Transversus Abdominis Plane Block Reduced Early Postoperative Pain after Robot-assisted Prostatectomy: a Randomized Controlled Trial.
Analgesic effect of transversus abdominis plane block (TAP block) in lower major abdominal laparoscopic surgery with about 5 cm of maximum surgical scar has been controversial. We hypothesized that TAP block has benefits, so the analgesic effect of TAP block after robot-assisted laparoscopic prostatectomy (RALP) was evaluated. One hundred patients were enrolled in this prospective, double-blinded, randomized study. Standardized general anesthesia with wound infiltration on camera port and fentanyl dose limit of 3 µg/kg was provided. Ultrasound-guided, single-shot subcostal TAP block with either 0.375% ropivacaine (Ropivacaine group, 48 patients) or normal saline (Control group, 52 patients) was performed by anesthesiologist in charge (34 anesthesiologists) after surgical procedure. Pain score using numerical rating scale (NRS) and postoperative intravenous fentanyl were evaluated for the first 24 postoperative hours. Median values (interquartile range) of NRS scores when the patients were transferred to post-anesthesia care unit (PACU) were 5 (2-7) in Ropivacaine group and 6 (4-8) in Control group at rest (P = 0.03), 5 (2-8) in Ropivacaine group and 7 (5-8) in Control group during movement (P < 0.01). These significant differences disappeared at the time of discharging PACU. Fentanyl doses for the first 24 postoperative hours were 210 µg (120-360) in Ropivacaine group and 200 µg (120-370) in Control group (P = 0.79). These results indicated that subcostal TAP block by anesthesiologists of varied level of training reduced postoperative pain immediate after RALP. TAP block had fundamental analgesic effect, but this benefit was too small to reduce postoperative 24-hour fentanyl consumption.


Forecasting distribution of body mass index in the United States: is there more room for growth?
Much of the literature on obesity has consistently documented the unprecedented rise in body weight over the past 2 decades. Less attention is paid to future projections of the population distribution of body mass index (BMI). To forecast the distribution of BMI in children (6-17 years) and adults (>17 years) in the United States (US) by age group, sex, and race over the period 2004-2014. Analysis of Medical Expenditure Panel Survey data (2001-2002 and 2004- 2005) to estimate and compare the 1-year transitions across BMI categories for children and adults. Forecasting distributions of obesity over 2004-2014 using a probabilistic population-level simulation model and validating it with prevalence data from 2005-2006 National Health and Nutrition Examination Survey. During 2004- 2005, a majority of adults in each BMI category remained in the same category after 1 year, these estimates being not significantly different than the corresponding estimates in 2001-2002. Among children, stabilities within BMI categories are low during 2004-2005, and compared with 2001-2002, transition probabilities into overweight class 2 from other BMI categories increase substantially. Forecasts reveal significant increases in the risk of overweight category among children 6 to 9 years old (5% to 14% in 5 years), with a greater increase anticipated in males, and increases in the overweight category for many years to come for adults, although the adult obesity prevalence remains at the current levels. Although the absolute levels of obesity remain high among US adults, the growth in obesity appears to have stagnated. On the contrary, continued growth in the prevalence of the highest BMI category for children is anticipated.


[Metastasis of an adenocarcinoma of the colon to the 1st metacarpal bone].
The authors report a clinical case of metastasis to the first metacarpal arising from carcinoma of the colon, treated surgically four years previously. Clinical examination revealed painful swelling over the right thenar eminence. The diagnosis was established by radiology and needle biopsy. No treatment was administered and the patient died one month later. Metastases of the hand are uncommon and, according to the review of the international literature concerning bone metastases in the hand conducted by Kerin (1987), are usually secondary to lung, renal and breast cancers. Only a few cases have been described in the literature of bone metastases of the hand from carcinoma of the colon. The authors feel that some of these cases probably remain undiagnosed, as they are of secondary importance in view to the severity of the disease.


Extracorporeal femoral to carotid artery perfusion in selective brain cooling for a giant aneurysm. Case report.
Giant partially thrombosed intracranial aneurysms are a challenge to treat surgically, and they are also unsuitable for coil embolization. The current options for treatment include extracranial-intracranial bypass followed by parent artery occlusion or direct surgical occlusion in which deep hypothermic circulatory arrest is used. The authors report the use of another approach in the treatment of a giant anterior circulation aneurysm: selective brain cooling accomplished by extracorporeal perfusion. This facilitated direct surgery on a 4.2-cm, partially thrombosed aneurysm of the middle cerebral artery (MCA). A brain temperature of 22 degrees C was achieved after 20 minutes of perfusion with blood cooled using an extracorporeal technique of femoral-common carotid artery perfusion. This was followed by a 20-minute period of surgical trapping of the MCA, then evacuation and clip occlusion of the aneurysm. During the period of selective brain cooling the patient's core body temperature was maintained above 35 degrees C. This technique of selective brain cooling may be a useful alternative to currently available surgical and endovascular methods of treatment for giant aneurysms.


Tyrosine transfer RNA levels and modifications during blood-feeding and vitellogenesis in the mosquito, Aedes aegypti.
Mosquitoes such as Aedes aegypti must consume a blood meal for the nutrients necessary for egg production. Several transcriptome and proteome changes occur post blood meal that likely corresponds with codon usage alterations. Transfer RNA (tRNA) is the adapter molecule that reads messenger RNA (mRNA) codons to add the appropriate amino acid during protein synthesis. Chemical modifications to tRNA enhance codons' decoding, improving the accuracy and efficiency of protein synthesis. Here, we examined tRNA modifications and transcripts associated with the blood meal and subsequent periods of vitellogenesis in A. aegypti . More specifically, we assessed tRNA transcript abundance and modification levels in the fat body at critical times post blood-feeding. Based on a combination of alternative codon usage and identification of particular modifications, we identified that increased transcription of tyrosine tRNAs is likely critical during the synthesis of egg yolk proteins in the fat body following a blood meal. Altogether, changes in both the abundance and modification of tRNA are essential factors in the process of vitellogenin production after blood-feeding in mosquitoes.


Three-year changes in leisure activities are associated with concurrent changes in white matter microstructure and perceptual speed in individuals aged 80 years and older.
Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we investigated the role of change in white matter microstructure in the activities-cognition link. We used repeated assessments of engagement, perceptual speed, and white matter microstructure (probed with diffusion tensor imaging) in a population-based sample of individuals over 80 years without dementia (n = 442, Mage = 85.1; n = 70 for diffusion tensor imaging; 2 occasions 3 years apart). Using multivariate latent change modeling, we observed positive correlations among changes in predominantly social activities, white matter microstructure, and perceptual speed. Interindividual differences in change in white matter microstructure statistically accounted for the association between change in leisure activities and change in perceptual speed. However, as analyses are based on observational data from 2 measurement occasions, causality remains unclear.


Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations.
The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.


[Cardiac metastasis as cause of therapy-resistant heart failure].
Ultrasonography revealed a renal tumour (4 x 4 cm) in a 67-year-old man with right-sided lumbar pain and macrohematuria. In addition he had marked nocturnal dyspnoea with dry cough. He had lost about 10 kg in weight. On admission he had atrial fibrillation with an irregular ventricular rate (140 beats/min) and engorgement of the neck veins. Two-dimensional echocardiography, undertaken because of signs of increasing heart failure and a fall of systolic blood pressure to below 100 mm Hg, demonstrated a space-occupying lesion in the right ventricle, 4 x 2 x 1 cm, indicating an intracardiac thrombus or solid tumour. The heart failure continued to worsen, despite treatment with cardiac glycosides, verapamil and diuretics. Hence an exploratory thoracotomy was performed. This revealed an intracardiac tumour which had markedly displaced the right ventricular inflow tract and infiltrated the entire myocardium, but not the tricuspid valve. As much of the tumour as possible was resected, but the patient died postoperatively of heart failure. The intracardiac tumour proved to be a metastasis from the papillary carcinoma of the kidney. This had infiltrated the renal capsule and pelvis and invaded the branches of the right renal vein.


Capacitive micromachined ultrasonic transducers with piston-shaped membranes: fabrication and experimental characterization.
Capacitive micromachined ultrasonic transducers (CMUTs) featuring piston-shaped membranes (piston CMUTs) were developed to improve device performance in terms of transmission efficiency, reception sensitivity, and fractional bandwidth (FBW). A piston CMUT has a relatively flat active moving surface whose membrane motion is closer to ideal piston-type motion compared with a CMUT with uniformly thick membranes (classical CMUT). Piston CMUTs with a more uniform surface displacement profile can achieve high output pressure with a relatively small electrode separation. The improved device capacitance and gap uniformity also enhance detection sensitivity. By adding a center mass to the membrane, a large ratio of second-order resonant frequency to first-order resonant frequency was achieved. This improved the FBW. Piston CMUTs featuring membranes of different geometric shapes were designed and fabricated using wafer bonding. Fabricating piston CMUTs is a more complex process than fabricating CMUTs with uniformly thick membranes. However, no yield loss was observed. These devices achieved ~100% improvement in transduction performance (transmission and reception) over classical CMUTs. For CMUTs with square and rectangular membranes, the FBW increased from ~110% to ~150% and from ~140% to ~175%, respectively, compared with classical CMUTs. The new devices produced a maximum output pressure exceeding 1 MPa at the transducer surface. Performance optimization using geometric membrane shape configurations was the same in both piston CMUTs and classical CMUTs.


