Barriers and facilitators for weight management interventions in breast cancer patients: a systematic review of qualitative studies.
This systematic review and meta-synthesis of qualitative studies provides an overview of barriers and facilitators that breast cancer patients experience in weight management interventions. We included qualitative studies describing barriers and facilitators for weight management interventions as experienced by adult breast cancer patients after the completion of initial treatment . The data was extracted and using thematic analysis. After analysis, eleven themes were determined. Six of those themes could be linked to the Attitude, Social Influence and self Efficacy (ASE)-model. Physical and mental benefits, anticipated regret and a lack of motivation were linked to attitude. Integrating a weight management programme in daily life, stigma and fears were linked to self-efficacy. With regard to the social influence determinant, encouragement and discouragement by family members were developed as a theme. Four additional themes were conducted related to weight management behaviour; external barriers, economic barriers, cultural barriers and physical barriers. In addition, integrating weight management in cancer care was described as a separate theme. Several disease specific issues, including feeling stigmatized after cancer treatment and treatment-related side effects and peer-support should be given specific attention to maximize adherence of weight management programmes.


Two new species of Anisocyrta Foerster (Hymenoptera: Braconidae: Alysiinae) from China.
Two new species of the genus Anisocyrta Foerster, 1863, from China are described and illustrated: Anisocyrta xiaoliyaoae Yao, sp. n. and Anisocyrta cvanachterbergi Yao, sp. n. Anisocyrta is reported from China for the first time. A key to the Palearctic species of the genus Anisocyrta is provided based on the keys of van Achterberg (1986) and Belokobylskij (1998). Type specimens of the two new species are deposited in the Beneficial Insects Institute Collection, Fujian Agriculture and Forestry University, Fuzhou, China (BIIC).


[Risks of specific hyposensitization treatment].
In appropriate cases of diseases mediated by IgE, specific hyposensitization may be a successful way of treatment. According to prospective studies, the risk of side effects ranges between 0.1 and 1% per injection. We report on cases with fatal outcome and suggest suitable strategies in order to avoid serious complications.


Review of the Children's Assessment of Participation and Enjoyment and the Preferences for Activity of Children.
The Children's Assessment of Participation and Enjoyment (CAPE) and Preferences for Activity of Children (PAC) are questionnaire-based assessments that are completed by self-report or by interview. The tool was published in 2004, and unless otherwise cited, all information describing the CAPE and PAC in this paper was obtained from the assessment manual (King et al., 2004) therefore the CAPE and PAC are not referenced except where direct quotations occur or alternate sources are used. The CAPE and PAC were developed using a clearly articulated conceptual model and focus. The CAPE measures multiple dimensions of participation, including participation diversity, intensity, with whom and where participation occurs, and enjoyment. The PAC measures activity preference. Both measures include 55 informal and formal activities that can be organized into five activity types: recreational, active-physical, social, skill-based, and self-improvement. Current evidence supports that the tools' validity and reliability is adequate. The detailed assessment of participation is highly useful for practice and research.


Experiences of UK patients with hepatitis C virus infection accessing phlebotomy: A qualitative analysis.
This study provides an understanding of the experiences and perceptions of phlebotomy in people with infection who have venous damage related to injecting drug use with the aim of improving their care. Narrative interviews were conducted with 10 attendees of a phlebotomy service within an acute Trust in the south-west of England. The participants had hepatitis C infection and poor venous access due to current or former drug use. Interview audiotapes were analyzed, and the themes - conflict, emotional responses, the patient as expert, and offering solutions - were identified. In the context of this study, we discuss the difficulties associated with phlebotomy, which might explain why individuals with hepatitis C infection and venous damage disengage from health services and are less likely to undertake antiviral treatment. This research adds to the literature on phlebotomy for vulnerable groups, and recommends hepatitis C virus clinics within drug agencies, the need to review training and policy, and the development of "phlebotomy passports" to enable continuity of care between services.


A Capillary Zone Electrophoresis Method with Multiresponse Chemometric Optimization for the Simultaneous Determination of Zofenopril Calcium and Hydrochlorothiazide in Presence of Hydrochlorothiazide Major Impurities.
In the present decade, great importance has been focused on the development of green analytical methods (GAM) as eco-friendly techniques. Minimizing the wastes, analysis time, hazardous reagents, sample size and energy are the main important principles for development of GAM. This manuscript describes a green, novel, rapid, accurate and reliable capillary zone electrophoresis method (CZE) for the simultaneous separation and determination of zofenopril calcium (ZOF) and hydrochlorothiazide (HCT) in presence of two major impurities of HCT, namely; chlorothiazide (CT) and salamide (DSA). Uncoated fused-silica capillary (50 μm i.d. × 48.5 cm and 40 cm effective length) was used. The main factors affecting the separation were the buffer concentration, pH of the buffer and applied voltage. Optimization of the experimental conditions was performed by applying response surface methodology (RSM). The experiments were designed using central composite face-centered design (CCD). The model obtained from the design described the linear, non-linear and interaction effects of factors on the responses. The optimum conditions given by the design were running buffer of sodium borate (pH 9.15; 10 mM) and 17 kV as positive mode applied voltage. Upon applying these conditions, baseline separation for the four compounds with short analysis time of 5.0 min was achieved. UV detection was performed at 225.0 nm and the capillary temperature was maintained at 25°C. The method was validated and applied for quantitative determination of the studied drugs according to the International Conference on Harmonization (ICH) guidelines. Good linearity was obtained in the range of 10.0-100.0 μg/mL for both ZOF and HCT. As for CT and DSA (HCT impurities), linearity range was 5.0-100.0 μg/mL. The proposed method was successfully applied for the analysis of these drugs in their synthetic mixtures and in their co-formulated pharmaceutical formulations.


Antimicrobial activity of a series of 1-alkyl-2-(4-pyridyl)pyridinium bromides against Gram-Positive and Gram-Negative bacteria.
To test a series of 1-alkyl-2-(4-pyridyl)pyridinium bromides with alkyl chains containing between 9 and 16 carbons against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia, Acinetobacter baumannii and Pseudomonas aeruginosa) bacteria. Chemical synthesis was based on the reaction of 2,4'-bipyridyl with alkyl bromide. Antimicrobial activity of the bipyridyls was measured by growing bacterial cultures on Mueller-Hinton agar in the presence and absence of inhibitors. The compounds were most active against S. aureus. The most active compounds had alkyl chain lengths of between 11 and 16 carbons. Methicillin-sensitive S. aureus was more susceptible to the inhibitors than methicillin-resistant S. aureus (MRSA). Two subclasses of MRSA existed which differed in their susceptibility to the inhibitors. The susceptibility of MRSA strains to the compounds was increased in the presence of the efflux pump inhibitor reserpine. The activity of the compounds against Gram-negative organisms was increased when the membrane-permeabilizing agent sodium citrate was introduced. Critical micelle concentrations of the compounds were much higher than minimum inhibitory concentrations of the inhibitors. The mechanism of action of the compounds may involve perturbing bacterial membranes. The resistance of some MRSA strains to the compounds may be related to efflux pumps.


Predicting results in the orthoptic treatment of accommodative dysfunction.
A retrospective analysis of the records of 114 orthoptic patients diagnosed as having accommodative dysfunction (accommodative insufficiency, fatigue of accommodation, infacility of accommodation, or spasm of accommodation) has allowed the construction of models of the results of orthoptic treatment. Discriminant analysis completed on various samples of the group provides linearized discriminant functions for the success of the treatment (either total or partial/none) and for the change in accommodative amplitude. These data indicate that linearized discriminant functions using the age and AC/A ratio of the patient are effective in postpredicting the success category of 60% of a calibration sample of 99 patients. Similar functions using the patient's age, initial accommodative amplitude, and blur value of the near positive vergences allow the postprediction of the category of change in accommodative amplitude with treatment (3 D or more vs. 2 D or less). Seventy-eight percent of a sample of 68 patients were correctly classified. The application of these models in predicting the results of treatment of similarly afflicted subjects is discussed.


