Antibiotic prophylaxis in obstetric and gynaecological procedures: a review.
Surgical site infections are a common complication of obstetric and gynaecological surgeries; up to 10% of gynaecological patients undergoing an operative procedure will develop a surgical site infection. In surgeries with high rates of post-operative infection, antibiotic prophylaxis (using an antibiotic with an appropriate microbiological spectrum and administered in a timely manner) can play a major role in improving outcomes. This review examines the medical literature to assess the indications and appropriate antibiotic choices for prophylaxis to prevent surgical site infection in obstetric and gynaecological surgery. For some procedures, such as caesarean section, surgical termination of pregnancy and hysterectomy, antibiotic prophylaxis is clearly indicated. For other procedures, such as insertion of an intrauterine device, medical termination of pregnancy and laparoscopy, antibiotic prophylaxis is usually not required. For several other procedures where the evidence for antibiotic prophylaxis is unclear or inadequate, we discuss the current evidence for and against prophylaxis. Guidelines for infective endocarditic prophylaxis with surgery are also discussed.


Self-Reported Prevalence of Chronic Non-Communicable Diseases in Relation to Socioeconomic and Educational Factors in Colombia: A Community-Based Study in 11 Departments.
Chronic non-communicable diseases are prevalent conditions in developing countries, such as Colombia. Several socioeconomic and educational factors have been associated with these pathologies. However, there is little country-specific information regarding the self-reported prevalence of chronic diseases and their association with the aforementioned factors in Colombia. To evaluate the current situation of chronic non-transmissible diseases in Colombia by self-report and to analyze its potential relationship with sociodemographic, economic and educational factors. This is a cross-sectional baseline sub-analysis from the prospective, standardized collaborative PURE study in Colombia. Participants were recruited between 2005 to 2009, in 11 departments of the country, and included 7,485 subjects of 35 to 70 years old. Questionnaires of self-reported chronic non-communicable diseases, and demographic, socioeconomic and educational variables were applied. Hypertension was the most prevalent chronic condition reported with a prevalence of 22.2% (21.2%-23.1%, 95% CI), followed by diabetes with a prevalence of 5.7% (5.1%-6.2%, 95% CI), asthma 2.7% (2.2%-3.0%, 95% CI), coronary heart disease 2.4% (2.0%-2.7%, 95% CI), stroke and heart failure 1.5% (1.2%-1.8%, 95% CI) each, chronic obstructive pulmonary disease 1.2% (0.6%-1.5%, 95% CI), and cancer 1.2% (1.0%-1.5%, 95% CI). Among the study sample, 23.3% (22.4%-24.3%, 95% CI) reported having one chronic NCDs, and 6.4% (5.9%-7.0%, 95% CI) reported having multiple chronic NCDs. The prevalence of multiple NCDs increased significantly with age, was more common in those from households with higher income, whereas it was significantly lower in persons with high education.The central and central-east regions of the country are those with the higher prevalence of self-reported NCDs. The results of the current study indicate the presence of socioeconomic and educational inequalities in the distribution of chronic NCDs in the Colombian population.


Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort.
Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m2; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02-1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09-1.54; p = 0.003). The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.


A novel cross-validation strategy for artificial neural networks using distributed-lag environmental factors.
In recent years, machine learning methods have been applied to various prediction scenarios in time-series data. However, some processing procedures such as cross-validation (CV) that rearrange the order of the longitudinal data might ruin the seriality and lead to a potentially biased outcome. Regarding this issue, a recent study investigated how different types of CV methods influence the predictive errors in conventional time-series data. Here, we examine a more complex distributed lag nonlinear model (DLNM), which has been widely used to assess the cumulative impacts of past exposures on the current health outcome. This research extends the DLNM into an artificial neural network (ANN) and investigates how the ANN model reacts to various CV schemes that result in different predictive biases. We also propose a newly designed permutation ratio to evaluate the performance of the CV in the ANN. This ratio mimics the concept of the R-square in conventional statistical regression models. The results show that as the complexity of the ANN increases, the predicted outcome becomes more stable, and the bias shows a decreasing trend. Among the different settings of hyperparameters, the novel strategy, Leave One Block Out Cross-Validation (LOBO-CV), demonstrated much better results, and the lowest mean square error was observed. The hyperparameters of the ANN trained by the LOBO-CV yielded the minimum number of prediction errors. The newly proposed permutation ratio indicates that LOBO-CV can contribute up to 34% of the prediction accuracy.


Studies and perspectives of protein kinase C.
Protein kinase C, an enzyme that is activated by the receptor-mediated hydrolysis of inositol phospholipids, relays information in the form of a variety of extracellular signals across the membrane to regulate many Ca2+-dependent processes. At an early phase of cellular responses, the enzyme appears to have a dual effect, providing positive forward as well as negative feedback controls over various steps of its own and other signaling pathways, such as the receptors that are coupled to inositol phospholipid hydrolysis and those of some growth factors. In biological systems, a positive signal is frequently followed by immediate negative feedback regulation. Such a novel role of this protein kinase system seems to give a logical basis for clarifying the biochemical mechanism of signal transduction, and to add a new dimension essential to our understanding of cell-to-cell communication.


Care Considerations for the LGBTQ+ Patient With Cancer.
The LGBTQ+ community is considered a sexual and gender minority and is a medically underserved patient population because of healthcare disparities and specific health risks. Oncology clinical teams can provide skilled, respectful care to LGBTQ+ communities through the collection of sexual orientation and gender identity information, provision of a welcoming care environment, and appropriate use of inclusive language. Healthcare providers can play a role in prevention and detection of cancer and quality of life post-treatment through the understanding of the unique needs of the LGBTQ+ patient population as they navigate the healthcare system.


What is the Role of Epidural Injections in the Treatment of Lumbar Discogenic Pain: A Systematic Review of Comparative Analysis with Fusion.
Lumbar discogenic pain without pain mediated by a disc herniation, facet joints, or the sacroiliac joints, is common and often results in chronic, persistent pain and disability. After conservative treatment failure, injection therapy, such as an epidural injection, is frequently the next step considered in managing discogenic pain. The objective of this systematic review is to determine the efficacy of lumbar epidural injections in managing discogenic pain without radiculopathy, and compare this approach to lumbar fusion or disc arthroplasty surgery. A systematic review of randomized trials published from 1966 through October 2014 of all types of epidural injections and lumbar fusion or disc arthroplasty in managing lumbar discogenic pain was performed with methodological quality assessment and grading of evidence. The level of evidence was based on the grading of evidence criteria which, was conducted using 5 levels of evidence ranging from levels I to V. Based on a qualitative assessment of the evidence for both approaches, there is Level II evidence for epidural injections, either caudal or lumbar interlaminar. The available evidence suggests fluoroscopically directed epidural injections provide long-term improvement in back and lower extremity pain for patients with lumbar discogenic pain. There is also limited evidence showing the potential effectiveness of surgical interventions compared to nonsurgical treatments.


Impacted Maxillary Canine with Curved Apex: Three-Dimensional Guided Protocol for Autotransplantation.
Maxillary canines play a crucial role in dental and facial aspect, arch expansion, and efficient occlusion. When surgical exposure measures cannot be executed or the patient does not agree to take the treatment, autotransplantation should be considered. The aim of this case report was to describe a novel surgical technique using virtually planned three-dimensional (3D)-printed templates for guided apicoectomy and guided drilling of the recipient site for autotransplantation of an impacted maxillary canine with a curved apex. A 42-year-old man complaining of pain and increased mobility in the maxillary left primary canine came to the clinic. Autotransplantation of the impacted canine was completed using altered methods from guided implant surgery to manufacture 3D-printed templates. After a full-thickness mucoperiosteal flap elevation, the surgical template for the guided osteotomy and apicoectomy was inserted. This 3D-printed guide allowed the clinician to perform a quick and precise removal of the curved apex, providing an atraumatic extraction of the impacted canine throughout the cyst. Three further 3D surgical guides for implant burs and a 3D replica tooth were printed to modify the recipient socket. After the final position, the tooth was semi-rigid splinted to the adjacent teeth. Follow-up at 2 years showed complete regeneration of the palatal defect and remodeling of the bone surrounding the maxillary canine. Digitally planned procedures can facilitate the complex execution of an autotransplantation, reducing the treatment chair time and the morbidity for the patient as well as increasing the predictability of the result.


Applications of biotechnological methods to studies of protozoan parasites.
Biotechnology applies and extends the concepts and techniques of molecular biology. An overview of the applications and potential uses of the technology is presented for selected protozoan parasites. The areas reviewed include the characterization of protozoa, the production of their antigens, and the uses of hybridomas for studies of the antigens and host responses. In addition to the traditional methods of classification, parasitic protozoa are identified and characterized according to stable molecular markers. Peptidemes, zymodemes, antigens, schizodemes, and chromosomal complements define isolates and correlate with biological activities of the parasites. While antigens are typically extracted from parasites obtained from infected hosts or grown in vitro, they may be produced with in vitro translation systems, recombinant procedures with bacteria, or more recently developed techniques such as co-transformation and electroporation with eucaryotic cells. Monoclonal antibodies produced by B-cell hybridomas are used to identify parasites, antigens, epitopes, and the locations and functions of specific antigens. T-cell hybridomas may provide insights into cell-mediated immunity and interactions with the parasites.