Posterior cingulate cross-hemispheric functional connectivity predicts the level of consciousness in traumatic brain injury.
Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.


Receptor activities for low-density lipoprotein and acetylated low-density lipoprotein in a mouse macrophage cell line (IC21) and in human monocyte-derived macrophages.
IC21 macrophages, a permanent culture of a line of cells derived from a single colony of mouse peritoneal macrophages transformed with simian virus 40, demonstrate most of the characteristics of lipoprotein metabolism that have been described for primary cultures of rodent or canine peritoneal macrophages. IC21 macrophages have low but demonstrable low-density lipoprotein (LDL) receptor activity. They actively degrade acetylated LDL (AcLDL), which has a negative charge and is not recognized by the LDL receptor. Incubation of IC21 macrophages with human lipoprotein-depleted serum leads to a marked increase in cholesterol synthesis, as measured by incorporation of labeled acetate into sterols. Sterol synthesis is inhibited by further incubation with AcLDL; incubation with LDL also decreases cholesterol synthesis with an accumulation of radioactivity from acetate in sterol intermediates, which indicates that some uptake of LDL occurs. Incubation with AcLDL but not LDL leads to a marked stimulation of cholesterol esterification, as measured by labeled oleic acid incorporation into cholesteryl esters, and a concomitant increase in cellular cholesteryl ester content. IC21 macrophages as compared with human monocyte-derived macrophages are shown to have marked difference in their abilities to degrade native LDL and AcLDL. Human monocyte-derived macrophages degrade LDL at low concentrations at a rate sevenfold greater than do IC21 macrophages. The rate of cholesteryl ester synthesis after LDL receptor induction and incubation with LDL increases linearly with LDL concentration in HMD macrophages, but no increase was found in similarly incubated IC21 macrophages. IC21 macrophages degrade AcLDL at a rate two- to fourfold greater than do human monocyte-derived macrophages.


Noncovalent Hydrogen Bonds Tune the Mechanical Properties of Phosphoester Polyethylene Mimics.
Polyethylene mimics of semicrystalline polyphosphoesters (PPEs) with an adjustable amount of noncovalent cross-links were synthesized. Acyclic diene metathesis copolymerization of a phosphoric acid triester (M1) with a novel phosphoric acid diester monomer (M2) was achieved. PPEs with different co-monomer ratios and 0, 20, 40, and 100% of phosphodiester content were synthesized. The phosphodiester groups result in supramolecular interactions between the polymer chains, with the P-OH functionality as an H-bond donor and the P=O group as an H-bond acceptor. A library of unsaturated and saturated PPEs was prepared and analyzed in detail by NMR spectroscopy, size exclusion chromatography, differential scanning calorimetry, thermogravimetry, rheology, and stress-strain measurements. The introduction of the supramolecular cross-links into the aliphatic and hydrophobic PPEs showed a significant impact on the material properties: increased glass-transition and melting temperatures were observed and an increase in the storage modulus of the polymers was achieved. This specific combination of a flexible aliphatic backbone and a supramolecular H-bonding interaction between the chains was maximized in the homopolymer of the phosphodiester monomer, which featured additional properties, such as shape-memory properties, and polymer samples could be healed after cutting. The P-OH groups also showed a strong adhesion toward metal surfaces, which was used together with the shape-memory function in a model device that responds to a temperature stimulus with shape change. This systematic variation of phosphodiesters/phosphotriesters in polyethylene mimics further underlines the versatility of the phosphorus chemistry to build up complex macromolecular architectures.


Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12–5-16L2 complex.
A large protein complex consisting of Atg5, Atg12 and Atg16L1 has recently been shown to be essential for the elongation of isolation membranes (also called phagophores) during mammalian autophagy. However, the precise function and regulation of the Atg12–5-16L1 complex has largely remained unknown. In this study we identified a novel isoform of mammalian Atg16L, termed Atg16L2, that consists of the same domain structures as Atg16L1. Biochemical analysis revealed that Atg16L2 interacts with Atg5 and self-oligomerizes to form an ~800-kDa complex, the same as Atg16L1 does. A subcellular distribution analysis indicated that, despite forming the Atg12–5-16L2 complex, Atg16L2 is not recruited to phagophores and is mostly present in the cytosol. The results also showed that Atg16L2 is unable to compensate for the function of Atg16L1 in autophagosome formation, and knockdown of endogenous Atg16L2 did not affect autophagosome formation, indicating that Atg16L2 does not possess the ability to mediate canonical autophagy. Moreover, a chimeric analysis between Atg16L1 and Atg16L2 revealed that their difference in function in regard to autophagy is entirely attributable to the difference between their middle regions that contain a coiled-coil domain. Based on the above findings, we propose that formation of the Atg12–5-16L complex is necessary but insufficient to mediate mammalian autophagy and that an additional function of the middle region (especially around amino acid residues 229–242) of Atg16L1 (e.g., interaction with an unidentified binding partner on phagophores) is required for autophagosome formation.


Quantitative and Qualitative Perturbations of CD8+ MAITs in Healthy Mycobacterium tuberculosis-Infected Individuals.
CD8 T cells are considered important contributors to the immune response against Mycobacterium tuberculosis, yet limited information is currently known regarding their specific immune signature and phenotype. In this study, we applied a cell population transcriptomics strategy to define immune signatures of human latent tuberculosis infection (LTBI) in memory CD8 T cells. We found a 41-gene signature that discriminates between memory CD8 T cells from healthy LTBI subjects and uninfected controls. The gene signature was dominated by genes associated with mucosal-associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell-specific signature between the two cohorts. We, therefore, investigated MAITs in more detail based on Vα7.2 and CD161 expression and staining with an MHC-related protein 1 (MR1) tetramer. This revealed two distinct populations of CD8+Vα7.2+CD161+ MAITs: MR1 tetramer+ and MR1 tetramer-, which both had distinct gene expression compared with memory CD8 T cells. Transcriptomic analysis of LTBI versus noninfected individuals did not reveal significant differences for MR1 tetramer+ MAITs. However, gene expression of MR1 tetramer- MAITs showed large interindividual diversity and a tuberculosis-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer- cells as compared with MR1 tetramer+ Thus, circulating memory CD8 T cells in subjects with latent tuberculosis have a reduced number of conventional MR1 tetramer+ MAITs as well as a difference in phenotype in the rare population of MR1 tetramer- MAITs compared with uninfected controls.


Long-Term Outcomes of Operatively Treated Medial Epicondyle Fractures in Pediatric and Adolescent Patients.
Medial epicondyle fractures are among the most common pediatric elbow injuries. The management of these fractures continues to be debated. To better understand patient results with operative fixation, we reviewed the outcomes of operatively treated medial epicondyle fractures. A retrospective review was performed to identify all patients less than 18 years of age at the time of injury who were treated surgically for medial epicondyle fractures. Outcomes were assessed based on the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity and Pain Interference domains, Visual Analog Scale for pain, subjective range of motion, ulnar nerve function, and requirement for secondary surgery. We identified a cohort of 95 patients treated for a medial epicondyle fracture with open reduction and screw fixation. Of these, 39 patients with a mean age of 12.2 years (SD, 2.2 years; range, 7.6-16.0 years) at surgery were assessed for an average follow-up of 6.3 years (SD, 3.2 years; range, 2.2-13.9 years). Outcome measures and pain scores were excellent. The mean PROMIS Upper Extremity score was 56.9, the mean Pain Interference score was 38.5, and the mean Visual Analog Scale score was 0.4.Sixteen patients (41%) required secondary surgery for symptomatic hardware removal. Seven patients (18%) developed sensory complaints and 2 (5%) developed motor complaints consistent with ulnar nerve irritability. Three patients (8%) reported dissatisfaction with elbow range of motion. Patients who required secondary surgeries had higher (worse) PROMIS Pain Interference scores. At an average of 6.3 years after surgery, the clinical outcomes for medial epicondyle fracture were excellent. While operative treatment for medial epicondyle fractures in children leads to excellent clinical outcomes, patients and surgeons should be aware of high rates of hardware removal. Therapeutic IV.


The impact of obesity on outcomes after critical illness: a meta-analysis.
To assess whether obesity is associated with mortality or other adverse intensive care unit (ICU) and post-ICU outcomes. A meta-analysis of studies from PubMed and EMBASE databases. Twenty-two studies (n = 88,051 patients) were included. Pooled analysis demonstrated no difference in ICU mortality, but lower hospital mortality for obese and morbidly obese subjects (RR 0.76; 95% CI 0.59, 0.92; RR 0.83; 95% CI 0.66, 1.04, respectively) versus normal weight subjects. There was no association between obesity and duration of mechanical ventilation or ICU stay. Morbidly obese versus normal weight patients had longer hospitalizations. No study reported physical function, mental health, or quality of life outcomes after discharge. Obesity is not associated with increased risk for ICU mortality, but may be associated with lower hospital mortality. There is a critical lack of research on how obesity may affect complications of critical illness and patient long-term outcomes.


