A new lipid storage myopathy observed in individuals with the Ruvalcaba-Myhre-Smith syndrome.
Four patients with the Ruvalcaba-Myhre-Smith syndrome (primary macrocephaly with associated anomalies including pigmented macules on the penis in affected males, hamartomatous intestinal polyps, and lipomas) had evidence of delayed psychomotor development and/or hypotonia in childhood. Electromyography in 3 patients showed evidence of a myopathic process. Muscle biopsy in all four demonstrated a lipid storage myopathy with increased numbers of neutral lipid droplets--predominatly in type 1 fibers. The type 2 fibers were consistently smaller than expected. Electron microscopy was unremarkable except for evidence of lipid accumulation. Muscle carnitine and carnitine palmityl transferase levels were normal in one patient. This appears to be a previously unreported type of lipid storage myopathy characteristic of the Ruvalcaba-Myhre-Smith syndrome, a probable autosomal dominant trait.


Screening for canine coronavirus, canine influenza virus, and severe acute respiratory syndrome coronavirus 2 in dogs during the coronavirus disease-2019 pandemic.
Although most cases of coronavirus disease-2019 (COVID-19) are in humans, there is scientific evidence to suggest that the virus can also infect dogs and cats. This study investigated the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), canine coronavirus (CCV), and canine influenza virus (CIV) in domiciled and/or stray dogs from different locations in the State of Minas Gerais, Brazil, during the COVID-19 pandemic. In total, 86 dogs living in homes, on the streets, or in shelters in the cities of Taiobeiras, Salinas, Araçuaí, and Almenara were randomly selected for this study. The COVID Ag Detect® Self-Test was used to detect SARS-CoV-2. The ACCUVET CCV AG TEST - CANINE CORONAVIROSIS® was used to detect CCV, whereas canine influenza was detected using the ACCUVET CIV AG TEST - INFLUENZA CANINA®. All collected data were mapped using QGIS 3.28.1 for spatial data analysis and the identification of disease distribution patterns. Descriptive analysis of the collected data, prevalence calculations, odds ratios (ORs), and 95% confidence intervals, when possible, was performed. Of the 86 animals tested, only one dog tested positive for SARS-CoV-2 using the rapid test for viral antigen detection. No animals tested positive for CIV. Canine coronavirus was detected in almost half of the animals tested in Almenara. Severe acute respiratory syndrome-CoV-2 had a low prevalence (1.16%), versus 15.62% for CCV. Although the results were not significant, the age and breed of animals appeared to be associated with the occurrence of CCV. The results indicated that younger animals were 2.375-fold more likely to be infected. Likewise, purebred animals were more likely to contract the disease (OR = 1.944). The results indicate the need to maintain preventive measures against CCV, canine influenza, and SARS-CoV-2 in dogs. More studies are needed to better elucidate the panorama of these diseases in dogs, mainly in underdeveloped and developing countries.


Chimeric Antigen Receptor T-Cell Therapy: Reach to Solid Tumor Experience.
Chimeric antigen receptor (CAR) modified T-cell therapy, a unique platform technology highlighting precision medicine through utilization of molecular biology and cell-based therapeutics has shown unprecedented rates in patients with hematological malignancies such as acute lymphocyte leukemia, non-Hodgkin's lymphoma and multiple myeloma (MM). With the approval of CD19-targeted CAR T-cells by the Food and Drug Administration in acute lymphoblastic leukemia (ALL) and NHL, this technology is positioned for aggressive expansion to combination therapeutic opportunities and proof of principle towards utility in other malignant disorders. However, despite the impressive results seen with hematological malignancies, CAR T-cells have shown limited efficacy in solid tumors with several unsuccessful preclinical studies. Regardless, these attempts have provided us with a better understanding of the imminent challenges specific to solid tumors even if they have not so far led to expanded clinical treatment opportunities outside ALL/NHL/MM. This review summarizes our current understanding of CAR T-cell mechanism of action, while presenting the major limitations of CAR T-cell derived treatments in solid tumors. We further discuss recent findings and present new potential strategies to overcome the challenges facing solid tumor targeting by CAR T-cell platforms.


A 30-year systematic review and meta-analysis of hepatitis B virus among blood donors in mainland China: revealing increase of new threats.
Although screening strategies have been routinely implemented in blood centers, the residual risk of transfusion-transmitted hepatitis B virus (HBV) still poses a public health concern in China. The aim of this study is to investigate the HBV blood screening reactive rate and to illustrate the demographics of the corresponding blood donors with revealing of heterogeneity between previous studies and discovering potentially negligent threats. Literature reporting the HBV screening reactive rate in Chinese blood donors was identified by systematic searching of four electronic databases. We followed the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines, and data manipulation and statistical analyses were performed by Stata 12.0. Our results showed that the pooled postdonation screening reactive rate was 1.32% (95% confidence interval [CI], 1.28%-1.36%) with a significant variation from 3.93% (95% CI, 3.45%-4.40%) before 1998 to 1.22% (95% CI, 1.18%-1.27%) after 1998 when the Blood Donation Law was implemented. Importantly, the HBV screening reactive rates were significantly higher among replacement and planned donors than among individual voluntary donors. Our results indicated blood centers in China should recruit more individual and group voluntary donors and convert more eligible first-time donors into repeat donors to reduce the risk of transfusion-transmitted HBV.


Variation in the level of fetal hemoglobin in (delta beta) (0)-thalassemia heterozygotes with different numbers of alpha-globin genes.
The Sicilian type of (delta beta) (0)-thalassemia characterized by a approximately 13 kb deletion, was present in a Turkish boy who is a homozygote and in his heterozygous parents who are first cousins. The father with approximately 21% Hb F had five alpha-globin genes (alpha alpha/alpha alpha alpha) and the mother with approximately 10% Hb F had an alpha-thal-2 heterozygosity (alpha alpha/-alpha). The difference in Hb F level is explained by a decreased formation of alpha 2 gamma 2 tetramers in the mother with an alpha-chain deficiency while the extra alpha-globin gene in the father will promote Hb F production.


Phyloanatomic characterization of the distinct T cell and monocyte contributions to the peripheral blood HIV population within the host.
Human immunodeficiency virus (HIV) is a rapidly evolving virus, allowing its genetic sequence to act as a fingerprint for epidemiological processes among, as well as within, individual infected hosts. Though primarily infecting the CD4+ T-cell population, HIV can also be found in monocytes, an immune cell population that differs in several aspects from the canonical T-cell viral target. Using single genome viral sequencing and statistical phylogenetic inference, we investigated the viral RNA diversity and relative contribution of each of these immune cell types to the viral population within the peripheral blood. Results provide evidence of an increased prevalence of circulating monocytes harboring virus in individuals with high viral load in the absence of suppressive antiretroviral therapy. Bayesian phyloanatomic analysis of three of these individuals demonstrated a measurable role for these cells, but not the circulating T-cell population, as a source of cell-free virus in the plasma, supporting the hypothesis that these cells can act as an additional conduit of virus spread.


Random urine analyses from drug addicts in a methadone treatment programme.
Random testing of urine from opiate addicts in the methadone treatment programme at the Drug Dependency Service, Brisbane Street, Sydney, was carried out for 18 months. Six samples from each of approximately 100 clients (that is, 580 specimens) have been analysed. It was found that clients receiving high methadone dosages (80 mg and over) used illegal opiates significantly less frequently than those on lower dosages. Furthermore, a decline in the use of illegal opiates and an increase in the proportion of "clear" urine specimens (that is, clear of all drugs except methadone) were indicators of the effectiveness of the methadone programme. It was concluded that urine testing was a useful and objective means of evaluating methadone or any other drug addiction treatment programme, and of monitoring what other drugs were being taken, both consciously or inadvertently in combinations. The results of urine testing can also be of value to counsellors in the therapeutic situation.


Socio-economic status and smoking in Canada, 1999-2006: has there been any progress on disparities in tobacco use?
Comprehensive tobacco control policies implemented in Canada have succeeded in lowering overall smoking prevalence; however, the extent to which they have impacted socio-economic disparities in tobacco use is not known. This study examined smoking rates and related measures across socio-economic groups over a 7-year period in Canada. Regression analyses tested associations between smoking-related outcomes (prevalence, frequency, consumption, quit intentions and attempts, quit ratios), education level and time, using data from adults 25 years and older who completed the 1999 to 2006 waves of the Canadian Tobacco Use Monitoring Survey (CTUMS), a repeated cross-sectional survey with nationally representative samples (n = 86,971). Between 1999 and 2006, smoking prevalence, daily smoking, and cigarette consumption decreased, while the proportion of smokers who planned to quit increased, as did the proportion of ever-smokers who had quit. However, significant educational differences were observed: Canadians with less education had greater odds of current smoking (prevalence approximately doubled between the most and least educated groups) and daily smoking, and consumed more cigarettes, compared to university graduates. Highly-educated ever-smokers were also more likely to have quit smoking. These disparities remained stable over the time period studied. Intentions and attempts to quit were not consistently associated with education. The decline in smoking among Canadians between 1999 and 2006 represents a major public health achievement. However, considerable smoking-related disparities exist between socio-economic groups, and have changed very little. Therefore, while recent programs and policies have succeeded in reducing overall tobacco use, they have not addressed socio-economic disparities.


Stress-induced deformation of the coating on large lightweight freeform optics.
Large aperture, lightweight optics are frequently utilized in modern optical systems. However, despite the use of advanced techniques for developing their materials, fabrication, and mechanical structure, the coatings placed on the substrates induce slight lattice mismatches and increase the thin film stress on polished surfaces. This significantly distorts nano-accuracy optical surfaces, especially on lightweight freeform surfaces. In this study, we construct a finite element model (FEM) and a ray tracing model to estimate the impact of the stress-induced deformation of the coating on a 1.5m class lightweight silicon carbine (SiC) mirror with a freeform surface. Our simulation results are within 10% deviation from the experimental results, and the deformation texture map matches these results as well. We discuss several possible strategies to overcome stress-induced deformation, including fabrication pre-compensation, lightweight structure redesign, and an inverse print-through effect.


