. Retention of older employees can appear in different forms, such as phased retirement, bridge jobs, career development, or health promotion. However, little is known about how the offering of these retention strategies may vary across workplaces with different core work activities because the opportunities to implement different types of retention strategies are preconditioned by differences in the economic and labor market climate. The study utilizes data from a survey conducted among Danish workplaces in 2018, which is linked to administrative register data to conduct Karlson-Holm-Breen-corrected logistic regression models. The study distinguishes among production workplaces, service and welfare workplaces, and information workplaces. Phased retirement is most prevalent in service and welfare workplaces, whereas job bridging is most prevalent in both service and welfare and production workplaces. Career development and health promotion strategies are least prevalent in production workplaces. These retention differences between workplaces with different core work activities are in most cases explained by differences in trade union influence, physical working demands, and knowledge intensity. Although the type of retention strategy offered in the workplace largely matches the core work activity within the workplace, particularly production workplaces could feasibly take more advantage of using career development or health promotion strategies because the employees of these workplaces are more likely to retire early due to poor health and physical working conditions.


Sociopathy and psychotherapy outcome.
One hundred ten nonpsychotic opiate addicts were randomly assigned to receive paraprofessional drug counseling alone or counseling plus professional psychotherapy. The outcomes of patients who received psychotherapy were examined in terms of their DSM-III diagnoses. Four groups were compared: those with opiate dependence alone (N = 16); opiate dependence plus depression (N = 16); opiate dependence plus depression plus antisocial personality disorder (N = 17); and opiate dependence plus antisocial personality disorder (N = 13). Those with opiate dependence plus antisocial personality disorder alone improved only on ratings of drug use. Patients with opiate dependence alone or with opiate dependence plus depression improved significantly and in many areas. Opiate-dependent patients with antisocial personality plus depression responded almost as well as those with only depression. Antisocial personality disorder alone is a negative predictor of psychotherapy outcome, but the presence of depression appears to be a condition that allows the patient to be amenable to psychotherapy, even though the behavioral manifestations of sociopathy are present.


Mixed aortic valve disease: midterm outcome and predictors of adverse events.
The aim of this article is to determine freedom from adverse events (AE) defined as symptoms, aortic valve replacement (AVR), or death in the mixed aortic valve disease (MAVD) population. We reviewed patients with moderate/severe MAVD followed at Mayo Clinic from 1994-2013. Only asymptomatic patients with normal ejection fraction and trileaflet aortic valve were included. Cox proportional-hazard models and Kaplan-Meier method were used. We identified 213 patients with moderate/severe MAVD; mean age was 69 years (±11) and 67% were males. An AE endpoint was reached in 172 patients, and 69% of these AEs occurred in moderate MAVD (peak velocity of 3-3.9 m/s). Mean follow-up was 10.1 ± 3 years, and mean time to AE was 2.9 ± 2.1 years. A mechanical prosthesis was implanted in 71/151 (47%), and 54/151 (36%) had concomitant coronary artery bypass grafting and/or aorta replacement during AVR. Early surgical mortality was 0.7%. Freedom from AE endpoint was 42% [confidence interval (CI) 39-45%] and 30% (CI 27-33%) at 3 and 5 years, respectively. Predictors of AE were peak aortic velocity [hazard ratio (HR) 2.73; CI 1.97-2.84, P < 0.0001] for every 1 m/s difference and having severe stenosis or severe regurgitation at presentation (HR 2.58; CI 2.01-4.44, P = 0.001). Moderate MAVD had high rate of AEs comparable to severe isolated aortic stenosis and should be followed as such. Patients with severe MAVD should be evaluated at least every 6 months because half of them will become symptomatic and require AVR within 1 year.


The impact of health-management training programs in Latin America on job performance.
A study was undertaken in Mexico, Colombia, and El Salvador to determine the impact of a management training program on health managers' job performance. A quasi-experimental design was used where in the baseline study an intervention group of 85 district health managers in the three countries was compared with a control group of 71 managers who did not receive the training program. After the implementation of an 18-month training program (which included 5-day training workshops and a series of tasks to be carried out between the workshops), the outcome in terms of improved job performance (i.e. use of predefined management techniques) was measured through twelve management performance indicators. The data collection tools were two questionnaires, participant observation in managers' workplaces, focus group discussions, staff interviews, and document analysis. In Mexico, the control group showed 8.3 times weaker management performance compared to the intervention group; in Colombia the value was 3.6 and in El Salvador 2.4. Factors associated with a successful training outcome were: (a) training techniques, (b) strengthening of enabling factors, and (c) reinforcement mechanisms.


Natural therapies for ocular disorders, part one: diseases of the retina.
Diseases of the retina are the leading causes of blindness throughout the world. Evidence points to potential benefit from nutritional and botanical interventions for the prevention and treatment of several of these conditions, including macular degeneration, diabetic retinopathy, retinopathy of the newborn, and retinitis pigmentosa. Epidemiological evidence points to the potential of antioxidant vitamins E and C, carotenoids, zinc, and selenium in the prevention and possible treatment of macular degeneration. In addition, dietary components such as red wine-high in important flavonoids-and fruits and vegetables high in carotenoids appear to offer some protection. While diabetic retinopathy can best be prevented by maintaining good blood sugar control, there are a number of nutrients and botanicals which may help prevent and treat retinopathy by inhibiting protein glycosylation, stabilizing collagen, decreasing capillary permeability, and providing important antioxidant effects. Extensive research on the use of vitamin E for the prevention of retrolental fibroplasia (retinopathy of the newborn), despite yielding promising results, has not resulted in incorporation of vitamin E into conventional standards of care protocols. Retinitis pigmentosa resembles the retinal damage seen in taurine-deficient cats. While patients with retinitis pigmentosa do not appear to be deficient in taurine, they appear to have faulty cellular uptake of this important amino acid. Disturbed utilization of vitamin A also appears to play a part in retinitis pigmentosa, and a subgroup of patients benefit from supplementation.


