Psychological Impact of Masks and Infection-Prevention Plastic Partitions on Anxiety for Infection and Patient-Doctor Relationships During the COVID-19 Pandemic.
Objective: To investigate the impact of masks and plastic partitions on patient-doctor communication and subjective anxiety for infection in patients with psychiatric disorders. Methods: Subjects were patients who visited a psychiatric clinic in Japan from April 27 to August 31, 2020. Anxiety of being infected and the psychological barrier to communication were evaluated on a 5-point scale. Results: The final analysis included 425 patients. Most participants answered that there was no change with regard to communication when the doctor was wearing a mask (n = 353, 91.0%) or using a plastic partition (n = 318, 82.8%). Most participants responded that anxiety for being infected was very mild, a little mild, or not changed by the doctor wearing a mask and using a plastic partition. Most participants felt significantly less anxiety with the doctor wearing a mask/using a plastic partition before than after the state of emergency declaration (P = .005 for mask and P < .001 for plastic partition). Participants in the older age range felt significantly higher anxiety compared to those in the younger and middle age range groups from doctors wearing masks (P < .001) and compared to those in the middle age range group from plastic partitions (P = .001). Conclusions: Use of masks and plastic partitions in psychiatric practice is recommended, as it may result in reduction of anxiety for infection without affecting patient-doctor communication in patients with psychiatric disorders. The generalizability of the results of the present study should be tested.


Arterial and Venous Doppler in Evaluation of the "At-Risk" Fetus.
Our practice utilizes Doppler ultrasound as one of the most objective and effective methods to assess at-risk pregnancies. This review will discuss the application of arterial and venous Doppler techniques in assessing and managing various diseases and conditions for high-risk fetuses.


Potential candidate genes for alveolar hypoxia identified by transcriptome network analysis.
BACKGROUND. Alveolar hypoxia is an important condition related to many disorders such as chronic pulmonary hypertension, pulmonary vasoconstriction, and pulmonary vascular remodeling. The aim of present study was to disclose the biological response and the potential transcriptome networks regulating the hypoxia response in the lungs. MATERIALS AND METHODS. In this study, the microarray dataset GSE11341 was used to construct a regulatory network and identify the potential genes related to alveolar hypoxia. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were also performed. RESULTS. Hypoxia inducible factor 1 alpha (HIF-1α), peroxisome proliferator-activated receptor gamma (PPARγ), and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB) were to be the hub nodes in the transcriptome network. HIF-1α may regulate potassium voltage-gated channel, shaker-related subfamily, member (5KCNA5), solute carrier family 2 (facilitated glucose transporter), member (1SLC2A1), and heme oxygenase (decycling) 1 (HMOX1) expression through the regulation of membrane potential, glucose metabolism, and anti-inflammation pathways. HMOX-1 mediates signaling pathways that relate to NF-кB. CCND1 (cyclin D1) expression could be regulated by PPARγ and HIF-1α via the cell cycle pathway. In addition, new transcriptional factors and target genes, such as phosphofructokinase (PFKL, liver), aldolase A (ALDOA, fructose-bisphosphate), and trefoil factor 3 (intestinal) (TFF3), were also identified. CONCLUSIONS. Transcriptome network analysis is a helpful method for the identification of the candidate genes in alveolar hypoxia. The KEGG pathway and GO term analysis are beneficial in the prediction of the underlying molecular mechanism of these identified genes in alveolar hypoxia.


Twenty-four hour versus extended antibiotic administration after surgery in complicated appendicitis: A randomized controlled trial.
Recent investigations noted noninferiority in short-course antimicrobial treatments following source control in abdominal infections. We set out to investigate noninferiority of a short and fixed (24 hours) antibiotic administration compared to extended treatment after source control in complicated appendicitis in a prospective single-center open-label randomized controlled trial. After Institutional Review Board (IRB) approval, all consecutive adult patients (age, ≥ 18 years) with complicated appendicitis including gangrenous appendicitis, perforated appendicitis, and appendicitis with periappendicular abscess between May 2016 and February 2018 were randomly allocated to antibacterial therapy limited to 24 hours (short) vs. >24 hours (extended) administration after appendectomy. Primary outcomes included composite postoperative complications and Comprehensive Complication Index (CCI). Secondary outcome was hospital length of stay (HLOS). Follow-up analysis at 1 month was conducted per intention and per protocol. A total of 80 patients were enrolled with 39 and 41 cases allocated to the short and the extended therapy group, respectively. Demographic profile and disease severity was similar between the study groups. Overall rate of complications was 17.9% and 29.3% in the short and extended group, respectively (p = 0.23). Mean CCI did not differ between the study groups (p = 0.29). Hospital length of stay was significantly reduced in the short therapy group (61 ± 34 hours vs. 81 ± 40 hours, p = 0.005). In the current prospective randomized investigation, the short (24 hours) antibiotic administration following appendectomy did not result in a worse primary outcome in complicated appendicitis. The short interval administration resulted in a significant reduction in HLOS with a major cost-saving and antibacterial stewardship perspective. Therapeutic Level IV.


[Rice pollen asthma and pollinosis in childhood: seasonal asthma and allergic rhinoconjunctivitis during the period of rice pollen emission in the surrouding area of rice field].
Although in 1969, rice pollen was first reported as a cause of asthma, rice pollen allergy has not been studied after the first report and thus the allergic significance of rice pollen is not well recognized at present. We investigated the sensitization to various allergens and the residential areas in children with the symptoms of asthma or rhinoconjunctivitis during the first decade of August, and measured rice pollen-specific IgE antibodies. Eighty-eight children (57 boys and 31 girls, mean age 8.5+/-2.9 years) with bronchial asthma or allergic rhinitis/conjunctivitis were included in this study and divided into two groups: children with (n=21) or without (n=67) symptoms during this period. The positivity rate to orchard grass pollen and the rate of residence in the surrounding area of rice field were high (81%, P=0.008 and 86%, P<0.001, respectively) in children with allergic symptoms, as compared to the values (48% and 27%, respectively) in children without symptoms. As the rice pollen season in Nagano occurs in the first decade of August, we measured rice pollen-specific IgE antibodies in 8 patients with symptoms during this period; all of these patients showed positive IgE antibodies to rice pollen. The RAST-inhibition assay using orchard grass and rice pollen indicated cross-allergenecity between these two pollen and also the existence of rice pollen-specific allergens. These results suggest that rice pollen induces seasonal asthma and allergic rhinoconjunctivitis during the first decade of August, which is the rice pollen season, in the surrounding area of rice fields.


Multilocus sequence typing and analysis of putative virulence factors in vancomycin-resistant and vancomycin-sensitive Enterococcus faecium isolates from Brazil.
Enterococci are leading causes of hospital-acquired infections that are often difficult to treat because of high-level aminoglycoside and glycopeptide resistance. Vancomycin-resistant enterococci are a global problem, and have been isolated with increasing frequency in hospitals in Brazil. The objective of this study was to determine the genetic relatedness of vancomycin-resistant Enterococcus faecium (VREFM) and vancomycin-sensitive E. faecium (VSEFM) isolated from human infections and faecal sources in Brazil, and to compare these isolates with those from domesticated animals. Isolates (n = 56) were classified by multilocus sequence typing (MLST) and assessed for putative virulence traits. The acm gene was detected in 98% of all isolates. The 56 isolates studied comprised 26 different MLST types. VSEFM isolates from the faeces of pigs were found to be distinct from all human isolates characterised previously by MLST, and were assigned new sequence type (ST) numbers. VREFM isolates were represented by four different STs (ST-114, ST-17, ST-281, ST-50). Among the 26 STs identified in this study, eBURST detected three groups of STs with related allelic profiles, and 19 unrelated STs. Among E. faecium isolates from Brazil, the esp gene was restricted to vancomycin-resistant isolates. Furthermore, isolates classified as ST-17 by MLST, an epidemic strain type isolated internationally with the purK-1 gene, were found among VREFM isolates from Brazil that also harboured the esp and hyl genes.


Multicomponent Reactions.
Multicomponent Reactions appear to be ideal for any form of synthesis, because of their numerous advantages in terms of sustainability and selectivity in building up complex molecular architectures, with high molecular diversity. This Special Issue collects seven contributions which expand our knowledge about Multicomponent Reactions, providing a good overview about innovative reactivities and applications.


Morphological changes of the upper gastrointestinal tract mucosa and Helicobacter pylori infection in HIV-positive patients with severe immunodeficiency and symptoms of dyspepsia.
HIV infection causes progressive immune defense system dysfunction, including the gastrointestinal (GI) tract. The aim of the study was to evaluate the morphological changes in the upper-GI tract mucosa in HIV-infected patients in relation to the degree of immunodeficiency, presence of H. pylori, fungal colonization, and antiretroviral treatment (HAART). One hundred forty-six patients (94 HIV positive, 52 HIV negative) with dyspeptic symptoms were evaluated by upper GI endoscopy and biopsy. The HIV-infected were divided into two groups: 47 patients with CD4+ count >200/mm(3) and 47 with severe immunodeficiency (CD4+ count <200/mm(3)); 42 of the total patients were treated with HAART. Gastric biopsies for histopathology and urease test, esophageal swabs, and gastric aspirates for mycological evaluation were taken. The HIV-infected patients with severe immunodeficiency had a lower prevalence of H. pylori infection and active chronic gastritis in the gastric antrum compared with the other HIV-infected patients and controls (H. pylori in 40%, 72%, and 69%, respectively; p<0.05). Mycotic esophagitis and mycotic colonization of the stomach were more frequent in patients with severe immunodeficiency. The prevalence of gastric mucosa changes was not different between the patients treated and not treated with HAART; H. pylori infection was less frequent in HIV-infected patients treated with HAART (p<0.05). In severely immunodeficient patients with dyspeptic symptoms, the prevalence of H. pylori and active chronic gastritis in the gastric antrum is much lower than in HIV-negative patients. H. pylori infection is less frequent in patients treated with HAART.