Physical exosome:exosome interactions.
Exosomes are extracellular nanovesicles that mediate a number of cellular processes, including intracellular signalling. There are many published examples of exosome-exosome dimers; however, their relevance has not been explored. Here, we propose that cells release exosomes to physically interact with incoming exosomes, forming dimers that we hypothesize attenuate incoming exosome-mediated signalling. We discuss experiments to test this hypothesis and potential relevance in health and disease.


Identifying gene-disease associations using centrality on a literature mined gene-interaction network.
Understanding the role of genetics in diseases is one of the most important aims of the biological sciences. The completion of the Human Genome Project has led to a rapid increase in the number of publications in this area. However, the coverage of curated databases that provide information manually extracted from the literature is limited. Another challenge is that determining disease-related genes requires laborious experiments. Therefore, predicting good candidate genes before experimental analysis will save time and effort. We introduce an automatic approach based on text mining and network analysis to predict gene-disease associations. We collected an initial set of known disease-related genes and built an interaction network by automatic literature mining based on dependency parsing and support vector machines. Our hypothesis is that the central genes in this disease-specific network are likely to be related to the disease. We used the degree, eigenvector, betweenness and closeness centrality metrics to rank the genes in the network. The proposed approach can be used to extract known and to infer unknown gene-disease associations. We evaluated the approach for prostate cancer. Eigenvector and degree centrality achieved high accuracy. A total of 95% of the top 20 genes ranked by these methods are confirmed to be related to prostate cancer. On the other hand, betweenness and closeness centrality predicted more genes whose relation to the disease is currently unknown and are candidates for experimental study. A web-based system for browsing the disease-specific gene-interaction networks is available at: http://gin.ncibi.org.


Internal structure of the temporomandibular joint and the circumferential bone: comparison between dentulous and edentulous specimens.
To clarify changes in the trabecular structure due to loss of the teeth, the author compared soft X-ray images and morphological measurement values of the mandibular condyle and articular eminence between dentulous and edentulous specimens. The center of the skull base containing the temporomandibular joint was removed along the Frankfort horizontal and median sagittal planes. A block in the center of the cranial base was rejected using the Frankfort horizontal plane and median sagittal plane as references. The specimens were embedded in polyester resin by the routine method. The hardened specimens were horizontally cut into 500 microns sections and photographed using soft X-ray films. Soft X-ray of each section was taken for observation by naked eye and morphometry by computer. Observation of the compact bone in the articular eminence showed thinner compact bone on the posterior slope of the articular eminence, which is a functional plane, than on the anterior slope of the articular eminence. There was a trabecular bone group on the lateral area running from the compact bone on the posterior surface of the articular eminence into the zygomatic arch and a thick trabecular bone group in a network pattern on the medial area. In the central area of the mandibular condyle, spongy bone was surrounded by oval compact bone, and the internal trabecular bone ran anteromedially in nearly the same pattern as the arrangement of the lateral pterygoid muscle. At all sites, the density, width, extent, and index indicating the complexity of the trabecular bone had higher values in dentulous specimens than in edentulous specimens.


Profiles and transition of mental health problems among Chinese adolescents: The predictive role of friendship quality, parental autonomy support, and psychological control.
Mental health problems have become a global crisis of the 21st century, with adolescence being a typical period of the outbreak of these problems. However, the profiles and transition of mental health problems in Chinese adolescents remain unclear. In addition, protective and risk factors that shape mental health problems require further clarification. We measured depression, anxiety, and stress as indicators to identify the profiles and transition patterns of mental health problems among Chinese adolescents, as well as environment-related predictors (i.e., friendship quality, parental psychological control, and autonomy support). A total of 722 participants (376 females; Mage = 15.21, SDage = 0.74) completed a set of questionnaires at two time points with a 1-year interval (T1: November 2018; T2: November 2019). The profile analysis revealed two groups: healthy and troubled. The development of mental health problems included four trajectories: steady low, steady high, increasing, and decreasing. Results indicated that parental autonomy support and friendship quality exerted protective and buffering effects, whereas parental psychological control acted as a risk factor for mental health problem profiles. Furthermore, friendship quality had a unique predictive effect on the decreasing trajectory. The profiles of mental health problems showed high concurrency of depression, anxiety, and stress symptoms, and developmental trajectories were largely stable over time. Friendship quality, parental autonomy support, and psychological control predicted the profiles of the mental health problems of Chinese adolescents, and only friendship quality predicted the transition from a troubled to healthy profile over 1 year.


Glucagon-like peptide-1 analogue liraglutide ameliorates atherogenesis via inhibiting advanced glycation end product-induced receptor for advanced glycosylation end product expression in apolipoprotein-E deficient mice.
Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10 weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group. All mice were fed a high-fat diet. The AGEs and AGEs+GLP-1 groups were treated with intraperitoneal injection of AGEs (30 mg/kg/day). The GLP-1 and AGEs+GLP-1 groups were treated with subcutaneous injections of liraglutide (0.4 mg/kg/day). After 9 weeks, blood was drawn and the aortas were rapidly procured. The serum levels of AGEs, soluble RAGE (sRAGE), stromal cell-derived factor-1α (SDF-1α), total cholesterol and triacylglycerol were measured. Atherosclerotic plaque area was determined by Sudan IV staining. The mRNA and protein expression levels of RAGE were determined using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that AGEs treatment increased serum AGEs levels, increased the expression of RAGE in the aorta, and aggravated atherosclerotic lesions compared with the control. Liraglutide treatment reduced serum AGEs levels, reduced the expression of RAGE in aorta, and relieved atherosclerotic lesions compared with the control. In conclusion, these data suggested that liraglutide serves an anti-atherosclerotic effect via inhibiting AGEs-induced RAGE expression in ApoE-/- mice. These findings provide novel evidence for the use of GLP-1-type agents for the treatment of diabetic vascular complications.


Coactosin Promotes F-Actin Protrusion in Growth Cones Under Cofilin-Related Signaling Pathway.
During brain development, axon outgrowth and its subsequent pathfinding are reliant on a highly motile growth cone located at the tip of the axon. Actin polymerization that is regulated by actin-depolymerizing factors homology (ADF-H) domain-containing family drives the formation of lamellipodia and filopodia at the leading edge of growth cones for axon guidance. However, the precise localization and function of ADF-H domain-containing proteins involved in axon extension and retraction remain unclear. We have previously shown that transcripts and proteins of coactosin-like protein 1 (COTL1), an ADF-H domain-containing protein, are observed in neurites and axons in chick embryos. Coactosin overexpression analysis revealed that this protein was localized to axonal growth cones and involved in axon extension in the midbrain. We further examined the specific distribution of coactosin and cofilin within the growth cone using superresolution microscopy, structured illumination microscopy, which overcomes the optical diffraction limitation and is suitable to the analysis of cellular dynamic movements. We found that coactosin was tightly associated with F-actin bundles at the growth cones and that coactosin overexpression promoted the expansion of lamellipodia and extension of growth cones. Coactosin knockdown in oculomotor neurons resulted in an increase in the levels of the inactive, phosphorylated form of cofilin and dysregulation of actin polymerization and axonal elongation, which suggests that coactosin promoted axonal growth in a cofilin-dependent manner. Indeed, the application of a dominant-negative form of LIMK1, a downstream effector of GTPases, reversed the effect of coactosin knockdown on axonal growth by enhancing cofilin activity. Combined, our results indicate that coactosin functions promote the assembly of protrusive actin filament arrays at the leading edge for growth cone motility.


In vitro human enamel wear by a hydrated high-alkali porcelain.
The purpose of this study was to examine the hydration of a high-alkali dental porcelain (Ducera LFC) and its relative abrasive wear against human enamel. The hypothesis is that the composition of the porcelain (LFC) will form a softer, hydrated layer in artificial saliva, which will reduce wear against enamel relative to other dental porcelains. The first experiment was to estimate the thickness of the hydrated layer formed on LFC by storage in artificial saliva using microindentation hardness. The second experiment involved an estimate of enamel wear relative to other porcelains (d-Sign, LFC, Ducera Gold, and the control substance, Ceramco II) of hydrated LFC using a pin-on-disk wear test. The mean microindentation hardness values of hydrated and unhydrated LFC and the Ceramco II control were 5750 Mpa, 8230 Mpa, and 7180 MPa, respectively, at a stylus depth of 400 nm. The average enamel wear values measured with the porcelains are (in microns): LFC saliva (hydrated), 23.8; d-Sign, 35.6; LFC, 59.4; Ducera Gold (hydrated), 75; Ducera Gold, 81.3; Ceramco II, 109.4. Using Tukey's analysis at a 5% error level, there were significant differences between the wear of enamel against hydrated LFC and the more abrasive Ceramco II control. Comparing the effect of hydration of LFC on enamel wear, using an independent t test, hydrated LFC was significantly less abrasive than LFC (P< .008), but was not significantly less abrasive than d-Sign.


Presence of psychiatric morbidity in prison population in Kuwait.
This paper surveys the prevalence of psychiatric morbidity in a Kuwaiti prison. The rate of major psychosis was considerably lower than the rate reported in other prison studies. Twenty-five percent of the sample had generalized anxiety disorder of a reactive nature which was most probably related to imprisonment itself. There was a preponderance of individuals suffering from personality disorder, alcoholism, and drug abuse problems. Prisoners with a diagnosis of major psychosis had very little exposure to psychiatrists and the large number of recidivists reflects the lack of a probation service. Financial embezzlement and drug/liquor smuggling remain the crimes of choice in Kuwait. Some underlying sociocultural factors are discussed and the need for an alternative prison-based therapeutic community service is emphasized.


