[Prophylactic and therapeutic vaccination against human papillomavirus].
Human papillomavirus is a necessary cause for the development of cervical cancer. Cervical cancer is attributed to 15 high-risk oncogenic HPV among the 120 genotypes present in human. The infection affects about 3 out of 4 women and is often transient thanks to immunological modulators leading to viral clearance. This characteristic made it possible to develop vaccines. Prophylactic vaccines are made of virus-like particles L1, non infectious, well tolerated and highly immunogenic. They prevent from viral infection by producing antibodies, which are secreted throughout the genital mucosa (humoral immunity). High-risk oncogenic HPV-16 and 18, responsible for 70% of cervical cancer, are included in Gardasil and Cervarix. Both vaccines prevent from HPV infection and related cervical and perineal lesions in more than 90% of the cases. Therapeutic vaccines are made of epitope peptides, recombinant proteins and bacteria, plasmid DNA or dendritic cells. All sensitize immunocompetent cells (cellular immunity). Ineffective in cervical cancers, they induce the regression of cervical dysplasia in about 50% of the cases. They are still under research and development, in opposition to prophylactic vaccines, which are available.


On educating and being a physician in the hospitalist era.
Among its responsibilities, the hospitalist movement in internal medicine must fulfill the educational needs of medical students and residents. Rigorous studies can discern what special objectives, curriculum, and funding will be effective for hospitalists to meet these obligations.


Correction: Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation.
Correction for 'Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation' by Brandon J. Vogt et al., Biomater. Sci., 2022, https://doi.org/10.1039/d2bm00844k.


Collagen synthesis and proteolytic activities in rat skeletal muscles: effect of cast-immobilization in the lengthened and shortened positions.
The activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, were measured in the gastrocnemius, soleus, and tibialis anterior muscles of rats after bilateral cast-immobilization of the muscles in lengthened and shortened positions for one and three weeks. The activities of muscular proteolytic and hydrolytic enzymes cathepsin D (CD), beta-glucuronidase (beta-GU), alkaline protease (AP), and the rate of acid autolysis (AA) were also studied. The biochemical results were compared to the morphologic changes by light microscopy. Compared to the results for a control group, there was a decrease of 37% and 53% in the specific PH activity of shortened gastrocnemius and soleus, respectively, after three weeks of immobilization. The corresponding decrease in GGT of the shortened gastrocnemius was 47%. At the same time, PH and GGT in the lengthened plantarflexors were at the control level. The proteolytic activities of the shortened plantarflexors were generally higher (CD by approximately 30%, beta-GU of gastrocnemius by 81%, AP of soleus by 63%, AA of gastrocnemius by 34%, and AA of soleus by 56%) than those of the lengthened ones. Light microscopy of the shortened muscles showed numerous atrophic fibers, but no pronounced inflammatory response in the disused muscle tissue. The results suggest that increased proteolysis and wasting of muscle tissue during cast-immobilization is associated with adaptive responses in the metabolism of the muscular collagen network.


High expression of SLC34A2 is a favorable prognostic marker in lung adenocarcinoma patients.
Dysregulation of SLC34A2 (NaPi2b) in tumors has attracted wide attention, but its expression and function in non-small cell lung cancer remains unclear. By examining its expression in lung adenocarcinoma and correlation to patient outcome, we aimed to explore its prognostic and therapeutic values in this deadly disease. Overall, 175 cases of lung adenocarcinoma sample were included in this study. Histological subtyping of them was diagnosed according to standards of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society in 2011. Protein expression of SLC34A2 and anaplastic lymphoma kinase in these samples was determined by immunohistochemistry. Epidermal growth factor receptor mutations were examined using amplification refractory mutation system. Statistical analysis was performed using software of Pearson's correlation coefficient. High expression of SLC34A2 was identified in about 2/3 patients and correlated with significantly better patient's overall survival. Epidermal growth factor receptor mutations were detected in about 53% of patients with no statistically significant difference to patient's overall survival. Anaplastic lymphoma kinase rearrangement was found in 8 out of 175 patients, harboring this abnormality leads to shorter overall survival. No correlation has been found between SLC34A2 expression and epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangements in lung adenocarcinoma. High expression of SLC34A2 is present in about 3/4 lung adenocarcinoma samples and predicts better outcome. Since it is a membrane protein, antibody-based drugs targeting this marker might bring new resolution to this deadly disease.


Cytotoxicity of GuttaFlow Bioseal, GuttaFlow2, MTA Fillapex, and AH Plus on Human Periodontal Ligament Stem Cells.
The aim of the present study was to evaluate the in vitro cytotoxicity of endodontic sealers (GuttaFlow Bioseal, GuttaFlow2, and MTA Fillapex) on human periodontal ligament stem cells (hPDLSCs). As a reference, AH Plus was compared with the more recent endodontic sealers regarding cell viability and cell attachment. Biological testing was carried out in vitro on hPDLSCs. Cell viability assay was performed by using eluates from each endodontic sealer. To assess cell morphology and attachment to the different sealers, the hPDLSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy. Chemical composition of the sealers was determined by energy-dispersive x-ray, and eluates were analyzed by inductively coupled plasma mass spectrometry. Statistical differences were assessed by analysis of variance and Tukey test (P < .05). Cell viability was evident after 24 hours in the presence of GuttaFlow Bioseal and GuttaFlow 2 but not in the case of AH Plus or MTA Fillapex. At 168 hours, GuttaFlow Bioseal and GuttaFlow 2 exhibited high and moderate cell viability, respectively, whereas AH Plus and MTA Fillapex revealed low rates of cell cell viability (P < .001). Finally, scanning electron microscopy studies revealed a high degree of proliferation, cell spreading, and attachment, especially when using GuttaFlow Bioseal disks. GuttaFlow Bioseal and GuttaFlow2 showed lower cytotoxicity than MTA Fillapex and AH plus. Further in vitro and in vivo investigations are required to confirm the suitability of GuttaFlow Bioseal for clinical application.


Anesthesia in underdeveloped countries: a teaching program.
A unique volunteer anesthesia teaching program in East Africa is described. Its object is to help correct the shortage of anesthesia personnel in underdeveloped countries, characteristically so severe that, in some areas, only 10-15 present of the surgery that should be performed can be performed. The design of this program, with its emphasis on teaching, may prove helpful for establishment of similar teaching programs in other medical disciplines in underdeveloped countries.


Moving National Breastfeeding Policies into Practice: A Plea to Integrate Lactation Education and Training into Nutrition and Dietetics Programs in the United States.
In 2011, the Surgeon General's Call to Action to Support Breastfeeding called on all health professional organizations, medical schools, and credentialing boards to establish and incorporate minimum lactation education and training requirements into their credentialing, licensing, and certification processes and to include breastfeeding education in undergraduate and graduate education and training programs. Given the commonalities between the fields of nutrition and breastfeeding, it has been proposed that nutrition professionals are an underutilized resource in the field of lactation management. Considering the lack of breastfeeding knowledge and skills among health professionals, nutrition professionals should be afforded opportunities to learn lactation management during their studies. The United States Breastfeeding Committee published Core Competencies in Breastfeeding Care and Services for All Health Professionals in 2010. However, professional nutrition and lactation credentialing boards should cooperate to integrate mandatory minimum standards of lactation education for nutrition professionals. Undergraduate and graduate programs in nutrition and dietetics should incorporate lactation content into their core curricula to comply with such standards. In addition, dietetics programs should offer optional clinical lactation experiences for students who aspire to become an International Board Certified Lactation Consultant.


Bacteriology of acute and chronic frontal sinusitis.
Aspirates of 15 acutely and 13 chronically infected frontal sinuses were processed for aerobic and anaerobic bacteria. A total of 20 isolates (1.3 per specimen) were recovered from the 15 cases of acute frontal sinusitis, 16 aerobic and facultative isolates (1.1 per specimen) and 4 anaerobic isolates (0.3 per specimen). Aerobic and facultative organisms alone were recovered in 13 specimens (87%), and mixed aerobic and anaerobic bacteria were recovered in 2 (13%). The predominant aerobic and facultative organisms were Haemophilus influenzae (6), Streptococcus pneumoniae (5), and Moraxella catarrhalis (3). A total of 32 isolates were recovered from the 13 cases (2.5 per patient) of chronic frontal sinusitis, 12 aerobic and facultative isolates (0.9 per specimen) and 20 anaerobic isolates (1.5 per specimen). Aerobic and facultative organisms only were recovered in 3 instances (23%), anaerobes only in 7 instances (54%), and mixed aerobic and anaerobic bacteria in 3 instances (23%). The predominant aerobic bacteria were gram-negative bacilli (H influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa). The predominant anaerobes included Prevotella species (8), Peptostreptococcus species (6), and Fusobacterium species (4). These findings illustrate the microbiologic features of acute and chronic frontal sinusitis.


Long-term outcomes of whole-pelvis radiation therapy using volumetric modulated arc therapy for high-risk prostate cancer†.
This study investigated the outcomes of whole-pelvis radiation therapy (WPRT) using volumetric modulated arc therapy (VMAT) for high-risk prostate cancer. We retrospectively analysed 112 patients with high-risk prostate cancer who started WPRT at our hospital between August 2011 and August 2015. The prescribed dose was 78 Gy in 39 fractions to the prostate and 46.8 Gy in 26 fractions to the pelvic lymph node (LN) area. All patients received long-term androgen deprivation therapy. We evaluated late gastrointestinal (GI) and genitourinary (GU) toxicities using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period for censored cases was 97 (interquartile range [IQR] = 85-108) months. The median age was 72 (IQR = 67-75) years. The high-risk and very-high-risk groups included 41 (36.6%) and 71 patients (63.4%), respectively. The median risk of LN invasion calculated by the Roach formula was 36.9 (IQR = 26.6-56.3) %. The 8-year overall survival, biochemical failure-free survival, disease-free survival and distant metastasis-free survival rates were 88.4, 91.9, 83.8 and 98.0%, respectively. Only one patient experienced common iliac LN recurrence, which was outside the pelvic irradiation area. All patients with recurrent disease were categorized into the very-high-risk group. The 8-year cumulative rates of ≥Grade 2 late GI and GU toxicities were 12.8 and 11.8%, respectively. No patients experienced Grade 4 or higher toxicities. WPRT using VMAT for high-risk prostate cancer was well tolerated and effective.