Reducing the glycemic index or carbohydrate content of mixed meals reduces postprandial glycemia and insulinemia over the entire day but does not affect satiety.
We evaluated the effects of mixed meals differing in glycemic index (GI) and carbohydrate content on postprandial serum glucose and insulin response, hunger, and satiety over the course of a 12-h day. In this randomized crossover trial, 26 overweight or obese adults received four diets in random order (high GI, high carbohydrate [HGI-HC]; high GI, low carbohydrate [HGI-LC]; low GI, high carbohydrate [LGI-HC]; and low GI, low carbohydrate [LGI-LC]). All meals were prepared by a metabolic kitchen. Participants received breakfast, lunch, and dinner over the course of a 12-h day. Primary outcomes were postprandial serum glucose and insulin quantified as area under the curve. Hunger, fullness, and satiety were assessed by visual analog scale. The HGI-LC, LGI-HC, and LGI-LC diets significantly reduced glucose and insulin area under the curve compared with the HGI-HC diet (P < 0.001 for all comparisons). There were no significant differences in ratings of hunger, fullness, or satiety between the different dietary treatments. Reducing the GI or carbohydrate content of mixed meals reduces postprandial glycemia and insulinemia, and these changes can be sustained over the course of an entire day. However, there were no differences in subjective hunger and satiety ratings between the diets. These results demonstrate that maintaining a low GI or glycemic load diet is an effective method of controlling serum glucose and insulin levels.


Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor alpha.
In this paper we investigated how the increase of human estrogen receptor alfa (ERalpha) gene expression may affect breast, osteoblast and osteoclast cells. Increase of ERalpha expression was obtained by interfering with the activity of a negative transcription factor and by removing it with a short and powerful decoy oligonucleotide (RA4-3') mimicking a region of distal promoter C of ERalpha gene. We provide evidence that this decoy was able to induce apoptosis in osteoclasts, but not in osteoblasts and in breast cancer cells, in an estrogen dependent manner. This effect was associated with increase of the levels of Caspase 3 and Fas receptor. Since ERalpha is important in the transcription of different genes and is involved in several pathological processes, including neoplastic and osteopenic diseases, our findings may be of relevance for a possible new therapeutical approach of such diseases.


Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation.
Primary culture of cancer cells is expected to be useful for investigating the biology of cancer and predicting chemosensitivity for individual patients, yet has been hampered by technical difficulties. We recently developed the cancer tissue-originated spheroid (CTOS) method for the primary culture of colorectal cancer cells. In the present study, we applied this system to the primary culture of non-small-cell lung cancer. We used 125 surgical specimens and 18 pleural effusions for CTOS preparation. Partially digested tumor fragments were cultured in a medium for embryonic stem cells. CTOSs were subjected to sensitivity assay and signal transduction assay for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib. We also investigated the effects of growth factors in culturing lung cancer CTOS. The success rate of CTOS preparation from surgical specimens was 80.0%. The CTOS method was also suitable for culturing tumor spheroids from pleural effusions. CTOSs from lung cancer consisted mostly of pure cancer cells. CTOSs and CTOS-derived xenografts retained the characteristics of the original tumors. In vitro assay results showed that EGFR mutation status and expression levels corresponded with erlotinib sensitivity, confirming previous clinical findings. Furthermore, we found that neuregulin 1, a ligand of HER3, potently induced CTOS growth. The CTOS method enables us to obtain primary lung tumor cells of high viability and purity. CTOS could be a new platform for studying lung cancer biology.


Effects of ascorbic acid supplementation on oxidative stress markers in healthy women following a single bout of exercise.
Ascorbic acid is a water-soluble chain breaking antioxidant. It scavenges free radicals and reactive oxygen species (ROS), which are produced during metabolic pathways. Exercise can produce an imbalance between ROS and antioxidants, leading to oxidative stress-related tissue damages. This study was designed to determine the effects of ascorbic acid supplementation on circulating biomarkers of oxidative stress and muscle damage following a single bout of exercise. In a crossover design with a 1 wk. wash-out period, 19 healthy women performed 30 min moderate-intensity cycling after ingesting 1000 mg of ascorbic acid (AA) or placebo. Blood samples were taken immediately before, immediately after and 30 min post-exercise to determine plasma albumin, total protein, glucose, oxidative stress and muscle damage markers. Plasma albumin and total protein levels increased immediately after exercise in placebo alongside slight reductions in glucose (p = 0.001). These effects were absent in AA cohort. Ferric reducing ability of plasma and vitamin C levels in AA cohort significantly increased after exercise (p < 0.05). Superoxide dismutase activity was significantly elevated after exercise (p = 0.002) in placebo but not AA. Plasma malondialdehyde did not change after exercise in placebo but was significantly decreased in AA (p < 0.05). The exercise protocol promoted slight muscle damage, reflected in significant increases in total creatine kinase in all subjects after exercise. On the other hand, plasma C-reactive protein and lactate dehydrogenase remained unchanged. Supplementation with ascorbic acid prior exercise improves antioxidant power but does not prevent muscle damage.


Family income inequalities and trajectories through childhood and self-harm and violence in young adults: a population-based, nested case-control study.
Childhood poverty is associated with elevated later risks for self-directed and externalised violence, but how risks are modified by parental socioeconomic mobility remains unclear. We investigated parental income trajectories during childhood and subsequent risks of self-harm and violent criminality in young adulthood. Using Danish national registers, we delineated a nested case-control study of Danish citizens born from Jan 1, 1982, to Dec 31, 2000, with first hospital-treated self-harm episodes and first violent crime convictions at ages 15-33 years. Each case was matched on age and gender to 25 randomly selected controls. Parental income was assessed in birth-year and at ages 5 years, 10 years, and 15 years. We considered parental age, the child's number of siblings, parental mental health, and parental education to be covariates. We estimated incidence rate ratios (IRRs) by conditional logistic regression inherently adjusted for age, gender, and calendar year; we then made additional adjustments for the covariates considered. We identified 21 267 first episodes of hospital-treated self-harm, to which we matched 531 675 controls, and 23 724 first violent crime convictions, to which we matched 593 100 controls. We observed inverse relationships between parental income and risks for the two outcomes for each of the ages parental income was measured. The longer a child lived in poorer circumstances, the higher their subsequent risks for self-harm and violent criminality, and vice versa for time spent living in affluent conditions. Associations were stronger for violent criminality than for self-harm. Compared with individuals who were born and remained in the most affluent families, all other income trajectories were associated with elevated risks for both outcomes. Those who remained in the least affluent quintile showed the highest risks for self-harm (IRR 7·2, 95% CI 6·6-7·9; 1174 [6%] cases) and for violent criminality (IRR 13·0; 95% CI 11·9-14·1; 1640 [7%] cases). The risk patterns were attenuated, but essentially persisted, after covariate adjustment. For any parental income level at birth, being upwardly mobile was associated with lower risk compared with downward mobility. Parental income represents a multitude of unmeasured familial sociodemographic indices. Tackling the causes of inequality and associated psychosocial and sociocultural challenges to enable upwards socioeconomic mobility could potentially reduce risks for self-directed and externalised violence. European Research Council.


An enzymatically active chimeric HIV-1 reverse transcriptase (RT) with the RNase-H domain of murine leukemia virus RT exists as a monomer.
The existence of retroviral reverse transcriptases as monomers or dimers is rather intriguing. A classical example of the former is murine leukemia virus reverse transcriptase (MuLV RT), while human immunodeficiency virus type 1 (HIV-1) RT represents the latter. A careful scrutiny of the amino acid sequence alignment of the two enzymes pinpoints the region tentatively responsible for this phenomenon. We report here the construction of a chimeric enzyme containing the first 425 amino acid residues from the N-terminal domain of HIV-1 RT and 200 amino acid residues from the C-terminal domain of MuLV RT. The chimeric enzyme exists as a monomer with intact DNA polymerase and RNase-H functions.


Physical genome map of the unicellular cyanobacterium Synechococcus sp. strain PCC 7002.
A physical restriction map of the genome of the cyanobacterium Synechococcus sp. strain PCC 7002 was assembled from AscI, NotI, SalI, and SfiI digests of intact genomic DNA separated on a contour-clamped homogeneous electric field pulsed-field gel electrophoresis system. An average genome size of 2.7 x 10(6) bp was calculated from 21 NotI, 37 SalI, or 27 SfiI fragments obtained by the digestions. The genomic map was assembled by using three different strategies: linking clone analysis, pulsed-field fragment hybridization, and individual clone hybridization to singly and doubly restriction-digested large DNA fragments. The relative positions of 21 genes or operons were determined, and these data suggest that the gene order is not highly conserved between Synechococcus sp. strain PCC 7002 and Anabaena sp. strain PCC 7120.