Viral vector mediated expression of mutant huntingtin in the dorsal raphe produces disease-related neuropathology but not depressive-like behaviors in wildtype mice.
Huntington׳s disease (HD) is a neurodegenerative disorder caused by a mutation in the HTT gene (mHTT) encoding the protein huntingtin. An expansion in the gene׳s CAG repeat length renders a misfolded, dysfunctional protein with an abnormally long glutamine (Q) stretch at the N terminus that often incorporates into inclusion bodies and leads to neurodegeneration in many regions of the brain. HD is characterized by motor and cognitive decline as well as mood disorders, with depression being particularly common. Approximately 40% of the HD population suffers from depressive symptoms. Because these symptoms often manifest a decade or more prior to the knowledge that the person is at risk for the disease, a portion of the early depression in HD appears to be a consequence of the pathology arising from expression of the mutant gene. While the depression in HD patients is often treated with serotonin agonists, there is scant experimental evidence that the depression in HD responds well to these serotonin treatments or in a similar manner to how non-HD depression tends to respond. Additionally, at very early sub-threshold depression levels, abnormal changes in several neuronal populations are already detectable in HD patients, suggesting that a variety of brain structures may be involved. Taken together, the serotonin system is a viable candidate. However, at present there is limited evidence of the precise nuclei or circuits that play a role in HD depression. With this in mind, the current study was designed to control for the widespread brain neuropathology that occurs in HD and in transgenic mouse models of HD and focuses specifically on the influence of the midbrain dorsal raphe nucleus (DRN). The DRN provides the majority of the serotonin to the forebrain and exhibits cell loss in non-HD depression. Therefore, we employed a viral vector delivery system to investigate whether the over-expression of mHTT in the DRN׳s ventral sub-nuclei alone is sufficient to produce depressive-like behaviors. Wildtype mice were injected with an adeno-associated virus (AAV2/1) encoding HTT containing either a pathogenic (N171-82Q) or control (N171-16Q) CAG repeat length into the ventral DRN and depressive-like behaviors and motor behaviors were assessed for 12 weeks post-surgery. Quantitative PCR and immunohistochemistry (IHC) verified positive transduction in the ventral aspects of the DRN, including the ventral sub-nucleus (DRv) and interfascicular sub-nucleus (DRif). IHC demonstrated microgliosis in and around the injection site and mHTT-positive inclusions in serotonin-producing neurons and a small percentage of astrocytes in animals injected with N171-82Q compared to controls. Moreover, N171-82Q injected mice showed a 75% reduction in cells that stained positive for the serotonin synthesis enzyme, tryptophan hydroxylase-2 (TPH2) compared to controls (p<0.05). Despite mHTT-mediated pathology in the DRv and DRif, no significant changes in depressive-like behavior were detected. Consequently, we conclude that 12 weeks of N171-82Q expression in the ventral sub-nuclei of the DRN of wildtype mice causes characteristic disease-related cellular neuropathology but is not sufficient to elicit depressive-like behaviors. Ongoing studies are investigating whether a larger injection volume that transfects a larger percentage of the DRN and/or a longer time course of mHTT expression might elicit depressive-like behaviors. Moreover, mHTT expression in other regions of the brain, such as the hippocampal dentate gyrus and/or the frontal cortex might be necessary to elicit HD depression. Together, these results may prove helpful in addressing which therapeutic and/or pharmacological strategies might be most efficacious when treating depressive symptomology in patients suffering from HD.


Towards a quantitative model of the post-synaptic proteome.
The postsynaptic compartment of the excitatory glutamatergic synapse contains hundreds of distinct polypeptides with a wide range of functions (signalling, trafficking, cell-adhesion, etc.). Structural dynamics in the post-synaptic density (PSD) are believed to underpin cognitive processes. Although functionally and morphologically diverse, PSD proteins are generally enriched with specific domains, which precisely define the mode of clustering essential for signal processing. We applied a stochastic calculus of domain binding provided by a rule-based modelling approach to formalise the highly combinatorial signalling pathway in the PSD and perform the numerical analysis of the relative distribution of protein complexes and their sizes. We specified the combinatorics of protein interactions in the PSD by rules, taking into account protein domain structure, specific domain affinity and relative protein availability. With this model we interrogated the critical conditions for the protein aggregation into large complexes and distribution of both size and composition. The presented approach extends existing qualitative protein-protein interaction maps by considering the quantitative information for stoichiometry and binding properties for the elements of the network. This results in a more realistic view of the postsynaptic proteome at the molecular level.


Flexing the principal gradient of the cerebral cortex to suit changing semantic task demands.
Understanding how thought emerges from the topographical structure of the cerebral cortex is a primary goal of cognitive neuroscience. Recent work has revealed a principal gradient of intrinsic connectivity capturing the separation of sensory-motor cortex from transmodal regions of the default mode network (DMN); this is thought to facilitate memory-guided cognition. However, studies have not explored how this dimension of connectivity changes when conceptual retrieval is controlled to suit the context. We used gradient decomposition of informational connectivity in a semantic association task to establish how the similarity in connectivity across brain regions changes during familiar and more original patterns of retrieval. Multivoxel activation patterns at opposite ends of the principal gradient were more divergent when participants retrieved stronger associations; therefore, when long-term semantic information is sufficient for ongoing cognition, regions supporting heteromodal memory are functionally separated from sensory-motor experience. In contrast, when less related concepts were linked, this dimension of connectivity was reduced in strength as semantic control regions separated from the DMN to generate more flexible and original responses. We also observed fewer dimensions within the neural response towards the apex of the principal gradient when strong associations were retrieved, reflecting less complex or varied neural coding across trials and participants. In this way, the principal gradient explains how semantic cognition is organised in the human cerebral cortex: the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared.


A study of using a simple 2D image analysis method to monitor the surface area of hypertrophic scars on hand during pressure therapy.
Hypertrophic scars are usually evaluated based on scar assessment scales such as Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS) which are difficult in recording small changes in the scar conditions over time. This study adopts a simple method to quantify the size of hypertrophic scars on hands by using a camera and tripod set-up for image capturing and a free software, ImageJ, for analysis. The ability to record the changes in scars condition and healing progress of this method were investigated. Four hypertrophic scar samples on the hands were captured at 8 time-points during 24-week of pressure therapy. Three operators were trained for 2h to use the software and then carried out image analysis on 32 scar images to obtain the surface areas of the hand and the scars and repeat the entire measurement for 3 times. The results show that the measured scar surface areas have good intra-operator reliability with an intraclass correlation coefficient (ICC) of 0.943 (0.922, 0.96) and moderate inter-operator reliability with an ICC of 0.554 (0.063, 0.795). No significant within-subject effect of the repeat of measurements (p>0.05) and between-subject effect of the three operators (p>0.05) were found on the scar area measurements and the proportion of the scars on hands but significant differences were found between different time-points of the image capturing (p<0.05). The image analysis method is more sensitive to the change of scars conditions over time than the VSS record. This is an economical and relatively easy method to quantify the changes in the hypertrophic scars which could be useful for monitoring the progress of therapy and encourage treatment compliance.


Implementation status of prediction models for type 2 diabetes.
Although a prediction model is expected to identify individuals who are at a high risk of type 2 diabetes, the implementation status of prediction models has not been well examined. Our review indicates that the implementation of predictive models in practice remains low despite the increase in models being developed.


The mammalian transcriptional repressor RBP (CBF1) regulates interleukin-6 gene expression.
The cellular interleukin-6 (IL-6) gene contains a target site for the mammalian transcriptional repressor RBP. The target site is contained within the interleukin response element (ILRE), which mediates IL-6 activation by NF-kappa B. In this study, we show by using transient-expression assays that RBP represses activated transcription from the IL-6 gene. The presence and position of the RBP target site are crucial in mediating repression by RBP. While RBP binds within the ILRE, it does not target NF-kappa B alone; nonetheless, NF-kappa B binding to the ILRE is required for repression. Our results indicate that RBP represses coactivation by NF-kappa B and another cellular transcription factor, C/EBP-beta.


Identification of New Tumor Suppressor Genes in Triple-Negative Breast Cancer.
Although genomic sequencing has provided a better understating of the genetic landmarks in triple-negative breast cancer (TNBC), functional validation of candidate cancer genes (CCG) remains unsolved. In this study, we used a transposon mutagenesis strategy based on a two-step sleeping beauty (SB) forward genetic screen to identify and validate new tumor suppressors (TS) in this disease. We generated 120 siRNAs targeting 40 SB-identified candidate breast cancer TS genes and used them to downregulate expression of these genes in four human TNBC cell lines. Among CCG, whose SB-mediated genetic mutation resulted in increased cellular proliferation in all cell lines tested, the genes ADNP, AP2B1, TOMM70A, and ZNF326 showed TS activity in tumor xenograft studies. Subsequent studies showed that ZNF326 regulated expression of multiple epithelial-mesenchymal transition and cancer stem cell (CSC) pathway genes. It also modulated expression of TS genes involved in the regulation of migration and cellular invasion and was a direct transcriptional activator of genes that regulate CSC self-renewal. ZNF326 expression associated with TNBC patient survival, with ZNF326 protein levels showing a marked reduction in TNBC. Our validation of several new TS genes in TNBC demonstrate the utility of two-step forward genetic screens in mice and offer an invaluable tool to identify novel candidate therapeutic pathways and targets. Cancer Res; 77(15); 4089-101. ©2017 AACR.


