How does CO capture process on microporous NaY zeolites? A FTIR and DFT combined study.
Reliable experimental IR and theoretical approaches, both investigating CO adsorption on NaY faujasites, are supporting that CO capture occurs through the completion of the vacant coordination of Na(+) cations located in the accessible S(II) sites. As a result, carbonyl adsorbed species are formed by the capture of one, two or three CO molecules and are experimentally discernable by their respective IR positions that are down-shifted by an average 11-12 cm(-1) value for each captured CO molecule. DFT analysis is proposed for comparison and reproduces well the observed experimental shift of the ν(CO) positions of the different polycarbonyls of interest. In addition, the effect of Si or Al composition surrounding the SII Na(+) cation is investigated and results suggest that polycarbonyls that are formed might be in connection with the acidic strength of the cationic sites. This combined study completes and improves the understanding of the complex issue of CO adsorption at 80 K widely used as a model to explain how physical adsorption takes place in NaY faujasites working as an efficient industrial adsorbent in gas separation or gas purification processes.


NeuroAIDS in Africa.
In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, and Zambia. Topics discussed included best practices for assessing neurocognitive disorders, patterns of central nervous system (CNS) involvement in the region, subtype-associated risk for HAND, pediatric HIV assessments and neurodevelopment, HIV-associated CNS opportunistic infections and immune reconstitution syndrome, the evolving changes in treatment implementation, and various opportunities and strategies for NeuroAIDS research and capacity building in the region.


Up-Regulation of hsa-miR-210 Promotes Venous Metastasis and Predicts Poor Prognosis in Hepatocellular Carcinoma.
Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in. Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package "limma," After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID. Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study. Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.


[High risk congenital diaphragmatic hernia. Factors predicting mortality].
A retrospective study of patients with high-risk congenital diaphragmatic hernia operated on in our hospital the last 15 years is made in order to establish some predictors involved in the final evolution of the patients. The best prognostic correlation has been demonstrated by preoperatory roentgenogram, Apgar-test and gasometric values 24 hours after surgical repair. A delayed surgical operation is also correlated with a better prognosis in accordance with the suitability of respiratory stabilization of the patient before the stress of surgery or because of a lesser respiratory insufficiency in patients operated on later.


A pilot study of regenerative therapy using controlled release of recombinant human fibroblast growth factor for patients with pre-collapse osteonecrosis of the femoral head.
We evaluated the safety and clinical outcomes of a single local administration of gelatin hydrogel impregnated with recombinant human fibroblast growth factor (rhFGF)-2 for the treatment of the precollapse stage of osteonecrosis of the femoral head (ONFH). Patients with ONFH (precollapse stage ≤2) received a single local administration of 800 μg of rhFGF-2-impregnated gelatin hydrogel and were followed up for one year. The surgery was performed using a minimally invasive technique involving a 1-cm skin incision, and walking was allowed from day one postoperatively. The primary outcomes included occurrence of adverse events and complications. The secondary outcomes included changes in the Harris hip scores, visual analog scale for pain scores, University of California, Los Angeles (UCLA) activity scores, and radiological images. We included ten patients, of which five experienced 14 adverse events, including one complication from spinal anesthesia. However, patients completely recovered from all adverse events. The mean clinical scores significantly improved by one year postoperatively compared with the pre-operative scores (before vs. after: visual analog score for pain, 21.2 vs. 5.3 mm; UCLA activity score, 5.5 vs. 6.6; Harris hip score, 81.0 vs. 96.9 points). There was only one case of femoral head collapse; however, this occurred in a hip with extensive necrosis. Stage progression and collapse did not occur in the other nine cases. Computed tomography confirmed bone regeneration in the femoral heads. Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse ONFH was feasible and safe.


Clinical spectrum and presentation of patients with absent contractility.
Primary absent contractility is an uncommon finding on high-resolution manometry (HRM). The goal of this study was to describe the clinical spectrum and presentation of patients with primary absent contractility. We queried a prospectively maintained esophageal testing registry to identify patients with absent contractility who presented between August 2016 and September 2018. Patients with poor quality studies and patients with insufficient clinical records as well as those with a history of previous foregut surgery or esophagram consistent with achalasia were excluded. A total of 2068 patients underwent HRM during the study period. Of these, 66 patients (3.2%) met the inclusion criteria and formed the study cohort; 52 patients in the cohort had an upper gastrointestinal contrast study, 50 had endoscopy, and 51 completed a foregut symptom questionnaire. Thirty-eight patients (57.6%) were women. The mean age was 56.6±13.86 years, and the mean body mass index was 26.37±5.7 kg/m2. Almost half of the patients (29/66, 43.9%) were undergoing lung transplant evaluation, and 22 patients (37.3%) had a history of autoimmune immune-mediated or myopathic diseases. On the symptom questionnaire, 42 of 51 patients (82.3%) reported heartburn, 24 of 51 (47.1%) reported dysphagia, and 23 of 51 patients (45.1%) reported both. On ambulatory pH monitoring, 23 of 37 patients (62.2%) had pathological esophageal acid exposure (acid exposure time >6%). Absent contractility on HRM is uncommon and is frequently associated with connective tissue, myopathic or autoimmune disorders. The usual clinical presentation is reflux, dysphagia or both.


Knockdown of alpha myosin heavy chain disrupts the cytoskeleton and leads to multiple defects during chick cardiogenesis.
Atrial septal defects are a common congenital heart defect in humans. Although mutations in different genes are now frequently being described, little is known about the processes and mechanisms behind the early stages of atrial septal development. By utilizing morpholino-induced knockdown in the chick we have analysed the role of alpha myosin heavy chain during early cardiogenesis in a temporal manner. Upon knockdown of alpha myosin heavy chain, three different phenotypes of the atrial septum were observed: (1) the atrial septum failed to initiate, (2) the septum was initiated but was growth restricted, or (3) incorrect specification occurred resulting in multiple septa forming. In addition, at a lower frequency, decreased alpha myosin heavy chain was found to give rise to an abnormally looped heart or an enlarged heart. Staining of the actin cytoskeleton indicated that many of the myofibrils in the knockdown hearts were not as mature as those observed in the controls, suggesting a mechanism for the defects seen. Therefore, these data suggest a role for alpha myosin heavy chain in modelling of the early heart and the range of defects to the atrial septum suggest roles in its initiation, specification and growth during development.


The traumatic impact of child sexual abuse: a conceptualization.
A framework is proposed for a more systematic understanding of the effects of child sexual abuse. Four traumagenic dynamics--traumatic sexualization, betrayal, stigmatization, and powerlessness--are identified as the core of the psychological injury inflicted by abuse. These dynamics can be used to make assessments of victimized children and to anticipate problems to which these children may be vulnerable subsequently. Implications for research are also considered.


The Nucleolus: A Multiphase Condensate Balancing Ribosome Synthesis and Translational Capacity in Health, Aging and Ribosomopathies.
The nucleolus is the largest membrane-less structure in the eukaryotic nucleus. It is involved in the biogenesis of ribosomes, essential macromolecular machines responsible for synthesizing all proteins required by the cell. The assembly of ribosomes is evolutionarily conserved and is the most energy-consuming cellular process needed for cell growth, proliferation, and homeostasis. Despite the significance of this process, the intricate pathophysiological relationship between the nucleolus and protein synthesis has only recently begun to emerge. Here, we provide perspective on new principles governing nucleolar formation and the resulting multiphase organization driven by liquid-liquid phase separation. With recent advances in the structural analysis of ribosome formation, we highlight the current understanding of the step-wise assembly of pre-ribosomal subunits and the quality control required for proper function. Finally, we address how aging affects ribosome genesis and how genetic defects in ribosome formation cause ribosomopathies, complex diseases with a predisposition to cancer.


Statistical approaches for the determination of cut points in anti-drug antibody bioassays.
Cut points in immunogenicity assays are used to classify future specimens into anti-drug antibody (ADA) positive or negative. To determine a cut point during pre-study validation, drug-naive specimens are often analyzed on multiple microtiter plates taking sources of future variability into account, such as runs, days, analysts, gender, drug-spiked and the biological variability of un-spiked specimens themselves. Five phenomena may complicate the statistical cut point estimation: i) drug-naive specimens may contain already ADA-positives or lead to signals that erroneously appear to be ADA-positive, ii) mean differences between plates may remain after normalization of observations by negative control means, iii) experimental designs may contain several factors in a crossed or hierarchical structure, iv) low sample sizes in such complex designs lead to low power for pre-tests on distribution, outliers and variance structure, and v) the choice between normal and log-normal distribution has a serious impact on the cut point. We discuss statistical approaches to account for these complex data: i) mixture models, which can be used to analyze sets of specimens containing an unknown, possibly larger proportion of ADA-positive specimens, ii) random effects models, followed by the estimation of prediction intervals, which provide cut points while accounting for several factors, and iii) diagnostic plots, which allow the post hoc assessment of model assumptions. All methods discussed are available in the corresponding R add-on package mixADA.