Higher Blood Pressure during Endovascular Thrombectomy in Anterior Circulation Stroke Is Associated with Better Outcomes.
Reports investigating the relationship between in-procedure blood pressure (BP) and outcomes in patients undergoing endovascular thrombectomy (EVT) due to anterior circulation stroke are sparse and contradictory. Consecutive EVT-treated adults (modern stent retrievers, BP managed in line with the recommendations, general anesthesia, invasive BP measurements) were evaluated for associations of the rate of in-procedure systolic BP (SBP) and mean arterial pressure (MAP) excursions to >120%/<80% of the reference values (serial measurements at anesthesia induction) and of the reference BP/weighted in-procedure mean BP with post-procedure imaging outcomes (ischemic lesion volume [ILV], hemorrhages) and 3-month functional outcome (modified Rankin Scale [mRS], score 0 to 2 vs. 3 to 6). Overall 164 patients (70.7% pharmacological reperfusion, 80.5% with good collaterals, 73.8% with successful reperfusion) were evaluated for ILV (range, 0 to 581 cm3) and hemorrhages (incidence 17.7%). Higher rate of in-procedure SBP/MAP excursions to >120% was independently associated with lower ILV, while higher in-procedure mean SBP/MAP was associated with lower odds of hemorrhages. mRS 0-2 was achieved in 75/155 (48.4%) evaluated patients (nine had missing mRS data). Higher rate of SBP/MAP excursions to >120% and higher reference SBP/MAP were independently associated with higher odds of mRS 0-2, while higher ILV was associated with lower odds of mRS 0-2. Rate of SBP/MAP excursions to <80% was not associated with any outcome. s In the EVT-treated patients with BP managed within the recommended limits, a better functional outcome might be achieved by targeting in-procedure BP that exceeds the preprocedure values by more than 20%.


Preparation, formation mechanism and photocatalysis of ultrathin mesoporous single-crystal-like CeO2 nanosheets.
For the first time we synthesized mesoporous CeO2 nanosheets with single-crystal-like, ultrathin and uniform-sized structures through the thermal decomposition of specially prepared intermediates of Ce(OH)CO3 nanosheets. The resulting single-crystal-like CeO2 porous nanosheets are only 2.4 nm thick, as measured by AFM. BET analysis indicated that the pores of the nanosheets were centered at 3.7 nm. A novel structure transformation mechanism from 1D to 0D, then to a 2D assembly was clearly revealed. Moreover, such ultrathin CeO2 porous nanosheets exhibited much higher photocatalytic activity for dye degradation than that of polycrystalline CeO2 nanoparticles.


Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway.
The microRNA-214 (miR-214) precursor is formed by the DNM3 gene on human chromosome 1q24.3, which is encoded and transcribed in the nucleus and processed into mature miR-214 in the cytoplasm. Association of miR-214 with the interstitial fibrosis of the kidney has been reported in existing research. Renal interstitial fibrosis is considered necessary during the process of various renal injuries in chronic kidney disease (CKD). One of the important mechanisms is the TGF- (transforming growth factor-) β1-stimulated epithelial interstitial transformation (EMT). The specific mechanisms of miR-214-3p in renal interstitial fibrosis and whether it participates in EMT are worthy of further investigation. In this paper, we first demonstrated modulation of the downstream PI3K/AKT axis by miR-214-3p through targeting phosphatase and tension protein homologues (PTEN), indicating the miRNA's participation in unilateral ureteral obstruction (UUO) nephropathy and TGF-β1-induced EMT. We overexpressed or silenced miR-214-3p and PTEN for probing into the correlation of miR-214-3p with PTEN and the downstream PI3K/AKT signalling pathways. According to the results of the study, miR-214-3p overexpression silenced PTEN, activated the PI3K/AKT signalling pathway, and exacerbated EMT induced by TGF-β1, while miR-214-3p knockdown had the opposite effect. In miR-214-3p knockdown mice, the expression of PTEN was increased, the PI3K/AKT signalling pathway was inhibited, and fibrosis was alleviated. In conclusion, miR-214-3p regulates the EMT of renal tubular cells induced by TGF-β1 by targeting PTEN and regulating the PI3K/AKT signalling pathway. Furthermore, miR-214-3p knockdown can reduce renal interstitial fibrosis through the PTEN/PI3K/AKT pathway.


Student leadership in medical school and its implications for health care and policy-making.
Approximately 5% of hospital chief executive officers are physicians, and that number is growing. Leadership is a vital skill for future physicians. We conducted a narrative review of the literature on student leadership in medical school and its implications for health care and policy-making. Qualities a good leader should possess include accountability, empathy, positivity, teamwork, and organization. Leadership skills need to be taught to students in their formative pre-clinical years so they can build upon this foundation during their clinical and residency years. Leadership is a multifaceted quality because unlike other lessons, it cannot be measured on a scale or under the microscope; it is largely developed through practice. Furthermore, among physicians, psychiatrists are especially well-trained to serve in active leadership roles because psychiatry training emphasizes interpersonal dynamics and emotional intelligence, qualities that are vital to the skill set of an effective leader. Medical leadership is essential because physicians relate best to other physicians, and those adept in administrative skills can help bridge the gap between administration and clinicians. There is a need for teaching an evidence-based leadership curriculum and training techniques that will fill a recognized educational void in medical student education (as well as for residents and junior faculty).


A gap-free reference genome reveals structural variations associated with flowering time in rapeseed (Brassica napus).
Allopolyploid oilseed rape (Brassica napus) is an important oil crop and vegetable. However, the latest version of its reference genome, with collapsed duplications, gaps, and other issues, prevents comprehensive genomic analysis. Herein, we report a gap-free assembly of the rapeseed cv. Xiang5A genome using a combination of ONT (Oxford Nanopore Technologies) ultra-long reads, PacBio high-fidelity reads, and Hi-C datasets. It includes gap-free assemblies of all 19 chromosomes and telomere-to-telomere assemblies of eight chromosomes. Compared with previously published genomes of B. napus, our gap-free genome, with a contig N50 length of 50.70 Mb, has complete assemblies of 9 of 19 chromosomes without manual intervention, and greatly improves contiguity and completeness, thereby representing the highest quality genome assembly to date. Our results revealed that B. napus Xiang5A underwent nearly complete triplication and allotetraploidy relative to Arabidopsis thaliana. Using the gap-free assembly, we found that 917 flowering-related genes were affected by structural variation, including BnaA03.VERNALIZATION INSENSITIVE 3 and BnaC04.HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1. These genes may play crucial roles in regulating flowering time and facilitating the adaptation of Xiang5A in the Yangtze River Basin of China. This reference genome provides a valuable genetic resource for rapeseed functional genomic studies and breeding.


Impact of cyanidin 3-O-glucoside on rat micro-and systemic circulation, possibly thorough angiogenesis.
Cyanidin 3-O-glucoside (C3G), an antioxidant, is one of the most abundant anthocyanin in plant foods. Intervention trials and subsequent meta-analyses have suggested that anthocyanins could reduce the risks of cardiovascular diseases. This study investigated hemodynamic alterations following a single intragastric dose of C3G by measuring blood flow in rat cremaster muscle arteriole for 60 min. Next, in excised aortas, we performed western blotting to measure the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). A single oral dose of C3G significantly increased blood flow soon after ingestion, and it was maintained throughout the experimental period. In addition, aortic Akt phosphorylation increased. Then, we examined the impact of repeated oral administrations of C3G for 14 days. The mean blood pressure was significantly reduced at 7 and 14 days after treatment, with a slight increase in aortic eNOS expression. Immunohistochemical analyses of the soleus showed that the level of CD31, an angiogenesis-marker protein, was significantly increased with C3G. These results suggested that an oral dose of C3G increased blood flow, which promoted angiogenesis within skeletal muscle, and consequently, blood pressure was reduced.


THE CHALLENGES OF METABOLIC SYNDROME IN EATING DISORDERS.
A number of studies have examined the association of the three major eating disorders - anorexia nervosa, bulimia nervosa, and binge-eating disorder - with metabolic syndrome, or with individual components of metabolic syndrome, such as obesity, type 2 diabetes, hypertension, and dyslipidemia. Present evidence suggests that anorexia nervosa confers no excess risk of metabolic syndrome and may be associated with lower risk of certain metabolic syndrome components, including obesity and type 2 diabetes. Bulimia nervosa shows associations with increased risk for metabolic syndrome components in some studies, but not in others. Binge-eating disorder, however, is strongly associated with increased risk for both metabolic syndrome and its components - and these associations appear to be mediated not only through elevated body weight, but also possible body-weight-independent factors. Given that binge-eating disorder is the most common eating disorder, treatment and prevention of metabolic syndrome in this group represents a significant clinical and public health challenge.


Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes.
We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance. Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft. Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection. The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.


Active immunity against rotavirus infection in mice is correlated with viral replication and titers of serum rotavirus IgA following vaccination.
Using an adult mouse model to study active immunity against rotavirus infection, it was previously shown that oral immunization with some, but not all, animal rotavirus strains induced protection against subsequent infection following oral challenge with the murine rotavirus strain EDIM. To determine if a specific rotavirus protein could be associated with protection in this model, mice were immunized with a series of 18 reassortants between the fully protective EDIM strain and a partially protective heterologous rotavirus strain (RRV-G). Reassortants that contained genes for EDIM proteins responsible for protection were anticipated to provide complete protection; however, no EDIM proteins were found to be both necessary and sufficient for full protection. Instead, protection was found to be highly correlated with viral shedding (P = 0.005) and with serum rotavirus IgA titers stimulated by the different reassortants (P < 0.001). This indicated that protection was related to the intestinal replication properties of the different reassortants rather than to specific immunogenic properties of EDIM proteins. This conclusion was supported by the finding that the titers of serum rotavirus IgA, but not IgG, stimulated in mice following oral immunization with a series of animal rotaviruses was directly related to protection against EDIM. If these findings can be extended to humans, they suggest that the efficiency of intestinal replication following oral inoculation with a live rotavirus vaccine candidate may be the primary determinant of successful immunization.


Intravitreal Bevacizumab: Indications And Complications.
Bevacizmab is still an unlicensed drug for intraocular use in spite of the fact that it has shown comparable efficacy to other anti-vascular endothelial growth factors (anti-VEGF) medications in some large sample randomized control trails. Although repackaged bevacizumab has got safety concerns but its use is growing because of easy availability and low cost. Our study focuses on the diverse and growing indications of intravitreal bevacizumab (IVB) and its ocular complications in our geographical setting. This interventional case series was carried out at my private practice in Said Anwar Medical Complex, Dabgari, Peshawar, from January 2008 to July 2015. Total of 6107 injections were given to 4352 eyes. Intravitreal bevacizumab was injected in proper operating room setting. Bevacizumab injections were prepared from same vial by multiple withdrawals taking care of aseptic precautions. Follow up was done at 1 week and 20 days and adverse effects were noted. Diabetic macular oedema (36%), central retinal vein occlusion (17.6%) and branched retinal vein occlusion (11%) were the top three indications of IVB. Other common indications were proliferative diabetic retinopathy (9.6%), neo-vascular glaucoma (5.9%), proliferative diabetic retinopathy with vitreous bleed (4.4%), proliferative diabetic retinopathy with tractional retinal detachment (3.7%), neo-vascular age related macular degeneration (2.9%), central serous retinopathy (1.48%) and Eale's disease (1.48%). Endohthalmitis occurred in 3 eyes (0.069%) while retinal detachment was found in only 2 eyes (0.046%). Common indications of bevacizumab are diabetic macular oedema, central retinal vein occlusion and branched retinal vein occlusion. Complications like endophthalmitis and retinal detachment are rare.


Ocular disease awareness and pattern of ocular manifestation in patients with biopsy-proven lung sarcoidosis.
The aim of this research is to study the patterns of ocular involvement in patients with biopsy-proven lung sarcoidosis and estimate the level of patients' awareness of possible ocular complications of sarcoidosis. Fifty patients with biopsy-proven lung sarcoidosis were referred from the Department of Respiratory Medicine, University Hospital of Larissa, Greece. The most prominent ocular symptom was foreign body sensation in 15/50 patients (30%); only 6/50 of our patients (12%) were completely asymptomatic with respect to ocular symptoms. Anterior segment findings were: episcleritis in 8/50 patients (16%), iris nodules in 9/50 patients (18%), and cataract in 19/50 patients (38%). Periphlebitis was observed in 8/50 patients (16%), periarteritis in 8/50 patients (16%), epiretinal membrane in 6/50 patients (12%), and branch retinal vein occlusion in 7/50 of our patients (14%). Ten out of 50 patients (20%) had never visited an ophthalmologist before, whereas eight out of 50 patients (16%) had undergone an ophthalmic exam more than 2 years ago. Eye involvement is common in patient with biopsy-proven lung sarcoidosis and may occur even without prominent ocular symptoms.


Schwannoma arising from the tentorium at an unusual location: case report.
We present a case of schwannoma attached to the tentorium. A 41-year-old woman without evidence of neurofibromatosis presented with a 3-month history of headache, positional vertigo, and truncal ataxia. Magnetic resonance imaging revealed an extra-axial cystic mass lesion in the left anteromedial cerebellar region with a dural tail sign. The tumor was removed completely by retrosigmoid craniotomy. Dense adhesion of the tumor to the inferior surface of the tentorium was confirmed during surgery. On light microscopic study, this neoplasm was composed of spindle cells and showed palisaded structures. Immunohistochemically, the tumor cells stained positive for S-100 protein and vimentin. Reticulin staining revealed a pericellular pattern of distribution of reticulin fibers. Electron microscopy confirmed the presence of a basement membrane encompassing the tumor cells. From these findings, the tumor was diagnosed as a schwannoma arising from the tentorium. To our knowledge, this case report is the first to describe a schwannoma arising from the tentorium. Our case report indicates that schwannoma is a possible pathology in the differential diagnosis of dura-based tumors.


LATENT RANK CHANGE DETECTION FOR ANALYSIS OF SPLICE-JUNCTION MICROARRAYS WITH NONLINEAR EFFECTS.
Alternative splicing of gene transcripts greatly expands the functional capacity of the genome, and certain splice isoforms may indicate specific disease states such as cancer. Splice junction microarrays interrogate thousands of splice junctions, but data analysis is difficult and error prone because of the increased complexity compared to differential gene expression analysis. We present Rank Change Detection (RCD) as a method to identify differential splicing events based upon a straightforward probabilistic model comparing the over- or underrepresentation of two or more competing isoforms. RCD has advantages over commonly used methods because it is robust to false positive errors due to nonlinear trends in microarray measurements. Further, RCD does not depend on prior knowledge of splice isoforms, yet it takes advantage of the inherent structure of mutually exclusive junctions, and it is conceptually generalizable to other types of splicing arrays or RNA-Seq. RCD specifically identifies the biologically important cases when a splice junction becomes more or less prevalent compared to other mutually exclusive junctions. The example data is from different cell lines of glioblastoma tumors assayed with Agilent microarrays.


Mechanisms of metal--salt methods in enzyme cytochemistry with special reference to acid phosphatase.
This review is concerned with theoretical and experimental aspects of the factors governing the localizing potentialities of cytochemical enzyme reactions that are based on the metal-salt principle, that is, the precipitation of the primary product of the enzymatic reaction by a heavy-metal ion at the enzymatic site. Special attention is given to the lead phosphate precipitation process in acid phosphatase cytochemistry. The various model systems developed for the study of the factors involved in precipitation are described and their advantages and disadvantages discussed. Furthermore, the various cytochemical methods so far used for the demonstration of acid phosphatase activity are critically evaluated in the light of the results obtained with the model systems.


CONUT Score or/and Peripheral Blood CD4+/CD8+ Ratio-Based Web Dynamic Nomograms to Predict the Individualized Survival of Patients with Advanced Osteosarcoma.
Nutritional and immune status is paramount for the overall survival (OS) of patients with advanced osteosarcoma. Comprehensive prognostic predictors based on the two indices are scarce. This study aimed to construct and validate individualized web dynamic nomograms based on CONUT score or/and peripheral blood CD4+/CD8+ ratio for OS in patients with advanced osteosarcoma. The clinical data of 376 advanced osteosarcoma patients from January 2000 to December 2019 were retrospectively collected. Data from the 301 patients (diagnosed in the first 15 years) were used as the development set and data from the remaining 75 patients were assigned as the validation set. Multivariate Cox regression analyses were conducted and three prediction models were constructed, namely, CD4+/CD8+ ratio univariate model (model 1), CONUT score univariate model (model 2), and CD4+/CD8+ ratio plus CONUT score (model 3). These models were visualized by conventional nomograms and individualized web dynamic nomograms, and their performances were further evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA), respectively. In multivariate Cox analysis, age, metastasis, ALP, CD4+/CD8+ ratio, chemotherapy, and CONUT score were identified as independent prognostic factors for OS. The calibration curves of the three models all showed good agreement between the actual observation and nomogram prediction for 1-year overall survival. In the development set, the C-index and area under the curve (AUC) of model 3 (0.837, 0.848) were higher than that of model 1 (0.765, 0.773) and model 2 (0.712, 0.749). Similar trends were observed in the validation set. The net benefits of model 3 were better than the other two models within the threshold probability of 36-80% in DCA. CONUT score and peripheral CD4+/CD8+ ratio are easily available, reliable, and economical prognostic predictors for survival prediction and stratification in patients with advanced osteosarcoma, but the two predictors combined can establish a better prognosis prediction model.