Field-scale evaluation of phosphorus leaching in acid sandy soils receiving swine waste.
Accurate descriptions of P leaching are important because excess P applied to soils can enter surface water via leaching and subsurface transport, thereby negatively impacting water quality. The objectives of this study were to monitor P leaching in soils with a long-term history of waste application, relate soil solution P concentrations to soil P status, and quantify P leaching losses. Soil solution was monitored for 20 mo with samplers installed at 45-, 90-, and 135-cm depths in two pits (1 x 3 x 1.5 m) in Autryville (loamy, siliceous, thermic Arenic Paleudults) and Blanton (loamy, siliceous, semiactive, thermic Grossarenic Paleudults) soils located in a grazed pasture in Sampson County, NC, which had received swine waste for >20 yr. Maximum soil solution P concentrations at 45 cm exceeded 18 mg L(-1) in both soils. Soil solution P concentrations at 90 cm in the Blanton soil were similar to that at 45 cm indicating low P sorption. Soil solution P concentrations at 90 cm in the Autryville soil averaged 0.05 mg L(-1) compared to 10 mg L(-1) at 45 cm. A split-line model related soil solution P concentration to the degree of phosphorus saturation (DPS), identifying a change point at 45% DPS. Phosphorus movement past 45 cm equaled or exceeded surplus P additions for both soils. Long-term waste applications resulted in DPS > 90%, high soil solution P concentrations, and substantial vertical P movement. Phosphorus leaching should be considered when assessing long-term risk of P loss from waste-amended soils.


Highly enhanced enantioselectivity in the memory of chirality via acyliminium ions.
[reaction: see text] Electrochemical oxidation of N-acylated serine derivative 1b in methanol gave optically active methoxylated compound 2b with an enantiomeric excess of up to 80%. The bulky o-phenyl benzoyl N-protecting group was found to be the main contributing factor for the enhanced enantioselectivity. The mechanistic aspect of this methoxylation reaction was investigated and found to proceed via a retention mechanism.


DENN/MADD/IG20 alternative splicing changes and cell death in Alzheimer's disease.
The potential effects of alternative splicing of death-domain expressing genes and neuronal death have not been determined in Alzheimer's disease (AD). We analyzed DENN/MADD/IG20 (DMI), the complex of four splice variants. IG20 is known to be involved in cell death and the DENN/MADD splice variant (DM-SV) in cell survival in non-neural systems. DENN/MADD (DM) and DENN/MADD splice variant 2 were also included. Using SH-SY5Y human neuroblastoma cultures exposed to high concentrations of oligomeric Aβ peptides (oAβ) as a model for neuronal death, there was initially an increased ratio of DM-SV to IG20 (DM-SV/IG20) and knockdown of DMI SVs including DM-SV with antisense DNA then increased cell death. Cultures transfected with small interfering RNAs (siRNAs) specific to subsets of DMI SVs but sparing DM-SV increased the DM-SV/IG20 ratio resulting in a reduction of cell death in the presence of oAβ. Effects on cell survival of DM and DM SV2, the other two SVs expressed in the CNS, are less clear. Compared to normal controls, alternative splicing changes in the CNS of AD patients during disease progression resulted in altered ratios of all of the SVs in a pattern over an extended time that mirrored that of the cultures, and coincided with the accumulation of endogenous, dimeric Aβ (dAβ). Thus, DM-SV may be required for neuronal survival by protecting against oAβ neurotoxicity, and IG20 may contribute to selective neuronal vulnerability in AD.


The Pursuit of Value in Musculoskeletal Imaging: Policy and Clinical Practice Intersect.
Rapidly rising health care costs coupled with variability in pricing and patient service have led to intense public scrutiny and pressure for health care providers to demonstrate value. Recent changes in legislation and payment models have intensified a shift from volume-based to value-based care, transferring risk from payers to providers. The American College of Radiology's Imaging 3.0 initiative encourages radiologists to become leaders in this changing health care landscape, helping to redefine value relative to health outcomes that matter to patients. Finding value and areas for improvement can prove difficult. However, through the imaging value chain, a plethora of opportunities are easily identifiable. It will be critical for musculoskeletal radiologists to leverage information technology and develop meaningful metrics to assess and demonstrate imaging's contribution to improved patient outcomes and reduction in costs, and to advocate for appropriate reimbursement.


Identification of GGT5 as a Novel Prognostic Biomarker for Gastric Cancer and its Correlation With Immune Cell Infiltration.
Gastric cancer (GC) is a common malignant tumor of the digestive system. Recent studies revealed that high gamma-glutamyl-transferase 5 (GGT5) expression was associated with a poor prognosis of gastric cancer patients. In the present study, we aimed to confirm the expression and prognostic value of GGT5 and its correlation with immune cell infiltration in gastric cancer. First, we compared the differential expression of GGT5 between gastric cancer tissues and normal gastric mucosa in the cancer genome atlas (TCGA) and GEO NCBI databases using the most widely available data. Then, the Kaplan-Meier method, Cox regression, and univariate logistic regression were applied to explore the relationships between GGT5 and clinical characteristics. We also investigated the correlation of GGT5 with immune cell infiltration, immune-related genes, and immune checkpoint genes. Finally, we estimated enrichment of gene ontologies categories and relevant signaling pathways using GO annotations, KEGG, and GSEA pathway data. The results showed that GGT5 was upregulated in gastric cancer tissues compared to normal tissues. High GGT5 expression was significantly associated with T stage, histological type, and histologic grade (p < 0.05). Moreover, gastric cancer patients with high GGT5 expression showed worse 10-years overall survival (p = 0.008) and progression-free intervals (p = 0.006) than those with low GGT5 expression. Multivariate analysis suggested that high expression of GGT5 was an independent risk factor related to the worse overall survival of gastric cancer patients. A nomogram model for predicting the overall survival of GC was constructed and computationally validated. GGT5 expression was positively correlated with the infiltration of natural killer cells, macrophages, and dendritic cells but negatively correlated with Th17 infiltration. Additionally, we found that GGT5 was positively co-expressed with immune-related genes and immune checkpoint genes. Functional analysis revealed that differentially expressed genes relative to GGT5 were mainly involved in the biological processes of immune and inflammatory responses. In conclusion, GGT5 may serve as a promising prognostic biomarker and a potential immunological therapeutic target for GC, since it is associated with immune cell infiltration in the tumor microenvironment.


Real-world treatment patterns, healthcare resource use and clinical outcomes of patients receiving second line therapy for advanced or metastatic gastric cancer.
Second-line (2 L) chemotherapies for advanced or metastatic gastric cancer have shown improved survival but there is no commonly accepted standard of care. This study examines real-world patient characteristics, treatment patterns, healthcare resource use (HCRU) and clinical outcomes in this setting. Retrospective chart reviews were performed at participating institutions from Australia, Canada, Italy and UK for adult patients receiving 2 L treatment for advanced/metastatic disease from January 2013 to July 2015. Data were collected for 12 months or until death. Two hundred eighty patients were included, mean age was 60.9 years and 68.9% were male. Half (51.8%) received monotherapy in 2 L, of whom 69.0% received taxanes. Irinotecan monotherapy was common in Australia (30.0% of monotherapy patients) and Canada (43.8%), but infrequent in Italy and UK. Doublet chemotherapy was used in 36.4% of 2 L patients, most commonly fluoropyrimidine + irinotecan. Use of targeted therapies (trastuzumab, ramucirumab) was infrequent except in Italy. Estimated median real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) from the time of 2 L treatment initiation was 3.09 (95% CI: 2.76-3.68) and 6.54 (5.29-7.76) months, respectively, and estimated 12-month rwPFS and rwOS rate was 8 and 26%, respectively. Only a minority (26.8%) of patients were hospitalized during the follow-up period, with the lowest hospitalization in Italy (16.7%). Laboratory and imaging tests were performed for 93.2 and 70.4%, respectively. About half of patients received monotherapy as 2 L chemotherapy for advanced/metastatic gastric cancer and a third received doublets. Real-world clinical outcomes for 2 L treatment are poor and HCRU is considerable.


