Crystal structure of a four-stranded intercalated DNA: d(C4).
The crystal structure of d(C4) solved at 2.3-A resolution reveals a four-stranded molecule composed of two interdigitated or intercalated duplexes. The duplexes are held together by hemiprotonated cytosine-cytosine base pairs and are parallel stranded, but the two duplexes point in opposite directions. The molecule has a slow right-handed twist of 12.4 degrees between covalently linked cytosine base pairs, and the base stacking distance is 3.1 A. This is in general agreement with the NMR studies. A biological role for DNA in this conformation is suggested.


Postoperative mortality in cancer patients with preexisting diabetes: systematic review and meta-analysis.
Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers. Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]). Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.


An unusual presentation of alveolar echinococcosis in a 12-yr-old immunocompetent child.
AE is a parasitic disease caused by Echinococcus multilocularis (E.m.). AE is a rare form of echinococcosis and mostly seen in 50- to 70-yr-old patients. Its asymptomatic invasive tumor-like lesion development period, which lasts as much as 20 yr, is too long. Hence, this disease is very rare in children. Herein, we report an AE in a 12-yr-old girl who was not eligible for surgical treatment because of a radiological evaluation of non-resectable lesion and was scheduled for a LT.


Impact of minimally invasive extracorporeal circuits on octogenarians undergoing coronary artery bypass grafting. Have we been looking in the wrong direction?
Minimally invasive extracorporeal circuits (MiECCs) aim at the preservation of physiologic reserves, the impact of which is expected to be most evident in patients in whom these are depleted. In this context, octogenarians present a subpopulation of specific interest. Based on the type of the utilized ECC, we performed a retrospective comparison between all octogenarians (n = 324) who received a primary coronary artery bypass in our institution from 2003 until 2010. An MiECC was used in 52% of patients. Preoperative variables showed that the MiECC patients were older (83 ± 2 vs 82 ± 2 years; P = 0.001), had higher incidence of renal dysfunction (8% vs 3%; P = 0.04), moderately reduced left ventricular function (43 vs 33%; P = 0.07) and lower incidence of unstable angina (20% vs 28%; P = 0.06). To overcome these differences, a propensity score matching was performed and yielded 126 matched pairs of patients. The overall transfusion of packed red blood cells (2.3 ± 2.3 vs 3.4 ± 3.2 units per patint; P = <0.001), the rate of low cardiac output (0% vs 6%; P = 0.01) and the 30-day postoperative mortality (2.4% vs 9.5%; P = 0.02) were all in favour of the MiECC group in the matched patient population. The MiECC concept has shown its benefits regarding both morbidity and mortality in this high-risk patient population. We believe that this beneficial effect finds its reason in a better preservation of physiologic reserves that are essential for a positive outcome in this patient group.


Toxoplasmic myocarditis and polymyositis in patients with acute acquired toxoplasmosis diagnosed during life.
The presence of both toxoplasmic myocarditis and myositis in the same individual has been reported only at autopsy. We report the first case of biopsy-proven toxoplasmic myocarditis and polymyositis simultaneously occurring in the same individual that was diagnosed during life. Results of her toxoplasmic serology were consistent with acute toxoplasmosis. She subsequently developed visual symptoms consistent with toxoplasmic chorioretinitis. She had a positive clinical response to therapeutic agents specific against Toxoplasma gondii. Her toxoplasmic serological profile established the diagnosis of acute toxoplasmosis. A toxoplasmic serological profile should be obtained for patients with myocarditis and/or polymyositis of unclear etiology. Endomyocardial or skeletal muscle tissue biopsies may establish the definitive diagnosis of toxoplasmic myocarditis or polymyositis, respectively. Examination of blood by polymerase chain reaction analysis before antitoxoplasmic treatment and early in the course of primary infection with T. gondii may prove useful.


Sphingomyelin metabolism is developmentally regulated in rat lung.
We investigated several indices involved in sphingomyelin metabolism in developing rat lung. The levels of sphingomyelin gradually increased during lung maturation, with highest levels observed postnatally. The content of sphingosine and ceramide, biologically active sphingomyelin degradation products, did not significantly change in microsomes during the prenatal period, but increased to peak levels in neonatal and adult lung, respectively. Sphingosine content increased 6-fold between the fetal (Day 21) and neonatal period. The developmental profiles of two enzymes involved in sphingomyelin synthesis, serine palmitoyltransferase and sphingomyelin synthase, were similar. Serine palmitoyltransferase activity increased progressively from the fetal to neonatal period, and plateaued at high levels in the adult lung. The activity of serine palmitoyltransferase correlated with the levels of endogenous sphingolipid in lung tissue. Sphingomyelin synthase activity also increased during fetal lung development, but attained highest levels at Day 21 gestation; postnatally, enzyme activity was detected at lower levels. The activities of the sphingolipid hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase, were elevated in fetal lung, thereafter declining to low levels after birth. Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II epithelial cells revealed that these developmental changes in enzyme activities in lung tissue were also occuring globally at the cellular level and were not restricted to any specific cell population. These studies suggest that the developmental increase in lung sphingomyelin content is due to coordinate regulation of enzymes involved in the biosynthesis and degradation of sphingomyelin. These observations also suggest a regulatory role for serine palmitoyltransferase in the generation of long chain sphingoid bases.


An industrial hygiene calibration manifold.
The industrial hygiene calibration manifold provides a continuous, stable, dynamic, reproducible vapor sample in the concentration range of fractional to thousands of parts per million. The principle of operation is the gravimetric determination of the sample diffusion or permeation rate and the measurement of total volumetric flow. The manifold consists of the following components: an organic-free air system, vapor jacketed diffusion-permeation chamber, jacketed multicomponent Venturi-type mixing manifold, exponential dilution flask and jacketed sampling manifold. This manifold can be used to validate or calibrate various industrial hygiene analyses such as charcoal and detector tube technology, impinger techniques, respirator cartridge testing, and various survey instruments.


Source investigation of two outbreaks of skin and soft tissue infection by Mycobacterium abscessus subsp. abscessus in Venezuela.
Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.


Trap placement and attractant choice affect capture and create sex and parity biases in collections of the biting midge, Culicoides sonorensis.
Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae) is the primary North American vector of bluetongue virus (BTV), which can cause high morbidity and mortality in ruminant livestock or wildlife. Worldwide, most Culicoides surveillance relies on light (usually UV) traps typically placed near animals or larval development sites. However, the trapping method can cause sex, species and parity biases in collections. We collected C. sonorensis from three dairies in California using suction traps baited with CO2 , UV light or CO2 + UV placed near animals, wastewater ponds, or in fields. Higher numbers of parous females were collected using CO2 + UV traps, although this difference was only significant on one dairy. UV traps were poor at collecting nulliparous females, but the addition of UV to a trap increased the abundance of males in a collection. Traps set in open fields collected significantly higher numbers of males and females than in either of the other two locations. In some cases, there was a significant interaction between the trap type and site. We discuss the limitations of traditional trapping methodologies for C. sonorensis and make suggestions for vector surveillance.


The importance of timing in optimizing cranial vault remodeling in syndromic craniosynostosis.
The purpose of this study was to gain insight into the impact of age at repair on relapse rates in syndromic patients undergoing cranial vault remodeling. Retrospective chart review was performed for patients surgically treated for syndromic craniosynostosis from 1990 to 2013. Surgical procedures were assigned a Whitaker category based on need for reoperation as follows: no additional surgery required (category I); minor contouring revisions required (II); major revisions required (III); or failure of original surgery (IV). Age at surgery was grouped as follows: younger than 6 months; aged 6 to 9 months; and older than 9 months. Multivariable logistic regression analysis was performed to determine the relationship between age at surgery and need for reoperation by Whitaker category. Fifty-two patients undergoing a total of 65 planned cranial vault remodeling procedures were included. Multivariate logistic regression analysis revealed that patients younger than 6 months at the time of primary surgery carried a 4.10 greater odds (95 percent CI, 1.31 to 12.87; p = 0.016) of requiring a subsequent major reoperation, and being older than 9 months of age carried a 13.2 greater odds (95 percent CI, 1.39 to 124.30; p = 0.024) of requiring a subsequent minor revision. Timing of surgery is an important factor to consider when planning vault remodeling in syndromic craniosynostosis. Based on our institution's experience, when there is no concern for elevated intracranial pressure the ideal operative window for these procedures in the syndromic population appears to be 6 to 9 months of age.


Identification of Oral Bacterial Biosynthetic Gene Clusters Associated with Caries.
Small molecules are a primary communication media of the microbial world, and play crucial, yet largely unidentified, roles in microbial ecology and disease pathogenesis. Many small molecules are produced by biosynthetic gene clusters, which can be predicted and analyzed computationally given a genome. A recent study examined the biosynthetic repertoire of the oral microbiome and cross-referenced this information against the disease status of the human host, providing leads for biosynthetic gene clusters, and their natural products, which may be key in the oral microbial ecology affecting dental caries and periodontitis. This chapter provides a step-by-step tutorial to bioinformatically to locate biosynthetic gene clusters within genomes, predict the type of natural products that are produced, and cross-reference the identified biosynthetic gene clusters to microbiomes associated with disease or health.


The DNA-binding protease, CND41, and the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase in senescent leaves of tobacco.
Plastids bear their own genome, organized into DNA-protein complexes (nucleoids). Recently, we identified a DNA-binding protease (CND41) in the chloroplast nucleoids of cultured tobacco (Nicotiana tabacum L.) cells. In this study, we examine the biochemical function of this novel DNA-binding protease, particularly in senescent leaves, because antisense tobacco with a reduced amount of CND41 showed retarded senescence. Nitrogen-depletion experiments clearly showed that CND41 antisense tobacco maintained green leaves and constant protein levels, especially ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), throughout the whole plant, whereas wild-type tobacco showed marked senescence and the reduction of protein levels in the lower leaves. In vitro analyses confirmed that CND41 showed proteolytic activity at physiological pH when denatured Rubisco was used as the substrate. These results suggest that CND41 is involved in Rubisco degradation and the translocation of nitrogen during senescence. The possible regulation of protease activity of CND41 through DNA-binding is discussed.