Nitric oxide-mediated neurogenic vasodilatation in isolated monkey lingual arteries.
In isolated monkey lingual arteries denuded of the endothelium and contracted with prostaglandin F2alpha, transmural electrical stimulation produced a contraction that was reduced by prazosin and reversed to a relaxation by additional treatment with alpha,beta-methylene ATP. The relaxation thus induced was abolished by tetrodotoxin and N(G)-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and L- but not D-arginine restored the response in the L-NNA-treated arteries. Under treatment with prazosin and alpha,beta-methylene ATP, the arterial strips responded to nicotine with a relaxation that was not influenced by atropine and timolol but was abolished by hexamethonium, oxyhemoglobin, and methylene blue. The nicotine-induced relaxation was abolished by L-NNA but not by N(G)-nitro-D-arginine and was reversed by L-arginine. Relaxations to exogenously applied NO (acidified NaNO2 solution) were not influenced by L-NNA but were abolished by oxyhemoglobin and methylene blue. The response was not affected in the strips made unresponsive to vasoactive intestinal polypeptide and calcitonin gene-related peptide by desensitization. Histochemical study demonstrated the presence of perivascular neurons containing neuronal NO synthase. It is concluded that monkey lingual arteries are innervated by vasoconstrictor nerves liberating norepinephrine and possibly ATP and also by nonadrenergic noncholinergic vasodilator nerves liberating NO as a neurotransmitter to activate soluble guanylate cyclase. Vasoactive intestinal polypeptide and calcitonin gene-related peptide do not appear to be involved in the neurogenic vasodilatation.


Surface functionalization of titanium with chitosan/gelatin via electrophoretic deposition: characterization and cell behavior.
The electrophoretic deposition (EPD) is a versatile and cost-effective technique for fabricating advanced coatings. In this study, chitosan/gelatin (CS/G) coatings were prepared on titanium substrates via EPD. The prepared coatings were characterized using fluorescence microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and shear bond strength testing. It was found that CS/G coatings had a similar macroporous structure. The gelatin content in the CS/G coatings gradually increased with the increase of the gelatin in the blend solutions. The shear bond strength of the CS/G coatings also increased with the increasing gelatin content. In vitro biological tests demonstrated that human MG63 osteoblast-like cells achieved better affinity on the coatings with higher gelatin content. Therefore, it was concluded that EPD was an effective and efficient technique to prepare CS/G coatings on the titanium surface and that CS/G coatings with higher gelatin content were promising candidates for further loading of functional agents.


Challenges integrating skin sensitization data for assessment of difficult to test substances.
Difficult to test substances including poorly soluble, mildly irritating, or Unknown or Variable Composition Complex reaction products or Biological Materials (UVCBs), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitates data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of Toxicological Prioritization Index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensitizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.


Accuracy of Self-reported Smoking Exposure Among Bladder Cancer Patients Undergoing Surveillance at a Tertiary Referral Center.
Smoking is a risk factor for developing bladder cancer (BCa). Even though continued exposure after diagnosis may adversely affect prognosis, patients may be reluctant to disclose to their physicians that they are currently smoking, leading to inaccurate reporting of exposure and missed opportunities to deliver smoking-cessation advice and treatment in the context of cancer care. We examined the extent of misclassification of recent smoking exposure among patients undergoing BCa surveillance. A consecutive sample of 145 patients with a self-reported smoking history and prior initial diagnosis of BCa was recruited from a tertiary referral urology clinic. Patients were asked if they had smoked a cigarette or used nicotine replacement therapy (NRT) within the past week and whether they lived with a smoker. At the same visit, we collected urine under a biospecimen protocol. We used urinary cotinine, the primary metabolite of nicotine, as an objective biomarker of recent smoking exposure. Nine patients whose urine could not be interpreted for cotinine were excluded. We calculated the smoking status misreporting rate by comparing biochemically verified smoking status (≥31.5 ng/ml vs <31.5 ng/ml) against self-reported current smoking status (yes vs no) while considering recent NRT use. Overall, 11% (15 of 136) of patients had cotinine values consistent with current smoking. Of these 15 patients, 7 reported being former smokers, resulting in a 47% misclassification rate. However, three of the seven patients who denied smoking in the past week were currently using NRT. Excluding NRT users, the misclassification rate was 33%. Future studies investigating the impact of postdiagnosis nicotine exposure on BCa outcomes should use biochemical verification combined with self-reported smoking exposure to classify patients accurately. Bladder cancer patients may misreport smoking exposure, thereby missing opportunities for smoking cessation.


The influence of diffusion gradient direction on diffusion-weighted imaging of breast mass-like lesions at 3.0T.
Background It has been challenging to achieve ideal breast diffusion-weighted imaging (DWI). The optimization of diffusion gradient direction is of great importance. Purpose To evaluate the effect of diffusion gradient direction on the apparent diffusion coefficient (ADC) values of breast mass-like lesions and the visual grades of image quality, lesion visibility, and sharpness of breast contour at 3.0T. Material and Methods Sixty consecutive patients with mass-like lesions were enrolled in this study. In addition to typical breast magnetic resonance imaging (MRI) protocols, the breasts were scanned with conventional orthogonal DWI (c-DWI), tetrahedral DWI (t-DWI), and 3in1 DWI (3in1-DWI) sequences. The DW images were observed and visually graded by two radiologists independently. For ADC measurement, one radiographer manually selected the region of interest (ROI). Results For both readers, t-DWI had better image quality and sharpness of breast contour than c-DWI. Regarding lesion visibility, no significant differences were observed among three sequences. The mean ADC values were 1.462 × 10-3, 1.490 × 10-3, and 1.446 × 10-3 mm2 s-1 for c-DWI, t-DWI, and 3in1-DWI, respectively. The ADC values extracted from both t-DWI and 3in1-DWI were not statistically different compared with those from c-DWI. In all DWI sequences, the ADC of malignant lesions was significantly reduced compared with benign lesions. Conclusion DWI with tetrahedral or 3in1 diffusion gradients is a more useful technique in clinical breast MRI than c-DWI because the image quality and sharpness of breast contour are improved. ADC is comparable to c-DWI.


Retinotopy with coordinates of lateral occipital cortex in humans.
The lateral occipital cortex in humans is known as the "extrastriate visual cortex." It is, however, an unexplored field of research, and the anatomical nomenclature for its surface has still not been standardized. This study was designed to investigate whether the lateral occipital cortex in humans has retinotopic representation. Four right-handed patients with a diagnosis of intractable epilepsy from space-occupying lesions in the occipital lobe or epilepsy originating in the occipital lobe received permanently implanted subdural electrodes. Electrical cortical stimulation was applied directly applied to the brain through metal electrodes by using a biphasic stimulator. The location of each electrode was measured on a lateral skull x-ray study. Each patient considered a whiteboard with vertical and horizontal median lines. The patient was asked to look at the midpoint on the whiteboard. If a visual hallucination or illusion occurred, the patient recorded its outline, shape, color, location, and motion on white paper one tenth the size of, and with vertical and horizontal median lines similar to those on, the whiteboard. Polar angles and eccentricities of the midpoints of the phosphenes from the coordinate origin were measured on the paper. On stimulation of the lateral occipital lobe, 44 phosphenes occurred. All phosphenes were circular or dotted, with a diameter of approximately 1 cm, except one that was like a curtain in the peripheral end of the upper and lower visual fields on stimulation of the parietooccipital region. All phosphenes appeared in the visual field contralateral to the cerebral hemisphere stimulated. On stimulation of the lateral occipital lobe, 22 phosphenes moved centrifugally or toward a horizontal line. From three-dimensional scatterplots and contour maps of the polar angles and eccentricities in relation to the x-ray coordinates of the electrodes, one can infer that the lateral occipital cortex in humans has retinotopic representation. The authors found that phosphenes induced by electrical cortical stimulation of the lateral occipital cortex represent retinotopy. From these results one can assert that visual field representation with retinotopic relation exists in the extrastriate visual cortex.


Single-step formation of ZnO/ZnWO(x) bilayer structure via interfacial engineering for high performance and low energy consumption resistive memory with controllable high resistance states.
A spontaneously formed ZnO/ZnWOx bilayer resistive memory via an interfacial engineering by one-step sputtering process with controllable high resistance states was demonstrated. The detailed formation mechanism and microstructure of the ZnWOx layer was explored by X-ray photoemission spectroscopy (XPS) and transmission electron microscope in detail. The reduced trapping depths from 0.46 to 0.29 eV were found after formation of ZnWOx layer, resulting in an asymmetric I-V behavior. In particular, the reduction of compliance current significantly reduces the switching current to reach the stable operation of device, enabling less energy consumption. Furthermore, we demonstrated an excellent performance of the complementary resistive switching (CRS) based on the ZnO/ZnWOx bilayer structure with DC endurance >200 cycles for a possible application in three-dimensional multilayer stacking.


The lack of melatonin rhythm in active acromegaly after radiotherapy.
The aim of the study was to evaluate the interrelation between the levels of growth hormone (GH), prolactin (PRL), somatomedin-C (Sm-C) and melatonin determined at 3 h intervals over a 24 h period (8.00, 11.00, 14.00, 17.00, 20.00, 23.00, 2.00 and 5.00) in 8 acromegalic patients after radiotherapy. The circadian rhythms and the interrelation between hormone and Sm-C levels were evaluated using Halberg's cosinor method and the correlation analysis, respectively. We observed a total abolition of melatonin rhythm with significantly lower nocturnal values in all patients which could be due to earlier radiotherapy.