[Social disparities in morbidity and mortality: what are the causes?].
In Germany, as in many other western industrialized nations, a paradoxical trend can be observed: On the one hand, life expectancy continues to rise and both prevalence and incidence rates decrease for many groups of diagnoses. On the other hand, social disparities in morbidity and mortality are becoming more pronounced. This review's aim is to introduce a teaching framework concerning initial conditions and related factors of this "social gradient" on the basis of a critical synopsis of the current state of the relevant research and discussions, taking into account aspects of material inequality as well as social differences in the distribution of working and living conditions. In addition, the role of cultural capital and the relationship between social background and lifestyle will be described in detail. Finally, psychosocial and biological determining factors as well as potential selective processes are also considered in our model. The growing gap of social inequalities in health and life expectancy is a potential source of social conflicts. The "teaching framework model of the social gradient of morbidity and mortality" that is presented in this article helps to minimize explanatory deficits and will present clinicians with new ideas about the multifactorial origin of global and specific morbidity as well as important new perspectives for future preventative policies.


Treatment of Ewing's sarcoma using an antisense oligodeoxynucleotide to regulate the cell cycle.
Ewing's sarcoma (ES) is one of the most malignant tumors of bone and soft tissue in children and young adults. ES belongs to a group of small round cell tumors (SRCTs) that also includes neuroblastoma, rhabdomyosarcoma, and malignant lymphoma. However, ES exhibits several specific chimeric genes (EWS-FLI1, EWS-ERG, EWS-ETV1, EWS-E1AF, and EWS-FEV) caused by chromosomal translocations that are not shared by other SRCTs. These chimeric genes regulate the expression of various other genes; that is, they activate inhibitors of DNA binding 2 (Id2) gene expression or they suppress transforming growth factor beta II (TbetaRII) receptor gene expression. The regulation of these chimeric genes may affect critical cell signal transductions, such as signals involved in cell cycle and apoptosis in ES tumor cells. Using an antisense oligodeoxynucleotide against a sequence containing the ATG initiation codon of the EWS-FLI1 chimeric gene that specifically reacts with the EWS-FLI1 and EWS-ERG chimeric genes, we were able to regulate the cell cycle through the down-regulation of Id2. Here, we report that treatment with an antisense oligodeoxynucleotide against this chimeric gene was very useful for inducing the regression of ES tumor growth; thus, this chimeric gene may be an important target for the treatment of ES patients.


Facilitators and Hindrances of Implementing Colorectal Cancer Screening Intervention Among Vietnamese Americans.
Little is published about the factors that facilitate and hinder the intervention implementation process. The aim of this study was to examine factors that facilitated and hindered the implementation of a culturally appropriate colorectal cancer screening intervention targeting Vietnamese Americans in a Federally Qualified Health Center located in the Puget Sound area of Washington. Three focus group discussions (2 during the implementation phase and 1 during the maintenance phase) with the medical assistants (N = 13) who were the intervention implementation agents were conducted at the Federally Qualified Health Center. Three research team members independently analyzed the data using content analysis and then compared for agreement. We reread and recoded the transcripts until consensus was reached. The themes were clustered by similar codes and categorized into 4 groups, each including facilitators and hindrances of implementation: identification of implementation agents, implementation environment, intervention recipients, and the colorectal cancer screening intervention. Facilitators included medical assistants' high motivation with a positive attitude toward the intervention, team approach, and simplicity of the intervention, whereas hindrances included lack of time, forgetfulness, staff turnover, and language barriers. The findings emphasized the importance of supporting implementation agents to ensure effective intervention program implementation. Oncology nurses need to particularly take into consideration the evidence-based findings when planning any intervention programs.


Non-monolithic fabrication of thin-film microelectrode arrays on PMUT transducers as a bimodal neuroscientific investigation tool.
Ultrasound (US)-based neuromodulation has recently emerged as a spatially selective yet non-invasive alternative to conventional electrically-based neural interfaces. However, the fundamental mechanisms of US neuromodulation are not yet clarified. Thus, there is a need for in-vitro bimodal investigation tools that allow us to compare the effect of US versus electrically-induced neural activity in the vicinity of the transducing element. To this end, we propose a MicroElectrode-MicroTransducer Array (MEMTA), where a dense array of electrodes is co-fabricated on top of a similarly dense array of US transducers.In this paper, we test the proof of concept for such co-fabrication using a non-monolithic approach, where, at its most challenging scenario, desired topologies require electrodes to be formed directly on top of fragile piezoelectric micromachined ultrasound transducer (PMUTs) membranes. On top of the PMUTs, a thin-film microelectrode array was developed utilizing microfabrication processes, including metal sputtering, lithography, etching and soft encapsulation. The samples were analysed through focused ion beam-scanning electron microscopy (FIB-SEM), and the results have shown that damage to the membranes does not occur during any of the process steps. This paper proves that the non-monolithic development of a miniaturised bimodal neuroscientific investigation tool can be achieved, thus, opening up a series of possibilities for further understanding and investigation of the nervous system.


Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands.
Progesterone receptor (PR) is expressed from a single gene as two isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed in equimolar ratios, but isoform ratio is altered during malignant progression, usually leading to high PRA:PRB ratios. We took advantage of a transgenic mouse model where PRA isoform is predominant (PRA transgenics) and identified the key transcriptional events and associated pathways underlying the preneoplastic phenotype in mammary glands of PRA transgenics as compared with normal wild-type littermates. The transcriptomic profiles of PRA transgenics and wild-type mammary glands were generated using microarray technology. We identified differentially expressed genes and analyzed clustering, gene ontology (GO), gene set enrichment analysis (GSEA), and pathway profiles. We also performed comparisons with publicly available gene expression data sets of human breast cancer. We identified a large number of differentially expressed genes which were mainly associated with metabolic pathways for the PRA transgenics phenotype while inflammation- related pathways were negatively correlated. Further, we determined a significant overlap of the pathways characterizing PRA transgenics and those in breast cancer subtypes Luminal A and Luminal B and identified novel putative biomarkers, such as PDHB and LAMB3. The transcriptional targets identified in this study should facilitate the formulation or refinement of useful molecular descriptors for diagnosis, prognosis, and therapy of breast cancer.


Profiling of the genetic features of patients with breast, ovarian, colorectal and extracolonic cancers: Association to CHEK2 and PALB2 germline mutations.
Cancer predisposition goes beyond BRCA and DNA Mismatch Repair (MMR) genes since multi-gene panel testing has become the routine diagnostic tool for hereditary cancer suspicion (HCS) cases. CHEK2 and PALB2 are some of the foremost-mutated non-BRCA/MMR actionable genes in families with a significant familial aggregation. Therefore, the purpose of this work is to unravel which tumours other than breast, ovary or colorectal display the patients. We have analysed 528 probands that meet the inclusion criteria for Hereditary Breast and Ovarian Cancer and Lynch Syndrome established by our Hereditary Cancer Regional Program with a customized 35 genes-panel by using Ion Torrent™ Technology. We have identified pathogenic variants (PVs) in 61 families (1.55%), of which more than half (31 probands) harboured PVs in CHEK2 and PALB2 genes. Ours results reveal that not only were PVs CHEK2 and PALB2 carriers more likely to have family history of cancer not limited to breast, ovarian or colorectal cancers, but also they are prone to other extracolonic cancers, noteworthy endometrial and gastric cancers. Multigene panel testing improves the chance of finding PVs in actionable genes in families with HCS. In addition, the coexistence of variants should be recorded to implement a polygenic risk algorithm that might explain the missing heritability in the aforementioned families.


In vitro methylation of bovine papillomavirus alters its ability to transform mouse cells.
Bovine papillomavirus (BPV) was methylated in vitro at either the 29 HpaII sites, the 27 HhaI sites, or both. Methylation of the HpaII sites reduced transformation by the virus two- to sixfold, while methylation at HhaI sites increased transformation two- to fourfold. DNA methylated at both HpaII and HhaI sites did not differ detectably from unmethylated DNA in its efficiency of transformation. These results indicate that specific methylation sites, rather than the absolute level of methylated cytosine residues, are important in determining the effects on transformation and that the negative effects of methylation at some sites can be compensated for by methylation at other sites. BPV molecules in cells transformed by methylated BPV DNA contained little or no methylation, indicating that the pattern of methylation was not faithfully retained in these extrachromosomally replicating molecules. Methylation at the HpaII sites (but not the HhaI sites) in the cloned BPV plasmid or in pBR322 also inhibited transformation of the plasmids into Escherichia coli HB101 cells.


Mutations in the bimC box of Cut7 indicate divergence of regulation within the bimC family of kinesin related proteins.
Members of the bimC family of kinesin related proteins (KRPs) play vital roles in the formation and function of the mitotic spindle. Although they share little amino acid homology outside the highly conserved microtubule motor domain, several family members do contain a 'bimC box', a sequence motif around a p34(cdc2) consensus phosphorylation site in their carboxy-terminal 'tail' region. One family member, Eg5, requires phosphorylation at this site for association with the mitotic spindle. We show that mutations in the Schizosaccharomyces pombe cut7+ gene that change the bimC box p34(cdc2) consensus phosphorylation site at position 1,011 and a neighbouring MAP kinase consensus phosphorylation site at position 1,020 to non-phosphorylatable residues did not affect the ability of S. pombe cut7 genes to complement temperature sensitive cut7 mutants. Phosphorylation site mutants expressed as fusions to green fluorescent protein associated with the mitotic spindle with a localisation indistinguishable from similarly expressed wild-type Cut7. Cells in which cut7.T1011A replaced the genomic copy of cut7+ were viable and formed normal spindles. Deletion of the entire carboxy-terminal tail region did not affect the ability of Cut7 to associate with the mitotic spindle but did inhibit normal spindle formation. Thus, unlike Eg5, neither the p34(cdc2) consensus phosphorylation site in the bimC box nor the entire tail region of Cut7 are required for association with the mitotic spindle.


Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.
The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM. These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.


Craniomandibular disorders in headache patients.
Fifty patients with recurrent headache who had been referred to a neurologist were randomly invited for an examination of their stomatognathic system. The prevalence and distribution of the findings in many ways resemble the clinical findings in CMD patients. In 66% of the patients, a myogenous or arthrogenous origin of CMD pain could be detected. Headache occurred more bilaterally, but unilateral findings were more common at the functional examination. The results did not show any statistical differences between the sexes.


Insights into peroxymonosulfate activation for carbofuran degradation under visible LED via a double-component photocatalyst of Fe (III) impregnated N-doped TiO2.
A hybrid process was proposed for carbofuran (CBF) degradation, a carbamate pesticide with a special refractory property, through peroxymonosulfate (PMS) activation under visible LED (Vis LED) by FeIII impregnated N-doped TiO2 photocatalyst (FeNT). An in-depth investigation was conducted to examine the synergistic effect of the FeNT/PMS/Vis LED process under various reaction conditions. An increase in the rate constant was observed with the increment of pH from 2.4 to 7.4, implying the feasibility of the process at neutral pH. A further increase in pH from 8.9 to 11 showed a sudden drop in the rate constant (if the role of base activation is ignored). The efficiency of CBF degradation is still more than 70% after adding NO3-, SO42-, HCO3-, and Cl-. Interestingly, the efficiency was not influenced even after the further increment of nitrate concentration. Furthermore, the high chloride concentrations caused an enhanced efficiency due to the generation of reactive halogens through two-electron transfer. Sixteen major intermediates were recognized and eight of them were never reported in the previous studies. Surprisingly, a new degradation pathway was noted in this study via H-abstractions and cyclization mechanisms. The FeNT/PMS/Vis LED process exhibited a dual functionality in terms of mineralization efficiency and about 90% TOC reduction can be achieved. Therefore, these findings provide new insights into the mechanism of PMS activation under Vis LED after coupling non-metal doped TiO2 photocatalyst with a metal component, and its implications for degradation of refractory and non-biodegradable pollutants in wastewater.


Intravenous metronidazole or clindamycin with tobramycin for therapy of pelvic infections.
Anaerobic bacteria are important pathogens in obstetric and gynecologic infections. As metronidazole has excellent in vitro activity against almost all clinically significant anaerobes, the newly available parenteral form of the drug was evaluated in a comparative study with clindamycin. Forty-seven patients with postpartum endomyometritis with or without wound infection, acute or chronic salpingo-oophoritis, tuboovarian abscess, postoperative pelvic cellulitis or wound infection, or other soft-tissue infection were included in the study. Initially 6 patients were treated with metronidazole, usually combined with tobramycin, in an open study. Subsequently, 41 patients were treated on a randomized schedule of either metronidazole or clindamycin, each combined with tobramycin. Anaerobic bacteria were isolated from 86% (37 of 43) of the patients who had positive cultures from sites cultured for aerobes and anaerobes. Anaerobic gram-negative rods and gram-positive cocci were the predominant isolates from infected tissues. Of the patients who received metronidazole, 96% (25 of 26) were considered clinically cured; the remaining patient initially responded but continued to have slight temperature elevations. There were no adverse reactions to this drug. Of the patients who received clindamycin, 100% were considered clinically cured. The excellent therapeutic response to intravenous metronidazole and the predominance of pathogenic anaerobes observed in these infections support its use in the treatment of infections of the female genital tract.


Microscopic theory of irreversible processes.
The microscopic theory of irreversible processes that we developed is summarized and illustrated, using as a simple example the Friedrichs model. Our approach combines the Poincaré's point of view (dynamical interpretation of irreversibility) with the Gibbs-Einstein ensemble point of view. It essentially consists in a nonunitary transformation theory based on the symmetry properties of the Liouville equation and dealing with continuous spectrum. The second law acquires a microscopic content in terms of a Liapounov function which is a quadratic functional of the density operator. In our new representation of dynamics, which is defined for a restricted set of observables and states, this functional takes a universal form. We obtain, in this way, a semi-group description, the generator of which contains a part directly related to the microscopic entropy production. The Friedrichs model gives us a simple field theoretical example for which the entropy production can be evaluated. The thermodynamical meaning of life-times is explicitly displayed. The transition from pure states to mixtures, as well as the occurrence of long tails in thermodynamic systems, are also briefly discussed.


Dataset on economic analysis of mass production of algae in LED-based photobioreactors.
The data presented in this article are related to the research article entitled "Sugar-stimulated CO2 sequestration by the green microalga Chlorella vulgaris" (Fu et al., 2019) [1]. The data describe a rational design and scale-up of LED-based photobioreactors for producing value-added algal biomass while removing waste CO2 from flu gases from power plants. The dataset were created from growth rate experiments for biomass production including direct biomass productivity data, PBR size and setup parameters, medium composition as well as indirect energy cost and overhead in Iceland. A complete economic analysis is formed through a cost breakdown as well as PBR scalability predictions.


Inter-study repeatability of circumferential strain and diastolic strain rate by CMR tagging, feature tracking and tissue tracking in ST-segment elevation myocardial infarction.
Strain assessment allows accurate evaluation of myocardial function and mechanics in ST-segment elevation myocardial infarction (STEMI). Strain using cardiovascular magnetic resonance (CMR) has traditionally been assessed with tagging but limitations of this technique have led to more widespread use of alternative methods, which may be more robust. We compared the inter-study repeatability of circumferential global peak-systolic strain (Ecc) and peak-early diastolic strain rate (PEDSR) derived by tagging with values obtained using novel cine-based software: Feature Tracking (FT) (TomTec, Germany) and Tissue Tracking (TT) (Circle cvi42, Canada) in patients following STEMI. Twenty male patients (mean age 56 ± 10 years, mean infarct size 13.7 ± 7.1% of left ventricular mass) were randomised to undergo CMR 1-5 days post-STEMI at 1.5 T or 3.0 T, repeated after ten minutes at the same field strength. Ecc and PEDSR were assessed using tagging, FT and TT. Inter-study repeatability was evaluated using Bland-Altman analyses, coefficients of variation (CoV) and intra-class correlation coefficient (ICC). Ecc (%) was significantly lower with tagging than with FT or TT at 1.5 T (- 9.5 ± 3.3 vs. - 17.5 ± 3.8 vs. -15.5 ± 5.2, respectively, p < 0.001) and 3.0 T (- 13.1 ± 1.8 vs. - 19.4 ± 2.9 vs. - 17.3 ± 2.1, respectively, p = 0.001). This was similar for PEDSR (.s-1): 1.5 T (0.6 ± 0.2 vs. 1.5 ± 0.4 vs. 1.0 ± 0.4, for tagging, FT and TT respectively, p < 0.001) and 3.0 T (0.6 ± 0.2 vs. 1.5 ± 0.3 vs. 0.9 ± 0.3, respectively, p < 0.001). Inter-study repeatability for Ecc at 1.5 T was good for tagging and excellent for FT and TT: CoV 16.7%, 6.38%, and 8.65%, respectively. Repeatability for Ecc at 3.0 T was good for all three techniques: CoV 14.4%, 11.2%, and 13.0%, respectively. However, repeatability of PEDSR was generally lower than that for Ecc at 1.5 T (CoV 15.1%, 13.1%, and 34.0% for tagging, FT and TT, respectively) and 3.0 T (CoV 23.0%, 18.6%, and 26.2%, respectively). Following STEMI, Ecc and PEDSR are higher when measured with FT and TT than with tagging. Inter-study repeatability of Ecc is good for tagging, excellent for FT and TT at 1.5 T, and good for all three methods at 3.0 T. The repeatability of PEDSR is good to moderate at 1.5 T and moderate at 3.0 T. Cine-based methods to assess Ecc following STEMI may be preferable to tagging.


Cognitive insight in psychosis: the relationship between self-certainty and self-reflection dimensions and neuropsychological measures.
Cognitive insight in schizophrenia encompasses the evaluation and reinterpretation of distorted beliefs and appraisals. We investigated the neuropsychological basis of cognitive insight in psychosis. It was predicted that, like clinical insight, cognitive insight would be associated with a wide range of neuropsychological functions, but would be most strongly associated with measures of executive function. Sixty-five outpatients with schizophrenia or schizoaffective disorder were assessed on tests of intelligence quotient (IQ), executive function, verbal fluency, attention and memory, and completed the Beck Cognitive Insight Scale, which includes two subscales, self-certainty and self-reflection. Higher self-certainty scores reflect greater certainty about being right and more resistant to correction (poor insight), while higher self-reflection scores indicate the expression of introspection and the willingness to acknowledge fallibility (good insight). The self-certainty dimension of poor cognitive insight was significantly associated with lower scores on the Behavioural Assessment of Dysexecutive Syndrome; this relationship was not mediated by IQ. There were no relationships between self-reflection and any neuropsychological measures. We conclude that greater self-certainty (poor cognitive insight) is modestly associated with poorer executive function in psychotic individuals; self-reflection has no association with executive function. The self-certainty and self-reflection dimensions of cognitive insight have differential correlates, and probably different mechanisms, in psychosis.


