A rare Hb H disease due to the - -(SEA) and 16.6 kb α-thalassemia-2 deletions.
A large deletional α-thalassemia-2 (α-thal-2) allele was identified in a Thai woman with Hb H disease. The proband has α-thal-1 (SEA type) in conjunction with a 16.6 kb deletion affecting the α2-globin allele. The proband had severe anemia and required a blood transfusion during puerperium.


In vitro stimulation with mitogen and antigen in patients with monoclonal gammopathy.
Peripheral blood lymphocytes from 32 patients with defined paraproteinaemia (16 IgG, 9 IgA and 7 IgM) and from 15 healthy donors were studied for their in vitro response to various stimuli, including for unspecific mitogens such as Phytohaemagglutinin (PHA), Pokeweed mitogen (PWM) and Concanavalin A (ConA) as well as specific antigens such as purified Tuberculin, Candida, Varidase, Tetanus Toxoid, Vaccinia antigen and Vaccinia-control antigen. Mitogens and antigens were lyophilized in Microtiter plates. The lymphocytes of all tested patient-groups responded (measured by H3-Thymidin-uptake) significantly lower towards the unspecific mitogens than those of the control group. If the patients' lymphocytes were stimulated by the specific antigens, their in vitro response was significantly diminished to candida and vaccinia. Macroglobulinaemia showed significantly lower response to ConA if compared to myelomas of IgG- and IgA-type. No correlation was found between mitogen and antigen response and the serum concentration of the paraproteins or immunoglobulins. The results show that monoclonal gammopathy and especially macroglobulinaemia are associated with abnormalities of the cellular immunity which correlates with the clinical observation of increased fungal and viral infections.


Effects of the shape of coronary arteries on the presence, extent, and severity of their disease.
It is now known that a C-shaped right coronary artery (RCA) (C-RCA) is associated with more atherosclerotic disease than a sigma-shaped RCA (S-RCA). This study was designed to investigate the relationship between the shape of the RCA and the presence, extent, and severity of coronary artery disease (CAD) in all coronary arteries. Two hundred and forty-five patients were divided into C-RCA (group 1, n = 161) and S-RCA (group 2, n = 84) groups. The vessel score, extent score, and Gensini score were higher in group 1 than in group 2 (P < 0.001 for all comparisons). In multivariate analyses, age (P = 0.001), male sex (P < 0.001), smoking (P = 0.002), and C-RCA (P < 0.001) were independent predictors of significant CAD (presence of at least one lesion causing at least >50% stenosis). Multiple linear regression analysis to predict vessel score identified C-RCA (P < 0.001), age (P = 0.004), and male sex (P = 0.020), to predict extent score identified C-RCA (P < 0.001), age (P = 0.005), and male sex (P = 0.003), and to predict Gensini score identified C-RCA (P < 0.001), male sex (P = 0.009), and dyslipidemia (P = 0.049) as independently associated variables. Sensitivity and specificity of C-RCA for detecting significant CAD were 79% and 46%, respectively. This study showed that C-RCA was an independent predictor of significant CAD, which was independently associated with vessel score, extent score, and Gensini score. However, it was not clinically useful, because it was not specific or sensitive enough to identify patients with significant CAD.


Three-dimensional phase contrast angiography.
Bipolar flow-encoding gradients can be used in a three-dimensional magnetic resonance imaging procedure to provide a noninvasive measure of in vivo blood flow. The resulting volume angiogram is a three-dimensional data matrix which can be retrospectively analyzed and displayed in a variety of ways. This angiographic technique provides good suppression of signals arising from stationary tissue, thereby permitting the visualization of small vessels having relatively slow flow. This suppression is obtained by modulating the amplitude of the flow-encoding gradient pulse to either cancel the stationary tissue signal or displace it relative to the flow signal in the volume image.


Fate of nickel in a lime-stabilized biosolid, a calcareous soil and soil-biosolid mixtures.
Soil contamination with anthropogenic metals resulting from biosolid application is widespread around the world. To better predict the environmental fate and mobility of contaminants, it is critical to study the capacity of biosolid-amended soils to retain and release metals. In this paper, nickel adsorption onto a calcareous soil, a lime-stabilized biosolid, and soil-biosolid mixtures (30, 75, and 150 t biosolid/ha) was studied in batch experiments. Sorption experiments showed that (1) Ni adsorption was higher onto the biosolid than the calcareous soil, and (2) biosolid acted as an adsorbent in the biosolid-soil mixtures by increasing Ni retention capacity. The sorption tests were complemented with the estimation of Ni adsorption reversibility by successive applications of extraction solutions with water, calcium (100 mg/L), and oxalic acid (equivalent to 100 mg carbon/L). It has been shown that Ni desorption rates in soil and biosolid-amended soils were lower than 30 % whatever the chemical reagent, indicating that Ni was strongly adsorbed on the different systems. This adsorption/desorption hysteresis effect was particularly significant at the highest biosolid concentration (150 t/ha). Finally, an adsorption empirical model was used to estimate the maximum permissible biosolid application rate using French national guideline. It has been shown that desorption effects should be quantitatively considered to estimate relevant biosolid loadings.


Improving Performance of Tin-Doped-Zinc-Oxide Thin-Film Transistors by Optimizing Channel Structure.
In this paper, we investigated the performance of thin-film transistors (TFTs) with different channel configurations including single-active-layer (SAL) Sn-Zn-O (TZO), dual-active-layers (DAL) In-Sn-O (ITO)/TZO, and triple-active-layers (TAL) TZO/ITO/TZO. The TAL TFTs were found to combine the advantages of SAL TFTs (a low off-state current) and DAL TFTs (a high mobility and a low threshold voltage). The proposed TAL TFTs exhibit superior electrical performance, e.g. a high on-off state current ratio of 2 × 108, a low threshold voltage of 0.63 V, a high field effect mobility of 128.6 cm2/Vs, and a low off-state current of 3.3 pA. The surface morphology and characteristics of the ITO and TZO films were investigated and the TZO film was found to be C-axis-aligned crystalline (CAAC). A simplified resistance model was deduced to explain the channel resistance of the proposed TFTs. At last, TAL TFTs with different channel lengths were also discussed to show the stability and the uniformity of our fabrication process. Owing to its low-processing temperature, superior electrical performance, and low cost, TFTs with the proposed TAL channel configuration are highly promising for flexible displays where the polymeric substrates are heat-sensitive and a low processing temperature is desirable.


Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration.
Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy.


Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: experience with imipenem/cilastatin.
Observations on 1,754 patients treated with imipenem/cilastatin in phase III dose-ranging studies in the United States were reviewed to determine risk factors for seizures. The patients were moderately to severely ill with numerous background disorders known to be associated with an increased risk of seizures. Fifty-two patients (3 percent) had seizures and in 16 (0.9 percent) of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem/cilastatin. An incidence of seizure of 2 to 3 percent was noted among patients treated with other antibiotics (usually including a beta-lactam in the regimen) at times when imipenem/cilastatin was not being given. The average time of onset of seizures for patients receiving imipenem/cilastatin was seven days after start of therapy. As with other beta-lactam antibiotics, central nervous system lesions and disorders including seizures and renal insufficiency were found to be strong risk factors for seizures. Imipenem/cilastatin dosages in excess of those currently recommended by the manufacturer, particularly in patients with renal insufficiency, were also associated with an increased risk of seizures. There was an association with Pseudomonas aeruginosa infection that remained statistically significant even after controlling for imipenem/cilastatin dosage as well as for the other factors indicated. A high background incidence of seizures in general in a group of severely ill patients makes it both difficult to assess the etiology of a seizure and important to consider the risk factors when choosing the appropriate dose of an antibiotic. Guidelines are presented for appropriate dosing of imipenem/cilastatin in relation to renal function, body weight, and infecting pathogen.


Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers.
A lab-on-fiber (LOF) optofluidic platform that provides physiologically relevant microenvironment was developed by integrating a long period grating (LPG) coupled with high order cladding mode to achieve high index sensitivity and a liquid-tight capillary tube assembly as a microfluidic chamber for LPG to mimic physiologically relevant microenvironment. We demonstrate the utility of LOF for in situ monitoring the construction of the [chitosan (CHI)/poly (acrylic acid) (PAA)/gentamicin sulfate (GS)/PAA]n multilayers at monolayer resolution as well as evaluating the rate of GS release at a flow rate of 0.127 mL/min at 37 °C in real time. We reveal that GS is released at a faster rate under the dynamic flow condition than in a static medium. Our findings underscore the importance of conducting drug release studies in physiologically relevant conditions.


Intacs for keratoconus and post-LASIK ectasia: mechanical versus femtosecond laser-assisted channel creation.
To evaluate the efficacy of intracorneal ring segments to treat keratoconus and post-laser in situ keratomileusis (LASIK) keratectasia implanted by using either mechanical dissection or a femtosecond laser. Thirty-three eyes of 29 patients had intracorneal ring segments implanted by using mechanical dissection (17 eyes) or a femtosecond laser (16 eyes). Mean follow-up was 10.3 months. Parameters assessed before and after surgery included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), refractive cylinder (RC), best contact lens-corrected visual acuity (BCLVA), and contact lens tolerance. Statistically significant changes occurred for all parameters when we analyzed all 33 eyes as 1 group. Mean UCVA LogMar values improved from 1.0 +/- 0.3 (20/200) to 0.6 +/- 0.4 (20/80) (P < 0.0005). Mean BSCVA changed from 0.3 +/- 0.2 (20/40) to 0.2 +/- 0.2 (20/30) (10%; P < 0.05), and MRSE from -9 +/- 4 to -7 +/- 4 D (P < 0.05; 20%). There was a decrease of 0.5 D or more of RC in 62% of eyes. BCLVA improved from 0.2 +/- 0.2 (20/30) to 0.1 +/- 0.1 (20/25) after surgery (P < 0.02). Contact lens tolerance improved in 81% of eyes. There was no statistically significant difference in outcomes between mechanical dissection and femtosecond laser-assisted techniques. However, although statistical power was adequate to detect changes in clinical parameters as a result of surgery, it was not sufficient to conclusively show such differences between surgical techniques. For mild to moderate cases of keratoconus and post-LASIK keratectasia, the use of a femtosecond laser for Intacs channel creation seems as effective as mechanical dissection. Future studies are warranted to further evaluate channel creation by a femtosecond laser.