Studies on components of the plasma kallikrein-kinin system in plasma samples from normal individuals and patients with septic shock.
Components of the plasma kallikrein-kinin system were determined in plasma samples from ten healthy subjects and eight patients with septic shock. Five of the patients died. Low levels of Hageman factor, prekallikrein, and high molecular weight kininogen, together with significantly reduced concentrations of alpha 2-macroglobulin, were observed during septic shock both in patients who died and in the survivors. The patients who died also revealed a pronounced reduction of functional kallikrein inhibition determined by a chromogenic peptide substrate assay. In the survivors, however, functional kallikrein inhibition was very well preserved during septic shock, being within the range of values found in normals. Also plasma prekallikrein and C1-esterase inhibitor levels were slightly higher in the survivors than in those who died. Our results confirm that the plasma kallikrein-kinin system becomes activated during septicemia and that consumption of components of this protease system occurs. Because both C1-esterase inhibitor concentrations and functional kallikrein inhibitory activities were higher in patients who survived septic shock than in the fatal cases, our results suggest that functional inhibition of plasma kallikrein appears to play a major role in the outcome of this condition.


Fatal reaction to transfusion of red-cell concentrate contaminated with Serratia liquefaciens.
A 60-year-old woman undergoing surgery died from endotoxic shock and DIC after receiving a 19-day-old unit of optimal additive red-cell concentrate found contaminated with Serratia liquefaciens. No source of contamination could be found. This normally free-living organism is usually of low pathogenicity. It is a very unusual contaminant of stored donated blood, although it appears to be on the increase. When transfused, blood contaminated with S. liquefaciens always causes severe morbidity and is associated with a high death rate. This is the fifth report in the English literature.


Advanced Heart Failure Therapies and Cardiorenal Syndrome.
Heart failure (HF) is extremely prevalent and for those with end-stage (stage D) disease, 1-year survival is only 25-50%. Several studies have captured the mortality impact of kidney disease on patients with HF, and measures of kidney function are a component of many HF risk stratification scores. The management of advanced HF complicated by cardiorenal syndrome (CRS) is challenging, and irreversible kidney failure often limits patient candidacy for advanced HF therapies, such as transplant or left ventricular assist device therapy. Thus, prompt institution of aggressive therapy is warranted in stage D HF patients with CRS to prevent irreversible kidney failure. In this chapter, we discuss the assessment and management of patients with CRS with end-stage HF. In addition to discussing medical therapy aimed at decongestion and increased cardiac inotropy, we provide a summary of temporary circulatory support devices that can be considered for those whom hospice is not desired. In all circumstances, a close collaboration between the advanced HF specialist and nephrologist is needed to achieve the best patient outcomes.


Consensus meeting on "Relevance of parenteral vitamin C in acute endothelial dependent pathophysiological conditions (EDPC)".
The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in the treatment of endothelial dysfunction. Scientists, who had published and reviewed scientific and regulatory papers on that topic were invited, among them basic researchers, toxicologists, clinicians and nutritionists. The participants were presented with eleven questions, which were discussed and answered at the workshop, with the aim of summarising the current state of knowledge. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. The therapeutic relevance of administration of the physiological antioxidant vitamin C in high parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC) was discussed. Endothelial dysfunction is defined as including disturbed endothelial dependant relaxation of resistance vessels, breakdown of the microvascular endothelial barrier and/or loss of anti-adhesive function. It occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma, and ischemic-reperfusion tissue injury and is induced by oxidative stress. Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and organ transplantation. Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids. There is experimental evidence that parenteral high-dose vitamin C restores endothelial function in sepsis. In vitro, supraphysiological concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and endothelial function. Only parenterally, can enough vitamin C be administered to combat oxidative stress. There is no evidence that parenteral vitamin C exerts prooxidant effects in humans. Theoretical concerns in relation to competitive interactions between vitamin C and glucose cellular uptake are probably only relevant for oxidised vitamin C (dehydroascorbate).


[Understanding allergy].
There is a correlation between the clinical expression of various allergic disorders and an abnormal production of IgEs. A series of factors were recently described which are probably involved in this hyperproduction of IgEs: the IgE binding factors SFA and EFa, the glycosylation enhancing or inhibiting factors GEF and GIF and interleukin 4. It seems that there is also a correlation between the incidence of viral infections of the respiratory tract and an abnormal production of IgEs. Finally there are hereditary predispositions for the development of allergic diseases. It is interesting to try to group in an hypothetical scheme all the different factors which seem to act in conjunction to produce a shift to an IgE overproduction by atopic B lymphocytes.


[Huge right atrial myxoma].
Myxomas are account for approximately half of primary cardiac tumors, and 75% cases originate in left atrium. We report our experience of a right atrial myxoma. A 68-year-old woman was referred to us due to anorexia, general fatigue and facial edema. Echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiocardiogram revealed a huge tumor in right atrium. The tumor was resected completely with the attached right atrial free wall under cardiopulmonary bypass. Pathological examination showed myxomatous tissue. Postoperative course was uneventful. She discharged the hospital on the 37th day after the operation, and is now doing well without any symptoms.


Fish consumption and risk of non-gallstone-related acute pancreatitis: a prospective cohort study.
Epidemiologic data on the role of diet in acute pancreatitis are sparse. We examined the association of total fish consumption, as well as of consumption of fatty fish and lean fish separately, with risk of non-gallstone-related acute pancreatitis. We used data from 2 prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, that included 39,267 men and 32,191 women who were aged 45-84 y at the start of a 13-y follow-up period (1998-2010). Fish consumption was assessed by using a food-frequency questionnaire at baseline, and cases of incident non-gallstone-related acute pancreatitis were identified by linkage to the Swedish National Patient Register. HRs were estimated by using Cox proportional hazard models. During a total follow-up of 860,176 person-years, 320 cases (209 cases in men and 111 cases in women) of incident non-gallstone-related acute pancreatitis were identified. We observed that total fish consumption ≤2.0-3.0 servings/wk was associated with a significantly decreased risk of the disease (P-nonlinearity = 0.017). In comparison with 0.9 servings/wk, multivariable-adjusted HRs were 0.86 (95% CI: 0.76, 0.96), 0.77 (95% CI: 0.62, 0.96), and 0.85 (95% CI: 0.65, 1.10) for 1.4, 2.4, and 3.5 servings/wk, respectively. In the analysis of fatty fish and lean fish, we observed that the consumption of each subtype had a similarly shaped association with risk of non-gallstone-related acute pancreatitis as that observed for total fish consumption, although neither was significant. Multivariable-adjusted HRs were 0.83 for fatty fish (95% CI: 0.65, 1.04) and 0.87 for lean fish (95% CI: 0.69, 1.11) when 0.6-2.0 servings/wk was compared with ≤0.5 servings/wk. Our data suggest that the consumption of total fish (fatty fish and lean fish combined) may be associated with decreased risk of non-gallstone-related acute pancreatitis.


Reversed-flow affinity elution applied to the purification of carboxypeptidase Y.
In the present study we describe a novel method for obtaining highly pure carboxypeptidase Y, or derivatives thereof, in a single-step purification procedure. The method is based on affinity chromatography and the results demonstrate that an efficient method is obtained only when the affinity gel is fully saturated with enzyme. Thus, pilot experiments are required to determine the binding capacity of the resin with respect to a given enzyme. To avoid this additional experimental effort, we have developed a method utilizing reversed-flow affinity elution. The method has been successfully employed to purify hundreds of carboxypeptidase Y mutant enzymes.


Conformational preferences of the flexible galactofuranose sugar in gas-phase.
In contrast with the predominant pyranose form of galactose, galactofuranose is known to be highly flexible. Such flexibility poses a remarkable challenge in terms of structural studies, thus hindering the in depth understanding of the structure/function relationship in this rare sugar. A thorough computational study based on molecular dynamics and density functional theory supported by vibrational spectroscopy in the gas phase was carried out to provide a better understanding of the instrinsic conformational preferences of galactofuranose. Based on energetic and spectroscopic criteria, we report a subtantially reduced conformational landscape: methyl α-D-galactofuranose adopts E2/1E conformations and methyl β-D-galactofuranose adopts 1T2/1E conformations.


The ability of different thermal aids to reduce hypothermia in neonatal piglets.
We investigated whether hypothermia in newborn piglets could be reduced by applying different thermal aids. The experiment was performed on 150 newborn piglets from 24 sows. Right after birth, the piglets were moved to a wire mesh cage for the first 2 h of life where they experienced 1 of 7 different combinations of flooring (solid vs. slatted) and treatments: control, with no additional thermal aids on a solid floor ( = 26) or a slatted floor ( = 26); built-in floor heating ( = 31) or floor heating as a radiant floor plate on solid floor (FloorPlate; = 19); radiant heater above a solid floor (RadiantC; = 22) or a slatted floor (RadiantSlat; = 18); and provision of straw on a solid floor (Straw; = 8). Piglets' rectal temperature was measured both continuously and manually every 10 min for the first 2 h after birth using a thermal sensor inserted in the rectum of the piglets. The rectal temperature curve was analyzed for differences in the slope of the drop in rectal temperature and the deflection tangent of the curve. Furthermore, differences in average rectal temperature, minimum rectal temperature, rectal temperature 2 h after birth, and time with rectal temperature below 35°C were analyzed. All statistical analyses were performed using a mixed model. All thermal aids/heat solutions resulted in a less steep drop in rectal temperature, a faster recovery, and, for the smaller piglets, also a greater average rectal temperature (except for built-in floor heating) and less time with rectal temperature below 35°C. The most efficient thermal aids to reduce hypothermia in newborn piglets were Straw and RadiantC. Furthermore, Straw, RadiantC, and FloorPlate also eliminated the effect of birth weight on some of these indicators of thermoregulatory success. Otherwise, FloorPlate and RadiantSlat showed an intermediate outcome for most measures. With no heating, piglets on a solid floor experienced more severe hypothermia than piglets on a slatted floor. In conclusion, several types of thermal aids can reduce hypothermia in newborn piglets, but some are more efficient and can partly eliminate the effect of birth weight on hypothermia. These results are especially important in countries where breeding for large litter sizes has resulted in a reduction in average birth weight of the piglets and, thus, creates a greater demand for an early, adequate thermal environment to secure piglet viability.