Quantitative immunocytochemical analysis of Mn SOD in alveolar type II cells of the hyperoxic rat.
We have analyzed the magnitude and uniformity of the expression of manganese superoxide dismutase (Mn SOD) protein in alveolar type II cells of rats exposed to hyperoxia using quantitative colloidal gold immunocytochemistry and morphometric techniques. Sprague-Dawley rats were exposed continuously to normal air or to 85% oxygen for 7 and 14 days. The lungs were fixed by intratracheal instillation of a paraformaldehyde-glutaraldehyde fixative. Lung samples were dehydrated in ethanol and embedded in LR-White. Thin sections for electron microscopy were labeled with anti-rat Mn SOD rabbit antiserum followed by protein-A gold. The labeling density (gold particles/micron 2) over subcellular compartments was determined, and relative organelle volumes were measured using a random point overlay. The results confirm that alveolar type II cells are a locus of Mn SOD response in the lungs of hyperoxic rats and contribute to this response through a combination of changes: an increase of Mn SOD concentration in the mitochondrial matrix, an increase of mitochondrial volume per cell, and type II cell hyperplasia.


Visual side effects of scopolamine/ dextroamphetamine among parabolic fliers.
Scopolamine/dextroamphetamine has been used to combat motion sickness generated aboard research aircraft for decades. While it has shown to be effective, previous studies differ as to the presence of visual side effects secondary to scopolamine's anticholinergic properties. This study sought to quantify any such effects in order to determine if they are operationally significant. Fliers in NASA's Reduced Gravity Program received a weight-based dose of scopolamine/ dextroamphetamine prior to boarding the aircraft. Measurements of pupil size, visual acuity, and accommodation were taken in identical conditions using subjects' dominant eyes prior to medication administration and again after landing. We enrolled 131 subjects ages 18-48. Pre- and postflight measurements of pupil size and acuity were available for 125 subjects. Average pupil size increased by 1.1 mm (95% CI 0.9-1.2). Only 1.6% of subjects experienced a change in visual acuity of greater than 10 ft. The average near-point accommodation changed from 8.61 to 7.84 diopters, a difference of -0.77 (-1.01 to -0.53) diopters or 1.34 cm (0.87-1.81). Increasing age also correlated significantly with worsening change in accommodation. This study found statistically significant changes in pupil size and near point accommodation that do not appear to be clinically important. No significant decrement in acuity was noted. While direct effects on in-flight performance could not be assessed, the use of scopolamine/dextroamphetamine among fliers aboard research aircraft does not appear to yield visual side effects sufficient to compromise later ground operations.


[Protective Effect of Component Compatibility Sini Decoction on Hypothyroidism Induced Renal Damage in Rats].
To investigate the protective effect of component compatibility Sini Decoction on hypothyroidism induced renal damage in rats. The hypothyroidism model were established by 0.1% propylthiouracil (PTU) solution 10 m/kg for consecutive 15 days. Rats were randomly divided into model group, component compatibility Sini Decoction groups[ CSD 9. 6,4. 8 and 2. 4 g/ (kg · d)] and positive control group [Euthyrox 9 µg/(kg · d)]. Radioimmunoassay was used to determine the serum T3 and T4 levels; serum BUN content was detected by UV spectrophotometer and ELISA method were used to measure the CYS-C content. The kidney was weighed, and the pathological changes of the renal were detected by HE stain. Compared with blank control group, kidney weight coefficient, serum T3 and T4 levels in model group were decreased, while serum BUN and CYS-C contents were increased (P < 0.05 or P < 0.01). Compared with model group, serum T3 and T4 contents were increased and serum BUN and CYS-C contents were decreased (P < 0.05) in Sini Decoction groups [CSD 9.6 and 4.8 g/(kg · d)] and positive control group. The HE stain results showed that component compatibility Sini Decoction and Euthyrox could relieve glomerular atrophy and renal tubular epithelial cell injury in rats. Component compatibility Sini Decoction has a curative effect on hypothyroidism induced renal damage in rats.


Intense pulsed light, a promising technique to develop molybdenum sulfide catalysts for hydrogen evolution.
We have demonstrated a simple and scalable fabrication process for defect-rich MoS2 directly from ammonium tetrathiomolybdate precursor using intense pulse light treatment in milliseconds durations. The formation of MoS2 from the precursor film after intense pulsed light exposure was confirmed with XPS, XRD, electron microscopy and Raman spectroscopy. The resulting material exhibited high activity for the hydrogen evolution reaction (HER) in acidic media, requiring merely 200 mV overpotential to reach a current density of 10 mA cm-2. Additionally, the catalyst remained highly active for HER over extended durability testing with the overpotential increasing by 28 mV following 1000 cycles. The roll-to-roll amenable fabrication of this highly-active material could be adapted for mass production of electrodes comprised of earth-abundant materials for water splitting applications.


"If an acute event occurs, what should we do?" Diverse ethical approaches to decision-making in the ICU.
The aim of this paper is to analyze an Intensive Care Unit case that required ethics consultation at a University Hospital in Northern Italy. After the case was resolved, a retrospective ethical analysis was performed by four clinical ethicists who work in different healthcare contexts (Italy, the United States, and Switzerland). Each ethicist used a different method to analyze the case; the four general approaches provide insight into how these ethicists conduct ethics consultations at their respective hospitals. Concluding remarks examine the similarities and differences among the various approaches and offer a reflection concerning the possibility of a shared resolution to the case. The authors' efforts to come to a tentative consensus may serve as an example for professionals working in medical contexts that reflect an increasing pluralism of values. This article aims to respond to some of these concerns by illustrating how different methods in clinical ethics would be used when considering a real case. The goal is not to establish the best model (if there is one) on a theoretical level, but to learn from actual practice in order to see if there are common elements in the different methods, and to validate their pertinence to clinical ethics consultation.


Elemental fingerprint analysis of barley (Hordeum vulgare) using inductively coupled plasma mass spectrometry, isotope-ratio mass spectrometry, and multivariate statistics.
Inductively coupled plasma mass spectrometry (ICP-MS) and isotope-ratio mass spectrometry (IR-MS) have been used to examine the multi-elemental composition and (15)N/(14)N and (13)C/(12)C isotope ratios of three spring barley (Hordeum vulgare) genotypes (Orthega, Barke, and Bartok) grown in three typical Danish agricultural soils (North Jutland, West Jutland, and East Zealand) differing in soil fertility. The aim of the study was to examine whether it was possible to generate a unique elemental fingerprint of individual barley genotypes irrespective of the elemental imprint plants had received from soils differing in fertility and agricultural practice. Multivariate statistics were used to analyze the elemental fingerprints of the barley genotypes at different times during a full growing season from early tillering to full maturity of the barley grains. Initially, 36 elements were analyzed in the plant samples but this number was subsequently reduced to 15 elements: B, Ba, C, Ca, Cu, Fe, K, Mg, Mn, N, Na, P, S, Sr, and Zn. These elements exceeded the limit of detection ( LOD) for all genotypes, soil types, and plant growth stages and for these elements the accuracy was better than 90% compared with apple leaf certified reference material (CRM). Principal component analysis (PCA) separated multi-elemental data in accordance with soil type when plants of similar physiological age were compared, whereas this separation disappeared if plants of all ages were compared simultaneously. Isotope ratios (delta(15)N) of plants also proved to be a highly accurate property for classification of samples according to soil type. In contrast, the differences in delta(13)C were too small to enable such classification. The differences in delta(15)N among soils were so pronounced that separation of samples according to the physiological age of plants became redundant. However, delta(15)N and the multi-elemental analysis revealed no differences between the three barley genotypes, indicating that the influence of soil chemistry and possibly also climate and agricultural practice was too large to allow an unique elemental fingerprint for the genotypes. This finding was substantiated by analyzing the multi-elemental composition of grain from two additional genotypes (Otira and Barthos) grown at the north and east locations, respectively. PCA showed not only that the elemental fingerprints of these two genotypes were similar to those of the others, but also that the soil in which the plant had been growing could be accurately predicted on the basis of the PCA scores from the genotypes Orthega, Barke, and Bartok. Similar conclusions could be drawn using delta(15)N data.


Chlamydia trachomatis vaccine research through the years.
Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium. It is the leading cause of bacterial sexual transmitted infections (STIs). World Health Organization figures estimated that over 90 million new cases of genital C. trachomatis infections occur worldwide each year. A vaccination program is considered to be the best approach to reduce the prevalence of C. trachomatis infections, as it would be much cheaper and have a greater impact on controlling C. trachomatis infections worldwide rather than a screening program or treating infections with antibiotics. Currently, there are no vaccines available which effectively protect against a C. trachomatis genital infection despite the many efforts that have been made throughout the years. In this paper, the many attempts to develop a protective vaccine against a genital C. trachomatis infection will be reviewed.


Fibroblast growth factor and cyclic AMP (cAMP) synergistically activate gene expression at a cAMP response element.
Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factor- and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Ras-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways.