Motion fluency and object preference: Robust perceptual but fragile memory effects.
In 8 experiments, we investigated motion fluency effects on object preference. In each experiment, distinct objects were repeatedly seen moving either fluently (with a smooth and predictable motion) or disfluently (with sudden and unpredictable direction changes) in a task where participants were required to respond to occasional brief changes in object appearance. Results show that (a) fluent objects are preferred over disfluent objects when ratings follow a moving presentation, (b) there is some evidence that object-motion associations can be learned with repeated exposures, (c) sufficiently potent motions can yield preference for fluent objects after a single viewing, and (d) learned associations do not transfer to situations where ratings follow a stationary presentation, even after deep levels of encoding. Episodic accounts of memory retrieval predict that emotional states experienced at encoding might be retrieved along with the stimulus properties. Though object-emotion associations were repeatedly paired, there was no evidence for emotional reinstatement when objects were seen stationary. This indicates that the retrieval process is a critical limiting factor when considering visuomotor fluency effects on behavior. Such findings have real-world consequences. For example, a product advertised with high perceptual fluency might be preferred at the time, but this preference might not transfer to seeing the object on a shelf. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Regulation of neurons in the dorsal motor nucleus of the vagus by SIRT1.
Neurons in the dorsal motor nucleus of the vagus (DMV) play a critical role in the regulation of autonomic functions. Previous studies indicated that central activation of sirtuin 1 (SIRT1) has beneficial effects on homeostasis, most likely via modulation of the autonomic output. Sirtuins are NAD(+)-dependent deacetylases and have been associated with longevity. SIRT1 is one of the best-characterized sirtuins expressed in mammals, and may be involved in the regulation of metabolism. Resveratrol, a SIRT1 activator reduced hyperglycemia likely through activation of vagal output; however, the cellular mechanisms of action have not been determined. In this study, whole-cell patch-clamp electrophysiology on acute brainstem slices was used to test the hypothesis that activation of SIRT1 with resveratrol enhances neurotransmission in DMV neurons. Application of resveratrol increased the frequency of spontaneous excitatory postsynaptic currents (sEPSC). This effect was KATP channel-dependent and was prevented with pre-application of SIRT1 inhibitor, EX527. Resveratrol also increased miniature EPSC (mEPSC) frequency without change in amplitude. Furthermore, our data demonstrated that resveratrol regulates excitatory neurotransmission in a PI3 kinase-dependent manner, since wortmannin, a PI3K inhibitor prevented the increase of mEPSC frequency caused by resveratrol. In conclusion, our data demonstrate that resveratrol via SIRT1 increases excitatory neurotransmission to DMV neurons. These observations suggest that activation of SIRT1 may regulate the function of subdiaphragmatic organs through controlling the activity of parasympathetic DMV neurons.


Ocean acidification impacts mussel control on biomineralisation.
Ocean acidification is altering the oceanic carbonate saturation state and threatening the survival of marine calcifying organisms. Production of their calcium carbonate exoskeletons is dependent not only on the environmental seawater carbonate chemistry but also the ability to produce biominerals through proteins. We present shell growth and structural responses by the economically important marine calcifier Mytilus edulis to ocean acidification scenarios (380, 550, 750, 1000 µatm pCO2). After six months of incubation at 750 µatm pCO2, reduced carbonic anhydrase protein activity and shell growth occurs in M. edulis. Beyond that, at 1000 µatm pCO2, biomineralisation continued but with compensated metabolism of proteins and increased calcite growth. Mussel growth occurs at a cost to the structural integrity of the shell due to structural disorientation of calcite crystals. This loss of structural integrity could impact mussel shell strength and reduce protection from predators and changing environments.


Perspective in statements of quantity, with implications for consumer psychology.
We demonstrate that presentation of information about quantities, whether expressed in natural language or by using numbers, induces a perspective that influences subsequent processing. Experiment 1 shows this to be true for natural language quantifiers, with negative and positive expressions inducing different perspectives. In Experiment 2, we examined the application of this idea to the specific case of perspectives induced by describing products as containing x% fat or as being x% fat free. We found that the percentage-fat description appears to induce a perspective that is sensitive to the level offat being depicted, with products being judged as less healthy at higher amounts of fat. However, this effect was lessened (Experiment 2) or eliminated (Experiment 3) with the percentage-fat-free description. The experiments suggest the fat-free perspective blocks access to assumptions about healthy fat levels.


The molecular through ecological genetics of abnormal abdomen in Drosophila mercatorum. I. Basic genetics.
The abnormal abdomen syndrome (aa) in Drosophila mercatorum is characterized by the persistence of juvenilized cuticle on the adult abdomen. The aa phenotype is shown to depend on at least two X-linked genetic elements that are about one map unit apart near the centromeric end of the X chromosome. These two genetic elements are necessary for aa expression; one behaves as a dominant element and the other as a recessive. Overlaying these genetic studies upon molecular work reported elsewhere, it is argued that the dominant element is the presence of a 5 kb insertion in a majority of the X-linked repeats coding for the 28S ribosomal RNA. The recessive element appears to be a locus controlling differential replication of noninserted over inserted 28S genes during polytenization. The aa syndrome requires both the presence of the inserted repeats and the failure to preferentially amplify noninserted repeats. Given the necessary X-linked elements for aa, a variety of modifiers are revealed. First, aa expression in males is Y-linked, apparently corresponding to a deletion of the 18S/28S rDNA gene cluster normally found on the Y. Moreover, all major autosomes can modify the penetrance of aa.


Quantitative evaluation by minisequencing and microarrays reveals accurate multiplexed SNP genotyping of whole genome amplified DNA.
Whole genome amplification (WGA) procedures such as primer extension preamplification (PEP) or multiple displacement amplification (MDA) have the potential to provide an unlimited source of DNA for large-scale genetic studies. We have performed a quantitative evaluation of PEP and MDA for genotyping single nucleotide polymorphisms (SNPs) using multiplex, four-color fluorescent minisequencing in a microarray format. Forty-five SNPs were genotyped and the WGA methods were evaluated with respect to genotyping success, signal-to-noise ratios, power of genotype discrimination, yield and imbalanced amplification of alleles in the MDA product. Both PEP and MDA products provided genotyping results with a high concordance to genomic DNA. For PEP products the power of genotype discrimination was lower than for MDA due to a 2-fold lower signal-to-noise ratio. MDA products were indistinguishable from genomic DNA in all aspects studied. To obtain faithful representation of the SNP alleles at least 0.3 ng DNA should be used per MDA reaction. We conclude that the use of WGA, and MDA in particular, is a highly promising procedure for producing DNA in sufficient amounts even for genome wide SNP mapping studies.


Synthesis, cytotoxicity, and DNA interactions of new cisplatin analogues containing substituted benzimidazole ligands.
Six new platinum(II) complexes with 1-H or methyl-2-chloromethyl or acetoxymethyl or 2'-hydroxyethylbenzimidazole carrier ligands were synthesized and evaluated for their reactivity against model nucleophile I(-), cellular uptake, and in vitro antiproliferative activities against the human MCF-7 breast and HeLa cervix cancer cell lines. The effect of the compounds on pBR322 plasmid DNA was studied by gel electrophoretic mobility measurements. Flow cytometric analysis was also carried out to study the effect of representative compounds 1 and 2, bearing 2-chloromethyl or -acetoxymethylbenzimidazole carrier ligands, on the cell cycle distribution of MCF-7 and HeLa cells, respectively. In general, it was found that Pt(II) complexes were less cytotoxic than cisplatin and were comparable to carboplatin. The results of the plasmid DNA interaction and the restriction studies suggest that changing the chemical structure of the benzimidazole ligands may modulate DNA binding mode and the sequence selectivity. Compounds 1 and 2 had no significant effect on the cell cycle profile of the cells used. However, compound 2 induced a significant increase in the SubG1 cell population at a concentration of 20 microM.


Imaging findings in primary central nervous system vasculitis.
Primary central nervous system vasculitis (PCNSV) is a rare primary vasculitis limited to the brain and spinal cord. It can affect any age group, but has a predilection for subjects aged 40 to 60 years without clear gender predominance. Clinical manifestations are nonspecific, including headache, non-focal neurological features and, less frequently, focal neurological signs. Brain biopsy is the diagnostic gold standard, but may be falsely negative when unaffected tissue is sampled. In addition, brain biopsy carries a small but significant risk of serious complications. Imaging procedures are a key part of the workup of PCNSV patients. They can be used to document the extent and type of lesions, to gauge response to treatment, and sometimes as surrogates for brain biopsy. Magnetic resonance is extremely sensitive but non-specific. The most common findings are multiple bilateral ischaemic lesions often involving white and grey matter. Conventional or magnetic resonance angiography (MRA) typically shows segmental narrowing and dilation in multiple cerebral arteries. However, atypical findings have also been described both with magnetic resonance and angiography. This review discusses the state-of-the-art of current imaging techniques in the workup of PCNSV patients and highlights future prospects.


Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate.
To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate. Thirty-eight patients, median age 68 (range 60-82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4-6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology. There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules. Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.