Surgery as a Principle and Technical Consideration for Primary Tumor Resection of Small Bowel Neuroendocrine Tumors.
Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.


Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods.
Serotonin (5-HT) is a monoamine neurotransmitter in the peripheral, enteric, and central nervous systems (CNS). Within the CNS, serotonin is principally involved in mood regulation and reward-seeking behaviors. It is a critical regulator in CNS pathologies such as major depressive disorder, addiction, and schizophrenia. Consequently, in vivo serotonin measurements within the CNS have emerged as one of many promising approaches to investigating the pathogenesis, progression, and treatment of these and other neuropsychiatric conditions. These techniques vary in methods, ranging from analyte sampling with microdialysis to voltammetry. Provided this diversity in approach, inherent differences between techniques are inevitable. These include biosensor size, temporal/spatial resolution, and absolute value measurement capabilities, all of which must be considered to fit the prospective researcher's needs. In this review, we summarize currently available methods for the measurement of serotonin, including novel voltammetric absolute value measurement techniques. We also detail serotonin's role in various neuropsychiatric conditions, highlighting the role of phasic and tonic serotonergic neuronal firing within each where relevant. Lastly, we briefly review the present clinical application of these techniques and discuss the potential of a closed-loop monitoring and neuromodulation system utilizing deep brain stimulation (DBS).


The complete mitochondrial DNA sequence of the horseshoe crab Limulus polyphemus.
We determined the complete 14,985-nt sequence of the mitochondrial DNA of the horseshoe crab Limulus polyphemus (Arthropoda: Xiphosura). This mtDNA encodes the 13 protein, 2 rRNA, and 22 tRNA genes typical for metazoans. The arrangement of these genes and about half of the sequence was reported previously; however, the sequence contained a large number of errors, which are corrected here. The two strands of Limulus mtDNA have significantly different nucleotide compositions. The strand encoding most mitochondrial proteins has 1. 25 times as many A's as T's and 2.33 times as many C's as G's. This nucleotide bias correlates with the biases in amino acid content and synonymous codon usage in proteins encoded by different strands and with the number of non-Watson-Crick base pairs in the stem regions of encoded tRNAs. The sizes of most mitochondrial protein genes in Limulus are either identical to or slightly smaller than those of their Drosophila counterparts. The usage of the initiation and termination codons in these genes seems to follow patterns that are conserved among most arthropod and some other metazoan mitochondrial genomes. The noncoding region of Limulus mtDNA contains a potential stem-loop structure, and we found a similar structure in the noncoding region of the published mtDNA of the prostriate tick Ixodes hexagonus. A simulation study was designed to evaluate the significance of these secondary structures; it revealed that they are statistically significant. No significant, comparable structure can be identified for the metastriate ticks Rhipicephalus sanguineus and Boophilus microplus. The latter two animals also share a mitochondrial gene rearrangement and an unusual structure of mt-tRNA(C) that is exactly the same association of changes as previously reported for a group of lizards. This suggests that the changes observed are not independent and that the stem-loop structure found in the noncoding regions of Limulus and Ixodes mtDNA may play the same role as that between trnN and trnC in vertebrates, i.e., the role of lagging strand origin of replication.


Psychiatric nurses' attitudes toward consumer and carer participation in care: part 2--barriers to participation.
Australian government policy has effectively mandated consumer and carer participation. However, the limited relevant literature suggests there are significant barriers to implementing participation in mental health services. Nurses have been identified as a professional group with an important role in creating the culture changes necessary for successful implementation, yet their views about consumer and carer participation have not been extensively explored. This article presents Part 2 of the findings of a qualitative study using focus group interviews with 30 nurses to explore opinions on the topic of consumer and carer participation. Data were analyzed using a content analysis approach, assisted by the software package NVivo. The themes explicated were systemic barriers and education, an essential ingredient. These findings emphasize the barriers and provide some sense of how educational techniques might assist with making some constructive inroads.


Dysregulated intracellular signaling impairs CTGF-stimulated responses in human mesangial cells exposed to high extracellular glucose.
High ambient glucose activates intracellular signaling pathways to induce the expression of extracellular matrix and cytokines such as connective tissue growth factor (CTGF). Cell responses to CTGF in already glucose-stressed cells may act to transform the mesangial cell phenotype leading to the development of glomerulosclerosis. We analyzed cell signaling downstream of CTGF in high glucose-stressed mesangial cells to model signaling in the diabetic milieu. The addition of CTGF to primary human mesangial cells activates cell migration which is associated with a PKC-zeta-GSK3beta signaling axis. In high ambient glucose basal PKC-zeta and GSK3beta phosphorylation levels are selectively increased and CTGF-stimulated PKC-zeta and GSK3beta phosphorylation was impaired. These effects were not induced by osmotic changes. CTGF-driven profibrotic cell signaling as determined by p42/44 MAPK and Akt phosphorylation was unaffected by high glucose. Nonresponsiveness of the PKC-zeta-GSK3beta signaling axis suppressed effective remodeling of the microtubule network necessary to support cell migration. However, interestingly the cells remain plastic: modulation of glucose-induced PKC-beta activity in human mesangial cells reversed some of the pathological effects of glucose damage in these cells. We show that inhibition of PKC-beta with LY379196 and PKC-beta siRNA reduced basal PKC-zeta and GSK3beta phosphorylation in human mesangial cells exposed to high glucose. CTGF stimulation under these conditions again resulted in PKC-zeta phosphorylation and human mesangial cell migration. Regulation of PKC-zeta by PKC-beta in this instance may establish PKC-zeta as a target for constraining the progression of mesangial cell dysfunction in the pathogenesis of diabetic nephropathy.


Peroxisomal localization of inducible nitric oxide synthase in hepatocytes.
Shock states induce the expression of inducible nitric oxide synthase (iNOS) in both Kupffer cells and hepatocytes in the liver, but little is known about its subcellular localization in these cells. Studies were undertaken to characterize the subcellular location of iNOS in hepatocytes in response to sepsis. By immunofluorescence analysis, intraperitoneal challenge with bacterial lipopolysaccharide induced cytosolic iNOS in Kupffer cells but punctate labeling in hepatocytes. Cultured rat hepatocytes exposed to interferon gamma, interleukin 1, and tumor necrosis factor alpha showed iNOS protein expression within peroxisomes as early as 4 hours after stimulation, as determined by colabeling for catalase or PMP70. To a lesser extent, iNOS was also observed associated with the plasma membrane and in undefined intracellular aggregates. The nitric oxide synthase (NOS) antagonist L-N-imino-ornithine (L-NIO) did not affect the expression of iNOS within peroxisomes, cytoplasmic aggregates, or cytosol but increased plasma membrane localization of iNOS. Human iNOS transduced into iNOS-null mouse hepatocytes using an adenoviral vector also localized to peroxisomes. The expression of iNOS often resulted in the disappearance of detectable catalase in many hepatocytes. In conclusion, these studies establish the peroxisome as a site of iNOS localization in hepatocytes and show a relationship between iNOS up-regulation and decreased expression of catalase.


Culotte stenting vs. TAP stenting for treatment of de-novo coronary bifurcation lesions with the need for side-branch stenting: the Bifurcations Bad Krozingen (BBK) II angiographic trial.
In percutaneous coronary intervention for de-novo coronary bifurcation lesions, the optimal technique for provisional side-branch stenting is still a matter of debate. We tested whether in this setting culotte stenting reduces the incidence of restenosis as compared with T-and-protrusion (TAP) stenting. This trial included 300 patients with a coronary bifurcation lesion requiring a side-branch stent. Patients were randomly assigned to culotte stenting or TAP stenting using drug-eluting stents in a 1:1 fashion. Primary endpoint was maximal per cent diameter stenosis of the bifurcation lesion at 9-month angiographic follow-up. As clinical endpoints we assessed target lesion re-intervention (TLR) and target lesion failure (composite of cardiac death, target vessel myocardial infarction, and TLR).Angiographic follow-up was available in 91% of the patients. After culotte stenting, the maximum per cent diameter stenosis in the treated bifurcation lesion was 21 ± 20% as compared with 27 ± 25% after TAP stenting (P = 0.038). The respective corresponding binary restenosis rates were 6.5 and 17% (P = 0.006). The 1-year incidence of TLR was 6.0% after culotte stenting vs. 12.0% after T-stenting (P = 0.069). Target lesion failure occurred in 6.7% of the culotte group and in 12.0% of the TAP group (P = 0.11). Only one patient of the culotte group incurred a definite stent thrombosis during 1-year follow-up. Compared with the TAP stenting, culotte stenting was associated with a significantly lower incidence of angiographic restenosis.