Human alpha 1-microglobulin: its measurement and clinical significance.
alpha 1-Microglobulin (alpha 1-M), also called protein HC, is a low-molecular-weight (LMW) glycoprotein (about 30 kDa) with unique physicochemical properties. Using purified urinary alpha 1-M a standard and specific antibody against alpha 1-M, an assay system for alpha 1-M was developed, and the clinical significance of this protein was investigated by measuring total levels of alpha 1-M under physiological and pathological conditions. alpha 1-M is distributed in various body fluids: in serum, it consists mainly of free LMW alpha 1-M and monomeric IgA-alpha 1-M complex. The total alpha 1-M level in serum and urine usually reflects LMW alpha 1-M variation sensitively, and its determination is quite useful as an indicator of renal glomerulotubular dysfunction and hepatic dysfunction. Serum levels can vary, depending on IgA-alpha 1-M complex level, in parallel with the IgA concentration. The heterogeneity of alpha 1-M purified from different sources of urine by different procedures and underestimation of IgA-alpha 1-M complex by solid-phase antibody assays can be important causes for the discrepancy of serum levels between assays.


Stillbirth Among Patients With Diabetes in Pregnancy in Ethiopia: Systematic Review and Meta-Analysis.
Purpose: Maternal diabetes mellitus and the resulting adverse fetal outcomes including stillbirth in low- and middle-income countries (LMICs) are high. Thus, setting specific evidence is pivotal to plan, evaluate, and improve national preventive measures and to achieve international sustainable development goals. Therefore, this systematic review and meta-analysis was the first of its kind to estimate the pooled prevalence of stillbirth and its determinants among diabetic mothers in Ethiopia. Methods: Primary studies were exhaustively searched using PubMed, ScienceDirect, Web of Science, SCOPUS, and Google Scholar databases, and gray literature found in Addis Ababa and Haramaya University online repositories was accessed. Eligible studies were selected and critically appraised for quality using the Joanna Briggs Institute (JBI) quality appraisal checklist. The overall prevalence of stillbirth among diabetic mothers was estimated using a weighted inverse random-effect model. I 2 statistic was used for evidence of heterogeneity. Egger's test and funnel plot were used to check the presence of publication bias. Results: The pooled prevalence of stillbirth among diabetic mothers was 2.39 [95% confidence interval (CI): -0.20, 4.97]. Being a housewife [adjusted odds ratio (AOR) = 2.25; 95% CI: 1.26, 3.23], maternal age of <30 years [AOR = 2.08 (95% CI: 1.02, 3.13)], and gestational age of <37 completed weeks [AOR = 9.76 (95% CI: 7.83, 11.70)] increased the risk of stillbirth among diabetic mothers. Conclusions: The national pooled prevalence of stillbirth among diabetic mothers was 2.39%. Maternal age of <30 years, gestational age of <37 completed weeks, and being a housewife were significantly associated with stillbirth. Trial registration: PROSPERO 2020: CRD4202016774.


Functionality and substrate specificity of human box H/ACA guide RNAs.
A large number of box H/ACA RNAs have been identified in human cells, and have been predicted to account for nearly all pseudouridylation sites in human rRNAs. However, the function of these mammalian H/ACA RNAs in directing pseudouridylation has been verified experimentally in only two cases. In this study, we used three in vitro reconstitution systems, including yeast and mammalian systems, to test the function of seven H/ACA RNAs guiding16 pseudouridylation sites. Our results verified 12 of these sites; four predictions were incorrect. Further analyses indicated that three components, including the stability of the hairpin structure harboring the pseudouridylation pocket, the stability of guide sequence-target RNA base-pairing interaction, and the distance between the target uridine and the box H or ACA, were critical for the guide function, as changes in these components were sufficient to alter the functionality and specificity of the pseudouridylation pocket. The dynamic functional changes in response to changes in these three important components were further tested in vivo, and the results were completely consistent with the in vitro results. Finally, we compared our results with predictions made by two computer programs, as well as predictions made by human experts using visual inspection. We found that the predictions of one program (snoGPS) agreed with our experimental results with 100% sensitivity (12/12) and 75% specificity (3/4).


Level of decontamination after washing textiles at 60°C or 70°C followed by tumble drying.
Several major outbreaks in healthcare facilities have occurred with the emergence of multi-resistant bacteria. A possible route for dissemination is the hospital textiles and inadequate laundering of them. The aim of this study was to develop an easy-to-use method for simulating the laundering process of hospital textiles, and thereafter apply the method when evaluating the decontaminating efficacy of two different washing temperatures. The laundering process, including tumble drying, took place at two professional laundries. Enterococcus faecium was used as bioindicator. The results showed that a lowering of the washing temperature from 70°C to 60°C did not affect the decontamination efficacy; the washing cycle alone reduced the number of bacteria with 3-5 log10 CFU, whereas the following tumble drying reduced the bacterial numbers with another 3-4 log10 CFU, yielding the same final result independent of washing temperature. Without tumble drying, there was an obvious risk of adding non-fermenting gram-negative bacteria to the fabric. These bacteria originated from the washing cycle. A simple method to simulate hospital laundering was developed. To save energy, it is possible to use a washing temperature of 60°C, but the washing cycle should be followed by tumble drying, and the whole laundering process needs to be monitored to maintain sufficient textile hygiene.


Identifying Cancer Care Team Competencies to Improve Care Coordination in Multiteam Systems: A Modified Delphi Study.
Identifying nontechnical, teamwork competencies (knowledge, skills, and attitudes) underlying coordination within and across the network of teams-or multiteam system (MTS) involved in cancer care is foundational to optimizing high-quality cancer care. A multidisciplinary group of cancer care stakeholders refined an initial list of competency statements during three rounds of a web-based modified Delphi survey. Panelists reached consensus on a final list of four domains and 20 associated team-based competencies important for effective coordination in cancer care MTS. This study provides an initial foundation for testing, modifying, measuring and evaluating the impact of identified competencies on care coordination, outcomes, and costs, for people being screened, treated, or surviving cancer.


Salivary carbonic anhydrase isoenzyme VI is located in the human enamel pellicle.
Salivary carbonic anhydrase (CA VI) appears to protect teeth from caries via mechanisms other than direct regulation of salivary pH and buffering capacity. To elucidate whether CA VI acts in the local microenvironment of the tooth surface, we studied the location and activity of the enzyme in the human enamel pellicle. The study was performed using a specific rabbit antiserum to human CA VI in conjunction with immunostaining and immunoblot techniques. CA activity was demonstrated using a histochemical staining method. CA VI immunostaining of extracted teeth having in vivo formed pellicle showed that the enzyme is present in the enamel pellicle. Immunostaining for salivary alpha-amylase, which is known to be present in the pellicle, showed a similar staining pattern. The presence of CA VI in the enamel pellicle was confirmed by immunoblotting of in vivo formed pellicle proteins. In vitro studies showed that CA VI binds to polished enamel surfaces from both saliva and solutions of purified enzyme. The intensity of the CA VI immunostaining on the enamel surface was dependent on the concentration of the applied enzyme. The histochemical staining of in vitro formed enamel pellicle confirmed that the bound enzyme retains its enzymatic activity. The presence of active CA VI in the human enamel pellicle suggests that it may accelerate the removal of acid by functioning locally in the pellicle layer on dental surfaces.


Long term results of balloon-occluded retrograde transvenous obliteration for portosystemic shunt encephalopathy in patients with liver cirrhosis and portal hypertension.
This study examined 19 patients with portosystemic shunt encephalopathy caused by a splenorenal shunt (SRS), which was treated with balloon-occluded retrograde transvenous obliteration (B-RTO). Long-term treatment outcomes were evaluated based on hepatic functional reserve and vital prognosis. Encephalopathy improved in all patients after shunt embolization and closure. Albumin, serum ammonia, and the Child-Pugh score, a measure of liver function, were significantly improved 3 years after B-RTO, and exacerbation of damage to liver function was avoided (p<0.01). During the follow-up period, three patients died from liver failure and two patients from hepatocellular carcinoma. Patients had a poor prognosis if their albumin levels were less than 2.8 mg / dL before B-RTO (p<0.05). Encephalopathy patients had complete response to B-RTO, but long-term prognosis was affected by hepatic functional reserve before B-RTO and by concurrent hepatocellular carcinoma. The results of this study suggest that in patients with SRS, it is important to perform B-RTO at an early stage when the hepatic functional reserve is still satisfactory.


Effects of closed and open kinetic chain exercises on pain, muscle strength, function, and quality of life in patients with knee osteoarthritis.
Therapeutic exercises are well documented for the treatment of osteoarthritis; there is less evidence on what the effect of closed kinetic chain exercises is for knee osteoarthritis. The aim of this study was to investigate the effects of open kinetic chain exercises and closed kinetic chain exercises on pain, muscle strength, functional status, and quality of life in patients with knee osteoarthritis. The study included a total of 60 patients with primary unilateral knee osteoarthritis grade I and II. The patients were categorized into three groups as open kinetic chain exercises (n=20), closed kinetic chain exercises (n=20), and control group (n=20). The outcome measures, including pain, isokinetic muscle strength, functional status, and quality of life, were collected at baseline and at the end of 6 and 12 weeks. Closed kinetic chain exercises and open kinetic chain exercises had significant improvement in pain, muscle strength, WOMAC, and SF-36 scores after the treatment and at their 6th and 12th week follow-ups compared to their baseline values and compared to the control group (p<0.05). The changes in all outcome measures were similar between closed kinetic chain exercises and open kinetic chain exercises (p>0.05). Closed kinetic chain exercises and open kinetic chain exercises were similar for knee osteoarthritis grade I and II. Closed kinetic chain exercises could be safely added to the exercise programs of patients with low-grade knee osteoarthritis.