Piezoeletric cold atmospheric plasma induces apoptosis and autophagy in human hepatocellular carcinoma cells through blocking glycolysis and AKT/mTOR/HIF-1α pathway.
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the fourth leading cause of cancer-related death worldwide. Advanced or metastatic HCC is currently managed using systemic drug therapy with unsatisfactory patient survival. Cold atmospheric plasma has emerged as a promising, physicochemical, and broad-spectrum oncotherapy. In this preclinical study, we investigated the anti-neoplastic functions and mechanism of piezoelectric direct discharge technology-based CAP, Piezo-CAP, on HCC in vitro and in vivo. Various HCC cells lines, such as SMMC7721, HepG2 and LM3, were used as in vitro cancer model for the phenotypic and mechanistic studies. Specifically, the cell counting Kit-8 and colony formation assay, flow cytometry, Transwell assay, Western blot, reactive oxygen species (ROS) assay, and glutathione to oxidized glutathione ratio (GSH/GSSG) assay were used to demonstrate plasma-induced changes in HCC cell proliferation, cell cycle progression, migration and invasion, epithelial-to-mesenchymal transition, intracellular ROS, and antioxidant capacity, respectively. In addition, the Acridine orange and ethidium bromide (AO/EB) staining and transmission electron microscopy were performed for cellular and subcellular assessment of HCC cell apoptosis. The Ad-mCherry-RFP-LC3B fluorescent double-labeled lentiviral system was used to detect autophagic flux. On the other hand, RNA-sequencing, quantitative real-time PCR, and Western blot were used to demonstrate plasma-induced metabolic and molecular disruption of tumor glycolysis and oncogenic proliferation, respectively. In vivo experiments using a human cell-line-derived xenograft model and immunohistochemistry (IHC) were utilized to investigate the mechanism. Piezo-CAP exerted anti-neoplastic functions through inhibiting cell proliferation, migration and invasion, and promote cell apoptosis and autophagy. Treatment of Piezo-CAP could suppress proliferation and induce autophagy of HCC cells through simultaneously disrupts cancer survival pathways of redox deregulation, glycolytic pathway, and PI3K/AKT/mTOR/HIF1α pathway signaling. Moreover, upon translation of these in vitro results into the tissue level, Piezo-CAP significantly suppressed in situ tumor growth. These findings collectively suggest that Piezo-CAP-induced apoptosis and autophagy of HCC cells though a multitargeted blockade of major cancer survival pathways of deregulated redox balance, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling.


The effect of improved hand hygiene on nosocomial MRSA control.
The purpose of this review is to examine studies that have assessed the association between hand hygiene enhancement and methicillin-resistant Staphylococcus aureus (MRSA) rates and to explore controversies surrounding this association. Many studies have been published confirming the link between improved hand hygiene compliance and reduction in MRSA acquisition and infections, including bacteremia. These studies have also shown the cost-beneficial nature of these programmes. Despite considerable research some issues remain unanswered still, including the temporal relationship between hand hygiene enhancement strategies and decrease in MRSA rates, association between hand hygiene enhancement and MRSA-related surgical site infections, diminishing effect of hand hygiene compliance on MRSA rates after reaching a threshold and the role of instituting contact precautions in the setting of low MRSA rates and sufficient hand hygiene compliance. In conclusion, enhancement of hand hygiene compliance has been shown to reduce MRSA rates; however, some open issues warrant further investigation.


VIQoR: a web service for visually supervised protein inference and protein quantification.
In quantitative bottom-up mass spectrometry (MS)-based proteomics, the reliable estimation of protein concentration changes from peptide quantifications between different biological samples is essential. This estimation is not a single task but comprises the two processes of protein inference and protein abundance summarization. Furthermore, due to the high complexity of proteomics data and associated uncertainty about the performance of these processes, there is a demand for comprehensive visualization methods able to integrate protein with peptide quantitative data including their post-translational modifications. Hence, there is a lack of a suitable tool that provides post-identification quantitative analysis of proteins with simultaneous interactive visualization. In this article, we present VIQoR, a user-friendly web service that accepts peptide quantitative data of both labeled and label-free experiments and accomplishes the crucial components protein inference and summarization and interactive visualization modules, including the novel VIQoR plot. We implemented two different parsimonious algorithms to solve the protein inference problem, while protein summarization is facilitated by a well-established factor analysis algorithm called fast-FARMS followed by a weighted average summarization function that minimizes the effect of missing values. In addition, summarization is optimized by the so-called Global Correlation Indicator (GCI). We test the tool on three publicly available ground truth datasets and demonstrate the ability of the protein inference algorithms to handle shared peptides. We furthermore show that GCI increases the accuracy of the quantitative analysis in datasets with replicated design. VIQoR is accessible at: http://computproteomics.bmb.sdu.dk/Apps/VIQoR/. The source code is available at: https://bitbucket.org/veitveit/viqor/. Supplementary data are available at Bioinformatics online.


Mental health service use and cost of care for older adults in assisted living facilities: implications for public policy.
With changing demographics prompting greater demand for assisted living facility (ALF) care, indigent older adults with mental health needs face underfunded residential care options and mental health systems currently unprepared to meet their service requirements. In particular, over-reliance on inpatient mental health services for older individuals with mental illness and inadequate reimbursement of ALF facilities potentially increase costs and threaten availability of ALF care. This article analyzes Florida's administrative data and presents findings on mental health service use and cost of care for poor older persons. Using Florida as an example, the authors recommend policy changes to ensure the quality and availability of residential care for low-income adults with mental health needs.


Metal-Free, Site-Selective Addition to Ynones: An Approach to Synthesize Substituted Quinoline Derivatives.
An efficient two component cycloaddition reaction to synthesize various substituted quinoline derivatives was developed. Ynone 1 was functionalizated by N-oxide attacking the C3-oxetium site and C3-site regioselectively to give 3 and 4. Analogues 3k and 4v have a high binding constant with Hg2+ in CH3CN.


The impact of an intensive care unit admission on the health status of relatives of intensive care survivors: A prospective cohort study in primary care.
Relatives of intensive care unit (ICU) survivors may suffer from various symptoms after ICU admittance of their relative, known as post-intensive care syndrome-family (PICS-F). Studies regarding PICS-F have been performed but its impact in primary care is unknown. To explore health problems of relatives of ICU survivors in primary care. This is an exploratory prospective cohort study in which we combined data from two hospitals and a primary care research network in the Netherlands. ICU survivors who had been admitted between January 2005 and July 2017 were identified and matched by sex and age with up to four chronically ill (e.g. COPD, cardiovascular disease) patients. In both groups, relatives living in the same household were identified and included in this study. Primary outcome was the number of new episodes of care (International Classification of Primary Care-2) for up to five years. Hazard ratios (HRs) for the total number of new episodes were calculated. Relatives of ICU survivors (n = 267, mean age 38.1 years, 41.0% male) had significantly more new care episodes compared to the reference group (n = 705, mean age 36.3 years, 41.1% male) 1-2 years (median 0.11 vs. 0.08, HR 1.26; 95% confidence interval (CI) 1.03-1.54) and 2-5 years (median 0.18 vs. 0.13, HR 1.28; 95%CI 1.06-1.56) after ICU discharge. No differences were found in the period before ICU admission. Relatives of ICU survivors present more morbidity in primary care than relatives of chronically ill patients up to five years after ICU discharge.


Mitral valve annuloplasty: the effect of the type on left ventricular function.
This study was undertaken to determine whether rigid-ring annuloplasty and flexible-ring annuloplasty have the same effect on left ventricular function in patients with chronic mitral regurgitation secondary to degenerative disease of the mitral valve. Twenty-five patients who underwent isolated mitral valve repair and required annuloplasty were randomized into two groups: rigid-ring and flexible-ring annuloplasty. Left ventricular function was assessed by echocardiography and radionuclide angiography on the day before operation and 2 to 3 months later. Preoperative left ventricular function was similar in the two groups of patients. Postoperatively, left ventricular end-diastolic diameter and volume decreased significantly in both groups. The left ventricular end-systolic diameter and volume decreased significantly only in patients with a flexible annuloplasty ring. Left ventricular systolic function as assessed by pressure-volume relationships was significantly better in patients with a flexible ring (p less than 0.02 by analysis of covariance), and left ventricular performance measured by stroke volume-end-diastolic volume relationships was also better in these patients (p less than 0.05 by analysis of covariance). These data indicate that patients with a flexible annuloplasty ring have better left ventricular systolic function than patients with a rigid annuloplasty ring 2 to 3 months after mitral valve reconstruction for chronic mitral regurgitation secondary to degenerative disease of the mitral valve.