Thermal properties of compacted pharmaceutical excipients.
Thermal properties of powders are critical material attributes that control temperature rise during tableting and roll compaction. In this study, various analytical methods were used to measure the thermal properties of widely used pharmaceutical excipients including microcrystalline cellulose (MCC) of three different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and mannitol. The effect of relative density on the measured thermal properties was investigated by compressing the powders into specimen of different relative densities. Differential thermal analysis (DTA) was employed to explore endothermic or exothermic events in the temperature range endured during typical pharmaceutical manufacturing processes, such as tabletting and roll compaction. Thermogravimetric analysis (TGA) was performed to analyse the water/solvent content, either in the form as solvates or as loosely bound molecules on the particle surface. Thermal conductivity analysis (TCA) was conducted to measure thermal conductivity and volumetric heat capacity. It is shown that, for the MCC powders, almost no changes in morphology or structural changes were observed during heating to temperatures up to 200°C. An increase in relative density or temperature leads to a high thermal conductivity and the volumetric heat capacity. Among all MCC powders considered, Avicel DG showed the highest increase in thermal conductivity and the volumetric heat capacity, but this heat capacity was not sensitive to the measurement temperature. For lactose and mannitol, some endothermic events occurred during heating. The thermal conductivity increased with the increase in temperature and relative density. A model was also developed to describe the variation of the thermal conductivity and the volumetric heat capacity with the relative density and the temperature. It was shown that the empirical model can well predict the dependency of the thermal conductivity and the volumetric heat capacity on the relative density and the temperature.


Quantitative risk assessment for Listeria monocytogenes in selected categories of deli meats: impact of lactate and diacetate on listeriosis cases and deaths.
Foodborne disease associated with consumption of ready-to-eat foods contaminated with Listeria monocytogenes represents a considerable pubic health concern. In a risk assessment published in 2003, the U.S. Food and Drug Administration and the U.S. Food Safety and Inspection Service estimated that about 90% of human listeriosis cases in the United States are caused by consumption of contaminated deli meats. In this risk assessment, all deli meats were grouped into one of 23 categories of ready-to-eat foods, and only the postretail growth of L. monocytogenes was considered. To provide an improved risk assessment for L. monocytogenes in deli meats, we developed a revised risk assessment that (i) models risk for three subcategories of deli meats (i.e., ham, turkey, and roast beef) and (ii) models L. monocytogenes contamination and growth from production to consumption while considering subcategory-specific growth kinetics parameters (i.e., lag phase and exponential growth rate). This model also was used to assess how reformulation of the chosen deli meat subcategories with L. monocytogenes growth inhibitors (i.e., lactate and diacetate) would impact the number of human listeriosis cases. Use of product-specific growth parameters demonstrated how certain deli meat categories differ in the relative risk of causing listeriosis; products that support more rapid growth and have reduced lag phases (e.g., turkey) represent a higher risk. Although reformulation of deli meats with growth inhibitors was estimated to reduce by about 2.5- to 7.8-fold the number of human listeriosis cases linked to a given deli meat subcategory and thus would reduce the overall risk of human listeriosis, even with reformulation deli meats would still cause a considerable number of human listeriosis cases. A combination of strategies is thus needed to provide continued reduction of these cases. Risk assessment models such as that described here will be critical for evaluation of different control approaches and to help define the combinations of control strategies that will have the greatest impact on public health.


Evaluating visual and auditory contributions to the cognitive restoration effect.
It has been suggested that certain real-world environments can have a restorative effect on an individual, as expressed in changes in cognitive performance and mood. Much of this research builds on Attention Restoration Theory (ART), which suggests that environments that have certain characteristics induce cognitive restoration via variations in attentional demands. Specifically, natural environments that require little top-down processing have a positive effect on cognitive performance, while city-like environments show no effect. We characterized the cognitive restoration effect further by examining (1) whether natural visual stimuli, such as blue spaces, were more likely to provide a restorative effect over urban visual stimuli, (2) if increasing immersion with environment-related sound produces a similar or superior effect, (3) if this effect extends to other cognitive tasks, such as the functional field of view (FFOV), and (4) if we could better understand this effect by providing controls beyond previous works. We had 202 participants complete a cognitive task battery, consisting of a reverse digit span task, the attention network task, and the FFOV task prior to and immediately after a restoration period. In the restoration period, participants were assigned to one of seven conditions in which they listened to natural or urban sounds, watched images of natural or urban environments, or a combination of both. Additionally, some participants were in a control group with exposure to neither picture nor sound. While we found some indication of practice effects, there were no differential effects of restoration observed in any of our cognitive tasks, regardless of condition. We did, however, find evidence that our nature images and sounds were more relaxing than their urban counterparts. Overall, our findings suggest that acute exposure to relaxing pictorial and auditory stimulus is insufficient to induce improvements in cognitive performance.


Amine-modified random primers to label probes for DNA microarrays.
DNA microarrays have been used to study the expression of thousands of genes at the same time in a variety of cells and tissues. The methods most commonly used to label probes for microarray studies require a minimum of 20 microg of total RNA or 2 microg of poly(A) RNA. This has made it difficult to study small and rare tissue samples. RNA amplification techniques and improved labeling methods have recently been described. These new procedures and reagents allow the use of less input RNA, but they are relatively time-consuming and expensive. Here we introduce a technique for preparing fluorescent probes that can be used to label as little as 1 microg of total RNA. The method is based on priming cDNA synthesis with random hexamer oligonucleotides, on the 5' ends of which are bases with free amino groups. These amine-modified primers are incorporated into the cDNA along with aminoallyl nucleotides, and fluorescent dyes are then chemically added to the free amines. The method is simple to execute, and amine-reactive dyes are considerably less expensive than dye-labeled bases or dendrimers.


[Carney complex: a case report and literature review].
Carney complex (CNC) is a familial multiple neoplasia syndrome associated with abnormal skin and mucosal pigmentation, primary pigmented nodular adrenocortical disease (PPNAD), cardiac and cutaneous myxomas, GH and PRL pituitary adenoma, testicular tumors, thyroid adenoma or carcinoma and ovarian cysts. CNC is inherited as an autosomal dominant trait and has some clinical similarities to McCune-Albright syndrome. Recently, genes related to stimulation of the cAMP signaling pathway have been considered candidates for causing CNC. We report a 17-yr-old man with PPNAD, lentigines on the face and severe osteoporosis. In this article we aim at describing the clinical aspects and molecular genetics of CNC and also summarizing diagnostic criteria for CNC and recommendations for follow-up.


Allerod--younger dryas lake temperatures from midge fossils in atlantic Canada.
Remains of freshwater midges are abundant in lake sediments, and their species distributions are closely related to the surface-water temperature of lakes; their distributions thus provide a powerful tool for paleoclimatology. The distribution of species in a core from Splan Pond in Atlantic Canada indicates that there were abrupt transitions in late-glacial temperatures between warm and cold states. The transitions are correlative with the well-known warm Allerød and cold Younger Dryas events in Europe. These data thus confirm the inference from palynological data that these events affected regions on both sides of the Atlantic.


Loss of basement membrane integrity in human gingival overgrowth.
Gingival overgrowth tissues have thickened connective tissue stroma, sometimes accompanied by the increased presence of collagen fibers, thickened epithelia, and elongated rete pegs. We have previously shown that expression of CCN2, also known as connective tissue growth factor (CTGF), correlates positively with the degree of gingival fibrosis, and that markers of epithelial to mesenchymal transition (EMT) are characteristic of all drug-induced forms of gingival overgrowth. Here we experimentally evaluate whether increased degradation of the basement membrane and apparent invasion of the underlying stroma by epithelial cells could be observed in human gingival overgrowth tissues. Tissues from 20 different individuals with human gingival overgrowth and 15 non-overgrowth samples were evaluated by histological analyses and by immunohistochemistry assays of basement membrane proteins. The results demonstrate that there are significantly higher numbers of basement membrane discontinuities in overgrowth tissues, sometimes containing epithelial-like cells. Disrupted basal membrane structure in gingival overgrowth tissues is accompanied by a discontinuous collagen type IV expression pattern and decreased laminin 5. These findings provide new additional support for the hypothesis that epithelial plasticity and EMT promote gingival overgrowth, resulting in compromised basal membrane structure and increased interactions between epithelial and connective tissue layers that contribute to fibrotic pathology.


How is the environment integrated into post-stroke rehabilitation? A qualitative study among community-dwelling persons with stroke who receive home rehabilitation in Sweden.
Studies have shown a need to consider environmental factors to best support the rehabilitation and recovery process after a stroke. In addition, despite intentions to increase individuals' participation in care and rehabilitation, patients and family members report weak participation. The aim of this study was to explore how the environment was integrated into rehabilitation at home from the perspective of patients after a stroke. We conducted as a qualitative study with 17 patients rehabilitated at home. Data on the participants' experiences of the rehabilitation process and their perceptions of how the environment was considered in the process were collected via interviews and analysed using qualitative content analysis. The main category that was constructed from the data was "Partial integration of person- environment dynamics in the rehabilitation", which was informed by three subcategories: (a) I recover in my home: Challenges and opportunities in the environment, (b) Following a generic approach to therapy: Limited integration of the environment, and (c) Informed more than involved. Our study showed that the environment was integrated in a limited manner. The participants were more informed about than involved in their planning of the rehabilitation. The results are important for informing the ongoing development of rehabilitation at home and person-centred care strategies.