The ethical challenges of providing fertility care to patients with chronic illness or terminal disease.
The field of fertility is rapidly evolving, bringing opportunities for improvement in our patients' quality of life as well as bringing new ethical dilemmas. As medical science continues to advance, significant numbers of the reproductive-aged population are living with chronic and/or terminal conditions but have reasonable odds of lengthy survival and wish to have children. Likewise, there are adolescents diagnosed with cancer who are increasingly expected to achieve an improved, if not normal, life expectancy after treatment. Oftentimes these children are told they must sacrifice their ability to later have genetically related offspring; however, technologies to preserve fertility are changing this prognosis. Patients with chronic infection are living longer, more normal lives and are increasingly seeking reproductive assistance. Moreover, there is an increasing number of patients' families desiring posthumous use of gametes, which also raises ethical and legal issues. This article discusses ethical principles of bioethics and then highlights specific ethical issues through four plausible cases that may be seen in a fertility practice providing medical care to patients with chronic illness or terminal disease. It concludes that prompt referral of patients to the reproductive endocrinologist, along with a multidisciplinary approach to care, provides increased chances of successful treatment of this group of patients.


The safety and efficacy of improvised tourniquets in life-threatening hemorrhage: a systematic review.
The increased incidence of mass casualty incident (MCI) with penetrating injuries in the civilian setting creates a call for implementing devices, such as a tourniquet (TQ), in civilian first aid. Bystanders could act as immediate responders after an MCI in order to prevent a victim from exsanguination using direct pressure or commercial tourniquets (C-TQ). Reports have shown that immediate access to C-TQs was not available and bystanders used objects available at the trauma scene to make an improvised tourniquet (I-TQ). The aim of this systematic review of literature was to summarize the existing literature on designs, efficacy and safety of I-TQs. A systematic review of the literature was performed. Bibliographic databases PubMed, EMBASE.com and Cochrane Library were searched. All types of original studies about I-TQ's were included. Review studies, exempts from textbooks or studies with TQs applied during elective surgeries were excluded. Twenty studies were included. In both simulated experiments and real-life situations, I-TQs outperformed commercial TQs (C-TQ) regarding success rate. Of the I-TQs, the band and windlass design performed most consistently. Although lacking any statistical analysis, there was no reported difference in adverse events between I-TQs and C-TQs. The use of- and training in I-TQ by civilian immediate responders is not recommended because of limited efficacy and safety concerns; direct pressure is a viable alternative. However, I-TQs may save lives when applied correctly with proper objects; therefore, future studies regarding the best design and training in application of effective and safe I-TQs should be encouraged.


Adrenomedullin prevents sex-dependent impairment of autoregulation during hypotension after piglet brain injury through inhibition of ERK MAPK upregulation.
Cerebrospinal fluid (CSF) adrenomedullin (ADM) levels are increased in female, but remain unchanged in male, piglets after fluid percussion injury (FPI) of the brain. Subthreshold vascular concentrations of ADM restore impaired hypotensive pial artery dilation after FPI more in males than females. Extracellular signal-related kinase (ERK) mitogen-activated protein kinase (MAPK) is upregulated and contributes to reductions in cerebral blood flow (CBF) after FPI. We hypothesized that ADM prevents sex-dependent impairment of autoregulation during hypotension after FPI through inhibition of ERK MAPK upregulation. FPI increased ERK MAPK more in males than in females. CBF was unchanged during hypotension in sham animals, was reduced more in males than in females after FPI during normotension, and was further reduced in males than in females during hypotension and after FPI. ADM and the ERK MAPK antagonist U 0126 prevented reductions in CBF during hypotension and FPI more in males than in females. Transcranial Doppler (TCD) blood flow velocity was unchanged during hypotension in sham animals, was decreased during hypotension and FPI in male but not in female pigs, and was ameliorated by ADM. Intracranial pressure (ICP) was increased after FPI more in male than in female animals. ADM blunted elevated ICP during FPI and hypotension in males, but not in females. ADM prevented reductions in cerebral perfusion pressure (CPP) during FPI and hypotension in males but not in females. The calculated autoregulatory index was unchanged during hypotension in sham animals, but was reduced more in males than females during hypotension and FPI. ADM prevented reductions in autoregulation during hypotension and FPI more in males than females. These data indicate that ADM prevented loss of cerebral autoregulation after FPI in a sex-dependent and ERK MAPK-dependent manner.


Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα. Phytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.


Individual skull model fabrication for craniofacial surgery.
The purpose of this report is to describe a milling procedure for the fabrication of skull models from 3-D CT data. Data from computer tomographic cuts are transferred to a computer and stored. Model fabrication takes place using high quality styrodur that is shaped with a high speed milling device. This allows the modeling of an individual life size skull in its skeletal as well as in its soft tissue contours. Smaller bone pieces and areas can be enlarged separately up to eight times normal size for better visualization. Planning and simulation of craniofacial surgery in three dimensions is possible, and bone implants or alloplastic biomaterials can be modeled for implantation.


Role and rationale of gene therapy and other novel therapies in the management of NMIBC.
Bladder cancer is the second most common urological malignancy with a one in 28 lifetime risk. Three-quarters of tumors are non-muscle-invasive (formerly termed superficial) at the time of presentation. Approximately half of all non-muscle-invasive bladder cancer (NMIBC) will recur and, depending on certain prognostic factors including grade, stage and presence of carcinoma in situ, a number will progress to muscle invasion. The standard of care for NMIBC is transurethral resection of bladder tumor (TURBT) to remove the mass lesion(s). Intravesical therapy of NMIBC post-TURBT therefore aims to delay/prevent recurrence and/or progression to muscle-invasive bladder cancer. While intravesical chemotherapy, such as mitomycin C, and immunotherapy, such as bacillus Calmette-Guérin are well established, there is current interest in novel therapies based on improved molecular understanding of bladder cancer. These novel therapies include gene therapy, using viral and non-viral vectors for transfer, monoclonal antibodies and direct tumoricidal viruses. While there is a sound theoretical basis for these therapies based on molecular targeting, there is little evidence in human studies that these therapies have clinical impact on NMIBC. However, it is certain that their use will be investigated further and they provide great hope for the future of NMIBC adjuvant therapy.


Language Skills in Children Born Preterm (<30 Wks' Gestation) Throughout Childhood: Associations With Biological and Socioenvironmental Factors.
To examine the individual and collective contribution of biological and socioenvironmental factors associated with language function at 2, 5, 7, and 13 years in children born preterm (<30 weeks' gestation or <1250 g birth weight). Language function was assessed as part of a prospective longitudinal study of 224 children born preterm at 2, 5, 7, and 13 years using age-appropriate tools. Language Z-scores were generated based on a contemporaneous term-born control group. A selection of biological factors (sex, small for gestational age, bronchopulmonary dysplasia, infection, and qualitatively defined brain injury) and early socioenvironmental factors at age 2 years (primary income earner employment status and type, primary caregiver education level, English as a second language, parental mental health history, parent sensitivity and facilitation, and parent-child synchrony) was chosen a priori. Associations were assessed using univariable and multivariable linear regression models applied to outcomes at each time point. Higher primary caregiver education level, greater parent-child synchrony, and parent sensitivity were independently associated with better language function across childhood. Socioenvironmental factors together explained an increasing percentage of the variance (9%-18%) in language function from 2 to 13 years of age. In comparison, there was little evidence for associations between biological factors and language function, even during early childhood years. This study highlights the importance of socioenvironmental factors over biological factors for language development throughout childhood. Some of these socioenvironmental factors are potentially modifiable, and parent-based interventions addressing parenting practices and education may benefit preterm children's language development.


Patterns of Non-Suicidal Self-Injury and Their Relationship with Suicide Attempts in Youth with Borderline Personality Disorder.
The study aimed to identify the relationships between patterns of non-suicidal self-injury (NSSI), their severity, and suicide attempts among 107 youth (aged 15-25 years) with borderline personality disorder (BPD). Two principal patterns were identified via a graphical representation of retrospectively reported 12-month histories of NSSI. These were habitual (NSSI occurring at regular intervals) and random patterns (NSSI inconsistently spaced). Habitual patterns of NSSI were associated with lower severity and fewer suicide attempts than random patterns. Within-person comparisons revealed a reduction in NSSI engaged within a habitual pattern and an increase in NSSI engaged within a random pattern in the month prior to a suicide attempt. Findings suggest that the accuracy of risk assessments among youth with BPD might be improved by identifying an individual's historical pattern of NSSI, as well as any relative increase in NSSI engaged within a random pattern or relative reduction in NSSI engaged within a habitual pattern.