ATR-FTIR observations of water structure in colloidal silica: implications for the hydration force mechanism.
Attenuated total internal reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was used to probe the change in water structure in silica colloids as a function of particle density. The absorption index (k) spectra were calculated from the ATR spectra using the subtractive Kramers-Kronig transform in order to avoid the effects of the density-dependent refractive index on the raw spectra and allow direct comparison of the different chemical environments. Normalized difference spectra were obtained by subtracting the k spectrum of bulk water from those of the silica colloids. At low particle densities, these difference spectra reveal the presence of a strongly hydrogen-bonded hydration layer at the surface of the colloidal particles. At higher particle densities, the hydrogen-bonding network is increasingly disrupted. The results provide direct experimental evidence of hydrogen-bond breaking as the mechanism for the hydration force, which provides the extraordinary stability of colloidal silica.


Percutaneous endoscopic lumbar discectomy (PELD).
Percutaneous endoscopic lumbar discectomy (PELD) is a new technique for the decompression of the lumbar disc space and removal of nucleus pulposus via a posterolateral approach. The technique was introduced in Germany by the authors in April 1987. The method is indicated in patients with nonsequestrated lumbar disc herniation with an intact dorsal longitudinal ligament. In local anesthesia, a working cannula (OD 5 mm) is placed at the dorsal lateral border of the disc. The disc space is opened with anulus trephines and the nucleus pulposus is removed with rigid and flexible forceps as well as with automated shaver systems under intermittent endoscopic control (discoscopy). The procedure is performed in local anesthesia. The results of the first thirty patients with a follow-up time between 6 months and 17 months could be graded as excellent in 13 cases, as good in 9 cases, as fair in 6 cases, and as bad in 2 cases. The relief of symptoms as judged by the patients was between 70-100 percent in the majority of the cases. Three patients had to be reoperated at the same level and site, because of either persistent or recurrent sciatica. The performance in local anesthesia, the atraumatic extraspinal approach, the reduced time of hospitalization and postoperative morbidity as well as the reduced time of work incapability are the main advantages of this new method.


Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest.
Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome. Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death). Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log2(FC) between 0.33 and 0.88), one reduced protein (log2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest. Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.


Are proteinases the reason for keratoconus?
Keratoconus is a degenerating disease of the eye that results in an irregularly-shaped cornea. The etiology of the disease is unknown and the prognosis is difficult due to the variability in outcome. Keratoconus has been associated with eye rubbing, atopy, contact lens wear, as well as genetic conditions, such as Down's syndrome, Ehlers-Danlos syndrome, and Marfan's syndrome. Thinning of the cornea in keratoconus has been well studied and is documented to occur as a result of degradation of corneal collagen. The reason for this tissue degradation is unknown but has been hypothesized to be linked with proteases. This study used a literature search to review the role of proteases and inflammatory molecules in the aetiology of keratoconus. Early studies demonstrated elevated levels of collagenolytic and gelatinolytic activities in laboratory cultures of keratoconic corneas. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteins that include collagenases and gelatinases. MMPs levels are altered in keratoconus corneas compared to normal corneas and the level of tissue inhibitor of metalloproteinases-1 (TIMP-1) is decreased in keratoconic corneas. Recent studies have demonstrated the involvement of Cathepsin B, G, and K in keratoconus. Although thought to be a non-inflammatory disease, inflammatory molecules, such as interleukins and tumor necrosis factor have been shown to be elevated in keratoconus, and these inflammatory molecules may mediate production and activation of proteases. Proteases may be implicated in keratoconus. An in-depth investigation of these proteases may help in better understanding the course of the disease.


Sesquiterpene Lactones from Vernonia cinerascens Sch. Bip. and Their in Vitro Antitrypanosomal Activity.
In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) and isolation of vernodalin (2), 11β,13-dihydrovernodalin (3), 11β,13-dihydrovernolide (4), vernolide (5), 11β,13-dihydrohydroxyvernolide (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone vernocinerascolide (8) from the dichloromethane extract of V. cinerascens leaves. Compounds 3-8 were characterized by extensive analysis of their 1D and 2D NMR spectroscopic and HR/MS spectrometric data. All the compounds were evaluated for their in vitro biological activity against bloodstream forms of Trypanosoma brucei rhodesiense and for cytotoxicity against the mammalian cell line L6. Vernodalin (2) was the most active compound with an IC50 value of 0.16 µM and a selectivity index of 35. Its closely related congener 11β,13-dihydrovernodalin (3) registered an IC50 value of 1.1 µM and a selectivity index of 4.2.


[The detection of specific antigens in experimental anthrax].
The dynamics of various specific antigens was studied in guinea pigs infected with strain 72/12 of Tsenkovskiĭ's second vaccine. The study showed that at the acute stage of the disease toxin antigens prevailed over the levels of somatic antigens and nonprotective protein with a molecular weight of 79 KD. The enzyme immunoassay system for the detection of the lethal toxin factor permitted the detection of the antigen in the blood sera of 100% of infected animals at the prodromal period and the acute stage of the disease. In pathological material obtained from skin lesions the presence of toxin antigens and nonprotective protein was registered in 90-100% of the animals. The diagnostic significance of these assays for the early rapid diagnosis of anthrax during lifetime, as well as for the postmortem rapid diagnosis of the disease.


Radiculopathy of C-5 after anterior decompression for cervical myelopathy.
The authors conducted a study to examine the incidence and causes of postoperative C-5 radiculopathy, and they suggest preventive methods for C-5 palsy after anterior corpectomy and fusion. The authors included in the study 18 patients with postoperative C-5 radiculopathy from 563 patients who underwent anterior decompression and fusion for cervical myelopathy. There were 10 cases of ossification of the posterior longitudinal ligament (OPLL) and eight cases of cervical spondylotic myelopathy (CSM). All patients received conservative treatment. Posttreatment full recovery was present in eight patients, and Grade 3/5 strength was documented in six in whom some weakness remained. Radiographic evaluation revealed that the C3-4 and C4-5 cord compression was significantly more severe in patients with paralysis than in those without paralysis. The incidence of paralysis was higher in patients with OPLL than in those with CSM (chi-square test, p = 0.03). The incidence of paralysis increased in parallel with the number of fusion levels (correlation coefficient r = 0.94). Multivariate analysis revealed that the final manual muscle testing (MMT) value was closely related to the preoperative MMT value (computed t value 4.17; p < 0.01) and preoperative Japanese Orthopaedic Association (JOA) score for cervical myelopathty (computed t value, 2.75; p < 0.05). Preexisting severe stenosis at C3-4 or C4-5 in patients with OPLL is a risk factor for paralysis. Preoperative muscle weakness and a low JOA score are factors predictive of poor recovery.


Assessing rheoencephalography dynamics through analysis of the interactions among brain and cardiac networks during general anesthesia.
Cerebral blood flow (CBF) reflects the rate of delivery of arterial blood to the brain. Since no nutrients, oxygen or water can be stored in the cranial cavity due to space and pressure restrictions, a continuous perfusion of the brain is critical for survival. Anesthetic procedures are known to affect cerebral hemodynamics, but CBF is only monitored in critical patients due, among others, to the lack of a continuous and affordable bedside monitor for this purpose. A potential solution through bioelectrical impedance technology, also known as rheoencephalography (REG), is proposed, that could fill the existing gap for a low-cost and effective CBF monitoring tool. The underlying hypothesis is that REG signals carry information on CBF that might be recovered by means of the application of advanced signal processing techniques, allowing to track CBF alterations during anesthetic procedures. The analysis of REG signals was based on geometric features extracted from the time domain in the first place, since this is the standard processing strategy for this type of physiological data. Geometric features were tested to distinguish between different anesthetic depths, and they proved to be capable of tracking cerebral hemodynamic changes during anesthesia. Furthermore, an approach based on Poincaré plot features was proposed, where the reconstructed attractors form REG signals showed significant differences between different anesthetic states. This was a key finding, providing an alternative to standard processing of REG signals and supporting the hypothesis that REG signals do carry CBF information. Furthermore, the analysis of cerebral hemodynamics during anesthetic procedures was performed by means of studying causal relationships between global hemodynamics, cerebral hemodynamics and electroencephalogram (EEG) based-parameters. Interactions were detected during anesthetic drug infusion and patient positioning (Trendelenburg positioning and passive leg raise), providing evidence of the causal coupling between hemodynamics and brain activity. The provided alternative of REG signal processing confirmed the hypothesis that REG signals carry information on CBF. The simplicity of the technology, together with its low cost and easily interpretable outcomes, should provide a new opportunity for REG to reach standard clinical practice. Moreover, causal relationships among the hemodynamic physiological signals and brain activity were assessed, suggesting that the inclusion of REG information in depth of anesthesia monitors could be of valuable use to prevent unwanted CBF alterations during anesthetic procedures.