Clusters of acidic and hydrophobic residues can predict acidic transcriptional activation domains from protein sequence.
Transcription factors activate gene expression in development, homeostasis, and stress with DNA binding domains and activation domains. Although there exist excellent computational models for predicting DNA binding domains from protein sequence, models for predicting activation domains from protein sequence have lagged, particularly in metazoans. We recently developed a simple and accurate predictor of acidic activation domains on human transcription factors. Here, we show how the accuracy of this human predictor arises from the clustering of aromatic, leucine, and acidic residues, which together are necessary for acidic activation domain function. When we combine our predictor with the predictions of convolutional neural network (CNN) models trained in yeast, the intersection is more accurate than individual models, emphasizing that each approach carries orthogonal information. We synthesize these findings into a new set of activation domain predictions on human transcription factors.


Health-Related Coping and Social Interaction in People with Multiple Sclerosis Supported by a Social Network: Pilot Study With a New Methodological Approach.
Social media are a vital link for people with health concerns who find in Web communities a valid and comforting source for information exchange, debate, and knowledge enrichment. This aspect is important for people affected by chronic diseases like multiple sclerosis (MS), who are very well informed about the disease but are vulnerable to hopes of being cured or saved by therapies whose efficacy is not always scientifically proven. To improve health-related coping and social interaction for people with MS, we created an MS social network (SMsocialnetwork.com) with a medical team constantly online to intervene promptly when false or inappropriate medical information are shared. The goal of this study was to assess the impact of SMsocialnetwork.com on the health-related coping and social interaction of people with MS by analyzing areas of interest through a Web-based survey. Referring to previous marketing studies analyzing the online platform's role in targeted health care, we conducted a 39-item Web-based survey. We then performed a construct validation procedure using a factorial analysis, gathering together like items of the survey related to different areas of interest such as utility, proximity, sharing, interaction, solving uncertainty, suggestion attitude, and exploration. We collected 130 Web-based surveys. The areas of interest analysis demonstrated that the users positively evaluated SMsocialnetwork.com to obtain information, approach and solve problems, and to make decisions (utility: median 4.2); improve feeling of closeness (proximity: median 5); catalyze relationships and text general personal opinions (sharing: median 5.6); get in touch with other users to receive innovative, effective, and practical solutions (interaction, solving uncertainty, and suggestion attitude medians were respectively: 4.1, 3, and 3); and share information about innovative therapeutic approaches and treatment options (suggestion attitude: median: 3.3). SMsocialnetwork.com was perceived by users to be a useful tool to support health-related coping and social interaction, and may suggest a new kind of therapeutic alliance between physicians and people with MS.


Transaortic transcatheter aortic valve implantation as a first-line choice or as a last resort? An analysis based on the ROUTE registry.
Transaortic transcatheter aortic valve implantation (TAo-TAVI) is a recently developed alternative to transapical (TA) or transfemoral (TF) TAVI. We aimed to analyse the effectiveness and safety of TAo-TAVI as a first line approach and to compare it to patients receiving TAo-TAVI as a last resort, which is current practice. ROUTE is a prospective, multicentre registry to assess the clinical outcomes of TAo-TAVI. Patients without contraindications for TA- and TF-TAVI (TAo-first) were compared to patients with contraindications for both of these access routes (TAo-last). Outcome analysis was based on VARC II defined clinical end-points. Three hundred and one patients were included, of which 224 patients met TAo-first and 77 TAo-last criteria. The valve was delivered and catheter retrieved successfully in all patients. In the TAo-first group, rates of conversion to open surgery and requirement for a second valve were low and not different compared to TAo-last patients (1% vs. 3%, P = 0.46 and 1% vs. 3%, P = 0.46, respectively). This was also true for the rate of paravalvular regurgitation (≥ moderate: 4% vs. 3%). All-cause mortality at 30-days was 6% vs. 5% ( P = 0.76), rates of stroke 2% vs. 0% ( P = 0.24), pacemaker implantation (11% vs. 4%, P = 0.093), and life-threatening bleeding 4% vs. 3% ( P = 0.70). Valve safety (both 85%, P = 0.98) and clinical efficacy (80% vs. 82%; P = 0.73) did not differ between groups. Although comparative data to TA and TF procedures were not available in the present analysis, findings suggest that TAo may be considered not only as a last resort strategy when classical access routes are deemed unfeasible, but also as a potential first-line option, with only low rates of paravalvular regurgitation and permanent pacemaker implantation. NCT01991431.


Clinically Driven Alpha/Beta Ratios for Melanoma Brain Metastases and Investigation of Biologically Effective Dose as a Predictor for Local Control After Radiosurgery: A Proof of Concept in a Retrospective Longitudinal Series of 274 Consecutive Lesions.
Brain metastases (BM) develop in nearly half of the patients with advanced melanoma. The aim of this retrospective historical cohort study was to analyze radiological response of melanoma BM to single-fraction Gamma Knife radiosurgery (GKRS), in relation to biologically effective dose (BED) for various alpha/beta ratios. Included in the study were 274 lesions. Primary outcome was local control (LC). Mean marginal dose was 21.6 Gy (median 22, range 15-25). Biologically effective dose was calculated for an alpha/beta ratio of 3 (Gy3), 5 (Gy10), 10 (Gy10), and 15 (Gy15). Receiver operating characteristic value for LC and BED was 85% (most statistically significant odds ratio 1.14 for BED Gy15, P = .006), while for LC and physical dose was 79% (P = .02). When comparing equality of 2 receiver operating characteristic areas, this was statistically significant (P = .02 and .03). Fractional polynomial regression revealed BED (Gy10 and Gy15) as statistically significant (P = .05) with BED of more than 63 Gy10 or 49 Gy15 as relevant, also for higher probability of quick decrease in volume first month after GKRS and lower probability of radiation necrosis. Shorter irradiation time was associated with better LC (P = .001), particularly less than 40 minutes (LC below 90%, P = .05). BED Gy10 and particularly Gy15 were more statistically significant than physical dose for LC after GKRS for radioresistant melanoma BM. Irradiation time (per lesion) longer than 40 minutes was predictive for lower rates of LC. Such results need to be validated in larger cohorts.


Functional screening of willow alleles in Arabidopsis combined with QTL mapping in willow (Salix) identifies SxMAX4 as a coppicing response gene.
Willows (Salix spp.) are important biomass crops due to their ability to grow rapidly with low fertilizer inputs and ease of cultivation in short-rotation coppice cycles. They are relatively undomesticated and highly diverse, but functional testing to identify useful allelic variation is time-consuming in trees and transformation is not yet possible in willow. Arabidopsis is heralded as a model plant from which knowledge can be transferred to advance the improvement of less tractable species. Here, knowledge and methodologies from Arabidopsis were successfully used to identify a gene influencing stem number in coppiced willows, a complex trait of key biological and industrial relevance. The strigolactone-related More AXillary growth (MAX) genes were considered candidates due to their role in shoot branching. We previously demonstrated that willow and Arabidopsis show similar response to strigolactone and that transformation rescue of Arabidopsis max mutants with willow genes could be used to detect allelic differences. Here, this approach was used to screen 45 SxMAX1, SxMAX2, SxMAX3 and SxMAX4 alleles cloned from 15 parents of 11 mapping populations varying in shoot-branching traits. Single-nucleotide polymorphism (SNP) frequencies were locus dependent, ranging from 29.2 to 74.3 polymorphic sites per kb. SxMAX alleles were 98%-99% conserved at the amino acid level, but different protein products varying in their ability to rescue Arabidopsis max mutants were identified. One poor rescuing allele, SxMAX4D, segregated in a willow mapping population where its presence was associated with increased shoot resprouting after coppicing and colocated with a QTL for this trait.


Different relationship of magnocellular-dorsal function and reading-related skills between Chinese developing and skilled readers.
Previous studies have indicated that the relationship between magnocellular-dorsal (M-D) function and reading-related skills may vary with reading development in readers of alphabetic languages. Since this relationship could be affected by the orthographic depth of writing systems, the present study explored the relationship between M-D function and reading-related skills in Chinese, a writing system with a deeper orthography than alphabetic languages. Thirty-seven primary school students and fifty-one undergraduate students participated. Orthographic and phonological awareness tests were adopted as reading-related skill measurements. A steady-pedestal paradigm was used to assess the low-spatial-frequency contrast thresholds of M-D function. Results showed that M-D function was only correlated with orthographic awareness for adults, revealing an enhancement with reading development; while being related to phonological awareness only for children revealing a developmental decrement. It suggested that the mechanism responsible for the relationship between M-D activity and reading-related skills was affected by the characteristics of literacy development in Chinese.


Impact of temperature on sea bass, Dicentrarchus labrax, retina: Fatty acid composition, expression of rhodopsin and enzymes of lipid and melatonin metabolism.
Teleost fish are ectothermic vertebrates. Their metabolism, physiology and behavior rely on the external temperature. This study, on the retina of the sea bass Dicentrarchus labrax, reports on the impact of temperature on the fatty acid composition and mRNA abundance of key enzymes of lipid metabolism: fatty acid desaturase-2 (FADS2), fatty acid elongase-5 (ELOVL5), sterol regulatory element-binding protein-1 (SREBP-1), triglyceride lipase and phospholipase A2 (PLA2). We also report on the effects on the photopigment molecule rhodopsin and on enzymes of the melatonin synthesis pathway, namely arylalkylamine N-acetyltransferases 1a and 1b and acetylserotonin methyltransferase. Juvenile fish were placed for 30 days at 18, 23 or 28 °C. At 23 °C, the fatty acid composition of D. labrax retina showed, as generally reported for the retina of other fish species, particularly high amounts of docosahexaenoic (DHA), palmitic and oleic acids. The fatty acids composition was not significantly (P > 0.05) altered between 23 and 28 °C, but did increase at 18 °C compared to 23 and 28 °C. At 18 °C there were noticeable increases in total DHA, ecosapentaenoic, arachidonic, oleic, linoleic, palmitoleic and stearic acids. A negative correlation was found in the abundance of neutral (NL) vs. polar (PL) lipids: 18 °C induced an increase in NL and a decrease in PL, while 28 °C induced higher PL with decreased NL. In NL the changes affected mainly triglycerides. FADS2 and ELOVL5 mRNA abundance decreased from 18° to 28 °C while SREBP-1 and triglyceride lipase mRNA remained stable. Conversely PLA2 mRNA was more abundant at 23 than at 18 and 28 °C. Temperature increased and decreased rhodopsin mRNA abundance, at 28 °C and 18 °C respectively, while there was no effect on mRNA from the melatonin synthesis enzymes. In conclusion the data indicate a temperature induced redistribution of fatty acids among the lipid classes that might affect the physical properties of the plasma membranes as well as functions associated with photoreception or generation of intracellular second messengers. In addition, the results suggest that temperature targets only the proteins and activities of retinal melatonin production. This study opens new lines of investigation related to the role temperature and fatty acids play in fish visual perception. They are relevant in the context of the global warming of seas affecting both the wild and the aquaculture species.