An individualized causal framework for learning intercellular communication networks that define microenvironments of individual tumors.
Cells within a tumor microenvironment (TME) dynamically communicate and influence each other's cellular states through an intercellular communication network (ICN). In cancers, intercellular communications underlie immune evasion mechanisms of individual tumors. We developed an individualized causal analysis framework for discovering tumor specific ICNs. Using head and neck squamous cell carcinoma (HNSCC) tumors as a testbed, we first mined single-cell RNA-sequencing data to discover gene expression modules (GEMs) that reflect the states of transcriptomic processes within tumor and stromal single cells. By deconvoluting bulk transcriptomes of HNSCC tumors profiled by The Cancer Genome Atlas (TCGA), we estimated the activation states of these transcriptomic processes in individual tumors. Finally, we applied individualized causal network learning to discover an ICN within each tumor. Our results show that cellular states of cells in TMEs are coordinated through ICNs that enable multi-way communications among epithelial, fibroblast, endothelial, and immune cells. Further analyses of individual ICNs revealed structural patterns that were shared across subsets of tumors, leading to the discovery of 4 different subtypes of networks that underlie disparate TMEs of HNSCC. Patients with distinct TMEs exhibited significantly different clinical outcomes. Our results show that the capability of estimating individual ICNs reveals heterogeneity of ICNs and sheds light on the importance of intercellular communication in impacting disease development and progression.


The intermediate filament protein peripherin is a marker for cerebellar climbing fibres.
Immunocytochemical staining with antibodies to the class III intermediate filament protein peripherin reveals discrete subpopulations of neurons and nerve fibres throughout the rat central nervous system. Some of these fibres enter the cerebellar granular and molecular layers. Here we use light and electron microscopic immunocytochemistry and confocal fluorescence microscopy to identify the peripherin positive fibres in the molecular layer of the cerebella of various mammals. (1) The peripherin positive fibres in the molecular layer have morphological attributes of climbing fibres, and peripherin positive fibres are also detected in the olivo-cerebellar tract. Furthermore peripherin positive neurons can be seen in the inferior olive, from which climbing fibres originate. (2) The peripherin positive molecular layer fibres rapidly degenerate in rats treated with 3-acetylpyridine (3-AP), a reagent which destroys neurons in the inferior olive, and the time course of degeneration of these mirrors that previously described for 3-AP induced destruction of climbing fibres. (3) Cerebella of other mammal species tested (mouse, rabbit, pig, cow and human) revealed a similar peripherin staining pattern in the cerebellum, including fibres in the molecular layer with the morphology of climbing fibres. (4) We also noted peripherin positive spinocerebellar and vestibulocerebellar mossy fibres in the cerebellar granular layer of folia known to receive these inputs. (5) A subset of perivascular nerve fibres are also peripherin positive. These results show that peripherin is a useful marker for mammalian cerebellar climbing fibres, and that a subset of morphologically distinct cerebellar mossy fibres are also peripherin positive.


Morphological characteristics in peritoneum in patients with neutral peritoneal dialysis solution.
Peritoneal dialysis solution (PDS) plays a role in functional and morphological damage to the peritoneum. This study aimed to clarify the effect of neutral PDS in preventing morphological changes by assessing peritoneal damage and comparing morphological alterations between PD patients treated with neutral PDS and acidic PDS. Sixty-one patients participated from seven hospitals. All patients were treated with neutral PDS excluding icodextrin, during their entire PD treatment, and experienced no episode of peritonitis. The thickness of submesothelial compact (SMC) zone and the presence of vasculopathy in the anterior parietal abdominal peritoneum were assessed. The impact of icodextrin, hybrid therapy, and peritoneal rest and lavage in morphological alterations were determined. There was no significant difference in the average SMC thickness between neutral and acidic PDS. The vessel patency in patients using neutral PDS was significantly higher compared to that in acidic PDS at any time during PD. There were no significant suppressive effects from interventions or use of icodextrin with respect to peritoneal morphological injury. A monolayer of mesothelial cell was observed in approximately half the patients, especially in their receiving lavage patients. Neutral PDS, accompanied by other preventive approaches against peritoneal injury, might suppress the development of peritoneal morphological alterations.


Postoperative calcium requirements in 6,000 patients undergoing outpatient parathyroidectomy: easily avoiding symptomatic hypocalcemia.
To determine the amount and duration of supplemental oral calcium for patients with varying clinical presentations discharged immediately after surgery for primary hyperparathyroidism. A 4-year, prospective, single-institution study of 6,000 patients undergoing parathyroidectomy for primary hyperparathyroidism and discharged within 2.5 hours. Based on our previous studies, patients are started on a sliding scale of oral calcium determined by a number of preoperative measures (ie, serum calcium, body weight, osteoporosis) beginning 3 hours postoperation and decreasing to a maintenance dose by week 3. Patients reported all hypocalcemia symptoms daily for 2 weeks. Seven parameters were found to have a substantial impact on the amount of calcium required to prevent symptomatic hypocalcemia: preoperative serum calcium >12 mg/dL, >13 mg/dL, and >13.5 mg/dL, bone density T score less than -3, morbid obesity, removal of >1 parathyroid, and manipulation/biopsy of all remaining glands (all p < 0.05). Each independent variable increased the daily calcium required by 315 mg/day. Using our scaled protocol, <8% of patients showed symptoms of hypocalcemia, nearly all of whom were successfully self-treated with additional oral calcium. Only 6 patients (0.1%) required a visit to the emergency room for IV calcium, all occurring on postoperative day 3 or later. After outpatient parathyroidectomy, a specific calcium protocol has been verified that eliminates development of symptomatic hypocalcemia in >92% of patients, identifies patients at high risk for hypocalcemia, and allows self-medication with confidence in a predictable fashion for those patients in whom symptoms develop.