VegaMC: a R/bioconductor package for fast downstream analysis of large array comparative genomic hybridization datasets.
Identification of genetic alterations of tumor cells has become a common method to detect the genes involved in development and progression of cancer. In order to detect driver genes, several samples need to be simultaneously analyzed. The Cancer Genome Atlas (TCGA) project provides access to a large amount of data for several cancer types. TGCA is an invaluable source of information, but analysis of this huge dataset possess important computational problems in terms of memory and execution times. Here, we present a R/package, called VegaMC (Vega multi-channel), that enables fast and efficient detection of significant recurrent copy number alterations in very large datasets. VegaMC is integrated with the output of the common tools that convert allele signal intensities in log R ratio and B allele frequency. It also enables the detection of loss of heterozigosity and provides in output two web pages allowing a rapid and easy navigation of the aberrant genes. Synthetic data and real datasets are used for quantitative and qualitative evaluation purposes. In particular, we demonstrate the ability of VegaMC on two large TGCA datasets: colon adenocarcinoma and glioblastoma multiforme. For both the datasets, we provide the list of aberrant genes which contain previously validated genes and can be used as basis for further investigations. VegaMC is a R/Bioconductor Package, available at http://bioconductor.org/packages/release/bioc/html/VegaMC.html. email@example.com Supplementary data are available at Bioinformatics online.


Effects of calcitonin on cytosolic Ca in a suspension of rabbit medullary thick ascending limb tubules.
A basal level of cytosolic free Ca (Caf) of 112 +/- 7 nM (n = 15) was measured in rabbit medullary thick ascending limb tubules that were loaded with the fluorescent Ca indicator quin 2. Calcitonin addition (10(-6) M) caused a greater than twofold increase in Caf. The KD for calcitonin stimulation of Caf was 8 X 10(-11) M. The rise in Caf had a half time of approximately 1.5 min. Neither parathyroid hormone (10(-6) M), dibutyryladenosine 3',5'-cyclic monophosphate (10(-4) M), nor forskolin (2 X 10(-5) M) had any significant effect on Caf levels, consistent with the rise in Caf being independent of an elevation in adenosine 3',5'-cyclic monophosphate. The effects of ouabain and the mitochondrial uncoupler, 1799, were also tested to obtain further information regarding the regulation of Caf. Ouabain (10(-4) M) caused no significant elevation in Caf; in contrast, 15 min of incubation with 1799 (10(-5) M) produced a twofold increase in Caf.


Speciation of metal-based nanomaterials in human serum characterized by capillary electrophoresis coupled to ICP-MS: a case study of gold nanoparticles.
The development and optimization of a versatile analytical system for the speciation analysis of metal-containing nanoscale materials in blood serum is reported herein. Based on capillary electrophoresis (CE) interfaced with inductively coupled plasma mass spectrometry (ICP-MS), the method was shown to be feasible to investigate the interactions between serum proteins and gold nanoparticles of potential medicinal use, which are their first and foremost occurrence upon their entry into the circulatory system. To improve the separation resolution between the intact nanoparticles and different protein conjugates, the CE system was optimized with an emphasis on compatibility with physiological conditions, avoiding aggregation effects, and analyte recovery. Optimization allowed also for acquiring the acceptable figures of merit such as migration time and peak area precision of 1.0-6.4% and 2.4-6.9%, respectively, detection limits in the range of 0.8-1.0 μg L(-1) Au, and capillary recoveries on the order of 86-97%, depending on the nanoparticle size and conjugate type. We sytematically investigated the role of size in mediating protein adsorption to gold nanoparticles in a real-serum environment. At the initial stage of surface coating, the speciation of smaller particles (5 and 10 nm) was found to be dominated by albumin, transferrin (both in apo- and holo-form) playing the secondary role in developing the protein corona. For 20 and 50 nm nanoparticles, the contribution of transferrin is initially comparable; however, with time it becomes replaced by albumin. The time of attaining equilibrium adsorption is also a function of particle size but for the whole size range investigated, albumin is the only equilibrium binding partner. These principal findings prove that for metal-based nanomaterials in general, serum protein conjugates could be variable in composition depending on the protein abundance and binding affinity, as well as the residence time in the bloodstream.


A polymeric iron oxide nanocomplex loaded with sulfasalazine: an approach for inducing ferritinophagy-assisted ferroptosis for anti-cancer therapy.
The approach of using ferroptosis to treat cancer has garnered attention due to its promising potential. However, the effectiveness of this therapy is often limited by the inherent redox system in cancer cells and the presence of ferritin as an iron ion storage molecule. To address this issue, we have designed a polymeric iron oxide nanocomplex loaded with sulfasalazine as a ferritinophagy-assisted ferroptosis inducing agent. The nanocomplex is based on a pH-responsive drug releasing platform that enables improved ferroptosis anti-cancer therapy. The nanocomplex was synthesized using polymerized phenylboronic acid decorated with iron oxide and further loaded with sulfasalazine by interacting with polymerized phenylboronic acid. Upon entering cancer cells, the nanocomplex releases sulfasalazine at the lysosomal acidic pH, which causes the complex to degrade into the labile iron ion (Fe2+). This process inhibits the production of GSH and reproduces the labile iron ion by degrading ferritin. As a result, an excess iron ion pool is formed, and the facilitated Fenton reaction induces an improved ferroptosis anti-cancer effect. Moreover, our research has demonstrated that the nanocomplex effectively regresses tumors, thereby representing significant inhibition of tumor growth using in vivo models. We believe that this ferritinophagy-assisted ferroptosis strategy using the nanocomplex provides a promising solution for iron-based anti-cancer therapy.


Overcoming drug impurity challenges in amorphous solid dispersion with rational development of biorelevant dissolution-permeation method.
Hot-melt extrusion is often used to prepare amorphous solid dispersion to overcome low drug solubility and enhance bio-performance of the formulation. Due to the uniqueness of each drug - polymer combination and its physico-chemical properties, setting the appropriate HME barrel temperature, feed rate and screw speed ensures drug amorphization, absence of residual crystallinity, absence of water, and a suitable drug release profile. In this research, samples with BCS II/IV model drug and PVP/VA polymer were prepared to evaluate the impact of HME process parameters, incoming drug form (anhydrous vs. hydrate), and drug supplier (i.e., impurity profile), on biorelevant drug release. This study provides a relationship between observed in vitro supersaturation and precipitation behavior of amorphous solid dispersion formulation with in vivo results, on patients, by using the acceptor profile of side-by-side dissolution-permeation apparatus. An in vitro dissolution method, in small volumes, in an apparatus with paddles and dissolution-permeation side-by-side method was developed on the MicroFlux™ apparatus to assess if the differences observed in vitro bears relevance to the bioequivalence outcome in vivo. The former was used to guide the generic drug product development due to high discriminatory strength, while the latter was biorelevant, due to the inclusion of the second compartment assuring absorptive environment to capture the impact of supersaturation and subsequent precipitation on bioavailability. Bio-relevancy of the in vitro method was confirmed with the in vivo dog study and clinical study on patients, and an in vitro - in vivo correlation was established. For the investigated BCS II/IV drug, this research highlights the importance of considering supersaturation and formation of colloidal species during amorphous solid dispersion release testing to assure product quality, safety and efficacy.


Analysis and preparation of Bartonella bacilliformis antigens.
Twenty-four antigens of Bartonella bacilliformis, a bacterium which causes bartonellosis in residents of high altitude valleys of the Andes, were identified by immunoblot and immunoprecipitation using rabbit anti-Bartonella sera as well as sera of patients. The antigens were designated according to their relative molecular mass which ranged from 16 to 160 kDa. Twelve antigens were detected by antibodies in sera of bartonellosis patients using immunoblot, of which six antigens were detected by immunoprecipitation. Antigens 25, 46, 65, 75, 99, and 160 were identified as probable cell wall antigens. Antigens 50, 65, and 75 detected long-persisting antibodies. Crude Bartonella antigen applied to ELISA reacted with anti-Chlamydia psittaci antibody as well as with antibody of unknown identity in human sera, whereas immunoblot and immunoprecipitation with Triton soluble antigens revealed Bartonella-specific results. Seven Bartonella antigens were prepared by high performance liquid chromatography of which one antigen (48 kDa) reacted Bartonella-specific when applied to ELISA. It was concluded that specificity of antibody determination with crude Bartonella antigen should be confirmed by either immunoblot or immunoprecipitation.


Critical role for the Oct-2/OCA-B partnership in Ig-secreting cells.
B and T lymphocytes arise from a common precursor in the bone marrow, but ultimately acquire very different functions. The difference in function is largely attributable to the expression of tissue-specific transcription factors that activate discrete sets of genes. In previous studies we and others have shown that the specialized genes expressed by Ig-secreting cells cease transcription when these cells are fused to a T lymphoma. The extinguished genes include those encoding Ig, J chain, and the transcription factors Oct-2, PU.1, and the coactivator OCA-B. Remarkably, if we sustain Oct-2 expression during cell fusion, all the other tissue-specific genes of the Ig-secreting cell simultaneously escape silencing. This suggests that Oct-2 plays a central role in maintaining the gene expression program of these cells. In the present studies we have investigated the roles of the transcription factor PU.1 and the coactivator OCA-B within the hierarchy of regulatory factors that sustain Ig-secreting cell function. Our results show that OCA-B and Oct-2 are regulatory partners in this process and that PU.1 plays a subordinate role at this cell stage.


Gold nanoparticles for biology and medicine.
Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic-level precision. This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates. There are now many examples of highly sensitive and selective assays based upon gold nanoconjugates. In recent years, focus has turned to therapeutic possibilities for such materials. Structures which behave as gene-regulating agents, drug carriers, imaging agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule-based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications.