Enhancing methyl parathion degradation by the immobilization of Burkholderia sp. isolated from agricultural soils.
Organophosphate pesticides are of great interest for research because they are currently the most commonly used pesticides. In this study, a bacterial strain capable of completely degrading methyl parathion (MP) was isolated from agricultural soils in central Mexico. This strain was designated strain S5-2 and was identified as Burkholderia cenocepacia. To increase degradation yields, cells were immobilized on three different supports: powdered zeolite and Opuntia sp. and Agave sp. fibers. The results indicated a significant increase in MP hydrolysis and p-nitrophenol (PNP) degradation with immobilized cells compared to free cell cultures. Furthermore, immobilized cells were capable of withstanding and degrading higher concentrations of PNP compared to cell suspension cultures. The cell viability in the free cell cultures, as well as PNP degradation, was affected at concentrations greater than 25 mg/L. In contrast, cells immobilized on Opuntia sp. and Agave sp. fibers completely degraded PNP at concentrations of 100 mg/L. To verify that MP solution toxicity was decreased by B. cenocepacia strain S5-2 via pesticide degradation, we measured the acetylcholinesterase activity, both before and after treatment with bacteria. The results demonstrate that the activity of acetylcholinesterase was unaffected after MP degradation by bacteria.


Will Mayaro virus be responsible for the next outbreak of an arthropod-borne virus in Brazil?
Mayaro virus is an alphavirus from the Togaviridae family and is transmitted mainly by Hemagogus mosquitoes. This virus circulates in high-density tropical forests or rural areas of Central and South America causing a disease characterized by high-grade fever, maculopapular skin rash and marked arthralgia that, in some patients, can persist for long periods after infection and may be misinterpreted as chikungunya. Although only a few outbreaks involving this virus have been reported, in the last years the number of Mayaro virus infections has increased in the central and northern regions of Brazil. In this review, we describe the reported prevalence of this infection over the years and discuss the circumstances that can contribute to the establishment of an urban mayaro virus epidemic in Brazil and the problems encountered with the specific diagnosis, especially the antigenic cross-reactivity of this pathogen with other viruses of the same family.


Tips from the toolkit: 1 - know yourself.
High performance organisations review their strategy and business processes as part of usual business operations. If you are new to the field of general practice, do you have a career plan for the next 5-10 years? If you are an experienced general practitioner, are you using much the same business model and processes as when you started out? The following article sets out some ideas you might use to have a fresh approach to your professional career. It is based on The Royal Australian College of General Practitioners' 'General practice management toolkit'.


Trichinella spiralis Infection Mitigates Collagen-Induced Arthritis via Programmed Death 1-Mediated Immunomodulation.
Helminth infection induces Th2-biased immune responses and inhibitory/regulatory pathways that minimize excessive inflammation to facilitate the chronic infection of helminth in the host and in the meantime, prevent host hypersensitivity from autoimmune or atopic diseases. However, the detailed molecular mechanisms behind modulation on inflammatory diseases are yet to be clarified. Programmed death 1 (PD-1) is one of the important inhibitory receptors involved in the balance of host immune responses during chronic infection. Here, we used the murine model to examine the role of PD-1 in CD4+ T cells in the effects of Trichinella spiralis infection on collagen-induced arthritis (CIA). Mice infected with T. spiralis demonstrated higher expression of PD-1 in the spleen CD4+ T cells than those without infection. Mice infected with T. spiralis 2 weeks prior to being immunized with type II collagen displayed lower arthritis incidence and significantly attenuated pathology of CIA compared with those of uninfected mice. The therapeutic effect of T. spiralis infection on CIA was reversed by blocking PD-1 with anti-PD-1 antibody, associated with enhanced Th1/Th17 pro-inflammatory responses and reduced Th2 responses. The role of PD-1 in regulating CD4+ T cell differentiation and proliferation during T. spiralis infection was further examined in PD-1 knockout (PD-1-/-) C57BL/6 J mice. Interestingly, T. spiralis-induced alteration of attenuated Th1 and enhanced Th2/regulatory T cell differentiation in wild-type (WT) mice was effectively diminished in PD-1-/- mice characterized by recovered Th1 cytokine levels, reduced levels of Th2 and regulatory cytokines and CD4+CD25+Foxp3+ cells. Moreover, T. spiralis-induced CD4+ T cell proliferation suppression in WT mice was partially restored in PD-1-/- mice. This study introduces the first evidence that PD-1 plays a critical role in helminth infection-attenuated CIA in a mouse model by regulating the CD4+ T cell function, which may provide the new insights into the mechanisms of helminth-induced immunomodulation of host autoimmunity.


Radiotherapy for cancer using X-ray fluorescence emitted from iodine.
Radiation treatment is popular and the apparatus is already available in many hospitals. Conventional radiation treatment by itself is not sufficient to achieve complete cure. Therefore, radiosensitizers have been developed to enhance the therapeutic effects of the treatment. The concept of radiosensitization with high-Z-elements was first considered many decades ago. However, radiosensitizers are not commonly used in the clinical setting. Here, we propose a radiotherapy method that utilizes fluorescent X-ray emissions from iodine. This approach should achieve a greater therapeutic effect than that of conventional radiotherapy treatments. In our radiotherapy, iomeprol was used as the iodine-donor. The X-ray apparatus with copper and aluminum filters could be used for the X-ray irradiation, the apparatus is not needed for exclusive use. The X-ray apparatus is only required to prepare the copper and aluminum filters. As proof-of-concept, we show that tumor growth was attenuated using this treatment with iomeprol.


Effect of ammonium ion and extracellular pH on hybridoma cell metabolism and antibody production.
The effects of NH(4)Cl addition on batch hybridoma cell growth at different external pH values (pH(e)) were investigated in a bioreactor at constant pH and dissolved oxygen concentration. In agreement with measurements in flasks, changes in pH(e) over the range 6.8-7.6 had minor effects on growth. Addition of 3 mM NH(4)Cl had little effect on cell growth while 10 mM NH(4)Cl caused a substantial growth inhibition, Measurements of the effects of pH(e) and NH(4)Cl concentration on cell metabolism gave similar results for cells grown in flasks in an incubator and in the bioreactor. As pH(e) decreases, the integral cell yield on glucose increases. There is a correlation between the effects of pH(e) on glycolysis and previous measurements of its effects on intracellular pH (pH(i)). Increases in NH(4)Cl concentration were previously determined to decrease pH(i) and are shown here to decrease the integral cell yield on glucose. At all pH(e) values in the absence of NH(4)Cl, glutamine is depleted at the time the maximum cell density is reached. Both pH(e) decreases and NH(4)Cl concentration increases lead to decreases in the integral cell yield on glutamine. Changes in pH(e) and in the NH(4)Cl concentration that cause growth inhibition have no effect on the specific antibody production rate for cells grown in flasks in an incubator or in the bioreactor. Changes in the NH(4)Cl concentration have no effect on the quality of the antibody produced, to a first level of characterization.


Consumption of some selected trace elements (Fe, Zn and Cu) and reproductive health of women from the Podkarpackie province.
The objective of the present research study was to estimate the average daily consumption of some selected trace elements (Fe, Zn and Cu) by women of reproductive age and connect it to some aspects of health-oriented behaviour in the Podkarpackie province. We noticed that patients under 30 years of age consumed more examined trace elements (Fe, Zn i Cu) in their daily food rations than patients over 30 years of age.


Leukaemia inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time.
Maternal endometrial leukaemia inhibitory factor (LIF) is required for successful implantation in mice. Mice with homozygous deletions in this gene fail to support implantation. The localization of immunoreactive LIF and the concentration of the mRNA encoding human LIF in normal endometrium during the menstrual cycle were investigated. The amount of RNA was low or undetectable in the proliferative phase but increased by approximately six times in the mid- to late secretory phase. The protein can only be detected by immunocytochemistry in glandular epithelium in the mid- or late secretory phase. To investigate the possible target for the endometrial LIF, we undertook reverse transcription-PCR analysis of early human embryos to determine whether they contain the mRNA encoding the LIF receptor. This study indicated that at the time of implantation in humans, the maternal endometrium produces LIF and that the blastocyst expresses LIF receptor mRNA and therefore may be capable of responding to this signal.


Hormonal and personal effects on estrogen receptors in breast cancer.
Since high estrogen receptor protein in breast cancer tissue has a favorable effect on patient prognosis, factors influencing estrogen receptor levels are the focus of this research. From April 1977 to December 1978, 246 histologically confirmed primary breast cancer patients from three North Carolina hospitals were interviewed and provided with photographic displays of hormonal products. Their tumor tissue was analyzed for estrogen receptor protein by the sucrose density gradient assay. Data were analyzed by multiple regression and logistic regression techniques. No statistically significant relationship was found between gonadal hormone usage and estrogen receptor levels, although recent users of either oral contraceptives or replacement estrogens had lower receptor levels. Users of progestogen-predominant and -intermediate types of oral contraceptives also had lower estrogen receptor protein. An effect of menopausal status, independent of age, was not evident. Statistically significant associations involved age and race among postmenopausal patients. With black breast cancer patients aged less than 70 years as the reference group, the relative odds of having high estrogen receptor protein (greater than 10 fmol/mg of cytosol protein) were 2.4 times greater among whites aged less than 70, 1.6 times greater in blacks aged greater than or equal to 70, and 12.8 times greater in whites greater than or equal to 70 years. These differences in estrogen receptor protein may contribute to the black-white differential in breast cancer survival.