Multiple mechanisms mediate motor neuron migration in the zebrafish hindbrain.
The transmembrane protein Van gogh-like 2 (Vangl2) is a component of the noncanonical Wnt/Planar Cell Polarity (PCP) signaling pathway, and is required for tangential migration of facial branchiomotor neurons (FBMNs) from rhombomere 4 (r4) to r5-r7 in the vertebrate hindbrain. Since vangl2 is expressed throughout the zebrafish hindbrain, it might also regulate motor neuron migration in other rhombomeres. We tested this hypothesis by examining whether migration of motor neurons out of r2 following ectopic hoxb1b expression was affected in vangl2(-) (trilobite) mutants. Hoxb1b specifies r4 identity, and when ectopically expressed transforms r2 to an "r4-like" compartment. Using time-lapse imaging, we show that GFP-expressing motor neurons in the r2/r3 region of a hoxb1b-overexpressing wild-type embryo migrate along the anterior-posterior (AP) axis. Furthermore, these cells express prickle1b (pk1b), a Wnt/PCP gene that is specifically expressed in FBMNs and is essential for their migration. Importantly, GFP-expressing motor neurons in the r2/r3 region of hoxb1b-overexpressing trilobite mutants and pk1b morphants often migrate, even though FBMNs in r4 of the same embryos fail to migrate longitudinally (tangentially) into r6 and r7. These observations suggest that tangentially migrating motor neurons in the anterior hindbrain (r1-r3) can use mechanisms that are independent of vangl2 and pk1b functions. Interestingly, analysis of tri; val double mutants also suggests a role for vangl2-independent factors in neuronal migration, since the valentino mutation partially suppresses the trilobite mutant migration defect. Together, the hoxb1b and val experiments suggest that multiple mechanisms regulate motor neuron migration along the AP axis of the zebrafish hindbrain.


Transcriptional dynamics of Phytophthora infestans during sequential stages of hemibiotrophic infection of tomato.
Hemibiotrophic plant pathogens, such as the oomycete Phytophthora infestans, employ a biphasic infection strategy, initially behaving as biotrophs, where minimal symptoms are exhibited by the plant, and subsequently as necrotrophs, feeding on dead plant tissue. The regulation of this transition and the breadth of molecular mechanisms that modulate plant defences are not well understood, although effector proteins secreted by the pathogen are thought to play a key role. We examined the transcriptional dynamics of P. infestans in a compatible interaction with its host tomato (Solanum lycopersicum) at three infection stages: biotrophy; the transition from biotrophy to necrotrophy; and necrotrophy. The expression data suggest a tight temporal regulation of many pathways associated with the suppression of plant defence mechanisms and pathogenicity, including the induction of putative cytoplasmic and apoplastic effectors. Twelve of these were experimentally evaluated to determine their ability to suppress necrosis caused by the P. infestans necrosis-inducing protein PiNPP1.1 in Nicotiana benthamiana. Four effectors suppressed necrosis, suggesting that they might prolong the biotrophic phase. This study suggests that a complex regulation of effector expression modulates the outcome of the interaction.


gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t-butylbicyclophosphorothionate binding to cerebellar granule cells.
t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, we have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [35S]TBPS. At 25 degrees C, and in a modified Locke solution, the [35S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [35S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [35S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [35S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [35S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [35S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical and immunological responses of cats to feline herpesvirus type 1 infection.
Cats which were challenged with feline herpesvirus type 1 developed clinical signs typical of feline viral rhinotracheitis whether or not they had been vaccinated against the disease. However, the clinical disease was less severe and of shorter duration in the vaccinated cats. After challenge, feline herpesvirus type 1 was recovered from the nostrils, oropharynx and peripheral blood leucocytes. Leucocytosis, primarily a neutrophilia, occurred initially in all the cats and was followed after clinical recovery by a mild lymphocytosis. Intradermal skin testing with feline herpesvirus type 1 and cell control antigens produced a positive delayed type skin reaction. Histology of the affected skin 72 hours after injection showed cellular infiltration, predominantly with eosinophils and neutrophils. The severity of the reaction was greater and more prolonged in the skin of the ear than in the skin of the abdomen.