Mental health and psychosocial support for families of missing persons in Sri Lanka: A retrospective cohort study.
The International Committee of the Red Cross (ICRC) has developed its 'Accompaniment model' to address the multi-faceted needs of relatives of people who go missing during armed conflict. In Sri Lanka an Accompaniment Programme was launched in 2015 for the relatives of the more than 16,000 missing persons who remain unaccounted for. One thousand seven hundred eighty-three relatives who took part in the mental health and psychosocial support (MHPSS) component of the ICRC's Accompaniment Programme in Sri Lanka between April 2016 and August 2017 were offered eight peer-support group sessions, individual home visits, referrals to local services, and commemoration events to pay tribute to their missing relatives. Symptoms of anxiety and depression (using the HADS scale), somatic difficulties (using the BSI scale) and daily functioning (ICRC scale) were assessed before and after the MHPSS intervention. Prior to receiving support, Tamil and Muslim ethnicity, ≥60 years of age and civilian status were predictors of severe symptoms of anxiety; Tamil ethnicity, ≥50 years of age and being the mother of a missing person were predictors of severe symptoms of depression; and ≥ 50 years of age and severe symptoms of anxiety and depression were predictors of severe somatic difficulties. After receiving support, the vast majority of the relatives of missing persons showed reduced levels of anxiety (81%), depression (79%) and somatic pain (77%), as well as increased functioning (75%). Predictors of improvement following support were severe levels of distress at baseline and Tamil and Muslim ethnicity. In addition, attending at least three group sessions was a predictor of decreased anxiety, age group 51-60 was a predictor of decreased depression, female gender was a predictor of decreased somatic difficulties, and referrals were a predictor of increased functioning. The MHPSS component of the ICRC's Accompaniment Programme is a relevant approach to helping families to cope with not knowing the fate and whereabouts of their missing relatives, to reduce distress, to break their social isolation and to resume more functional lives. However, further research is needed, possibly through a controlled trial, to better establish the effectiveness of this approach.


Observation of extraordinary optical activity in planar chiral photonic crystals.
Control of light polarization is a key technology in modern photonics including application to optical manipulation of quantum information. The requisite is to obtain large rotation in isotropic media with small loss. We report on extraordinary optical activity in a planar dielectric on-waveguide photonic crystal structure, which has no in-plane birefringence and shows polarization rotation of more than 25 degrees for transmitted light. We demonstrate that in the planar chiral photonic crystal, the coupling of the normally incident light wave with low-loss waveguide and Fabry-Pérot resonance modes results in a dramatic enhancement of the optical activity.


Expression of cytosolic sulfotransferases in normal mammary epithelial cells and breast cancer cell lines.
Breast cancers require the presence of estrogens for the maintenance of growth at some time in the course of their development, as does normal breast tissue. Sulfation is an important process in the metabolism and inactivation of steroids, including estrogens, because the addition of the charged sulfonate group prevents the binding of the steroid to its receptor. Also, many of the therapeutic and chemopreventive agents used in the treatment of breast cancer are substrates for the sulfotransferases (STs). The activity and expression of four cytosolic STs, which are the human phenol-sulfating and monoamine-sulfating forms of phenol ST (PST), dehydroepiandrosterone ST, and estrogen ST (hEST), were assayed in normal breast cells and in breast cancer cell lines. ST activities and immunoreactivities were assayed in the estrogen receptor-positive human breast cancer cell lines ZR-75-1, T-47D and MCF-7; in the estrogen receptor-negative breast cancer cell lines BT-20, MDA-MB-468, and MDA-MB-231; and in normal human mammary epithelial cells. The PSTs were the most highly expressed ST activities in the breast cancer cell lines, although the levels of activity varied significantly. ZR-75-1 and BT-20 cells possessed the highest levels of activity of the human phenol-sulfating form of PST. The breast cancer cell lines showed only trace levels of dehydroepiandrosterone ST and hEST activities. In contrast, hEST was the only ST detectable in human mammary epithelial cells. Understanding the regulation of ST activity in these breast cancer and normal breast cell lines will improve our knowledge of the role of sulfation in breast cancer and provide a model with which to study the mechanism of action of estrogens in mammary cells.


Asthma in an urban population in Portugal: a prevalence study.
The prevalence and incidence of asthma are believed to be increasing but research on the true incidence, prevalence and mortality from asthma has met methodological obstacles since it has been difficult to define and diagnose asthma in epidemiological terms. New and widely accepted diagnostic criteria for asthma present opportunities for progress in this field. Studies conducted in Portugal have estimated the disease prevalence between 3% and 15%. Available epidemiological data present a significant variability due to methodological obstacles. To estimate the true prevalence of asthma by gender and age groups in the population of the area covered by one urban Health Centre in Portugal. An observational study was conducted between February and July 2009 at the Horizonte Family Health Unit in Matosinhos, Portugal. A random sample of 590 patients, stratified by age and gender was obtained from the practice database of registered patients. Data was collected using a patient questionnaire based on respiratory symptoms and the physician's best knowledge of the patient's asthma status. The prevalence of asthma was calculated by age and gender. Data were obtained from 576 patients (97.6% response rate). The mean age for patients with asthma was 27.0 years (95% CI: 20.95 to 33.16). This was lower than the mean age for non-asthmatics but the difference was not statistically significant. Asthma was diagnosed in 59 persons giving a prevalence of 10.24% (95% CI: 8.16 to 12.32). There was no statistically significant difference in the prevalence of asthma by gender. The prevalence of asthma found in the present study was higher than that found in some studies, though lower than that found in other studies. Further studies in other regions of Portugal are required to confirm these findings.


Langerhans cell histiocytosis mimicking molluscum contagiosum: A case series.
Langerhans cell histiocytosis (LCH) is a disorder characterized by accumulation of Langerhans-like cells in one or various organs. A correct staging work-up is essential since there are multiorgan presentations with a poor prognosis. We report three patients with LCH skin lesions mimicking molluscum contagiosum in association with both high and low risk organ involvement. This peculiar cutaneous presentation can be a clue for the diagnosis of LCH, a disease with potentially severe systemic involvement.


The functionality of the DC pair in a Rhodopsin Guanylyl Cyclase from Catenaria anguillulae.
Rhodopsin guanylyl cyclases (RGCs) belong to the class of enzymerhodopsins catalyzing the transition from GTP into the second messenger cGMP, whereas light-regulation of enzyme activity is mediated by a membrane-bound microbial rhodopsin domain, that holds the catalytic center inactive in the dark. Structural determinants for activation of the rhodopsin moiety eventually leading to catalytic activity are largely unknown. Here, we investigate the mechanistic role of the D283-C259 (DC) pair that are hydrogen bonded via a water molecule as a crucial functional motif in the homodimeric C. anguillulae RGC. Based on a structural model of the DC pair in the retinal binding pocket obtained by MD simulation, we analyzed formation and kinetics of early and late photocycle intermediates of the rhodopsin domain wild type and specific DC pair mutants by combined UV-Vis and FTIR spectroscopy at ambient and cryo-temperatures. By assigning specific infrared bands to S-H vibrations of C259 we are able to show that the DC pair residues are tightly coupled. We show that deprotonation of D283 occurs already in the inactive L state as a prerequisite for M state formation, whereas structural changes of C259 occur in the active M state and early cryo-trapped intermediates. We propose a comprehensive molecular model for formation of the M state that activates the catalytic moiety. It involves light induced changes in bond strength and hydrogen bonding of the DC pair residues from the early J state to the active M state and explains the retarding effect of C259 mutants.


Beneficial Effects of Silibinin Against Kainic Acid-induced Neurotoxicity in the Hippocampus in vivo.
Silibinin, an active constituent of silymarin extracted from milk thistle, has been previously reported to confer protection to the adult brain against neurodegeneration. However, its effects against epileptic seizures have not been examined yet. In order to investigate the effects of silibinin against epileptic seizures, we used a relevant mouse model in which seizures are manifested as status epilepticus, induced by kainic acid (KA) treatment. Silibinin was injected intraperitoneally, starting 1 day before an intrahippocampal KA injection and continued daily until analysis of each experiment. Our results indicated that silibinin-treatment could reduce seizure susceptibility and frequency of spontaneous recurrent seizures (SRS) induced by KA administration, and attenuate granule cell dispersion (GCD), a morphological alteration characteristic of the dentate gyrus (DG) in temporal lobe epilepsy (TLE). Moreover, its treatment significantly reduced the aberrant levels of apoptotic, autophagic and pro-inflammatory molecules induced by KA administration, resulting in neuroprotection in the hippocampus. Thus, these results suggest that silibinin may be a beneficial natural compound for preventing epileptic events.


Minimal deviation melanoma. Borderline and intermediate melanocytic neoplasia.
In the concept of MDM, the term melanoma has been reserved for lesions showing a vertical growth component. Vertical growth, divorced from any prognostic implications, is simply a morphologic designation. Such a maneuver also serves to validate the category of MDM, although it might then be inappropriate to characterize such lesions as melanoma. From my view, the modifier "minimal deviation" takes the onus of prognosis out of the equation. For common melanomas, size of a vertical growth component has relativity to prognosis. It is unlikely that, in comparable size-ranges, the MDM have a more aggressive nature than the common melanoma. It seems appropriate to propose that MDM measuring less than 1.5 mm in vertical dimensions could be characterized as melanocytic neoplasia of indeterminant malignant potential. Those less than 1 mm in vertical dimensions would be borderline variants and those in the range of 1 to 1.5 mm would be intermediate examples. Those greater than 1.5 mm could be characterized as melanocytic neoplasias of indeterminant (uncertain) malignant potential without additional qualifications.