Prevalence of suspected hypertrophic cardiomyopathy or left ventricular hypertrophy based on race and gender in teenagers using screening echocardiography.
The goal of this study was to evaluate the prevalence of suspected hypertrophic cardiomyopathy (HCM) in a population of teenagers undergoing screening echocardiography for the detection of HCM. The Anthony Bates Foundation performs screening echocardiography for the prevention of sudden death. A total of 2,066 students were studied between the ages of 13 to 19 years. Suspected HCM was defined as any wall thickness ≥ 15 mm. LVH was defined as wall thickness ≥ 13 mm Prevalence of suspected HCM was 0.7% (14/2066). After adjusting for hypertension (HTN), the total prevalence was 0.5% (8/1457). In a subgroup analysis, 551 teenagers with documented race and LV wall thickness were identified between the ages of 13-19 years. African American teenagers [6% (3/50)] had higher prevalence of suspected HCM [0.8% (4/501), OR 7.93, CI 1.72-36.49, p = 0.002]. After multivariate adjustment for age, gender, BMI and HTN (systolic BP >140 and diastolic BP of > 90), African American race remained independently associated with suspected HCM (OR 4.89, CI 1.24-39.62, p = 0.02). The prevalence of suspected HCM in young teenagers is approximately 0.2%. This prevalence appears to be higher in African Americans. However, due to small number of African Americans in our population, our result needs to be confirmed in larger trials.


Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Although the mechanisms linking obesity to insulin resistance (IR) and type 2 diabetes (T2D) are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR) or sensitive (OIS) adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT) in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in adipocytes in women independently of obesity. KFL15 and SLC25A10 are inhibitors of insulin-stimulated lipogenesis under conditions when glucose transport is the rate limiting step.


Growth mechanism of glucose-based hydrochar under the effects of acid and temperature regulation.
Improving the tailorability of hydrochar synthesis is an effective way to enhance its performance and utilization efficiency. In this study, the growth rate, morphology, and molecular structure of hydrochar were controlled by regulating the pH and temperature of the hydrothermal carbonization process. Growth process analysis indicates that hydrochar has three growth periods: induction, rapid, and stable growth periods. It is mainly controlled by 5-hydroxymethylfurfural (HMF), which is formed by converting glucose and its transformation products. The regulation of acid can significantly shorten the induction period of hydrochar, even under low-temperature conditions (<180℃), and increase the growth rate of hydrochar. However, the degree of hydrochar adhesion varies: the lower the temperature, the greater the degree of its adhesion. Molecular structural analysis demonstrates that hydrochar mainly consists of furan structural domains and aromatic clusters, and its surface is rich in oxygen-containing functional groups. The degree at which hydrochar was aromatized was improved by increasing the reaction temperature (160-220℃); whereas the regulation of acid reduced it and increased the content of oxygen-containing functional groups on the hydrochar surface. Based on these results, it is proposed that hydrochar formation has five stages and three growth periods with or without acid regulation.


Catalytic dehydration of carbohydrates suspended in organic solvents promoted by AlCl3 /SiO2 coated with choline chloride.
We show that the coating of choline chloride on silica-supported AlCl3 allows the dehydration of carbohydrates to successfully proceed in low boiling point organic solvents. The concept is based on the in situ formation of a deep eutectic liquid phase on the catalyst surface, thus facilitating the interaction between the solid catalyst and insoluble carbohydrate.


Electron states in semiconductor quantum dots.
In this work, the electronic structures of quantum dots (QDs) of nine direct band gap semiconductor materials belonging to the group II-VI and III-V families are investigated, within the empirical tight-binding framework, in the effective bond orbital model. This methodology is shown to accurately describe these systems, yielding, at the same time, qualitative insights into their electronic properties. Various features of the bulk band structure such as band-gaps, band curvature, and band widths around symmetry points affect the quantum confinement of electrons and holes. These effects are identified and quantified. A comparison with experimental data yields good agreement with the calculations. These theoretical results would help quantify the optical response of QDs of these materials and provide useful input for applications.


Cell-free DNA - Minimally invasive marker of hematological malignancies.
Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow-up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies.


Antiurolithiasis Activity of Bioactivity Guided Fraction of Bergenia ligulata against Ethylene Glycol Induced Renal Calculi in Rat.
Dried rhizome of Bergenia ligulata (pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract of B. ligulata was prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM), n-butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly (p < 0.05) greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant (p < 0.05) decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims.


The systemic arterial pattern of the guinea pig: the abdomen.
The systemic arterial pattern of the guinea pig was studied to determine the arrangement of the major arterial trunks and their branches. Fiftynine specimens were examined by dissection, angiography or corrosion casting. The arterial arrangement was found to resemble a typical mammalian pattern, although some exceptions were noted. For example, the guinea pig usually has a single vessel, the celiacomesenteric trunk, instead of separate celiac and cranial mesenteric arteries. The celiac components of this vascular axis were found to originate in four different patterns. Also, the renal arteries were found to be single or double on either side with double origins more frequent.


[Treatment of severe cow's milk protein allergy using Neocate].
A hydrolysate of proteins is considered to be adapted to treatment of allergy to cow's milk proteins when it is tolerated by 90% of allergic children. This suggestion implies that 10% of the children who are allergic to cow's milk proteins do not tolerate the preparations based on hydrolysates of proteins and presupposes the case of intolerance or allergy henceforth widely reported. The diagnosis must mention before the existence or the persistence in an infant fed with a hydrolysate of proteins of non-specific clinical signs often attached to more frequent pathologies, such as gastro-oesophageal reflux or colic. Substitution of a hydrolysate by another is one alternative, but the level of residual peptides of protein hydrolysates explains only the cases of severe allergy, the child may show reactions to these residual epitopes. The alternative is use of a formulation based on amino-acids, which allows diagnosis by an elimination-provocation test of protein hydrolysate. An elementary formulation based on amino-acids may permit to await the period of acquisition of tolerance.


[Utility of methoxy isobutyl isonitrile (MIBI) scintigraphy, ultrasound and computerized axial tomography in preoperative topographic diagnosis of hiperparathyroidism].
1. To assess the sensitivity of scintigraphy using methoxy isobutyl isonitrile (MIBI). 2. To compare its resolution with that of ultrasound (US) and computerized axial tomography (CAT). 3. To use its diagnostic reliability to determine whether selective approaches can be used to treat hyperparathyroidism (HPT). A study of 76 patients who underwent surgery for HPT between 1996 and 2005 was performed. MIBI scintigraphy and cervical US were used for whole-body scanning in all patients; CAT was used in 47 patients. Intraoperative and postoperative biopsies were used for final evaluation of the tests, after visualization and surgical extirpation. The results of scintigraphy were positive in 65 patients (85.52%). The diagnosis was correct in all of the single images. Multiple images were due to hyperplasia and parathyroid adenomas with thyroid disease (5.2%). Three images, incorrectly classified as negative (3.94%), were positive. The sensitivity of US was 63% and allowed detection of three MIBI-negative adenomas (4%). CAT was less sensitive (55%), but detected a further three MIBI-negative adenomas (4%). 1. The sensitivity of MIBI reached 89.46%. In the absence of thyroid nodules, MIBI diagnosed 100% of single lesions. Pathological thyroid processes produced false-positive results (5.2%) and there were diagnostic errors (4%). 2. MIBI scintigraphy was more sensitive than US and CAT. 3. Positive, single image scintigraphy allows a selective cervical approach. US and CAT may help to save a further 8% of patients (with negative scintigraphy).


[Exploratory and confirmatory factor analyses for testing validity and reliability of the Chinese language questionnaire for urinary incontinence diagnosis].
To translate questionnaire for urinary incontinence diagnosis (QUID) into Chinese and to test its reliability and validity. The English version of QUID was translated into Chinese. The clinaical data of 95 patinents with urinary incontinence who were test by urinary dynamic study in Peking Union Medical College Hospital from May 2014 to May 2015 were analyzed prospectively. The reliability of QUID was evaluated by completing QUID twice. The validity of QUID was evaluated by the standard of urinary dynamic study. Internal consistency (Cronbach α) of the items that pertained to stress urinary incontinence (SUI) and to urge urinary incontinence (UUI) were 0.91 and 0.89, respectively. Test-retest reliability (Kappa) was 0.795 and criterion validity (Kappa) was 0.62. Sensitivity and specificity were 83% (43/52) and 86% (37/43), respectively, for SUI, and 72% (13/18) and 86% (66/77), respectively, for UUI. QUID has good reliability and validity. It could be used in Chinese urinary incontinence women.


Designing for Patient Safety and Efficiency: Simulation-Based Hospital Design Testing.
In the schematic design phase of a new freestanding children's hospital, Simulation-based Hospital Design Testing (SbHDT) was used to evaluate the proposed design of 11 clinical areas. The purpose of this article is to describe the SbHDT process and how it can help identify and mitigate safety concerns during the facility design process. In the design of new healthcare facilities, the ability to mitigate risk in the preconstruction period is imperative. SbHDT in a full-scale cardboard mock-up can be used to proactively test the complex interface between people and the built environment. This study was a prospective investigation of SbHDT in the schematic design planning phase for a 400-bed freestanding children's hospital where frontline staff simulated episodes of care. Latent conditions related to design were identified through structured debriefing. Failure mode and effect analysis was used to categorize and prioritize simulation findings and was used by the architect team to inform design solutions. A second round of testing was conducted in order to validate design changes. A statistically significant reduction in criticality scores between Round 1 (n = 201, median = 16.14, SD = 5.8) and Round 2 (n = 201, median score of 7.68, SD = 5.26, p < .001) was identified. Bivariate analysis also demonstrated a statistically significant reduction in very high/high criticality scores between Round 1 and Round 2. SbHDT in the schematic phase of design planning was effective in mitigating risk related to design prototypes through effective identification of latent conditions and validation of design changes.