Autonomous Pointing Control of a Large Satellite Antenna Subject to Parametric Uncertainty.
With the development of satellite mobile communications, large antennas are now widely used. The precise pointing of the antenna's optical axis is essential for many space missions. This paper addresses the challenging problem of high-precision autonomous pointing control of a large satellite antenna. The pointing dynamics are firstly proposed. The proportional-derivative feedback and structural filter to perform pointing maneuvers and suppress antenna vibrations are then presented. An adaptive controller to estimate actual system frequencies in the presence of modal parameters uncertainty is proposed. In order to reduce periodic errors, the modified controllers, which include the proposed adaptive controller and an active disturbance rejection filter, are then developed. The system stability and robustness are analyzed and discussed in the frequency domain. Numerical results are finally provided, and the results have demonstrated that the proposed controllers have good autonomy and robustness.


Development of a growth-coupled selection platform for directed evolution of heme biosynthetic enzymes in Corynebacterium glutamicum.
Heme is an important tetrapyrrole compound, and has been widely applied in food and medicine industries. Although microbial production of heme has been developed with metabolic engineering strategies during the past 20 years, the production levels are relatively low due to the multistep enzymatic processes and complicated regulatory mechanisms of microbes. Previous studies mainly adopted the strategies of strengthening precursor supply and product transportation to engineer microbes for improving heme biosynthesis. Few studies focused on the engineering and screening of efficient enzymes involved in heme biosynthesis. Herein, a growth-coupled, high-throughput selection platform based on the detoxification of Zinc-protoporphyrin IX (an analogue of heme) was developed and applied to directed evolution of coproporphyrin ferrochelatase, catalyzing the insertion of metal ions into porphyrin ring to generate heme or other tetrapyrrole compounds. A mutant with 3.03-fold increase in k cat/K M was selected. Finally, growth-coupled directed evolution of another three key enzymes involved in heme biosynthesis was tested by using this selection platform. The growth-coupled selection platform developed here can be a simple and effective strategy for directed evolution of the enzymes involved in the biosynthesis of heme or other tetrapyrrole compounds.


Trace element contents in fine particulate matter (PM2.5) in urban school microenvironments near a contaminated beach with mine tailings, Chañaral, Chile.
Air quality in schools is an important public health issue because children spend a considerable part of their daily life in classrooms. Particulate size and chemical composition has been associated with negative health effects. We studied levels of trace element concentrations in fine particulate matter (PM2.5) in indoor versus outdoor school settings from six schools in Chañaral, a coastal city with a beach severely polluted with mine tailings. Concentrations of trace elements were measured on two consecutive days during the summer and winter of 2012 and 2013 and determined using X-ray fluorescence. Source apportionment and element enrichment were measured using principal components analysis and enrichment factors. Trace elements were higher in indoor school spaces, especially in classrooms compared with outdoor environments. The most abundant elements were Na, Cl, S, Ca, Fe, K, Mn, Ti, and Si, associated with earth's crust. Conversely, an extremely high enrichment factor was determined for Cu, Zn, Ni and Cr; heavy metals associated with systemic and carcinogenic risk effects, whose probably origin sources are industrial and mining activities. These results suggest that the main source of trace elements in PM2.5 from these school microenvironments is a mixture of dust contaminated with mine tailings and marine aerosols. Policymakers should prioritize environmental management changes to minimize further environmental damage and its direct impact on the health of children exposed.


Characterization of Aeromonas salmonicida subsp. salmonicida: a comparative study of strains of different geographic origin.
A total of 130 strains of the fish pathogen Aeromonas salmonicida isolated in Denmark, Norway, Scotland, Canada and the USA were examined. The strains originated from farmed salmonid fish. The biochemical, physiological and serological characteristics, antibiotic resistance patterns and cell surface-related properties were compared. Aeromonas salmonicida was found to be remarkably consistent in general cultural and biochemical characteristics. It is noteworthy that the strains were positive in the fermentation of L-arabinose and were negative in the fermentation of D-arabinose. All the strains were highly proteolytic. It was observed, however, that 5% of the strains did not digest calf and trout serum and the production of haemolysin and degradation of casein by the same strains were delayed compared with the other strains. Common to all of the rough strains were auto-aggregation and ability to bind the dyes Coomassie brilliant blue and Congo red and the majority of these strains were highly hydrophobic. The strains were tested for their susceptibility to 22 antibacterial agents. Antibiotic resistance profiles of Aer. salmonicida indicated that resistance to the quinolones and oxytetracycline was increasing and that multi-resistant strains were found in several countries. The variation found in antibiograms could have potential as epidemiological markers in certain geographic areas.


A fiber matrix model for the filtration through fenestral pores in a compressible arterial intima.
We advance a new hypothesis to explain the changes in hydraulic conductivity of an intact artery wall with transmural pressure previously observed by Tedgui and Lever [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H784-H791, 1984] and Baldwin and Wilson [Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H26-H32, 1993]. This hypothesis suggests that compaction due to pressure loading of the proteoglycan matrix in the arterial intima near fenestral pores of the internal elastic lamina (IEL) leads to a narrowing of the pore entrance area and a large decrease in local intrinsic Darcy permeability of the matrix. To quantitatively assess the feasibility of this mechanism, a local two-dimensional model is proposed to study filtration flow in the vicinity of fenestral pores in a compressible intima. Using a heterogenous fiber matrix theory, we first predict the change in Darcy permeability with intimal thickness (Li). The model then calculates local velocity profiles and pressure distributions in the intima and media. The results show a marked nonlinear steepening of intimal pressure profiles near fenestral pores when the intima thins at higher luminal pressures. The predicted relative change in resistances of the IEL (with intima, R(I)) and of the media (Rm) shows a steep increase in R(I)/Rm when Li is <20% of its unstressed value. Numerical results also suggest that intimal compression has a limiting behavior in which the much stiffer collagen fibrils inhibit further compaction at high pressures after the proteoglycan matrix is maximally compressed. Predictions are also presented to show how different transmural pressures alter growth of an intimal horseradish peroxidase spot that derives from a localized (a single cell's boundary) endothelial leakage. Such a prediction is amenable to experimental verification.


Psychogeriatrics and general practice in Australia.
We describe the interface between general practice and psychogeriatrics in Australia. While aged care services are complex and there are serious deficiencies in the management of the elderly, several initiatives appear set to improve the level of care. Economic considerations, mutual education of general practitioners and psychogeriatricians, and social factors are strong determinants of good primary care of the mental health needs of older people.


Rat monoclonal antibodies produced against rat colorectal adenocarcinomas define tumor- and colon-associated, auto-immunogenic antigens.
Monoclonal antibodies (MAbs) were derived from rats immunized against allo- and syngeneic rat colon carcinomas. Screening was performed by immunohistochemistry modified for MAbs of the same species as the tissue used for frozen sections. From 2 fusions, several MAbs were found that bound to syngeneic tumor tissue but showed little or no staining of normal adult tissues. Another group of MAbs demonstrated an intracellular staining of tumor cells and staining of mucus and goblet cells in the distal 2/3 of the normal colon. A third group of MAbs showed staining of both tumor and normal colon tissue. Staining patterns were reproduced with 6 MAbs selected from the first 2 groups after purification and biotinylation. One MAb, 10B12, recognized an antigen expressed in 10/11 colon carcinomas, the lowest parts of colonic crypts, intracellularly in a subpopulation of pancreatic acinar cells and mucus in antrum. It was used for affinity purification of a high-molecular-weight antigen, to which 3 of the other rat MAbs also bound. This antigen was also bound by antibodies to blood group A and isogloboseries carbohydrate determinants. Competition with the labelled 10B12 MAb for binding to the purified antigen was demonstrated in sera of tumor-bearing and immune rats. Thus, this high-molecular-weight glycoprotein expressed both auto-antigenic, tumor-associated and tissue-type-restricted epitopes. The 10B12 MAb homogeneously stained the majority of colorectal carcinomas and the antigenic determinant was expressed on the cell surface of 12/13 tissue-cultured colon-carcinoma clones. Modulation of the cell-surface antigen phenotype by recombinant rat interferon-gamma markedly increased expression of this determinant.