Sequence and expression of four coral G protein-coupled receptors distinct from all classifiable members of the rhodopsin family.
A measure of the functional importance of G protein-coupled receptors (GPCRs) as signalling molecules is that over seven hundred have been cloned and identified in the human genome alone. Yet few have been characterized in the lower metazoan phyla, especially in the phylum Cnidaria which is well positioned phylogenetically for tracing the early evolution of GPCRs owing to their possession of the first-evolved nervous systems. We report here the cloning and characterization of four novel rhodopsin-like GPCR cDNAs from the staghorn coral Acropora millepora that share significant similarity with each other but not with the majority of other members of the rhodopsin alpha subfamily. The deduced proteins lack many of the conserved residues and motifs that form the signature of the different groups of alpha rhodopsin receptors. Maximum likelihood phylogenetic analysis likewise implies that the coral receptors do not have a simple or close relationship with any of the major groups within the alpha rhodopsin subfamily. In situ hybridization revealed transcripts in endodermal cells of planula larvae of all ages and in post-settlement polyps. These GPCRs appear to belong to a alpha rhodopsin-like group unique to corals. Comparisons with other cnidarian GPCRs suggest also that GPCRs diverged early in metazoan evolution.


Construction of a clinical survival prognostic model for middle-aged and elderly patients with stage III rectal adenocarcinoma.
Nomograms for prognosis prediction in colorectal cancer patients are few, and prognostic indicators differ with age. To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma. A total of 2773 eligible patients were divided into the training cohort (70%) and the validation cohort (30%). Optimal cutoff values were calculated using the X-tile software for continuous variables. Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival (OS) and cancer-specific survival (CSS)-related prognostic factors. Two nomograms were successfully constructed. The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis. The 95%CI in the training group was 0.719 (0.690-0.749) and 0.733 (0.702-0.74), while that in the validation group was 0.739 (0.696-0.782) and 0.750 (0.701-0.800) for the OS and CSS nomogram prediction models, respectively. In the validation group, the AUC of the three-year survival rate was 0.762 and 0.770, while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms, respectively. The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades. The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system. The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.


Induction of pseudopregnancy in the rat by electrochemical stimulation of the brain.
Electrochemical stimulation of the neocortex, VMH-arcuate hypothalamus, medial preoptic area, corticomedial amygdala, and dorsal hippocampus was performed under pentobarbital anesthesia to determine the brain regions involved in prolactin release as evidenced by pseudopregnancy. Stimulation occurred on the day of vaginal estrus, followed 4 days later by uterine traumatization. All animals were sacrificed 8 days after brain stimulation. Medial preoptic sitmulation resulted in an 83% incidence of pseudopregnancy while VMH-arcuate stimulation resulted in 43% incidence. Amygdaloid and hippocampal stimulation resulted in a lower incidence of pseudopregnancy (20 and 24%, respectively). Stimulation of the neocortex or sham stimulation of the five brain regions did not induce pseudopregnancy. These data indicate that the MPOA and VMH-arcuate hypothalamus are areas which may facilitate the release of prolactin necessary for the development of pseudopregnancy. The lower incidence of deciduomata formation resulting from electrochemical stimulation on the amygdala and hippocampus suggest that these areas have a minor effect on stimulating the induction of pseudopregnancy.


Are computer numerical control (CNC)-manufactured patient-specific metal templates available for posterior thoracic pedicle screw insertion? Feasibility and accuracy evaluation.
Accurate and safe posterior thoracic pedicle insertion (PTPI) remains a challenge. Patient-specific drill templates (PDTs) created by rapid prototyping (RP) can assist in posterior thoracic pedicle insertion, but pose biocompatibility risks. The aims of this study were to develop alternative PDTs with computer numerical control (CNC) and assess their feasibility and accuracy in assisting PTPI. Preoperative CT images of 31 cadaveric thoracic vertebras were obtained and then the optimal pedicle screw trajectories were planned. The PDTs with optimal screw trajectories were randomly assigned to be designed and manufactured by CNC or RP in each vertebra. With the guide of the CNC- or RP-manufactured PDTs, the appropriate screws were inserted into the pedicles. Postoperative CT scans were performed to analyze any deviations at entry point and midpoint of the pedicles. The CNC group was found to be significant manufacture-time-shortening, and cost-decreasing, when compared with the RP group (P < 0.01). The PDTs fitted the vertebral laminates well while all screws were being inserted into the pedicles. There were no significant differences in absolute deviations at entry point and midpoint of the pedicle on either axial or sagittal planes (P > 0.05). The screw positions were grade 0 in 90.3% and grade 1 in 9.7% of the cases in the CNC group and grade 0 in 93.5% and grade 1 in 6.5% of the cases in the RP group (P = 0.641). CNC-manufactured PDTs are viable for assisting in PTPI with good feasibility and accuracy.


Phage cocktail to control the exponential growth of normal flora in processed sputum specimens grown overnight in liquid medium for rapid TB diagnosis.
The mechanical pressure exerted during centrifugation and the chemical pressure experienced when sputum specimens are processed, leave the tubercle bacilli in the sputum unsuitable for rapid detection especially in phage based assays. Thus, growing Mycobacterium tuberculosis in broth, at least overnight, is mandatory for allowing the tubercle bacilli to recoup. During this time the surviving colonizing flora grow faster and overgrow tubercle bacilli interfering with TB diagnosis. In the present study normal flora surviving the action of 4% NaOH was isolated and characterized. Phages capable of killing 14 different species representing this normal flora were isolated from soil and sewage samples and characterized. A novel and bio-friendly approach to treat sputum samples with a cocktail of three phages capable of killing most of the 14 representative organisms and not infecting mycobacteria is explored to control the overgrowth of colonizing bacteria in broth culture. While 26 of the 100 sputum samples processed by modified Petroff's procedure showed growth of colonizing flora on blood agar, all of them when grown in broth overnight showed mixed, confluent growth. The addition of phagebiotics controlled them all, showing a significant reduction in colony forming units but resulting in few discrete colonies in 54 samples. Isolation of phages capable of controlling these surviving organisms and including them in the phagebiotics mixture should lead to the control of colonizing bacteria effectively.


ACUTE CATATONIC REACTION OF ADOLESCENCE.
In a study of 21 cases of catatonic schizophrenic reaction of adolescence, sexual conflict situations and stern religious orientation of the family were noted in most cases. Incest was a factor in four of the female patients and masturbatory guilt was a prominent reaction in the remainder. Sex education was mostly misinformation and threats of dire consequences for sexual activity. Fourteen of the cases involved broken homes for significant periods of childhood or adolescence. It was hypothesized that sexual conflict situations grew out of incompatible socio-cultural attitudes and normal adolescent psychological and physiological drives. We formulated the "defined body contact" technique as a means of facilitating the reversal of the catatonic behavior, which we saw as the primary device whereby the patient limited physical contacts. The contacts we used in this technique were defined explicitly and implicitly as non-sexual.The catatonic symptoms remitted in days to several weeks in 13 of the cases. Seven patients required electroshock therapy. Twenty of the 21 patients returned to their homes or to non-institutional residences. The length of hospitalization was materially influenced by the degree of readiness of the outside environment to accept the returnee.


Acoustic manipulation of small droplets.
Surface acoustic waves are used to actuate and process smallest amounts of fluids on the planar surface of a piezoelectric chip. Chemical modification of the chip surface is employed to create virtual wells and tubes to confine the liquids. Lithographically modulated wetting properties of the surface define a fluidic network, in analogy to the wiring of an electronic circuit. Acoustic radiation pressure exerted by the surface wave leads to internal streaming in the fluid and eventually to actuation of small droplets along predetermined trajectories. This way, in analogy to microelectronic circuitry, programmable biochips for a variety of assays on a chip have been realized.


Medical similes in religious discourse: the case of Giovanni di San Gimignano OP (ca. 1260-ca. 1333).
By the beginning of the fourteenth century, medicine had acquired a cultural role in addition to its traditional function as a therapeutic art. Medical subject matter infiltrated the religious discourse via the new thirteenth-century encyclopedic literature. Preachers came to employ in their moral analogies a wider range of medical topics, using sophisticated medical examples and citations attributed to recognized medical authorities. These developments coincided with the growing prestige of medicine as an academic discipline.


Texture corrections for total scattering functions.
Many functional materials are today synthesized in the form of nanoparticles displaying preferred orientation effects to some small or large extent. The analysis of diffraction data of such kinds of systems is best performed in the framework of the total scattering approach that prescinds from translation symmetry assumptions. Therefore modified expressions were derived for the most common total scattering functions, in particular the Debye scattering equation (DSE) which yields the texture-averaged differential cross section as a function of atomic coordinates and texture parameters. The modified DSE encodes higher-order even spherical Bessel functions which account for the texture effect. Selection rules arising from experimental geometries and symmetries are discussed. In addition the duality of the texture effect is introduced showing the effects of texture on both the I(Q) and {\cal{G}}(r). The paper includes several definitions and appendices which are meant to be useful for those involved in the development of crystallographic computing.