Werner syndrome protein contains three structure-specific DNA binding domains.
Werner syndrome (WS) is a premature aging syndrome caused by mutations in the WS gene (WRN) and a deficiency in the function of the Werner protein (WRN). WRN is a multifunctional nuclear protein that catalyzes three DNA-dependent reactions: a 3'-5'-exonuclease, an ATPase, and a 3'-5'-helicase. Deficiency in WRN results in a cellular phenotype of genomic instability. The biochemical characteristics of WRN and the cellular phenotype of WRN mutants suggest that WRN plays an important role in DNA metabolic pathways such as recombination, transcription, replication, and repair. The catalytic activities of WRN have been extensively studied and are fairly well understood. However, much less is known about the domain-specific interactions between WRN and its DNA substrates. This study identifies and characterizes three distinct WRN DNA binding domains using recombinant truncated fragments of WRN and five DNA substrates (long forked duplex, blunt-ended duplex, single-stranded DNA, 5'-overhang duplex, and Holliday junction). Substrate-specific DNA binding activity was detected in three domains, one N-terminal and two different C-terminal WRN fragments (RecQ conserved domain and helicase RNase D conserved domain-containing domains). The substrate specificity of each DNA binding domain may indicate that each protein domain has a distinct biological function. The importance of these results is discussed with respect to proposed roles for WRN in distinct DNA metabolic pathways.


Dietary pattern and physical development in China-- based on the 1992 national nutrition survey.
Based on information gathered in the l992 Chinese national nutrition survey, the energy consumption on average is about adequate for the whole population. Dietary protein and fat have increased, and now provide 11.8% and 22.0%, respectively, of the total dietary energy. The adequacy of nutrient intake, expressed as percentages of RDA, is higher for urban populations than for rural, and higher for high income groups than for low income groups. Child growth has improved substantially compared to ten years ago. However, there are still 32.6% of preschool children with stunted growth and 17.7% are underweight. Rural children have a higher incidence of chronic energy deficiency (CED) than their urban counterparts. The improvement in children's growth and the increase of overweight adults are in line with the country's overall food production and the average food consumption of the population. The difference between urban and rural nutritional status deserves more attention.


Grand canonical Monte Carlo investigations of electrical double layer in molten salts.
Results of the Monte Carlo simulation of the electrode/molten salt interface are reported. The system investigated was modeled by the restricted primitive model of electrolyte being in contact with the charged hard wall (hard spheres of diameter d=400 pm and relative permittivity epsilon(r)=10). The temperature analysis of the mean activity coefficient gamma(+/-), heat capacity C(v) and radial distribution function, g, indicated the range of temperatures of the study. Calculations for the electrode/electrolyte interface were carried out for temperatures 1300, 1400, and 1500 K and in the range of the electrode charge densities sigma from 0.025 to 0.5 C m(-2). Singlet distribution functions showed a multilayer structure of the electrolyte in the vicinity of the electrode surface. The structure depended on the electrode charge, but not much on temperature. The capacitance curves had a parabolalike shape with the maximum located at sigma=0. This result is not consistent with the Gouy-Chapman theory, but has been confirmed by the modified Poisson-Boltzmann theory, which includes the correlation and exclusion volume effects.


Validating the scalability of soft X-ray spectromicroscopy for quantitative soil ecology and biogeochemistry research.
Synchrotron-based soft-X-ray scanning transmission X-ray microscopy (STXM) has the potential to provide nanoscale resolution of the associations among biological and geological materials. However, standard methods for how samples should be prepared, measured, and analyzed to allow the results from these nanoscale imaging and spectroscopic tools to be scaled to field scale biogeochemical results are not well established. We utilized a simple sample preparation technique that allows one to assess detailed mineral, metal, and microbe spectroscopic information at the nano- and microscale in soil colloids. We then evaluated three common approaches to collect and process nano- and micronscale information by STXM and the correspondence of these approaches to millimeter scale soil measurements. Finally, we assessed the reproducibility and spatial autocorrelation of nano- and micronscale protein, Fe(II) and Fe(III) densities in a soil sample. We demonstrate that linear combination fitting of entire spectra provides slightly different Fe(II) mineral densities compared to image resonance difference mapping but that difference mapping results are highly reproducible between among sample replicates. Further, STXM results scale to the mm scale in complex systems with an approximate geospatial range of 3 μm in these samples.


Shifting sands: the role of radiotherapy for patients with gastric and gastroesophageal adenocarcinoma.
Gastric adenocarcinoma, a leading cause of cancer-related mortality worldwide, is treated primarily with surgical resection in the non-metastatic setting. However, the optimal role and sequencing of adjunctive therapies, including radiotherapy (RT) as well as systemic therapy, remains unclear. A complex milieu of trials spanning several decades has evaluated different treatment strategies for gastric cancer, including the role of RT. In this review, we summarize the trial-level evidence for the diverse gastric cancer treatment paradigms. Despite initial success, postoperative RT has not shown a clear benefit in modern prospective studies in the setting of more aggressive surgical nodal dissection. On the other hand, the role of preoperative RT in optimizing oncologic outcomes for gastric cancer patients remains relatively under-explored; ongoing trials assessing preoperative RT aim to illuminate the optimal treatment strategy for non-metastatic gastric cancer patients.


Pulmonary heat shock protein expression after exposure to a metabolically activated Clara cell toxicant: relationship to protein adduct formation.
Heat shock proteins/stress proteins (Hsps) participate in regulation of protein synthesis and degradation and serve as general cytoprotectants, yet their role in lethal Clara cell injury is not clear. To define the pattern of Hsp expression in acute lethal Clara cell injury, mice were treated with the Clara cell-specific toxicant naphthalene (NA), and patterns of expression compared to electrophilic protein adduction and previously established organellar degradation and glutathione (GSH) depletion. In sites of lethal injury (distal bronchiole), prior to organellar degradation (1 h post-NA), protein adduction is detectable and ubiquitin, Hsp 25, Hsp 72, and heme-oxygenase 1 (HO-1) are increased. Maximal Hsp expression, protein adduction, and GSH depletion occur simultaneous (by 2-3 h) with early organelle disruption. Hsp expression is higher later (6-24 h), only in exfoliating cells. In airway sites (proximal bronchiole) with nonlethal Clara cell injury elevation of Hsp 25, 72, and HO-1 expression follows significant GSH depletion (greater than 50% 2 h post-NA). This data build upon our previous studies and we conclude that (1) in lethal (terminal bronchiole) and nonlethal (proximal bronchiole) Clara cell injury, Hsp induction is associated with the loss of GSH and increased protein adduction, and (2) in these same sites, organelle disruption is not a prerequisite for Hsp induction.


Adding Prandial Insulin to Basal Insulin Plus Oral Antidiabetic Drugs in Chinese Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Single-Arm Study.
There is relatively little data from China on the efficacy and safety of adding prandial insulin to basal insulin plus oral antidiabetic drugs (OADs) in people with poorly controlled type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of basal insulin dose optimization followed by the addition of prandial insulin in Chinese people with T2DM achieving suboptimal glycemic control with basal insulin and OADs. In this open-label, single-arm study, adults with T2DM receiving basal insulin plus OADs underwent insulin dose optimization for 12 weeks. At week 12, subjects who achieved fasting blood glucose (FBG) ≤6.5 mmol/L but not HbA1c ≤7% added one injection of prandial insulin at the main meal for an additional 24 weeks. Endpoints included mean HbA1c, the achievement rate of HbA1c ≤7%, hypoglycemia, and other adverse events (AEs). A total of 120 subjects underwent basal insulin optimization; At week 12, 110 study subjects achieved FBG ≤6.5 mmol/L, of whom 66 did not achieve HbA1c ≤7% and therefore initiated prandial insulin. Three patients discontinued prandial insulin due to dissatisfaction with treatment outcome (n = 1), accidental injury (n = 1), or personal reasons (n = 1). After 24 weeks of basal-plus treatment, mean HbA1c significantly decreased (8.06% to 7.17%; p < 0.001), 65.1% of subjects achieved HbA1c ≤7%, there was no change in FBG (6.23-6.20 mmol/L; p = 0.118), and mean post-prandial blood glucose decreased (13.17-10.14 mmol/L; p < 0.001). During basal-plus treatment, three individuals experienced hypoglycemia, and no significant change in the mean subject weight was observed (73.2 vs. 73.3 kg; p = 0.379). In people with T2DM who are achieving suboptimal glycemic control with basal insulin plus OADs, basal insulin dose optimization followed by the addition of prandial insulin improves glycemic control, is well tolerated, and is associated with a low incidence of hypoglycemia.