Pyloroduodenal duplication cysts: treatment of 11 cases.
Abdominal enteric duplications are found in 1 out of 4,500 autopsies, and only 4 to 5% of them are located in the duodenum, where they may be connected with the biliary or pancreatic ducts. The aim of this study was to describe the clinical features, management, and outcome of a large series of duodenal duplication cysts. The charts of all patients treated at our institution between 1985 and 2011 were reviewed retrospectively with particular attention to imaging, surgical technique, pathology, and outcome. During that period, 11 cases (81.8% females) were treated. Out of the 11 patients, 8 were symptomatic (vomiting in 3, recurrent acute pancreatitis in 2, and abdominal pain in 3) and 3 were tentatively diagnosed prenatally as choledochal cysts. Median age at surgery was 2.3 years (0 to 13.7) and preoperative diagnosis was correct in five cases. Five cysts were developed intraluminally and three communicated with the biliary duct (one), pancreatic duct (one), or both (one). Surgical treatment consisted of complete resection (four cases, including one pancreaticoduodenectomy), partial removal including all mucosa (four cases), and internal marsupialization (three cases). In all cases, the ductal communications were divided and opened into the duodenal lumen. In six cases, ectopic gastric mucosa was found. All patients recovered uneventfully. Duodenal duplication cysts are rare and may have bizarre anatomical patterns due to biliopancreatic involvement. Optimal treatment is complete surgical removal, and, if this is not possible, partial removal including the mucosa or marsupialization are also good alternatives. In cases with biliary and pancreatic tract connections, these have to be taken down carefully and drained into the duodenum.


[Preliminary study on the relationship between chronic sinusitis histomorphology and aerosol].
To observe the relationship between histomorphological changes in mucosa of chronic sinusitis (CS) and aerosol particles. The ethmoidal sinus mucus specimens of 60 patients with CS type I, II and III, and 16 cases of normal controls were collected. Meanwhile the pulmonary specimens in autopsy of 5 adult and 5 fetus cases were also collected. The specimens were stained by HE staining and Warthin-Starry (W-S) special aerosol particles staining method respectively, the ethmoidal sinus mucosa basement membrane were displayed by Van Gieson's (VG) special staining method, and its thickness was measured. By the W-S staining, some black aerosol particles were found depositing on the epithelial cells layer of damaged mucosa and in the plasm of the epithelial cells. The degree of deposition was gradually increased in type I, II and III of CS. The number of cases of slight, medium and heavy depositing in type I were 11/20, 7/20, 2/20, in type II 5/20, 9/20, 6/20, and in type III 3/20, 6/20, 11/20 respectively; the more particles deposited, the more thickening the basement membrane. The thickness of the basement membrane in type I, II and III of CS were (12.15 +/- 4.73), (16.67 +/- 2.22), (23.75 +/- 3.48) microm respectively. There were significant differences among type I, II and III (P < 0.01). The black particles in the mucosa epithelium tissues of normal control group and non-damaged mucosa epithelium and desquamation area were seldom seen. On the other hand, the aerosol particles were not seen in the pulmonary specimens of the fetal autopsy. In damaged mucosa epithelial cells of the CS, there are aerosol particles existing which may relate with the morphological changes of CS.


Cellular Pathology of Pelizaeus-Merzbacher Disease Involving Chaperones Associated with Endoplasmic Reticulum Stress.
Disease-causing mutations in genes encoding membrane proteins may lead to the production of aberrant polypeptides that accumulate in the endoplasmic reticulum (ER). These mutant proteins have detrimental conformational changes or misfolding events, which result in the triggering of the unfolded protein response (UPR). UPR is a cellular pathway that reduces ER stress by generally inhibiting translation, increasing ER chaperones levels, or inducing cell apoptosis in severe ER stress. This process has been implicated in the cellular pathology of many neurological disorders, including Pelizaeus-Merzbacher disease (PMD). PMD is a rare pediatric disorder characterized by the failure in the myelination process of the central nervous system (CNS). PMD is caused by mutations in the PLP1 gene, which encodes a major myelin membrane protein. Severe clinical PMD phenotypes appear to be the result of cell toxicity, due to the accumulation of PLP1 mutant proteins and not due to the lack of functional PLP1. Therefore, it is important to clarify the pathological mechanisms by which the PLP1 mutants negatively impact the myelin-generating cells, called oligodendrocytes, to overcome this devastating disease. This review discusses how PLP1 mutant proteins change protein homeostasis in the ER of oligodendrocytes, especially focusing on the reaction of ER chaperones against the accumulation of PLP1 mutant proteins that cause PMD.


A MALT lymphoma prognostic index.
There are no widely accepted prognostic indices for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). This study aimed to develop and validate a specific prognostic tool to personalize and optimize treatment of patients with MALT lymphoma. A prognostic index was built by Cox regression (stepwise selection) using data from 401 patients enrolled in the international randomized International Extranodal Lymphoma Study Group 19 (IELSG-19) trial (NCT 00210353). A validation set, including 633 patients, was obtained by merging 3 independent cohorts of MALT lymphoma patients. The 3 individual features maintaining the greatest prognostic significance for event-free survival (EFS, the main endpoint of the IELSG-19 trial) were age ≥70 years (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.26-2.33), Ann Arbor stage III or IV (HR, 1.79; 95% CI ,1.35-2.38), and an elevated lactate dehydrogenase level (HR, 1.87; 95% CI, 1.27-2.77). The prognostic index (MALT-IPI) constructed using these 3 parameters identified 3 groups: low, intermediate, and high risk (corresponding to the presence of 0, 1, or ≥2 of these factors, respectively). The 5-year EFS rates in the low-, intermediate-, and high-risk groups were 70%, 56%, and 29%, respectively. The MALT-lymphoma International Prognostic Index (MALT-IPI) also significantly discriminated between patients with different progression-free, overall, and cause-specific survival. The prognostic utility was retained in gastric and nongastric lymphomas, in each treatment arm (chlorambucil, rituximab, and rituximab plus chlorambucil), and was confirmed in the validation set. The new index, MALT-IPI, is a simple, accessible, and effective tool to identify MALT lymphoma patients at risk of poor outcomes. It may help define appropriate treatment approaches for individual patients.


ODELAY: A Large-scale Method for Multi-parameter Quantification of Yeast Growth.
Growth phenotypes of microorganisms are a strong indicator of their underlying genetic fitness and can be segregated into 3 growth regimes: lag-phase, log-phase, and stationary-phase. Each growth phase can reveal different aspects of fitness that are related to various environmental and genetic conditions. High-resolution and quantitative measurements of all 3 phases of growth are generally difficult to obtain. Here we present a detailed method to characterize all 3 growth phases on solid media using an assay called One-cell Doubling Evaluation of Living Arrays of Yeast (ODELAY). ODELAY quantifies growth phenotypes of individual cells growing into colonies on solid media using time-lapse microscopy. This method can directly observe population heterogeneity with each growth parameter in genetically identical cells growing into colonies. This population heterogeneity offers a unique perspective for understanding genetic and epigenetic regulation, and responses to genetic and environmental perturbations. While the ODELAY method is demonstrated using yeast, it can be utilized on any colony forming microorganism that is visible by bright field microscopy.


Binding of Bacteria to Poly(N-isopropylacrylamide) Modified with Vancomycin: Comparison of Behavior of Linear and Highly Branched Polymers.
The behavior of a linear copolymer of N-isopropylacrylamide with pendant vancomycin functionality was compared to an analogous highly branched copolymer with vancomycin functionality at the chain ends. Highly branched poly(N-isopropylacrylamide) modified with vancomycin (HB-PNIPAM-van) was synthesized by functionalization of the HB-PNIPAM, prepared using reversible addition-fragmentation chain transfer polymerization. Linear PNIPAM with pendant vancomycin functionality (L-PNIPAM-van) was synthesized by functionalization of poly(N-isopropylacrylamide-co-vinyl benzoic acid). HB-PNIPAM-van aggregated S. aureus effectively, whereas the L-PNIPAM-van polymer did not. It was found that when the HB-PNIPAM-van was incubated with S. aureus the resultant phase transition provided an increase in the intensity of fluorescence of a solvatochromic dye, nile red, added to the system. In contrast, a significantly lower increase in fluorescence intensity was obtained when L-PNIPAM-van was incubated with S. aureus. These data showed that the degree of desolvation of HB-PNIPAM-van was much greater than the desolvation of the linear version. Using microcalorimetry, it was shown that there were no significant differences in the affinities of the polymer ligands for d-Ala-d-Ala and therefore differences in the interactions with bacteria were associated with changes in the probability of access of the polymer bound ligands to the d-Ala-d-Ala dipeptide. The data support the hypothesis that generation of polymer systems that respond to cellular targets, for applications such as cell targeting, detection of pathogens etc., requires the use of branched polymers with ligands situated at the chain ends.


