Mechanochemical properties of human myosin-1C are modulated by isoform-specific differences in the N-terminal extension.
Myosin-1C is a single-headed, short-tailed member of the myosin class I subfamily that supports a variety of actin-based functions in the cytosol and nucleus. In vertebrates, alternative splicing of the MYO1C gene leads to the production of three isoforms, myosin-1C0, myosin-1C16, and myosin-1C35, that carry N-terminal extensions of different lengths. However, it is not clear how these extensions affect the chemomechanical coupling of human myosin-1C isoforms. Here, we report on the motor activity of the different myosin-1C isoforms measuring the unloaded velocities of constructs lacking the C-terminal lipid-binding domain on nitrocellulose-coated glass surfaces and full-length constructs on reconstituted, supported lipid bilayers. The higher yields of purified proteins obtained with constructs lacking the lipid-binding domain allowed a detailed characterization of the individual kinetic steps of human myosin-1C isoforms in their productive interaction with nucleotides and filamentous actin. Isoform-specific differences include 18-fold changes in the maximum power output per myosin-1C motor and 4-fold changes in the velocity and the resistive force at which maximum power output occurs. Our results support a model in which the isoform-specific N-terminal extensions affect chemomechanical coupling by combined steric and allosteric effects, thereby reducing both the length of the working stroke and the rate of ADP release in the absence of external loads by a factor of 2 for myosin-1C35. As the large change in maximum power output shows, the functional differences between the isoforms are further amplified by the presence of external loads.


Cricoid cartilage necrosis after arytenoidectomy in a previously irradiated larynx.
Several open and endoscopic surgical techniques are available to provide an adequate airway for patients with bilateral vocal cord paralysis. Transoral laser arytenoidectomy has repeatedly been reported to be a reliable and effective minimally invasive procedure for airway restoration. To our knowledge, there have been no previous reports of serious complications, other than poor vocal results, aspiration, and failed decannulation in individual patients, that have resulted from this intervention. We report a case in which arytenoidectomy led to severe complications and death. Prior irradiation is suspected to be a causative factor. To prevent such an outcome, we believe that operative settings should be chosen that avoid deep thermal injury of the laryngeal framework.


Bacterial Communities: Interactions to Scale.
In the environment, bacteria live in complex multispecies communities. These communities span in scale from small, multicellular aggregates to billions or trillions of cells within the gastrointestinal tract of animals. The dynamics of bacterial communities are determined by pairwise interactions that occur between different species in the community. Though interactions occur between a few cells at a time, the outcomes of these interchanges have ramifications that ripple through many orders of magnitude, and ultimately affect the macroscopic world including the health of host organisms. In this review we cover how bacterial competition influences the structures of bacterial communities. We also emphasize methods and insights garnered from culture-dependent pairwise interaction studies, metagenomic analyses, and modeling experiments. Finally, we argue that the integration of multiple approaches will be instrumental to future understanding of the underlying dynamics of bacterial communities.


Migratory and invasive behavior of pigment cells in normal and animalized sea urchin embryos.
Pigment cell precursors in the vegetal plate of late mesenchyme blastulae of the sea urchin Strongylocentrotus purpuratus begin to express a cell surface epitope recognized by the monoclonal antibody SP-1/20.3.1. When one-quarter gastrulae are dissociated into ectodermal and mesenchymal fractions, most SP-1/20.3.1 immunoreactive cells separate into the mesenchymal fraction, whereas at the full gastrula and all later stages almost all epitope-bearing cells are in the ectodermal fraction. Exposure of embryos to sulfate-free seawater p-nitrophenyl beta-D-xyloside, and tunicamycin, all of which prevent primary mesenchyme migration, does not inhibit SP-1/20.3.1 immunoreactive cells from distributing similarly to those in controls, although pigment synthesis is completely inhibited in sulfate-free conditions. Time-lapse video sequences reveal that pigment cells, and a small set of rapidly migrating, SP-1/20.3.1 immunoreactive amoeboid cells that appear in the pluteus, remain closely associated with the ectodermal epithelium during most of larval development. Transmission electron microscopy observations of plutei show pigment cells tightly apposed to the ectodermal epithelium at discontinuities in the basal lamina and sandwiched between the basal lamina and the epithelial cells. It is concluded that SP-1/20.3.1 immunoreactive mesenchymal cells invade the ectodermal epithelium and may use migratory substrates other than those used by primary mesenchymal cells.


Immunosuppressive therapy reduction and early post-infection graft function in kidney transplant recipients with COVID-19.
Background: Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes due to the high burden of comorbidities and immunosuppression. The effects of immunosuppressive therapy (IST) reduction are unclear in patients with COVID-19. Methods: A retrospective study on 45 KT recipients followed at the University Hospital of Modena (Italy) who tested positive for COVID-19 by RT-PCR analysis. Results: The median age was 56.1 years (interquartile range,[IQR] 47.3-61.1), with a predominance of males (64.4%). Kidney transplantation vintage was 10.1 (2.7-16) years, and 55.6 % of patients were on triple IST before COVID-19. Early immunosuppression minimization occurred in 27 (60%) patients (reduced-dose IST group) and included antimetabolite (88.8%) and calcineurin inhibitor withdrawal (22.2%). After SARS-CoV-2 infection, 88.9% of patients became symptomatic and 42.2% required hospitalization. One patient experienced irreversible graft failure. There were no differences in serum creatinine level and proteinuria in non-hospitalized patients before and post-COVID-19, whereas hospitalized patients experienced better kidney function after hospital discharge (P=0.019). Overall mortality was 17.8%. without differences between full- and reduced-dose IST. Risk factors for death were age (odds ratio [OR]: 1.19; 95%CI: 1.01-1.39), and duration of kidney transplant (OR: 1.17; 95%CI: 1.01-1.35). One KT recipient developed IgA glomerulonephritis and two ones experienced symptomatic COVID-19 after primary infection and SARS-CoV-2 mRNA vaccine, respectively. Conclusions: Despite the reduction of immunosuppression, COVID-19 affected the survival of KT recipients. Age of patients and time elapsed from kidney transplantation were independent predictors of death . Early kidney function was favorable in most survivors after COVID-19.


Epidural blood patch for spontaneous intracranial hypotension with subdural hematoma: A case report and review of literature.
Cerebrospinal fluid (CSF) leakage at C1/2 in spontaneous intracranial hypotension (SIH) is rare. Subdural hematoma (SDH), a serious complication of SIH, may lead to neurological deficits. This report presents a case of SDH after spontaneous C1/2 CSF leakage, which was treated with a targeted epidural blood patch (EBP). A 60-year-old man with no history of trauma was admitted to our hospital with orthostatic headache, nausea, and vomiting. Brain computed tomography imaging revealed bilateral, subacute to chronic SDH. Brain magnetic resonance imaging (MRI) findings were SDH with dural enhancement in the bilateral cerebral convexity and posterior fossa and mild sagging, suggesting SIH. Although the patient underwent burr hole trephination, the patient's orthostatic headache was aggravated. MR myelography led to a suspicion of CSF leakage at C1/2. Therefore, we performed a targeted cervical EBP using an epidural catheter under fluoroscopic guidance. At 5 d after EBP, a follow-up MR myelography revealed a decrease in the interval size of the CSF collected. Although his symptoms improved, the patient still complained of headaches; therefore, we repeated the targeted cervical EBP 6 d after the initial EBP. Subsequently, his headache had almost disappeared on the 8th day after the repeated EBP. Targeted EBP is an effective treatment for SDH in patients with SIH due to CSF leakage at C1/2.


Multi-Kernel Graph Attention Deep Autoencoder for MiRNA-Disease Association Prediction.
Accumulating evidence indicates that microRNAs (miRNAs) can control and coordinate various biological processes. Consequently, abnormal expressions of miRNAs have been linked to various complex diseases. Recognizable proof of miRNA-disease associations (MDAs) will contribute to the diagnosis and treatment of human diseases. Nevertheless, traditional experimental verification of MDAs is laborious and limited to small-scale. Therefore, it is necessary to develop reliable and effective computational methods to predict novel MDAs. In this work, a multi-kernel graph attention deep autoencoder (MGADAE) method is proposed to predict potential MDAs. In detail, MGADAE first employs the multiple kernel learning (MKL) algorithm to construct an integrated miRNA similarity and disease similarity, providing more biological information for further feature learning. Second, MGADAE combines the known MDAs, disease similarity, and miRNA similarity into a heterogeneous network, then learns the representations of miRNAs and diseases through graph convolution operation. After that, an attention mechanism is introduced into MGADAE to integrate the representations from multiple graph convolutional network (GCN) layers. Lastly, the integrated representations of miRNAs and diseases are input into the bilinear decoder to obtain the final predicted association scores. Corresponding experiments prove that the proposed method outperforms existing advanced approaches in MDA prediction. Furthermore, case studies related to two human cancers provide further confirmation of the reliability of MGADAE in practice.