A cluster randomised controlled trial to reduce respiratory effects of cotton dust exposure among textile workers - the MultiTex RCT study.
We determined the effectiveness of an intervention to reduce cotton dust-related respiratory symptoms and improve lung function of textile workers. We undertook a cluster-randomised, controlled trial at 38 textile mills in Karachi. The intervention comprised: training in occupational health for all workers; formation of workplace committees to promote a health and safety plan that included wet mopping, safe disposal of cotton dust, simple face masks, and further publicity about the risks from cotton dust. Participating mills were randomised following baseline data collection. The impact of the intervention was measured through surveys at 3, 12 and 18 months using questionnaires, spirometry, and dust measurements. The primary outcomes were (1) changes in prevalence of a composite respiratory symptom variable; (2) changes in post-bronchodilator percentage-predicted forced expiratory volume in the first second (FEV1), and (3) changes in cotton dust levels. These were assessed using two-level mixed-effects linear and logistic regression. Of 2031 participants recruited at baseline, 807 (40%) were available at the third follow-up. At that point, workers in the intervention arm were more likely to report an improvement in respiratory symptoms (OR=1.58; 95% CI: 1.06-2.37) and lung function (%predicted FEV1, β=1.31%; 95% CI: 0.04-2.57). Personal dust levels decreased, more so in intervention mills, although we did not observe this in adjusted models due to the small number of samples. We found the intervention to be effective in improving the respiratory health of textile workers and recommend scaling-up of such simple and feasible interventions in low- and middle-income countries.


Complex spikes perturb movements and reveal the sensorimotor map of Purkinje cells.
Computations that are performed by the cerebellar cortex are transmitted via simple spikes of Purkinje cells (P-cells) to downstream structures, but because P-cells are many synapses away from muscles, we do not know the relationship between modulation of simple spikes and control of behavior. Here, we recorded the spiking activities of hundreds of P-cells in the oculomotor vermis of marmosets during saccadic eye movements and found that following the presentation of a visual stimulus, the olivary input to a P-cell coarsely described the direction and amplitude of the visual stimulus as well as the upcoming movement. Occasionally, the complex spike occurred just before saccade onset, suppressing the P-cell's simple spikes and disrupting its output during that saccade. Remarkably, this brief suppression of simple spikes altered the saccade's trajectory by pulling the eyes toward the part of the visual space that was preferentially encoded by the olivary input to that P-cell. Thus, there is an alignment between the sensory space encoded by the complex spikes and the behavior conveyed by the simple spikes: a reduction in simple spikes is a signal to bias the ongoing movement toward the part of the sensory space preferentially encoded by the olivary input to that P-cell.


Isolation of a mutant auxotrophic for L-alanine and identification of three major aminotransferases that synthesize L-alanine in Escherichia coli.
For Escherichia coli, it has been assumed that L-alanine is synthesized by alanine-valine transaminase (AvtA) in conjunction with an unknown alanine aminotransferase(s). We isolated alanine auxotrophs from a prototrophic double mutant deficient in AvtA and YfbQ, a novel alanine aminotransferase, by chemical mutagenesis. A shotgun cloning experiment identified two genes, uncharacterized yfdZ and serC, that complemented the alanine auxotrophy. When the yfdZ- or serC-mutation was introduced into the double mutant, one triple mutant (avtA yfbQ yfdZ) showed alanine auxotrophy, and another (avtA yfbQ serC), prototrophy. In addition, we found that four independent alanine auxotrophs possessed a point mutation in yfdZ but not in serC. We also found that yfdZ expression was induced in minimal medium. Furthermore, yfbQ-bearing plasmid conferred the ability to excrete alanine on the mutant lacking D-amino acid dehydrogenase-encoding gene, dadA. From these results, we concluded that E. coli synthesizes L-alanine by means of three aminotransferases, YfbQ, YfdZ, and AvtA.


Forest Soil Bacteria: Diversity, Involvement in Ecosystem Processes, and Response to Global Change.
The ecology of forest soils is an important field of research due to the role of forests as carbon sinks. Consequently, a significant amount of information has been accumulated concerning their ecology, especially for temperate and boreal forests. Although most studies have focused on fungi, forest soil bacteria also play important roles in this environment. In forest soils, bacteria inhabit multiple habitats with specific properties, including bulk soil, rhizosphere, litter, and deadwood habitats, where their communities are shaped by nutrient availability and biotic interactions. Bacteria contribute to a range of essential soil processes involved in the cycling of carbon, nitrogen, and phosphorus. They take part in the decomposition of dead plant biomass and are highly important for the decomposition of dead fungal mycelia. In rhizospheres of forest trees, bacteria interact with plant roots and mycorrhizal fungi as commensalists or mycorrhiza helpers. Bacteria also mediate multiple critical steps in the nitrogen cycle, including N fixation. Bacterial communities in forest soils respond to the effects of global change, such as climate warming, increased levels of carbon dioxide, or anthropogenic nitrogen deposition. This response, however, often reflects the specificities of each studied forest ecosystem, and it is still impossible to fully incorporate bacteria into predictive models. The understanding of bacterial ecology in forest soils has advanced dramatically in recent years, but it is still incomplete. The exact extent of the contribution of bacteria to forest ecosystem processes will be recognized only in the future, when the activities of all soil community members are studied simultaneously.


Association Between High Perceived Stress Over Time and Incident Hypertension in Black Adults: Findings From the Jackson Heart Study.
Background Chronic psychological stress has been associated with hypertension, but few studies have examined this relationship in blacks. We examined the association between perceived stress levels assessed annually for up to 13 years and incident hypertension in the Jackson Heart Study, a community-based cohort of blacks. Methods and Results Analyses included 1829 participants without hypertension at baseline (Exam 1, 2000-2004). Incident hypertension was defined as blood pressure≥140/90 mm Hg or antihypertensive medication use at Exam 2 (2005-2008) or Exam 3 (2009-2012). Each follow-up interval at risk of hypertension was categorized as low, moderate, or high perceived stress based on the number of annual assessments between exams in which participants reported "a lot" or "extreme" stress over the previous year (low, 0 high stress ratings; moderate, 1 high stress rating; high, ≥2 high stress ratings). During follow-up (median, 7.0 years), hypertension incidence was 48.5%. Hypertension developed in 30.6% of intervals with low perceived stress, 34.6% of intervals with moderate perceived stress, and 38.2% of intervals with high perceived stress. Age-, sex-, and time-adjusted risk ratios (95% CI) associated with moderate and high perceived stress versus low perceived stress were 1.19 (1.04-1.37) and 1.37 (1.20-1.57), respectively (P trend<0.001). The association was present after adjustment for demographic, clinical, and behavioral factors and baseline stress (P trend=0.001). Conclusions In a community-based cohort of blacks, higher perceived stress over time was associated with an increased risk of developing hypertension. Evaluating stress levels over time and intervening when high perceived stress is persistent may reduce hypertension risk.