A case of extraskeletal Ewing sarcoma originating from the visceral pleura.
Extra skeletal Ewing Sarcoma (EES) is a rare entity which predominantly occurs in adolescents and young adults. It usually arises from the soft tissues of the trunk or the extremities. We present a case of EES arising from the left visceral pleura in a 21 year old female patient who presented to the emergency room of our institution with fever, productive cough and sternal pain radiating to the back for the last 3 days. Chest radiograph was firstly performed, followed by chest CT examination. Finally open lung biopsy revealed a small round cell malignancy. The mass was resected and the histological examination revealed Extra skeletal Ewing Sarcoma (EES) of the visceral pleura without involvement of the adjacent lung. Secondary multiple nodules at the lateral wall of the pleura were also noticed and so postoperative multiagent chemotherapy was performed. EES should be considered in the differential diagnosis of any patient, especially adolescents or young adults, with a soft tissue mass of the trunk or the extremities.


Does shuttling of glycogen-derived lactate from astrocytes to neurons take place during neurotransmission and memory consolidation?
Glycogen levels in resting brain and its utilization rates during brain activation are high, but the functions fulfilled by glycogenolysis in living brain are poorly understood. Studies in cultured astrocytes have identified glycogen as the preferred fuel to provide ATP for Na+ ,K+ -ATPase for the uptake of extracellular K+ and for Ca2+ -ATPase to pump Ca2+ into the endoplasmic reticulum. Studies in astrocyte-neuron co-cultures led to the suggestion that glycogen-derived lactate is shuttled to neurons as oxidative fuel to support glutamatergic neurotransmission. Furthermore, both knockout of brain glycogen synthase and inhibition of glycogenolysis prior to a memory-evoking event impair memory consolidation, and shuttling of glycogen-derived lactate as neuronal fuel was postulated to be required for memory. However, lactate shuttling has not been measured in any of these studies, and procedures to inhibit glycogenolysis and neuronal lactate uptake are not specific. Testable alternative mechanisms to explain the observed findings are proposed: (i) disruption of K+ and Ca2+ homeostasis, (ii) release of gliotransmitters, (iii) imposition of an energy crisis on astrocytes and neurons by inhibition of mitochondrial pyruvate transport by compounds used to block neuronal monocarboxylic acid transporters, and (iv) inhibition of astrocytic filopodial movements that secondarily interfere with glutamate and K+ uptake from the synaptic cleft. Evidence that most pyruvate/lactate derived from glycogen is not oxidized and does not accumulate suggests predominant glycolytic metabolism of glycogen to support astrocytic energy demands. Sparing of blood-borne glucose for use by neurons is a reasonable explanation for the requirement for glycogenolysis in neurotransmission and memory processing.


[Bile acid stimulation test with ceruletide].
The bile acid stimulation test is a sensitive and liver specific test to check liver function. In contrast to the postprandial estimation of serum bile acids which has been used up to now, it offers the advantage of a better standardization. Furthermore there are hardly any side effects. The test requires three blood samples at 0, 20, and 40 minutes after an i.m. injection of 0.3 micrograms/kg KM Ceruletid (Takus). The normal values in the fasting state are under 5.0 mumol/l, 20 and 40 minutes after stimulation under 15.0 mumol/l serum bile acids.


Novel murine norovirus-like genes in wild rodents in Japan.
Novel murine norovirus (MNV)-like sequences were detected in 7 (14.9%) of 47 fecal and intestinal samples obtained from wild rodents in Japan. Sequencing and genetic analyses of the 7 MNV-like genes, 6 derived from Apodemus speciosus and 1 from Rattus rattus, suggested that these sequences form a cluster distinct from known MNV within genogroup V and differed even among clusters of wild rodents. Considering these results, MNV might be genetically diverse depending on the host species or distribution. This is the first report suggesting the prevalence of MNV in A. speciosus and R. rattus.


Unsupervised analysis of background noise sources in active offices.
Inside open-plan offices, background noise affects the workers' comfort, influencing their productivity. Recent approaches identify three main source categories: mechanical sources (air conditioning equipment, office devices, etc.), outdoor traffic noise, and human sources (speech). Whereas the first two groups are taken into account by technical specifications, human noise is still often neglected. The present paper proposes two procedures, based on machine-learning techniques, to identify the human and mechanical noise sources during working hours. Two unsupervised clustering methods, specifically the Gaussian mixture model and K-means clustering, were used to separate the recorded sound pressure levels that were recorded while finding the candidate models. Thus, the clustering validation was used to find the number of sound sources within the office and, then, statistical and metrical features were used to label the sources. The results were compared with the common parameters used in noise monitoring in offices, i.e., the equivalent continuous and 90th percentile levels. The spectra obtained by the two algorithms match with the expected shapes of human speech and mechanical noise tendencies. The outcomes validate the robustness and reliability of these procedures.


Survival, Incidence, and Mortality Trends in Female Cancers in the Nordic Countries.
Female cancers cover common breast cancers, relatively common endometrial, ovarian, and cervical cancers and rare vulvar cancer. Survival in these cancers is known to be relatively good compared to all cancers but long-term studies for these cancers are rare, and to fill the gap, here, we generate survival data through 50 years. We applied generalized additive models to data from the NORDCAN database and analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over half a century (1971-2020). Conditional 5/1-year survival for patients who survived the 1st year after diagnosis and annual survival changes was also estimated. In 2016-20, 5-year survival was best for breast cancer reaching 92.3% (in SE), followed by endometrial cancer at 86.1% (SE) and cervical cancer at 75.6% (NO). Improvement in 5-year survival over the 50 years was the largest for ovarian cancer (20% units), finally reaching 52.9% (SE). For vulvar cancer, the final survival was between 70 and 73%. The best 5-year survival rate in 2016-20 was recorded for SE in breast, endometrial, and ovarian cancers; NO showed the highest rate for cervical and DK for vulvar cancers. DK had the lowest survival for breast and ovarian cancers, and FI, for the other cancers. The overall survival development appeared to consist of continuous improvements, most likely because of novel treatment and imaging techniques as well as overall organization of patient care. The large survival improvement for ovarian cancer was probably achieved by a surgical focus on tumors spread in the peritoneal cavity. For cervical and vulvar cancers, the high early mortality requires attention and could be helped by raising increasing public awareness of early symptoms in these cancers and developing pathways for fast initiation of treatment.


Interpretation of sonotubometric data based on phase-shift detection.
Sonotubometry is a non-invasive means of assessing Eustachian tube (ET) function. Its interpretation remains a complex task with questionable results due to wide variation between trials. A study was conducted to ascertain whether the measurement of phase shift in sonotubometric signals would be a more reliable indicator of ET patency than fluctuating Sound Pressure Level (SPL). The ears of six healthy participants and two participants with patulous ET (PET) were probed with a 100 Hz signal. Five recordings of SPL were performed at the external auditory canal. Cross-correlation was performed among filtered SPL signals and among extracted phase shift waveforms. Peak coefficients were averaged to provide a measure of waveform similarity between trials. Mean peak cross correlation coefficient for SPL signal measured 0.603 ± 0.057 Standard Error of Mean (SEM) whilst that for Phase-Shift signal measured 0.884 ± 0.027 (SEM). All normal participants demonstrated an observable phase change between the ear and nasal signal during swallowing indicating an acoustic impedance change during the event. For the PET patients tested, the phase measurements in ear and nasal signals follow one another reasonably closely, indicating little or no impedance change during swallowing. It is thought that this impedance change is indicative of opening of the ET in normal patients, and the lack impedance change indicates ET either remaining open or remaining closed throughout the swallow. Experimental data suggest that phase-shift detection is a more consistent means of interpreting sonotubometric data than SPL analysis.


Zerynthia polyxena Locally Monophagous on Aristolochia pallida in the Susa Valley.
In insect-plant biology, oviposition choices and larval development on different host plants are crucial factors to be investigated. To design conservation strategies for protected Lepidoptera, which are overall oligophagous but locally monophagous, it is important to understand which host plant species is locally preferred. We thus investigated oviposition choices and larval development of the protected butterfly Zerynthia polyxena in controlled laboratory conditions, using three possible host plant species which are present in the Piedmont region: Aristolochia pallida, A. clematitis, and A. rotunda. We found that laboratory conditions are not favorable for Z. polyxena oviposition, even if the fertility of the females was in normal range for Papilionidae. However, we were able to understand the local monophagy of the species on A. pallida in the Susa Valley through larval survival and development stages. Egg hatching was similar among the three host plant species; however, even if larvae eat and grow similarly on the different host plant species until the third larval stage, the only larvae that reached the pupal stage were those fed with A. pallida. In conclusion, whereas Z. polyxena is oligophagous in the rest of Europe for the genus Aristolochia, the species is locally monophagous on A. pallida in the Susa Valley.