Alloactinosynnema iranicum sp. nov., a rare actinomycete isolated from a hypersaline wetland, and emended description of the genus Alloactinosynnema.
A Gram-staining-positive actinobacterial strain, Chem10(T), was isolated from soil around Inche-Broun hypersaline wetland in the north of Iran. Strain Chem10(T) was strictly aerobic, and catalase- and oxidase-positive. The isolate grew with 0-3 % NaCl, at 20-40 °C and at pH 6.0-8.0. The optimum temperature and pH for growth were 30 °C and pH 7.0, respectively. The cell wall of strain Chem10(T) contained meso-diaminopimelic acid as diamino acid and galactose, ribose and arabinose as whole-cell sugars. The polar lipid pattern contained diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain Chem10(T) synthesized cellular fatty acids of the straight-chain saturated and mono-unsaturated, and iso- and anteiso-branched types C14 : 0, C16 : 0, iso-C16 : 1, anteiso-C17 : 0, iso-C16 : 0, iso-C14 : 0 and iso-C15 : 0, and the major respiratory quinone was MK-9(H4). The G+C content of the genomic DNA was 70.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Chem10(T) belonged to the family Pseudonocardiaceae and showed the closest phylogenetic similarity to Alloactinosynnema album KCTC 19294(T) (98.3 %) and Actinokineospora cibodasensis DSM 45658(T) (97.9 %). DNA-DNA relatedness values between the novel strain and strains Alloactinosynnema album KCTC 19294(T) and Actinokineospora cibodasensis DSM 45658(T) were only 52 % and 23 %, respectively. On the basis of phylogenetic analysis, phenotypic characteristics and DNA-DNA hybridization data, a novel species of the genus Alloactinosynnema is proposed, Alloactinosynnema iranicum sp. nov. The type strain is Chem10(T) ( = IBRC-M 10403(T) = CECT 8209(T)). In addition, an emended description of the genus Alloactinosynnema is proposed.


The knowledge, acceptability, and use of misoprostol for self-induced medical abortion in an urban US population.
To assess the knowledge, acceptability, and use of misoprostol as an abortifacient in a primarily Latina population in the United States. This was a cross-sectional study of 610 women who used one of three obstetrics/gynecology clinics in New York City. Participants answered a self-administered questionnaire about their demographic and obstetrical characteristics; patterns of contraceptive use, including emergency contraception; general acceptability of abortion; perceptions of accessibility to abortion; prevalence of misoprostol use; and knowledge, attitudes, and availability of misoprostol. A substantial proportion (37%) of respondents admitted familiarity with the use of misoprostol as an abortifacient. The proportion of women who reported personal use of misoprostol (5%, 29/610) exceeded that reported in a large Brazilian prenatal care population (2.2%, 133/6102). Those who had taken misoprostol were more likely to have had abortions (p < 0.01), to be foreign born (p < 0.01), and to have known someone else who had used the drug (p < 0.01). Although the majority of women surveyed (73%) were Medicaid recipients, only half were aware that Medicaid covers abortion in New York State. The results of this descriptive study indicate a need to increase awareness of pre- and post-conception family planning methods and to remove barriers to access to these methods. Further research is essential to elucidate the knowledge and unsupervised use of misoprostol in other US populations.


Action potentials in macrophages derived from human monocytes.
The electrical activity of macrophages derived from human blood monocytes was recorded in vitro with intracellular microelectrodes and was analyzed with computer-assisted data acquisition and analysis techniques. In cells impaled 6 to 8 days after the cultures were prepared, the resting potentials reached a maximum value of -72 millivolts. The cells were electrically excitable; spikes exhibited a slow upstroke, a fast downstroke, a discrete threshold, a large overshoot, and a brief undershoot. Repetitive firing was induced by a maintained depolarizing current. A positive relation was observed between transmembrane currents and resting potential. Voltage-current relations were nonrectifying for subthreshold current injections. Since these cells had not been treated with any specific activation factors, the electrical activity recorded is evidence for the presence of voltage-dependent inward and outward currents in the membranes of mature macrophages. The electrical signals generated by these cells may be useful for the assay of sensor and effector functions of macrophages, such as chemotaxis, receptor-ligand interactions, and phagocytosis.


Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis.
Biosensors are being developed to provide rapid, quantitative, diagnostic information to clinicians in order to help guide patient treatment, without the need for centralised laboratory assays. The success of glucose monitoring is a key example of where technology innovation has met a clinical need at multiple levels – from the pathology laboratory all the way to the patient's home. However, few other biosensor devices are currently in routine use. Here we review the challenges and opportunities regarding the integration of biosensor techniques into body fluid sampling approaches, with emphasis on the point-of-care setting.


Intraspinal synovial cyst causing sciatica.
Four patients who had low-back pain and sciatica were diagnosed as having a lumbar intraspinal extradural synovial cyst adjacent to a facet joint between the fourth and fifth lumbar vertebrae. The patients ranged in age from forty-nine to seventy-one years, and the symptoms and signs involved the fourth or fifth lumbar-nerve roots. Roentgenographically, degeneration of the intervertebral discs and facet joints was noted in every patient. Degenerative spondylolisthesis was also a frequent finding. Myelography and computed tomographic scans aided in diagnosis, revealing a soft-tissue lesion, occasionally rimmed with calcification, adjacent to the involved facet joint. The treatment was surgical excision of the cyst, as well as complete laminectomy if there was concomitant spinal stenosis. Follow-up, ranging from eighteen to twenty-five months, revealed complete resolution of the sciatica in all patients.


[The epidemiology of congenital defects in central nervous system development in children].
The prevalence and structure as well as risk factors for congenital developmental abnormalities (CDA) of the central nervous system (CNS) have been studied over recent 17 years among the newborn's population (217,000 births) and 7,845 dead children of varying age. The stage I work involved a retrospective analysis of the medical documentation up to broad-scale introduction of ultrasonography (US) of fetal abnormalities during pregnancy, the stage II work consisted in an analysis of the genetic monitoring after the introduction of US of the fetal states, comprising the pregnant, which approximated 98%. The significant risk factors for CDA of the CNS were the pregnancy rate (the IV and consequent ones), some types of pregnancy pathology (toxemia of the first half of pregnancy, infectious diseases) as well as prematurity, intrauterine hypotrophy, previous exposures of the mother and father of the future child to ionizing radiation. Over the recent years a stable tendency has been noted toward decrease of both the prevalence of CDA of the CNS among the newborn and dead children and of anencephalies and hydrocephalus, the developmental abnormalities most clearly diagnosed on US.


Dynamic Consolidation Measurements in a Well Field Using Fiber Bragg Grating Sensors.
Currently available groundwater flow prediction tools and methods are limited by insufficient spatial resolution of subsurface data and the unknown local heterogeneity. In this field study, fiber Bragg grating (FBG) sensors were installed in an extraction well field to investigate its potential to measure groundwater flow velocity. Reference in-situ pore pressure and temperature measurements were used to identify possible sources of FBG responses. FBG strain sensors were able to detect soil consolidation caused by groundwater extraction from 250 m distance. The results show that FBG responses were influenced by interface friction between soil and FBG packaging. FBG packaging slipped in soil and the effect was more pronounced during higher groundwater flow around a nearby well. These FBG fibers could be applied for indirect flow monitoring that does not require any tracer and provide real-time and long-term data during regular operation of extraction wells.


Viral infections in the acquired immunodeficiency syndrome.
The following communication is a tripartite synopsis of the role of viral infection in the acquired immunodeficiency syndrome (AIDS). The first section describes the impact of viral opportunistic infection in AIDS; for each virus, clinical presentation and diagnosis, laboratory diagnostic approaches (with emphasis on electron microscopy), and therapeutic interventions attempted to date are discussed. The second segment explores current theories on the pathogenesis of AIDS, and describes diagnostic and therapeutic approaches to the syndrome itself. The final section catalogues ultrastructural anomalies in the cells of AIDS patients, many of which have been mistakenly identified as etiologic agents.


Color Crafting: Automating the Construction of Designer Quality Color Ramps.
Visualizations often encode numeric data using sequential and diverging color ramps. Effective ramps use colors that are sufficiently discriminable, align well with the data, and are aesthetically pleasing. Designers rely on years of experience to create high-quality color ramps. However, it is challenging for novice visualization developers that lack this experience to craft effective ramps as most guidelines for constructing ramps are loosely defined qualitative heuristics that are often difficult to apply. Our goal is to enable visualization developers to readily create effective color encodings using a single seed color. We do this using an algorithmic approach that models designer practices by analyzing patterns in the structure of designer-crafted color ramps. We construct these models from a corpus of 222 expert-designed color ramps, and use the results to automatically generate ramps that mimic designer practices. We evaluate our approach through an empirical study comparing the outputs of our approach with designer-crafted color ramps. Our models produce ramps that support accurate and aesthetically pleasing visualizations at least as well as designer ramps and that outperform conventional mathematical approaches.


Assessing protein co-evolution in the context of the tree of life assists in the prediction of the interactome.
The identification of the whole set of protein interactions taking place in an organism is one of the main tasks in genomics, proteomics and systems biology. One of the computational techniques used by many investigators for studying and predicting protein interactions is the comparison of evolutionary histories (phylogenetic trees), under the hypothesis that interacting proteins would be subject to a similar evolutionary pressure resulting in a similar topology of the corresponding trees. Here, we present a new approach to predict protein interactions from phylogenetic trees, which incorporates information on the overall evolutionary histories of the species (i.e. the canonical "tree of life") in order to correct by the expected background similarity due to the underlying speciation events. We test the new approach in the largest set of annotated interacting proteins for Escherichia coli. This assessment of co-evolution in the context of the tree of life leads to a highly significant improvement (P(N) by sign test approximately 10E-6) in predicting interaction partners with respect to the previous technique, which does not incorporate information on the overall speciation tree. For half of the proteins we found a real interactor among the 6.4% top scores, compared with the 16.5% by the previous method. We applied the new method to the whole E.coli proteome and propose functions for some hypothetical proteins based on their predicted interactors. The new approach allows us also to detect non-canonical evolutionary events, in particular horizontal gene transfers. We also show that taking into account these non-canonical evolutionary events when assessing the similarity between evolutionary trees improves the performance of the method predicting interactions.