Descriptive modelling to predict deoxynivalenol in winter wheat in the Netherlands.
Predictions of deoxynivalenol (DON) content in wheat at harvest can be useful for decision-making by stakeholders of the wheat feed and food supply chain. The objective of the current research was to develop quantitative predictive models for DON in mature winter wheat in the Netherlands for two specific groups of end-users. One model was developed for use by farmers in underpinning Fusarium spp. disease management, specifically the application of fungicides around wheat flowering (model A). The second model was developed for industry and food safety authorities, and considered the entire wheat cultivation period (model B). Model development was based on observational data collected from 425 fields throughout the Netherlands between 2001 and 2008. For each field, agronomical information, climatic data and DON levels in mature wheat were collected. Using multiple regression analyses, the set of biological relevant variables that provided the highest statistical performance was selected. The two final models include the following variables: region, wheat resistance level, spraying, flowering date, several climatic variables in the different stages of wheat growing, and length of the period between flowering and harvesting (model B only). The percentages of variance accounted for were 64.4% and 65.6% for models A and B, respectively. Model validation showed high correlation between the predicted and observed DON levels. The two models may be applied by various groups of end-users to reduce DON contamination in wheat-derived feed and food products and, ultimately, reduce animal and consumer health risks.


Intestinal lactase as an autologous beta-galactosidase reporter gene for in vivo gene expression studies.
Intestinal lactase has potential as an autologous beta-galactosidase reporter gene for long-term gene expression studies in vivo, using chromogenic, luminescent, and fluorogenic substrates developed for Escherichia coli beta-galactosidase. In normal rat tissues, reactivity with a chromogenic fucopyranoside (X-Fuc, the preferred substrate of lactase) was present only at the lumenal surface of small intestine epithelial cells. Full-length lactase (domains I-IV), mature lactase (domains III and IV), and a cytosolic form of mature lactase (domains III and IV, without the signal sequence or transmembrane region) were evaluated. Transfection of HuH-7 cells in vitro, and hydrodynamic gene delivery to the liver in vivo, resulted in excellent gene expression. The full-length and mature (homodimeric, membrane-bound) forms reacted strongly with X-Fuc but not with the corresponding galactopyranoside (X-Gal). However, the presumptively monomeric cytosolic lactase unexpectedly reacted equally well with both substrates. The fluorogenic substrate fluorescein-di-beta-D-galactopyranoside was cleaved by cytosolic lactase, but not by full-length or mature lactase. Full-length lactase, when expressed ectopically in hepatocytes in vivo, localized exclusively to the bile canalicular membrane. Intestinal lactase is highly homologous in mice, rats, and humans and has considerable potential for evaluating long-term gene expression in experimental animals and the clinic.


The prevalence of enterobiasis in children attending mobile health clinic of Huachiew Chalermprakiet University.
A cross sectional survey of Enterobius vermicularis was carried out in 808 children in the Bangkok metropolis and nearby provinces. This was accomplished in a mobile health clinic from Huachiew Chalermprakiet University provided for communities in the areas during April 1999 to May 2000. Children 5-10 years of age were investigated for infestation of Enterobius vermicularis. Diagnosis was done by means of the transparent tape swab technique to recover eggs in the perianal region for examination under a light microscope. The average infection rate in children was 21.91%. The highest infection rate (38.59%) was found in Ang Thong Province, while the lowest one (11.66%) was found in Chonburi Province. The rate of infection seemed to relate to household environmental factors. The infection rate was significantly higher (p<0.05) in agricultural areas and areas farthest from urban Bangkok. Industrial and urban areas had the lower rates of infection. There was no significant difference (p>0.05) in the incidence of infection between males and females.


Low bone mineral density and associated risk factors in HIV-infected patients.
Aging of persons with human immunodeficiency virus (HIV) resulted in high rates of osteopenia and osteoporosis. Multiple cohort studies have reported an increased prevalence of bone demineralization among HIV-infected individuals. The aim of this study was to evaluate bone mineral density (BMD) and risk factors for osteopenia/osteoporosis among HIV-positive patients attending the National Institute for Infectious Diseases "Prof.Dr. Matei Balș", Bucharest, Romania. We performed a cross-sectional study that enrolled 60 patients with HIV. The association between BMD and lifestyle habits (smoking), body mass index (BMI), nadir cluster of differentiation 4 (CD4) cell count, current CD4 cell count, HIV viral load and history of combination antiretroviral therapy (cART) were investigated. The BMD was measured at the lumbar spine, hips and total body using dual-energy X-ray absorptiometry (DEXA). In the present study, DEXA evaluation showed an overall prevalence of osteoporosis of 16.66% (ten patients) and a prevalence of osteopenia of 48.33% (29 patients). In men, low BMI and cigarette smoking showed significant association with the diagnosis of lumbar spine demineralization (p=0.034 and p=0.041, respectively). Duration of exposure to cART classes in relation to BMD was also evaluated. The use of non-nucleoside reverse-transcriptase inhibitors (NNRTIs) was associated with low lumbar spine BMD in all patients (p=0.015). Reduced BMD was significantly associated with protease inhibitors (PIs)-containing treatment (p=0.043) in women. At lumbar spine DEXA, male gender was statistically associated with reduced BMD. At the left hip Ward's area, decreased BMD T scores were significantly associated with aging. The reduced BMD was higher in patients receiving PI- or NNRTI-containing regimens.


Malignant mixed müllerian tumor of the fallopian tube.
Malignant mixed müllerian tumor of the fallopian tube is an extremely rare neoplasm, with less than 30 cases reported. Clinical signs and symptoms are usually nonspecific and include lower abdominal pain, fever, and vaginal bleeding. The age at diagnosis varies from 14 to 76 years, with a mean of 55 years. Prognosis is poor, with only one woman surviving more than five years. Surgery is the treatment of choice, although chemotherapy may be of some benefit.


Inhibition of alcohol self-administration by positive allosteric modulators of the GABAB receptor in rats: lack of tolerance and potentiation of baclofen.
Treatment with positive allosteric modulators (PAMs) of the GABAB receptor (GABAB PAMs) inhibits several alcohol-motivated behaviors in rodents, including operant, oral alcohol self-administration. The present study assessed the effects of (a) repeated administration of the GABAB PAMs, GS39783, and rac-BHFF and (b) a combination of an ineffective dose of either GS39783, or rac-BHFF, and an ineffective dose of the prototypic GABAB receptor agonist, baclofen, on operant, oral alcohol self-administration. Studies were conducted using selectively bred Sardinian alcohol-preferring (sP) rats exposed to a standard procedure of fixed ratio (FR) 4 (FR4) schedule of reinforcement for 15 % (v/v) alcohol. Repeated treatment with GS39783 (50 mg/kg, i.g.) or rac-BHFF (50 mg/kg, i.g.) produced an initial 40 % reduction in number of lever responses for alcohol and amount of self-administered alcohol that was maintained unaltered throughout the 10-day period of the GS39783 treatment and increased throughout the 5-day period of the rac-BHFF treatment. Combination of per se ineffective doses of GS39783 (5 mg/kg, i.g.), or rac-BHFF (5 mg/kg, i.g.), and baclofen (1 mg/kg, i.p.) reduced, by 35-45 %, both number of lever responses for alcohol and amount of self-administered alcohol. GS39783 and rac-BHFF (a) reduced alcohol reinforcing properties when given repeatedly, with no development of tolerance, and (b) potentiated baclofen effect. Both sets of data possess translational interest, as they suggest potential effectiveness of GABAB PAMs under chronic treatment and selective potentiation of baclofen effect.


A 69-year-old man with excessive sweating of the right hemithorax.
The pure autonomic failure is a rare entity, with only a few cases reported in the literature. The authors describe a case with compensatory excessive sweating of the right hemithorax as an initial manifestation of a pure autonomic failure, and the authors review the clinical characteristics of this disease. A 69-year-old man presented excessive sweating of the right hemithorax. Physical examination revealed orthostatic hypotension. No other neurological features were present. The autonomic study showed a low heart rate response to the Valsalva maneuver and reduced supine plasma norepinephrine levels. A pure autonomic failure was diagnosed. Treatment did not improve patient's symptoms. Anhidrosis with asymmetrical compensatory hyperhidrosis can be the only symptom of a pure autonomic failure. The authors highlight an unusual form of presentation of a rare disease, difficult to diagnose if it is not taken into consideration.


Compatibility in the Ustilago maydis-maize interaction requires inhibition of host cysteine proteases by the fungal effector Pit2.
The basidiomycete Ustilago maydis causes smut disease in maize, with large plant tumors being formed as the most prominent disease symptoms. During all steps of infection, U. maydis depends on a biotrophic interaction, which requires an efficient suppression of plant immunity. In a previous study, we identified the secreted effector protein Pit2, which is essential for maintenance of biotrophy and induction of tumors. Deletion mutants for pit2 successfully penetrate host cells but elicit various defense responses, which stops further fungal proliferation. We now show that Pit2 functions as an inhibitor of a set of apoplastic maize cysteine proteases, whose activity is directly linked with salicylic-acid-associated plant defenses. Consequently, protease inhibition by Pit2 is required for U. maydis virulence. Sequence comparisons with Pit2 orthologs from related smut fungi identified a conserved sequence motif. Mutation of this sequence caused loss of Pit2 function. Consequently, expression of the mutated protein in U. maydis could not restore virulence of the pit2 deletion mutant, indicating that the protease inhibition by Pit2 is essential for fungal virulence. Moreover, synthetic peptides of the conserved sequence motif showed full activity as protease inhibitor, which identifies this domain as a new, minimal protease inhibitor domain in plant-pathogenic fungi.