Coincidence between geographical distribution of Leptotrombidium scutellare and scrub typhus incidence in South Korea.
To clarify the geographical distribution of scrub typhus vectors in Korea, a survey of larval trombiculid mites was conducted from 2005 to 2007 by collecting wild small mammals twice a year (spring and autumn) at 24 sites nationwide. A total of 67,325 mites representing 4 genera and 14 species were collected from 783 trapped rodents, corresponding to a chigger index (number of chigger mites per rodent) of 86.0. The predominant mite species were Leptotrombidium pallidum (52.6%), Leptotrombiduim scutellare (27.1%), Leptotrombidium palpale (8.2%), Leptotrombidium orientale (5.6%), and Neotrombicula tamiyai (1.7%). However, the proportions of L. scutellare in southern areas, including endemic provinces such as Jeollabuk-Do (34.3%), Jeollanam-Do (49.0%), and Gyeongsangnam-Do (88%), were relatively higher than in central Korean regions where L. pallidum was predominant. In autumn, the ratio of L. scutellare increased to 42% while the ratio of L. pallidum decreased. The geographical distribution map of the L. scutellare chigger index was identical to the incidence pattern of scrub typhus, whereas those of overall mites and L. pallidum showed no relationship with case incidence patterns. Distribution mapping analysis shows an identical geographical distribution of L. scutellare and epidemic incidence of scrub typhus in South Korea. L. pallidum could be another vector at all other parts of the Korean peninsula, including the eastern and northern regions that have a low level of scrub typhus incidence.


A highly selective and efficient single molecular FRET based sensor for ratiometric detection of Fe3+ ions.
A highly selective and efficient single molecular FRET based sensor has been developed for the ratiometric detection of Fe(3+) in aqueous samples and live cells.


A single-center 14-year follow-up study of the BalMedic® bovine pericardial bioprosthetic valve.
The causes of valvular disease in China are complex, with a broad age distribution. For patients with early mechanical valve replacement, the quality of life is affected by postoperative anticoagulation-related complications. Since 2005, we have used bioprosthetic valves to provide more options for patients. In this study, we retrospectively analyzed the 14-year follow-up data of patients undergoing BalMedic bovine pericardial bioprosthetic valve replacement (manufacturer: Beijing Balance Medical Tech Co., Ltd.) to evaluate its intermediate- to long-term clinical effectiveness. From 2005 to 2014, 336 BalMedic pericardial bioprosthesis valves were implanted in 299 patients (mean age 53.5 years, 59.86% female) at The First People's Hospital of Yulin. Among followed up 290 discharged patients, 284 underwent aortic valve replacement and mitral valve replacement (AVR group, MVR group) for further grouping analysis, 6 underwent tricuspid valve replacement (TVR). The mean follow-up was 7.7±2.5 years (5 to 14), for a total of 2,196 valve-years, 98.28% of the patients completed follow-up. The perioperative mortality was 3% (9/299). After discharge, 68 patients (23.4%, 68/290) died, and 36 (12.4% 36/290) underwent the second valve replacement. The overall 5- and 10-year survival rates were 89.95% and 72.53%, respectively. For patients undergoing AVR alone, the overall 10-year survival rates were 80.64%, the reoperation-free rates were 92.94%, and the SVD-free rates were 90.95%. For patients undergoing MVR and double valve replacement (DVR group), the 10-year survival rates were 67.21% and 82.90%, the reoperation-free rates were 72.26% and 73.33%, the SVD-free rates were 58.90% and 53.80%, respectively. Subgroup analysis by age showed no significant intergroup difference in overall survival but a significant intergroup difference in reoperation-free and SVD-free rates (P<0.05). With a similar 10-year overall survival rate as its foreign counterparts, BalMedic bovine pericardial bioprosthesis is reliable choice for both aortic valve and mitral valve. In patients undergoing AVR, the BalMedic valve is superior to the similar foreign counterparts in overall survival, reoperation-free survival, and SVD-free rates. While in MVR or DVR, Chinese patients are younger because of different etiology, postoperative outcomes show non-inferior to those from the foreign counterparts.


Isokinetic evaluation of wrist muscle strength in patients of carpal tunnel syndrome.
This study aims to investigate the isokinetic characteristics of wrist strength in flexion, extension, supination, pronation, radial, and ulnar deviation in patients with moderate or severe carpal tunnel syndrome (CTS). Thirteen patients (23 hands) (2 males, 11 females; mean age 45 years; range 29 to 60 years) with moderate or severe CTS were compared to six healthy control subjects (12 hands) (2 males, 4 females; mean age 41 years; range 27 to 63 years) in this study, which was conducted between January 2016 and April 2016. Wrist flexion, extension, supination, pronation, radial, and ulnar deviation muscle strengths were measured at 30°/second (5 sets) angular velocity with isokinetic dynamometer. Grip strength was measured with hand dynamometer (kilograms). Boston Questionnaire was used for clinical assessment. Grip strength (p=0.003); wrist flexion 30°/second (p=0.014); extension 30°/second (p=0.016); and ulnar deviation 30°/second (p=0.017) muscle strengths were lower in CTS patients compared with the control group. An evaluation according to symptom duration did not reveal any significant relationship in any of the isokinetic tests with the exception of pronation 30°/second (p=0.039, r= -0.432) and ulnar deviation 30°/second (p=0.034, r=0.443) in CTS patients. No significant relationship was found between Boston Questionnaire, grip strength, and isokinetic test results. Quantitative wrist strength measurements with isokinetic dynamometers are beneficial in conservative exercise treatments and motor assessments of CTS patients.


Antimicrobial resistance of Salmonella serovars isolated from beef at retail markets in the north Vietnam.
Approximately 39.9% (63/158) of beef samples collected from retail markets in Hanoi from January to June 2009 were Salmonella-positive. Nine Salmonella serovars, Anatum (28.6%), Rissen (25.4%), Weltevreden (12.7%), Typhimurium (7.9%), Derby (7.9%), Lexington (7.9%), Dublin (4.6%), Newport (3.2%) and London (1.8%), were identified. Thirty-seven (58.7%) of the 63 Salmonella isolates were resistant to at least one antimicrobial tested, of which 29 (46%) isolates showed multidrug resistance (MDR). The isolates were commonly resistant to tetracycline (46.0%), sulphonamide (39.7%), ampicilline (31.7%), streptomycin (30.2%), trimethoprim (28.6%), kanamycin (28.6%) and chloramphenicol (22.2%). Fourteen (bla(TEMV), bla(OXA-1), aadA1, aadA2, sul1, tetA, tetB, tetG, cmlA1, floR, dfrA1, dfrA12, aac (3)-IV and aphA1-1AB) out of 22 antimicrobial resistance genes were detected by PCR from the resistant isolates. The catA1, Kn, blaPSE-1 genes and plasmid-mediated quinolones resistance (PMQR) genes such as qnrA, qnrB, qnrS, qepA and acc (6')-ib-cr were not detected. Mutations in the gyrA gene leading to the amino acid changes Ser83Phe and/or Asp87Asn were found in 6 out of the 11 quinolone-resistant isolates. The data revealed that multidrug resistant Salmonella strains were widely distributed in north Vietnam via the food chain and might contain multiple genes specifying identical resistant phenotypes. Thus, continuous studies are necessary to clarify the mechanisms of MDR in Salmonella and its spread in the livestock market.


The importance of differentiating urban and rural phenomena in examining the unequal distribution of locally desirable land.
Previous research addressing the unequal distribution of locally desirable land (LDL) has mainly ignored their associated environments (i.e., rural or urban). However, this study proposed a new framework that treats rural and urban regions separately. In rural areas, the LDLs included all public lands. In urbanized areas, the LDLs were defined as green open spaces. Potential inequities in the distribution of LDL were assessed with respect to socioeconomic characteristics of residents in the State of Georgia. Using US Census Bureau Data (2000), Census Block Groups (CBGs) adjacent to LDLs were compared to CBGs outside of LDLs on four socioeconomic variables (per capita income, occupation, education, and race) in urban, suburban and rural environments. Results showed that CBGs adjacent to LDLs were composed of statistically significant upper-class communities containing fewer blue-collar workers, more whites, and higher income and higher educated people in rural, suburban and urban areas.


C-reactive protein and fibrinogen in acute stroke patients with and without sleep apnea.
Although sleep apnea (SA) is a risk factor for ischemic stroke and an important prognosticator in affected patients, the exact pathophysiological link between SA and stroke remains to be established. We investigated whether levels of C-reactive protein (CRP) and fibrinogen are increased in patients with acute stroke and SA compared with stroke patients without SA. 117 consecutive patients with ischemic stroke admitted to our stroke unit within 12 h after stroke onset were included in this study. On admission, CRP and fibrinogen levels were determined. All patients received cardiorespiratory polygraphy during the first 72 h of their hospital stay. In all patients, demographic data, National Institutes of Health Stroke Scale score and cerebrovascular risk factors were assessed. SA defined by an apnea-hypopnea index (AHI) of > or =10/h was found in 64 (55%) patients. Elevated CRP and fibrinogen levels were seen twice as often in patients with SA than in patients without (CRP: 52 vs. 26%; fibrinogen: 72 vs. 37%). After multivariate logistic regression analysis, an AHI of > or =10/h was independently correlated with raised levels of both of these parameters. SA is independently associated with raised levels of CRP and fibrinogen in patients with acute ischemic stroke. We assume that both proteins are part of the pathophysiological pathway linking SA to stroke.


Developing monitoring and evaluation tools for event-based surveillance: experience from Vietnam.
In 2016-2017, Vietnam's Ministry of Health (MoH) implemented an event-based surveillance (EBS) pilot project in six provinces as part of Global Health Security Agenda (GHSA) efforts. This manuscript describes development and design of tools for monitoring and evaluation (M&E) of EBS in Vietnam. A strategic EBS framework was developed based on the EBS implementation pilot project's goals and objectives. The main process and outcome components were identified and included input, activities, outputs, and outcome indicators. M&E tools were developed to collect quantitative and qualitative data. The tools included a supervisory checklist, a desk review tool, a key informant interview guide, a focus group discussion guide, a timeliness form, and an online acceptability survey. An evaluation team conducted field visits for assessment of EBS 5-9 months after implementation. The quantitative data collected provided evidence on the number and type of events that were being reported, the timeliness of the system, and the event-to-signal ratio. The qualitative and subjective data collected helped to increase understanding of the system's field utility and acceptance by field staff, reasons for non-compliance with established guidelines, and other factors influencing implementation. The use of M&E tools for the EBS pilot project in Vietnam provided data on signals and events reported, timeliness of reporting and response, perceptions and opinions of implementers, and fidelity of EBS implementation. These data were valuable for Vietnam's MoH to understand the function of the EBS program, and the success and challenges of implementing this project in Vietnam.