Research on the coagulant aid effects of modified diatomite on coal microbial flocculation.
Diatomite was modified by chitosan to prepare modified diatomite, and the modified diatomite in an optimized ratio was utilized in coal bio-flocculation. The interaction behavior and flocculation mechanism of modified diatomite on coal slurry water were investigated by single factor experiments, infrared spectroscopy, Brunauer-Emmett-Teller (BET) measurements, and zeta potential measurements. The single factor experiments showed that when the amount of microbial flocculant added was 1.5 ml, the temperature of coal slurry water was 39 °C, the pH was 5, and the amount of modified diatomite was 0.2 g, after 30 min of sedimentation, the flocculation transmittance of the coal slurry water reached 84.3%. The infrared spectra showed that the -NH2 and -OH of the chitosan molecule had a polar interaction with the Si-OH bond in diatomite. The BET measurements showed that the specific surface area of diatomite was not a decisive factor affecting the flocculation effect. Zeta potential measurements indicated that the amino protonation of chitosan increased the isoelectric point (IEP) of modified diatomite. These results showed that modified diatomite has a good effect on coal bio-flocculation.


Oppression and discrimination among lesbian, gay, bisexual, and Transgendered people and communities: a challenge for community psychology.
Lesbian, gay, bisexual, and transgendered (LGBT) people continue to experience various forms of oppression and discrimination in North America and throughout the world, despite the social, legal, and political advances that have been launched in an attempt to grant LGBT people basic human rights. Even though LGBT people and communities have been actively engaged in community organizing and social action efforts since the early twentieth century, research on LGBT issues has been, for the most part, conspicuously absent within the very field of psychology that is explicitly focused on community research and action--Community Psychology. The psychological and social impact of oppression, rejection, discrimination, harassment, and violence on LGBT people is reviewed, and recent advances in the areas of LGBT health, public policy, and research are detailed. Recent advances within the field of Community Psychology with regard to LGBT research and action are highlighted, and a call to action is offered to integrate the knowledge and skills within LGBT communities with Community Psychology's models of intervention, prevention, and social change in order to build better theory and intervention for LGBT people and communities.


Oceanographic and biogeochemical insights from diatom genomes.
Diatoms are the most successful group of eukaryotic phytoplankton in the modern ocean and have risen to dominance relatively quickly over the last 100 million years. Recently completed whole genome sequences from two species of diatom, Thalassiosira pseudonana and Phaeodactylum tricornutum, have revealed a wealth of information about the evolutionary origins and metabolic adaptations that have led to their ecological success. A major finding is that they have incorporated genes both from their endosymbiotic ancestors and by horizontal gene transfer from marine bacteria. This unique melting pot of genes encodes novel capacities for metabolic management, for example, allowing the integration of a urea cycle into a photosynthetic cell. In this review we show how genome-enabled approaches are being leveraged to explore major phenomena of oceanographic and biogeochemical relevance, such as nutrient assimilation and life histories in diatoms. We also discuss how diatoms may be affected by climate change-induced alterations in ocean processes.


A survey of Australian haematology reference intervals.
This study was designed to create a snapshot of Australian haematology reference intervals (RIs) in use, in particular red cell parameters. We present an analysis of survey results conducted across Australian laboratories between November 2012 and January 2013.All Australian laboratories enrolled in the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were invited to participate in the December 2012 Survey Monkey survey, with a response from 85 laboratories (17%) received. The scope included laboratory demographics (location, size/throughput, and network), RIs in use for the full blood count and selected derived parameters, their frequency of revision, source and statistical approach for derivation. Further questions related to uncertainty of measurement, pregnancy values, paediatric/adult cut-off, haematology profiles reported and the use of extended parameters.There is more consistency with some upper and lower limits than others, and wide ranges for reported uncertainty of measurement (UM). There is no apparent consistency with RIs used for particular instruments and technologies. When laboratories change their RIs, most obtain them from a text book, paper or another laboratory and have difficulty in determining the source. If they do determine their own, most don't have a standard operating procedure and calculations are not consistent in terms of sample size and statistical methods used.We have presented evidence of the wide variations in RIs used in Australian laboratories and that arguably these do not differ significantly from each other. The paediatric age cut-off requires standardisation.


Intraspecific variation in expression of candidate genes for osmoregulation, heme biosynthesis and stress resistance suggests local adaptation in European flounder (Platichthys flesus).
Despite the recent discovery of significant genetic structuring in a large number of marine organisms, the evolutionary significance of these often minute genetic differences are still poorly understood. To elucidate the adaptive relevance of low genetic differentiation among marine fish populations, we studied expression differences of osmoregulatory and stress genes in genetically weakly differentiated populations of the European flounder (Platichthys flesus), distributed across a natural salinity gradient. Flounders were maintained in a long-term reciprocal transplantation experiment mimicking natural salinities in the North Sea and the Baltic Sea. Applying real-time quantitative PCR and microarray analysis we studied expression of four candidate genes (hsp70, angiotensinogen, Na/K-ATPase-alpha and 5-aminolevulinic acid synthase (ALAS)) in gill, kidney and liver tissues. Genes involved in osmoregulative processes (Na/K-ATPases-alpha and angiotensinogen) showed highly plastic but similar expression in the two populations dependent on environmental salinity. However, we observed a unique sixfold up-regulation of hsp70 in kidney tissue of flounder from the North Sea following long-term acclimation to Baltic salinities. Similarly, significant differences between North Sea and Baltic flounders in expression of ALAS in response to different salinities were found in gill and liver tissue. These findings strongly suggest that gene expression in flounders is shaped by adaptation to local environmental conditions. This identification of adaptive differences in high gene flow marine organisms adds a new dimension to our current understanding of evolutionary processes in the sea and is of paramount importance for identification, protection and sustainable management of marine biodiversity.


SIRT1 is downregulated in gastric cancer and leads to G1-phase arrest via NF-κB/Cyclin D1 signaling.
Sirtuin 1 (SIRT1) is a class III histone/protein deacetylase, and its activation status has been well documented to have physiologic benefits in human health. However, the function of SIRT1 in cancer remains controversial. Here, the expression and role of SIRT1 in gastric cancer is delineated. SIRT1 was present in all normal gastric mucosa specimens; however, it was only present in a portion of the matched gastric cancer tumor specimens. In SIRT1-positive tumors, both mRNA and protein levels were downregulated as compared with the corresponding nonneoplastic tissue. Ectopic expression of SIRT1 inhibited cell proliferation, diminished clonogenic potential, and induced a G1-phase cell-cycle arrest, the effects of which were not apparent when a catalytic-domain mutant form of SIRT1 was introduced, suggesting that SIRT1 functions in gastric cancer are dependent on its deacetylase activity. Further evidence was obtained from depletion of SIRT1. At the molecular level, SIRT1 inhibited the transcription of Cyclin D1 (CCND1), and inhibition of NF-κB in SIRT1-depleted cells rescued Cyclin D1 expression. Furthermore, inhibition of either NF-κB or Cyclin D1 in SIRT1-depleted cells reversed the inhibitory effects of SIRT1. The inhibitory role of SIRT1 was also verified in vivo using xenografts. This work characterizes SIRT1 status and demonstrates its inhibitory function in gastric cancer development, which involves NF-κB/Cyclin D1 signaling, offering a therapeutic role for SIRT1 activators. The inhibitory functions of SIRT1, which involve NF-κB/Cyclin D1 signaling, suggest the utility of SIRT1 activators in the prevention and therapy of gastric cancer.


Co-encapsulation of probiotics with prebiotics and their application in functional/synbiotic dairy products.
Oral administration of live probiotics along with prebiotics has been suggested with numerous beneficial effects for several conditions including certain infectious disorders, diarrheal illnesses, some inflammatory bowel diseases, and most recently, irritable bowel syndrome. Though, delivery of such viable bacteria to the host intestine is a major challenge, due to the poor survival of the ingested probiotic bacteria during the gastric transit, especially within the stomach where the pH is highly acidic. Although microencapsulation has been known as a promising approach for improving the viability of probiotics in the human digestive tract, the success rate is not satisfactory. For this reason, co-encapsulation of probiotics with probiotics has been practised as a novel alternative approach for further improvement of the oral delivery of viable probiotics toward their targeted release in the host intestine. This paper discusses the co-encapsulation technologies used for delivery of probiotics toward better stability and viability, as well the incorporation of co-encapsulated probiotics and prebiotics in functional/synbiotic dairy foods. The common encapsulation technologies (and the materials) used for this purpose, the stability and survival of co-encapsulated probiotics in the food, and the release behavior of the co-encapsulated probiotics in the gastrointestinal tract have also been explained. Most studies reported a significant improvement particularly in the viability of bacteria associated with the presence of prebiotics. Nevertheless, the previous research has mostly been carried out in the simulated digestion, meaning that future systematic research is to be carried out to investigate the efficacy of the co-encapsulation on the survival of the bacteria in the gut in vivo.


[Lymphedema after breast carcinoma. A study of 5868 cases].
According to published reports, the incidence of lymphoedema of the arm in patients with cancer of the breast, treated by either surgery or radiotherapy, varies widely. We obtained basic data on the treatment of breast cancer in a large number of patients in order to determine the relationship between the incidence of lymphoedema and the radical nature of the primary treatment. Data were collected on all women with lymphoedema of the arm after treatment for breast cancer between 1972 and 1995. The increase in arm circumference was measured by a standardised method. Only those patients were included in the final analysis whose arm circumference had increased by at least 2 cm. The type of operation and(or) radiotherapy, tumor histology and TNM classification were recorded. There were 1405 cases of arm lymphoedema after treatment of 5868 cases of breast cancer (24%). 2515 breast cancers had been treated surgically. 3353 surgically and by radiotherapy. Lymphoedema occurred in 22.3% after radical mastectomy without radiotherapy and in 44.4% with it; after modified radical mastectomy without radiotherapy in 19.1%, in 28.9% with radiotherapy; after breast-preserving operation without radiotherapy in 6.7%, with radiotherapy in 10.1%. Until the 1970s radical mastectomy with conventional postoperative radiotherapy has been the treatment of choice, with 38% cases of lymphoedema. This incidence gradually decreased to 16% in subsequent years. The incidence of lymphoedema of the arm depends on the radical nature of the primary treatment. The quality of life could be easily improved through minimising the incidence of lymphoedema if current standards of breast-preserving surgery were generally practised.