Five Hundred Seventy-Six Cases of Video-Assisted Thoracic Surgery Using Local Anesthesia and Sedation: Lessons Learned.
General anesthesia and endotracheal intubation are a luxury rather than a necessity for many video-assisted thoracic surgery (VATS) operations. Twenty-three years ago, I began using local anesthesia and sedation for pleural disease and subsequently, for pericardial and lung disease. The records of all patients undergoing VATS using local anesthesia and sedation at hospitals of the Geisinger Health System (Danville and Wilkes-Barre, PA), from June 1, 2002 to June 30, 2011, and the Lifebridge Health System (Baltimore, MD) from July 1, 2011 to March 1, 2017, were retrospectively reviewed. There was 1 unsuccessful attempt at this technique, and it was eligible for inclusion. No patient was excluded based on age, BMI, or comorbidities. No patient had endotracheal intubation, laryngeal mask airway, or epidural or nerve block analgesia; all patients breathed spontaneously. Five hundred twenty-nine patients ranging in age from 21 to 104 years (mean 67 years) underwent 576 procedures: pleural biopsy-drainage with or without talc (n = 368); drainage of empyema (n = 112); lung biopsy (n = 56); evacuation of chronic hemothorax (n = 23); pericardial window (n = 10); treatment of chylothorax (n = 2); lung abscess draining (n = 2); treatment of pneumothorax (n = 2); and mediastinal mass biopsy (n = 1). No patient required intubation or conversion to thoracotomy. There were 12 complications (2%). There were no deaths due to operation. Video-assisted thoracic surgery using local anesthesia and sedation is safe and effective for many indications. A review of the lessons learned caring for 529 patients will allow any thoracic surgeon and any anesthesiologist to practice this technique.


Genetic Diversity in Drug Transporters: Impact in African Populations.
Polymorphisms in drug transporters, like the adenosine triposphate-binding cassette (ABC) and solute carrier (SLC) superfamilies, may contribute to the observed diversity in drug response in African patients. This review aims to provide a comprehensive summary and analysis of the frequencies and distributions in African populations of ABC and SLC variants that affect drug pharmacokinetics (PK) and pharmacodynamics (PD). Of polymorphisms evaluated in African populations, SLCO1B1 rs4149056 and SLC22A6 rs1158626 were found at markedly higher frequencies than in non-African populations. SLCO1B1 rs4149056 was associated with reduction in rifampin exposure, which has implications for dosing this important anti-tuberculosis therapy. SLC22A6 rs1158626 was associated with increased affinity for antiretroviral drugs. Genetic diversity in SLC and ABC transporters in African populations has implications for conventional therapies, notably in tuberculosis and HIV. More PK and PD data in African populations are needed to assess potential for a different response to drugs compared with other global populations.


[Subjective and objective voice assessment following partial resection of the larynx].
There is no generally accepted, standardized approach for evaluation of voice quality and of intelligibility after partial laryngectomy. A voice evaluation which considers some aspects of voice quality is possible by assessing physical and acoustic voice parameters. But this approach does not consider how the patient subjectively assesses his postoperatively altered voice and how the patient believes he is understood by various communication partners. In this study objective and subjective variables of the voice quality of 32 patients with partial laryngectomies were measured. First, selected physical and acoustic variables of voice quality were quantified. Second, subjective criteria of voice quality and of intelligibility were assessed by a questionnaire. A significant correlation between variables of objective and subjective voice quality was found. The maximum vocal intensity, the maximum pitch, and the intensity range correlated significantly with the subjective assessment of intelligibility. No relationship was found between the acoustic variables and the subjectively perceived degree of vocal disability.


Access to healthcare services and confidence in healthcare professionals' management of malaria: the views of Francophone sub-Saharan African Immigrants living in western Canada.
There is a paucity of knowledge about the healthcare attitudes and practices of French-speaking immigrants originating from Sub-Saharan Africa (FISSA) living in minority settings. The purpose of this study was to characterize FISSA healthcare experiences and confidence in the malaria-related knowledge of health professionals in Edmonton. A structured survey was used to examine a cohort of 382 FISSA (48% female; 52% male) living in Edmonton. FISSA general healthcare attitudes, experiences and satisfaction with the Canadian healthcare system were studied. Healthcare Competency Perception (HCP) was characterized by using an index score. Statistical analyses were performed to evaluate the impact of healthcare experiences and other outcomes. Intriguingly, while only 42% of FISSA had a French-speaking family physician, 83% (197/238) of those who had received health care services in Alberta found that access to medical treatment was easy, and 77% (188/243) were satisfied with received care. Although 70% (171/243) of FISSA did not receive services in French, 82% (199/243) surprisingly reported having good levels of comprehension during their visits. Satisfaction with care was associated with having a family physician (p = 0.018) and having health insurance (p = 0.041). Nevertheless, confidence in the healthcare system's ability to treat malaria effectively was significantly lower, with only 39% (148/382) receiving a positive score on the HCP index. This study provides an important insight into FISSA experience with and perception of the Alberta's healthcare system.


Borrelia spirochetes in European exotic farm animals.
Ticks transmit a broad spectrum of pathogens, threatening both animal and human health. Tick survival and proliferation are strongly dependent on host selection and suitability. The hard tick Ixodes ricinus, which is widespread throughout most of Europe, is a host generalist capable of feeding on many different vertebrate species. Pasture-kept exotic farm animals may be at a high risk for tick and tick-borne pathogens infestations but research characterizing this is currently lacking. This study focused on the detection of Borrelia spirochetes (including Borrelia miyamotoi) in exotic farm animals. Using nested-PCR with Borrelia-specific primers, 121 serum samples from 54 exotic farm animals of several species bred in four different farms in Bohemia and Moravia (Czechia) were tested. Positive samples were sequenced for the identification of Borrelia species. The prevalence of Borrelia DNA in the samples ranged from 13 to 67%, depending on the sampling site. The sequencing results confirmed the DNA presence of multiple spirochete species from the Borrelia burgdorferi sensu lato complex. Only one sample from an ostrich (Struthio camelus) was found to be positive for Borrelia myiamotoi. The results show that exotic farm animals can serve as hosts for hard ticks and can be infected by Borrelia spirochetes, transmitted by hard ticks. Therefore, these animals could play a relevant role in maintaining Borrelia spirochetes in nature.


Strategies to identify, engineer, and validate antibodies targeting blood-brain barrier receptor-mediated transcytosis systems for CNS drug delivery.
Numerous therapeutics for neurological diseases have been developed, but many have failed in clinical trials in part due to limited brain bioavailability, mainly stemming from inefficient transport through the blood-brain barrier (BBB). One potential approach to noninvasive, BBB-targeted drug delivery to the brain is the use of engineered antibodies as delivery vehicles that can transport conjugated drug cargo across the BBB and into the brain via receptor-mediated transcytosis (RMT). Effective development of these RMT targeting systems includes novel target discovery, along with antibody engineering and subsequent validation. This review focuses on both known and emerging RMT systems, targeting antibody properties in relation to BBB trafficking, and antibody validation strategies. Clinical development of known RMT targeting systems and identification of novel BBB RMT targets will be complementary strategies for overcoming the BBB in central nervous system (CNS) disease treatment. The search for new RMT targets with higher brain specificity and enriched expression in the brain has given rise to some new targets which may offer unique benefits. It is our opinion that the expansion of BBB RMT system identification, along with targeting molecule engineering and validation strategies, will substantially contribute to the treatment of a wide range of neurological diseases.


Biological Oxidation of Manganese Mediated by the Fungus Neoroussoella solani MnF107.
Manganese oxides are highly reactive minerals and influence the geochemical cycling of carbon, nutrients, and numerous metals in natural environments. Natural Mn oxides are believed to be dominantly formed by biotic processes. A marine Mn-oxidizing fungus Neoroussoella solani MnF107 was isolated and characterized in this study. SEM observations show that the Mn oxides are formed on the fungal hyphal surfaces and parts of the hypha are enveloped by Mn oxides. TEM observations show that the Mn oxides have a filamentous morphology and are formed in a matrix of EPS enveloping the fungal cell wall. Mineral phase analysis of the fungal Mn oxides by XRD indicates that it is poorly crystalline. Chemical oxidation state analysis of the fungal Mn oxides confirms that it is predominantly composed of Mn(IV), indicating that Mn(II) has been oxidized to Mn (IV) by the fungus.


A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients.
Fifteen patients (11 males, four females; median age 57) manifested a disease characterized by (1) the histopathologic features of Castleman's disease, plasma cell type, in lymph node biopsies; (2) predominantly lymphadenopathic disease, involving multiple, preferentially peripheral nodal groups; (3) varied manifestations of multisystemic involvement (such as constitutional symptoms; splenomegaly and hypergammaglobulinemia; elevated ESR, anemia, and thrombocytopenia; hepatomegaly and altered liver function tests (LFTs); signs of renal disease); and (4) idiopathic nature. Two main patterns of evolution were recognized: persistent, with sustained clinical manifestations, and episodic, with recurrent exacerbations and remissions. Seventy-three percent of patients had infectious complications, and 27% developed malignancies. Complete remissions were obtained occasionally with antineoplastic agents and with splenectomy but not with glucocorticosteroids alone. The median survival time is 30 months; 60% of patients have died. Median follow-up in the six surviving patients is 97+ months. A review of 50 cases in the literature revealed similar clinical and laboratory features. Despite some similarities with autoimmune diseases, the main features of this process seem to best fit a hyperplastic-dysplastic lymphoid disorder in a setting of immunoregulatory deficit.


Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry.
This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA1c, coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m2), and elevated levels of HbA1c (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.