Melanocortin receptor variants with phenotypic effects in horse, pig, and chicken.
The melanocortin system is of considerable interest in domestic animals because their energy metabolism and pigmentation have been under strong selection. This article reviews our work on MC1R variants in horse, pig, and chicken, as well as a study on MC4R polymorphism in the pig. The chestnut coat color in horses is caused by an MC1R missense mutation (S83F). In the pig, we have described seven MC1R alleles controlling four different coat color phenotypes (wild type, dominant black, black spotting, and recessive red). The most interesting allele is the one causing black spotting because it carries two causative mutations, a frameshift and a missense mutation. The frameshift mutation is somatically unstable, and the black spots reflect somatic reversion events restoring the reading frame. Classic genetics have established eight alleles at the Extended black locus in chicken, which is assumed to correspond to the Extension locus in mammals. We have analyzed the co-segregation of alleles at MC1R and Extended black using a red jungle fowl x White Leghorn intercross and provide compelling evidence that these loci are identical. A previous study indicated that a missense mutation (D298N) in pig MC4R has an effect on fatness, growth, and feed intake. We could not confirm this association using an intercross between the wild boar and Large White domestic pigs, but it is possible that our F(2) generation was too small to detect the rather modest effect reported for this polymorphism.


Neurons derived from PC12 cells have the potential to develop synapses with primary neurons from rat cortex.
Neuron transplantation is considered to be a promising therapeutic method to replace functions lost due to central nervous system (CNS) damage. However, little is known about the extent to which implanted neuron-like cells can develop into mature neurons and acquire essential properties, and especially formation of synapses with host neurons. In this investigation we seeded PC12 cells labeled with GFP into primary cultured neurons isolated from rat cerebral cortex to build a co-culture system, and then induced the PC12 cells to differentiate into neuron-like cells with NGF. Seven days later, we observed the relationship between the PC12-derived neurons and primary neurons using FM1-43 imaging and immunoelectron microscopy, and found that GFP-labeled neurons could form typical synapses with host primary neurons. These observations showed that immigrant neurons differentiated from PC12 cells could develop into mature neurons and could form intercellular contacts with host neurons. Both the immigrant and host neurons could construct neuronal networks in vitro.


Succinic semialdehyde as a substrate for the formation of gamma-aminobutyric acid.
The conversion of succinic semialdehyde into gamma-aminobutyric acid (GABA) by GABA-transaminase was measured in rat brain homogenate in the presence of different concentrations of the cosubstrate glutamate. The calculated kinetic parameters of succinic semialdehyde for GABA-transaminase were a limiting Km value of 168 microM and a limiting Vmax value of 38 mumol g-1 h-1. Combination with previously obtained data for the conversion of GABA into succinic semialdehyde revealed a kEq value of 0.04, indicating that equilibrium of GABA-transaminase is biased toward the formation of GABA. The increased formation of GABA in the presence of succinic semialdehyde was not due to an increased conversion of glutamate into GABA by glutamic acid decarboxylase. Therefore these results indicate that succinic semialdehyde can act as a precursor for GABA synthesis.


[Analysis of bactericidal material generated by electrical devices advertising bactericidal ability against bacteria on the agar gel plates].
Several Japanese companies sell electrical devices advertised as effective in inactivating viruses and killing bacteria by releasing special materials, e.g., Plasmacluster ions, Nanoe particle and minus ions, into the air. These companies claim that their devices killed bacteria on plates in their own experiments. We tested device effectiveness using the same experiments from the Plasmacluster ioniser SHARP Co., Japan, the Nanoe generator Panasonic Co., Japan, and the Vion KING JIM Co., Japan, to test their advertising claims. Bactericidal ability on agar plate was tested, using Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus, and Enterococcus faecalis as follows: the medium containing a certain amount of each bacterium was put onto an agar plate and smeared. Plates were kept in a closed chamber (inner volume 14.4 m3) or a glove box (inner volume 0.2 m), with one of the devices run for 2 hours. Plates not exposed to any device were used as controls. Each plate was retrieved and put in an incubator to count the number of bacterial colonies formed on the plate. There was no significant difference in the number of colonies on plates exposed to devices compared to control, in the number for all devices, or in all bacteria tested in experiments in the 14.4 m3 chamber. These results strongly suggest that these devices have almost no bactericidal effect, at least in space exceeding this volume. Colony formation was suppressed in the glove box in all devices and in all bacteria tested except P. aeruginosa, although the degree of suppression differed among experiments. The colony formation suppression mechanism was analyzed, and indicated that:colony formation did not change even after the removal of Plasmacluster ions, Nanoe particles, or negative ions from the air, while colony formation was decreased drastically by the removal of ozone from space, which was revealed to be generated inevitably during device operation. These results strongly suggest that the bactericidal effect seen only on the agar plate in narrow space was explained by ozone released in space as a by-product, not by special materials as advertising claimed. It is thus important to analyze the effect of special materials such as those done in this study and to suggest the involvement of ozone as the true cause, as have been done in this study, in evaluating bactericidal effect or viral inactivation as advertised by these companies.


Inference-based time-resolved stability analysis of nonlinear whole-cortex modeling: application to Xenon anaesthesia.
This study characterizes the neurophysiological mechanisms underlying electromagnetic imaging signals using stability analysis. Researchers have proposed that transitions between conscious awake and anaesthetised states, and other brain states more generally, may result from system stability changes. The concept of stability in dynamical systems theory provides a mathematical framework to describe this possibility. In particular, the degree to which a system's trajectory in phase space is affected by small perturbations determines the stability. Previous studies using linear or oscillator-based whole-brain models cannot represent complex cerebrocortical dynamics, or model parameters were pre-assumed or inferred from data but did not change over time. This study proposes a nonlinear neurophysiologically plausible whole-cortex modeling framework to analyze the stability of brain dynamics for the emergence and disappearance of consciousness using time-varying parameters estimated from the data.Clinical relevance- Depth of anaesthesia is typically measured through changes in EEG statistics like the bispectral index and spectral entropy. However, these monitors have been found to fail in preventing awareness during surgery and postoperative recall. Our whole-cortex stability analysis may be useful in measuring anaesthesia levels in clinical settings, as it changes with the level of consciousness and is independent of individual differences and anaesthetic agents. The proposed method can also be used to, for example, identify critical brain regions for consciousness, locate the epileptogenic zone and investigate the dominance of extrinsic or intrinsic factors in brain functions.


The role of interstitial starling forces in the pathogenesis of burn edema.
The formation and sustainability of burn edema require substantial change in net microvascular forces. We directly measured interstitial hydrostatic pressure (Pi) and total interstitial absorptive pressure (Pi + IIi), in dermis of anesthetized sheep, before and after a 70% to 85% total body surface area scald and during fluid resuscitation. The most rapid change occurred in Pi in the burn wound, which rapidly decreased from its baseline value of approximately -2 mm Hg to -11 mm Hg in the first 5 minutes, and thereafter increased but remained approximately -4 mm Hg through 4 hours of resuscitation. Pi in nonburned skin slowly increased from its preburn level -2 mm Hg, to become positive +1 mm Hg after 4 hours of resuscitation. The total interstitial absorptive pressure, Pi + IIi, slowly declined similarly from 15 to 16 mm Hg to approximately 10 to 11 mm Hg over 6 hours of resuscitation in both burned and nonburned dermis. Taken together, these data suggest that the rapid formation of burn edema is the result of development of a negative Pi in the burn wound, and its sustainability is the result of a large increase in interstitial compliance. Edema in nonburned skin did not start until after fluid resuscitation was initiated, and then developed as the plasma oncotic pressure declined from 21 to 10 mm Hg.


Effect of Lovastatin on Wound-Healing Modulation After Glaucoma Filtration Surgery in a Rabbit Model.
To investigate the efficacy of lovastatin as an antifibrotic agent after glaucoma filtration surgery (GFS) in a rabbit model. Thirty New Zealand white rabbits underwent GFS on the right eye. The rabbits were randomly assigned to one of three groups: (1) the mitomycin-C (MMC) group, which received 0.2 mg/mL MMC-soaked Weck-Cel under the conjunctival flap; (2) the control group, which received postoperative subconjunctival injections with 0.1 mL balanced salt solution (BSS); and (3) the lovastatin group, which received postoperative subconjunctival injection with 0.1 mL lovastatin (10 μM). Intraocular pressure (IOP), bleb survival, and bleb morphology were examined until blebs showed evidence of failure. Three rabbits in each group were killed on postoperative day (POD) 5, and analyzed for histology and immunohistochemistry. Lovastatin significantly improved bleb survival compared with that in the control group (P = 0.002); however, no significant difference in bleb survival was observed between the MMC and lovastatin groups (P = 0.097). The lovastatin group showed significantly larger and higher blebs than did the control group. Further, the IOPs of the lovastatin and MMC groups were significantly lower than that of the control group (8.0 ± 1.4 mm Hg, 7.9 ± 3.2 mm Hg, and 11.1 ± 2.9 mm Hg, respectively; P = 0.016) on POD 5. Histologic analyses revealed decreased inflammatory response and reduced fibrosis in the lovastatin group than in the control group. Postoperative injection of lovastatin improved bleb survival in the rabbit model of GFS. Therefore, lovastatin may have potential as a novel wound-modulating agent after GFS.