Calculation of vibrational energy of molecule using coupled cluster linear response theory in bosonic representation: convergence studies.
Vibrational excited state energies have been calculated using vibrational coupled cluster linear response theory (CCLRT). The method has been implemented on formaldehyde and water molecule. Convergence studies have been shown with varying the cluster operator from S(4) to S(6) as well as the excitation operator from four bosons to six bosons. A good agreement with full configuration interaction results has been observed with S(6) truncation at coupled-cluster method level and six bosonic excitations at CCLRT level.


Comparison of surgically induced astigmatism among different surgeons performing the same incision.
To compare surgically induced astigmatism (SIA) of different surgeons, who perform the same main incision. Two hundred and seventy eyes underwent cataract surgery with phacoemulsification by four different surgeons (A, B, C, and D). A 3-step, 3.0 mm, superotemporal for the right eye and superonasal for the left eye clear corneal incision was performed. A comparison in SIA among A, B, C and D surgeon was made. No significant difference was found in SIA at both first and sixth postoperative month between different surgeons (P>0.05). SIA is more dependent on incisional characteristics and preoperative astigmatism and less on the surgeon.


The impact of staff suicide on a psychiatric inpatient unit.
A staff nurse on a psychiatric inpatient unit committed suicide. A retrospective study of patients and staff reactions was conducted. It showed that the inpatients dealt openly and effectively with grieving. Staff had a great deal of difficulty with the situation. One of the nurse's outpatients required rehospitalization. Recommendations for more attention to the staff mourning process were made.


Selective inhibition of E. coli 1-deoxy-D-xylulose-5-phosphate synthase by acetylphosphonates().
DXP synthase catalyzes the formation of 1-deoxy-D-xylulose 5-phosphate, an essential precursor in pathogen isoprenoid biosynthesis. The selective inhibition of this ThDP-dependent transformation is a challenging goal in the development of isoprenoid biosynthesis inhibitors. Potent, selective inhibitors could lead to new anti-infective agents. Here, we demonstrate selective inhibition of E. coli DXP synthase by butylacetylphosphonate.


Capillary gas chromatographic separation of urinary organic acids. Retention indices of 101 urinary acids on a 5% phenylmethyl silicone capillary column.
Gas chromatographic retention indices (methylene units) are reported for 101 urinary organic acids as their trimethylsilyl and oximated trimethylsilyl derivatives on a 5% phenylmethyl silicone fused silica capillary column. Using anion exchange chromatography, organic acids were extracted from urines of five healthy individuals, seven patients with neuroblastoma, and nine patients with inherited organic acidurias. Separation of the various acids was achieved by capillary gas chromatography and identification was done by mass spectrometry using a computerized library search program. All identifications were confirmed by visual comparison with reference mass spectra. Standard deviations of the retention indices for all acids were less than 0.035 methylene units and for 46 acids less than 0.01 methylene units. Three chromatograms of urine from individuals with neuroblastoma, phenylketonuria, and propionic acidemia and one from a healthy individual are shown.


Inhibition of constitutive activation of STAT3 by curcurbitacin-I (JSI-124) sensitized human B-leukemia cells to apoptosis.
Phosphorylation of STAT3 on serine 727 regulates gene expression and is found to be elevated in many B-leukemia cells including chronic lymphocytic leukemia (CLL). It is, however, unclear whether targeting STAT3 will be an effective antileukemia therapy. In this study, we assessed in vitro antileukemia activity of the STAT3 inhibitor JSI-124 (cucurbitacin I). JSI-124 potently induces apoptosis in 3 B-leukemia cell lines (BJAB, I-83, and NALM-6) and in primary CLL cells and was associated with a reduction in serine 727 phosphorylation of STAT3. Similarly, knockdown of STAT3 expression induced apoptosis in these leukemia cells. In addition, we found that JSI-124 and knockdown of STAT3 decreased antiapoptotic protein XIAP expression and overexpression of XIAP blocked JSI-124-induced apoptosis. Furthermore, we found that combined treatment of JSI-124 and TRAIL increased apoptosis associated with an increase in death receptor 4 expression. Besides apoptosis, we found that JSI-124 also induced cell-cycle arrest prior to apoptosis in B-leukemia cells. This corresponded with reduced expression of the cell-cycle regulatory gene, cdc-2. Thus, we present here for the first time that JSI-124 induced suppression of serine 727 phosphorylation of STAT3, leading to apoptosis and cell-cycle arrest through alterations in gene transcription in B-leukemia cells.


H3K27 acetylation activated-CD109 evokes 5-fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway.
Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5-fluorouracil (5-FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5-FU-resistant GC cells. CD109 deficiency lessened the IC50 value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5-FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5-FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation-induced changes of IC50 values, cell viability, metastasis and apoptosis in NCI-N87/5-FU and SNU-1/5-FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated-CD109 enhanced 5-FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC.


Recent advances in artificial pacemakers.
Electronic pacing is now the accepted therapy for patients with symptomatic slow ventricular heart rates. Pacing may be temporary or permanent, epicardial or endocardial, fixed, synchronous or demand. The choice of pacing mode is dictated by the clinical status of the patient, his progress during temporary pacing, and the presence or absence of competitive rhythm.


[Intraluminal crystalloids in prostatic carcinoma: morphologic and histochemical study].
The histological sections of 302 diagnosed cases of prostate carcinoma were analyzed for intraluminal crystalloids, correlating their presence, number and characteristics with other morphological parameters used for the diagnosis of prostate carcinoma. Evidence of these structures was found in 65 cases (21.5%). The majority developed in malignant glands though they were also found in benign glands adjacent to cancerous foci. Their presence indicates good tumoral differentiation and both their number and shape are dependent on the tumour's histological grade.


Prevalence of Paget's disease of bone in Italy.
We examined the prevalence of PDB in Italy from radiological, scintigraphic, and biochemical surveys in two Italian towns. Prevalence rates varied from 0.7% to 2.4%, were higher in males than in females, and slightly differed between the two towns. Unlike previous studies in populations of British descent, no secular trend for a decreasing prevalence emerged. Clinical, radiological, and necropsy data from different countries suggested pronounced geographical variations in the prevalence of Paget's disease of bone (PDB). Despite the impact of the disease on the population, there are limited data on the prevalence of PDB in Italy. The objective of this study was to estimate the prevalence of PDB in the district of Siena (Central Italy) and Turin (Northern Italy) from radiological, biochemical, and scintigraphic surveys. We examined a sample of 1778 consecutive pelvic radiographs performed between 1999 and 2000 at the Hospital Radiology Unit in Siena and 6609 pelvic radiographs performed in 1986-1987, 1992-1993, and 1999-2002 from the Radiology Department of Molinette Hospital in Turin. In Siena, 7906 consecutive (99m)TC-MDP bone scans performed over a 4-year period (January 2000 to May 2004) were also screened for the presence of PDB, and the prevalence of elevated alkaline phosphatase (ALP) levels (>300 UI/liter) was estimated from 7449 computerized medical records over a 3-year period (January 2000 to February 2003). The finding of PDB on the pelvic radiograph and bone scan was based on standardized radiological criteria. At the end of the radiological surveys, 16/1778 pelvic PDB cases (8 males and 8 females) were observed in Siena and 41/6609 (27 males and 14 females) in Turin. The crude prevalence of the disease was 0.89% in Siena and 0.62% in Turin. Given that pelvic involvement is commonly described in 60-90% of PDB patients, the estimated overall prevalence of PDB ranged from 1.0% to 1.5% in Siena and from 0.7% to 1.0% in Turin. No decrease in the prevalence of PDB was evident after comparison of prevalence rates from different periods. Biochemical analyses showed 296/7449 subjects with elevated ALP levels and normal liver enzymes, 87 of whom had confirmed diagnosis of PDB. The estimated prevalence of biochemical PDB was 1.5%. The scintigraphic survey showed a PDB prevalence of 194/7906 (2.4%), which was significantly higher than the radiological and biochemical estimates. Our surveys suggest that PDB in Italy has an estimated prevalence of at least 1%, comparable with that observed in United States and other European countries, but lower than that described in Britain and New Zealand. No secular trend for a decreasing prevalence of PDB was observed.


The Interaction of Genetic Background and Mutational Effects in Regulation of Mouse Craniofacial Shape.
Inbred genetic background significantly influences the expression of phenotypes associated with known genetic perturbations and can underlie variation in disease severity between individuals with the same mutation. However, the effect of epistatic interactions on the development of complex traits, such as craniofacial morphology, is poorly understood. Here, we investigated the effect of three inbred backgrounds (129X1/SvJ, C57BL/6J, and FVB/NJ) on the expression of craniofacial dysmorphology in mice (Mus musculus) with loss of function in three members of the Sprouty family of growth factor negative regulators (Spry1, Spry2, or Spry4) in order to explore the impact of epistatic interactions on skull morphology. We found that the interaction of inbred background and the Sprouty genotype explains as much craniofacial shape variation as the Sprouty genotype alone. The most severely affected genotypes display a relatively short and wide skull, a rounded cranial vault, and a more highly angled inferior profile. Our results suggest that the FVB background is more resilient to Sprouty loss of function than either C57 or 129, and that Spry4 loss is generally less severe than loss of Spry1 or Spry2 While the specific modifier genes responsible for these significant background effects remain unknown, our results highlight the value of intercrossing mice of multiple inbred backgrounds to identify the genes and developmental interactions that modulate the severity of craniofacial dysmorphology. Our quantitative results represent an important first step toward elucidating genetic interactions underlying variation in robustness to known genetic perturbations in mice.