Multiple dimensions of spirituality in recovery: a lagged mediational analysis of Alcoholics Anonymous' principal theoretical mechanism of behavior change.
Alcoholics Anonymous (AA) states that recovery is possible through spiritual experiences and spiritual awakenings. Research examining spirituality as a mediator of AA's effect on drinking has been mixed. It is unknown whether such findings are due to variations in the operationalization of key constructs, such as AA and spirituality. To answer these questions, the authors used a longitudinal model to test 2 dimensions of AA as focal predictors and 6 dimensions of spirituality as possible mediators of AA's association with drinking. Data from the first 18 months of a 3-year longitudinal study of 364 alcohol-dependent individuals were analyzed. Structural equation modeling was used to replicate the analyses of Kelly et al. (Alcohol Clin Exp Res. 2011;35:454-463) and to compare AA attendance and AA involvement as focal predictors. Multiple regression analyses were used to determine which spirituality dimensions changed as the result of AA participation. A trimmed, data-driven model was employed to test multiple mediation paths simultaneously. The findings of the Kelly et al. study were replicated. AA involvement was a stronger predictor of drinking outcomes than AA attendance. AA involvement predicted increases in private religious practices, daily spiritual experiences, and forgiveness of others. However, only private religious practices mediated the relationship between AA and drinking.


Four weeks lithium treatment alters neuronal dendrites in the rat hippocampus.
A large body of evidence from molecular, cellular and human studies suggests that lithium may enhance synaptic plasticity, which may be associated with its therapeutic efficacy. However, only a small number of studies have directly assessed this. To determine whether lithium treatment alters structural synaptic plasticity, this study examined the effect of 4 wk lithium treatment on the amount and distribution of dendrites in the dentate gyrus (DG) and hippocampal area CA1 of young adult rats. Following 4 wk lithium or control chow feeding, animals were decapitated, the hippocampi were prepared and stained using a rapid Golgi staining technique and the amount and distribution of the dendritic branching was evaluated using Sholl analyses (method of concentric circles). In the DG, lithium treatment increased the amount and distribution of dendritic branches in the proximal half of dendritic trees of the granule cells and reduced branching in the distal half. In area CA1, the same treatment also increased the number of dendritic branches in the proximal half of apical dendritic trees of CA1 pyramidal cells and reduced branching in the distal half of apical dendritic trees but had no effect on basilar dendritic trees. The lithium treatment altered the total density of dendritic trees in neither the DG nor area CA1. These findings suggest that, in the DG and apical CA1, chronic lithium treatment rearranges neuronal morphology to increase dendritic branching and distribution to where major afferent input is received.


Can ablation win against partial nephrectomy and become first line therapy in cT1a renal tumours?
Currently, small renal masses account for the largest proportion of renal tumour and small renal cell carcinomas (RCC). Although partial nephrectomy, whenever possible, is recognized as the gold standard for treatment, thermal ablation has gained increasing attention as optional treatment in a population sector harbouring small renal masses/small RCCs. The purpose of this review is to update comparative outcomes between these two options of treatment. Recent observational case-control and population-based cohorts applying propensity score or inverse probability treatment weighted methodology adjusting for baseline patient and tumour characteristics, compare outcomes between partial nephrectomy and thermal ablation (both cryotherapy and radiofrequency), radical nephrectomy and thermal ablation and between thermal ablation and nonsurgical management. Most of them focus on T1aRCC. Comparative outcomes' evidence is limited to population-based or institutional series adjusted for baseline differences and systematic reviews. With exception of special clinical situations, thermal ablation provides similar estimated 5-year cancer and overall survival with a clear benefit in postoperative outcomes when compared to partial nephrectomy in cT1a older patients. The trade-off is more evident when thermal ablation is compared to radical nephrectomy. The advantages in terms of adverse events persist up to 1 year after treatment. Benefits are less apparent in solitary kidneys and when synchronous bilateral approaches are performed.


Effects of litigation settlements on posttraumatic stress symptoms in motor vehicle accident victims.
In order to investigate the effects of the initiation of litigation and its settlement on victims of motor vehicle accidents (MVAs), we followed up 132 MVA victims from an initial assessment 1 to 4 months post-MVA for 1 year. Of the 67 who had initiated litigation, 18 (27%) settled within the 12 months, while 49 still had litigation pending; 65 never initiated litigation. Those who initiated litigation had more severe injuries and higher initial levels of posttraumatic stress (PTS) symptoms. All three groups improved in major role function and had reduced PTS symptoms over the 1 year follow-up. Those whose suits were still pending, as well as those whose suits had been settled, showed no reduction in measures of anxiety or depression, whereas the nonlitigants did show improvement on these measures.


Liver X receptor agonist treatment attenuates cardiac dysfunction in type 2 diabetic db/db mice.
Liver X receptor (LXR) plays a critical regulatory role in metabolism and inflammation, and has been demonstrated to be involved in cardiovascular physiology/pathology. In the present study, we investigated the effect of GW3965, a potent LXR agonist, on diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice. Non-diabetic db/+ mice and diabetic db/db mice received either vehicle or LXR agonist GW3965 for 12 weeks. Systemic insulin resistance was evaluated by glucose tolerance test and homeostasis model assessment for insulin resistance. Endpoint cardiac function was assessed by echocardiography and catheterization. Ventricular tissue was collected for histology and gene/protein expression analysis. Untreated db/db diabetic mice exhibited diastolic dysfunction with adverse structural remodeling (including myocardial fibrosis and increased apoptosis). Treatment with GW3965 remarkably attenuated myocardial dysfunction and structural remodeling in diabetic db/db mice. Mechanistically, GW3965 restored Akt phosphorylation and inhibited MAP kinases phosphorylation, and reduced oxidative/nitrative stress and inflammation response in the diabetic myocardium. Our data demonstrate that GW3965 exerts a cardioprotective effect against DCM by (at least in part) attenuating insulin resistance, modulating Akt and MAP kinases pathways, and reducing oxidative/nitrative stress and inflammatory response. These findings strongly suggest that LXR agonist may have therapeutic potential in treating DCM.


Vascular surgery training: is there enough case material?
In recent years, vascular surgery fellowships have changed substantially to meet the requirements for interventional as well as open surgical training. Data from the Residency Review Committee for Surgery indicate that the average vascular fellow performed fewer than 15 interventional procedures in 2000, but that this volume had increased to more than 200 interventional procedures by 2005, an increase of 255%. During the same interval, there was a slight (4%) decrease in the average number of major open vascular reconstructions performed. In 2005, the average vascular fellow performed 450 primary procedures, nearly equally divided between open and interventional cases. Selected open operations, such as aortic aneurysm repair, have decreased in volume due to the substitution by endovascular procedures. Operative volume for vascular fellows has been preserved in part by a 19% reduction in major vascular operations performed by general surgery residents. However, with added overall volume due to the increased prevalence of vascular disease in the aging population, there appears to be adequate case material to train future vascular surgeons, as long as less commonly performed operations continue to be focused on vascular trainees.


Prevalence of Oral Mucosal Lesions among Tobacco Consumers: Cross-Sectional Study.
Different lesions of mucosa can arise in people with a habit of tobacco usage. An assessment of prevalence of such lesions among tobacco consumers was done through this study. A total of 1000 persons were included in this cross-sectional survey. Individuals with a habit of tobacco usage in any form were included in the study. Demographic data were recorded for each study participant. Furthermore, all the participants were examined for associated oral lesions through toluene blue staining method. Types of tobacco consumption reported were for bidi, cigarette, hookah, gutkha, zarda, pan masala, and supari. Different types of associated lesions that were observed included tobacco pouch keratosis, leukoplakia, smoker's melanosis, erythroplakia, erythroleukoplakia, squamous cell carcinoma, sub-mucous fibrosis, and lichen planus in descending order. The oral sites involved were buccal mucosa, labial mucosa, floor of the mouth, gingiva, palate, and tongue in descending order. Various types of oral lesions can arise due to tobacco usage in different forms. The most common change observed is pouch keratosis in chewers and leukoplakia in smokers.


Unsupervised Phonocardiogram Analysis With Distribution Density Based Variational Auto-Encoders.
This paper proposes an unsupervised way for Phonocardiogram (PCG) analysis, which uses a revised auto encoder based on distribution density estimation in the latent space. Auto encoders especially Variational Auto-Encoders (VAEs) and its variant β-VAE are considered as one of the state-of-the-art methodologies for PCG analysis. VAE based models for PCG analysis assume that normal PCG signals can be represented by latent vectors that obey a normal Gaussian Model, which may not be necessary true in PCG analysis. This paper proposes two methods DBVAE and DBAE that are based on estimating the density of latent vectors in latent space to improve the performance of VAE based PCG analysis systems. Examining the system performance with PCG data from the a single domain and multiple domains, the proposed systems outperform the VAE based methods. The representation of normal PCG signals in the latent space is also investigated by calculating the kurtosis and skewness where DBAE introduces normal PCG representation following Gaussian-like models but DBVAE does not introduce normal PCG representation following Gaussian-like models.


Variations in purine metabolism of cultured skin fibroblasts from patients with gout.
Purine metabolism was studied in fibroblasts cultured from three patients with gout in an attempt to determine the biochemical bases of their disease. The rate of purine biosynthesis de novo was normal in one line of cells, but the rate of catabolism of adenine nucleotides to hypoxanthine and inosine was greatly increased. The rate of purine biosynthesis de novo was increased in two lines of cells, and this was associated with increased concentrations of 5-phosphoribosyl 1-pyrophosphate. Purine synthesis was also less sensitive than normal to feedback inhibition. The catabolism of inosinate synthesized de novo was increased.