A scalable field study using leaves as a novel passive air sampler to evaluate the potential source of organophosphate esters in street dust.
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in industrial and commercial products. It is generally believed that OPEs in street dust mainly originate from road traffic and anthropogenic activities. The influence of atmospheric deposition is still unknown. In this study, leaves were employed as a novel passive air sampler to collect particle matters (PM) in 12 cities in the central province of Henan, China. Similar compositional profiles of OPEs were found in street dust and PM samples. The concentrations of individual OPEs in PM were 1-4 times higher than in street dust. Chlorinated OPEs concentration in PM shows a moderate correlation (r2 = 0.538, p < 0.01) with that in street dust. The concentration of alkyl OPEs in PM has a high correlation (r2 = 0.843, p < 0.01) with that in street dust. No significant correlation (r2 = 0.133, p = 0.132) was found on the aryl OPEs concentrations between street dust and PM. Spearman correlation reveals that the emission sources of tricresyl phosphate (TCrP) and triethyl phosphate (TEP) may be different from other OPEs in dust and PM samples. Principle component analysis (PCA) provides an appropriate explanation that tris (2-chloroethyl) phosphate (TCEP), triphenyl phosphate (TPhP), tris (chloropropyl) phosphate (TCPP), tributyl phosphate (TnBP), and TEP in street dust and PM may be emitted from the same sources, suggesting that PM has a significant influence on the occurrence of OPEs in street dust. The estimated dry deposition fluxes of particle-bound OPEs show a significant correlation (R2 = 0.969, p < 0.01) with OPEs concentrations in street dust, revealing that the input of atmospheric deposition could be a major source of OPEs in street dust.


Inter-rater agreement of the Pain and Disability Drivers Management rating scale.
A framework to establish the biopsychosocial patient profile for persons with low back pain has been recently proposed and validated: The Pain and Disability Drivers Management model (PDDM). In order to facilitate its clinical integration, we developed the PDDM rating scale. To determine the inter-rater agreement of the PDDM rating scale. A second objective was to determine if this inter-rater agreement varies according to the complexity of patients' clinical presentation. We recruited physiotherapists during one-day workshops on the PDDM. We asked each participant to assess two clinical vignettes using the rating scale. One vignette presented a typical clinical presentation (moderate level of difficulty) and one presented an atypical presentation (complex level of difficulty). We determined inter-rater agreement with the proportion of participants who gave the same answer for each PDDM domain. For the typical vignette, the inter-rater agreement per domain was moderate to good (between 0.54 and 0.97). For the complex vignette, the inter-rater agreement per domain was poor to good (between 0.49 and 0.81). The comparison between the two vignettes showed a significant difference (p< 0.01) for nociceptive and cognitive-emotional domains. Overall performance indicates that the rating scale present adequate agreement for clinical use, but specific domains require further development.


Advances in Pyrazole Based Scaffold as Cyclin-dependent Kinase 2 Inhibitors for the Treatment of Cancer.
The transformation of a normal cell into a tumor cell is one of the initial steps in cell cycle deregulation. The cell cycle is regulated by cyclin-dependent kinases (CDKs) that belong to the protein kinase family. CDK2 is an enchanting target for specific genotype tumors since cyclin E is selective for CDK2 and the deregulation of specific cancer types. Thus, CDKs inhibitor, specifically CDK2/cyclin A-E, has the potential to be a valid cancer target as per the currently undergoing clinical trials. Most of the pyrazole scaffolds have shown selectivity and potency for CDK2 inhibitors. This review aims at examining pyrazole and pyrazole fused with other heterocyclic rings for antiproliferative activity. Based on the in vitro and molecular docking studies, the most potent analogues for CDK2 inhibition are exhibited by IC50 value. Moreover, the review emphasizes the various lead analogs of pyrazole hybrids which can be very potent and selective for anti-cancer drugs.


Integrated loss- and gain-of-function screens define a core network governing human embryonic stem cell behavior.
Understanding the genetic control of human embryonic stem cell function is foundational for developmental biology and regenerative medicine. Here we describe an integrated genome-scale loss- and gain-of-function screening approach to identify genetic networks governing embryonic stem cell proliferation and differentiation into the three germ layers. We identified a deep link between pluripotency maintenance and survival by showing that genetic alterations that cause pluripotency dissolution simultaneously increase apoptosis resistance. We discovered that the chromatin-modifying complex SAGA and in particular its subunit TADA2B are central regulators of pluripotency, survival, growth, and lineage specification. Joint analysis of all screens revealed that genetic alterations that broadly inhibit differentiation across multiple germ layers drive proliferation and survival under pluripotency-maintaining conditions and coincide with known cancer drivers. Our results show the power of integrated multilayer genetic screening for the robust mapping of complex genetic networks.


Perceptual characteristics of tracheoesophageal speech production using the new indwelling Provox Vega voice prosthesis: a randomized controlled crossover trial.
The objective of this study was to determine if the design enhancements incorporated into the new Provox Vega Indwelling Voice prostheses result in any positive benefits in vivo. Using a randomized, crossover study design, 31 participants using tracheoesophageal speech postlaryngectomy completed a 3-week trial of the Provox Vega and a comparator device. Main outcome measures included patient perceptions of vocal effort and quality using each device, and perceptual judgments of voice quality produced. The majority of patients (72%) indicated the Provox Vega gave them overall better voice quality and 52% felt they required less effort to phonate. Voice samples produced with the Provox Vega were also perceived by listeners to be significantly (p < .05) less strained, easier to understand, produced with less effort, and the better speech sample overall. Results support that the aerodynamic improvements incorporated in the design of the new Provox Vega facilitate enhanced voice and speech qualities.


Anion recognition by alpha-arylazo-N-confused calix[4]pyrroles.
The first example of substitution reaction in the free alpha-position of N-confused calix[4]pyrroles is reported: azo-coupling with various arenediazonium salts. The obtained azocompounds were used for studies of their anion-binding properties by UV-Vis spectroscopy.


Minimally invasive treatment of varicose veins: Endovenous laser ablation (EVLA).
Varicose veins are a frequently encountered medical condition. In the era of minimally invasive surgery, several techniques, in the treatment of varicose veins, have been developed in the last few years. One of the most frequently used new techniques is endovenous laser ablation. Fibrotic sealing of the treated vein lumen is the final result. The vein ablation is obtained under local - tumescent anaesthesia and the patients can be treated in an office setting with immediate return to full activity. Safety and effectiveness seem to be the major characteristics and advantages of this technique.


One-stop endoscopic hernia surgery: efficient and satisfactory.
One-stop surgery offers patients diagnostic work-up and subsequent surgical treatment on the same day. In the present study, patient satisfaction and efficiency from an institutional perspective were evaluated in patients who were referred for one-stop endoscopic inguinal hernia repair. In a high-volume inguinal hernia clinic, all consecutive patients referred for one-stop surgical treatment, were registered prospectively. An instructed secretary screened patients for eligibility for the one-stop option when the appointment was made. Totally extraperitoneal hernia repair under general anaesthesia was the preferred operative technique. Patient's satisfaction, successful day surgery and institutional efficiency were evaluated. Between January 2010 and January 2012 a total of 349 patients (17 % of all patients in the hernia clinic) were referred for one-stop hernia repair. Mean age was 47.5 years and 96.3 % were males. Three hundred thirty-six patients underwent hernia surgery on the same day (96.3 %). In thirteen patients (3.7 %) no operative repair was done on the day of presentation due to an incorrect diagnosis (n = 7), a watchful waiting policy for asymptomatic hernia (n = 3), rescheduling due to a large scrotal hernia, and there were two "no shows". Following hernia repair 97 % of the patients were discharged on the same day, while ten patients required hospitalization. Based on the questionnaires the main satisfaction score among patients was 9.0 (8.89-9.17 95 % CI) on a scale ranging from 0 to 10. One-stop hernia surgery is feasible and satisfactory from an institutional as well as from a patient's perspective.


Chronic stress and sympathetic-adrenal medullary responsiveness.
Acute exposure of animals to stressful stimulation is attended by a significant activation of the sympathetic-adrenal medullary system. If animals are exposed to the same stressful stimulus each day for several weeks, a number of adaptive changes occur in the sympathetic-adrenal medullary system, including increased synthesis and storage of catecholamines, increased basal levels of circulating catecholamines, and decreased release of catecholamines into the circulation following exposure to the identical (homotypic) stressful stimulus. If chronically stressed animals are exposed to a novel (heterotypic) stressful stimulus, there is an exaggerated response of the sympathetic-adrenal medullary system compared to animals exposed to the same stressful stimulus for the first time. Other neuroendocrine systems share some characteristics with the sympathetic-adrenal medullary system in its pattern of adaptation to chronic stress. Several variables appear to influence this pattern of neuroendocrine adaptation to stressful stimulation, including predictability of the stressor, the intensity and duration of the stressor, the interval between each episode of stress, and the number of presentations of the stressor. The pattern of neuroendocrine adaptation to chronic intermittent stressful stimulation resembles in some respects the processes of habituation and sensitization.


Multiplexed Viability Assays for High-Throughput Screening of Spheroids of Multiple Sizes.
High-throughput (HT) drug screening is in high demand for successful drug discovery and personalized medicine. Spheroids act as a promising preclinical model for HT drug screening, which may decrease drug failures in clinical trials. Numerous spheroid-forming technological platforms are currently under development, which include synchronous, jumbo-sized, hanging drop, rotary, and nonadherent surface spheroid growth. Initial cell seeding concentration and time of culture play a vital role for spheroids to mimic the extracellular microenvironment of natural tissue, especially for HT preclinical evaluation. Hence microfluidic platforms become a potential technology to provide a confined space for the oxygen and nutrient gradients within the tissues while controlling the cell count and spheroid size in an HT manner. We describe here a microfluidic platform capable of generating spheroids of multiple sizes in a controlled manner with a predefined cell concentration for HT drug screening. Ovarian cancer spheroids grown on this microfluidic platform were evaluated for viability using a confocal microscope and flow cytometer. In addition, screening of the HT chemotherapeutic drug carboplatin was carried out on-chip to evaluate the impact of spheroid size on drug toxicity. This chapter summarizes a detailed protocol on microfluidic platform fabrication for spheroid growth, on-chip multi-sized spheroid analysis, and chemotherapeutic drug screening.