Magnetic resonance microdynamic imaging reveals distinct tissue microenvironments.
Magnetic resonance imaging (MRI) provides a powerful set of tools with which to investigate biological tissues noninvasively and in vivo. Tissues are heterogeneous in nature; an imaging voxel contains an ensemble of different cells and extracellular matrix components. A long-standing challenge has been to infer the content of and interactions among these microscopic tissue components within a macroscopic imaging voxel. Spatially resolved multidimensional relaxation-diffusion correlation (REDCO) spectroscopy holds the potential to deliver such microdynamic information. However, to date, vast data requirements have mostly relegated these type of measurements to nuclear magnetic resonance applications and prevented them from being widely and successfully used in conjunction with imaging. By using a novel data acquisition and processing strategy in this study, spatially resolved REDCO could be performed in reasonable scanning times with excellent prospects for clinical applications. This new MR imaging framework-which we term "magnetic resonance microdynamic imaging (MRMI)"-permits the simultaneous noninvasive and model-free quantification of multiple subcellular, cellular, and interstitial tissue microenvironments within a voxel. MRMI is demonstrated with a fixed spinal cord specimen, enabling the quantification of microscopic tissue components with unprecedented specificity. Tissue components, such as axons, neuronal and glial soma, and myelin were identified on the basis of their multispectral signature within individual imaging voxels. These tissue elements could then be composed into images and be correlated with immunohistochemistry findings. MRMI provides novel image contrasts of tissue components and a new family of microdynamic biomarkers that could lead to new diagnostic imaging approaches to probe biological tissue alterations accompanied by pathological or developmental changes.


Two host clades, two bacterial arsenals: evolution through gene losses in facultative endosymbionts.
Bacterial endosymbiosis is an important evolutionary process in insects, which can harbor both obligate and facultative symbionts. The evolution of these symbionts is driven by evolutionary convergence, and they exhibit among the tiniest genomes in prokaryotes. The large host spectrum of facultative symbionts and the high diversity of strategies they use to infect new hosts probably impact the evolution of their genome and explain why they undergo less severe genomic erosion than obligate symbionts. Candidatus Hamiltonella defensa is suitable for the investigation of the genomic evolution of facultative symbionts because the bacteria are engaged in specific relationships in two clades of insects. In aphids, H. defensa is found in several species with an intermediate prevalence and confers protection against parasitoids. In whiteflies, H. defensa is almost fixed in some species of Bemisia tabaci, which suggests an important role of and a transition toward obligate symbiosis. In this study, comparisons of the genome of H. defensa present in two B. tabaci species (Middle East Asia Minor 1 and Mediterranean) and in the aphid Acyrthosiphon pisum revealed that they belong to two distinct clades and underwent specific gene losses. In aphids, it contains highly virulent factors that could allow protection and horizontal transfers. In whiteflies, the genome lost these factors and seems to have a limited ability to acquire genes. However it contains genes that could be involved in the production of essential nutrients, which is consistent with a primordial role for this symbiont. In conclusion, although both lineages of H. defensa have mutualistic interactions with their hosts, their genomes follow distinct evolutionary trajectories that reflect their phenotype and could have important consequences on their evolvability.


Deconvoluting BAC-gene relationships using a physical map.
Deconvolution of relationships between bacterial artificial chromosome (BAC) clones and genes is a crucial step in the selective sequencing of regions of interest in a genome. It often includes combinatorial pooling of unique probes obtained from the genes (unigenes), and screening of the BAC library using the pools in a hybridization experiment. Since several probes can hybridize to the same BAC, in order for the deconvolution to be achievable the pooling design has to be able to handle a large number of positives. As a consequence, smaller pools need to be designed, which in turn increases the number of hybridization experiments, possibly making the entire protocol unfeasible. We propose a new algorithm that is capable of producing high-accuracy deconvolution even in the presence of a weak pooling design, i.e. when pools are rather large. The algorithm compensates for the decrease of information in the hybridization data by taking advantage of a physical map of the BAC clones. We show that the right combination of combinatorial pooling and our algorithm not only dramatically reduces the number of pools required, but also successfully deconvolutes the BAC-gene relationships with almost perfect accuracy. Software is available on request from the first author.


Socio-cultural features and sex profile of the individuals with serious suicide attempts in southeastern Turkey: a one-year survey.
Our objective was to elucidate potential causes of higher rates of suicide attempts in females compared to males in southeastern Turkey through a 1-year survey. Gender-related differences observed in 96 subjects who attempted suicide by poisoning for the first time were as follows: in comparison to male, females were predominantly within the age interval of 15-24 years, experienced more stressful events in the previous week before suicide attempt, had lower education level, and had a lower rate of employment. One year after the suicide attempt, unfavorable attitude of family, lack of support, persisting unfavorable lifestyle comparable with that prior to the first attempt, and higher rates of domestic violence were more pronounced in females compared to males. These findings might be contributing factors to the higher suicide attempt rates observed in females compared to the males.


General considerations of sleep and sleep deprivation.
The state of affairs in the field of sleep deprivation has been discussed in this chapter. Special emphasis was placed on total sleep deprivation, a domain in which the most important work has been done since the dawning of this century, and especially during the 'golden years' between 1955 and 1975. After a discussion of the biorhythmical aspects, the general condition of sleep deprived subjects was pointed out. Psychological-psychiatric changes and impairment of performance were further topics of discussion, followed by sections on EEG, neurological, autonomic and metabolic changes. The relationship of SD to epileptic phenomena and endogenous depression has been considered. The characteristics of recovery sleep have also been presented. Most of the author's impressions are based on personal data, and especially on 2 subjects who underwent most elaborate testing. A discussion of partial sleep deprivation and selective sleep deprivation is also included.


[Hereditary areflexic dysstasia (Roussy-Lévy syndrome)].
Clinical and electroneurographic investigations of 22 cases of hereditary areflectory dysstasia (Roussy-Levy's syndrome). 20 cases of Charcot-Marie's neural amyotrophy and 8 cases of Friedreich's familial ataxia were carried out. In the patients with Roussy-Levy's syndrome, the speed of the impulse conduction along the peripheral nerves of the extremities, as well as the amplitudes of evoked potentials were lowered to the greatest extent: this was an evidence of nosological independence of the disease.


Mindfulness interventions in the workplace: A critique of the current state of the literature.
There is growing research interest regarding the significance of mindfulness in the workplace. Within this body of knowledge, research investigating the effects of mindfulness interventions on employee health and well-being has strong practical implications for organizations. A sound understanding of the current state of the workplace mindfulness intervention literature will help inform the suitability of these interventions within the workplace domain, and how to improve the conduct and communication of intervention-oriented research. Accordingly, in this article, we systematically review 40 published articles of mindfulness interventions in the workplace to identify ways in which these interventions could be improved, and how to overcome methodological concerns that threaten study validity. Studies selected for review were published peer-reviewed, primary empirical research studies written in English, with a focus on a workplace mindfulness intervention. We discuss a range of issues evident within this body of literature, including conceptualizations of mindfulness; the adaptation of protocols to work settings; internal validity in relation to random allocation and control conditions; the use of manipulation checks; attrition, adherence, acceptability, and maintenance of interventions; utilizing objective cognitive measures; examining organizational and well-being outcomes; and establishing boundary conditions. Overall, this review provides a resource to inform scholars to advance this line of inquiry and practitioners who are considering implementing a mindfulness intervention for employees. (PsycINFO Database Record


[Hemorrhage caused by cerebral arterial aneurysm].
The analysis of clinical pictures and pathomorphology of cerebral damage (intra-operative and autopsy material) was performed on 387 patients with first or second rupture of cerebral arterial aneurysms. Clinicopathological peculiarities of the aneurysmic intracranial hemorrhages were derived. Intracranial pathomorphological determinants of the severity of the patients' conditions at the acute stage were determined, including the intracerebral hematomas resulting in dislocation syndrome and paving the way to penetration of arterial blood spring into the ventricles on the second rupture of the aneurysm. The clinical course of the condition featured a stabilization period whose duration depended on both the type of hemorrhage and cerebral response. This period was regarded as optimal for reconsidering an option of surgical intervention.


[Occurrence and biological characteristics of parasitoid phorids (Diptera: Phoridae) of the leaf-cutting ant Atta laevigata (Smith) (Hymenoptera: Formicidae) in Porto Nacional, TO, Brazil].
The purpose of this study was to verify the occurrence of parasitism in Atta laevigata (Smith) by phorids in Porto Nacional, Tocantins, Brazil and to evaluate some biological characteristics of those flies. From October/2002 to September/2003, at 15-day intervals, 22 samplings were carried out (149.5 +/- 82.9 workers each) comprising 3,704 ants. In the laboratory, the ants were distributed in groups of five individuals per petri dish and maintained at temperature of 25 +/- 1 masculineC and 80 +/- 5% of RH. They were fed daily with a 50% honey solution until death. The total of 106 workers (2.8%), collected with or without load (plant fragment), were parasitized by phorids: 72 workers (68%) were parasitized by Apocephalus vicosae Disney, 28 individuals (26.4%) by Neodohrniphora erthali Brown, and six (5.6%) by Apocephalus attophilus Borgmeier. The higher parasitism rates by A. vicosae (3.9-5.4%) were observed during the dry season (June-August), while the parasitism by N. erthali was lower than 2.3% throughout the year. The bigger workers were parasitized by bigger parasitoid N. erthali or by parasitoid with larger number of larvae A. attophilus. The occurrence of three phorid species in Tocantins broadens the distribution of these flies in Brazil. The development of A. vicosae larva within the thorax of the host as well as the rupture between the ant pronotum and propleuron so that the emergence of the fly can take place are characteristics not yet described on parasitism of leaf-cutting ants by phorids.