Activities of daily living, instrumental activities for daily living and predictors of functional capacity of older men in Jamaica.
An extensive search of the literature found no studies that have examined functional capacity [Activities of Daily Living (ADL) and Instrumental Activities for Daily Living (I) ADL)] of Jamaican older men as well as factors that determine their functional capacity. The current study examines 1) ADL, 2) (I) ADL), 3) self-reported health status, 4) functional capacity, and 5) factors that determine functional capacity of older men. METHODS AND METHOD: Stratified multistage probability sampling technique was used to draw a sample of 2,000 55+ year men. A132-item questionnaire was used to collect the data. Descriptive statistics provide background information on the sample, cross tabulations were used to examine non-metric variables and logistic regression provides a model of predictors of functional capacity. Fifty-five percent of sample indicated good current health status. Four percent was mostly satisfied with life; 21.7% had moderate dependence; 77.1% had high dependence (i.e. independence); 1.2% had low dependence; 21.9% were ages 75 years and older; 35.6% were ages 65 to 74 years and 42.6% reported ages 55 to 64 years. Functional capacity can be determined by church attendance (β=0.245; 95% CI: 0.264, 1.291); social support (β=0.129; 95% CI: 0.129, 0.258), area of residence (β=-0.060; 95% CI: -0.427, -0.061) and lastly by age of respondents. Ageing in explains deterioration in their (I) ADL, suggesting the challenges of ageing men's independence. More rural men were rarely satisfied with life; but more of them had a greater functional capacity than urban men. Depression was found to negatively relate to functional capacity, and church attendees had a greater functional status than non-attendees.


Contribution of anthropogenic and natural sources to atmospheric methane variability.
Methane is an important greenhouse gas, and its atmospheric concentration has nearly tripled since pre-industrial times. The growth rate of atmospheric methane is determined by the balance between surface emissions and photochemical destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably, this growth rate has decreased markedly since the early 1990s, and the level of methane has remained relatively constant since 1999, leading to a downward revision of its projected influence on global temperatures. Large fluctuations in the growth rate of atmospheric methane are also observed from one year to the next, but their causes remain uncertain. Here we quantify the processes that controlled variations in methane emissions between 1984 and 2003 using an inversion model of atmospheric transport and chemistry. Our results indicate that wetland emissions dominated the inter-annual variability of methane sources, whereas fire emissions played a smaller role, except during the 1997-1998 El Niño event. These top-down estimates of changes in wetland and fire emissions are in good agreement with independent estimates based on remote sensing information and biogeochemical models. On longer timescales, our results show that the decrease in atmospheric methane growth during the 1990s was caused by a decline in anthropogenic emissions. Since 1999, however, they indicate that anthropogenic emissions of methane have risen again. The effect of this increase on the growth rate of atmospheric methane has been masked by a coincident decrease in wetland emissions, but atmospheric methane levels may increase in the near future if wetland emissions return to their mean 1990s levels.


Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients.
Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer. Tamoxifen is the most commonly used antiestrogen, but toremifene is gaining in popularity. We compared here the effects of tamoxifen and toremifene on bone metabolism and density in 30 postmenopausal patients with breast cancer, who were randomized to receive tamoxifen (20 mg/day, n = 16) or toremifene (40 mg/day, n = 14) for 1 yr. Biochemical markers of bone resorption [urinary hydroxyproline, serum cross-linked carboxyterminal telopeptide of type I collagen, urinary cross-linked aminoterminal telopeptide of type I collagen (NTx)] and bone formation [serum bone-specific alkaline phosphatase, osteocalcin, and aminoterminal and carboxyterminal propeptide of type I procollagen] were assessed before treatment and at 6 and 12 months of the antiestrogen regimen. Bone mineral density (BMD) in the lumbar spine and proximal femur (neck, trochanter, and Ward's triangle) was measured using dual-energy x-ray absorptiometry before treatment and at 12 months of treatment. Urinary NTx decreased after 6 months' use of tamoxifen (mean fall: 33%) and of toremifene (mean fall: 16%). Use of tamoxifen was associated with a significant decrease in osteocalcin (mean fall: 25%) and aminoterminal propeptide of type I procollagen (mean fall: 22%), whereas toremifene failed to influence these markers. Tamoxifen increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and 5% in Ward's triangle. Toremifene failed to increase BMD at any site measured, and in contrast, a slight trend toward a fall (-0.3 to -0.9%) in BMD was seen in patients treated with toremifene. Falls in urinary NTx, from baseline to 6 months, correlated significantly with changes in the lumbar spine BMD (r = -0.57, P = 0.0002) in the whole patient series. We conclude that tamoxifen (20 mg/day) increases BMD in postmenopausal breast cancer patients, whereas toremifene (40 mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged studies on bone metabolism, comparing these two antiestrogens, are needed; but even now, clinicians should be aware of these differences between tamoxifen and toremifene.


A psychodynamic model of behavior after acute central nervous system damage.
This article describes a conceptual psychodynamic model for understanding the neurobehavioral manifestations of acute central nervous system damage (ACNSD) displayed by patients during the rehabilitation process. According to the proposed model, patientsO behavioral responses are viewed as their only means of emotional expression and therefore may not be considered entirely abnormal when viewed from the perspective of patientsO interpersonal contexts. An improved understanding of the dynamic processes through which recovering patients with ACNSD journey may lead to better interaction between the patient and the therapeutic environment, the interdisciplinary team, and family members. Combining this proposed psychodynamic model with an emerging understanding of the neurobehavioral foundations of aggression and depression may also lead to a more rational approach to intervention with various psychopharmacologic agents. During the rehabilitation process, understanding patients' cognitive deficits, motivational drives, and emotional needs and proper implementation of medical and environmental treatment can ultimately lead to a better psychosocial outcome.


Patients at risk for peritoneal surface malignancy of colorectal cancer origin: the role of second look laparotomy.
Peritoneal surface malignancy (PSM) is a frequent occurrence in the natural history of colorectal cancer (CRC). Although significant advances have been made in screening of CRC, similar progress has yet to be made in the early detection of PSM of colorectal cancer origin. The fact that advanced CRC can be confined to the peritoneal surface without distant dissemination forms the basis for aggressive multi-modality therapy consisting of cytoreductive surgery (CRS) plus hyperthermic intra-peritoneal chemotherapy (HIPEC), and neoadjuvant and/or adjuvant systemic therapy. Reported overall survival with complete CRS+HIPEC exceeds that of systemic therapy alone for the treatment of PSM from CRC, underscoring the advantage of this multi-modality therapeutic approach. Patients with limited peritoneal disease from CRC can undergo complete cytoreduction, which is associated with the best reported outcomes. As early or limited peritoneal carcinomatosis is undetectable by conventional imaging modalities, second look laparotomy is an important means to identify disease in high-risk patients at a stage most amenable to complete cytoreduction. This review focuses on the identification of patients at risk for PSM from CRC and discusses the role of second look laparotomy.


Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic lymphoma kinase in embryonal and alveolar rhabdomyosarcoma: a rational choice.
Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly affecting children and adolescents. Since survival of high-risk patients remains poor, new treatment options are awaited. The aim of this study is to investigate anaplastic lymphoma kinase (ALK) and insulin-like growth factor-1 receptor (IGF-1R) as potential therapeutic targets in RMS. One-hundred-and-twelve primary tumours (embryonal RMS (eRMS)86; alveolar RMS (aRMS)26) were collected. Expression of IGF-1R, ALK and downstream pathway proteins was evaluated by immunohistochemistry. The effect of ALK inhibitor NVP-TAE684 (Novartis), IGF-1R antibody R1507 (Roche) and combined treatment was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in cell lines (aRMS Rh30, Rh41; eRMS Rh18, RD). IGF-1R and ALK expression was observed in 72% and 92% of aRMS and 61% and 39% of eRMS, respectively. Co-expression was observed in 68% of aRMS and 32% of eRMS. Nuclear IGF-1R expression was an adverse prognostic factor in eRMS (5-year survival 46.9 ± 18.7% versus 84.4 ± 5.9%, p=0.006). In vitro, R1507 showed diminished viability predominantly in Rh41. NVP-TAE684 showed diminished viability in Rh41 and Rh30, and to a lesser extent in Rh18 and RD. Simultaneous treatment revealed synergistic activity against Rh41 and Rh30. Co-expression of IGF-1R and ALK is detected in eRMS and particularly in aRMS. As combined inhibition reveals synergistic cytotoxic effects, this combination seems promising and needs further investigation.


Hypoxia Treatment of Adipose Mesenchymal Stem Cells Promotes the Growth of Dermal Papilla Cells via HIF-1α and ERK1/2 Signaling Pathways.
Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α (HIF-1α) increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (BMP7). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning.


An analysis of the delivery of anaesthetic training sessions in the United Kingdom.
We analysed data from the electronic rota system CLWRota, covering 2,689,962 anaesthetic sessions between 01/01/2014 and 31/12/2015, in 91 UK Trusts, in order to investigate trainees' supervision. There were 8209 trainee attachments analysed, during which 618,695 sessions were undertaken by trainees. The number of supervised sessions per week that trainees worked varied considerably (median (IQR [range]) 2.6 (1.6-3.6 [0-10]) for all grades combined), with senior trainees more likely than junior trainees to be supervised for fewer than the three sessions per week mandated by the Royal College of Anaesthetists. The number of supervised sessions was unrelated to Trusts' size, suggesting that trainees in smaller hospitals receive the same level of supervision as in larger teaching hospitals. Analysis of a dataset of this size should be a good reflection of the delivery of anaesthesia training in the UK.