Molecular modeling study on the water-electrode surface interaction in hydrovoltaic energy.
The global energy problem caused by the decrease in fossil fuel sources, which have negative effects on human health and the environment, has made it necessary to research alternative energy sources. Renewable energy sources are more advantageous than fossil fuels because they are unlimited in quantity, do not cause great harm to the environment, are safe, and create economic value by reducing foreign dependency because they are obtained from natural resources. With nanotechnology, which enables the development of different technologies to meet energy needs, low-cost and environmentally friendly systems with high energy conversion efficiency are developed. Renewable energy production studies have focused on the development of hydrovoltaic technologies, in which electrical energy is produced by making use of the evaporation of natural water, which is the most abundant in the world. By using nanomaterials such as graphene, carbon nanoparticles, carbon nanotubes, and conductive polymers, hydrovoltaic technology provides systems with high energy conversion performance and low cost, which can directly convert the thermal energy resulting from the evaporation of water into electrical energy. The effect of the presence of water on the generation of energy via the interactions between the ion(s) and the liquid-solid surface can be enlightened by the mechanism of the hydovoltaic effect. Here, we simply try to get some tricky information underlying the hydrovoltaic effect by using DFT/B3LYP/6-311G(d, p) computations. Namely, the physicochemical and electronic properties of the graphene surface with a water molecule were investigated, and how/how much these quantities (or parameters) changed in case of the water molecule contained an equal number of charges were analyzed. In these computations, an excess of both positive charge and negative charge, and also a neutral environment was considered by using the Na+, Cl-, and NaCl salt, respectively.


Chinese species of egg-parasitoids of the genera Oxyscelio Kieffer, Heptascelio Kieffer and Platyscelio Kieffer (Hymenoptera: Platygastridaes.l., Scelioninae).
To date, the known Chinese fauna of egg-parasitoids of the genus Oxyscelio Kieffer encompasses two species from the mainland - Oxysceliodoumao Burks and Oxyscelionubbin Burks. Here we record eighteen species of Oxyscelio from collections in mainland China: Oxyscelioarvi Burks, Oxyscelioceylonensis (Dodd), Oxyscelioconvergens Burks, Oxysceliocordis Burks, Oxysceliocrebritas Burks, Oxysceliocuculli Burks, Oxysceliodermatoglyphes Burks, Oxysceliodoumao Burks, Oxyscelioflorus Kononova, Oxysceliogranorum Burks, Oxysceliointermedietas Burks, Oxysceliojugi Burks, Oxysceliokramatos Burks, Oxysceliolongiventris Burks, Oxyscelionaraws Kozlov & Lê, Oxyscelioperpensus Kononova, Oxyscelioplanocarinae Burks, and Oxysceliostriarum Burks. Oxyscelio is primarily found in the tropics, and most of these species are shared with Taiwan and southeast Asia. Three species previously known only from Japan, Oxyscelioarvi, Oxyscelioflorus, Oxyscelioperpensus, are shared. The Chinese species are recorded from Guangdong, Guangxi, Hainan, Hebei, Hunan, Shaanxi, Sichuan, Yunnan and Zhejiang as well as additional material from Taiwan. Heptasceliohamatus Masner & Johnson and Platysceliopulchricornis Kieffer are both recorded from Hainan and Guangdong, as well as records of Platysceliopulchricornis from Sarawak and Thailand.


How Can Ozone and Relative Humidity Affect Artists' Alkyd Paints? A FT-IR and Py-GC/MS Systematic Study.
Knowledge of the chemical-physical reactions that determine the main degradation behaviour of artists' alkyd paints represents one of the main problems within the museum exhibitions. The collection and interpretation of these data on degradation phenomena, especially after ozone exposure at different relative humidity values, can be useful for their conservation needs. Therefore, a systematic investigation of these materials may help achieve this goal. Firstly, surface-level identification of the main functional groups of ad hoc created and aged alkyd paints was performed using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). Subsequently, these paints were investigated by pyrolysis-gas chromatography and mass spectrometry (Py-GC/MS), allowing for precise bulk identification of the organic compounds before and after accelerated ageing. A first successful attempt to provide quantitative Py-GC/MS data on alkyd-based paints is here presented and discussed. Comparing the results, it was possible to obtain new insights into the degradation behaviour of alkyd paints when exposed to ozone, allowing us to devise specific preventive and conservation strategies for these artistic materials.


Corrections in saccade endpoints scale to the amplitude of target displacements in a double-step paradigm.
It is widely held that discrete goal-directed eye movements (saccades) are ballistic in nature because their durations are too short to allow for sensory-based online correction. Recent studies, however, have provided evidence that saccadic endpoints can be mediated via online corrections. Specifically, it has been reported that saccade trajectories adapt to the eccentricity of an unexpectedly perturbed target location (i.e., target 'jump' paradigm). If saccades are subject to online correction mechanisms, then the magnitude of such changes should scale to the amplitude of the target jump. To test this hypothesis, saccadic endpoints for trials on which the target jumped one of three amplitudes (Small: 2.5°, Medium: 5.0°, and Large: 7.5°; i.e., Jump trials) immediately after saccade onset were compared with the endpoints of trials in which the target location did not change (i.e., Reference trials). Results showed that primary saccade endpoints for Jump trials were longer than for Reference trials. Importantly, the magnitude of this increase in endpoint scaled with the amplitude of the target jump. Thus, these results support emerging and coalescent evidence that saccade trajectories are subject to online corrections.


Element speciation definitions, analytical methodology, and some examples.
This paper gives definitions related to element speciation and the reasons for the need for speciation. The problems focused on, involve sampling, sample preparation and storage, as well as changes in species information that occur during the use of various separation technologies. However, the potential and advantages of the separation methods in element speciation are also discussed. In addition, problems arising during element detection that are attributable to analytes or mobile-phase composition are outlined, as well as the pronounced advantages of detection by inductively coupled plasma-mass spectrometry (ICP-MS). The combination of the various separation systems with element- or molecule-specific detectors creates problems especially in element speciation. These difficulties are described along with recent developments for overcoming them or for improving their coupling efficiency. Finally, several elements for which the issue of speciation is important are discussed, with examples from some recent publications on arsenic, selenium and iodine speciation.


Risk assessment and resistance inheritance of triflumezopyrim resistance in Laodelphax striatellus.
Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae) is one of the most important insect pests of rice, and it has been able to develop strong resistance to many insecticides. Triflumezopyrim, a new type of mesoionic insecticide developed by Corteva Agriscience, showed high biological activity in controlling piercing-sucking insect pests such as planthopper and leafhopper. In this study, we continuously selected a susceptible laboratory stain (Unsel) of L. striatellus for 16 generations by exposing it to triflumezopyrim in the laboratory. A 45.1-fold triflumezopyrim-resistant strain (Tri-sel) was established, in which cross-resistance to nitenpyram and acetamiprid was not detected. The realized heritability (h2 ) of the Tri-sel strain was estimated at 0.13. The mortalities of the testing F1 (the offspring of a cross between Unsel and Tri-sel strains) suggested that the resistance of L. striatellus to triflumezopyrim was autosomal and incompletely dominant, as well as a polygenic inheritance. In addition, the results of synergist experiment showed that P450s potentially contributed to the triflumezopyrim resistance. The activities of detoxification enzymes in the Unsel and Tri-sel strains indicated that the activity of P450s in the Tri-sel strain was significantly increased, consistent with the results of synergist experiments. Furthermore, 12 P450 genes demonstrated significant up-regulation. L. striatellus has a certain risk of resistance to triflumezopyrim after continuous selection. Triflumezopyrim resistance did not result in cross-resistance to neonicotinoid insecticides. The up-regulation of multiple P450 genes may mediate triflumezopyrim resistance in L. striatellus. © 2022 Society of Chemical Industry.


Teaching pelvic examination technique using professional patients: a controlled study evaluating students' skills.
To compare the skills in pelvic examination technique between students who have had training with professional patients and a control group of students trained using clinical patients. Prospective controlled study. University hospital. Students attending three consecutive courses in obstetrics and gynecology at Karolinska University Hospital. A study group of 53 students received training in pelvic examination with professional patients and was compared with a control group of 34 students who were trained using clinical patients. The students' skills in pelvic examination technique were examined by teachers in a practical test. Students' skills were also evaluated by the students themselves and by the patients who participated in the examination. Students who had training with professional patients were more skilled in performing a pelvic examination and better prepared to examine their own patients than students trained using clinical patients. Training with professional patients is more effective in teaching pelvic examination technique than training with clinical patients. We recommend that the use of professional patients is considered in the training of medical students.


Synthesis and biological evaluation of novel imidazolone derivatives as potential COX-2 inhibitors.
Three novel series of 2-(substituted phenyl)-4-(substituted arylidene)-imidazolone-5-(4H)-ones were derived from the corresponding oxazolones by condensation with different arylamines. Eleven of the synthesized compounds were selected and evaluated for their effect on carrageenan-induced rat paw edema. Compound 4b had the same efficacy as the reference standard (indomethacin), and compounds 3b, 3c, 4a, 4d and 9a showed good to excellent activities, with other compounds only weakly active. The potent compounds were evaluated for their inhibitory activities against COX-2-catalyzed PGE(2) production, with 4a, 4b and 3c showing strong inhibitory activity.


[Human seminal plasma allergy type I].
Human seminal plasma allergy (HSPA) is a rare allergic reaction to specific protein fractions of seminal plasma, whereof PSA seems to be a relevant allergen. Predominantly Type I-immunoreactions can occur. The main symptoms are localized and generalized urticaria and sometimes anaphylactic symptoms. The diagnosis is based on history, skin tests and on the determination of specific IgE-levels for (un)fractionated seminal plasma. Here we report a patient with recurrent episodes of generalized urticaria after unprotected sexual intercourse and positive prick-test-reaction on seminal plasma.