Dissociation of Unit Activity and Gamma Oscillations during Vocalization in Primate Auditory Cortex.
Vocal production is a sensory-motor process in which auditory self-monitoring is used to ensure accurate communication. During vocal production, the auditory cortex of both humans and animals is suppressed, a phenomenon that plays an important role in self-monitoring and vocal motor control. However, the underlying neural mechanisms of this vocalization-induced suppression are unknown. γ-band oscillations (>25 Hz) have been implicated a variety of cortical functions and are thought to arise from activity of local inhibitory interneurons, but have not been studied during vocal production. We therefore examined γ-band activity in the auditory cortex of vocalizing marmoset monkeys, of either sex, and found that γ responses increased during vocal production. This increase in γ contrasts with simultaneously recorded suppression of single-unit and multiunit responses. Recorded vocal γ oscillations exhibited two separable components: a vocalization-specific nonsynchronized ("induced") response correlating with vocal suppression, and a synchronized ("evoked") response that was also present during passive sound playback. These results provide evidence for the role of cortical γ oscillations during inhibitory processing. Furthermore, the two distinct components of the γ response suggest possible mechanisms for vocalization-induced suppression, and may correspond to the sensory-motor integration of top-down and bottom-up inputs to the auditory cortex during vocal production.SIGNIFICANCE STATEMENT Vocal communication is important to both humans and animals. In order to ensure accurate information transmission, we must monitor our own vocal output. Surprisingly, spiking activity in the auditory cortex is suppressed during vocal production yet maintains sensitivity to the sound of our own voice ("feedback"). The mechanisms of this vocalization-induced suppression are unknown. Here we show that auditory cortical γ oscillations, which reflect interneuron activity, are actually increased during vocal production, the opposite response of that seen in spiking units. We discuss these results with proposed functions of γ activity during inhibitory sensory processing and coordination of different brain regions, suggesting a role in sensory-motor integration.


Positron emission tomography during transcranial magnetic stimulation does not require mu-metal shielding.
Recording brain activity using positron emission tomography (PET) during the stimulation of different parts of the brain by transcranial magnetic stimulation (TMS) permits the mapping of neural connections in the living human brain. However, controversy remains regarding the need for micro-metal shielding of the PET scanner during magnetic stimulation. The aim of this study was to test the effects of magnetic fields generated by TMS on PET data acquisition. With TMS-on and -off in the PET field of view, transmission scans with a (68)Ge/(68)Ga pin source and emission scans with an uniform phantom filled with water and (18)F were acquired. The frequency and intensity of stimulation were set at 3-5 Hz and 70-80% of the maximum output of the stimulator, respectively. The TMS coil was placed at several locations inside the PET gantry, and the main field direction of the TMS coil was varied between parallel and perpendicular orientation to the scanner's axis. Qualitative and quantitative evaluation of the sinograms of transmission PET scans and reconstructed emission images indicated no measurable differences between TMS-on and -off and post-TMS conditions for any position or orientation. The long distance between the TMS coil and the detector block in the PET scanner, as well as the rapid reduction of the magnetic field with distance (3% of maximum field at 10 cm, in air), could explain the lack of TMS interference. The brief duration (approximately 250 micros) of the TMS pulses relative to the total PET acquisition time would also explain the lack of TMS effects. The lack of TMS effects on the PET scanner, as well as PET imaging without any shielding, has been reported by other laboratories.


Reversing the relative 3MLCT-3MC order in Fe(ii) complexes using cyclometallating ligands: a computational study aiming at luminescent Fe(ii) complexes.
Following a computational approach, the use of strongly electron-donating cyclometallating ligands has allowed us to increase the (3)MC-(3)MLCT gap dramatically in Fe(ii) bis(tridentate) polypyridine complexes, and eventually to reverse the ordering between these states, yielding a (3)MLCT state that is clearly more stable than the (3)MC state. Simultaneously, the quintet excited states ((5)MC and (5)MLCT) are displaced away from the region (in terms of geometry and energy) where classical photophysics occur, allowing us to avoid magnetism. The situation is thus similar to that of classical ruthenium polypyridine complexes. This opens the way towards luminescent iron(ii) complexes, in particular Fe(ii)bis(6-phenyl-2,2'-bipyridine) Fe(NNC)(2).


Development and specificities of anti-interferon neutralizing antibodies in patients with chronic hepatitis C treated with pegylated interferon-α.
Only limited data are available on the development of neutralizing antibodies (NAB) in patients with chronic hepatitis C (CHC) treated with pegylated interferon-α (PEG-IFN-α). The aim of this study was to evaluate the immunogenicity of PEG-IFN-α when administered to CHC patients who had or had not previously received standard IFN-α therapy. In addition, the specificities of NAB, together with the ability of leucocyte (LE) -IFN-α to re-establish therapeutic responsiveness in NAB-positive patients, were evaluated. NAB were assessed using a quantitative, standardized, virus-induced cytopathic effect assay. The seroconversion rate to PEG-IFN-α was higher in patients who had received previous standard IFN-α treatment than in those treated exclusively with PEG-IFN-α. Also, NAB produced during PEG-IFN-α therapy were unable to neutralize LE-IFN-α entirely, even though they can neutralize several IFN-α subtypes. In addition, the results indicate that a change to LE-IFN-α therapy can be associated with restoration of clinical responses in NAB-positive patients who had become resistant after showing an initial response to PEG-IFN-α treatment. This study emphasizes the importance of evaluating NAB development in CHC patients who become resistant to PEG-IFN-α treatment, and suggests management alternatives for patients who develop NAB.


Association between Testicular Microlithiasis and Testicular Neoplasia: Large Multicenter Study in a Pediatric Population.
Purpose To retrospectively define the strength of association between testicular microlithiasis and testicular neoplasia in a large geographically diverse pediatric population. Materials and Methods Retrospective review of scrotal ultrasonographic (US) examination reports and pathology specimens obtained between January 2000 and May 2014 at six academic pediatric hospitals in North America was performed. Reported cases were reviewed to confirm microlithiasis. Radiology and pathology data bases were searched for pathology-proven testicular tumors (benign or malignant germ cell or stromal tumors). Association strength (risk) was expressed in terms of odds ratios (ORs) with and without adjustment for fixed study site effects based on logistic regression. Results A total of 37 863 individuals underwent scrotal US during the study period. Mean age was 11.1 years ± 4.7 [standard deviation] in boys with microlithiasis and 9.1 years ± 5.9 in boys without microlithiasis (P < .001). Microlithiasis was confirmed in 2.90% of patients (1097 of 37 863; range, 1.61%-5.25% across sites). It was unilateral in 21.97% (241 of 1097) of patients and bilateral in 78.0% (856 of 1097). Tumor was identified in 4.64% (51 of 1097) of boys with microlithiasis and 0.33% (122 of 36 766) of boys without (unadjusted OR, 14.65; 95% confidence interval [CI]: 10.29, 20.84; adjusted OR, 14.19). Malignant germ cell tumors were identified in 2.8% (31 of 1097) of boys with microlithiasis and 0.12% (45 of 36 766) of boys without microlithiasis (unadjusted OR, 17.26; 95% CI: 11.8, 25.25; adjusted OR, 22.37). Sex cord-stromal tumors were identified in 0.46% (five of 1097) of boys with microlithiasis and 0.079% (29 of 36 766) of boys without (unadjusted OR, 5.8; 95% CI: 2.1, 16; adjusted OR, 6.39). Conclusion There is a strong association between testicular microlithiasis and primary testicular neoplasia in this pediatric population. © RSNA, 2017.


Theory-based behavior change interventions: comments on Hobbis and Sutton.
Hobbis and Sutton (this issue) suggest that Cognitive Behavior Therapy (CBT) techniques can be used in interventions based on the Theory of Planned Behavior (TPB). Although this suggestion has merit, CBT is only one of many applicable methods for producing belief and behavior change. Moreover, CBT's primary purpose is to help people carry out intended behaviors, not to influence intentions, and that it is more useful in face-to-face than in community-level interventions. Contrary to Hobbis and Sutton's critique, TPB can accommodate core beliefs or fundamental assumptions, but the theory suggests that interventions targeted at such beliefs are less effective than interventions targeted at behavior specific beliefs.


Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.
BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.


Medial prefrontal theta bursts precede rapid motor responses during visual selective attention.
After visual target stimuli presented infrequently at a covertly attended location, quicker speeded button presses immediately followed a larger positive (P3f) ramp in averaged electroencephalographic (EEG) recordings from the forehead. We show this peak in the mean response time locked to the button press to be principally composed of triphasic, primarily low-theta band (4.5 Hz) complexes preceding but only partially phase-locked to the button press, with larger complexes preceding quicker motor responses. For 10 of 15 subjects, independent component analysis of the unaveraged 31-channel data identified a temporally independent medial frontal EEG process contributing to these phenomena. Low-resolution tomographic modeling localized related components of two 253-channel data sets to medial frontal polar cortex (BA32/10). The far-frontal low-theta complexes and concomitant mean P3f positivity may index cortical activity induced by paralimbic processes involved in disinhibiting impulsive motor responses to rewarding or goal-fulfilling stimuli or events.