Space-time dynamics of a triple epidemic: dengue, chikungunya and Zika clusters in the city of Rio de Janeiro.
Dengue, an arboviral disease transmitted by Aedes mosquitoes, has been endemic in Brazil for decades. However, vector-control strategies have not led to a significant reduction in the disease burden and have not been sufficient to prevent chikungunya and Zika entry and establishment in the country. In Rio de Janeiro city, the first Zika and chikungunya epidemics were detected between 2015 and 2016, coinciding with a dengue epidemic. Understanding the behaviour of these diseases in a triple epidemic scenario is a necessary step for devising better interventions for prevention and outbreak response. We applied scan statistics analysis to detect spatio-temporal clustering for each disease separately and for all three simultaneously. In general, clusters were not detected in the same locations and time periods, possibly owing to competition between viruses for host resources, depletion of susceptible population, different introduction times and change in behaviour of the human population (e.g. intensified vector-control activities in response to increasing cases of a particular arbovirus). Simultaneous clusters of the three diseases usually included neighbourhoods with high population density and low socioeconomic status, particularly in the North region of the city. The use of space-time cluster detection can guide intensive interventions to high-risk locations in a timely manner, to improve clinical diagnosis and management, and pinpoint vector-control measures.


Spectator Sports as Context for Examining Observers' Agreeableness, Social Identification, and Empathy in a High-Stakes Conflict Situation.
In a high-stakes conflict or dilemma situation, observers often feel empathy for one side versus the other. Using a high-profile conflict situation in a world-renowned spectator sport (the US Open) as context, the authors of this study examined the roles of personality and social-cognitive factors, specifically agreeableness and social identification, on empathic concern towards three individuals (a focal actor or instigator, a target, and an "innocent" bystander) involved in an emotionally charged conflict situation. Results showed direct and indirect effects of agreeableness on identification with the focal actor and empathic concern towards the individuals involved in the conflict situation. Participants' social-cognitive processes of identification with the focal actor or instigator fully mediated the effect of personality trait of agreeableness on empathic concern towards the focal actor, whereas agreeableness was directly related to empathic concern towards the target and the bystander without (full) mediation by social identification. Gender differences were found with women reporting higher empathic concern and identification towards the female focal actor and lower empathic concern towards the male target in the conflict situation, suggesting potential automatic or implicit in-group bias. Study results highlight the complex integration of personality and social-cognitive processes, including intersectionality of social identities, in the dynamics of empathic reactions during high-stakes and emotionally charged conflict situations.


Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production.
The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-gamma) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.


The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle.
It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. Ten subjects performed two exercise trials (120 min at 50% VO(2max)). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. Basal plasma adiponectin concentrations averaged 6.57+/-0.7 and 6.63+/-0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles. Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres.


Chronic effects of norepinephrine and vasopressin on urinary prostaglandin E and kallikrein excretions in conscious rats.
To assess in vivo functional interactions of vasopressor substances, norepinephrine and vasopressin, with renal prostaglandins and kallikrein-kinin system which are responsible for the vasodepressor mechanism in the kidney, we evaluated chronic effects of norepinephrine (1.8 mg/kg/day ip) and vasopressin (7.2 U/kg/day ip) on urinary prostaglandin E excretion and urinary kallikrein excretion in conscious rats. Both norepinephrine and vasopressin induced a sustained increase in systolic blood pressure. Norepinephrine induced slight but significant increases in urinary prostaglandin E excretion and urinary kallikrein excretion which were sustained for up to 6 days. Vasopressin induced a marked increase in urinary prostaglandin E excretion which was sustained for up to 6 days, whereas it induced a sustained decrease in urinary kallikrein excretion. Circulating angiotensin II levels was not changed by norepinephrine, but was decreased by vasopressin. These results indicate that renal prostaglandin E may not correlate with renal kallikrein-kinin and renin-angiotensin system in the responses to norepinephrine and vasopressin, and that vasopressin may be a more potent stimulator of the synthesis or release of renal prostaglandin E.


Antimicrobial activity of ultrasonic cleaners.
This study assessed the antimicrobial activity of two cleaning solutions and tap water after varying periods of use in one ultrasonic cleaner. Testing involved filling the cleaner's tank and a centred glass beaker with the same test solution. An aluminium foil strip test first determined that no significant differences in cavitational activity existed inside the beaker compared with outside. Standardized solutions of Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella choleraesuis were left at room temperature for 10 min. Aliquots were exposed to both cleaning solution and ultrasonic action. Unused test solution was removed from the tank, filter-sterilized, mixed with bacterial suspension and placed into a sterile beaker. Cleaning was allowed for 10 min. The beaker was removed and its contents examined. The tank was allowed to cool for 30 min and the process was repeated four times. The entire experimental set was repeated once. Exposure to test solution alone in all but one case produced reductions in bacterial numbers from initial >/=2 x 10(9) by 19.9-52.6%. Application of both chemical exposure and ultrasonic cleaning produced greater bacterial kill (46.4-99.7% reductions). However, kill became less effective on repeated use of a commercial cleaning solution. Reduction was highest when fresh ultrasonic cleaning solutions were used. In no case did complete sterilization occur. As well as removing adherent material, ultrasonic cleaning may also markedly reduce the number of viable organisms present.