OPTN/SRTR 2017 Annual Data Report: Kidney.
Many positive trends in kidney transplantation were notable in 2017. Deceased donor kidney transplant rates and counts continued to rise, the kidney transplant waiting list declined for the third year in a row after decades of growth, and both short- and long-term allograft survival continued to improve year over year. In total, more than 220,000 patients were living in the United States with a functioning allograft. With 3 years of data available since implementation of the new kidney allocation system, better prediction of longer-term results of the allocation policy changes became possible. The data also reveal several areas in need of improvement and attention. Overall, the challenge of providing adequate access to kidney transplant persisted nationally, with additional dramatic regional variation. The proportion of living donor kidney transplants in both adults and children continued to fall, and racial disparities in living donor kidney transplant grew in the past decade.


Retraction: IL-6 Promotes Cancer Stemness and Oncogenicity in U2OS and MG-63 Osteosarcoma Cells by Upregulating the OPN-STAT3 Pathway.
[This retracts the article DOI: 10.7150/jca.29931.].


Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing SODs expressions.
It is well known that neurons in the dentate gyrus (DG) of the hippocampus are resistant to short period of ischemia. Hyperthermia is a proven risk factor for cerebral ischemia and can produce more extensive brain damage related with mortality rates. The aim of this study was to examine the effect of hyperthermic conditioning (H) on neuronal death, gliosis and expressions of SODs as anti-oxidative enzymes in the gerbil DG following 5 min-transient cerebral ischemia. The animals were randomly assigned to 4 groups: 1) (N+sham)-group was given sham-operation with normothermia (N); 2) (N+ischemia)-group was given 5 min-transient ischemia with N; 3) (H+sham)-group was given sham-operation with H; and 4) (H+ischemia)-group was given 5 min-transient cerebral ischemia with H. H (39±0.5°C) was induced by subjecting the animals to a heating pad for 30 min before and during the operation. In the (N+ischemia)-groups, a significant neuronal death was observed in the polymorphic layer (PL) from 1 day after ischemia-reperfusion. In the (H+ischemia)-groups, neuronal death was also observed in the PL from 1day post-ischemia; the degree of the neuronal death was severer than that in the (N+ischemia)-groups. In addition, we examined the gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti- ionized calcium-binding adapter molecule 1 (Iba-1). GFAP(+) and Iba-1(+) glial cells were much more activated in the (H+ischemia)-groups than those in the (N+ischemia)-groups. On the other hand, immunoreactivities and levels of SOD1 rather than SOD2 were significantly lower in the (H+ischemia)-groups than those in the (N+ischemia)-groups. In brief, on the basis of our findings, we suggest that cerebral ischemic insult with hyperthermic conditioning brings up severer neuronal damage and gliosis in the polymorphic layer through reducing SOD1 expression rather than SOD2 expression in the DG.


Transcriptional regulation of the human Wilms' tumor gene (WT1). Cell type-specific enhancer and promiscuous promoter.
The Wilms' tumor gene, WT1, is expressed in few tissues, mainly the developing kidney, genitourinary system, and mesothelium, and in immature hematopoietic cells. To develop an understanding of the role of WT1 in development and tumorigenesis, we have identified transcriptional regulatory elements that function in transient reporter gene constructs transfected into kidney and hematopoietic cell lines. We found three transcription start sites of the WT1 gene and have identified an essential promoter region by deletion analysis. The WT1 promoter is a member of the GC-rich, TATA-less, and CCAAT-less class of polymerase II promoters. Whereas the WT1 promoter is similar to other tumor suppressor gene promoters, the WT1 expression pattern (unlike Rb and p53) is tissue-restricted. The WT1 GC-rich promoter is promiscuous, functioning in all cell lines tested, independent of WT1 expression. This finding suggests that the promoter is not tissue-specific, but that tissue-specific expression of WT1 is modulated by additional regulatory elements. Indeed, we have identified a transcriptional enhancer located 3' of the WT1 gene > 50 kilobases downstream from the promoter. This orientation-independent enhancer increases the basal transcription rate of the WT1 promoter in the human erythroleukemia cell line K562, but not in any of the other cell lines tested.


Emergency Considerations of Infective Endocarditis.
Although still a rare bacterial infection of the endocardium of the heart, the incidence of infective endocarditis continues to increase with the increased use of intracardiac devices, indwelling lines, and surgical procedures being done on patients. The diagnosis of infective endocarditis remains challenging and requires a high level of suspicion to initiate the appropriate investigation and treatment. Serious complications can still occur despite optimal care, so it is helpful that these patients be managed by a team that includes infectious disease, cardiology, and cardiac surgeons.


Structural disorder throws new light on moonlighting.
A basic mechanism by which individual proteins can increase network complexity is moonlighting, whereby a given protein fulfils more than one function. Traditionally, this phenomenon is attributed to separate binding surfaces of globular, folded proteins but we suggest that intrinsically unstructured proteins (IUPs) might provide radically different mechanisms. Eleven IUPs have been identified that suggest that the structural malleability of IUPs gives rise to unprecedented cases of moonlighting by eliciting opposing (inhibiting and activating) action on different partners or even the same partner molecule. Unlike classical cases, these proteins use the same region or overlapping interaction surfaces to exert distinct effects and employ non-conventional mechanisms to switch function, enabled by their capacity to adopt different conformations upon binding. Owing to the apparent functional benefits, we expect to see many more examples of this parsimonious use of protein material in complex metabolic networks.


Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine carrier Cys residues by glutathionylation.
The mitochondrial carnitine/acylcarnitine carrier (CAC) is essential for cell metabolism since it catalyzes the transport of acylcarnitines into mitochondria allowing the β-oxidation of fatty acids. CAC functional and structural properties have been characterized. Cys residues which could form disulfides suggest the involvement of CAC in redox switches. The effect of GSH and GSSG on the [(3)H]-carnitine/carnitine antiport catalyzed by the CAC in proteoliposomes has been studied. The Cys residues involved in the redox switch have been identified by site-directed mutagenesis. Glutathionylated CAC has been assessed by glutathionyl-protein specific antibody. GSH led to increase of transport activity of the CAC extracted from liver mitochondria. A similar effect was observed on the recombinant CAC. The presence of glutaredoxin-1 (Grx1) accelerated the GSH activation of the recombinant CAC. The effect was more evident at 37°C. GSSG led to transport inhibition which was reversed by dithioerythritol (DTE). The effects of GSH and GSSG were studied on CAC Cys-mutants. CAC lacking C136 and C155 was insensitive to both reagents. Mutants containing these two Cys responded as the wild-type. Anti-glutathionyl antibody revealed the formation of glutathionylated CAC. CAC is redox-sensitive and it is regulated by the GSH/GSSG couple. C136 and C155 are responsible for the regulation which occurs through glutathionylation. CAC is sensitive to the redox state of the cell switching between oxidized and reduced forms in response to variation of GSSG and GSH concentrations.


Hydroxyapatite coating of hip prostheses. Effect on migration into the femur.
We studied two groups of femoral hip prostheses: 43 TiAlV ridged press-fit stems, and 26 with similar stems coated with hydroxyapatite on the proximal half. At one year, radiological measurement showed a mean downward migration of 0.99 mm for the TialV prostheses and 0.12 mm for the HA-coated prostheses (p = 0.0002). Hydroxyapatite coating appeared to provide effective bio-active supplementary fixation.


Association of Shokeir syndrome (congenital universal alopecia, epilepsy, mental subnormality and pyorrhea) and giant pigmented nevus.
The second case of Shokeir syndrome (congenital total permanent alopecia, psychomotor epilepsy, mental retardation and pyorrhea) is described in a Hungarian boy. This syndrome was associated with a giant pigmented nevus in this case.


Somatostatin analogue SMS 201-995 (octreotide) as a possible solution to the dumping syndrome after gastrectomy or vagotomy.
The dumping syndrome, which may follow partial gastrectomy or truncal vagotomy and drainage, may be refractory to treatment. The aim of this study was to determine the effect of the somatostatin analogue, SMS 201-995 (octreotide), on dumping provoked by hypertonic glucose. Ten patients with symptoms and signs of dumping were studied. After a dumping provocation test with placebo, all patients developed severe symptoms: seven patients had early dumping, two had both early and late dumping and one had late dumping alone. With either 50 or 100 micrograms SMS 201-995, the symptoms of early dumping were much reduced in all patients, and those of late dumping were completely abolished. The packed cell volume, pulse and systolic blood pressure changes of early dumping were significantly reduced by SMS 201-995 and the fall in blood glucose in patients with late dumping was abolished. SMS 201-995 may be a useful treatment for early and late dumping.


Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory.
We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. On each occasion, they underwent a series of tasks engaging working memory function in verbal and visuo-spatial domains. Further tasks explored aspects of long-term memory, planning, attention, and perceptual processing. With respect to working memory/executive function, a highly specific pattern of impairment was observed. Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes.


Ratiometric multimodal chemosensors based on cubic silsesquioxanes for monitoring solvent polarity.
We report the multi-functionalized cubic silsesquioxane (POSS) as the ratiometric multimodal chemosensors for monitoring solvent polarity with fluorescence and (19)F NMR. The alteration of the dispersion state of the modified POSS by changing solvent polarity can be reflected into the orthogonal signal responses for the fluorescence and (19)F NMR. In addition, the ratiometric dual monitoring for the enzymatic reaction was performed using the POSS-based chemosensor.