Changes in the liver function tests during the attacks of familial Mediterranean fever.
The present study aims to investigate whether or not FMF patients display abnormal liver functions during attack periods. About 41 consecutive FMF patients with attacks were enrolled on this study. Bilirubin levels, liver transaminases, erythrocyte sedimentation rate and C-reactive protein (C-RP) levels were determined within the first 72 h after the onset of attacks. This procedure could be performed on only 28 of these 41 FMF patients, 4 weeks after the attack of the patients' had completely disappeared. As for the disease control group, 44 patients were determined to be eligible for the study. Another 31 healthy individuals were also included. Hyperbilirubinemia was determined in 11 of the 41 patients (26.8%) with FMF. The number of FMF patients with hyperbilirubinemia was significantly higher than in DC and HC (P < 0.001, P = 0.03, respectively). Levels of liver transaminases slightly increased in four patients with FMF during the attack and two of these four patients had also mild hyperbilirubinemia. A significant correlation was found between C-RP levels and total and unconjugated bilirubin levels in FMF patients with attack (r = 0.43, P = 0.01; r = 0.40, P = 0.02, respectively). In conclusion, mild hyperbilirubinemia may occur in one-fourth of the patients with FMF during the attack period.


Centromeric localization and adaptive evolution of an Arabidopsis histone H3 variant.
Centromeric H3-like histones, which replace histone H3 in the centromeric chromatin of animals and fungi, have not been reported in plants. We identified a histone H3 variant from Arabidopsis thaliana that encodes a centromere-identifying protein designated HTR12. By immunological detection, HTR12 localized at centromeres in both mitotic and meiotic cells. HTR12 signal revealed tissue- and stage-specific differences in centromere morphology, including a distended bead-like structure in interphase root tip cells. The anti-HTR12 antibody also detected spherical organelles in meiotic cells. Although the antibody does not label centromeres in the closely related species Arabidopsis arenosa, HTR12 signal was found on all centromeres in allopolyploids of these two species. Comparison of the HTR12 genes of A. thaliana and A. arenosa revealed striking adaptive evolution in the N-terminal tail of the protein, similar to the pattern seen in its counterpart in Drosophila. This finding suggests that the same evolutionary forces shape centromeric chromatin in both animals and plants.


Transition of distinctive symptoms of semantic dementia during longitudinal clinical observation.
The aim of this study is to examine the clinical symptoms in a number of semantic dementia (SD) patients and to reveal the longitudinal progression and clinical course of these distinctive symptoms of SD. 19 consecutive SD patients were examined. Symptoms were classified into 23 distinct categories: behavioral symptoms, language and cognitive symptoms and symptoms concerning the impairment of activities of daily living (ADL). We divided patients into two subgroups, left- and right-dominant SD, and compared the onset of each symptom. Language impairments occurred as the initial symptom in 16 cases. At the first examination, all cases showed both anomia and impairment of word comprehension. By around 3 years after onset, almost all language impairments were observed. Approximately 3-5 years after onset, prosopagnosia and behavioral symptoms appeared. Around the period when the loss of the language faculty and apathy became remarkable, impairment of ADL appeared. Patients spent all day in bed at this stage. Moreover, prosopagnosia appeared significantly earlier in right-dominant SD. Our findings clarify the progression of distinctive symptoms of SD patients. It is necessary to create a treatment strategy for SD patients with such a disease-specific course of SD.


Association of body mass index with morbidity in patients hospitalised with COVID-19.
To evaluate the association between body mass index (BMI) and clinical outcomes other than death in patients hospitalised and intubated with COVID-19. This is a single-centre cohort study of adults with COVID-19 admitted to New York Presbyterian Hospital-Weill Cornell Medicine from 3 March 2020 through 15 May 2020. Baseline and outcome variables, as well as lab and ventilatory parameters, were generated for the admitted and intubated cohorts after stratifying by BMI category. Linear regression models were used for continuous, and logistic regression models were used for categorical outcomes. The study included 1337 admitted patients with a subset of 407 intubated patients. Among admitted patients, hospital length of stay (LOS) and home discharge was not significantly different across BMI categories independent of demographic characteristics and comorbidities. In the intubated cohort, there was no difference in in-hospital events and treatments, including renal replacement therapy, neuromuscular blockade and prone positioning. Ventilatory ratio was higher with increasing BMI on days 1, 3 and 7. There was no significant difference in ventilator free days (VFD) at 28 or 60 days, need for tracheostomy, hospital LOS, and discharge disposition based on BMI in the intubated cohort after adjustment. In our COVID-19 population, there was no association between obesity and morbidity outcomes, such as hospital LOS, home discharge or VFD. Further research is needed to clarify the mechanisms underlying the reported effects of BMI on outcomes, which may be population dependent.


Determinants of ocular deviation in esotropic subjects under general anesthesia.
The authors attempted to identify the determinants of ocular deviation in a population of patients with esotropia under general anesthesia. Forty-one patients with esotropia were included. Horizontal ocular deviation was evaluated by the photographic Hirschberg test both in the awakened state and under general anesthesia before surgery. Changes in ocular deviation were measured and a multivariate analysis was used to assess its clinical determinants. The mean age (± standard deviation [SD]) of study subjects was 13 ± 11 years and 51% were females. The mean spherical equivalent refraction of the right eye was 2.44 ± 2.50 diopters (D), with no significant difference between eyes (P = .26). The mean ocular deviation changed significantly, from 33.5 ± 12.5 prism diopters (PD) at preoperative examination to 8.8 ± 11.4 PD under general anesthesia (P = .0001). The changes in ocular deviation positively correlated with the pre-operative ocular deviation (correlation coefficient r = 0.59, P = .0001) and negatively correlated with patient age (correlation coefficient r = -0.53, P = .0001). These two determinants remained significant after multivariate adjustment of the following variables: preoperative ocular deviation; age; gender; spherical equivalent refraction; and number of previous strabismus surgeries (model r(2) = 0.49, P = .0001). The ocular position under general anesthesia was reported as a key factor in the surgical treatment of subjects with esotropia; therefore, its clinical determinants were assessed. The authors observed that preoperative ocular deviation and patient age were the main factors that influenced the ocular position under general anesthesia.


Debris and 1/f noise in sliding friction dynamics under wear conditions.
Friction force time series showing irregular fluctuations have been since long considered one of the possible stick-slip regimes in sliding friction. However, it has not been until recently that a 1/f power spectrum in friction force time series derived from sliding friction experiments under wear conditions has been identified. A variety of models, mostly inspired in the field of earthquakes, has been explored, without reaching a fully satisfactory explanation of that behavior. Recently, the present authors have reported results of sliding friction experiments on steel with alumina pins, carried out with and without debris blowing, that proved the role of loose debris in determining the 1/f character of the friction force. A damped-forced harmonic oscillator with two friction terms was proposed to describe the dynamics of friction under wear conditions: one purely random, which accounts for surface roughness, and another inversely proportional to the amount of loose debris that was calculated by means of a modified sand-pile model. This paper presents a full discussion of the experiments that allowed to reach that conclusion and of the model proposed to rationalize the results. In addition, the results of experiments devised to understand the transition from friction with debris to friction without debris (experiment initiated without blowing and after some time switching on blowing) and vice versa are reported. The results of further studies of the wear track are presented, namely, the variation in the track width with sliding distance and results of chemical analyses and surface roughness measurements of the track, for both with or without debris blowing experiments. These additional data give further support to the crucial role of debris in the 1/f character of the friction force.


The behavior of pyrrolyl ligands within the rare-earth metal alkyl complexes. Insertion of C=N and C=O double bonds into Ln-sigma-C bonds.
This paper presents some unusual reactions of lanthanide tris(alkyl)s or lanthanide mono-Cp' (Cp' = (C(5)Me(4))SiMe(3)) bis(alkyl)s with pyrrolyl ligands, and the eta(5)- or eta(1)-coordination mode of the pyrrolyl ring, as well as C=N and C=O double bonds insertion into Ln-sigma-C moities. N,N,O-tridentate ligand HL(1), 2-(2-CH(3)OC(6)H(3)N=CH)-C(4)H(3)NH, was prepared. Treatment of HL(1) with rare-earth metal tris(alkyl)s, Ln(CH(2)SiMe(3))(3)(THF)(2), generated centrosymmetric bimetallic (pyrrolylaldiminato)lanthanide mono(alkyl) complexes [{2-(2-CH(3)OC(6)H(3)NC(H)R)-C(4)H(3)N}LnR](2) (1a: Ln = Y; 1b: Ln = Lu) (R = CH(2)SiMe(3)). In this process, HL(1) was deprotonated by the metal alkyl and its imino C=N group was deactivated by the intramolecular alkylation, generating dianionic species that bridged the two metal alkyl units in eta(5)/eta(1):kappa(1) modes. When the reaction was carried out in dimethoxyethane (DME), asymmetric complex [2-(2-CH(3)OC(6)H(3)NC(H)R)-C(4)H(3)N](2)Y(2)R(2)(DME) (2) was given. Furthermore, the reaction of alkyl complex 1b and benzophenone (Ph(2)C=O) afforded alkyl-insertion product [{2-(2-CH(3)OC(6)H(3)NC(H)R)-C(4)H(3)N}LuOC(R)Ph(2)](2) (3). Both the intermolecular alkylation and the pyrrole's behavior as the hetero-cyclopentadienyl ligand were also observed in complexes 2 and 3. HL(1) reacted with (eta(5)-Cp')Y(CH(2)SiMe(3))(2)(THF) (E) to form a mixed ligands supported alkyl complex [(eta(5)-Cp')(L(1))]Y(CH(2)SiMe(3))(THF) (4), whilst complex E was treated with 2-(2,6-iPr(2)C(6)H(3)N=CH)-C(4)H(3)NH (HL(2)) to yield [(eta(5)-Cp')(L(2))]Y(CH(2)SiMe(3))(THF) (5). However, reaction of E and 2-(Me(2)NCH(2))-C(4)H(3)NH (HL(3)) afforded Y[(eta(5)-Cp')(L(3))(2)] (6), and ligand redistribution was found in this process. The molecular structures of complexes 5 and 6 were confirmed by X-ray diffraction, which indicated that the C=N double bond survived and the pyrrolyl ring coordinated to the metal center in eta(1)-mode.