Wearable Activity Tracking Device Use in an Adolescent Weight Management Clinic: A Randomized Controlled Pilot Trial.
The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity. Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, 12, and 18 weeks were examined. Forty-eight participants were enrolled in the study. Eighteen subjects were randomly assigned to the ATI group and 30 to control. The average age was 14.5 years. Overall, the majority of participants were Hispanic (56%). Sexes were equally distributed. The average baseline BMI was 37.5 kg/m2. At the study conclusion, the overall attrition rate was 52.1%, 44.4% in the ATI group versus 56.6% in the control group, with a differential attrition of 12.2%. The ATI and control groups each showed an absolute decrease in BMI of -0.25 and -2.77, respectively, with no significant differences between the groups. The attrition rate in our study was >50%. Participation in the AWMC by the ATI and control groups resulted in maintenance of BMI and body weight for the study duration. However, the use of an activity tracking device was not associated with greater weight loss. This trial is registered with NCT03004378.


Gaussian beam scattering from a dielectric cylinder, including the evanescent region.
The scattering of a two-dimensional Gaussian beam from a homogeneous dielectric cylinder is analyzed using a plane-wave spectrum. Special attention is given to the computation of the evanescent field of the beam and its effect in the scattering. A comparison is made between the evanescent field in Cartesian coordinates and in cylindrical coordinates as a sum of cylindrical waves. The field given by the cylindrical wave equation is found to converge spatially as we include more Bessel modes. The evanescent field incident on the dielectric cylinder is found to cause radiating waves to form and propagate outward.


Testing for optic ataxia in a blind field.
Optic ataxia is a component of Balint's syndrome and is a disorder that results from damage to the posterior parietal cortex (PPC) leading to deficits in reaching and grasping objects presented in the visual field opposite to the damaged hemisphere. It is also often the case that Balint's syndrome is accompanied by visual field defects due to the proximity of parietal and occipital cortices and also due to the subcortical pathway relaying visual information from the retina to the visual cortex passing underneath the parietal cortex. The presence of primary visual defects such as hemianopia often prevents clinicians from diagnosing higher-level visual deficits such as optic ataxia; the patient cannot reach to targets he/she cannot see. Here, we show that through the use of a paradigm that takes advantage of remapping mechanisms, we were able to observe optic ataxia in the blind field. We measured reach endpoints of a patient presenting with left optic ataxia as well as a quadrantanopia in the left lower visual field in eye-static and eye-dynamic conditions. In static conditions, we first asked the patient to reach to targets viewed in her non-optic ataxic intact right visual field (fixating on the left of the target array). In this case, the patient showed undershoots equivalent to controls. Next, we asked her to reach to (the same) targets viewed in the upper left optic ataxic but intact visual field (fixating to the right of the target array). The undershooting pattern increased greatly, consistent with unilateral left optic ataxia. In dynamic conditions, we asked her to view targets in her good (right lower) visual field before reorienting her line of sight to the opposite side, causing the internal representation of the target to be updated into the opposite (ataxic) blind visual field. The patient then reached to the remembered (and updated) location of the target. We found errors typical of optic ataxia for reaches guided toward the quadrantanopic field. This confirmed that reaching errors depended on the updated internal representation of the target and not on where the target was viewed initially. In both the patient and the controls, the updating of target location was partial, with reaching errors observed subsequent to an eye movement made from left to right fixation positions being intermediate between the left and right static conditions. Thus, using this remapping paradigm, we were able to observe optic ataxia in the blind field. In conclusion, this remapping paradigm would allow clinicians to test for visuo-manual transformation deficits (optic ataxia) even when it is associated with hemianopia.


Machine Learning on Signal-to-Noise Ratios Improves Peptide Array Design in SAMDI Mass Spectrometry.
Emerging peptide array technologies are able to profile molecular activities within cell lysates. However, the structural diversity of peptides leads to inherent differences in peptide signal-to-noise ratios (S/N). These complex effects can lead to potentially unrepresentative signal intensities and can bias subsequent analyses. Within mass spectrometry-based peptide technologies, the relation between a peptide's amino acid sequence and S/N remains largely nonquantitative. To address this challenge, we present a method to quantify and analyze mass spectrometry S/N of two peptide arrays, and we use this analysis to portray quality of data and to design future arrays for SAMDI mass spectrometry. Our study demonstrates that S/N varies significantly across peptides within peptide arrays, and variation in S/N is attributable to differences of single amino acids. We apply supervised machine learning to predict peptide S/N based on amino acid sequence, and identify specific physical properties of the amino acids that govern variation of this metric. We find low peptide-S/N concordance between arrays, demonstrating that different arrays require individual characterization and that global peptide-S/N relationships are difficult to identify. However, with proper peptide sampling, this study illustrates how machine learning can accurately predict the S/N of a peptide in an array, allowing for the efficient design of arrays through selection of high S/N peptides.


Role of human Keap1 S53 and S293 residues in modulating the binding of Keap1 to Nrf2.
Keap1 is deemed as a suppressor of Nrf2 in cytoplasm by sequestrating Nrf2 to proteolysis as an adapter of the Cul3-Rbx1 E3 ubiquitin ligase complex. In the study, it was proposed that post-translational modification might affect the interaction between Nrf2 and Keap1, and the profiles of the phosphorylation of amino acid residues of Keap1 and its effects on the binding of Keap1 to Nrf2 was investigated. A mass spectrometry analysis revealed that S53 and S293 were phosphorylated upon an oxidative stress. Using Keap1 proteins with amino acid residues mutated to glutamate to simulate the introduction of a negative charge by phosphorylation, it was found that a potential phosphorylation of S53 affected Keap1-Nrf2 binding in the pull-down assay, and induced nuclear translocation of Nrf2 in the electrophoretic mobility shift assay. Sequence homology analysis showed that S53 was highly conserved. Structural modeling around BTB domain of wild type and S53E-mutant Keap1 showed that the negative charge introduced by S53E mutation generates a salt bridge between E53 and ionized guanidine group of Arg50. Real-time qRT-PCR for transcription levels of antioxidant genes that are modulated by Nrf2 further proved the effects of the potential phosphorylation of S53 under an oxidative stress condition. In summary, S53 is a potential phosphorylation site of Keap1, and the phosphorylation could enhance the antioxidative capacity of cells in response to an oxidative stress.


[Toxicity of benzhydrylurea under experimental conditions].
Benzhydrylurea, which displays an anticonvulsant action and is of low acute toxicity in capable after a 3-month administration to rats to inhibit the growth of male-rats, intensify the excretion of protein with the urine, raise the blood sugar level (with its single administration--to reduce), provoke dystrophic changes in the liver, kidneys and central nervous system. Following a 1--3-week introduction of the substance guinea pigs and cats demonstrate hemorrhagic erosions in the stomach and small intestine (but not rabbits, dogs and rats), the appearance of pathological forms of erythrocytes, while guinea pigs suffer from leucopoietic disorders.


[Impression technique with tubes].
Description of a technique that allows the copy of the finishing line even when this line es deep in to the sulcus and without the need of gingival retraction which is very painful, bleeds easily and is limited to few teeth. The impression technique with acrylic tubes allows the operator to duplicate models if it is so desired, at the same time full arch impressions with multiple preparations can be taken in one attempt.


Effects of lead on the adult brain: a 15-year exploration.
Historically, there has been minimal concern about the effect of adult lead exposure on the brain. Evidence from recent longitudinal studies raise concerns about the long-term effects of past exposure. We initiated three independent longitudinal studies to determine whether cumulative lead exposure was associated with persistent or progressive brain effects. The studies include 1,109 former U.S. organolead manufacturing workers, 803 current and former inorganic lead workers in Korea, and 1,140 50- to 70-year-old Baltimore residents with environmental lead exposure. The organolead workers had past exposure to inorganic and tetraethyl lead (TEL); in the other two studies, exposure was to inorganic lead. In each of these studies, we measured blood lead and tibia and patella lead by 109Cd K-shell-induced X-ray fluorescence. Higher tibia lead was consistently associated with poorer measures of cognitive function. Longitudinal analysis of the Korean and organolead cohort indicate that the effect of lead is persistent. Moreover, MRI data on organolead workers indicates a possible progressive effect from past exposure; higher tibia lead was associated with lower brain volume. The latter study indicates that a difference in tibia lead equivalent to about one-sixth of the overall range was associated with a mean difference in these cognitive tests that was equivalent, on average, to what was observed for a five-year age difference. Our data suggest that a significant proportion of what is considered to be "normal" age-related cognitive decline may, in fact, be due to past exposure to neurotoxicants such as lead.


Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.
Low reprogramming efficiency and reduced pluripotency have been the two major obstacles in induced pluripotent stem (iPS) cell research. An effective and quick method to assess the pluripotency levels of iPS cells at early stages would significantly increase the success rate of iPS cell generation and promote its applications. We have identified a conserved imprinted region of the mouse genome, the Dlk1-Dio3 region, which was activated in fully pluripotent mouse stem cells but repressed in partially pluripotent cells. The degree of activation of this region was positively correlated with the pluripotency levels of stem cells. A mammalian conserved cluster of microRNAs encoded by this region exhibited significant expression differences between full and partial pluripotent stem cells. Several microRNAs from this cluster potentially target components of the polycomb repressive complex 2 (PRC2) and may form a feedback regulatory loop resulting in the expression of all genes and non-coding RNAs encoded by this region in full pluripotent stem cells. No other genomic regions were found to exhibit such clear expression changes between cell lines with different pluripotency levels; therefore, the Dlk1-Dio3 region may serve as a marker to identify fully pluripotent iPS or embryonic stem cells from partial pluripotent cells. These findings also provide a step forward toward understanding the operating mechanisms during reprogramming to produce iPS cells and can potentially promote the application of iPS cells in regenerative medicine and cancer therapy.


Synthetic Immunogenic Cell Death Mediated by Intracellular Delivery of STING Agonist Nanoshells Enhances Anticancer Chemo-immunotherapy.
Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.


Cr2 O3 Promoted In2 O3 Catalysts for CO2 Hydrogenation to Methanol.
Cr2 O3 was applied to study the modification of In2 O3 based catalysts for CO2 hydrogenation to methanol reaction. Combined with X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), X-ray photoelectron spectroscopy (XPS), etc., the structure of the catalysts was characterized. The reaction performances for CO2 hydrogenation to methanol were evaluated on a stainless-steel fix-bed reactor. The results showed that solid solutions were formed for the Cr2 O3 promoted In2 O3 catalysts. The important role of electronic interaction between Cr2 O3 and In2 O3 was revealed in the hydrogenation reaction. In1.25 Cr0.75 O3 sample exhibited the highest methanol yield, which was 2.8 times higher than that of pure In2 O3 . No deactivation was observed for In1.25 Cr0.75 O3 sample during the 50 hours of reaction. The improved catalytic performance may be due to the formation of the solid solutions and the highest amount of oxygen vacancies.


Mitochondrial genomic markers confirm the presence of the camel strain (G6 genotype) of Echinococcus granulosus in north-western China.
Twenty-eight isolates of E. granulosus, collected from humans at surgery, and a range of intermediate hosts, including sheep, cattle and camels from abattoirs in North and South Xinjiang Uygur Autonomous Region, People's Republic of China, were analysed for DNA sequence variation within regions of the mitochondrial cytochrome c oxidase I (COI) and NADH dehydrogenase subunit I (NDI) genes. The isolates were categorized into 2 distinct and uniform genotypic groupings, based on the sequences obtained, and the data clearly indicated that the camel/dog strain (G6 genotype) of E. granulosus as well as the cosmopolitan, common sheep strain (G1 genotype) occur in north Xinjiang. The presence of the camel strain has thus been confirmed in Xinjiang but it is evident from this and a previous molecular genetic survey of E. granulosus isolates from north-western China that the common sheep strain is the most predominant in the region. From the public health perspective, the majority of infected livestock will act as reservoirs of human infection there. During the course of the study, a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay, based on the NDI sequence variation, was developed that allows rapid discrimination of the G1 and G6 genotypes.


[Analysis of tracheal morphology by spiral CT in 126 cleft palate children].
Objective: To discuss the surgical safeness of the cleft palate children with airway stenosis by means of analyzing characteristics of the shape of the upper airway and comparing clinical data of cleft palate children with airway stenosis and non-airway stenosis. Methods: Tracing back from Apirl 2015 to Apirl 2017, 126 cleft palate children treated in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, were included (46 male and 80 female, age of 7 to 74 months, median age 18 months). According to the spiral CT scan of neck, patients were categorized to airway-stenosis group (65 patients) and non-airway-stenosis group (61 patients). For airway-stenosis group, suspected difficult intubation plan is applied, guiding endotracheal intubation via visible laryngoscope. For non-airway-stenosis group, ordinary plan of endotracheal intubation is applied. Study the statistics of both groups in the measurement of the upper airway, the success rate of tracheal intubation, operation time, hospital day. Results: Based on anatomical location of the airway stenosis, cleft palate children were divided into: nasopharynx, 5 cases; laryngel, 55 cases; initiation part of trachea to arch of aorta, 2 cases; arch of aorta to bronchial bifurcation, 3 cases. Regardless of airway stenosis, the upper airway of cleft palate children in the subglottic area and the cricoid area was elliptical, with the transverse dimension narrow and the anteroposterior dimension wide. Comparing to non-airway-stenosis group, the airway in airway-stenosis group remained narrower in the anteroposterior dimension in the subglottis area [(7.69±1.76) mm]; also remained narrower in the transverse dimension [(5.96±1.27) mm] and the anteroposterior dimension [(8.16±1.31) mm] in the cricoid area (P<0.05). Pre-and post-operative monitor blood oxygen saturation of all patients were normal. Ventilator weaning of all patients was successful. There were no statistical significance in operation time and hospital day between airway-stenosis group and non-airway-stenosis group (P>0.05). Conclusions: The upper airway of the subglottic area and the cricoid area in cleft palate children are elliptical, with the transverse dimension narrow and the anteroposterior dimension wide. Cleft palate children with airway stenosis underwent surgery smoothly by using a portable visible laryngoscope.


Comparing smoking and smoking cessation process in the Republic of Karelia, Russia and North Karelia, Finland.
The aims of this study were to assess and validate self reported smoking prevalence and to assess smoking cessation related process variables in the Republic of Karelia, Russia and in North Karelia, Finland. Comparative population surveys of random population samples from both areas in spring 1992. The study included a self administered questionnaire, physical measurements and laboratory tests. The validity of self reported smoking prevalence was assessed by serum cotinine analyses. The district of Pitkäranta in the Republic of Karelia, Russia and province of North Karelia, Finland. The study population was a 25 to 64 year old population in both areas. A stratified random sample of 1000 people in Pitkäranta and 2000 people in North Karelia was drawn from the population registers. In Pitkäranta 380 men and 455 women, and in North Karelia 673 men and 803 women, participated in the survey. The self reported prevalence rates of daily smoking in Pitkäranta were 65% among men and 10% among women. In North Karelia the respective rates were 29% and 13%. Women in Pitkäranta greatly underreported their smoking status, which was assessed by comparing the self reported data to the serum cotinine measurements. The smoking prevalence among women in Pitkäranta would rise from 10% to 21% if all participants with high cotinine values would be regarded as smokers. Compared with smokers in North Karelia, a higher percentage of smokers in Pitkäranta expressed their wish to quit and believed that they would succeed. However, on average they had fewer previous smoking cessation attempts than smokers in North Karelia. In addition, the health personnel in North Karelia were more active in advising smokers to quit. High smoking prevalence among men in Pitkäranta obviously contributes much to the high premature death rate in the Republic of Karelia. There is considerable underreporting of smoking in Pitkäranta, especially among women, which is probably attributable to the cultural unacceptability of female smoking in Russia. The common wish to quit, few previous cessation attempts and much lower rates of ex smokers, together with less smoking cessation counselling from health personnel, need to be considered in tailoring antismoking interventions in the area.


Fish migration, dams, and loss of ecosystem services in the Mekong basin.
The past decade has seen increased international recognition of the importance of the services provided by natural ecosystems. It is unclear however whether such international awareness will lead to improved environmental management in many regions. We explore this issue by examining the specific case of fish migration and dams on the Mekong river. We determine that dams on the Mekong mainstem and major tributaries will have a major impact on the basin's fisheries and the people who depend upon them for food and income. We find no evidence that current moves towards dam construction will stop, and consider two scenarios for the future of the fisheries and other ecosystems of the basin. We conclude that major investment is required in innovative technology to reduce the loss of ecosystem services, and alternative livelihood strategies to cope with the losses that do occur.


Link between diet and chemotherapy related gastrointestinal side effects.
To evaluate an association between food products consumption, dietary intake and the incidence of selected gastrointestinal symptoms (nausea, vomiting, diarrhea and constipation) in cancer patients undergoing chemotherapy. Fifty six women receiving chemotherapy for ovarian cancer were eligible for the study. Anthropometrical measurements were assessed. The dietary intake was evaluated by 24-hours food records. The association between the consumption of selected food products and gastrointestinal symptoms incidences was assessed by modified semi-quantitative food frequency questionnaire including 77-different food items that was developed and applied in cancer patients undergoing chemotherapy. BMI values indicated 9%, 45%, 30% and 16% of patients as underweight, normal weight, overweight and obese respectively. Only 23% and 32% of patients never experienced nausea and constipation when 43% and 45% never experienced vomiting and diarrhea. Nausea was promoted by oils, constipation by chocolate and chocolate products and diarrhea by dairy products, stone fruit and apple. Significant inverse correlations were found between vomiting and the intake of energy, fat, protein, carbohydrates, B groups vitamins, vitamin D, phosphorus and zinc. The difference in energy intake between marginal values of vomiting incidence exceeded 400 kcal. Dietary intake as well as specific food products influence on gastrointestinal side effect of chemotherapy in cancer patients. The dietary approach based on either exclusion or limited intake of selected food products and improvement of diet could reduce and prevent chemotherapy induced gastrointestinal symptoms therefore should be taken under consideration in clinical practice.