Lamellipodial tension, not integrin/ligand binding, is the crucial factor to realise integrin activation and cell migration.
The molecular clutch (MC) model proposes that actomyosin-driven force transmission permits integrin-dependent cell migration. To investigate the MC, we introduced diverse talin (TLN) and integrin variants into Flp-In™ T-Rex™ HEK293 cells stably expressing uPAR. Vitronectin variants served as substrate providing uPAR-mediated cell adhesion and optionally integrin binding. This particular system allowed us to selectively analyse key MC proteins and interactions, effectively from the extracellular matrix substrate to intracellular f-actin, and to therewith study mechanobiological aspects of MC engagement also uncoupled from integrin/ligand binding. With this experimental approach, we found that for the initial PIP2-dependent membrane/TLN/f-actin linkage and persistent lamellipodia formation the C-terminal TLN actin binding site (ABS) is dispensable. The establishment of an adequate MC-mediated lamellipodial tension instead depends predominantly on the coupling of this C-terminal TLN ABS to the actomyosin-driven retrograde actin flow force. This lamellipodial tension is crucial for full integrin activation eventually determining integrin-dependent cell migration. In the integrin/ligand-independent condition the frictional membrane resistance participates to these processes. Integrin/ligand binding can also contribute but is not necessarily required.


c-FLIP efficiently rescues TRAF-2-/- cells from TNF-induced apoptosis.
For the past 20 years, it has been known that preparations of Tumor Necrosis Factor alpha (TNF) fail to induce apoptosis due to cytoprotective responses that render cells resistant to its cytotoxic activity. Here we show that TRAF-2-/- embryonic fibroblasts express reduced levels of the anti-apoptotic molecule c-FLIP due to extensive degradation of the protein. Reconstitution of TRAF-2-/- EF with c-FLIP is sufficient for resistance to TNF toxicity. Our results strengthen the role of c-FLIP in protecting cells from the cytotoxic effect of TNF and have implication for the treatment of inflammatory and proliferative disorders.


Age-related changes in the subcortical afferents to the medial frontal cortex in mice: a WGA-HRP study.
The subcortical afferent projections to the mediodorsal part of the frontal cortex were studied both qualitatively and quantitatively in young (3 months), adult (12 months) and aged (22 months) Balb/c mice by means of the retrograde transport of wheat germ agglutinine-horseradish peroxidase (WGA-HRP). A progressive decrease in the number of afferents was observed during aging with a differential pattern of reduction as a function of the subcortical structures. In adult mice a large reduction of afferents occurs in the diagonal band of Broca, the posterior thalamic nucleus, the zona incerta, the lateral hypothalamic area, the nuclei of amygdaloid complex, the posterior hypothalamic nucleus, the reticular pontine nucleus, the dorsal and medial raphe nuclei and the dorsal tegmental nucleus. In aged animals, only the anteromedial and mediodorsal thalamic nuclei, as well as the locus coeruleus appear to be clearly affected.


Synergism between chemisorption and unique electron transfer pathway in S-scheme AgI/g-C3N4 heterojunction for improving the photocatalytic H2 evolution.
AgI/g-C3N4 S-scheme heterojunction with a unique electron transfer pathway was developed as a catalyst for H2 evolution. We discussed the behavior of chemisorption and photoexcited charge carriers in photocatalytic reduction on the S-scheme AgI/g-C3N4 heterojunction. It was demonstrated that the path of charge transfer mediated by S-scheme AgI/g-C3N4 heterojunction was favorable for the improvement of electron utilization in photocatalysis. The advantage of S-scheme heterojunction was that the holes in the valence band (VB) of g-C3N4 could recombine with the electrons in the conduction band (CB) of AgI due to the built-in electric field. Electrons on the CB of g-C3N4 and holes on the VB of AgI were preserved for further photocatalytic reaction. Therefore, a distinctive electron transfer pathway was introduced in the S-scheme heterojunction. In addition, the lifetime of charge carriers was prolonged, and the reduced ability of electrons was increased as compared to reference g-C3N4. It not only decreased the energy required for electron excitation, but also reduced the energy consumption for the charge transfer. This paper provided a new strategy to improve the utilization of photogenerated electrons and chemisorption of water for photocatalytic H2O splitting.


Survey of iron prescribing practices for post-partum anaemia.
Treatment for postpartum anaemia frequently entails iron supplementation, but questions remain regarding its optimal dosing, frequency, and efficacy. Our objective was to learn about the current prescribing practices of obstetrical providers at multiple hospitals, including indications and regimens used; further, we sought to understand how these practices are learned. A 10-question web-based survey was developed via expert consensus. The survey was distributed via email to obstetrical providers (including trainees) practising at seven hospitals affiliated with the University of Toronto, including from Obstetrics & Gynaecology (OBGYN), Family Practice (FP-OB) and midwifery. The survey was directly sent to 469 participants and 140 responses were collected from the direct email recruitment pool (response rate 30%). Half of respondents were OBGYN physicians. The most common indication was a post-partum haemoglobin threshold of 90 g/L. Both intravenous and oral formulations were used; the most common oral formulation was ferrous fumarate (77%). Prescribing practices were most commonly shaped using passed-down knowledge. Through this survey, we have learned about the most common post-partum iron supplementation indications, formulations and regimens used in both academic and community hospitals in the greater Toronto area. This insight will help inform future studies investigating the efficacy of oral iron supplementation in the treatment of post-partum anaemia.


Molecular evidence and diversity of the spotted-fever group Rickettsia spp. in small mammals from natural, suburban and urban areas of Eastern Slovakia.
Rickettsiae of the spotted fever group are considered as emerging pathogens; ticks, fleas and mites are known to be their vectors. However, the prevalence and species diversity of rickettsiae in small mammals and the role of these hosts in the circulation of bacteria are much less studied. During 2014-2016, a total of 250 small mammals (Apodemus agrarius, Apodemus flavicollis, Apodemus uralensis, Myodes glareolus, Crocidura leucodon, Crocidura suaveolens, Micromys minutus, Microtus arvalis, Microtus subterraneus, Neomys fodiens and Sorex minutus) were captured in natural, suburban and urban habitats of eastern Slovakia. Ear biopsies of 245 individuals were examined for the presence of SFG rickettsiae by molecular methods. The overall prevalence of Rickettsia spp. in small mammals was 11%. The predominant species, Rickettsia helvetica was confirmed in the striped field mouse (A. agrarius), the yellow-necked mouse (A. flavicollis), the bank vole (M. glareolus) and the common vole (M. arvalis) in natural and suburban habitats, followed by Rickettsia sp. closely related to R. felis identified in A. flavicollis captured in a suburban habitat. Finally, R. slovaca was found in only one yellow-necked mouse (A. flavicollis) captured in a natural habitat, with the sympatric occurrence of Dermacentor marginatus and Dermacentor reticulatus ticks. We assume the presence of R. slovaca especially in sites with the occurrence of Dermacentor spp. All small mammals captured in the urban habitat tested were negative for the presence of rickettsiae. This study brings the first molecular evidence of R. slovaca in a rodent captured in Slovakia. Rickettsia sp. closely related to R. felis was first time detected in A. flavicollis in suburban site of Slovakia. The highest species diversity of rickettsiae was observed in A. flavicollis, and the highest prevalence of bacteria was recorded in M. glareolus. The highest occurrence of rickettsiae-positive small mammals was recorded during the spring and autumn months, May, June and September, respectively. This may be related with the seasonal activity of the tick vectors. This study confirms the long-term persistence of Rickettsia spp. in small mammals in natural and suburban habitats of Slovakia. Some rodent species that have a wider ecological valency may contribute to the maintenance, circulation and dissemination of rickettsiae within and out the natural foci more significantly than those species that have narrower relation to the certain type of habitat.


Sarcoidosis: A rare cause of penile edema.
Reports of penile sarcoidosis are rare in the literature. We describe the case of a male who presented with several months of distal penile swelling and progressive inability to retract the foreskin. Firm, non-tender subcutaneous nodules were palpated near the base of the penis. The patient ultimately underwent penile skin resection, partial scrotal resection, and split thickness skin graft to the penis after failing multiple conservative treatments. Pathology revealed non-caseating granulomatous lesions which in addition to CT chest findings of bilateral hilar adenopathy suggested a diagnosis of penile sarcoidosis.


Effects of race and test preparation resources on standardized test scores, a pilot study.
Little research exists on the relationship between pre-examination resources, race, and standardized test outcomes. This study aimed to determine the effect of test preparation resources and race on test scores. We surveyed medical students at an allopathic institution on the use of test preparation materials and their test scores. Students were grouped by self-identified race. Underrepresented in Medicine (URiM) students were defined as Black/African American (AA), Hispanic/Latino (HL), Native American (NA) and multiple races. Univariate analysis and linear regression were used for statistical analysis. 192 students completed the survey (response rate = 33%). URiM students reported more MCAT attempts than other students. No differences between scores existed between races. There was no association between scores and the use of test preparation resources. We found that URiM students took the MCAT more times than their peers; however, we found no racial/ethnic differences in examination preparation resources or scores.


The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions.
In this work, the full-length hTERT gene was isolated and the sequence of the previously unknown region in intron 6 as well as that of upstream and downstream hTERT regions was determined. We have shown that intron 6 includes a variable number of tandem repeats (VNTR) of a 38 bp sequence, (hTERT-VNTR 6-1). Eight alleles of hTERT-VNTR 6-1 were identified among 103 unrelated individuals, ranging from 27 to 47 repeats. hTERT-VNTR 2-2 is another new 61 bp minisatellite repeat found in intron 2 of hTERT. At least four alleles of hTERT-VNTR 2-2 can be distinguished. Previous studies have described polymorphisms for minisatellites hTERT-VNTR 2-1, a 42 bp repeat in intron 2, and hTERT-VNTR 6-2, a 36 bp repeat in intron 6. These, together with another minisatellite found in intron 12, add up to five such structures within the hTERT gene. The segregation of hTERT minisatellites was analysed in families, revealing that the VNTRs are transmitted through meiosis following a Mendelian inheritance. Minisatellites in hTERT were also analysed in matching normal and cancer tissues from patients with tumors; in one patient with a kidney tumor, the two VNTRs in intron 6 had undergone concomitant rearrangements. This observation suggests that chromosomal rearrangements implicating these VNTRs may be associated with the activation of telomerase expression in cancer cells.