Effects of selective drugs for dopaminergic D1 and D2 receptors on conditioned locomotion in rats.
Classically conditioned locomotor activity has been demonstrated by pairing injections of dopamine agonists or antagonists with specific environmental stimuli. The present studies investigated conditioning using drugs with varying selectivity for the dopamine D1 or D2 receptor. Experiment 1 assessed conditioning in groups of rats using the indirect acting agonist (+)-amphetamine (2.0 mg/kg), and the D1 agonist SKF 38393 (10.0 mg/kg), the D2 agonist quinpirole (2.5 mg/kg), the D1 and D2 antagonists, SCH 23390 (0.05 mg/kg) and metoclopramide (25.0 mg/kg), respectively. Paired groups received nine 2-h drug-environment (automated activity monitoring chambers) pairings whereas Unpaired groups received the stimuli explicitly unpaired. Test revealed conditioned hyperactivity with each agonist and metoclopramide whereas conditioned hypoactivity was seen with SCH 23390. Experiment 2 assessed the interaction of these agonists and antagonists on the establishment of conditioned activity. Paired groups received an agonist and antagonist during conditioning sessions. SCH 23390 blocked conditioning based on (+)-amphetamine and SKF 38393 but not quinpirole. Metoclopramide (10.0 mg/kg) blocked conditioning based on quinpirole but not SKF 38393. Metoclopramide (25.0 mg/kg) also did not block (+)-amphetamine-induced conditioning. These studies suggested that drug-induced alterations at either D1 or D2 receptors may be involved in conditioned locomotion.


[Structural features of the intrinsic venous bed of the human urinary bladder].
The intraorganic veins of the human urinary bladder have been studied in a vast sectional material. The veins within the organ make an enormous multilayered plexus which is differently organized in various layers of its wall. Abundant anastomoses, multiplicated ways for outflow from every layer, manifested interactions between the venous plexuses are specific for the intraorganic venous bed of the urinary bladder. The structures for an active regulating the hemomicrocirculatory blood stream are widely presented in the urinary bladder. In its every tunic certain specific morpho-functional features for organization and adaptation of the intraorganic venous bed are revealed.


Some optimum conditions for proton induced ultrasoft x-ray production.
The proton beam from an AN700 van de Graaff accelerator has been used to bombard solid targets of C, TiB2, SiC, SiN, Al and Au in the energy range 250-700 keV. A study of target surface contamination, the nature of the angular dependence in the x-ray emission and the dependence of the x-ray yield on proton energy has been undertaken. Our findings suggest that the optimum target angle is 30 degrees with respect to the incident proton direction and the detector angle 90 degrees to the target surface. In a vacuum of 10(-5) Torr (approximately 1.33 mPa) and at proton currents of 50-100 muA, a carbon deposit can be expected to build up with time on the target surface to reduce the characteristic x-ray intensity from the target. In the comparison between the energy dependent yields of CK and AlK x-rays, we find a slightly smaller dependence on energy than that predicted by the empirical cross section formula of Paul (1984) although the latter is not expected to be valid down to Z = 6.


Validation of a deep learning-based material estimation model for Monte Carlo dose calculation in proton therapy.
Objective. Computed tomography (CT) to material property conversion dominates proton range uncertainty, impacting the quality of proton treatment planning. Physics-based and machine learning-based methods have been investigated to leverage dual-energy CT (DECT) to predict proton ranges. Recent development includes physics-informed deep learning (DL) for material property inference. This paper aims to develop a framework to validate Monte Carlo dose calculation (MCDC) using CT-based material characterization models.Approach.The proposed framework includes two experiments to validatein vivodose and water equivalent thickness (WET) distributions using anthropomorphic and porcine phantoms. Phantoms were irradiated using anteroposterior proton beams, and the exit doses and residual ranges were measured by MatriXX PT and a multi-layer strip ionization chamber. Two pre-trained conventional and physics-informed residual networks (RN/PRN) were used for mass density inference from DECT. Additional two heuristic material conversion models using single-energy CT (SECT) and DECT were implemented for comparisons. The gamma index was used for dose comparisons with criteria of 3%/3 mm (10% dose threshold).Main results. The phantom study showed that MCDC with PRN achieved mean gamma passing rates of 95.9% and 97.8% for the anthropomorphic and porcine phantoms. The rates were 86.0% and 79.7% for MCDC with the empirical DECT model. WET analyses indicated that the mean WET variations between measurement and simulation were -1.66 mm, -2.48 mm, and -0.06 mm for MCDC using a Hounsfield look-up table with SECT and empirical and PRN models with DECT. Validation experiments indicated that MCDC with PRN achieved consistent dose and WET distributions with measurement.Significance. The proposed framework can be used to identify the optimal CT-based material characterization model for MCDC to improve proton range uncertainty. The framework can systematically verify the accuracy of proton treatment planning, and it can potentially be implemented in the treatment room to be instrumental in online adaptive treatment planning.