Aryl selenonium vs. aryl sulfonium counterions in polyoxometalate chemistry: the impact of Se+ cationic centers on the photocatalytic reduction of dichromate.
A selenonium organic counter ion has been used in polyoxometalate chemistry to develop a new aryl selenonium polyoxometalate (POM) hybrid, and its photocatalytic properties have been explored in comparison with an aryl sulfonium POM-hybrid counterpart for the first time. The chalcogenonium counterions, namely, methyldiphenylsulfonium trifluoromethane sulfonate (MDPST) and methyldiphenylselenonium trifluoromethane sulfonate (MDPSeT), and their octamolybdate ([Mo8O26]4-) hybrids, 1 and 2, with the general formula (C13H13X)4[Mo8O26] (where X = S for 1 and Se for 2) were synthesized and characterized. Hybrids 1 and 2 vary in their chalcogenonium cationic center (S+vs. Se+), which enabled a direct comparison of their photocatalytic properties as a function of the cationic center. The photocatalytic activities of hybrids 1 and 2 were tested using the reduction of dichromate (Cr2O72-) as a model reaction under UV irradiation. A 99% photocatalytic reduction of Cr2O72- with a rate constant of 0.0305 min-1 was achieved with hybrid 2, while only a 67% reduction with a rate constant of 0.0062 min-1 was observed with hybrid 1 in 180 minutes. The better catalytic performance of hybrid 2 may be correlated to the larger atomic radii of Se than S, which helps in better stabilizing the photogenerated electron-hole (e--h+) pair on the POM cluster by polarizing its lone pair more efficiently compared to S. The catalytic recyclability was tested for up to 4 cycles using hybrid 2, and up to 98% reduction was obtained even after the 4th cycle. Recyclability tests and control experiments also indicated the generation of some elemental Se through possible cleavage of some C-Se bonds of MDPSe under prolonged UV exposure during catalysis, and the Se thus generated was found to contribute to the catalytic reduction of dichromate. This study, therefore, opens new avenues for aryl selenonium moieties and their POM hybrids for potential catalytic applications.


CGS 16949A, a new nonsteroidal aromatase inhibitor: effects on hormone-dependent and -independent tumors in vivo.
CGS 16949A is a very potent and highly selective inhibitor of the aromatase enzyme system in vitro and of estrogen biosynthesis in vivo. These characteristics are reflected in the marked efficacy with which it affects growth of estrogen-dependent 7,12-dimethylbenz(a)antracene-induced mammary carcinomas in intact female Sprague-Dawley rats. Daily p.o. treatment of tumor-bearing rats for 42 days with CGS 16949A at doses of 1.0 to 8.0 mg/kg caused almost complete regression of palpable tumors and almost totally suppressed the appearance of new tumors. A dose of about 0.1 mg/kg corresponded to the 50% effective dose, and a fully effective dose was estimated to be about 2.0 mg/kg. Eight to 10 days after cessation of treatment, tumor regrowth was observed. No unexpected side-effects were noted during the course of treatment. Tumors, which were allowed to regrow after a first treatment with CGS 16949A, were similarly efficaciously suppressed with a second treatment with CGS 16949A. Continuous long-term treatment with 2.0 mg/kg for 27 wk caused complete regression of tumors, suppressed the appearance of new tumors completely, and significantly prolonged the survival time of the tumor-bearing rats. This treatment schedule caused no major hematological or blood chemistry changes and was very well tolerated. CGS 16949A was ineffective against transplantable hormone-independent tumors such as R-3230AC mammary carcinoma, 11095 prostate carcinoma, leukemia L1210, and B16 melanoma.


[Variability in chromosomes number during plant ontogenesis].
The experiments on chromosome variability of cells in the ontogenesis of higher plants are reviewed. The polyploidization of somatic cells during the ontogenesis is shown to be the natural phenomenon for most plant tissues and it is correlated with the intensification of cellular metabolism. The functional and chromosome variability of somatic cells is supposed to depend mostly on the hormonal regulation. The possible role of the phytochrome system in this process is discussed.


Rosmarinic acid down-regulates the LPS-induced production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in bone-marrow derived dendritic cells.
In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and MIP-lalpha induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of NF-kappaB. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.


[Efficacy of experimental renal embolization with microspheres. Additionally, a critical report on the complication rate of intra-arterial embolization with particles (author's transl)].
Renal embolization was performed in 12 dogs using the Seldinger technique and microspheres 250 +/- 40 micrometer in diameter. Periodical arteriography, microangiographies and histological analysis was carried out to control the efficacy of embolization. As a result, renal arteries could be embolized wi. th microspheres, however, because of statistical distribution there were histologically anemic and normal parenchyma situated closely together. In more than 50% there was a reflux of microspheres which could only be detected by histological examination, while angiographies showed a totally normal vascular pattern. Microspheres should not be used in clinical embolization. Experimental investigation of embolization materials must almost embrace histological analysis.


Improved data validity in the Swedish Register of Palliative Care.
The Swedish Register of Palliative Care (SRPC) is a national quality register that collects data about end-of-life care from healthcare providers that care for dying patients. Data are used for quality control and research. Data are mainly collected with an end-of-life questionnaire (ELQ), which is completed by healthcare staff after the death of a patient. A previous validity assessment of the ELQ showed insufficient validity in some items including symptom relief. The aim of this study was to examine the validity of the revised ELQ. Data from 100 consecutive patients' medical records at two specialised palliative care units were used to complete new ELQs, which were then compared to the ELQ registrations from the SRPC for the same patients. The level of agreement was calculated for each ELQ item. To account for the possibility of the agreement occurring by chance, Cohen's kappa was calculated for suitable items. To examine the extent of registration mistakes when transferring the paper form to the web, the original paper versions of the ELQ filled out at the units were compared to data from the ELQs reported to the SRPC. Level of agreement between ELQ registrations from the SRPC and the new ELQs based on the medical records varied between 0.55 and 1.00, where 24 items showed level of agreement above 0.80 and 9 items showed level of agreement below 0.80. Cohen's kappa with 95% confidence intervals was calculated for 24 items. The kappa values showed that two items had poor agreement, four fair agreement, 11 moderate agreement, five good agreement and two very good agreement. The level of agreement varied between 0.93 and 1.00 when comparing the ELQ registrations in the SRPC and the paper forms. The revised ELQ contains more items with high levels of agreement between registrations in the SRPC and notes in the patients' medical records when compared to the previous version. Validating issues around symptom assessment remains a challenge in our model of quality assessment.


Systematic Comparison of Amber and Rosetta Energy Functions for Protein Structure Evaluation.
An accurate energy function is an essential component of biomolecular structural modeling and design. The comparison of differently derived energy functions enables analysis of the strengths and weaknesses of each energy function and provides independent benchmarks for evaluating improvements within a given energy function. We compared the molecular mechanics Amber empirical energy function to two versions of the Rosetta energy function (talaris2014 and REF2015) in decoy discrimination and loop modeling tests. In decoy discrimination tests, both Rosetta and Amber (ff14SBonlySC) energy functions performed well in scoring the native state as the lowest energy conformation in many cases, but several false minima were found in with both talaris2014 and Amber ff14SBonlySC scoring functions. The current default version of the Rosetta energy function, REF2015, which is parametrized on both small molecule and macromolecular benchmark sets to improve decoy discrimination, performs significantly better than talaris2014, highlighting the improvements made to the Rosetta scoring approach. There are no cases in Rosetta REF2015, and 8/140 cases in Amber, where a false minimum is found that is absent in the alternative landscape. In loop modeling tests, Amber ff14SBonlySC and REF2015 perform equivalently, although false minima are detected in several cases for both. The balance between dihedral, electrostatic, solvation and hydrogen bonding scores contribute to the existence of false minima. To take advantage of the semi-orthogonal nature of the Rosetta and Amber energy functions, we developed a technique that combines Amber and Rosetta conformational rankings to predict the most near-native model for a given protein. This algorithm improves upon predictions from either energy function in isolation and should aid in model selection for structure evaluation and loop modeling tasks.


The Role of Technical Assistance in School Wellness Policy Enhancement.
School settings offer an opportunity to impact student health and wellness. Quality wellness policies are important in establishing strong wellness environments, but current resources to support policy development, maintenance, and dissemination are lacking. The Building Healthy Schools Program aimed to develop capacity of school districts to improve the strength and comprehensiveness of wellness policies and sustain these activities. Fifteen school districts in Pennsylvania participated in a program to facilitate the improvement of district wellness policies and practices. Program staff provided technical assistance to evaluate wellness policies before and after program implementation. Professional development and tailored training was provided for school personnel to create sustainability. Statistical analysis was performed to evaluate policy improvement. Thirteen of the 15 participating districts completed a policy revision. Median strength (p = .001) and comprehensiveness (p = .002) scores improved from baseline to post-program and there were significant improvements in most assessment sub-sections. Some districts were hesitant to make strong language improvements due to their limited capacity (ie, staff) for implementation. Champions (n = 13; 87%) reported confidence to revise wellness policy language independently in the future. Technical assistance provided to districts facilitated significant improvements to wellness policy language, especially in the implementation, evaluation, and communication; critical components for policy impact on school wellness environments. In addition, participant feedback suggested an ability to sustain activities in the future. Both external (ie, technical assistance) and internal resources are needed to facilitate school districts' ongoing wellness policy improvement and implementation, including improved model wellness policy language and enforcement within schools, respectively.