Stem Cell Theory of Cancer: Rude Awakening or Bad Dream from Cancer Dormancy?
To be dormant or not depends on the origin and nature of both the cell and its niche. Similar to other cancer hallmarks, dormancy is ingrained with stemness, and stemness is embedded within dormancy. After all, cancer dormancy is dependent on multiple factors such as cell cycle arrest, metabolic inactivity, and the microenvironment. It is the net results and sum effects of a myriad of cellular interactions, interconnections, and interplays. When we unite all cancer networks and integrate all cancer hallmarks, we practice and preach a unified theory of cancer. From this perspective, we review cancer dormancy in the context of a stem cell theory of cancer. We revisit the seed and soil hypothesis of cancer. We reexamine its implications in both primary tumors and metastatic lesions. We reassess its roles in cell cycle arrest, metabolic inactivity, and stemness property. Cancer dormancy is particularly revealing when it informs us about the mysteries of late relapse, prolonged remission, and second malignancy. It is paradoxically rewarding when it delivers us the promises and power of cancer prevention and maintenance therapy in patient care.


Primary shunt hyperbilirubinemia with secondary iron overload: a case report.
A patient with familial primary shunt hyperbilirubinemia is described. Splenomegaly, arthritis, and iron overload were striking features of the illness.


The prevalence and natural history of periodontal disease in Britain from prehistoric to modern times.
To investigate the prevalence of periodontitis in British populations during the past 3000 years. To discuss the relevance of these findings to modern populations denied access to modern dental treatment. Observation and assessment of periodontal status of skeletal material using a recently developed method of assessment. Archaeological material from various collections throughout UK covering prehistoric, mediaeval and seventeenth to nineteenth century. 504 individuals. The periodontal status of individual septa was recorded as to whether they were healthy, had gingivitis or periodontitis. The prevalence of periodontitis among individuals and populations was assessed. The prevalence of periodontitis appears to have remained virtually constant during the past 3000 years in Britain, despite considerable changes in the oral environment. The significance of these findings in respect of untreated populations in underdeveloped countries today is considerable. It is considered essential that clinical and field studies record and report on oral environmental factors that may mimic or, by themselves, be responsible for periodontal attachment loss.


Physiological changes in circulating mannose levels in normal, glucose-intolerant, and diabetic subjects.
Mannose is an essential hexose that is required for glycoprotein synthesis. Although circulating mannose levels are known to be influenced by metabolic disorders, how physiological levels of mannose fluctuate in normal and diabetic subjects is largely unknown. We describe a new accurate and sensitive assay for determining circulating mannose levels, which we used to measure plasma mannose levels in 273 normal and diabetic (DM) subjects. Our results revealed a clear correlation (r = 0.754) between fasting plasma mannose (FPM) and fasting plasma glucose (FPG) levels. Our mannose assay showed sensitivity and specificity comparable to that seen for hemoglobin A(1c) (HbA(1c)) assay in subjects with impaired glucose tolerance (IGT) or DM whose FPG levels were normal. Mannose levels were found to increase less than glucose levels in response to an oral glucose tolerance test (OGTT). Furthermore, plasma mannose levels did not significantly change following a meal and more closely correlated with the coefficient of variation (CV) of daily glucose levels than did glucose itself. In conclusion, the close correlation between FPM and FPG levels taken together with the small fluctuations seen in plasma mannose in response to glucose suggests that the measurement of mannose using our assay could potentially play a supplementary role in the diagnosis and screening of patients with mild DM.


The LCNetWork: An electronic representation of the mRNA-lncRNA-miRNA regulatory network underlying mechanisms of non-small cell lung cancer in humans, and its explorative analysis.
Advancement in genomics technologies have made it possible to identify the genes and their interaction/regulation involved in NSCLC, but the interaction information are scattered over the literature. Thus, there is a need of assembling all the available interaction/regulation information in a single platform which will provide a complete view of NSCLC mechanisms. Further, analysis of the mechanisms underlying NSCLC in humans would benefit substantially from easy access to an electronic network. We, therefore, used manual literature curation and integrated all the existing knowledge of NSCLC biomarkers (mRNA, lncRNA and miRNA) into a single conceptual platform represented through a biological network, termed the LCNetWork which represents 345 genes (195 mRNA, 46 lncRNA and 104 miRNA) and 500 direct interactions that are crucial to the regulation of NSCLC in humans. Furthermore, through exploratory data analysis, we have reported four mRNAs (PLK1, ZNF300, NKX2-1, and EGR1), one lncRNA (UCA1) and five miRNAs (MIR133B, MIR326, MIR429, MIR451A, and MIR944) and MIR193A/UCA1/EGFR axis crucial to NSCLC mechanisms. The GO results suggested their role in post-transcriptional gene silencing and RNA polymerase II activities as causes leading to cancer metastasis. The LCNetWork provides up-to-date knowledge of the genes and their interaction/regulation information in NSCLC and is capable of revealing multiple cancer-gene landscapes. Additionally, the LCNetWork has been provided in the Network Data Exchange portal as an electronic circuit for growth by community-level effort.


Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time.
Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole-brain coverage with isotropic (2.5 x 2.5 x 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum-intensity projection algorithm. Finally, reconstruction of fiber-tract trajectories i.e., "tractography" was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 x 2.5 x 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols.


Multi-locus species tree of the chub genus Squalius (Leuciscinae: Cyprinidae) from western Iberia: new insights into its evolutionary history.
The phylogenetic relationships of the genus Squalius are believed to be well established based on the mitochondrial cytochrome b gene. Here, we inferred the phylogenetic relationships of all species inhabiting most of the western Iberia river systems using a nuclear multi-locus approach and different species tree methods: concatenation and coalescent-based methods (BEST and minimize-deep-coalescence). The dataset comprised sequences of seven coding and three non-coding regions belonging to seven nuclear genes, which were chosen to cover multiple biological functions: amh, bmp4, ef1a, egr2, irbp, rh and rpl8. We provide evidence for a conflicting topology between the nuDNA species tree and the widely reported mtDNA gene tree. S. pyrenaicus is rendered paraphyletic in all nuDNA species trees, with populations of the Tagus/Colares clustering with S. carolitertii, while populations from the Guadiana, Sado and Almargem form a separate clade. Although a larger sampling size encompassing the full spectrum of Squalius populations in western Iberia is still needed to fully elucidate the phylogeography and species delimitation of this genus, our results suggest that the two S. pyrenaicus clades may represent different species.


The prevalence of pain in a pediatric and young adult cancer population.
The prevalence and nature of pain in the population of children and young adults with malignancy treated by the Pediatric Branch of the National Cancer Institute were assessed over a 6 month period. One hundred and thirty-nine patients were evaluated during 161 in-patient days and 195 out-patient clinic visits. Approximately 50% of the patients assessed in the hospital and 25% of the patients assessed in the out-patient clinic were found to be experiencing some degree of pain at the time of assessment. Therapy-related pain predominated in both in-patients and out-patients; only one-third of the pain experienced by in-patients and less than 20% of the pain experienced by out-patients was due to tumor. Tumor pain was due primarily to bony invasion. In order to control pain in those individuals experiencing pain, narcotic analgesics were being used by one-half of the in-patients and one-third of the out-patients. Overall pain control was good, with the medium visual analogue scale score being 26 mm on a 0-100 mm scale. During the study period 7 patients were identified to have chronic pain for greater than 1 year following eradication of all known tumor from the site of pain. One was receiving massive doses of narcotics (120 mg/day of methadone) apparently out of proportion to his underlying pain.


Association between Helicobacter pylori infection and carotid atherosclerosis in patients with vascular dementia.
Accumulating evidence indicates that various infections contribute to the pathogenesis of atherosclerosis. Helicobacter pylori (Hp) has been implicated as a risk factor of atherosclerosis for stroke and other cardiovascular disease, but limited data exist regarding vascular dementia (VD). This study aimed to investigate the relationship between Hp infection and carotid atherosclerosis in patients with VD. A total of 354 patients who were diagnosed with VD were enrolled. Patients were divided into Hp positive VD group (n=208) and Hp negative VD group (n=156) using the (13)C-urea breath test ((13)C-UBT). Serum YKL-40, a marker for inflammation, were analyzed by ELISA. Traditional atherosclerotic risk factors including age, gender, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (FBG) were collected or detected. Carotid intima-media thickness (CIMT) was determined by color Doppler ultrasound. CIMT values and serum YKL-40 significantly increased in Hp positive VD group in comparison with Hp negative VD group (p<0.05). In Hp positive VD group, serum YKL-40 was positively correlated with CIMT (r=0.412, p<0.05), and the association was independent of traditional atherosclerotic risk factors (β=0.381, p<0.001). CIMT and serum YKL-4 were significantly higher in Hp positive patients than Hp negative patients. Hp-induced inflammation may be a risk factor for atherosclerosis in patients with VD.