MsNRAMP2 Enhances Tolerance to Iron Excess Stress in Nicotiana tabacum and MsMYB Binds to Its Promoter.
Iron(Fe) is a trace metal element necessary for plant growth, but excess iron is harmful to plants. Natural resistance-associated macrophage proteins (NRAMPs) are important for divalent metal transport in plants. In this study, we isolated the MsNRAMP2 (MN_547960) gene from alfalfa, the perennial legume forage. The expression of MsNRAMP2 is specifically induced by iron excess. Overexpression of MsNRAMP2 conferred transgenic tobacco tolerance to iron excess, while it conferred yeast sensitivity to excess iron. Together with the MsNRAMP2 gene, MsMYB (MN_547959) expression is induced by excess iron. Y1H indicated that the MsMYB protein could bind to the "CTGTTG" cis element of the MsNRAMP2 promoter. The results indicated that MsNRAMP2 has a function in iron transport and its expression might be regulated by MsMYB. The excess iron tolerance ability enhancement of MsNRAMP2 may be involved in iron transport, sequestration, or redistribution.


The challenges of offering public second trimester abortion services in South Africa: health care providers' perspectives.
Around 25% of abortions in South Africa are performed in the second trimester. This study aimed to better understand what doctors, nurses and hospital managers involved in second trimester abortion care thought about these services and how they could be improved. Nineteen in-depth interviews with abortion-related service providers and managers in the Western Cape Province, South Africa, were undertaken. Data were analysed using a thematic analysis approach. Participants expressed resistance to the dilation and evacuation (D&E) procedure, as this required more active provider involvement. Medical abortion was preferred as it required less provider involvement in the abortion process. A shortage of providers willing to perform D&E resulted in most public sector services being outsourced to private sector doctors. Respondents noted an increased demand for services and a concomitant lack of infrastructure, physical space and personnel to respond to these demands, sometimes resulting in fragmented or poor quality care. At medical induction sites, most thought introducing the combined mifepristone-misoprostol regimen would improve service capacity, although they were concerned about cost. Improving contraceptive services was also seen as a much-needed intervention to improve care and prevent abortion. Ongoing training, including values clarification, as well as emotional support and team-building for providers are needed to ensure sustainable, high-quality second trimester abortion services.


Specific recruitment of SPA-1 to the immunological synapse: involvement of actin-bundling protein actinin.
SPA-1 is involved in the regulation of T cell activation in response to antigens through the control of Rap1 GTPase signaling. In this study, the subcellular localization of SPA-1 in the T cells was examined by using anti-SPA-1 antibody and GFP-SPA-1. While SPA-1 was detected diffusely at the surface cortical region in the floating unpolarized T cells, it was concentrated at the matrix-adhesion region with dense actin-cytoskeleton. Upon interaction with specific antigen-presenting cells, SPA-1 was highly concentrated at the immunological synapse closely co-localizing with actin. By yeast two-hybrid system, SPA-1 was shown to interact with an actin-bundling protein alpha-actinin, and it was indicated that SPA-1 co-localized with alpha-actinin at the immunological synapse. The results have suggested that SPA-1 in the T cells is selectively recruited to the immunological synapse with dense actin-cytoskeletal reorganization and keeps restraining the levels of Rap1GTP at the local TCR-signaling complex for the T cell activation.


Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?
An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m(2). NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11-1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84-87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02-1.16; P = 0.017) were associated with high LSM. 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors.


Why Does the Shift from "Personalized Medicine" to "Precision Health" and "Wellness Genomics" Matter?
Efforts to conceptualize the application of human genomics to health care have displayed an evolving set of translational research goals. Under personalized genomic medicine, the aim was to individualize treatment and empower patients to take more responsibility for their own health. With the rise of interest in expert interpretation of multifactorial risk stratification, emphasis shifted to giving clinicians better tools and more authority to use them under the rubric of precision medicine. The statistical nature of risk stratification, in turn, led to the movement's importing public health goals and expanding its scope to precision prevention at the population level. Today, the confluence of precision medicine and precision prevention in precision health is leading to wellness genomics aimed at achieving goals beyond health care entirely. Each of these reorientations suggests important ethical questions for the medical community.


The effect of nondirective questioning on women's decisions whether to undergo bone density screening: an experimental study.
This study investigated the effects of nondirective counseling on health screening decisions. Ninety women (mean age = 51 years) received information about bone density screening and osteoporosis. They were then randomly allocated to 1 of 4 groups and were encouraged to focus on positive issues about bone density screening (positive group), on negative issues (negative group), on both positive and negative issues (all-focusing group), or on issues relating to the common cold (control group). Women were asked to rate how likely they would be to opt for bone density screening if they saw it available. After being informed that they could have bone density screening, actual uptake was assessed. It was found that the issues on which individuals focused significantly influenced their rate likelihood of opting for the scan. Rated likelihood of testing was significantly associated with whether individuals actually did opt for testing when it was subsequently offered to them.