Apgar score and blood coagulation factors.
Blood coagulation tests were performed in 93 newborn infants with different Apgar score at the 1st and 5th minutes of life. The laboratorial determinations were periodically performed at 0, 24 and 48 hours of life. The following tests were performed: bleeding time, whole blood clotting time, prothrombin time, kaolin-cephalin clotting time, thrombin time, dosage of factors I, V, VIII and X, clot retraction, platelet count, englobulin lysis time and the tourniquet test. Immediately after birth, the mean values of the blood coagulation factors were significantly different among the groups, with the exception of the whole blood clotting time and the platelet count. Those differences were due to the presence of the more depressed neonates. Although these results could indicate some degree of hepatic damage, it was apparent that an activation of the blood coagulation mechanisms took place, leading to a consumption coagulopathy. The infants who died (10) presented clinical and laboratorial data suggestive of disseminated intravascular coagulation (DIC). Necroscopic findings of microthrombosis in the liver and in the central nervous system were diagnosed in two infants.


Social Welfare Expenditures and Infant Mortality.
This study examines the effects of social welfare expenditures on infant mortality (deaths younger than age 1 per 1,000 live births) across 19 Organisation for Economic Co-operation and Development (OECD) countries from 1980 to 2010. Data are obtained from various sources including the OECD, World Health Organization, and World Bank. The findings indicate that among three social welfare expenditure measures for families, the expenditures on family cash allowances are predicted to reduce infant mortality. However, the other two measures-the expenditures on parental and maternity leave and expenditures on family services-have no significant effects on infant mortality.


A One-Penny Imputed Genome from Next-Generation Reference Panels.
Genotype imputation is commonly performed in genome-wide association studies because it greatly increases the number of markers that can be tested for association with a trait. In general, one should perform genotype imputation using the largest reference panel that is available because the number of accurately imputed variants increases with reference panel size. However, one impediment to using larger reference panels is the increased computational cost of imputation. We present a new genotype imputation method, Beagle 5.0, which greatly reduces the computational cost of imputation from large reference panels. We compare Beagle 5.0 with Beagle 4.1, Impute4, Minimac3, and Minimac4 using 1000 Genomes Project data, Haplotype Reference Consortium data, and simulated data for 10k, 100k, 1M, and 10M reference samples. All methods produce nearly identical accuracy, but Beagle 5.0 has the lowest computation time and the best scaling of computation time with increasing reference panel size. For 10k, 100k, 1M, and 10M reference samples and 1,000 phased target samples, Beagle 5.0's computation time is 3× (10k), 12× (100k), 43× (1M), and 533× (10M) faster than the fastest alternative method. Cost data from the Amazon Elastic Compute Cloud show that Beagle 5.0 can perform genome-wide imputation from 10M reference samples into 1,000 phased target samples at a cost of less than one US cent per sample.


[A classic example of infectious endocarditis?].
A 15-year-old girl in whom the diagnosis of infective endocarditis was established was sent to our cardiothoracic centre for mitral valve replacement because of a streptococcal endocarditis resistant to adequate antibiotic therapy. Despite the combination of fever, a 'new' heart murmur, 'positive blood cultures' and 'vegetations' on the mitral valve, the clinical picture gave rise to some doubt about the diagnosis. Finally the diagnosis of systemic lupus erythematosus was made and after treatment with corticosteroids all symptoms disappeared. In our modern era 'simple symptoms' still play a very important part in clinical decision making.


Two stage thermophilic anaerobic-aerobic mineralization-stabilization of excess activated sludge.
At the National Institute of Chemistry, Ljubljana, Slovenia, new procedure for excess activated sludge was developed and patented. The main principle of the sludge mineralization is two-step process--the first is anaerobic, and the second step is aerobic. In the first step maximal biogas production is acquired in the second step at smaller VSS the optimal VSS and COD is achieved. Anaerobic, aerobic, and combined sludge mineralization was studied. The next combinations of different successive anaerobic and aerobic mineralization have been studied: 3 + 3 (3 days of anaerobic + 3 days of aerobic digestion), 3 + 6, 5 + 5, 3 + 12, and 10 + 10 days, respectively. The best combination considering biogas production, VSS and COD reduction have been gained for the combination of 3 + 6 days, and 3 + 12 days. At 3 + 6 days digestion about 49% of VSS, and about 51% of COD reduction was gained, at 3 + 12 days about 62% of VSS, and about 57% of COD reduction was achieved. For the optimal system operation, economics, biogas production, and necessary VSS and COD reduction have to be considered.


Variations in the relative mRNA levels of actins and myosin heavy chains do not produce corresponding differences in their proteins in the adult human heart.
This paper examines the quantitative relationship between the expression of myosin heavy chain (MHC) and actin at both the levels of their mRNAs and their proteins. Explanted human left ventricle tissues were obtained from non-diseased (ND) individuals and from dilated cardiomyopathy (DCM) patients with terminally failing hearts who underwent heart transplantation. We found: (1) there are substantial differences in the stoichiometry of sarcomeric MHC and actin transcripts in hearts of DCM patients as well as in ND individuals; (2) there are substantial differences between levels of total sarcomeric actin transcripts from different individual patients; (3) by and large variations in transcript levels between samples from the same heart are much less than between samples from different hearts; and (4) the ratio of MHC to sarcomeric actin proteins expressed by different ND and DCM hearts remains essentially constant. We conclude that the human ventricle can accommodate a substantial imbalance between sarcomeric MHC and actin mRNA levels while maintaining a constant ratio of their corresponding proteins.


Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities.
Extracellular nucleotides and nucleosides mediate diverse signaling effects in virtually all organs and tissues. Most models of purinergic signaling depend on functional interactions between distinct processes, including (i) the release of endogenous ATP and other nucleotides, (ii) triggering of signaling events via a series of nucleotide-selective ligand-gated P2X and metabotropic P2Y receptors as well as adenosine receptors and (iii) ectoenzymatic interconversion of purinergic agonists. The duration and magnitude of purinergic signaling is governed by a network of ectoenzymes, including the enzymes of the nucleoside triphosphate diphosphohydrolase (NTPDase) family, the nucleotide pyrophosphatase/phosphodiesterase (NPP) family, ecto-5'-nucleotidase/CD73, tissue-nonspecific alkaline phosphatase (TNAP), prostatic acid phosphatase (PAP) and other alkaline and acid phosphatases, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). Along with "classical" inactivating ectoenzymes, recent data provide evidence for the co-existence of a counteracting ATP-regenerating pathway comprising the enzymes of the adenylate kinase (AK) and nucleoside diphosphate kinase (NDPK/NME/NM23) families and ATP synthase. This review describes recent advances in this field, with special emphasis on purine-converting ectoenzymes as a complex and integrated network regulating purinergic signaling in such (patho)physiological states as immunomodulation, inflammation, tumorigenesis, arterial calcification and other diseases. The second part of this review provides a comprehensive overview and basic principles of major approaches employed for studying purinergic activities, including spectrophotometric Pi-liberating assays, high-performance liquid chromatographic (HPLC) and thin-layer chromatographic (TLC) analyses of purine substrates and metabolites, capillary electrophoresis, bioluminescent, fluorometric and electrochemical enzyme-coupled assays, histochemical staining, and further emphasizes their advantages, drawbacks and suitability for assaying a particular catalytic reaction.


Brain structural alterations in obese children with and without Prader-Willi Syndrome.
Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed that there is a significant difference in brain activation patterns between obese children with and without PWS. However, whether there are differences in the brain structure of obese children with and without PWS remains elusive. In the current study, we used T1-weighted and diffusion tensor magnetic resonance imaging to investigate alterations in the brain structure, such as the cortical volume and white matter integrity, in relation to this eating disorder in 12 children with PWS, 18 obese children without PWS (OB) and 18 healthy controls. Compared with the controls, both the PWS and OB groups exhibited alterations in cortical volume, with similar deficit patterns in 10 co-varying brain regions in the bilateral dorsolateral and medial prefrontal cortices, right anterior cingulate cortex, and bilateral temporal lobe. The white matter integrities of the above regions were then examined with an analysis method based on probabilistic tractography. The PWS group exhibited distinct changes in the reduced fractional anisotropy of white matter fibers connected to the co-varying regions, whereas the OB group did not. Our findings indicated that PWS and OB share similar gray matter alterations that are responsible for the development of eating disorders. Additionally, the distinct white matter alterations might explain the symptoms associated with food intake in PWS, including excessive hyperphagia and constant hunger. Hum Brain Mapp 38:4228-4238, 2017. © 2017 Wiley Periodicals, Inc.


Making the case for evidence-based design in healthcare: a descriptive case study of organizational decision making.
The aim of this study was to describe the organizational decision-making process used in the selection of evidence-based design (EBD) concepts, the criteria used to make these decisions, and the extent to which leadership style may have influenced the decision-making process. Five research questions were formulated to frame the direction of this study, including: (1) How did healthcare leaders learn of innovations in design? (2) How did healthcare leaders make decisions in the selection of healthcare design concepts? (3) What criteria did healthcare leaders use in the decision-making process? (4) How did healthcare leaders consider input from the staff in design decisions? and (5) To what extent did the leadership style of administrators affect the outcomes of the decision-making process? Current issues affecting healthcare in the community led the principal investigator's organization to undertake an ambitious facilities expansion project. As part of its planning process, the organization learned of EBD principles that seemingly had a positive impact on patient care and safety and staff working conditions. Although promising, a paucity of empirical research addressed the cost/benefit of incorporating many EBD concepts into one hospital setting, and there was no research that articulated the organizational decision-making process used by healthcare administrators when considering the use of EBD in expansion projects. A mixed-method, descriptive, qualitative, single-case study and quantitative design were used to address the five research questions. The Systems Research Organizing Model provided the theoretical framework. A variety of data collection methods was used, including interviews of key respondents, the review of documentary evidence, and the Multifactor Leadership Questionnaire. A participatory process was used throughout the design decision phases, involving staff at all levels of the organization. The Internet and architects facilitated learning about EBD. Financial considerations were a factor in decision making. The prevalence of the transformational leadership style among the organization's administrators exceeded the U.S. mean.