Severe depletion of cellular thiols and glutathione-related enzymes of a carmustine-resistant L1210 strain associates with collateral sensitivity to cyclophosphamide.
Cyclophosphamide (CPA) increased the life span of both carmustine (BCNU)-resistant (L1210/BCNU) and BCNU-sensitive L1210 (L1210/0) leukaemic mice; their sensitivity to CPA, however, was extremely different. The BCNU-resistant strain was much more sensitive (collaterally) to CPA than was its sensitive counterpart. The collateral sensitivity was accompanied by a severe reduction in the activity of glutathione-related enzymes and in protein thiol (SH) and non-protein SH levels in BCNU-resistant cells. The activity of glutathione reductase (GSSG-R) was 2 times higher in the L1210/0 cells than in the L1210/BCNU cells. Glutathione-S-transferase (GST) was also almost 2 times more active in the sensitive cells than in the resistant strain. To develop resistance against CPA with a single treatment (60 mg/kg) per passage, the L1210/BCNU strain needed 26 passages, whereas the L1210/0 strain required significantly fewer. The resistance developed against CPA was associated with a moderate elevation of thiols in the L1210/CPA cells, whereas this elevation was approximately 3 times more pronounced in the L1210/BCNU/CPA cells. The severely reduced activity of GST in the L1210/BCNU strain was markedly increased when these cells were made resistant to CPA; the GSSG-R activity, however, remained low, suggesting an irreversible injury of this enzyme by BCNU.


Identifying infectiousness of SARS-CoV-2 by ultra-sensitive SnS2 SERS biosensors with capillary effect.
The current COVID-19 pandemic urges us to develop ultra-sensitive surface-enhanced Raman scattering (SERS) substrates to identify the infectiousness of SARS-CoV-2 virions in actual environments. Here, a micrometer-sized spherical SnS2 structure with the hierarchical nanostructure of "nano-canyon" morphology was developed as semiconductor-based SERS substrate, and it exhibited an extremely low limit of detection of 10-13 M for methylene blue, which is one of the highest sensitivities among the reported pure semiconductor-based SERS substrates. Such ultra-high SERS sensitivity originated from the synergistic enhancements of the molecular enrichment caused by capillary effect and the charge transfer chemical enhancement boosted by the lattice strain and sulfur vacancies. The novel two-step SERS diagnostic route based on the ultra-sensitive SnS2 substrate was presented to diagnose the infectiousness of SARS-CoV-2 through the identification standard of SERS signals for SARS-CoV-2 S protein and RNA, which could accurately identify non-infectious lysed SARS-CoV-2 virions in actual environments, whereas the current PCR methods cannot.


Synthesis of gamma-hydroxyalkyl substituted piperidine iminosugars from D-glucose.
D-Glucose was converted to synthetic equivalent of meso-pentodialdose, namely 3-C-(1'-aminoethyl)-alpha-d-ribo-pentodialdo-1,4-furanose 10 that gives an easy access to manipulate the aldehyde functionalities on either sides to get enantiomeric pair of 3. Thus, reduction of C5-aldehyde followed by hydrolysis of 1,2-acetonide functionality and reductive aminocyclization with C1-aldehyde afforded gamma-1,2-dihydroxyethyl piperidine iminosugar 3. On the other hand, first reductive aminocyclization with C5-aldehyde gave piperidine ring skeleton 12 that on removal of 1,2-acetonide and reduction of C1-aldehyde gave ent-3 while chopping of C1-aldehyde in 12 and reduction afforded gamma-hydroxymethyl piperidine iminosugar 4.


Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].
Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from Venezuelan post-vaccine G1P[8] could have conditioned their re-emergence and a more efficient dissemination into susceptible population. The results suggest that natural fluctuations of genotypes in combination with forces driving the genetic evolution could determine the spread of novel strains, whose long-term effect on the efficacy of available vaccines should be determined.


Informal use of restraint in nursing homes: A threat to human rights or necessary care to preserve residents' dignity?
Use of restraint in nursing homes is highly controversial and fundamentally transgresses human rights and freedom of movement and choice. While different forms of formal restraint use in nursing homes are broadly delineated, the use of informal restraint is less understood. The aim of this article is to identify different kinds of informal restraint, and how staff use informal restraint under which circumstances. This article illuminates informal restraint use based on an ethnographic study in four nursing homes in the Western part of Norway. We have identified five different forms of informal restraint use which are as follows: (1) diversion of residents' attention; (2) white lies; (3) persuasion and interpersonal pressure; (4) offers and finally (5) threats. These different forms of informal restraint are actions by staff against residents' will, limiting residents' freedom of movement and their personal preferences. In addition, we have identified 'grey-zone restraint' which comprises actions by staff towards residents which lie in-between formal and informal restraint. The use of informal restraint can be explained by institutional circumstances such as location, architecture and institutional collectivist constraints in relation to care work. Moreover, and paradoxically, informal restraint can be explained as a consequence of neo-liberal policies with establishment of extended premises for freedom of movement and practices of resident preferences in nursing homes. Informal restraint practices call into question whether these practices are compatible with fundamental human rights and the preservation of residents' dignity.


Determinants of late survival of 105 patients operated for dissection of the aorta.
In the surgery of aortic dissection, only a small section of aorta compared to the extent of the aortic damage, is usually replaced. The disease is not cured by surgery and needs continuous postoperative surveillance and medical therapy. We report the follow-up of 105 patients who were operated upon between January 1970 and April 1986 and discharged from hospital. Overall actuarial survival was 90% at 5 years, 52% at 10 years and 39% at 15 years. There were 20 deaths, mostly (85%) related to cardiovascular causes. Survival times were correlated, using multivariate methods, with several pre-, peri- and postoperative variables to identify significant risk factors and to calculate actuarial survivals. We found that postoperative low output syndrome (p = 0.007) and stroke (p = 0.04) adversely affected survival and that previous aortic disease or operation (p = 0.004) was associated with an increased rate of dissection-related complications. On the contrary, preoperative hypertension was related to a significantly better survival (p = 0.01) and survival free of dissection-related complications (p = 0.001). When dissection was related to hypertension, adequate postoperative medical treatment neutralized the progression of the aortic damage and its consequences. When dissection was not due to hypertension, the observed survival was unsatisfactory, probably because of a more fragile aorta and inadequate medical follow-up therapy.


Melittin induces fusion of unilamellar phospholipid vesicles.
Melittin, the soluble lipophilic peptide of bee venom, causes fusion of phospholipid vesicles when vesicle suspensions are heated or cooled through their thermal phase transition. Fusion was detected using a new photochemical method (Morgan, C.G., Hudson, B. and Wolber, P. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 26-30) which monitors lipid mixing. Electron microscopy and gel filtration confirmed that most of the lipid formed large vesicular structures. Fluorescence experiments with a water-soluble, membrane-impermeable complex of terbium (Wilschut, J. and Papahadjopoulos, D. (1979) Nature 281, 690-692) demonstrate that these ionic contents are released during fusion. The large structures formed by melittin-induced fusion are impermeable to these ions and are resistant to further fusion. This is in contrast to the behavior observed for the cationic detergent cetyltrimethylammonium bromide (CETAB). The large size of the vesicles formed, the extreme speed of the fusion event and the appearance of electron microscope images of the vesicles prior to fusion suggest that the mechanism of the fusion process includes a preaggregation step.


Attributes of the food and physical activity built environments from the Southern Cone of Latin America.
Previous studies have shown the influence of the physical and social environments on the development of obesity and non-communicable diseases (NCD). An obesogenic environment promotes higher dietary energy intakes and sedentary behaviors while limiting opportunities or incentives for active living. This paper presents a dataset with key attributes of the food and physical activity built environment, including green spaces, quality of streets and sidewalks, and different types of food retail outlets in four cities of the Southern Cone of Latin America. A total of 139 representative neighborhoods randomly selected from: Marcos Paz and Bariloche (Argentina), Temuco (Chile) and Canelones-Barros Blancos (Uruguay) were evaluated, where standardized community walks were conducted for direct observation of the built environment. This dataset will contribute valuable data to the evaluation of obesogenic environments in the region, and could be linked to additional ecological information about risk factors for NCDs and socio-economic features from other sources. Understanding environmental influences on cardiovascular risk factors and individual habits may help explain NCD outcomes and plan urban policies.


Tabun scavengers based on hydroxamic acid containing cyclodextrins.
Arrangement of several hydroxamic acid-derived substituents along the cavity of a cyclodextrin ring leads to compounds that detoxify tabun in TRIS-HCl buffer at physiological pH and 37.0 °C with half-times as low as 3 min.


Associations of exposure to polycyclic aromatic hydrocarbons and kidney stones in U.S. general population: results from the National Health and Nutrition Examination Survey 2007-2016.
It has been reported that polycyclic aromatic hydrocarbons (PAHs) exposure was associated with the increasing risk of various diseases. Utilizing the data from the general population of the U.S., we tried to assess the association between PAHs exposure and KS. The dataset was extracted from National Health and Nutrition Examination Survey (NHANES) 2007-2016. The hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) were detected as representative of urinary PAHs. Ranking-based PAHs score was used to evaluate the total PAHs exposure burden. Multivariable logistic regression analyses were performed to assess the association between PAHs exposure and KS after adjusting a series of confounding factors. 8975 eligible participants were included. In multivariable logistic regression analyses, after adjusting confounding variables, 2-hydroxynaphthalene (OR 1.38, 1.16-1.65; p = 0.038) and 9-hydroxyfluorene (OR 1.39, 1.06-1.84, p = 0.019) were still observed to have significant positive correlations with the prevalence of KS, respectively. The incidence of KS increased significantly with the increase of total PAHs burden (p for trend = 0.011). Significant interaction effects were observed in the subgroup of gender (p for interaction < 0.05). Among female participants, PAHs exposure was more significantly correlated with KS. Higher 2-hydroxynaphthalene (OR 1.94, 1.39-2.70; p < 0.001), 1-hydroxyphenanthrene (OR 1.57, 1.07-2.30; p = 0.022) and 2-hydroxyphenanthrene (OR 1.85, 1.11-3.06; p = 0.018) were significantly associated with the increased incidence of KS in women. There is a significant association between a high level of PAHs exposure and increased prevalence of KS. In particular, in the female population, the relationship between PAHs exposure and KS is especially significant.