Nanoarchitectonics with Porphyrin Functionalized DNA.
DNA is well-known as bearer of the genetic code. Since its structure elucidation nearly seven decades ago by Watson, Crick, Wilkins, and Franklin, much has been learned about its detailed structure, function, and genetic coding. The development of automated solid-phase synthesis, and with it the availability of synthetic DNA with any desired sequence in lengths of up to hundreds of bases in the best case, has contributed much to the advancement of the field of DNA research. In addition, classic organic synthesis has allowed introduction of a very large number of modifications in the DNA in a sequence specific manner, which have initially been targeted at altering the biological function of DNA. However, in recent years DNA has become a very attractive scaffold in supramolecular chemistry, where DNA is taken out of its biological role and serves as both stick and glue molecule to assemble novel functional structures with nanometer precision. The attachment of functionalities to DNA has led to the creation of supramolecular systems with applications in light harvesting, energy and electron transfer, sensing, and catalysis. Functional DNA is clearly having a significant impact in the field of bioinspired nanosystems. Of particular interest is the use of porphyrins in supramolecular chemistry and bionanotechnology, because they are excellent functional groups due to their electronic properties that can be tailored through chemical modifications of the aromatic core or through insertion of almost any metal of the periodic table into the central cavity. The porphyrins can be attached either to the nucleobase, to the phosphate group, or to the ribose moiety. Additionally, noncovalent templating through Watson-Crick base pairing forms an alternative and attractive approach. With this, the combination of two seemingly simple molecules gives rise to a highly complex system with unprecedented possibilities for modulation of function, and with it applications, particularly when combined with other functional groups. Here, an overview is given on the developments of using porphyrin modified DNA for the construction of functional assemblies. Strategies for the synthesis and characterization are presented alongside selected applications where the porphyrin modification has proven to be particularly useful and superior to other modifiers but also has revealed its limitations. We also discuss implications on properties and behavior of the porphyrin-DNA, where similar issues could arise when using other hydrophobic and bulky substituents on DNA. This includes particularly problems regarding synthesis of the building blocks, DNA synthesis, yields, solubility, and intermolecular interactions.


[DNA damages of liver cells and expressions of DNA damage repair genes in rats exposed to vinyl chloride monomer].
To study DNA damages of liver cells in rats exposed to vinyl chloride monomer (VCM), and the expressions of DNA damage repair enzymes including O(6)-methyl guanine-DNA methyl transferase (MGMT), X-ray repair cross-complementing group 1 (XRCC1) and X-ray repair cross-complementing group 3 (XRCC3); and to explore the repair mechanism of DNA damage induced by VCM. Rats were exposed to VCM by intraperitoneal injection. DNA damages were detected by single cell gel electrophoresis (comet assay). The expressions of DNA damage repair enzymes were measured by immunohistochemical methods. The percentages of comet cells in low, moderate, and high dose groups (11.75%, 12.38%, and 17.63%, respectively) were greater than that of control (5.67%). The latter two groups were significantly different from that of control (P < 0.05, P < 0.01). The expressions of MGMT and XRCC1 decreased, and XRCC3 increased with the dose of VCM increased. DNA damage was correlated with the expression of XRCC3 (r = 0.438, P = 0.067). VCM can cause DNA damage of liver cells with dose-response relationship. DNA damage repair enzymes take part in the repairing of DNA damage induced by VCM.


Influence of the body mass index on postoperative outcome and long-term survival after pancreatic resections in patients with underlying malignancy.
While the long-term survival rate among patients with pancreatic and periampullary carcinomas remains low, it can be influenced by various factors. The purpose of this retrospective study was to investigate the effects of body mass index (BMI) on postoperative complications and patient survival after pancreatic resections for underlying malignancy over a 20-year observation period. We analyzed 1,384 patients, 918 patients with pancreatic ductal adenocarcinoma (PDAC) (66.3%), 229 patients with distal cholangiocarcinoma (16.5%), 206 ampullary carcinoma patients (14.8%), and 31 duodenal carcinoma patients (2.2%). Patients were classified into four groups (group 1 <18.5; group 2, 18.5-25.0; group 3, 25.1-30.0; group 4 >30.0) according to their BMI (kg/m2). We analyzed differences in postoperative complications, postoperative length of hospital stays, reoperations, postoperative mortality and survival rate among the groups. Within a mean observation period of 687.7 [2-8,500] days, 735 (53.1%) patients died. There were important differences in postoperative complications (group 1, 16.2%; group 2, 20.3%; group 3, 27.2%, group 4, 41.6%) with the type of postoperative complications also varying between the groups. Overall 1-, 5-, 10- and 15-year survival rates were 66.4%, 25.5%, 17.9%, and 12.1%, respectively, with survival rates varying amongst the four groups. Patients with a BMI between 18.5 and 30 show better postoperative outcomes, regarding complications, hospitalization duration, and reoperation rates than underweight or obese patients. Short-term survival depends strongly on postoperative complications while patients with a higher BMI show better long-term survival rates.


WIDE-FIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF DIABETIC TRACTIONAL RETINAL DETACHMENTS BEFORE AND AFTER SURGICAL REPAIR.
Wide-field (WF) swept-source (SS) optical coherence tomography angiography (SS-OCTA) was used to image diabetic tractional retinal detachments (TRDs) before and after pars plana vitrectomy. The clinical utility of SS-OCTA was assessed. Patients with diabetic TRDs were imaged prospectively with SS-OCTA. Ultrawide-field imaging was obtained when possible. Postoperative WF SS-OCTA imaging was performed. From January 2018 through December 2019, 31 eyes of 21 patients with diabetic TRDs were imaged. Wide-field SS-OCTA en-face images captured all areas of TRD and fibrovascular proliferation within the posterior pole that were visualized on ultrawide-field imaging. Optical coherence tomography angiography B-scans revealed the vascularity of preretinal membranes and identified areas of vitreoretinal traction and posterior vitreous detachment. Ten eyes underwent pars plana vitrectomy. Postoperative SS-OCTA imaging demonstrated removal of fibrovascular membranes, relief of traction, and resolution of TRDs. Retinal ischemia before and after surgical repair appeared similar. All clinically relevant features of diabetic TRDs were identified at baseline and assessed longitudinally after pars plana vitrectomy using WF SS-OCTA, which showed resolution of vitreoretinal traction and no apparent change in the status of retinal perfusion after surgery. If the media are clear and fixation is adequate, WF SS-OCTA is likely the only imaging modality needed for the diagnosis and longitudinal evaluation of diabetic TRDs.


Regional transarterial chemoembolization combined with chemoradiotherapy for locally advanced rectal cancer: a retrospective study of a new combination.
Locally advanced rectal cancer (LARC) has a high risk of distant metastasis (DM). Currently, many treatment courses of LARC have arisen, but patients' DM status has not significantly improved. This study was designed to compare the effect between preoperative regional transarterial chemoembolization combined with neoadjuvant chemoradiotherapy and standard neoadjuvant therapy on preventing DM in patients with LARC. A total of 81 LARC patients between July 2013 and May 2018 were enrolled in this retrospective study. Among them, 44 patients received preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy (the interventional group), and 37 patients received only neoadjuvant chemoradiotherapy (the control group). The baseline data; preoperative toxicities; postoperative DM rate within 1, 2, and 3 years; and postoperative complications were compared between the two groups. All patients successfully completed their treatments. There were no significant differences between the two groups in age, gender, tumor size, distance between the tumor and anal verge, CEA level, lymphovascular invasion, or tumor stage before treatment. The pathological T staging post-treatment in the interventional group was significantly reduced compared to that of the control group (p = 0.025). There were no significant differences between groups in DM rates within 1 and 2 years after surgery. In terms of DM rate within 3 years after surgery, the interventional group was significantly lower than that of the control group (9.1% vs. 29.7%, p = 0.036). Preoperative regional transarterial chemoembolization combined with concurrent chemoradiotherapy may play an important role in reducing postoperative DM in LARC.


[Annular elastolytic giant cell granuloma--differential diagnosis of cutaneous granulomatosis].
Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease characterized by phagocytosis of elastic fibres by multinucleated giant cells. A 46-year-old female patient developed multiple annular lesions with elevated borders and central atrophy on the limbs. Histological examination revealed the absence of elastic material in the granulomatous infiltrate and fragments of elastic fibrils in the cytoplasm of the multinucleated giant cells. Immunohistological investigation revealed that the ratio of CD4+ to CD8+ T-lymphocytes was 3:1. Our patient was treated with clofazimine orally, 200 mg daily for the first 10 days, then 100 mg daily. After 12 weeks a definite improvement was achieved. Our case demonstrates that AEGCG, which is mostly localized on head and neck, has to be taken into account in the differential diagnosis of generalized cutaneous granulomatous disease.


Assessment of Diastolic Function in Congenital Heart Disease.
Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease.


Computation of optimal metamers.
A fast, accurate model for computing Logvinenko's optimal metamers is introduced. The spectral reflectance of an optimal metamer is uniquely determined from a class of metamers with common tristimulus values. A set of optimal metamers is useful for evaluating the color reproduction and gamut of object colors under different illuminants. In conventional methods, optimal metamers are calculated by interpolating the coordinates of precomputed optimal colors. This model optimizes the spectral reflectance parameters efficiently without switching between bandpass (Type I) and bandstop (Type II) optimal metamers, or requiring any stored optimal-color datasets. Some optimal metamer loci computed using MATLAB are presented.