Identification of peptide coatings that enhance diffusive transport of nanoparticles through the tumor microenvironment.
In solid tumors, increasing drug penetration promotes their regression and improves the therapeutic index of compounds. However, the heterogeneous extracellular matrix (ECM) acts as a steric and interaction barrier that hinders effective transport of therapeutics, including nanomedicines. Specifically, the interactions between the ECM and surface physicochemical properties of nanomedicines (e.g. charge, hydrophobicity) affect their diffusion and penetration. To address the challenges using existing surface chemistries, we used peptide-presenting phage libraries as a high-throughput approach to screen and identify peptides as coatings with desired physicochemical properties that improve diffusive transport through the tumor microenvironment. Through iterative screening against the ECM and identification by next-generation DNA sequencing and analysis, we selected individual clones and quantify their transport by diffusion assays. Here, we identified a net-neutral charge, hydrophilic peptide P4 that facilitates significantly higher diffusive transport of phage than negative control through in vitro tumor ECM. Through alanine mutagenesis, we confirmed that the hydrophilicity, charge, and spatial ordering impact diffusive transport. The P4 phage clone exhibited almost 200-fold improved uptake in ex vivo pancreatic tumor xenografts compared to the negative control. Nanoparticles coated with P4 exhibited ∼40-fold improvement in diffusivity in pancreatic tumor tissues, and P4-coated particles demonstrated less hindered diffusivity through the ECM compared to functionalized control particles. By leveraging the power of molecular diversity using phage display, we can greatly expand the chemical space of surface chemistries that can improve the transport of nanomedicines through the complex tumor microenvironment to ultimately improve their efficacy.


Characterising live cell behaviour: Traditional label-free and quantitative phase imaging approaches.
Label-free imaging uses inherent contrast mechanisms within cells to create image contrast without introducing dyes/labels, which may confound results. Quantitative phase imaging is label-free and offers higher content and contrast compared to traditional techniques. High-contrast images facilitate generation of individual cell metrics via more robust segmentation and tracking, enabling formation of a label-free dynamic phenotype describing cell-to-cell heterogeneity and temporal changes. Compared to population-level averages, individual cell-level dynamic phenotypes have greater power to differentiate between cellular responses to treatments, which has clinical relevance e.g. in the treatment of cancer. Furthermore, as the data is obtained label-free, the same cells can be used for further assays or expansion, of potential benefit for the fields of regenerative and personalised medicine.


An assessment of low-lying excitation energies and triplet instabilities of organic molecules with an ab initio Bethe-Salpeter equation approach and the Tamm-Dancoff approximation.
The accurate prediction of singlet and triplet excitation energies is an area of intense research of significant fundamental interest and critical for many applications. Most calculations of singlet and triplet energies use time-dependent density functional theory (TDDFT) in conjunction with an approximate exchange-correlation functional. In this work, we examine and critically assess an alternative method for predicting low-lying neutral excitations with similar computational cost, the ab initio Bethe-Salpeter equation (BSE) approach, and compare results against high-accuracy wavefunction-based methods. We consider singlet and triplet excitations of 27 prototypical organic molecules, including members of Thiel's set, the acene series, and several aromatic hydrocarbons exhibiting charge-transfer-like excitations. Analogous to its impact in TDDFT, we find that the Tamm-Dancoff approximation (TDA) overcomes triplet instabilities in the BSE approach, improving both triplet and singlet energetics relative to higher level theories. Finally, we find that BSE-TDA calculations built on effective DFT starting points, such as those utilizing optimally tuned range-separated hybrid functionals, can yield accurate singlet and triplet excitation energies for gas-phase organic molecules.


Molecular characterization of a lizard adenovirus reveals the first atadenovirus with two fiber genes and the first adenovirus with either one short or three long fibers per penton.
Although adenoviruses (AdVs) have been found in a wide variety of reptiles, including numerous squamate species, turtles, and crocodiles, the number of reptilian adenovirus isolates is still scarce. The only fully sequenced reptilian adenovirus, snake adenovirus 1 (SnAdV-1), belongs to the Atadenovirus genus. Recently, two new atadenoviruses were isolated from a captive Gila monster (Heloderma suspectum) and Mexican beaded lizards (Heloderma horridum). Here we report the full genomic and proteomic characterization of the latter, designated lizard adenovirus 2 (LAdV-2). The double-stranded DNA (dsDNA) genome of LAdV-2 is 32,965 bp long, with an average G+C content of 44.16%. The overall arrangement and gene content of the LAdV-2 genome were largely concordant with those in other atadenoviruses, except for four novel open reading frames (ORFs) at the right end of the genome. Phylogeny reconstructions and plesiomorphic traits shared with SnAdV-1 further supported the assignment of LAdV-2 to the Atadenovirus genus. Surprisingly, two fiber genes were found for the first time in an atadenovirus. After optimizing the production of LAdV-2 in cell culture, we determined the protein compositions of the virions. The two fiber genes produce two fiber proteins of different sizes that are incorporated into the viral particles. Interestingly, the two different fiber proteins assemble as either one short or three long fiber projections per vertex. Stoichiometry estimations indicate that the long fiber triplet is present at only one or two vertices per virion. Neither triple fibers nor a mixed number of fibers per vertex had previously been reported for adenoviruses or any other virus. Here we show that a lizard adenovirus, LAdV-2, has a penton architecture never observed before. LAdV-2 expresses two fiber proteins-one short and one long. In the virion, most vertices have one short fiber, but a few of them have three long fibers attached to the same penton base. This observation raises new intriguing questions on virus structure. How can the triple fiber attach to a pentameric vertex? What determines the number and location of each vertex type in the icosahedral particle? Since fibers are responsible for primary attachment to the host, this novel architecture also suggests a novel mode of cell entry for LAdV-2. Adenoviruses have a recognized potential in nanobiomedicine, but only a few of the more than 200 types found so far in nature have been characterized in detail. Exploring the taxonomic wealth of adenoviruses should improve our chances to successfully use them as therapeutic tools.


Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range.
Determining how different populations adapt to similar environments is fundamental to understanding the limits of adaptation under changing environments. Snowshoe hares (Lepus americanus) typically molt into white winter coats to remain camouflaged against snow. In some warmer climates, hares have evolved brown winter camouflage-an adaptation that may spread in response to climate change. We used extensive range-wide genomic data to (1) resolve broad patterns of population structure and gene flow and (2) investigate the factors shaping the origins and distribution of winter-brown camouflage variation. In coastal Pacific Northwest (PNW) populations, winter-brown camouflage is known to be determined by a recessive haplotype at the Agouti pigmentation gene. Our phylogeographic analyses revealed deep structure and limited gene flow between PNW and more northern Boreal populations, where winter-brown camouflage is rare along the range edge. Genome sequencing of a winter-brown snowshoe hare from Alaska shows that it lacks the winter-brown PNW haplotype, reflecting a history of convergent phenotypic evolution. However, the PNW haplotype does occur at low frequency in a winter-white population from Montana, consistent with the spread of a locally deleterious recessive variant that is masked from selection when rare. Simulations of this population further show that this masking effect would greatly slow the selective increase of the winter-brown Agouti allele should it suddenly become beneficial (e.g., owing to dramatic declines in snow cover). Our findings underscore how allelic dominance can shape the geographic extent and rate of convergent adaptation in response to rapidly changing environments.


Teratogenic Rubella Virus Alters the Endodermal Differentiation Capacity of Human Induced Pluripotent Stem Cells.
The study of congenital virus infections in humans requires suitable ex vivo platforms for the species-specific events during embryonal development. A prominent example for these infections is rubella virus (RV) which most commonly leads to defects in ear, heart, and eye development. We applied teratogenic RV to human induced pluripotent stem cells (iPSCs) followed by differentiation into cells of the three embryonic lineages (ecto-, meso-, and endoderm) as a cell culture model for blastocyst- and gastrulation-like stages. In the presence of RV, lineage-specific differentiation markers were expressed, indicating that lineage identity was maintained. However, portrait analysis of the transcriptomic expression signatures of all samples revealed that mock- and RV-infected endodermal cells were less related to each other than their ecto- and mesodermal counterparts. Markers for definitive endoderm were increased during RV infection. Profound alterations of the epigenetic landscape including the expression level of components of the chromatin remodeling complexes and an induction of type III interferons were found, especially after endodermal differentiation of RV-infected iPSCs. Moreover, the eye field transcription factors RAX and SIX3 and components of the gene set vasculogenesis were identified as dysregulated transcripts. Although iPSC morphology was maintained, the formation of embryoid bodies as three-dimensional cell aggregates and as such cellular adhesion capacity was impaired during RV infection. The correlation of the molecular alterations induced by RV during differentiation of iPSCs with the clinical signs of congenital rubella syndrome suggests mechanisms of viral impairment of human development.


Reef coral from aldabra: new mode of reproduction.
A unique mode of asexual reproduction in recently collected specimens of Goniopora (Scleractinia) is reported. Skeleton is absent from new polyps; the skelton develops independently of the parent colony as the new polyps themselves increase. The young colonies eventually become detached. The cycle seems to be a response to a sandy habitat, a conclusion reached by analogy With Fungia and Manicina.


Mitigating Metal Dendrite Formation in Lithium-Sulfur Batteries via Morphology-Tunable Graphene Oxide Interfaces.
Despite issues related to dendrite formation, research on Li metal anodes has resurged because of their high energy density. In this study, graphene oxide (GO) layers are decorated onto Li metal anodes through a simple process of drop-casting and spray-coating. The self-assembly of GO is exploited to synthesize coatings having compact, mesoporous, and macroporous morphologies. The abilities of the GO coatings to suppress dendrite formation are compared through Li|Li symmetrical cell charging at a current density of 5 mA cm-2 for 2000 cycles-a particularly abusive test. The macroporous structure possesses the lowest impedance, whereas the compact structure excels in terms of stability. Moreover, GO exhibits a low nucleation overpotential and is transformed into reduced GO with enhanced conductivity during the operation of the cells; both factors synergistically mitigate the issue of dendrite formation. Li-S batteries incorporating the GO-decorated Li anodes exhibit an initial capacity of 850 mA h g-1 and maintain their stability for 800 cycles at a C-rate of 1 C (1675 mA h g-1), suggesting the applicability of GO in future rechargeable batteries.