The aetiology of lateral cervical (branchial) cysts: past and present theories.
Four theories have been suggested to explain the aetiology of lateral cervical cysts. Ascherson (1832) suggested that the cysts arose due to incomplete obliteration of branchial cleft mucosa, which remained dormant until stimulated to grow later in life. His (1886) suggested these cysts were vestiges of the precervical sinus. Wenglowski (1912) believed lateral cervical cysts developed from the third pharyngeal pouch (thymopharyngeal duct). A number of investigators during the 19th century noted the close relationship between lateral cervical cysts and lymphoid tissue (Lucke, 1861). Luschka (1848) suggested that cystic degeneration of cervical lymph nodes was the mechanism by which lateral cervical cysts were formed. This theory received little support until King (1949) studied the histology of a large number of lateral cervical cysts and concluded that these cysts resulted from cystic transformation of cervical lymph nodes. The evidence for and against these theories of aetiology is discussed. The debate is centred on a study of 20 patients with lateral cervical cysts operated on in the Department of Otolaryngology, Bedford Hospital, between January 1986 and December 1991. In all twenty cases the wall of the cyst was found to be composed of lymphoid tissue, histologically identical to the present in lymph nodes. The mean age of presentation was 31 years, and in no case was a tract or cord found which connected the cyst to the skin or pharynx. The evidence strongly suggests that lateral cervical cysts develop from the cystic transformation of cervical lymph nodes. Mechanisms by which this may occur are discussed.


Maternal and environmental factors in early cloned embryo development.
Cloning by somatic cell nuclear transfer (SCNT) in mammals has revealed the remarkable ability of an oocyte to reprogram somatic cell nuclei and induce them to recapitulate the developmental program. Despite the success, cloning remains very inefficient. This review summarizes recent observations from cloning in mice that reveal some of the likely causes for the present inefficiency. One cause appears to be the slow pace of reprogramming combined with the early onset of genome transcription, which together cause cloned embryos to elaborate many somatic cell characteristics even before the first cleavage division. The altered phenotypes of cloned embryos render standard embryo culture conditions grossly sub-optimum. Another cause appears to be a hitherto unappreciated contribution of spindle-associated factors to early embryo development. As current procedures remove the spindle and associated factors, cloned embryos lack these factors. These observations are providing new insight into basic mammalian embryology. They also reveal possible changes to protocols that could improve the overall success of cloning.


Efficacy of carbon dioxide, 1-octen-3-ol, and lactic acid in modified Fay-Prince traps as compared to man-landing catch of Aedes aegypti.
The attractants 1-octen-3-ol and lactic acid significantly decreased catches of Aedes aegypti in Townsville, Australia, by 50% in a controlled laboratory environment and by 100% in the field when compared to carbon dioxide baited bidirectional Fay-Prince trap catches. Evaluation of an omnidirectional alteration on a bidirectional Fay-Prince trap revealed no significant improvement in catch size when compared to both the bidirectional trap and man-landing catch (MLC). Cumulative evening MLC (1730-2000 h) was twice that of the morning MLC (0600-0830 h), which has implications on the precise estimation of the man-biting rate. The MLC sampling method is shown to be a quick, simple, effective and cheap alternative to expensive traps in areas not currently experiencing arbovirus transmission.


Bilateral primary congenital glaucoma in monozygotic twins.
Primary congenital glaucoma is an uncommon pediatric ocular disease contributing to a disproportionately high percentage of childhood blindness worldwide. This case report describes bilateral primary congenital glaucoma in monozygotic twins who first presented to an ophthalmologist in Ethiopia at 6 years of age. Both had severe, protracted disease, with only moderate improvement after surgical intervention.


Is cervical disc arthroplasty good for congenital cervical stenosis?
OBJECTIVE Cervical disc arthroplasty (CDA) has been demonstrated to be as safe and effective as anterior cervical discectomy and fusion (ACDF) in the management of 1- and 2-level degenerative disc disease (DDD). However, there has been a lack of data to address the fundamental discrepancy between the two surgeries (CDA vs ACDF), and preservation versus elimination of motion, in the management of cervical myelopathy associated with congenital cervical stenosis (CCS). Although younger patients tend to benefit more from motion preservation, it is uncertain if CCS caused by multilevel DDD can be treated safely with CDA. METHODS Consecutive patients who underwent 3-level anterior cervical discectomy were retrospectively reviewed. Inclusion criteria were age less than 50 years, CCS (Pavlov ratio ≤ 0.82), symptomatic myelopathy correlated with DDD, and stenosis limited to 3 levels of the subaxial cervical (C3-7) spine. Exclusion criteria were ossification of the posterior longitudinal ligament, previous posterior decompression surgery (e.g., laminoplasty or laminectomy), osteoporosis, previous trauma, or other rheumatic diseases that might have caused the cervical myelopathy. All these patients who underwent 3-level discectomy were divided into 2 groups according to the strategies of management: preservation or elimination of motion (the hybrid-CDA group and the ACDF group). The hybrid-CDA group underwent 2-level CDA plus 1-level ACDF, whereas the ACDF group underwent 3-level ACDF. Clinical assessment was measured by the visual analog scales (VAS) for neck and arm pain, Japanese Orthopaedic Association (JOA) scores, and Nurick grades. Radiographic outcomes were measured using dynamic radiographs for evaluation of range of motion (ROM). RESULTS Thirty-seven patients, with a mean (± SD) age of 44.57 ± 5.10 years, were included in the final analysis. There was a male predominance in this series (78.4%, 29 male patients), and the mean follow-up duration was 2.37 ± 1.60 years. There were 20 patients in the hybrid-CDA group, and 17 in the ACDF group. Both groups demonstrated similar clinical improvement at 2 years' follow-up. These patients with 3-level stenosis experienced significant improvement after either type of surgery (hybrid-CDA and ACDF). There were no significant differences between the 2 groups at each of the follow-up visits postoperatively. The preoperative ROM over the operated subaxial levels was similar between both groups (21.9° vs 21.67°; p = 0.94). Postoperatively, the hybrid-CDA group had significantly greater ROM (10.65° vs 2.19°; p < 0.001) than the ACDF group. Complications, adverse events, and reoperations in both groups were similarly low. CONCLUSIONS Hybrid-CDA yielded similar clinical improvement to 3-level ACDF in patients with myelopathy caused by CCS. In this relatively young group of patients, hybrid-CDA demonstrated significantly more ROM than 3-level ACDF without adjacent-segment disease (ASD) at 2 years' follow-up. Therefore, hybrid-CDA appears to be an acceptable option in the management of CCS. The strategy of motion preservation yielded similar improvements of cervical myelopathy to motion elimination (i.e., ACDF) in patients with CCS, while the theoretical benefit of reducing ASD required further validation.


Inhibition of respiratory syncytial virus by RhoA-derived peptides: implications for the development of improved antiviral agents targeting heparin-binding viruses.
The respiratory syncytial virus (RSV) fusion glycoprotein (F) can interact with the small intracellular GTPase RhoA, and peptides derived from RhoA inhibit RSV replication. These observations initially suggested that RhoA-derived peptides might inhibit RSV replication by disrupting an in vivo interaction between RSV F and RhoA. However, recent data indicate that the antiviral activity of RhoA-derived peptides is not due to competitive inhibition of an hypothesized F-RhoA interaction, but is rather a function of the peptides' intrinsic biophysical properties. We summarize here what is known about the mechanism of RSV inhibition by these peptides and give our opinion regarding the potential implications of this work with regards to RSV biology, and to the development of antiviral agents targeting RSV and other enveloped viruses.


Amlodipine/ARB fixed-dose combinations for the treatment of hypertension: focus on amlodipine/olmesartan combination.
The incidence of hypertension continues to increase worldwide and, according to recent estimates, its incidence is approximately 30% of the U.S. population. However, the control of blood pressure (BP) to recommended levels of < 140/90 mmHg for uncomplicated hypertension, recommended in the 7th Report of the Joint National Committee (JNC-7) on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, remains low at 36.8%. Because the level of BP is directly related to cardiovascular and stroke morbidity and mortality, aggressive treatment and control of hypertension are strongly indicated. Since monotherapy alone is not effective for the control of stage 2 hypertension, fixed-dose combination therapy with two complementary drugs has been recommended by the JNC-7 guidelines as initial therapy for subjects with diastolic BP > or = 100 mmHg and systolic BP > or = 160 mmHg. There are several fixed-dose combination preparations already available, each with its individual indications. The recently FDA-approved fixed-dose combinations of amlodipine with either olmesartan or valsartan are very effective in treating hypertension and are safe and well tolerated. In addition to reducing BP, these new fixed-dose combinations have also demonstrated significant reductions in the inciendence of edema associated with amlodipine monotherapy, which makes them more acceptable to patients. In addition, due to the metabolic neutrality of both component drugs, these preparations are preferable for the treatment of hypertensive patients with diabetes or the metabolic syndrome, in addition to other cardiovascular risk factors.


The interaction of the bioinsecticide PA1b (Pea Albumin 1 subunit b) with the insect V-ATPase triggers apoptosis.
PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin, extracted from Legume seeds, with a lethal activity towards several insect pests, such as mosquitoes, some aphids and cereal weevils. This toxin acts by binding to the subunits c and e of the plasma membrane H+-ATPase (V-ATPase) in the insect midgut. In this study, two cereal weevils, the sensitive Sitophilus oryzae strain WAA42, the resistance Sitophilus oryzae strain ISOR3 and the insensitive red flour beetle Tribolium castaneum, were used in biochemical and histological experiments to demonstrate that a PA1b/V-ATPase interaction triggers the apoptosis mechanism, resulting in insect death. Upon intoxication with PA1b, apoptotic bodies are formed in the cells of the insect midgut. In addition, caspase-3 enzyme activity occurs in the midgut of sensitive weevils after intoxication with active PA1b, but not in the midgut of resistant weevils. These biochemical data were confirmed by immuno-histochemical detection of the caspase-3 active form in the midgut of sensitive weevils. Immuno-labelling experiments also revealed that the caspase-3 active form and V-ATPase are close-localized in the insect midgut. The results concerning this unique peptidic V-ATPase inhibitor pave the way for the utilization of PA1b as a promising, more selective and eco-friendly insecticide.


Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease.
Linked hospital admission data for 1968-1983 were used to identify 723 children aged 16 years or less at the time of first admission to any Scottish hospital with an ICD coded diagnosis of Crohn's disease (282) or ulcerative colitis (441). The accuracy of the coded diagnoses was checked by examination of the hospital notes of 144 patients. The coded diagnosis was incorrect in 11/83 coded as Crohn's disease and 13/61 as ulcerative colitis; frequency of incorrect coding did not change significantly with time. Despite an 18% fall in the population aged less than or equal to 16 during this time, the number of new cases of Crohn's disease rose from 10 in 1968 to 28 in 1983. Thus the recorded incidence of Crohn's disease in Scottish children has risen more than three-fold in 16 years, from 6.6 to 22.9 per million (p less than 0.0001), with no difference between the sexes. Parallel data for ulcerative colitis were rendered inaccurate by miscoding of infective gastroenteritis as colitis. In an attempt to reduce this source of error cases aged five years and under were excluded from analysis, resulting in an incidence of 19.1 cases per million aged six to 16 in 1968 and 15.6 in 1983, not a significant change (r = 0.42, p = 0.052). When males and females were analysed separately, however, there was a significant decrease in the incidence of UC in male children (r = -0.4, p = 0.028), with no change for female children (r = 0.1, p = 0.595).


Hypolipidemic activity of 4-phenyl-5,5-dicarbethoxy-2-pyrrolidinone in rodents.
A series of pyrrolidinones have been reported to possess hypolipidemic activity in mice. The most active agent, 4-phenyl-5-5-dicarbethoxy-2-pyrrolidinone, effectively lowered both serum cholesterol and triglyceride levels at 20-30 mg/kg/d. The agent suppressed liver mitochondrial citrate exchange, phosphatidate phosphohydrolase, and sn-glycerol-3-phosphate acyl transferase activities. Lipid content of the liver, small intestine, and serum lipoprotein fractions was reduced by drug treatment, but lipid levels increased in the bile and fecal samples, suggesting the drug accelerated lipid excretion. The mode of action of the pyrrolidinone appears similar to that of the cyclic imides.


High adsorptive properties of covalent triazine-based frameworks (CTFs) for surfactants from aqueous solution.
Carbonaceous covalent triazine-based frameworks from 1,4-dicyanobenzene (CTF-1) can adsorb up to about 4 g g(-1) of the surfactants alkyl polyglycolether, C12EO7 and sodium dodecylsulfate, SDS from aqueous solution (c = 8.0 mmol L(-1)) which is more than 20-times the gravimetric uptake capacity of a carbon black (Printex L from Evonik). This high uptake is due to CTF sheet exfoliation. Taking into account the thermal and chemical stability of CTFs this first surfactant adsorption study with CTFs shows that CTFs are especially interesting for the uptake of substances from solution.


An analysis of peer, self, and tutor assessment in problem-based learning tutorials.
The purpose of this study was to explore self-, peer-, and tutor assessment of performance in tutorials among first year medical students in a problem-based learning curriculum. One hundred and twenty-five students enrolled in the first year of the Bachelor of Medicine and Bachelor of Surgery Program at the University of Queensland were recruited to participate in a study of metacognition and peer- and self-assessment. Both quantitative and qualitative data were collected from the assessment of PBL performance within the tutorial setting, which included elements such as responsibility and respect, communication, and critical analysis through presentation of a case summary. Self-, peer-, and tutor assessment took place concurrently. Scores obtained from tutor assessment correlated poorly with self-assessment ratings (r = 0.31-0.41), with students consistently under-marking their own performance to a substantial degree. Students with greater self-efficacy, scored their PBL performance more highly. Peer-assessment was a slightly more accurate measure, with peer-averaged scores correlating moderately with tutor ratings initially (r = 0.40) and improving over time (r = 0.60). Students consistently over-marked their peers, particularly those with sceptical attitudes to the peer-assessment process. Peer over-marking led to less divergence from the tutor scoring than under-marking of one's own work. According to the results of this study, first-year medical students in a problem-based learning curriculum were better able to accurately judge the performance of their peers compared to their own performance. This study has shown that self-assessment of process is not an accurate measure, in line with the majority of research in this domain. Nevertheless, it has an important role to play in supporting the development of skills in reflection and self-awareness.


Renin-Angiotensin-Aldosterone System in the Pathogenesis of Pregnancy-Induced Hypertension.
Hypertension occurs in 7-10% of pregnant women. Despite the continuous development of medicine, it is still an important risk factor for perinatal mortality of both mothers and fetuses. Pregnant women with hypertension are at greater risk of complications such as: placental abruption, cerebral and cardiac incidents, multiorgan failure, and disseminated intravascular coagulation. The aim of this review was to discuss multilevel disorders of the renin-angiotensin-aldosterone system in the etiopathogenesis of pregnancy-induced hypertension.


Updates on Sturge-Weber Syndrome.
Sturge-Weber syndrome (SWS) is a rare, noninherited neurovascular disorder characterized by abnormal vasculature in the brain, skin, and eye. Patients with SWS characteristically have facial capillary malformation, also known as port-wine birthmark, a leptomeningeal vascular malformation seen on contrast-enhanced magnetic resonance imaging images, abnormal blood vessels in the eye, and glaucoma. Patients with SWS have impaired perfusion to the brain and are at high risk of venous stroke and stroke-like episodes, seizures, and both motor and cognitive difficulties. While the activating R183Q GNAQ somatic mutation is the most common somatic mutation underlying SWS, recent research also implicates that GNA11 and GNB2 somatic mutations are related to SWS. Recent retrospective studies suggest the use of low-dose aspirin and vitamin D in treatment for SWS and prospective drug trials have supported the usefulness of cannabidiol and Sirolimus. Presymptomatic treatment with low-dose aspirin and antiepileptic drugs shows promising results in delaying seizure onset in some patients. This review focuses on the latest progress in the field of research for Sturge-Weber syndrome and highlights directions for future research.


Crosstalk between Aldosterone and Glycation through Rac-1 Induces Diabetic Nephropathy.
Background: Advanced glycation end products (AGEs) interaction with its receptor (RAGE) and aldosterone (Aldo) through the mineralocorticoid receptor (MR) activates Rac-1 and NF-κB independently in diabetic nephropathy (DN). However, the crosstalk of Aldo with AGEs-RAGE is still unresolved. Our study examined the impact of the AGEs-Aldo complex on renal cells and its effect on the RAGE-MR interaction. Methods and results: Glycation of human serum albumin (HSA) (40 mg/mL) with methylglyoxal (10 mM) in the presence of Aldo (100 nM) and aminoguanidine (AG) (100 nM) was performed. Glycation markers such as fructosamine and carbonyl groups and fluorescence of AGEs, pentosidine, and tryptophan followed by protein modification were measured. Renal (HEK-293T) cells were treated with the glycated HSA-Aldo (200 μg/mL) along with FPS-ZM1 and spironolactone antagonists for RAGE and Aldo, respectively, for 24 h. Glycation markers and esRAGE levels were measured. Protein and mRNA levels of RAGE, MR, Rac-1, and NF-κB were estimated. Glycation markers were enhanced with Aldo when albumin was only 14-16% glycated. AGEs-Aldo complex upregulated RAGE, MR, Rac-1 and NF-κB expressions. However, FPS-ZM1 action might have activated the RAGE-independent pathway, further elevating MR, Rac-1, and NF-κB levels. Conclusion: Our study concluded that the presence of Aldo has a significant impact on glycation. In the presence of AGEs-Aldo, RAGE-MR crosstalk exerts inflammatory responses through Rac-1 in DN. Insights into this molecular interplay are crucial for developing novel therapeutic strategies to alleviate DN in the future.


Antibacterial Mode of Eucommia ulmoides Male Flower Extract Against Staphylococcus aureus and Its Application as a Natural Preservative in Cooked Beef.
The research was conducted to elucidate the antibacterial performance and mode of action of Eucommia ulmoides male flower extract (EUMFE) against Staphylococcus aureus and its application as a natural preservative in cooked beef. The antibacterial activity was evaluated by determining the diameter of inhibition zone (DIZ), minimum inhibitory concentration (MIC), and minimum bactericide concentration (MBC). The changes in membrane potential, contents of bacterial DNA and protein, integrity and permeability of the cell membrane, and cell morphology were analyzed to reveal the possible mode of action. The effect of EUMFE on the counts of S. aureus, pH, color, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS) of the cooked beef stored at 4°C for 9 days were studied. The results showed that the DIZ, MIC, and MBC of EUMFE against S. aureus were 12.58 ± 0.23 mm, 40 mg/mL, and 80 mg/mL, respectively. The mode of action of EUMFE against S. aureus included hyperpolarization of cell membrane, decrease in bacterial DNA and protein contents, destruction of cell membrane integrity, increase in cell membrane permeability, and damage of cell morphology. After treatments with EUMFE, the growth of S. aureus and lipid oxidation in cooked beef were significantly inhibited (P < 0.05). The pH and TVB-N values of cooked beef treated with EUMFE were significantly reduced as compared to control group (P < 0.05). The color of cooked beef samples containing EUMFE showed decreased L* and b* values, and increased a* and ΔE* values. Therefore, our findings showed that EUMFE had a good antibacterial effect on S. aureus, and provided a theoretical basis for the application of EUMFE as a natural preservative in the preservation of cooked beef.


The use of intrapartum ultrasound to diagnose malpositions and cephalic malpresentations.
Fetal malpositions and cephalic malpresentations are well-recognized causes of failure to progress in labor. They frequently require operative delivery, and are associated with an increased probability of fetal and maternal complications. Traditional obstetrics emphasizes the role of digital examinations, but recent studies demonstrated that this approach is inaccurate and intrapartum ultrasound is far more precise. The objective of this review is to summarize the current body of literature and provide recommendations to identify malpositions and cephalic malpresentations with ultrasound. We propose a systematic approach consisting of a combination of transabdominal and transperineal scans and describe the findings that allow an accurate diagnosis of normal and abnormal position, flexion, and synclitism of the fetal head. The management of malpositions and cephalic malpresentation is currently a matter of debate, and individualized depending on the general clinical picture and expertise of the provider. Intrapartum sonography allows a precise diagnosis and therefore offers the best opportunity to design prospective studies with the aim of establishing evidence-based treatment. The article is accompanied by a video that demonstrates the sonographic technique and findings.