Activation of apoptosis by rationally constructing NIR amphiphilic AIEgens: surmounting the shackle of mitochondrial membrane potential for amplified tumor ablation.
In recent years, the use of aggregation-induced emission luminogens (AIEgens) for biological imaging and phototherapy has become an area of intense research. However, most traditional AIEgens suffer from undesired aggregation in aqueous media with "always on" fluorescence, or their targeting effects cannot be maintained accurately in live cells with the microenvironment changes. These drawbacks seriously impede their application in the fields of bio-imaging and antitumor therapy, which require a high signal-to-noise ratio. Herein, we propose a molecular design strategy to tune the dispersity of AIEgens in both lipophilic and hydrophilic systems to obtain the novel near-infrared (NIR, ∼737 nm) amphiphilic AIE photosensitizer (named TPA-S-TPP) with two positive charges as well as a triplet lifetime of 11.43 μs. The synergistic effects of lipophilicity, electrostatic interaction, and structure-anchoring enable the wider dynamic range of AIEgen TPA-S-TPP for mitochondrial targeting with tolerance to the changes of mitochondrial membrane potential (ΔΨ m). Intriguingly, TPA-S-TPP was difficult for normal cells to be taken up, indicative of low inherent toxicity for normal cells and tissues. Deeper insight into the changes of mitochondrial membrane potential and cleaved caspase 3 levels further revealed the mechanism of tumor cell apoptosis activated by AIEgen TPA-S-TPP under light irradiation. With its advantages of low dark toxicity and good biocompatibility, acting as an efficient theranostic agent, TPA-S-TPP was successfully applied to kill cancer cells and to efficiently inhibit tumor growth in mice. This study will provide a new avenue for researchers to design more ideal amphiphilic AIE photosensitizers with NIR fluorescence.


Genetics of human aggressive behaviour.
A consideration of the evolutionary, physiological and anthropological aspects of aggression suggests that individual differences in such behaviour will have important genetic as well as environmental underpinning. Surveys of the likely pathways controlling the physiological and neuronal processes involved highlight, as obvious targets to investigate, genes implicated in sexual differentiation, anxiety, stress response and the serotonin neurotransmitter pathway. To date, however, association studies on single candidates have provided little evidence for any such loci with a major effect size. This may be because genes do not operate independently, but function against a background in which other genetic and environmental factors are crucial. Indeed, a series of recent studies, particularly concentrating on the serotonin and norepinephrine metabolising enzyme, monoamine oxidase A, has emphasised the necessity of examining gene by environmental interactions if the contributions of individual loci are to be understood. These findings will have major significance for the interpretation and analysis of data from detailed whole genome association studies. Functional imaging studies of genetic variants affecting serotonin pathways have also provided valuable insights into potential links between genes, brain and aggressive behaviour.


Pixelation effect removal from fiber bundle probe based optical coherence tomography imaging.
A method of eliminating pixelization effect from en face optical coherence tomography (OCT) image when a fiber bundle is used as an OCT imaging probe is presented. We have demonstrated that applying a histogram equalization process before performing a weighted-averaged Gaussian smoothing filter to the original lower gray level intensity based image not only removes the structural artifact of the bundle but also enhances the image quality with minimum blurring of object's image features. The measured contrast-to-noise ratio (CNR) for an image of the US Air Force test target was 14.7dB (4.9dB), after (before) image processing. In addition, by performing the spatial frequency analysis based on two-dimensional discrete Fourier transform (2-D DFT), we were able to observe that the periodic intensity peaks induced by the regularly arrayed structure of the fiber bundle can be efficiently suppressed by 41.0dB for the first nearby side lobe as well as to obtain the precise physical spacing information of the fiber grid. The proposed combined method can also be used as a straight forward image processing tool for any imaging system utilizing fiber bundle as a high-resolution imager.


[Radiological findings in endomyocardial fibrosis].
To determine through conventional radiology the type of ventricular involvement in endomyocardial fibrosis (EMF). We analyzed 56 cases with EMF confirmed by angiocardiography and 9 by postmortem study, aged between 16 and 56 years (mean 32); there were 42 females. Only one radiologist analyzed X-rays without any knowledge of the cineangiography findings. The right side of the heart was primarily involved in 9 patients and the cardiac silhouette was characteristically globular and had oligemic pulmonary fields (66.66%). The cardiothoracic ratio was 0.62 +/- 0.11. Out of 9 patients, 8 were female. The left side of the heart was established as being primarily involved in 11 cases and simulated rheumatic mitral disease. The cardiothoracic ratio was 0.51 +/- 0.09 and there were increased pulmonary fields in 63.6%. The biventricular disease occurred in 36 cases. There were radiologic findings of right and left side. The cardiothoracic ratio was 0.63 +/- 0.06 and there was oligemic pulmonary fields in 38.8%, increased pulmonary fields in 33.3% and was normal in 27.7%. There were 4:1 females. The radiological study is fundamental in the initial diagnosis of EMF. The type of involvement could be done in 66.07% of all cases by chest X-ray.


Detention of British citizens as hostages in the Gulf--health, psychological, and family consequences.
To describe the physical, psychological, and family consequences of the detention of British subjects as hostages in Kuwait or Iraq, or both, after the invasion of Kuwait on 2 August 1990 and to investigate the relation between types of trauma experienced and these reactions. Postal questionnaire. 381 respondents. Many health, social, and psychological sequelae were identified. Problems with present finance, accommodation, and work are important causes of distress. Many hostages coped well and gained self esteem. A minority of respondents require further support and treatment. Expatriates in risk areas should retain assets in their home country.


Rilzabrutinib, an Oral BTK Inhibitor, in Immune Thrombocytopenia.
Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies. In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of ≥50×103 per cubic millimeter and an increase from baseline of ≥20×103 per cubic millimeter without the use of rescue medication). Sixty patients were enrolled. At baseline, the median platelet count was 15×103 per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50×103 per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50×103 per cubic millimeter was 65%. Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment. (Funded by Sanofi; ClinicalTrials.gov number, NCT03395210; EudraCT number, 2017-004012-19.).


Chronic angiotensin II inhibition increases levels of calcitonin gene-related peptide mRNA of the dorsal root ganglia in spontaneously hypertensive rats.
We previously reported that the vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing nerves and level of CGRP mRNA in the dorsal root ganglia (DRG) in spontaneously hypertensive rats (SHR) decreased with age, and that the reduced function of CGRP nerves was restored by chronic inhibition of angiotensin II. The present study was performed to investigate the effect of long-term treatment with angiotensin II type-1 receptor antagonists (L-158,809 and olmesartan), an angiotensin converting enzyme inhibitor (temocapril) and hydralazine on levels of CGRP mRNA in DRG of SHR and the contents of CGRP in the mesenteric artery and atrium. The level of CGRP mRNA and degree of CGRP-like immunoreactivities (CGRP-LI) were measured by Northern blot hybridization assay and enzyme-linked immunosorbent assay, respectively. Seven week-treatment of 8 week-old SHR with temocapril (0.005%), L-158,809 (0.001%), olmesartan (0.01%) or hydralazine (0.01%) administered in drinking water significantly lowered the systolic blood pressure of SHR. The level of CGRP mRNA in the DRG of control SHR was significantly lower than that in normotensive Wistar Kyoto rats (WKY), whereas the level of CGRP-LI in the mesenteric artery and atrium of SHR were significantly greater than those in WKY. Treatment of SHR with temocapril, L-158,809, or olmesartan, but not hydralazine, significantly elevated the levels of CGRP mRNA in DRG, markedly increased the level of CGRP-LI in the mesenteric artery, and slightly increased the CGRP-LI level in the atrium. These results suggest that long-term inhibition of angiotensin II restores the reduced expression of CGRP mRNA in DRG and may facilitate neurotransmission of CGRP-containing vasodilator nerves in SHR.


Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity.
To define whether minor adult hemoglobin A2 (HbA2, α2δ2) exerts any protective activity in multiple sclerosis (MS). HbA2 levels were measured in 146 MS patients with high performance liquid chromatography and association with MS Severity Scores (MSSS) were determined. HbA2 associations with blood count parameters were also studied using blood counts evaluated on the same day of high performance liquid chromatography sampling. Routine biochemical parameters were also determined to rule out elusively influential factors, such as anemia and thyroid disorders. HbA2 levels negatively correlated with MSSS (Spearman correlation, R: -0.186, P=0.025). Exclusion of confounding factors with a generalized linear model revealed an even stronger negative correlation between HbA2 and MSSS (P<0.001). HbA2 positively correlated with red blood cells (RBCs) (R=0.350, P<0.001) and in turn, RBCs negatively correlated with MSSS (R=-0.180, P=0.031). Average HbA2 levels were highest among patients treated with interferon β1a. RBC fragility is increased in MS, and recent data suggest that circulating free Hb contributes to neural injury in MS. HbA2 and its oxidative denaturation product hemichrome A2 enhance RBC membrane stability to a greater extent than do major HbA or hemichrome A. Reductions in ischemic cerebrovascular vascular events are reported in β-thalassemia carriers and HbA2 levels are considerably higher in this population. Episodic declines of cerebral blood flow were shown in bipolar disorder, and we have recently shown a protective role of HbA2 against postpartum episodes in females with bipolar disorder. HbA2's erythroprotective functions may reduce free Hb and long-term neural injury in MS.


FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype.
Homozygous mutations in the gene for fatty acid 2-hydroxylase (FA2H) have been associated in humans with three neurodegenerative disorders: complicated spastic paraplegia (SPG35), leukodystrophy with spastic paraparesis and dystonia, and neurodegeneration with brain iron accumulation. Here, we describe a novel homozygous c.270+3A>T mutation in an Italian consanguineous family. In two affected brothers (age at molecular diagnosis 22y and 15y; age at last follow-up 24y and 17y), altered FA2H function led to a severe phenotype, with clinical features overlapping those of the three FA2H-associated disorders. Both patients showed childhood onset progressive spastic paraparesis, mild pyramidal and cerebellar upper limb signs, severe cognitive impairment, white-matter disease, and cerebellar, brainstem, and spinal cord atrophy. However, absence of dystonia, drowsiness episodes, and a subtle globus pallidus involvement suggested that FA2H mutations result in a clinical spectrum, rather than causing distinct disorders. Although clinical heterogeneity is apparent, larger numbers of patients are needed to establish more accurate genotype-phenotype correlations.