Iopamidol vs. metrizamide myelography: clinical comparison of side effects.
One hundred myelographies with iopamidol and 100 with metrizamide were performed in order to compare the side effects of the two contrast media after injection into the spinal subarachnoid space. All patients were observed for a follow-up period of at least 4 days. The most frequently observed side effect, headache, was more common, of longer duration, and more severe with the use of metrizamide than with iopamidol. Only neck pain was more common with iopamidol. More severe side effects such as meningeal irritation, psychoorganic syndrome, and epileptic seizures occurred only with metrizamide. The results seem to indicate a lower neurotoxicity and better patient tolerance for iopamidol than for metrizamide.


Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth.
Survival after stress requires the precise orchestration of cell-signalling events to ensure that biosynthetic processes are alerted and cell survival pathways are initiated. Here we show that Bag1, a co-chaperone for heat-shock protein 70 (Hsp70), coordinates signals for cell growth in response to cell stress, by downregulating the activity of Raf-1 kinase. Raf-1 and Hsp70 compete for binding to Bag1, such that Bag1 binds to and activates Raf-1, subsequently activating the downstream extracellular signal-related kinases (ERKs). When levels of Hsp70 are elevated after heat shock, or in cells conditionally overexpressing Hsp70, Bag1-Raf-1 is displaced by Bag1-Hsp70, and DNA synthesis is arrested. Mutants Bag1C204A and Bag1E208A, which cannot bind Hsp70, constitutively activate Raf-1/ERK kinases but are unaffected by Hsp70; consequently neither Bag1-Raf-1 nor DNA synthesis is negatively affected during heat shock. Likewise, mutants Hsp70F245S, Hsp70R262W and Hsp70L282R, which retain chaperone activity but do not bind to Bag1, fail to repress Bag1 activation of Raf-1/ERK kinase. We propose that Bag1 functions in the heat-shock response to coordinate cell growth signals and mitogenesis, and that Hsp70 functions as a sensor in stress signalling.


Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway.
Glioma is the most common type of malignant brain tumor. Due to its highly aggressive and metastatic features, glioma is associated with poor prognosis and a lack of effective treatments. Eriodictyol, a natural flavonoid compound, has been reported to possess anti-inflammatory and antioxidant effects. However, the anti-tumor effects of eriodictyol and the underlying mechanisms have rarely been reported. In this study, we found that eriodictyol has anti-tumor activity in lung, colon, breast, pancreas, and liver cancer, and most significantly in glioma cell lines. Eriodictyol dose- and time-dependently suppresses cell proliferation, migration, and invasion in U87MG and CHG-5 glioma cells. In addition, eriodictyol induces apoptosis in U87MG and CHG-5 cells, as evaluated by flow cytometry, immunofluorescence, and Western blot. Furthermore, eriodictyol downregulates the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway in a concentration-dependent manner. Moreover, the effects of eriodictyol on the apoptosis of glioma cells are enhanced by LY294002 (a PI3K inhibitor) and reversed by 740 Y-P (a PI3K agonist). In a mouse xenograft model, eriodictyol not only dramatically suppressed tumor growth but also induced apoptosis in tumor cells. In summary, our data illustrate that eriodictyol effectively inhibits proliferation and metastasis and induces apoptosis of glioma cell lines, which might be a result of the blockade of the PI3K/Akt/NF-κB signaling pathway.


Selegiline-citalopram combination in patients with Parkinson's disease and major depression.
We evaluated the efficacy and safety of the selegiline citalopram combination in the treatment of major depression in patients with Parkinson's disease. Eight consecutive depressed outpatients who had received previously selegiline monotherapy or (one patient) selegiline-levodopa combination (the dose of selegiline was 5-10 mg/day in each case) for mild to severe Parkinson's disease were treated with 20 mg citalopram/day. The severity of depression was evaluated on the Hamilton Depression Rating Scale before and 8 weeks after citalopram treatment. The majority of the patients (six) responded well to citalopram treatment and no adverse events occurred. The combination of a low dose of selegiline (5-10 mg daily) and citalopram (20 mg daily) may be an effective and safe method in the treatment of major depression in patients with Parkinson's disease. (Int J Psych Clin Pract 2000; 4:123-125).


[Monoclonal immunoenzyme test-system for evaluating secretory immunity to influenza A and B viruses].
Enzyme immunoassay system has been developed for measuring the titers of secretory IgA in secretion from the upper respiratory airways (SURA). Russian ingredients are used. The conjugate includes monoclonal antibodies to heavy chains of human secretory IgA. The sensitivity and specificity of the kit was tested with SURA of normal subjects and patients with influenza. The initial level of specific secretory IgA antibodies detected by the kit clearly correlated with defense from natural influenza infection. The protective concentrations of the antibodies corresponded to at least 1:64 dilutions. The titers of serum and secretory antibodies in convalescents after influenza A or B were virtually the same. The level of secretory antibodies dropped sooner than that of serum antibodies.


Inpatient healthcare utilisation in patients with alcoholic liver disease: what are the costs and outcomes?
Alcoholic liver disease (ALD) carries a significant cost burden and often leads to inpatient care. It is unclear whether inpatient care for ALD is any more costly than admission for other reasons. To compare the costs and outcomes of inpatient care for ALD to two groups: a control group of matched cases admitted in the same time frame and people admitted for other chronic liver diseases (CLD). All admissions for ALD and other CLD in a 3-month period were retrospectively identified. Five randomly identified gender- and age-matched contemporaneously admitted controls were allocated. Length of stay (LoS), mortality, inpatient costs, blood product utilisation and discharge destination were compared. Of the 71 admissions due to CLD, ALD was the most frequent cause (53/71, 75%). ALD admissions cost more (median $10 100 vs $5294; P = 0.0012) and had greater LoS (median LoS 7.2 days (interquartile range (IQR) 0.2-40.7)) than controls (2.6 days (IQR 1.1-6.8); P = 0.0001). A larger proportion of the ALD cohort required blood transfusion and had a higher mortality than controls (24.5 vs 6.4%, P = 0.002 and 13.2 vs 0.2%; P < 0.0001 respectively). Self-discharge was more common in the ALD group (13.2 vs 1.1%, P < 0.0001). ALD inpatient hospital admissions have greater median total cost, longer LoS, greater blood product utilisation, higher mortality and greater rate of discharge against medical advice than age- and gender-matched controls. These data emphasise the large inpatient care burden, high mortality and suboptimal engagement in those with ALD, which justifies the more active provision of services for ALD.


The effectiveness of a cognitive behavioral exercise approach (CBEA) compared to usual care in patients with a Whiplash Associated Disorder: A quasi-experimental clinical trial.
Whiplash Associated Disorders (WAD) is a biopsychosocial problem, education may be an essential part in the treatment and the prevention of chronic WAD. However, it is still unclear which type of educative intervention has already been used in WAD patients and how effective such interventions are. To examine the effectiveness of a cognitive behavioral exercises approach (CBEA) for self-training of the neck relative to usual care in individuals with WAD in acute phase. Forty-one patients, 65.9% female (mean ± SD age: 41 ±11 years), with WAD were recruited immediately after the accident (within 48 hours) and assigned according to patient choice to receive a CBEA self-training of the neck or usual care for 15 days. The primary outcome measure was pain intensity and disability as measured with the Neck Disability Index (NDI). Secondary outcome measures included the presence of headaches, dizziness, nausea, and difficulties with concentration and memory. Measurements were taken at pre-treatment, 2 weeks post-treatment and 4- and 12- weeks after the injury. Patients receiving the CBEA intervention experienced a greater reduction in pain as compared to those receiving the usual care at the end as well as 4 and 12 weeks after the intervention (P< 0.001), for the Neck Disability Index (NDI) decreased more in the CBEA than controls over the 15 days and (F=[3.0] 552.383; P= 0.001), and in both groups at all follow-up periods (all, P= 0.001). This quasi-experimental clinical trial provides evidence that a CBEA for self-training of the neck may be more beneficial in treating pain than usual care in patients with WAD. However, the CBEA had limited value in improving NDI. Future studies should include several therapists, a measure of a long-term outcomes and randomize patients to groups.


Cancer in Australia: Actual incidence data from 1982 to 2013 and mortality data from 1982 to 2014 with projections to 2017.
Cancer is a major cause of illness in Australia and therefore ongoing monitoring of cancer in Australia is important. This study sources data from the Australian Institute of Health and Welfare (AIHW) and reports actual number of cases diagnosed and deaths, for all cancers combined and selected cancers, from 1982 to 2013 for incidence and from 1982 to 2014 for mortality, with projections to 2017 for both. It is estimated that 134 174 new cases of cancer (excluding basal and squamous cell carcinomas of the skin) will be diagnosed in 2017. The number of new cancer cases more than doubled from 47 414 in 1982. Prostate cancer is estimated to be the most commonly diagnosed cancer in males in 2017, whereas breast cancer is estimated to be the most commonly diagnosed cancer in females. It is estimated that there will be 47 753 deaths from cancer in Australia in 2017. Although the mortality rate decreased, the number of people who died in Australia from cancer almost doubled from 24 922 in 1982. Lung cancer was the most common cause of cancer death in both males and females. In 2011, cancer was the leading cause of disease burden in Australia.