How xylitol-containing products affect cariogenic bacteria.
The authors examined the effect of xylitol, a naturally occurring sweetener, on levels of Streptococcus mutans and S. sobrinus. They also investigated xylitol's mechanism of action. The authors compared cariogenic bacteria levels before and after exposure to xylitol products in children and adults. In the first study, 187 children received xylitol-containing snacks in school for four weeks. In the second study, two adults received xylitol candy for four weeks. Unstimulated saliva samples were taken from all subjects. Gingival samples also were taken from the adults. The authors plated the samples on selective microbiological media. Individual isolates were plated on media with varying concentrations of xylitol, and were identified using specific DNA probes. Genetic relatedness was determined via pulse-field gel electrophoresis. The children's salivary S. mutans levels remained stable before and after xylitol exposure. Further analysis of the S. mutans isolates was conducted for seven children. Bacteria from five of these children grew with 10 percent or less xylitol at baseline, while the bacteria from all seven children grew with 15 percent xylitol after exposure to the xylitol-containing snacks, suggesting that the S. mutans increased in tolerance to xylitol during exposure. Six children had isolates with the same genotype at both time points. S. mutans and S. sobrinus levels were reduced in one of the adults as a result of xylitol exposure, and the bacterial isolates became more xylitol tolerant. In the second adult, S. mutans and S. sobrinus levels increased, while the subject maintained the same proportion of susceptible and tolerant strains as that at baseline. Overall, consumption of xylitol-containing snacks and candy did not reduce S. mutans levels. However, bacteria from five children and one adult became more xylitol tolerant. These results provide a basis on which xylitol-containing products can be recommended and xylitol's mechanism of action can be explained to patients.


cProx1 immunoreactivity distinguishes progenitor cells and predicts hair cell fate during avian hair cell regeneration.
In birds, mature sensory hair cells are regenerated continually in vestibular epithelia and after damage in the auditory basilar papilla. Molecular mechanisms governing the cellular processes associated with hair cell regeneration are poorly understood. Transcription factors are critical regulators of cell proliferation and differentiation in developing tissues. We examined immunoreactivity for cProx1 during both ongoing and damage-induced hair cell regeneration in chickens. Homologues of this divergent homeobox transcription factor are required for cell cycle withdrawal and differentiation in several vertebrate and invertebrate tissues. In the mitotically quiescent basilar papilla, a population of resting progenitor cells (supporting cells) shows faint nuclear immunoreactivity for cProx1. When auditory hair cell regeneration is triggered by experimental damage, nuclear cProx1 immunolabel is highly elevated in approximately 50% of dividing progenitor cells. Shortly after cytokinesis, all sibling pairs show symmetric patterns of nuclear cProx1 labeling, but pairs with asymmetric labeling emerge shortly thereafter. Strongly immunoreactive cells acquire the hair cell fate, whereas cells with low nuclear immunoreactivity differentiate as supporting cells. By contrast, cProx1 is not detected in any dividing progenitor cells during ongoing regeneration in the utricle. However, nuclear cProx1 immunoreactivity becomes asymmetric in postmitotic sibling cells, and as in the basilar papilla, cells with elevated cProx1 label differentiate as hair cells. In conclusion, cProx1 immunolabeling varies across sensory epithelial progenitors and distinguishes early differentiating hair cells from supporting cells. cProx1 may regulate the proliferative or differentiative capacities of progenitor cells and specify hair cell fate in postmitotic cells during avian hair cell regeneration.


Cell-Dock: high-performance protein-protein docking.
The application of docking to large-scale experiments or the explicit treatment of protein flexibility are part of the new challenges in structural bioinformatics that will require large computer resources and more efficient algorithms. Highly optimized fast Fourier transform (FFT) approaches are broadly used in docking programs but their optimal code implementation leaves hardware acceleration as the only option to significantly reduce the computational cost of these tools. In this work we present Cell-Dock, an FFT-based docking algorithm adapted to the Cell BE processor. We show that Cell-Dock runs faster than FTDock with maximum speedups of above 200×, while achieving results of similar quality. The source code is released under GNU General Public License version 2 and can be downloaded from http://mmb.pcb.ub.es/~cpons/Cell-Dock. firstname.lastname@example.com or email@example.com Supplementary data are available at Bioinformatics online.


Antagonism of antigen-induced contraction of isolated guinea-pig trachea by 5-lipoxygenase inhibitors.
Tracheal strips were obtained from guinea pigs actively sensitized to chicken ovalbumin (OA). OA-induced contractile responses, obtained by cumulative log addition, were found to be comparable both temporally and in magnitude with responses obtained by single addition of OA. The concentration-response curve obtained by cumulative addition of OA was partially inhibited by pretreatment of tissues with chlorpheniramine. On tracheal spirals treated with chlorpheniramine, indomethacin enhanced OA-induced contractile responses. In the presence of chlorpheniramine and indomethacin, pretreatment with one of the reference 5-lipoxygenase inhibitors (ETYA, NDGA, phenidone or BW-755C) both reduced the maximum contractile response and produced a rightward shift of the OA concentration-response curve. The data suggest that cumulative log addition of OA, on the indomethacin- and chlorpheniramine-treated guinea-pig trachea, is a useful model for evaluating compounds active as either inhibitors of 5-lipoxygenase or antagonists of the products of this pathway.


Biodegradation of food waste using microbial cultures producing thermostable α-amylase and cellulase under different pH and temperature.
The aim of this work was to study the biodegradation of food waste employing thermostable α-amylase and cellulase enzymes producing bacteria. Four potential isolates were identified which were capable of producing maximum amylase and cellulase and belong to the amylolytic strains, Brevibacillus borstelensis and Bacillus licheniformis; cellulolytic strains, Bacillus thuringiensis and Bacillus licheniformis, respectively. These strains were selected based on its higher cell density, enzymatic activities and stability at a wide range of pH and temperature compared to other strains. The results indicated that 1:1 ratio of pre and post consumed food wastes (FWs) were helpful to facilitate the degradation employing bacterial consortium. In addition, organic matter decomposition and chemical parameters of the end product quality also indicated that bacterial consortium was very effective for 1:1 ratio of FWs degradation as compared to the other treatments.


Chronic myelogenous leukemia.
Chronic myelogenous leukemia (CML) is a relatively rare disease, with a number of features that make it especially suitable for observations on leukemogenesis in man. These include known etiologic agents, often a prolonged preclinical and active stage, cells with identifiable morphological and histochemical characteristics and the presence of the unique Ph' chromosome. The transition of CML to blast crisis is a catastrophic event; however, recent clinical and biochemical studies have raised important questions as to the nature and origin of blast cells in this disease. During the past 10 years, we have followed 113 cases olf CML throughout their course and results of observations on the clinical, hematological and other apsects of the disease are presented in this communication.


Status of school children's hearing aids relative to monitoring practices.
Data concerning hearing aid monitoring practices and hearing aid malfunction were collected for three groups of mainstreamed hearing-impaired children: 248 children receiving services from itinerant teachers of the hearing impaired, 43 who participated in a study involving extensive psychoeducational evaluation, and 10 children who attended a 6 week residential treatment program in which hearing aid function was checked at least twice each day. Comparisons of the three data sets revealed that even conscientious parental and professional monitoring practices prove inadequate. As a result, it is hypothesized that children must take active roles in the monitoring process. A program to help children develop hearing aid monitoring skills is outlined.


Soft drinks: time trends and correlates in twenty-four European countries. A cross-national study using the DAFNE (Data Food Networking) databank.
To evaluate time trends in the availability of soft drinks, to identify food choices associated with their consumption and to assess the relationship between socio-economic status and daily soft drink availability in a wide range of European countries. Data on food and beverage availability collected through the national household budget surveys and harmonized in the DAFNE (Data Food Networking) project were used. Averages and variability of soft drink availability were estimated and tests for time trends were performed. The daily availability of food groups which appear to be correlated with that of soft drinks was further estimated. Multivariate logistic and linear regression models were applied to evaluate the association between socio-economic status and the acquisition of soft drinks. Twenty-four European countries. Nationally representative samples of households. The availability of soft drinks is steadily and significantly increasing. Households in West and North Europe reported higher daily availability of soft drinks in comparison to other European regions. Soft drinks were also found to be correlated with lower availability of plant foods and milk and higher availability of meat and sugar products. Lower socio-economic status was associated with more frequent and higher availability of soft drinks in the household. Data collected in national samples of twenty-four European countries showed disparities in soft drink availability among socio-economic strata and European regions. The correlation of soft drinks with unfavourable dietary choices has public health implications, particularly among children and adolescents.


Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Virus Matrix Protein 1 with Lipid Membranes.
Influenza A virus matrix protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and the budding process is required in order to devise new therapeutic approaches. We performed a detailed investigation of the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane [PM]), as well as the distribution of PS itself, both in model membranes and in living cells. To this end, we used a combination of techniques, including Förster resonance energy transfer (FRET), confocal microscopy imaging, raster image correlation spectroscopy, and number and brightness (N&B) analysis. Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine and in living cells. The viral protein M1 interacts specifically with PS-enriched domains, and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. For living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor lactadherin. Also, colocalization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered. Taken together, our observations provide novel evidence regarding the role of PS-rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells.IMPORTANCE Influenza virus particles assemble at the plasma membranes (PM) of infected cells. This process is orchestrated by the matrix protein M1, which interacts with membrane lipids while binding to the other proteins and genetic material of the virus. Despite its importance, the initial step in virus assembly (i.e., M1-lipid interaction) is still not well understood. In this work, we show that phosphatidylserine can form lipid domains in physical models of the inner leaflet of the PM. Furthermore, the spatial organization of PS in the plane of the bilayer modulates M1-M1 interactions. Finally, we show that PS domains appear to be present in the PM of living cells and that M1 seems to display a high affinity for them.