Hemochromatosis (HFE) and transferrin receptor-1 (TFRC1) genes in sporadic porphyria cutanea tarda (sPCT).
Porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis, is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (UROD). Two forms of PCT have been described: a familial one (fPCT) with an inherited decrease of UROD activity in all tissues and a sporadic one (sPCT) with a decreased UROD activity restricted to the liver. Iron overload and acquired factors including hepatic viral infections, alcohol, drugs contribute to the expression of PCT. In 65 French sPCT patients and 108 controls we have evaluated the respective role of iron and HCV status, the hemochromatosis (HFE) gene mutations frequencies (H63D. S65C, C282Y), and in a case control study we searched for an association between sPCT and the human transferrin receptor-1 (TFRC1) gene whose product is thought to be in functional association with the HFE protein: three single nucleotide polymorphisms (SNPs) previously characterized and 2 novel ones were studied. The iron-related parameters and transaminases were higher in sPCT patients than those of non-porphyric controls. Of the sPCT patients studied, 28% were HCV positive. In the HFE gene, 17% of sPCT patients carried C282Y mutation compared to 4% in controls, no significant differences were found with H63D and S65C variants. Compound heterozygous genotypes, C282Y/H63D or C282Y/S65C, were not significantly different in sPCT and control groups. Independently from HFE gene mutations, an association was found between the IVS4+198 T allele in the TFRC1 gene and sPCT patients. Analysis of HFE genotypes indicated that C282Y (but not H63D nor S65C) is a susceptibility factor for the development of sPCT in West European continental patients. However, analysis of TFRC1 genotypes suggest that sPCT should be considered as a multifactorial disorder in which other intracellular iron metabolism genes could be involved.


[16S rRNA sequence analysis: application and pitfalls].
16S rRNA gene sequencing is a useful tool for identification of non-cultured or hard-to-identify bacteria. This technique can be used to detect and identify bacteria in clinical materials, such as cerebrospinal fluid and heart valves, if conventional methods do not reveal pathogens. A major advantage compared with other techniques is that it is not necessary to know in advance what pathogen is the likely cause of the disease. An important drawback is the background noise generated by traces of bacterial DNA in reagents.


Toxicity of ionic liquids to Clostridium sp. and effects on uranium biosorption.
As green solvents ionic liquids (ILs) show high potential in nuclear industry for extraction and purification of actinides. However, to date relatively little information has been gained on ILs application in microbial processes, for example biosorption of radionuclides. We investigated the effects of three ILs, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), N-ethylpyridinium trifluoroacetate (EtPyCF3COO) and N-ethylpyridinium tetrafluoroborate (EtPyBF4) on the growth and biosorption of uranium by Clostridium sp. The ILs affected the growth of the bacterium as evidenced by decreases in optical density, total gas production, and organic acids production from glucose metabolism. The IC50-48h of three ILs decreased in the order of BMIMPF6 (8.26mM)>EtPyBF4 (7.04mM)>EtPyCF3COO (4.05mM). Uranium biosorption by the bacterial cells decreased by 75% in the presence of 1% (v/v) BMIMPF6 and by about 90% with 1% (v/v) EtPyBF4 or EtPyCF3COO, in comparison to the control without ILs. The diminished biosorption may be attributed to the membrane damages induced by EtPyBF4 and EtPyCF3COO, which can be visualized by Transmission Electron Microscope (TEM) analysis. Energy-dispersive X-ray spectroscopy (EDS) analysis revealed the accumulation of uranium inside peripheral membrane of the cells exposed to uranium alone or with BMIMPF6, while little or no accumulation was observed in the presence of EtPyBF4 and EtPyCF3COO. These results imply that potential toxicity of ILs towards microorganisms is a particularly important issue in limiting its biotechnological applications.


Dalbavancin: a lipoglycopeptide antibacterial for Gram-positive infections.
Dalbavancin is a lipoglycopeptide antibacterial agent with in vitro and in vivo activity against a number of Gram-positive organisms, including some with multidrug resistance. This is a review of the available literature explaining the pertinent information regarding dalbavancin's pharmacodynamics/pharmacokinetics, clinical efficacy, adverse event profile and potential place in therapy. The aim of the study was to explain the relevant data on dalbavancin's administration, efficacy and tolerability. A PubMed/MEDLINE search was used to review data published from January 1966 through to February 2008 with the keywords dalbavancin, lipoglycopeptide or BI 397. Dalbavancin, currently pending full FDA approval, has favorable minimum inhibitory concentrations against many Gram-positive organisms as compared to currently available antimicrobials. Dalbavancin has a prolonged half-life (149 - 300 h), which may lead to a therapeutic option that is different from available antimicrobials. Its efficacy and tolerability have been established in treating complicated skin and skin structure infections. Future data are required in order to determine dalbavancin's true place in therapy, if approval is achieved.


Hypothalamic expression of genes for appetite regulators and estrogen α, estrogen β and leptin receptors in obese dams and their fetuses.
Under- and over-nutrition during gestation may influence fetal hypothalamic development resulting in individuals predisposed to adverse health effects. This study examined fetuses from obese and control ewes to determine whether dam obesity alters hypothalamic expression of fetal appetite regulatory genes. A second objective was to contrast the expression of appetite regulatory genes in ewes that become the most obese to those that remained in moderate body condition on the same energy-rich diet. Multiparous, western white-faced ewes were weighed and individually fed 100% (control) or 150% (obese) of National Research Council requirements from day 60 before mating until day 75 of gestation. At day 75 of gestation, fetuses were collected and weighed. Hypothalamic tissue from fetal lambs and dams was collected and frozen for mRNA extraction. Dam obesity (P ≥ 0.16), fetal sex (P ≥ 0.44) or their interaction (P ≥ 0.42) did not affect the relative expression of fetal hypothalamic regulators of appetite, including neuropeptide Y, agouti-related protein, pro-opiomelanocortin, cocaine- and amphetamine-regulated transcript and receptors for leptin. Maternal obesity at day 75 of gestation in ewes did not affect developmental mechanisms responsible for the expression of fetal appetite regulatory genes and would not be expected to predispose offspring to adult-onset obesity through disrupted appetite regulation at this developmental time point. In the ewe, appetite regulatory genes did not differ (P > 0.20) with ewe adiposity; however, expression of estrogen receptor α, but not β (P = 0.37), in the medial basal hypothalamus was greater (P = 0.04) in obese than in control ewes.


Perspectives and experiences of community health workers in Brazilian primary care centers using m-health tools in home visits with community members.
Mobile health (m-health) tools are a promising strategy to facilitate the work of community health workers (CHWs) in low- and middle-income countries (LMICs). Despite their potential value, little is known about CHWs' experiences working with m-health tools in their outreach activities with community members. To understand the benefits of and barriers to using m-health tools for CHWs, we conducted semi-structured interviews with 57 CHWs employed in six primary care centers in São Paulo, Brazil. All CHWs had experience using a cell phone application called Geohealth for collecting health and demographic data of community members. We assessed their experiences using Geohealth and recommendations for improvements. CHWs described key benefits of using Geohealth as helping them save time with bureaucratic paperwork, organizing the data that they needed to collect, and by replacing sheaves of paper, reducing the weight that they carried in the field. However, there were many technical and social barriers to the successful adoption of the m-health tool. Key among these were poor quality hardware, faulty software programs, and negative community member perceptions of the m-health program. The CHWs provided valuable input as to how Geohealth could be improved to fit their needs. m-health tools have the potential to facilitate the work of CHWs in LMICs. However, such tools must be designed and implemented thoughtfully. Technical barriers related to both hardware and software must be anticipated and addressed to maximize their efficiency and successful adoption. CHW input on the design of the tool should be sought to maximize its utility and minimize barriers to use.


When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.
Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.


A Bioimpedance-Based Device to Assess the Volume Conduction Properties of the Tongue in Neurological Disorders Affecting Bulbar function.
Goal: Current instruments for bulbar assessment exhibit technical limitations that hinder the execution of clinical studies. The volume conduction properties (VCP) of the tongue reflect ionic content and myofiber integrity and they can serve as a new biomarker for evaluating neurological disorders with bulbar dysfunction. Methods: We designed a standalone bioimpedance measurement system that enables accurate, multi-frequency measurement of tongue anisotropic VCP including conductivity and relative permittivity. The system includes a tongue depressor with 16 non-invasive surface sensors for electrical contact with the tongue at directions 0[Formula: see text], 45[Formula: see text], 90[Formula: see text] and 150[Formula: see text]. The depressor is interfaced with the tongue electronic system with Bluetooth connectivity, and a smartphone application. De-identified patient data is sent by email. Results: We first determined the accuracy of the hardware performing phantom measurements mimicking a broad range of tongue values and determined the error to be [Formula: see text]1%. We then validated our new technology measuring a cohort of 7 healthy human subjects under Institutional Review Board approval. Conclusions: None of the subjects who participated suffered discomfort or gag reflexes. The novel technique presented for intra-oral assessment of tongue VCP provides standard, objective and quantitative data potentially sensitive to alterations in tongue internal structure and composition.