Comparative deep transcriptional profiling of four developing oilseeds.
Transcriptome analysis based on deep expressed sequence tag (EST) sequencing allows quantitative comparisons of gene expression across multiple species. Using pyrosequencing, we generated over 7 million ESTs from four stages of developing seeds of Ricinus communis, Brassica napus, Euonymus alatus and Tropaeolum majus, which differ in their storage tissue for oil, their ability to photosynthesize and in the structure and content of their triacylglycerols (TAG). The larger number of ESTs in these 16 datasets provided reliable estimates of the expression of acyltransferases and other enzymes expressed at low levels. Analysis of EST levels from these oilseeds revealed both conserved and distinct species-specific expression patterns for genes involved in the synthesis of glycerolipids and their precursors. Independent of the species and tissue type, ESTs for core fatty acid synthesis enzymes maintained a conserved stoichiometry and a strong correlation in temporal profiles throughout seed development. However, ESTs associated with non-plastid enzymes of oil biosynthesis displayed dissimilar temporal patterns indicative of different regulation. The EST levels for several genes potentially involved in accumulation of unusual TAG structures were distinct. Comparison of expression of members from multi-gene families allowed the identification of specific isoforms with conserved function in oil biosynthesis. In all four oilseeds, ESTs for Rubisco were present, suggesting its possible role in carbon metabolism, irrespective of light availability. Together, these data provide a resource for use in comparative and functional genomics of diverse oilseeds. Expression data for more than 350 genes encoding enzymes and proteins involved in lipid metabolism are available at the 'ARALIP' website (http://aralip.plantbiology.msu.edu/).


VCAM1-α4β1 integrin interaction mediates interstitial tissue reconstruction in 3-D re-aggregate culture of dissociated prepubertal mouse testicular cells.
Roles of interstitial tissue in morphogenesis of testicular structures remain less well understood. To analyze the roles of CD34+ cells in the reconstruction of interstitial tissue containing Leydig cells (LCs), and testicular structures, we used 3D-reaggregate culture of dissociated testicular cells from prepubertal mouse. After a week of culture, adult Leydig cells (ALCs) were preferentially incorporated within CD34+ cell-aggregates, but fetal LCs (FLCs) were not. Immunofluorescence studies showed that integrins α4, α9 and β1, and VCAM1, one of the ligands for integrins α4β1 and α9β1, are expressed mainly in CD34+ cells and ALCs, but not in FLCs. Addition of function-blocking antibodies against each integrin and VCAM1 to the culture disturbed the reconstruction of testicular structures. Antibodies against α4 and β1 integrins and VCAM1 robustly inhibited cell-to-cell adhesion between testicular cells and between CD34+ cells. Cell-adhesion assays indicated that CD34+ cells adhere to VCAM1 through the interaction with α4β1 integrin. Live cell imaging showed that CD34+ cells adhered around ALC-aggregates. CD34+ cells on the dish moved toward the aggregates, extending filopodia, and entered into them, which was disturbed by VCAM1 antibody. These results indicate that VCAM1-α4β1 integrin interaction plays pivotal roles in formation of testicular interstitial tissues in vitro and also in vivo.


Profile of microbial keratitis after corneal collagen cross-linking.
To report the profile of microbial keratitis occurring after corneal collagen cross-linking (CXL) in keratoconus patients. A retrospective analysis of 2350 patients (1715 conventional CXL, 310 transepithelial CXL, and 325 accelerated CXL) over 7 years (from January 2007 to January 2014) of progressive keratoconus, who underwent CXL at a tertiary eye care centre, was performed. Clinical findings, treatment, and course of disease of four eyes that developed postprocedural moxifloxacin resistant Staphylococcus aureus (MXRSA) infectious keratitis are highlighted. Four eyes that underwent CXL (0.0017%) had corneal infiltrates. All eyes that developed keratitis had conventional CXL. Corneal infiltrates were noted on the third postoperative day. Gram's stain as well as culture reported MXRSA as the causative agent in all cases. Polymerase chain reaction (PCR) in each case was positive for eubacterial genome. All patients were treated with fortified antibiotic eye drops, following which keratitis resolved over a 6-week period with scarring. All these patients were on long-term preoperative oral/topical steroids for chronic disorders (chronic vernal keratoconjunctivitis, bronchial asthma, and chronic eczema). The incidence of infectious keratitis after CXL is a rare complication (0.0017%). MXRSA is a potential organism for causing post-CXL keratitis and should be identified early and treated aggressively with fortified antibiotics.


Approaches to Capture Variance Differences in Rest fMRI Networks in the Spatial Geometric Features: Application to Schizophrenia.
Identification of functionally connected regions while at rest has been at the forefront of research focusing on understanding interactions between different brain regions. Studies have utilized a variety of approaches including seed based as well as data-driven approaches to identifying such networks. Most such techniques involve differentiating groups based on group mean measures. There has been little work focused on differences in spatial characteristics of resting fMRI data. We present a method to identify between group differences in the variability in the cluster characteristics of network regions within components estimated via independent vector analysis (IVA). IVA is a blind source separation approach shown to perform well in capturing individual subject variability within a group model. We evaluate performance of the approach using simulations and then apply to a relatively large schizophrenia data set (82 schizophrenia patients and 89 healthy controls). We postulate, that group differences in the intra-network distributional characteristics of resting state network voxel intensities might indirectly capture important distinctions between the brain function of healthy and clinical populations. Results demonstrate that specific areas of the brain, superior, and middle temporal gyrus that are involved in language and recognition of emotions, show greater component level variance in amplitude weights for schizophrenia patients than healthy controls. Statistically significant correlation between component level spatial variance and component volume was observed in 19 of the 27 non-artifactual components implying an evident relationship between the two parameters. Additionally, the greater spread in the distance of the cluster peak of a component from the centroid in schizophrenia patients compared to healthy controls was observed for seven components. These results indicate that there is hidden potential in exploring variance and possibly higher-order measures in resting state networks to better understand diseases such as schizophrenia. It furthers comprehension of how spatial characteristics can highlight previously unexplored differences between populations such as schizophrenia patients and healthy controls.