[Epiphysiodesis and hemiepiphysiodesis : Physeal arrest and guided growth for the lower extremity].
The principals of growth arrest by epiphysiodesis and growth guidance by hemiepiphysiodesis are effective and powerful surgical techniques in pediatric orthopedics. These procedures can be used to correct leg length discrepancies as well as sagittal, coronal and oblique deformities. A differentiation is made between temporary and permanent techniques. The most significant advantage is that these techniques are minimally invasive and have low complication rates compared to acute osteotomy and gradual deformity correction. For optimal outcome an exact preoperative planning is needed to ensure accurate timing of the procedure, especially when permanent epiphysiodesis techniques are used. Although epiphysiodesis and hemiepiphysiodesis around the pediatric knee are most frequently used and can be considered the gold standard treatment of coronal plane deformities and leg length discrepancies, novel techniques for the hip and ankle are increasingly being performed. The successful clinical results with low complications support the broad use of hemiepiphysiodesis and epiphysiodesis for a variety of indications in the growing skeleton with deformities and leg length differences.


Hepatocyte injury by activated neutrophils in vitro is mediated by proteases.
This study determined the mechanism used by neutrophils (PMNs) to induce hepatocellular injury. Neutrophils have been shown to be potent mediators of cell and tissue injury and have been hypothesized to contribute to the hepatic injury that occurs after trauma and infection. Oxygen radical scavengers protect the liver in vivo from inflammatory injury and it has been suggested that PMNs are the source of these toxic oxygen radicals. The specific mechanism used by PMNs to produce hepatocellular damage, however, has not been determined. Neutrophils were cultured in vitro with hepatocytes (HCs) and stimulated with phorbol 12-myristate 13-acetate (PMA) to induce HC injury in the presence of oxygen radical scavengers and protease inhibitors. PMA induced a PMN-mediated HC injury that was dependent on the number of PMNs present and the concentration of PMA. Protease inhibitors reduced the extent of HC injury, while oxygen radical scavengers had no effect. Hydrogen peroxide, directly applied, was able to injure HCs, but only at concentrations greater than those that could be produced by PMA-stimulated PMNs. PMNs are cytotoxic to cultured HCs, predominantly due to the release of proteolytic enzymes, while HCs appear relatively resistant to oxidative injury. Involvement of neutrophil toxic oxygen radicals in hepatic damage in vivo may require impairment of HC antioxidant defenses or may involve injury to nonparenchymal liver cells with secondary effects on HCs.


Usefulness of susceptibility-weighted imaging for voxel placement in MR spectroscopy.
MR spectroscopy is used to provide in vivo biochemical information about cerebral metabolites. Magnetic field homogeneity secondary to anatomic interfaces, hemorrhage, or necrosis may lead to suboptimal MR spectroscopy. Susceptibility-weighted imaging (SWI) can identify field inhomogeneity and could be used to guide MR spectroscopy voxel placement, leading to higher-quality MR spectroscopy examinations.


Probing the Backbone Topology of DNA: Synthesis and Properties of 7',5'-Bicyclo-DNA.
We describe the synthesis and pairing properties of the novel DNA analogue 7',5'-bicyclo(bc)-DNA. In this analogue, the point of attachment of the connecting phosphodiester group is switched from the 3' to the 7' position of the underlying bicyclic sugar unit and is thus in a topological position that is inaccessible in natural DNA. The corresponding phosphoramidite building blocks carrying all natural nucleobases were synthesized and incorporated into oligonucleotides. From Tm experiments of duplexes with complementary DNA and RNA we find that single modifications are generally well tolerated with some variability as to the nature of the nucleobase. Fully modified oligonucleotides show low affinity for RNA and DNA complements. However, they form antiparallel homo-duplexes with similar thermal stability as DNA. CD spectra of the homo-duplexes show distinct changes in the helix conformation compared to natural DNA. A conformational analysis at the ab initio level of the mononucleosides revealed two minimal energy structures which primarily deviate in the conformation of the cyclopentane ring. Molecular dynamics simulation of a 7',5'-bc-DNA homo-duplex revealed a right-handed structure with a smaller helical rise and a significantly wider minor groove compared to DNA. Interestingly, this duplex is characterized by an atypical, alternating 6'-endo/6'-exo conformational pattern of consecutive nucleotides which seems to be responsible for the poor binding to natural nucleic acids.


Historical trends in the mass and chemical species concentrations of coarse particulate matter in the Los Angeles Basin and relation to sources and air quality regulations.
To assess the impact of past, current and proposed air quality regulations on coarse particulate matter (CPM), the concentrations of CPM mass and its chemical constituents were examined in the Los Angeles Basin from 1986 to 2009 using PM data acquired from peer-reviewed journals and regulatory agency database. PM10 mass levels decreased by approximately half from 1988 to 2009 at the three sampling sites examined- located in downtown Los Angeles, Long Beach and Riverside. Annual CPM mass concentrations were calculated from the difference between daily PM10 and PM2.5 from 1999 to 2009. High CPM episodes driven by high wind speed/stagnant condition caused year-to-year fluctuations in the 99th/98th percentile CPM levels. The reductions of average CPM levels were lower than those of PM10 in the same period, therefore the decrease of PM10 level was mainly driven by reductions in the emission levels of PM2.5 (or fine) particles, as demonstrated by the higher annual reduction of average PM2.5 (0.92 microg/m3) compared with CPM (0.39 microg/m3) from 1999 to 2009 in downtown Los Angeles despite their comparable concentrations. This is further confirmed by the significant decrease of Ni, Cr, V and EC in the coarse fraction after 1995. On the other hand, the levels of several inorganic ions (sulfate, chloride and to a lesser extent nitrate) remained comparable. From 1995 to 2008, levels of Cu, a tracer of brake wear, either remained similar or decreased at a smaller rate compared with elements of combustion origins. This differential reduction of CPM components suggests that past and current regulations may have been more effective in reducing fugitive dust (Al, Fe and Si) and combustion emissions (Ni, Cr, V, and EC) rather than CPM from vehicular abrasion (Cu) and inorganic ions (NO3(-), SO4(2-) and Cl(-)) in urban areas. Limited information is currently available to provide the scientific basis for understanding the sources and physical and chemical variations of CPM, and their relations to air quality regulations and adverse health effects. This study investigates the historical trends of CPM mass and its chemical components in the Los Angeles Basin to advance our understanding on the impact of past and current air quality regulations on the coarse fraction of PM. The results of this study will aid policy makers to design more targeted regulations to control CPM sources to ensure substantial protection of public health from CPM exposure. Supplemental Materials: Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of the Air & Waste Management Association for (1) details of the sampling sites and (2) the daily concentrations of high CPM/PM10 episodes.


Prevalence, factors and inequalities in chronic disease multimorbidity among older adults in India: analysis of cross-sectional data from the nationally representative Longitudinal Aging Study in India (LASI).
This study examines the prevalence, patterns and factors of chronic disease-related multimorbidity. Also, this study examines the inequality in the prevalence of multimorbidity among older adults in India. Cross-sectional study; large nationally representative survey data. We have used the first wave of a Longitudinal Ageing Study in India conducted in 2017-2018 across all the 35 states (excluded Sikkim) and union territories in India. This study used information from 31 373 older people aged 60+years in India. The outcome variable for this study is multimorbidity. The study used multinomial logistic regression to examine the risk factors for multimorbidity among older adults. To measure the inequality in multimorbidity, the slope of index inequality and relative index of inequality have been used to understand the ranked-based inequality. Almost one-fourth (24.1%) reported multimorbidity. The relative risk ratio (RRR) of multimorbidity (RRR=2.12; 95% CI=1.49 to 3.04) was higher among higher educated older adults than uneducated older adults. Furthermore, the RRR of multimorbidity (RRR=2.35; 95% CI=2.02 to 2.74) was higher among urban older adults than their rural counterparts. Older adults in the richest wealth quintile were more likely to report multimorbidities (RRR=2.86; 95% CI=2.29 to 3.55) than the poorest older adults. Good self-rated health and no activities of daily living disability were associated with a lower risk of multimorbidities. This study contributes to the comprehensive knowledge of the prevalence, factors and inequality of the chronic disease-related multimorbidity among older adults in India. Considering India's ageing population and high prevalence of multimorbidity, the older adults must be preferred in disease prevention and health programmes, however, without compromising other subpopulations in the country. There is a need to develop geriatric healthcare services in India. Additionally, there is a need to disseminate awareness and management of multimorbidity among urban and highly educated older adults.


HLA-DR alleles among Pakistani patients of coeliac disease.
To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01--DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2 +/- 4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6 +/- 5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n = 23; 92% versus n=31; 21% in controls, p < 0.01) was observed. HLA-DRB1*03 is associated with increased risk of developing coeliac disease.


Teacher Feedback Practices, Student Feedback Motivation, and Feedback Behavior: How Are They Associated With Learning Outcomes?
In spite of much recent theorizing about teacher provision of feedback, relatively fewer studies look at the dynamic relationships between teacher feedback practices, student feedback experience, and their learning outcomes in higher education settings. To fill this gap, this study looked at 308 university students' perceived teacher feedback practices and their feedback experiences in an English Studies course context at a key and non-key university, and explored how teacher feedback, student feedback motivation and feedback behavior were associated with students' course satisfaction and course exam performance. Results showed that students from the key university reported a higher level of teacher feedback use as well as student feedback motivation and behavior. Structural equation modeling (SEM) suggested that in the case of the non-key university, student feedback behavior significantly predicted course satisfaction and course exam results; teacher feedback also indirectly influenced course satisfaction and course exam results. In the case of the key university, while teacher feedback and student feedback behavior each had significant influence on course satisfaction, student feedback behavior showed no direct significant effect on course exam results, and teacher feedback also showed no significant indirect influence on course exam results.