A Comparison of Two Depression Scales in a Geriatric Assessment Clinic.
Two commonly used geriatric depression rating scales are the Geriatric Depression Scale (GDS) and the Cornell Scale for Depression in Dementia (CS). The GDS is a self-rating scale used to identify depressed older adults, whereas the CS is used to assess severity of depression based on a clinical interview. Because the scales may thus be complementary, their use was examined in 182 patients undergoing an outpatient geriatric assessment. Geriatric psychiatrists, blind to the results of the GDS, completed the CS and assigned clinical diagnoses. Both scales distinguished depressed from nondepressed individuals by means of ROC-generated cutoff scores relative to a clinical diagnosis of depression. The scores on the depression scales were not affected by cognitive status as measured by the Mini-Mental State Examination. The mean GDS scores did not vary by geriatric psychiatrist. The mean CS scores, however, did significantly differ across psychiatrists despite the fact that the psychiatrists were not blind to patients' clinical diagnosis.


Photosynthetic acclamatory response of Panicum antidotale Retz. populations to root zone desiccation stress.
Growth of plants is severely reduced due to water stress by affecting photosynthesis including photosystem II (PSII) activity and electron transport. This study emphasised on comparative and priority targeted changes in PSII activity due to progressive drought in seven populations of Panicum antidotale (P. antidotale) collected from Cholistan Desert and non-Cholistan regions. Tillers of equal growth of seven populations of P. antidotale grown in plastic pots filled with soil were subjected progressive drought by withholding water irrigation for three weeks. Progressive drought reduced the soil moisture content, leaf relative water content, photosynthetic pigments and fresh and dry biomass of shoots in all seven populations. Populations from Dingarh Fort, Dingarh Grassland and Haiderwali had higher growth than those of other populations. Cholistani populations especially in Dingarh Grassland and Haiderwali had greater ability of osmotic adjustment as reflected by osmotic potential and greater accumulation of total soluble proteins. Maximum H2O2 under water stress was observed in populations from Muzaffargarh and Khanewal but these were intermediate in MDA content. Under water stress, populations from Muzaffargarh and Dingarh Fort had greater K+ accumulation in their leaves. During progressive drought, non-Cholistani populations showed complete leaf rolling after 23 days of drought, and these populations could not withstand with more water stress condition while Cholistani populations tolerated more water stress condition for 31 days. Moreover, progressive drought caused PSII damages after 19 days and it became severe after 23 days in non-Cholistani populations of P. antidotale than in Cholistani populations.


Aelurostrongylus abstrusus Antibody Seroprevalence Reveals That Cats Are at Risk of Infection throughout Germany.
Cats infected with the metastrongylid nematode Aelurostrongylus abstrusus may show clinical signs ranging from mild to severe respiratory disease or remain unobserved, despite damages present in the lung tissue. This study aimed to determine the seroprevalence and distribution of A. abstrusus in cats by testing serum samples from all over Germany to identify potential risk areas and strengthen disease awareness accordingly. Sera of 2998 cats were screened for the presence of antibodies against A. abstrusus by ELISA, and the data were evaluated by a geographic information system to visualise the regional distribution of the analysed samples. Overall, 12.0% of the samples tested positive (361/2998 cats, 95% confidence interval: 10.9-13.3%). Seropositive cats were identified throughout the country, suggesting that all cats in Germany with outdoor access are at risk of A. abstrusus infection and that the infection is overall underdiagnosed. Increased testing for A. abstrusus infection would allow earlier detection of infected animals, hence improving the life quality and health of cats and preventing potential death under anaesthesia.


A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to body mass index and long term body weight change in the Danish population.
Variability of the uncoupling protein 3 (UCP3) promoter has been associated with increased body mass index (BMI) and altered lipid profiles. Here we tested the hypothesis that variation of the UCP3 promoter is associated with either juvenile or maturity-onset obesity or body weight change over a 26-yr follow-up among Danish subjects. Mutation screening of approximately 1 kb 5' upstream of the UCP3 gene revealed one previously described -55 C-->T variant. The frequency of the polymorphism was evaluated by restriction fragment length polymorphism analysis in four groups of subjects: 1) a group of 744 obese Danish men who at the draft board examinations had a body mass index (BMI) of at least 31 kg/m(2), 2) a randomly selected control group consisting of 857 draftees, 3) 258 middle-aged subjects, and 4) 409 60-yr-old subjects. The frequency of the T allele was 26.0% (95% confidence interval, 23.8-28.2%) among the obese draftees and 26.9% (24.8-29.0%) in the control group (P = 0.6). The variant was not associated with BMI at a young age or with weight gain after a 26-yr follow-up. The frequency of the T allele was 29.5% (25.6-33.4%) in the middle-aged group and 25.8% (22.8-28.8%) among the 60-yr-old subjects. The polymorphism was not associated with increased BMI or percent body fat in these 2 groups. It is concluded that this variant does not play a major role in the development of common obesity among Danish subjects.


Mutational analysis of Hungarian patients with androgen insensitivity syndrome.
To support the clinical diagnosis of androgen insensitivity syndrome (AIS), we performed mutational analysis of the androgen receptor gene. Clinical, hormonal and molecular genetic data of ten undervirilized genetic male patients living in Hungary were recorded. PCR-based single strand conformation polymorphism (SSCP) analysis was used to study the whole coding region of the androgen receptor gene. Direct fluorescent sequencing was applied when aberrant migration was detected by SSCP. Five different mutations were identified in five unrelated genetic male patients with abnormal sexual differentiation. One of these mutations was novel, while the other four mutations have been described previously in the literature. One of the mutations identified earlier in individuals with sporadic AIS showed a familial inheritance pattern in our study group. No abnormality of the androgen receptor gene was identified in three patients clinically suspected to have partial AIS. Application of molecular techniques helped to clarify the diagnosis in patients with disorders of male sexual differentiation.


Thermoresponsive Polymers and Inverse Opal Hydrogels for the Detection of Diols.
Responsive inverse opal hydrogels functionalized by boroxole moieties were synthesized and explored as sensor platforms for various low molar mass as well as polymeric diols and polyols, including saccharides, glycopolymers and catechols, by exploiting the diol induced modulation of their structural color. The underlying thermoresponsive water-soluble copolymers and hydrogels exhibit a coil-to-globule or volume phase transition, respectively, of the LCST-type. They were prepared from oligoethylene oxide methacrylate (macro)monomers and functionalized via copolymerization to bear benzoboroxole moieties. The resulting copolymers represent weak polyacids, which can bind specifically to diols within an appropriate pH window. Due to the resulting modulation of the overall hydrophilicity of the systems and the consequent shift of their phase transition temperature, the usefulness of such systems for indicating the presence of catechols, saccharides, and glycopolymers was studied, exploiting the diol/polyol induced shifts of the soluble polymers' cloud point, or the induced changes of the hydrogels' swelling. In particular, the increased acidity of benzoboroxoles compared to standard phenylboronic acids allowed performing the studies in PBS buffer (phosphate buffered saline) at the physiologically relevant pH of 7.4. The inverse opals constructed of these thermo- and analyte-responsive hydrogels enabled following the binding of specific diols by the induced shift of the optical stop band. Their highly porous structure enabled the facile and specific optical detection of not only low molar mass but also of high molar mass diol/polyol analytes such as glycopolymers. Accordingly, such thermoresponsive inverse opal systems functionalized with recognition units represent attractive and promising platforms for the facile sensing of even rather big analytes by simple optical means, or even by the bare eye.


VEXAS syndrome, a new kid on the block of auto-inflammatory diseases: A hematologist's point of view.
The recently discovered VEXAS syndrome is caused by the clonal expansion of hematopoietic stem or progenitor cells with acquired mutations in UBA1 gene, which encodes for a key enzyme of the ubiquitylation proteasome system. As a result, a shorter cytoplasmic isoform of UBA1 is transcribed, which is non-functional. The disease is characterized by non-specific and highly heterogeneous inflammatory manifestations and macrocytic anemia. VEXAS syndrome is a unique acquired hematological monogenic disease with unexpected association with hematological neoplasms. Despite its hematopoetic origin, patients with VEXAS syndrome usually present with multi-systemicinflammatory disease and are treated by physicians from many different specialties (rheumatologists, dermatologists, hematologistis, etc.). Furthermore, manifestations of VEXAS may fulfill criteria for existing diseases: relapsing polychondritis, giant cell arteritis, polyarteritis nodosa, and myelodysplastic syndrome. The goal of this review is to depict VEXAS syndrome from a hematologic point of view regarding its consequences on hematopoiesis and the current strategies on therapeutic interventions.


Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells.
The heat shock protein (HSP) 90 chaperone machine involved in numerous oncogenic signaling pathways is overexpressed in cancer cells and is currently being evaluated for anticancer therapy. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a heterogeneous group of tumors with increasing incidence and poor prognosis. Here, we report the antiproliferative effects of the HSP90 inhibitors AUY922 and HSP990 in neuroendocrine tumor cells. Treatment of human pancreatic BON1, bronchopulmonary NCI-H727 and midgut carcinoid GOT1 neuroendocrine tumor cells with increasing concentrations of AUY922 and HSP990 dose-dependently suppressed cell viability. Significant effects on neuroendocrine cell viability were observed with inhibitor concentrations as low as 5 nM. Inhibition of cell viability was associated with the induction of apoptosis as demonstrated by an increase in sub-G1 events and PARP cleavage. HSP90 inhibition was associated with decreased neuroendocrine ErbB and IGF-I receptor expression, decreased Erk and Akt phospho-rylation and the induction of HSP70 expression. These findings provide evidence that targeted inhibition of upregulated HSP90 activity could be useful for the treatment of aggressive neuroendocrine tumors resistant to conventional therapy.