A dark side of the American dream: correlates of financial success as a central life aspiration.
Aspiring for financial success is an important aspect of capitalist cultures. Three studies examine the hypothesis that values and expectancies for wealth and money are negatively associated with adjustment and well-being when they are more central to an individual than other self-relevant values and expectancies. Studies 1 and 2 use 2 methods to show that the relative centrality of money-related values and expectancies is negatively related to college students' well-being and mental health. Study 3, using a heterogeneous noncollege sample, extends these findings by showing that a high centrality of aspirations for financial success is associated with interview ratings of lower global adjustment and social productivity and more behavioral disorders. Discussion is focused on the deleterious consequences of materialistic world views and the need to examine differential effects of content regarding goals and values.


Weight change and 15 year mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study.
Studies have reported a higher mortality risk associated with weight loss, particularly in middle-aged and older adults, although some of these studies did find that gaining weight was also associated with an increased mortality risk. We examined changes in weight in relation to mortality in a prospective population-based cohort study of men and women, resident in Norfolk, UK. Participants were assessed at baseline (1993-1997) and at a second examination (1998-2000), as part of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, and followed up to 2015 for mortality. Participants with a self-reported history of cancer or cardiovascular disease, body mass index < 18.5 kg/m2 or missing data on adjustment variables, at either time-point were excluded, leaving 12,580 participants, aged 39-78 in 1993-1997, eligible for analyses. Cox proportional hazards models were used to determine Hazard Ratios (HRs) for all-cause (2603 deaths), cardiovascular (749 deaths), cancer (981 deaths), respiratory (226 deaths) and other causes of mortality (647 deaths) by categories of weight change. After multivariate adjustment, the HRs (95% CIs) for all-cause mortality for men and women who lost more than 5 kg were 1.85 (1.48-2.31) and 1.64 (1.31-2.05) respectively. Higher hazards were also found for specific causes of mortality and weight loss > 5 kg. Similar associations were observed after excluding deaths in the first 5 years of follow-up. Results for weight gain were inconclusive. We conclude that objectively measured weight loss, but not weight gain, was associated with subsequent higher mortality risk in this population-based study of middle-aged and elderly men and women. However, undiagnosed, pre-existing disease and the inability to account for weight cycling need to be remembered when interpreting these results. Unravelling the causal pathways underlying this association will require more detailed studies, including that of changes in body composition.


Energy expenditure of rats subjected to long-term food restriction.
Food restriction, even when expressed per unit of metabolic mass, leads to energy conservation as seen by decreased oxygen consumption. The objective of the present study was to verify whether the energy conservation mechanism reduces energy expenditure for as long as food restriction lasts or whether a return to basal level may occur without realimentation, mainly in mildly food-restricted rats. Wistar rats were brought to the laboratory on weaning. They were then assigned to control group that received ad libitum food intake, R10 and R20 groups that received 90 and 80%, respectively, of the food eaten by control group and RM group that received an amount of food enough only to keep body weight. The food restriction period lasted for 3 months and was followed by another month during which all groups received ad libitum food intake. The results showed that even in animals subjected to mild food restriction (10%) there was a sustained decrease in oxygen consumption that lasted until refeeding of the animals. The results led to the conclusion that the energy conservation mechanism is active from little food restriction until more stronger levels of restriction, in a proportional manner, and the decreased energy expenditure is maintained during the whole food restriction period.


Cyst-ventricle stent as primary or salvage treatment for posterior fossa arachnoid cysts.
The optimal treatment of symptomatic posterior fossa arachnoid cysts is controversial. Current options include open or endoscopic resection, fenestration, or cyst-peritoneal shunt placement. There are potential drawbacks with all options. Previous authors have described stenting a cyst into the ventricular system for supratentorial lesions. The current authors have used a similar strategy for posterior fossa cysts. The authors performed a retrospective review of 79 consecutive patients (1993-2010) with surgically treated intracranial arachnoid cysts. The authors identified 3 patients who underwent placement of a stent from a posterior fossa arachnoid cyst to a supratentorial ventricle. In 2 patients the stent construct consisted of a catheter placed into a posterior fossa arachnoid cyst and connecting to a lateral ventricle catheter. Both patients underwent stent placement as a salvage procedure after failure of open surgical fenestration. In the third patient a single-catheter cyst-ventricle stent was stereotactically placed. All 3 patients improved clinically. Two patients remained asymptomatic, with radiographic stability in a follow-up period of 1 and 5 years, respectively. The third patient experienced initial symptom resolution with a demonstrable reduction of intracystic pressure. However, he developed recurrent headaches after 2 years. Posterior fossa cyst-ventricle stenting offers the benefits of ease of surgical technique and a low morbidity rate. It may also potentially reduce the incidence of shunt-related headaches by equalizing the pressure between the posterior fossa and the supratentorial compartments. While fenestration is considered the first-line therapy for most symptomatic arachnoid cysts, the authors consider cyst-ventricle stenting to be a valuable additional strategy in treating these rare and often difficult lesions.


Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors.
The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, and both males and females of this strain are sensitive to chemical induction of liver tumors. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors, and such activated oncogenes frequently contain a particular point mutation. In light of indications that the transforming capacity of some oncogenes is directly related to the level of the gene product, we hypothesized that transcriptional control of Ha-ras, Ki-ras, and myc is compromised in B6C3F1 mouse liver tumors. A positive correlation has been established between gene expression and hypomethylation. Therefore, the methylation states of these genes were examined in spontaneous liver tumors and in tumors induced by two diverse hepatocarcinogens: phenobarbital and chloroform. Ha-ras was found to be hypomethylated in all tumors examined, whereas Ki-ras was sometimes hypomethylated; such hypomethylation might play a role in the promotion stage of carcinogenesis. The methylation state of myc was unaltered, although this gene appeared to be amplified in tumors. These results suggest that a component of the mechanism by which these oncogenes are activated in B6C3F1 mouse liver tumors involves loss of stringent control of expression, via hypomethylation of the ras oncogenes and, possibly, amplification of myc. These results support the assertion that tumors induced by different classes of carcinogens or arising spontaneously share common biochemical pathways of oncogene activation during tumorigenesis.


Cognitive life expectancy by educational attainment in Mexican adults aged 60 and older.
To estimate cognitively healthy life expectancy (CHLE), cognitive impairment life expectancy (CILE), and dementia life expectancy (DLE) in Mexican adults aged 60 and older stratified by educational attainment. The data were obtained from Waves 1 (2001) to 5 (2018) of the Mexican Health and Aging Study. The life expectancy was estimated using a multistate life table analysis. CHLE at age 60 increased with higher educational attainment and ranged from 17.9 to 24.4 years in female participants, and 17.2 to 21.3 in male participants. The CILE and DLE decreased with greater educational attainment. The CILE ranged from 0.7 to 2.8 years in female participants and 0.7 to 2.6 in male participants. Older adults in Mexico with higher education live more years with good cognitive health and fewer years with cognitive impairment and dementia. Education has a stronger effect on the length of cognitively healthy life expectancies than on total life expectancies.


Regulation of reductive dehalogenase gene transcription in Dehalococcoides mccartyi.
The remarkable capacity of the genus Dehalococcoides to dechlorinate a multitude of different chlorinated organic compounds reflects the number and diversity of genes in the genomes of Dehalococcoides species encoding reductive dehalogenase homologues (rdh). Most of these genes are located in the vicinity of genes encoding multiple antibiotic resistance regulator (MarR)-type or two-component system regulators. Here, the transcriptional response of rdhA genes (coding for the catalytic subunit) to 2,3- and 1,3-dichlorodibenzo-p-dioxin (DCDD) was studied in Dehalococcoides mccartyi strain CBDB1. Almost all rdhA genes were transcribed in the presence of 2,3-DCDD, albeit at different levels as shown for the transcripts of cbrA, cbdbA1453, cbdbA1624 and cbdbA1588. By contrast, 1,3-DCDD did not induce rdhA transcription. The putative MarR CbdbA1625 was heterologously produced and its ability to bind in vitro to the overlapping promoter regions of the genes cbdbA1624 and cbdbA1625 was demonstrated. To analyse regulation in vivo, single-copy transcriptional promoter-lacZ fusions of different rdhA genes and of cbdbA1625 were constructed and introduced into the heterologous host Escherichia coli, and expression levels of the fusions were measured. The cbdbA1625 gene was cloned into a vector allowing a regulation of expression by arabinose and it was transformed into the strains containing the rdh-promoter-lacZ fusion derivatives. CbdbA1625 was shown to downregulate transcription from its own promoter resulting in a 40-50% reduction in the β-galactosidase activity, giving the first hint that it acts as a repressor.


Passively minimizing structural sound radiation using shunted piezoelectric materials.
Two methods are presented to determine optimal inductance and resistance values of the shunt circuit across a piezoceramic material, which is bonded to a simply supported plate in order to minimize sound radiation from the plate. The first method (DH) makes use of den Hartog's damped vibration absorber principle. The second method (SM) uses the Sherman Morrison matrix inversion theorem. The effectiveness of each method is compared with regard to minimizing total acoustic sound-power radiation and acoustic pressure at a point. Optimization algorithms and case studies are presented using a linearized model for the piezoceramic and using a nonlinear model for the piezoceramic that accounts for the inherent dielectric hysteresis. Case studies demonstrate that the second method (SM) results in superior performance, under both linear and nonlinear system assumptions. Studies also illustrate that, if the nonlinearity in the system is significant, it must be incorporated in the optimization process.