The GTPase Rho has a critical regulatory role in thymus development.
The present study employs a genetic approach to explore the role of Rho GTPases in murine thymic development. Inactivation of Rho function in the thymus was achieved by thymic targeting of a transgene encoding C3 transferase from Clostridium botulinum which selectively ADP-ribosylates Rho within its effector domain and thereby abolishes its biological function. Thymi lacking functional Rho isolated from C3 transgenic mice were strikingly smaller and showed a marked (90%) decrease in cellularity compared with their normal litter mates. We also observed a similar decrease in levels of peripheral T cells in C3 transgenic mice. Analysis of the maturation status of thymocytes indicated that differentiation of progenitor cells to mature T cells can occur in the absence of Rho function, and both positive and negative selection of T cells appear to be intact. However, transgenic mice that lack Rho function in the thymus show maturational, proliferative and cell survival defects during T-cell development that severely impair the generation of normal numbers of thymocytes and mature peripheral T cells. The present study thus identifies a role for Rho-dependent signalling pathways in thymocyte development. The data show that the function of Rho GTPases is critical for the proliferative expansion of thymocytes. This defines a selective role for the GTPase Rho in early thymic development as a critical integrator of proliferation and cell survival signals.


Pathogenesis of pelvic inflammatory disease. What are the questions?
Pelvic inflammatory disease is usually caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Chlamydiae and gonococci are primary pathogens of the cervix and often ascend. Resultant damage to the cervix may permit organisms to move upward, but this mechanism of action is not well understood. Puberty and hormones, particularly oral contraceptives, may enhance chlamydial infection, but the mechanisms and likelihood of spread to the upper tract are ill defined. Upper tract infection with C trachomatis involves an acute phase, characterized by an influx of polymorphonuclear leukocytes and a chronic or persistent phase characterized by the presence of mononuclear cells (delayed hypersensitivity). Gonococci invade nonciliated epithelial cells, but are toxic to ciliated cells, due to elaborated lipooligosaccharides and peptidoglycan. Certain gonococci stimulate chemotaxis of polymorphonuclear leukocytes whose release of toxic metabolites may damage tissue. The immunologic mechanisms that permit specific host responses to these two organisms are now being elucidated and should receive more attention by researchers.


Air puff versus shock unconditioned stimuli in rabbit heart rate conditioning.
The present study examined whether corneal air puff can be used as an unconditioned stimulus to elicit reliable classically conditioned heart rate (HR) responses in rabbits. The conditioned and unconditioned HR responses were assessed during Pavlovian conditioning with different intensities of paraorbital shock (2.7, 1.2, or 0.5 mA) or corneal air puff (18.3, 5.9, or 2.2 N/cm2) unconditioned stimuli (UCSs). Each experimental group was given one acquisition session during which an acoustic conditioned stimulus was paired with either the high, medium, or low intensity of a shock or air puff UCS. The results suggest that: a) HR is reliably conditioned with a high-intensity air puff UCS, and with medium- or high-intensity paraorbital shock stimuli; and b) only UCSs that elicit a tachycardiac unconditioned HR response reliably support HR conditioning. It was concluded that either air puff or paraorbital shock can serve as an effective UCS for HR conditioned responses.


Determining the Photoisomerization Quantum Yield of Photoswitchable Molecules in Solution and in the Solid State.
Photoswitchable molecules are able to isomerize between two metastable forms through light stimuli. Originally being studied by photochemists, this type of molecule has now found a wide range of applications within physics, chemistry and biology. The extensive usage of photochromic molecules is due to the two isomers having fundamentally different physical and chemical properties. The most important attribute of a photoswitch is the photoisomerization quantum yield, which defines the efficiency of the photoisomerization event. Here we show how to determine the photoisomerization quantum yield in the solid state and in solution when taking thermal processes into account. The described method together with provided software allows for rapid and accurate determination of the isomerization process for this important class of molecules.


Segregation distortion in Drosophila melanogaster: genomic organization of Responder sequences.
The heterochromatic Responder (Rsp) locus of Drosophila melanogaster is the target of the two distorter loci Sd and E(SD). Rsp is located in a specific heterochromatic region of the second chromosome and is made up of AT-rich satellite sequences whose abundance is related to its sensitivity to the distorter chromosomes. Here we report that a cluster of Rsp sequences is also located in the third chromosome. The third-chromosome cluster has the same flanking sequences as the clone originally used to identify the Rsp elements, and one of the flanking sequences is a rearranged 412 retrotransposon. The presence of a second, unlinked Rsp-sequence cluster makes re-interpretation necessary for some earlier experiments in which segregation of the third chromosome had not been followed and raises interesting possibilities for the origin of the Rsp locus.


Regional and socio-economic disparity in use of insecticide-treated nets to prevent malaria among pregnant women in Kenya.
Insecticide-treated net (ITN) use is among the most recommended strategies to prevent malaria in pregnancy. We analysed the regional and socio-economic patterns of ITN use among pregnant women in Kenya using data from the 2003, 2008 and 2014 Kenyan Demographic and Health Surveys (KDHSs). Inequality was assessed using four dimensions: economic status, education, place of residence and region. Both relative and absolute summary measures were applied. In addition, simple and complex summary measures, i.e. difference, population attributable fraction, population attributable risk and ratio were considered based on the number of subgroups in each variable. There was overt inequality in the use of ITNs among pregnant women, with greater use among the better-off group in 2003 and 2014. Greater ITN use was also observed among pregnant women with a higher level of education. Pregnant women from urban settings tended to use ITNs (slept under a net the night before the survey) more than their rural counterparts in the 2003 KDHS. There were significant regional variations across the three surveys in all inequality summary measures, except ratio in the 2014 survey. Significant inequality in ITN use among pregnant women was observed at a macro scale.


Antioxidant biomarkers and cardiometabolic risk markers in an Aboriginal community in remote Australia: a cross-sectional study.
High-quality diets, characterised by nutrient-rich foods, are one of the foundations for health and well-being. Indicators of diet quality, antioxidants, are associated with protection against cardiometabolic diseases. The current study explores relationships between plasma antioxidants and cardiometabolic risk among Aboriginal people in Australia. As part of a community-driven health promotion programme, we conducted a cross-sectional study including a health-behaviour questionnaire, plasma antioxidants and cardiometabolic risk markers (anthropometric, blood pressure measurements, fasting glucose, glycated Hb (HbA1c), lipids, C-reactive protein and albumin-creatinine-ratio) continuous and categorised into population-specific cut-offs. Antioxidants (β-carotene, β-cryptoxanthin, lycopene, lutein-zeaxanthin, retinol and α-tocopherol measured using HPLC) were applied to a principal component analysis, which aggregated these into a single component. Linear regression models were applied to investigate associations between the antioxidant component and cardiometabolic risk markers. Community in a remote area in Northern Territory, Australia. A total of 324 Aboriginal people, mean age 35·5 (range 15-75) years. Antioxidant component levels were higher among individuals with higher self-reported vegetable intake (P < 0·01), higher among individuals with higher self-reported fruit intake (P = 0·05) and lower among current smokers (P = 0·06). Linear regression revealed an inverse association between the antioxidant component and C-reactive protein (β = -0·01, P < 0·01) after adjusting for confounders. Higher plasma antioxidant levels, indicators of diet quality, were associated with lower levels of high-sensitivity C-reactive protein in this Aboriginal population in remote Australia. This association suggests plasma antioxidants may be protective against inflammation; however, longitudinal studies are needed to examine this potentially protective relationship.


Is physiotherapy effective in the management of child and adolescent conversion disorder? A systematic review.
Child and adolescent conversion disorder has the potential to impart significant burden on health-care services and affect quality of life. Clinically, physiotherapists are involved in conversion disorder management; however, no systematic reviews have examined physiotherapy effectiveness in its management. The aim of this review is to identify the efficacy of physiotherapy management of child and adolescent conversion disorder. A search of multiple databases (Medline, CINAHL, Embase, PsychINFO, PEDro and the Cochrane Library) was completed along with manual searching of relevant reference lists to identify articles including children 0-18 years with a diagnosis of conversion disorder who received physical management. Two independent reviewers screened titles and abstracts using criteria. Data were extracted regarding study characteristics, functional outcome measures, length of stay, physiotherapy service duration and resolution of conversion symptoms. Methodological quality was assessed using a tool designed for observational studies. Twelve observational studies were included. No functional outcome measures were used to assess the effectiveness of the treatment protocols in the case studies. Resolution of symptoms occurred in all but two cases, with conversion symptoms still present at 11 months and at 2 years. Length of stay varied from 3 days to 16 weeks, with similar variation evident in length of physiotherapy service provision (2.5 weeks to 16 weeks). There was limited and poor quality evidence to establish the efficacy of physiotherapy management of child and adolescent conversion disorders. More rigorous study designs with consistent use of reliable, valid and sensitive functional outcome measures are needed in this area.


Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy.
Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive non-Hodgkin lymphomas. It is curable but one-third of cases are refractory to therapy or relapse after initial response highlighting the urgent need for developing novel therapeutic approaches. Targeting sirtuins, particularly SIRT1 by genetic approaches or using pharmaceutical inhibitor tenovin-6, has shown promising therapeutic potential in various hematopoietic malignancies. However, it remains unknown whether these approaches are effective for DLBCL. In this study, we have found that tenovin-6 potently inhibits the proliferation and survival of DLBCL cells. Surprisingly, specific knockdown of SIRT1/2/3 has no effect on DLBCL. Mechanistically, tenovin-6 increases the level of microtubule-associated protein 1 light chain 3B (LC3B)-II in a SIRT1/2/3- and p53-independent manner in DLBCL cell lines. Tenovin-6-mediated increase of LC3B-II is through inhibition of classical autophagy pathway. Furthermore, inhibition of the autophagy pathway by using other inhibitors or by knocking down key genes in the pathway impairs cell proliferation and survival of DLBCL cells. These results indicate that targeting the autophagic pathway could be a novel therapeutic strategy for DLBCL and that precaution should be taken to interpret data where tenovin-6 was used as an inhibitor of sirtuins.


BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress.
Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death in both animal and plant cells. We characterized mice in which the bi-1 gene was ablated. Cells from BI-1-deficient mice, including fibroblasts, hepatocytes, and neurons, display selective hypersensitivity to apoptosis induced by ER stress agents (thapsigargin, tunicamycin, brefeldin A), but not to stimulators of mitochondrial or TNF/Fas-death receptor apoptosis pathways. Conversely, BI-1 overexpression protects against apoptosis induced by ER stress. BI-1-mediated protection from apoptosis induced by ER stress correlated with inhibition of Bax activation and translocation to mitochondria, preservation of mitochondrial membrane potential, and suppression of caspase activation. BI-1 overexpression also reduces releasable Ca(2+) from the ER. In vivo, bi-1(-/-) mice exhibit increased sensitivity to tissue damage induced by stimuli that trigger ER stress, including stroke and tunicamycin injection. Thus, BI-1 regulates a cell death pathway important for cytopreservation during ER stress.


Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiency.
Seventeen patients with antibody immunodeficiency (9 subclass IgG immunodeficiencies, 8 common variable immunodeficiencies) and clinically unambiguous immunodeficiency symptomatology participated in the study with 14 healthy donors. The patients were given regular intravenous immunoglobulin (IVIG) infusions with Endobulin. Blood was collected before and 7 days after infusion of the usual IVIG dose. Mononuclear cells were isolated from peripheral blood (PBMC) of the patients by Ficoll-Paque gradient centrifugation. In order to monitor the ability to inhibit or activate polyclonal production of immunoglobulins in vitro, we stimulated PBMC with pokeweed mitogen (PWM) and with a mixture of pokeweed mitogen + concanavalin A (PWM+ConA). We found that an immunomodulatory effect of IVIG persists in vitro even one week after infusion. Polyclonally stimulated IgA and IgM production was suppressed by IVIG infusion mainly in patients with IgG subclass deficiency. The positive stimulatory effect of IVIG infusion on IgG production was confirmed. The IgG production increased in vitro after infusion in both groups of patients and was significantly higher than in healthy donors. Co-stimulation of PWM-stimulated cells with ConA caused an inhibition of immunoglobulin release in normal healthy donors. The infusion supported the capability of ConA to inhibit IgG production in vitro in patients with IgG subclass deficiency, whereas an increase in IgG production with PWM+ConA stimulation after infusion was found in CVID patients. We assume that lymphocytes activated by ConA produce suppressive factors, which can be affected by the IVIG infusion and which can have both an immunostimulatory and an immunosuppressive effect.


Novel high-resolution targeted sequencing of the cervicovaginal microbiome.
The cervicovaginal microbiome (CVM) plays a significant role in women's cervical health and disease. Microbial alterations at the species level and characteristic community state types (CST) have been associated with acquisition and persistence of high-risk human papillomavirus (hrHPV) infections that may result in progression of cervical lesions to malignancy. Current sequencing methods, especially most commonly used multiplex 16S rRNA gene sequencing, struggle to fully clarify these changes because they generally fail to provide sufficient taxonomic resolution to adequately perform species-level associative studies. To improve CVM species designation, we designed a novel sequencing tool targeting microbes at the species taxonomic rank and examined its potential for profiling the CVM. We introduce an accessible and practical circular probe-based RNA sequencing (CiRNAseq) technology with the potential to profile and quantify the CVM. In vitro and in silico validations demonstrate that CiRNAseq can distinctively detect species in a mock mixed microbial environment, with the output data reflecting its ability to estimate microbes' abundance. Moreover, compared to 16S rRNA gene sequencing, CiRNAseq provides equivalent results but with improved sequencing sensitivity. Analyses of a cohort of cervical smears from hrHPV-negative women versus hrHPV-positive women with high-grade cervical intraepithelial neoplasia confirmed known differences in CST occurring in the CVM of women with hrHPV-induced lesions. The technique also revealed variations in microbial diversity and abundance in the CVM of hrHPV-positive women when compared to hrHPV-negative women. CiRNAseq is a promising tool for studying the interplay between the CVM and hrHPV in cervical carcinogenesis. This technology could provide a better understanding of cervicovaginal CST and microbial species during health and disease, prompting the discovery of biomarkers, additional to hrHPV, that can help detect high-grade cervical lesions.


Herbicide bioremediation: from strains to bacterial communities.
There is high demand for herbicides based on the necessity to increase crop production to satisfy world-wide demands. Nevertheless, there are negative impacts of herbicide use, manifesting as selection for resistant weeds, production of toxic metabolites from partial degradation of herbicides, changes in soil microbial communities and biogeochemical cycles, alterations in plant nutrition and soil fertility, and persistent environmental contamination. Some herbicides damage non-target microorganisms via directed interference with host metabolism and via oxidative stress mechanisms. For these reasons, it is necessary to identify sustainable, efficient methods to mitigate these environmental liabilities. Before the degradation process can be initiated by microbial enzymes and metabolic pathways, microorganisms need to tolerate the oxidative stresses caused by the herbicides themselves. This can be achieved via a complex system of enzymatic and non-enzymatic antioxidative stress systems. Many of these response systems are not herbicide specific, but rather triggered by a variety of substances. Collectively, these nonspecific response systems enhance the survival and fitness potential of microorganisms. Biodegradation studies and remediation approaches have relied on individually selected strains to effectively remediate herbicides in the environment. Nevertheless, it has been shown that microbial communication systems that modulate social relationships and metabolic pathways inside biofilm structures among microorganisms are complex; therefore, use of isolated strains for xenobiotic degradation needs to be enhanced using a community-based approach with biodegradation pathway integration. Bioremediation efforts can use omics-based technologies to gain a deeper understanding of the molecular complexes of bacterial communities to achieve to more efficient elimination of xenobiotics. With this knowledge, the possibility of altering microbial communities is increased to improve the potential for bioremediation without causing other environmental impacts not anticipated by simpler approaches. The understanding of microbial community dynamics in free-living microbiota and those present in complex communities and in biofilms is paramount to achieving these objectives. It is also essential that non-developed countries, which are major food producers and consumers of pesticides, have access to these techniques to achieve sustainable production, without causing impacts through unknown side effects.


Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.
Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis. The serologic hallmark of PBC is the presence of antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex. The mechanisms by which (and if) such antibodies produce liver tissue injury are unknown. However, the presence of these antibodies has allowed detailed immunological definition of the antigenic epitopes, the nature of reactive autoantibodies and the characterization of T-cell responses. Several mechanisms may now be proposed regarding the immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and intracellular interaction between the IgA class of antimitochondrial antibodies and mitochondrial autoantigens. There are major questions which remain unanswered, including, of course, etiology, but also the reasons for female predominance, the absence of PBC in children, the relative ineffectiveness of immunosuppressive drugs, and the specific role of mitochondrial antigens. The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.


Low-molecular weight plasma proteome analysis using centrifugal ultrafiltration.
The low-molecular weight fraction (LMF) of the human plasma proteome is an invaluable source of biological information, especially in the context of identifying plasma-based biomarkers of disease. This protocol outlines a standardized procedure for the rapid/reproducible LMF profiling of human plasma samples using centrifugal ultrafiltration fractionation, followed by 1D-SDS-PAGE separation and nano-LC-MS/MS. Ultrafiltration is a convective process that uses anisotropic semipermeable membranes to separate macromolecular species on the basis of size. We have optimized centrifugal ultrafiltration for plasma fractionation with respect to buffer and solvent composition, centrifugal force, duration and temperature to facilitate >95% recovery, and enrichment of low-M (r) components from human plasma. Using this protocol, >260 unique peptides can be identified from a single plasma profiling experiment using 100 μL of plasma (Greening and Simpson, J Proteomics 73:637-648, 2010). The efficacy of this method is demonstrated by the identification, for the first time, of several plasma proteins (e.g., protein KIAA0649 (Q9Y4D3), rheumatoid factor D5, serine protease inhibitor A3, and transmembrane adapter protein PAG) previously not reported in extant high-confidence Human Proteome Organization Plasma Proteome Project datasets.