[Thalassaemia intermedia. Clinical and laboratory study. Therapeutic suggestions (author's transl)].
The clinical and laboratory criteria which distinguish thalassaemia intermedia (T.I.) from thalassaemia major were analyzed in a series of 30 patients with homozygous beta- thalassaemia, 8 of whom had T.I. The appearance of the first symptoms after the age of 2 years, the moderate spleen enlargement, the haemoglobin levels approaching 8 g/100 ml and the response to moderate transfusions over 1-year observation period were in favour of T.I. Since patients who had transfusions were clinically better than those who had none, it is suggested that T.I. patients should be treated with regular transfusions and iron chelating agents.


FTO rs9939609 Gene Polymorphism and Obesity: Lack of Association in Kidney Transplantation.
The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation. In 198 kidney transplant recipients, FTO rs9939609 was investigated in association with body mass index (BMI)/obesity and with other clinical markers of posttransplant risk, then monitored up to 5 years after transplantation. Genotyping was performed using an allelic discrimination method on a real-time polymerase chain (PCR) system. Associations were analyzed using the chi-square test; differences between genotypes were examined with analysis of variance or Kruskal-Wallis test; tests for repeated measures and a general linear model analysis controlling for age and gender were also utilized. Allele and genotype frequencies of FTO rs9939609 in recipients (T/T, 29.8%; T/A, 49.0%; A/A, 21.2%; A, 45.7%; T, 54.3%) reflect those present in healthy Caucasian populations. In the face of pre-/posttransplant differences in total cholesterol, triglycerides, or fasting glucose, results did not show significant changes in these factors among genotypes either before or after transplantation. This study highlights a lack of association of FTO rs9939609T>A genotypes and posttransplant weight gain, plasma lipids, and fasting blood glucose in kidney transplantation.


Continuous glucose monitoring in type 2 diabetes.
The utility and efficacy of self-monitoring of blood glucose (SMBG), using single capillary glucose determinations, in the management of non-insulin treated type 2 diabetes has been called into question. The use of continuous sub-cutaneous glucose monitoring (CGM) systems provides an answer for at least some of the inadequacies attributed to point capillary SMBG. The use of CGM adds information on postprandial glucose excursions, nocturnal hypoglycemia or hyperglycemia not previously detected by SMBG. This added information facilitates the tailoring of treatment regimens to the individual patient in order to achieve treatment targets without incurring an increased risk of hypoglycemia and provides a useful tool for patient self-management education.


The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides.
The ErbB1 and ErbB2 receptor tyrosine kinases (RTKs) play important roles in the development of numerous types of human cancer and, as such, have been pursued as anticancer targets. To understand the mechanisms contributing to the response of tumor cells to receptor-directed therapeutics, the sensitivity of the ErbB receptor-overexpressing tumor cell lines BT474 and MKN7 to specific inhibitors has been examined. The inhibitors used included monoclonal antibody (mAb) 4D5, which targets ErbB2, and the small molecular weight kinase inhibitors CGP59326 and PKI166, which block the activity of ErbB1 or both ErbB1 and ErbB2, respectively. We had reported previously that although both BT474 and MKN7 cells overexpress ErbB2, only BT474 cells show an antiproliferative response to mAb 4D5 treatment. Here, we show that MKN7 cells, which also overexpress ErbB1, are sensitive to CGP59326, displaying a 60% decrease in their proliferation after treatment with this inhibitor. Most carcinomas express multiple ErbB receptors as well as EGF-related ligands, a situation favoring activation of numerous combinations of ligand-activated receptors. Considering this, the sensitivity of MKN7 and BT474 cells to CGP59326 and mAb 4D5, respectively, was also tested in the presence of exogenous ligands. Treatment of MKN7 cells with CGP59326 in the presence of heregulin (HRG), which activates ErbB2/ErbB3, attenuated the antiproliferative effect of CGP59326 by 50%; MKN7 cells engineered to overexpress ErbB3 were completely rescued from CGP59326 by HRG. Likewise, BT474 cells treated with mAb 4D5 in the presence of epidermal growth factor, betacellulin, and HRG were rescued from its antiproliferative effects by 57, 84, and 90%, respectively. In both MKN7 and BT474 tumor cells, the degree of ligand-induced rescue from the inhibitors correlated with the potency of ErbB receptor activation and stimulation of the PI3K and MAPK intracellular signaling pathways. In comparison with the monospecific agents, treatment with the bispecific ErbB1/ErbB2 kinase inhibitor PKI166 almost completely prevented the EGF-related ligand-induced bypass of the proliferation block in the MKN7 and BT474 cells. These data suggest that the efficacy of anticancer drugs that block a single ErbB receptor may be compromised by the presence of exogenous epidermal growth factor-related ligands, a phenomenon that could be averted by simultaneously blocking multiple ErbB receptors.


Occult traumatic lesions of the cervical vertebrae.
The numerous general and special techniques for examination of the cervical spine, with particular reference to the demonstration of occult traumatic lesions will be presented and evaluated. The advantages and limitations of each technique will be presented. Optimal procedures will be suggested for the examination of the acutely injured patient, with injuries of unknown severity, as well as for the longer term followups and minor injuries. The mechanisms of the production of cervical spine traumatic lesions and the long term abnormalities to be anticipated will be related, together with the types of radiographic findings associated with them. These will be presented in the context of the anatomy, function and dynamic physiology of the cervical spine. The dynamic interrelationship between segments of the cervical spine and the cervical spine as a whole, as well as the interrelation of the cervical spine with the skull and the remainder of the spine will be considered. The clinical data available in the literature will be collected and correlated with the radiographic findings. The results will be used to evaluate the clinical significance of these occult traumatic lesions, and the efficacy of therapy.


Structure of a putative fluorinated natural product from Streptomyces sp. TC1.
Fluorine-containing natural products are extremely rare. The recent report on the isolation and biological activity of the bacterial secondary metabolite 3-(3,5-di-tert-butyl-4-fluorophenyl)propionic acid was thus highly remarkable. The compound contained the first aromatic fluorine substituent known to date in any natural product. The promise to discover an enzyme capable of aromatic fluorination in the producing strain Streptomyces sp. TC1 prompted our immediate interest. A close inspection of the originally reported analytical data of the fluoro metabolite revealed inconsistencies that triggered us to validate the reported structure. The results of these efforts are presented in this communication.


Acute angle-closure glaucoma after general anesthesia for bone grafting.
Acute angle-closure glaucoma (AACG) is a rare complication of general anesthesia. The coexistence of individual risk factors for postoperative AACG and factors associated with intraocular hypertension are considered to be required for postoperative AACG to develop. We present a case of AACG after general anesthesia for oral bone grafting in a patient with no preoperative eye symptoms. In this case, several factors such as postoperative care in a darkened room, psychological stress, and postoperative hypertension may have precipitated the event in this patient, who may have had preexisting undiagnosed elevated intraocular pressure. The interval between the earliest appearance of symptoms at 9 hours and the ultimate diagnosis was 36 hours. In the postoperative period following general anesthesia, any patient is at risk for AACG. It is important that a postoperative diagnosis of AACG should be considered and a timely consultation with an ophthalmologist be considered if a postoperative patient complains of red eyes, visual disorder, eye pain, headache, and nausea.


Predicting subsequent contralateral slipped capital femoral epiphysis: an evidence-based approach.
The purpose of this study was to identify risk factors for developing a subsequent contralateral slipped capital femoral epiphysis (SCFE) and provide a prediction score to quantify risk of subsequent slip at the time of initial presentation. This retrospective study included patients that presented with a unilateral SCFE between 2006 and 2017. Chart and radiographic review were performed to collect demographic, clinical and radiographic risk factors. Descriptive statistics, univariate analyses and multivariate regression analysis were used to compare risk factors between patients that did or did not develop a subsequent contralateral SCFE. This study included 183 patients and 33 patients (18%) developed a subsequent contralateral SCFE. Younger age at time of initial presentation, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between both sides during index presentation were significant predictors of subsequent contralateral SCFE. Specifically, age ≤ 11 years, modified Oxford Score ≤ 20 and difference in epiphyseal-diaphyseal angle of ≤ 21° between both hips were predictive of a contralateral slip (Area Under the Curve = 0.78; p < 0.05). The presence of each risk factor increased the risk of subsequent contralateral SCFE and having all three risk factors increased the risk to 73%. There is a significant risk of subsequent contralateral SCFE in patients with unilateral SCFE, and predictive risk factors include younger age, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between the affected and unaffected hips. Level III.


Simulating proteins at constant pH: An approach combining molecular dynamics and Monte Carlo simulation.
For the structure and function of proteins, the pH of the solution is one of the determining parameters. Current molecular dynamics (MD) simulations account for the solution pH only in a limited way by keeping each titratable site in a chosen protonation state. We present an algorithm that generates trajectories at a Boltzmann distributed ensemble of protonation states by a combination of MD and Monte Carlo (MC) simulation. The algorithm is useful for pH-dependent structural studies and to investigate in detail the titration behavior of proteins. The method is tested on the acidic residues of the protein hen egg white lysozyme. It is shown that small structural changes may have a big effect on the pK(A) values of titratable residues.