Effectiveness of a feedback signal in a computer mouse on upper extremity musculoskeletal symptoms: a randomised controlled trial with an 8-month follow-up.
To study the effectiveness of using a computer mouse with a feedback signal for upper extremity musculoskeletal symptoms in office workers. A randomised controlled trial with 8 months of follow-up was carried out. The intervention consisted of a computer mouse with a feedback signal. In total, 354 subjects were allocated to the intervention group or the control group. Measurements were performed with electronic questionnaires at baseline, after 4 months and after 8 months. Outcome variables were the prevalence and incidence of upper extremity musculoskeletal symptoms and disability in the upper extremities. The intervention process was evaluated by software registration. The use of the mouse with a feedback signal resulted in a significant decrease in duration of mouse usage over time. No differences were found in the number of mouse usage rest breaks. No differences were found in the prevalence (p = 0.29) or incidence (p = 0.832) of upper extremity musculoskeletal symptoms between the groups 8 months after baseline. The prevalence decreased from 49% at baseline to 44% after 8 months in the control group, while it remained at 36% in the intervention group. The incidence was 21% in the control group and 22% in the intervention group. Among the population with upper extremity musculoskeletal symptoms at baseline, the risk of experiencing symptoms after 8 months did not differ between the groups (p = 0.49). Minor disability was found in both groups. In the intervention group, a lower level of physical disability over time was reported than in the control group (p = 0.02). A feedback signal computer mouse does not affect the prevalence and incidence of upper extremity musculoskeletal symptoms, but it does lower disability scores. Given the high prevalence, studying preventive interventions for upper extremity musculoskeletal symptoms is of high importance. ISRCTN13222474.


LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR-155.
The development of drug resistance is the main obstacle for successful treatment in acute myeloid leukemia (AML). Noncoding RNAs have been implicated in biological function in AML drug resistance. Aberrant protein glycosylation is associated with AML progression. The aim of the study was to explore the potential regulatory mechanism of lncRNA MEG3/miR-155/ALG9 axis in drug resistance of AML. QRT-PCR and Western blot were used for comparison analyses of ALG9, MEG3, and miR-155 levels. CCK-8 and colony formation assays were determined for drug sensitivity and proliferative capability of AML cells. Luciferase reporter assay was used to confirm the targets of miR-155. The mannosyltransferase ALG9 and MEG3 was downregulated in peripheral blood mononuclear cells (PBMCs) of M5/multidrug resistance (MDR) AML patients and adriamycin (ADR)-resistant AML cell lines, which determined a positive correlation in AML patients. Low expression of ALG9 and MEG3 predicted poor prognosis of AML patients. The altered level of ALG9 was found corresponding to the drug-resistant phenotype and sphere formation of AML cells. MiR-155 was overexpressed in M5/MDR patients and ADR-resistant AML cells, as well as inversely correlated to ALG9 expression. MEG3 was a direct target of miR-155 and could sponge miR-155 in AML cells. MEG3 interacted with miR-155 to regulate ALG9 expression, which reversed the effects of ALG9 regulation on proliferation and drug resistance in AML cells. MEG3 sponged miR-155 by competing endogenous RNA (ceRNA) mechanism, which further modulated ALG9 expression and AML procession, providing a novel therapeutic target for AML chemoresistance.


Quantitation of cholesterol-carrying particles in human gallbladder bile.
The inter-mixed micellar/vesicular (non-phospholipid-associated) bile salt concentration (IMC) can be rapidly measured in model biles by centrifugal ultrafiltration, thus allowing reliable separation of vesicular and micellar cholesterol carriers by gel filtration with an elution buffer containing bile salts at the correct IMC (Donovan, J. M., and A. A. Jackson. 1993. J. Lipid Res. 34: 1121-1129). We adapted this method to the more complex human gallbladder bile and examined the relationship between cholesterol solubilization and crystallization in gallbladder biles from 10 cholesterol gallstone patients. The IMC (mean +/- SEM) was 9.67 +/- 1.97 (range 3.56-35.02) mM with significant enrichment with hydrophilic bile salt species. Upon gel filtration of these biles with an eluant buffer containing 10 major bile salts at concentrations according to their IMC, cholesterol was found to be solubilized mainly in mixed micelles. Vesicles were detected in all 10 biles after separation by KBr density gradient ultracentrifugation but in only 5 of these biles with the IMC method. Biles without vesicles had a lower CSI (1.15 +/- 0.12 vs. 1.90 +/- 0.28, P < 0.05), a higher total lipid concentration (11.9 +/- 2.3 vs. 5.9 +/- 1.1, P < 0.05), and a higher bile salt/ (bile salt + phospholipid) ratio (0.83 +/- 0.01 vs. 0.74 +/- 0.04, P = 0.07). For both IMC and ultracentrifugation methods, vesicular cholesterol concentration showed a negative correlation with crystal observation time and a positive correlation with cumulative crystal score during 21 days. Our data indicate that methods such as density gradient ultracentrifugation overestimate vesicular cholesterol solubilization in human biles.


For better or for worse: Social influences on risk-taking.
This study investigated changes in risk-taking propensity on a behavioral decision-making task as a function of varying social conditions with peers. In contrast to the effects of direct peer influence (pro-risk and anti-risk messages by peers), we included a socially ambiguous context (neutral messages by peers) and a no-peer control (participants alone) as comparison conditions. Using a counterbalanced mixed factorial design, college students (N = 187) completed the Balloon Analogue Risk Task-Youth (BART-Y) twice during two consecutive sessions, including once alone and once with a confederate; the control group completed two sessions of the task alone. The findings showed that, in general, direct pro-risk messages led to the most robust and consistent changes in risk-taking. The findings are discussed in terms of the multidimensional and multidirectional nature of peer influence during the college years.


Cutaneous vascular response to calcitonin gene-related peptide in psoriasis and normal subjects.
To determine whether cutaneous blood vessels in subjects with psoriasis possess a generalized inherently abnormal response to neuropeptides, the effect of three doses of intradermally injected calcitonin gene-related peptide (CGRP) on skin blood flow in normal subjects (n = 10), and on clinically normal skin (greater than 5 cm from psoriatic lesions) in subjects with psoriasis (n = 9) was measured using a laser Doppler technique. Calcitonin gene-related peptide caused a dose-dependent increase in local blood flow in both psoriatic and normal subjects, which was not statistically different between the two groups. This study has shown that the cutaneous vasculature at sites distant from lesions of psoriasis (> 5 cm) is not inherently different from normal skin in its response to CGRP.


Hyperprolactinemia and sexual disturbances among uremic women on hemodialysis.
The investigation of a sample of 99 women on maintenance hemodialysis has shown the presence of sexual disturbances to a great extent: the rate of sexual intercourse and the ability to reach orgasm were significantly lower than in age-matched control women. 80% declared a reduction in their sexual desire and the frequency of intercourse was also lower as compared to the period prior to dialysis. Ageing decreased the sexual activity in both the ill and healthy population, but in uremic patients the sexual activity ended at an earlier age. The patients with hyperprolactinemia reported lower frequencies of intercourse and lower percentages of orgasm than normoprolactinemic ones. The incidence of sexual dysfunction and the role of hyperprolactinemia in this respect were similar to those which are found among male patients on hemodialysis.


FVIII half-life extension by coadministration of a D'D3 albumin fusion protein in mice, rabbits, rats, and monkeys.
A novel mechanism for extending the circulatory half-life of coagulation factor VIII (FVIII) has been established and evaluated preclinically. The FVIII binding domain of von Willebrand factor (D'D3) fused to human albumin (rD'D3-FP) dose dependently improved pharmacokinetics parameters of coadministered FVIII in all animal species tested, from mouse to cynomolgus monkey, after IV injection. At higher doses, the half-life of recombinant FVIII (rVIII-SingleChain) was calculated to be increased 2.6-fold to fivefold compared with rVIII-SingleChain administered alone in rats, rabbits, and cynomolgus monkeys, and it was increased 3.1-fold to 9.1-fold in mice. Sustained pharmacodynamics effects were observed (ie, activated partial thromboplastin time and thrombin generation measured ex vivo). No increased risk of thrombosis was observed with coadministration of rVIII-SingleChain and rD'D3-FP compared with rVIII-SingleChain alone. At concentrations beyond the anticipated therapeutic range, rD'D3-FP reduced the hemostatic efficacy of coadministered rVIII-SingleChain. This finding might be due to scavenging of activated FVIII by the excessive amount of rD'D3-FP which, in turn, might result in a reduced probability of the formation of the tenase complex. This observation underlines the importance of a fine-tuned balance between FVIII and its binding partner, von Willebrand factor, for hemostasis in general.


Toward a new generation of agricultural system data, models, and knowledge products: State of agricultural systems science.
We review the current state of agricultural systems science, focusing in particular on the capabilities and limitations of agricultural systems models. We discuss the state of models relative to five different Use Cases spanning field, farm, landscape, regional, and global spatial scales and engaging questions in past, current, and future time periods. Contributions from multiple disciplines have made major advances relevant to a wide range of agricultural system model applications at various spatial and temporal scales. Although current agricultural systems models have features that are needed for the Use Cases, we found that all of them have limitations and need to be improved. We identified common limitations across all Use Cases, namely 1) a scarcity of data for developing, evaluating, and applying agricultural system models and 2) inadequate knowledge systems that effectively communicate model results to society. We argue that these limitations are greater obstacles to progress than gaps in conceptual theory or available methods for using system models. New initiatives on open data show promise for addressing the data problem, but there also needs to be a cultural change among agricultural researchers to ensure that data for addressing the range of Use Cases are available for future model improvements and applications. We conclude that multiple platforms and multiple models are needed for model applications for different purposes. The Use Cases provide a useful framework for considering capabilities and limitations of existing models and data.


DNA base changes in benzo[a]pyrene diol epoxide-induced dihydrofolate reductase mutants of Chinese hamster ovary cells.
We previously treated Chinese hamster ovary (CHO) cells with benzo[a]pyrene diol epoxide (BPDE) and mutants at the dihydrofolate reductase (dhfr) locus were isolated. On the basis of Southern blotting and RNA heteroduplex mapping experiments, 14 of the 15 mutants were presumed to carry point mutations. Two restriction fragment length polymorphism mutants were cloned and sequenced; one carried a point mutation, the other a -1 frameshift mutation. Using polymerase chain reaction techniques and direct sequencing of amplified mutant DNA, we have now determined the induced changes in the remaining 12 cell lines. All changes occurred at guanine bases; all target guanines except one were on the non-transcribed coding strand. Most mutants (79%) contained base substitutions; the rest (3/14) carried frameshift mutations. Of the point mutations, all but one (91%) were GC----TA transversions either in the dhfr coding sequence or at splice sites. The single exception was a GC----AT transition. Of the frameshift mutations, two were deletions of a GC pair and the other was an insertion of an AT pair. Four different mutations (29%) were clustered in a 3 bp region in exon 4. Tandem guanine bases adjacent to adenine were favored sites for mutation occurring in 9/14 cases (64%). These results are consistent with data previously obtained by others in the supF shuttle vector system and the CHO aprt gene.