Graphene in therapeutics delivery: Problems, solutions and future opportunities.
Graphene based nanomaterials are being used experimentally to deliver therapeutic agents to cells or tissues both in vitro and in vivo. However, substantial challenges remain before moving to safe and effective use in humans. In particular, it is recognised that graphene molecules undergo complex interactions with solutes, proteins or cellular systems within the body, and that these interactions impact significantly on the behaviour or toxicity of the molecule. Approaches to overcome these problems include modification of the graphene or its combination with other molecules to accentuate favourable characteristics or modify adverse interactions. This has led to an emerging role for graphene as one part of highly-tailored multifunctional delivery vehicles. This review examines the knowledge that underpins present approaches to exploit graphene in therapeutics delivery, discussing both favourable and unfavourable aspects of graphene behaviour in biological systems and how these may be modified; then considers the present place of the molecule and the challenges for its further development.


Electrochemical Properties of Laser-Printed Multilayer Anodes for Lithium-Ion Batteries.
New electrode architectures promise huge potential for improving batteries' electrochemical properties, such as power density, energy density, and lifetime. In this work, the use of laser-induced forward transfer (LIFT) was employed and evaluated as a tool for the development of advanced electrode architectures. For this purpose, it was first confirmed that the printing process has no effect on the transferred battery material by comparing the electrochemical performance of the printed anodes with state-of-the-art coated ones. For this, polyvinylidene fluoride (PVDF) was used as a binder and n-methyl-2-pyrrolidone (NMP) as a solvent, which is reported to be printable. Subsequently, multilayer electrodes with flake-like and spherical graphite particles were printed to test if a combination of their electrochemical related properties can be realized with measured specific capacities ranging from 321 mAh·g-1 to 351 mAh·g-1. Further, a multilayer anode design with a silicon-rich intermediate layer was printed and electrochemically characterized. The initial specific capacity was found to be 745 mAh·g-1. The presented results show that the LIFT technology offers the possibility to generate alternative electrode designs, promoting research in the optimization of 3D battery systems.


Open adrenalectomy surgery: an obsolete technique? About a case of Conn's syndrome.
The authors report a case of an adenoma of Conn brought to their attention and treated by them in open surgery. The forms of primary hyperaldosteronism are essentially referable: 1) to the adenoma producing aldosterone, responsive to the ACTH, which represents the most common form (60-70%), responsive to surgery and with full recovery (70%) of cases. 2) to the bilateral hyperplasia, responsive to the angiotensine II, 25-30% of the cases, susceptible to medical therapy with receptorial antagonists of aldosterone. The diagnosis, based on the suspected clinical symptomatology, is determined by laboratory and imaging studies. Laparoscopic surgery is the orientation for this pathology. Comparative studies have shown that laparoscopic surgery adopted by experienced surgeons can treat the adrenal pathology in a mininvasive way, with good results for effectiveness and safety, and for these reasons the laparoscopic treatment is considered the gold standard for this pathology. But adrenal pathology is rare, 4% in people suffering hypertension, and from 0.35 to 4.4% in tumours. There are, however, only a few medical centres which have the possibility of observing a high number of such a pathology with a consequent accepted learning curve for laparoscopic treatment. For this reason the authors believe that "open" surgery in adrenal pathology is not obsolete and that surgical teams which have experience in retroperitoneal pathology must intervene adopting a laparotomic approach, with the aim to operate the sick person, who totally confides himself to the surgeon, in an appropriate way.


Prevalence and genotypic diversity of cervical human papillomavirus infection among women from an urban center in Brazil.
Human papillomavirus (HPV) infection is a common viral sexually transmitted infection and the main cause of cervical cancer in women worldwide. Epidemiological data on the prevalence of HPV in a given population is essential for the establishment of effective prevention strategies. The aim of this study was to determine HPV prevalence in women who attended a public health service within an urban center in Brazil. Cervical samples were collected from 337 women recruited from a primary public health care clinic in the city of Cruz Alta located in Rio Grande do Sul, the southernmost State of Brazil. Samples were analyzed for HPV DNA and with Pap smear screening tests. HPV was detected in 114 (34%) women. HPV type analysis revealed that 95 (83.3%) of those represented infections with a single genotype, while 19 (16.7%) were mixed genotype infections. High- and low-risk HPV genotypes were detected in 83 (72.8%) and 48 (42.1%) samples, respectively. Furthermore, a great diversity of HPV genotypes was observed (18 high-risk, 12 low-risk, and 1 indeterminate). The most commonly identified low-risk types were candHPV62 (7.9%) and 61 (5.3%), while the most common high-risk types were 16 and 33 (8.8% each). Abnormal cytology was observed in 10 (3.0%) women, 9 of which were infected with HPV. Of the remaining 327 women with normal cytology results, 107 (32.7%) were positive for HPV DNA. HPV infection was correlated with younger age (less than 40 years), a first Pap smear, and other vaginal infections.


[MRI in patients with cardiac pacemakers: in vitro and in vivo evaluation at 0.5 tesla].
MRI is currently regarded as absolutely contraindicated in patients with implanted cardiac pacemakers. In this prospective study safety and feasibility of MRI in patients with new generation pacemakers (PM) was evaluated in vitro and in vivo. 14 PM models in vitro and 18 patients with implanted new generation PM underwent a MRI exam at 0.5 Tesla with standard spin, turbo spin, and gradient echo (FFE) sequences under continuous ECG-monitoring. PM inquiry was performed before and after the MRI exam, including assessment of stimulation thresholds. In the static magnetic field all PM switched to the asynchronous mode due to activation of the Reed switch, resulting in continuous pacing at a fixed rate. In three PM models in vitro, however, after activation of the Reed switch, there was a software-induced switch back to the demand mode. In these PM inhibition and triggering were observed after starting the MRI scan due to influence of the pulsed magnetic fields. PM program changes, damage of PM components, dislocation/torque of the PM and rapid pacing of the PM were observed neither in vitro nor in vivo. Atrial and ventricular stimulation thresholds remained unchanged. MRI at 0.5 Tesla should not be regarded as absolutely contraindicated in patients with implanted new generation PM. However, knowledge of the behaviour of the specific PM model in static and pulsed magnetic fields is required, if necessary also changes of the PM program prior to the MRI exam, continuous ECG monitoring and cardiological stand-by.


A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.


No need to search for the source of haematogenous arthroplasty infections.
Prosthetic joint infections (PJI) may be a potential sentinel event for an unknown neoplastic or infectious source in elderly patients. However, the value and cost-effectiveness of investigations to determine the origin of these infections is unknown. Retrospective study at Geneva University Hospitals, evaluating associated medical examinations performed in search of the origin of all presumed surgical site and haematogenous arthroplasty infections. A total of 182 PJI were found in 182 patients (median age 75 years). Seventy PJI (38%) were classified as probably haematogenous, occurring more than 2 years post-implantation, with 27 (15%) due to Gram-negative pathogens. Overall, the origin of PJI was found solely by admission history in 28 cases (15%). Among the remaining 154 cases, no remote origin could be detected despite 17 echocardiograms, 17 other sonograms, 49 chest x-rays, 23 computed tomograms, 107 urinary cultures, 11 endoscopies, 9 scintigraphies and 31 medical specialist consultations. The average cost of these exams was 675 Swiss francs (845 US$) per PJI. At long-term follow-up six patients were found to have developed a neoplasm, of which only one (hepatocellular carcinoma after PJI due to Streptococcus bovis) could eventually be attributed to prior infection. From an epidemiologic point of view, patient history is the best way to predict the origin of PJI. Blind additional radiographic or endoscopic exams are costly, inconclusive and do not contribute to the management of these cases.


Evaluating the effect of resident involvement on physician productivity in an academic general internal medicine practice.
To estimate the effect of resident involvement across three years of resident training in a general internal medicine practice on the productivity of faculty physicians at Rush University Medical Center. Productivity was measured by work relative value units (RVUs) per clinical full-time equivalent attending physician generated in the ambulatory practice between July 2004 and June 2005. Random-effects linear regression models were used to estimate the impact of resident involvement by year of resident on attending physician productivity, controlling for faculty physician demographic characteristics. Resident involvement significantly reduced physician productivity. Each first-year resident was associated with a loss of 0.81 work RVUs per attending physician per four-hour clinic session. Each second-year and third-year resident was associated with a loss of 0.88 work RVUs and 0.49 work RVUs per attending physician per session, respectively. The loss per resident per session translated into a loss of 2,447 work RVUs for the year for the practice. Physician productivity significantly decreased with resident involvement, but the impact varied across resident training years. The loss in productivity for the year was $164,000 in revenue or $49 per resident per session. Results of this study provide insight into the importance of considering teaching responsibilities when establishing productivity targets, particularly in practices where the level of teaching involvement varies across faculty physicians. External benchmarks with other general internal medicine practices would be more accurate when resident teaching responsibilities are accounted for.