Has the time come to include low-level laser photobiomodulation as an adjuvant therapy in the treatment of impaired endometrial receptivity?
Low-level laser therapy (LLLT) has been used in photobiomodulation to promote healing, regenerate, and restore tissue function. Women with persistent thin endometrium were assumed to encounter diminished activity in the regenerative and functional capacity of their endometrium. The aim of this study was to examine the ability of LLLT in 635 nm wavelength to enhance the proliferation and gene expression of in vitro cultured endometrial cells. Single (SE) versus multiple exposures (ME) to LLLT were examined in the study groups and compared to controls. A fluence dose of 4.27 J/cm2 for 16 min was given once in the SE or divided in three equal sessions in days 2, 4, and 6 of the culture in ME. Cellular response was evaluated by measuring viable cell numbers and surface area. Pattern of MUC1, ITGA5, ITGB3, LIF, and PTEN gene expression was assessed using the qRT-PCR. Greater numbers of cells were found in both study groups (P < 0.001) as compared to controls. The surface area of cells at the end of culture phase was highly significant (P < 0.001) in ME when compared to SE and controls. A statistically significant difference was found in terms of gene expression in both irradiated groups (P < 0.001) as compared to controls, although greater difference in PTEN tumour suppressor gene (Phosphatase and tensin homolog) expression was toward ME. The introduction of LLLT to the armamentarium of infertility will serve as a new adjuvant therapy in this field. The current study proofed that LLLT was able to increase the proliferative and functional capacity of cultured endometrial cells.


Surviving survivors. Coping with caring for patients who have been victimized.
Caring for survivors of victimization is very hard work, in ways that are similar to and different from other difficult patient interactions. Careful attention to basic physiologic and psychological needs of the physicians is necessary to tolerate the stress and to prevent the burnout that can accompany this work. In addition, understanding survivors' interpersonal dynamics may help physicians provide better care. Consultation with colleagues is essential to remaining healthy and effective as givers of care.


Validation of computerized wheeze detection in young infants during the first months of life.
Several respiratory diseases are associated with specific respiratory sounds. In contrast to auscultation, computerized lung sound analysis is objective and can be performed continuously over an extended period. Moreover, audio recordings can be stored. Computerized lung sounds have rarely been assessed in neonates during the first year of life. This study was designed to determine and validate optimal cut-off values for computerized wheeze detection, based on the assessment by trained clinicians of stored records of lung sounds, in infants aged <1 year. Lung sounds in 120 sleeping infants, of median (interquartile range) postmenstrual age of 51 (44.5-67.5) weeks, were recorded on 144 test occasions by an automatic wheeze detection device (PulmoTrack®). The records were retrospectively evaluated by three trained clinicians blinded to the results. Optimal cut-off values for the automatically determined relative durations of inspiratory and expiratory wheezing were determined by receiver operating curve analysis, and sensitivity and specificity were calculated. The optimal cut-off values for the automatically detected durations of inspiratory and expiratory wheezing were 2% and 3%, respectively. These cutoffs had a sensitivity and specificity of 85.7% and 80.7%, respectively, for inspiratory wheezing and 84.6% and 82.5%, respectively, for expiratory wheezing. Inter-observer reliability among the experts was moderate, with a Fleiss' Kappa (95% confidence interval) of 0.59 (0.57-0.62) for inspiratory and 0.54 (0.52 - 0.57) for expiratory wheezing. Computerized wheeze detection is feasible during the first year of life. This method is more objective and can be more readily standardized than subjective auscultation, providing quantitative and noninvasive information about the extent of wheezing.


MYB-QKI rearrangement in angiocentric glioma.
To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.


lincRNA-Cox2 Functions to Regulate Inflammation in Alveolar Macrophages during Acute Lung Injury.
Our respiratory system is vital to protect us from the surrounding nonsterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of inflammatory cues. Recent studies have shown that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. lincRNA-Cox2 is one such example of an inflammatory inducible long intergenic noncoding RNA functioning to fine-tune immune gene expression. Using bulk and single-cell RNA sequencing, in addition to FACS, we find that lincRNA-Cox2 is most highly expressed in the lung and is most upregulated after LPS-induced lung injury (acute lung injury [ALI]) within alveolar macrophages, where it functions to regulate inflammation. We previously reported that lincRNA-Cox2 functions to regulate its neighboring protein Ptgs2 in cis, and in this study, we use genetic mouse models to confirm its role in regulating gene expression more broadly in trans during ALI. Il6, Ccl3, and Ccl5 are dysregulated in the lincRNA-Cox2-deficient mice and can be rescued to wild type levels by crossing the deficient mice with our newly generated lincRNA-Cox2 transgenic mice, confirming that this gene functions in trans. Many genes are specifically regulated by lincRNA-Cox2 within alveolar macrophages originating from the bone marrow because the phenotype can be reversed by transplantation of wild type bone marrow into the lincRNA-Cox2-deficient mice. In conclusion, we show that lincRNA-Cox2 is a trans-acting long noncoding RNA that functions to regulate immune responses and maintain homeostasis within the lung at baseline and on LPS-induced ALI.


Coexpression of different antigenic markers on moieties that bear CA 125 determinants.
CA 125 has been extensively evaluated as a serum marker for monitoring patients with epithelial ovarian carcinoma. Recently, consideration has been given to the use of CA 125 as one component in a strategy for early detection of this disease. A number of benign conditions can, however, increase CA 125 in serum, limiting the utility of a single antigen determination for identifying ovarian cancer patients. Coexpression of different epitopes on the high molecular weight complexes that express CA 125 determinants might provide a more specific test for malignant disease, provided that adequate sensitivity were maintained. To determine how frequently determinants are coexpressed, macromolecular moieties containing CA 125 determinants have been isolated from ascites fluid of ovarian cancer patients by immunoaffinity chromatography. CA 125+ moieties have been probed on Western transfers with several murine monoclonal antibodies that recognize distinct tumor-associated epitopes. Marked heterogeneity was observed between patients with regard to antigenic determinants that could be coexpressed with CA 125. A fraction of ascites fluids from different ovarian cancer patients contained moieties which bound to OC 125 on a solid phase immmunoadsorbent and which also bound 125I-labeled monoclonal antibodies NS 19-9, B72.3, DF3, or the novel murine monoclonal antibody OC 3632 in a double determinant immunoradiometric assay. Serum samples were evaluated from patients with ovarian cancer and from apparently healthy individuals. Coexpression of TAG 72 and CA 125 was observed most frequently. When the double determinant assay for coexpression of TAG 72 and CA 125 was compared to assays for the individual antigens, the assay for coexpression was substantially less sensitive than those for the individual markers.


The induction of hapten-specific immunologic tolerance and immunity in B lymphocytes. I. The effect of delayed immunization on the adoptive response to TNP-LPS.
An improved adoptive transfer procedure has been developed for the thymus-independent conjugate TNP-LPS. This technique involving delayed immunization results in increased sensivity and makes possible studies of various cell types, the response of which is normally very low or which are difficult to manipulate experimentally in situ. The standard adoptive immune response of adult spleen cells to TNP-LPS was low in comparison to the primary AFC response of intact mice. Adult bone marrow cells gave a 30-fold lower and neonatal spleen cells an 8-fold lower adoptive response than an equivalent number of adult spleen cells. If the administration of antigen was delayed past the normal time of immunization (1 hr after cell transfer), the resulting AFC response of adult spleen, adult bone marrow, and neonatal cells was enhanced. The peak response occurred with a delay interval of 4 days, and the magnitude decreased with greater delay. Part of the reason for the decline was an acceleration in the attainment of a peak response in mice given antigen past the 4-day optimum. The enhancement of the adult splenic response was not restricted to the antigen TNP-LPS, and was a transferrable phenomenon which did not require antigen to persist past the 4-day optimum delay period. The ineffectiveness of host pre-irradiation indicated that host recovery alone was not involved. Although the results are more compatible with B cell proliferation causing the enhancement, a combination of effects may be involved.


A characterization of the H3 and H4 histone genes from the ascidian Styela plicata.
Information about histone sequences and histone gene organization from invertebrate chordates is completely lacking. A genomic clone containing linked H3 and H4 histone genes from the urochordate Styela plicata was analyzed. The nucleotide sequence indicates that the two genes are transcribed in opposite directions and have structural similarities to cell cycle-dependent histones. Unique amino acid replacements occur in H3 at positions 88 (serine) and 98 (arginine). In H4, the methionine at position 84 is replaced by a leucine, a replacement found only in fungi. Codon usage patterns are nonrandom and resemble invertebrate patterns. The H3 and H4 genes are polymorphic and are represented five times per haploid genome.


Power in the hypnotic relationship: therapeutic or abusive?
The unique relationship between hypnotist and subject has been theorized as one explanation for the effectiveness of hypnosis. This relationship carries a power differential, present in most therapeutic relationships, but accentuated by hypnosis. The power differential is sometimes perceived as the ability of the hypnotist to control the subject. Perceptions of hypnosis offered by stage hypnotists, the popular media, and some clinicians perpetuate the notion that the hypnotist has the ability to exert undue influence upon the client. The present article examines the relationship between hypnotist and subject focusing on issues of power and control. The authors examine the unique dynamics accompanying the use of hypnosis and their impact on the therapeutic dyad. Evidence is offered demonstrating the power differential, and how this differential can serve as either a positive or negative agent of change. Therapists should be aware of the dynamics created by using hypnosis. Implications for training therapists in the use of hypnosis are suggested.


Dual-Action Cancer Therapy with Targeted Porous Silicon Nanovectors.
There is a pressing need to develop more effective therapeutics to fight cancer. An idyllic chemotherapeutic is expected to overcome drug resistance of tumors and minimize harmful side effects to healthy tissues. Antibody-functionalized porous silicon nanoparticles loaded with a combination of chemotherapy drug and gold nanoclusters (AuNCs) are developed. These nanocarriers are observed to selectively deliver both payloads, the chemotherapy drug and AuNCs, to human B cells. The accumulation of AuNCs to target cells and subsequent exposure to an external electromagnetic field in the microwave region render them more susceptible to the codelivered drug. This approach represents a targeted two-stage delivery nanocarrier that benefits from a dual therapeutic action that results in enhanced cytotoxicity.