3D coronary artery imaging with phase reordering for improved scan efficiency.
Three-dimensional (3D) coronary imaging has the potential to overcome problems resulting from vessel tortuosity and to reduce partial volume effects. With these techniques, however, acquisition times are long and respiratory motion artifacts problematical. This work describes the development of a method that applies phase encode reordering to 3D acquisitions, allowing larger navigator acceptance windows to be used, with a consequent reduction in acquisition time. This method is compared with navigator acceptance window methods (the acceptance-rejection algorithm and the diminishing variance algorithm) and the retrospective respiratory gating technique, both in vitro and in vivo. The use of phase reordering with a 10 mm acceptance window provided a significant increase in scan efficiency over a non-reordered 5 mm method (P<0.001) with no significant change in image quality, and a significant increase in image quality compared with a non-reordered image acquired in the same time (P<0.05). A significant improvement in both image quality and scan efficiency was demonstrated over the retrospective respiratory gating method (P<0.05).


Mulberry leaf polyphenol extract induced apoptosis involving regulation of adenosine monophosphate-activated protein kinase/fatty acid synthase in a p53-negative hepatocellular carcinoma cell.
The polyphenols in mulberry leaf possess the ability to inhibit cell proliferation, invasion, and metastasis of tumors. It was reported that the p53 status plays an important role in switching apoptosis and the cell cycle following adenosine monophosphate-activated protein kinase (AMPK) activation. In this study, we aimed to detect the effect of the mulberry leaf polyphenol extract (MLPE) on inducing cell death in p53-negative (Hep3B) and p53-positive (Hep3B with transfected p53) hepatocellular carcinoma cells and also to clarify the role of p53 in MLPE-treated cells. After treatment of the Hep3B cells with MLPE, apoptosis was induced via the AMPK/PI3K/Akt and Bcl-2 family pathways. Transient transfection of p53 into Hep3B cells led to switching autophagy instead of apoptosis by MLPE treatment. We demonstrated that acridine orange staining and protein expressions of LC-3 and beclin-1 were increased in p53-transfected cells. These results implied induction of apoptosis or autophagy in MLPE-treated hepatocellular carcinoma cells can be due to the p53 status. We also found MLPE can not only activate AMPK but also diminish fatty acid synthase, a molecular target for cancer inhibition. At present, our results indicate MLPE can play an active role in mediating the cell death of hepatocellular carcinoma cells and the p53 might play an important role in regulating the death mechanisms.


Seven-Year Follow-Up of an Online Critical Care Curriculum.
Background: In July of 2013, the University of Maryland launched MarylandCCProject.com. This free-access educational website delivers asynchronous high-quality multidisciplinary critical care education targeted at critical care trainees. The lectures, presented in real time on-site, are recorded and available on the website or as a podcast on iTunes or Android. Thus, the curriculum can be easily accessed around the world. Objective: We sought to identify the impact this website has on current and former University of Maryland critical care trainees. Methods: A 32-question survey was generated using a standard survey generation tool. The survey was e-mailed in the fall of 2019 to the University of Maryland Multi-Departmental Critical Care current and graduated trainees from the prior 7 years. Survey data were collected through December 2019. The questions focused on user demographics, overall experience with the website, scope of website use, and clinical application of the content. Anonymous responses were electronically gathered. Results: A total of 186 current trainees and graduates were surveyed, with a 39% (n = 72) response rate. Of responders, 76% (55) use the website for ongoing medical education. The majority use the website at least monthly. Most users (63%, n = 35) access the lectures directly through the website. All 55 current users agree that the website has improved their medical knowledge and is a useful education resource. Platform use has increased and includes users from around the world. Conclusion: Based on our current data, the MarylandCCProject remains a valuable and highly used educational resource, impacting patient care both during and after critical care fellowship training.


IMMUNOHISTOCHEMISTRY IN ENDOMETRIAL HYPERPLASIA AND ENDOMETRIAL ADENOCARCINOMA.
Endometrial hyperplasia is a proliferation of endometrial glands due to the prolonged stimulation with estrogens of the endometrium that occurs in women receiving exogenous estrogens, with anovulatory cycles, or in patients with ovarian tumours with estrogen secretion. The study performed by the authors included 575 patients with endometrial hyperplasia and 163 patients with endometrial adenocarcinoma admitted to the "Cuza-Vodă" Obstetrics and Gynaecology Clinical Hospital of Iasi, between 2005-2007. There were selected, for these immunohistochemistry reactions, 22 cases of simple hyperplasia without atypia, 26 cases of complex hyperplasia without atypia, 23 cases of endometrial adenocarcinoma of endometrioid type, well differentiated, 22 cases of endometrial adenocarcinoma of endometrioid type, moderately differentiated, and 19 cases of non-endometrioid adenocarcinomas represented by nine clear cells and 10 serous endometrial adenocarcinomas. Estrogen receptors have been positive in about 85-90% of the tumour cells of the well-differentiated endometrial adenocarcinomas of endometrioid type (GI). In endometrioid-type endometrial adenocarcinomas moderately differentiated (GII), the estrogen receptors were positive in approximately 70-85% of the tumour cells. Endometrial hyperplasia, especially complex endometrial hyperplasia with atypia, increase the risk for endometrial adenocarcinoma, and their early detection becomes mandatory under cancer prevention. Well-differentiated endometrioid endome- trial adenocarcinomas were ER and PR-positive, so that the ER expression correlated with the PR expression. Well-differentiated endometrioid endometrial adenocarcinomas (GI) in the studied group also showed a higher content of ER and PR compared to the endometrial moderately-differentiated endometrioid endometrial adenocarcinomas (GII). In nonendometrioid adenocarcinomas, represented by clear-cell endometrial adenocarcinomas, the ER content was reduced and the PR expression was negative. Serous adenocarcinomas failed to show an immunohistochemically expression for ER and PR.


Fear Learning Regulates Cortical Sensory Representations by Suppressing Habituation.
Projections from auditory cortex to the amygdala are thought to contribute to the induction of auditory fear learning. In addition, fear conditioning has been found to enhance cortical responses to conditioned tones, suggesting that cortical plasticity contributes to fear learning. However, the functional role of auditory cortex in the retrieval of fear memories is unclear and how fear learning regulates cortical sensory representations is not well understood. To address these questions, we use acute optogenetic silencing and chronic two-photon calcium imaging in mouse auditory cortex during fear learning. Longitudinal imaging of neuronal ensemble activity reveals that discriminative fear learning modulates cortical sensory representations via the suppression of cortical habituation.


Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression.
Opticin is a recently discovered glycoprotein present predominantly in the vitreous humour. It is synthesised and secreted by the ciliary body epithelium (CBE) from the initiation of CBE development in the embryo, and production continues throughout life. To determine whether a variety of ciliary body tumours synthesise opticin to characterise further its role in ciliary body health and disease. Immunohistochemistry was used to determine the distribution of opticin in normal human CBE, and in hyperplastic and neoplastic CBE lesions. Opticin was immunolocalised to the basal cell surface and basement membrane material of the non-pigmented CBE in nine donor eyes as well as four hyperplastic lesions of the CBE (Fuchs's adenoma). By contrast, none of eight neoplastic lesions (two adenoma and six adenocarcinoma) of CBE stained for opticin. The present series supports the theory that opticin is produced by the non-pigmented CBE throughout adult life. Loss of opticin expression by this tissue is associated with and could contribute towards neoplastic transformation.


Influence of backward bifurcation on interpretation of r(0) in a model of epidemic tuberculosis with reinfection.
the extent to which reinfection of latently infected individuals contributes to the dynamics of tuberculosis (TB) epidemics. In this study we present an epidemiological model of Mycobacterium tuberculosis infection that includes the process of reinfection. Using analysis and numerical simulations, we observe the effect that varying levels of reinfection has on the qualitative dynamics of the TB epidemic. We examine cases of the model both with and without treatment of actively infected individuals. Next, we consider a variation of the model describing a heterogeneous population, stratified by susceptibility to TB infection. Results show that a threshold level of reinfection exists in all cases of the model. Beyond this threshold, the dynamics of the model are described by a backward bifurcation. Uncertainty analysis of the parameters shows that this threshold is too high to be attained in a realistic epidemic. However, we show that even for sub-threshold levels of reinfection, including reinfection in the model changes dynamic behavior of the model. In particular, when reinfection is present the basic reproductive number, R(0), does not accurately describe the severity of an epidemic.


Trion-Induced Distinct Transient Behavior and Stokes Shift in WS2 Monolayers.
Understanding the excitonic behavior in two-dimensional transition-metal dichalcogenides (2D TMDs) is of both fundamental interest and critical importance for optoelectronic applications. Here, we investigate the transient excitonic behavior and Stokes shift in WS2 monolayers on both sapphire and glass substrates. Trion formation was confirmed as the origin of the distinct photoluminescence (PL) emission and Stokes shift in WS2 monolayers. Moreover, the transient studies demonstrate faster recombination of both the exciton and the short-lived trion on the glass substrate as compared to that on the sapphire substrate, owing to the heavier n-doping and greater number of defects introduced by the glass substrate. In addition, a long-lived trion species attributed to the intervalley triplet trion was observed on the glass substrate, with a lifetime on the nanosecond time scale. These findings offer a comprehensive understanding of the excitonic behavior and Stokes shift in WS2 monolayers and will lay the foundation for further fundamental investigations in the field.