Student life - Flexible pathway into the profession for support staff.
As the shape of the UK nursing workforce changes, partnership working between employers and educational institutions can help recruit and retain staff.


Deformity progression in congenital posteromedial bowing of the tibia: a report of 44 cases.
congenital posteromedial bowing of tibia (CPMBT) is a very rare birth defect, characterized by shortened bowed leg and ankle deformity. We described a single institution experience in the management of CPMBT. we identified 44 CPMBT in 44 children. The age at presentation was 5.5 ± 5.6 years and the mean age at the final review was 10.1 ± 4.8 years. Radiographic evaluation included the antero-posterior and lateral inter-physeal angle (AP-IPA and L-IPA), the limb length discrepancy (LLD), the morphology of the distal tibia and the lateral distal tibial angle (LDTA). During the study period, 26 children underwent surgical treatment. the estimated curves showed a progressive spontaneous correction of both AP-IPA and L-IPA during growth, but a progressive increase of the LLD. The L-IPA showed a more predictable behaviour while the AP-IPA showed a scattered correction, with a wider variation of the estimated final angle. The final LDTA was 85.3° ± 4.2° and was correlated with the L-IPA (r = 0.5; p = 0.02). Among the 26 children who underwent surgical treatment, 23 cases had limb lengthening, 1 case had contralateral epiphysiodesis, 1 child underwent tibial osteotomy, 1 patient was treated by hemiepiphysiodesis of the distal tibia to correct ankle valgus deformity. our study described the largest case series of CPMBT. A combination of surgical treatments, in a staged surgical process, should be tailored to the developmental characteristics of this abnormality. An experience-based algorithm of treatment is also proposed. Further studies are needed to understand which is the best strategy to correct this deformity during childhood. level IV prognostic study.


Efficient and highly aldehyde selective Wacker oxidation.
A method for efficient and aldehyde-selective Wacker oxidation of aryl-substituted olefins using PdCl(2)(MeCN)(2), 1,4-benzoquinone, and t-BuOH in air is described. Up to a 96% yield of aldehyde can be obtained, and up to 99% selectivity can be achieved with styrene-related substrates.


Characterization of an antiserum to guinea pig antithrombin III (AT III). II. Stimulation of T lymphocyte proliferation.
A goat antibody specific for an antigenic determinant shared between guinea pig antithrombin III (AT III) and thymocytes was shown to be mitogenic for lymph node T lymphocytes in the presence of macrophages. Although the antiserum was not mitogenic for purified populations of B lymphocytes, B lymphocytes were as efficient as T lymphocytes in absorbing the mitogenic activity of the serum. The shared antigenic determinant appeared to be carbohydrate in nature in that native and guanidine-treated AT III, but not periodate oxidized AT III, were capable of inhibiting the mitogenic activity of the serum when added continuously to the cultures. The possibility that the plasma protease inhibitor AT III or an antigenically related membrane protein are involved in the regulation of T cell activation is discussed.


Method to manage integration error in the Green-Kubo method.
The Green-Kubo method is a commonly used approach for predicting transport properties in a system from equilibrium molecular dynamics simulations. The approach is founded on the fluctuation dissipation theorem and relates the property of interest to the lifetime of fluctuations in its thermodynamic driving potential. For heat transport, the lattice thermal conductivity is related to the integral of the autocorrelation of the instantaneous heat flux. A principal source of error in these calculations is that the autocorrelation function requires a long averaging time to reduce remnant noise. Integrating the noise in the tail of the autocorrelation function becomes conflated with physically important slow relaxation processes. In this paper we present a method to quantify the uncertainty on transport properties computed using the Green-Kubo formulation based on recognizing that the integrated noise is a random walk, with a growing envelope of uncertainty. By characterizing the noise we can choose integration conditions to best trade off systematic truncation error with unbiased integration noise, to minimize uncertainty for a given allocation of computational resources.


A 13C comparative nuclear magnetic resonance study of organic solute production and excretion by the yeasts Hansenula anomala and Saccharomyces cerevisiae in saline media.
Glycerol, arabitol and trehalose were the principle solutes detected in cellular extracts of Hansenula anomala, using natural-abundance 13C nuclear magnetic resonance spectroscopy. Only the two polyols accumulated in response to increased salinity, glycerol increase being far greater. Arabitol content also increased with culture age, independently of the presence or absence of salt and in line with the evolution of trehalose content. Glycerol retention potential was 15 times greater for Hansenula than for Saccharomyces cerevisiae. The former displayed the specific property of increasing this capacity in high salt concentrations. Under such conditions its growth was associated with a limited increase in glucose consumption per unit biomass, relative to S. cerevisiae, the salt-sensitive reference yeast. In addition, a polysaccharide, the chemical nature of which was not further characterized, was detected exclusively in the external medium of Hansenula growing in the presence of salt.


Italian regional health system structure and expected cancer survival.
Few studies deal with the association of socioeconomic and health system resource variables with cancer survival at the Italian regional level, where the greatest number of decisions about social and health policies and resource allocations are taken. The present study aimed to describe the causal relationships between socioeconomic and health system resource factors and regional cancer survival and to compute the expected cancer survival at provincial, regional and area levels. Age-standardized relative survival at 5 years from diagnosis of cases incident in 1995-1998 and followed up to 2004 were derived by gender for 11 sites from the Italian Association of Cancer Registries data bank. The socioeconomic and health system resource variables, describing at a regional level the macro-economy, demography, labor market, and health resources for 1995-2005, came from the Health for All database. A principal components factor analysis was applied to the socioeconomic and health system resource variables. For every site, linear regression models were computed considering the relative survival at 5 years as a dependent variable and the principal components factor analysis factors as independent variables. The factors described the socioeconomic and health-related features of the regional systems and were causally related to the characteristics of the patient taken in charge. The models built by the factors allowed computation of the expected relative survival at 5 years with very good concordance with those observed at regional, macro-regional and national levels. In the regions without any cancer registry, survival was coherent with that of neighboring regions with similar socioeconomic and health system resources characteristics. The models highlighted the causal correlations between socioeconomic and health system resources and cancer survival, suggesting that they could be good evaluation tools for the efficiency of the resources allocation and use.


Simultaneous catalyst-free growth of highly oriented ZnO nanowires and microtubes.
Through a catalyst-free chemical vapor deposition method, highly oriented ZnO nanowires and microtubes were simultaneously grown on the side and the top surface of Si substrate respectively. The ZnO nanowires and microtubes were characterized by scanning electron microscopy, X-ray diffraction, transmission electron microscopy and selected area electron diffraction. The growth mechanism of the microtubes was discussed and the room temperature photoluminescence properties of individual microtubes were investigated.


Influence of age, sex, and oral contraceptives on human blood cholinesterase activity.
We estimated cholinesterase (EC 18.104.22.168) activities in erthrocytes and plasma of 443 men, 188 women not taking oral contraceptives, and 70 women who were taking oral contraceptives. Men in the first six decades of life had higher plasma cholinesterase activity than did women who were not taking oral contraceptives, and these women had higher plasma cholinesterase activity than women taking oral contraceptives. After the age of 60 there was no intersex difference. Activity of erythrocytes from the oral contraceptive group was higher than in the other groups, men had the lowest activity, and there was an increased activity with age in both sexes until the age of 60. These findings suggest that there is no single "normal" value for cholinesterase activity for adults.


Lethal and Sublethal Effects of Cantharidin on Development and Reproduction of Plutella xylostella (Lepidoptera: Plutellidae).
The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a major pest of cruciferous vegetables throughout the world. Cantharidin, a natural toxin isolated from beetles in the families Meloidae and Oedemeridae, has been reported to be toxic to some pests, including the diamondback moth. However, the effects of cantharidin, especially its sublethal effects on development and reproduction of diamondback moth, are less known. In this study, we investigated the sublethal effects of cantharidin at LC2 (0.41 mg liter(-1)), LC10 (1.33 mg liter(-1)), LC25 (3.38 mg liter(-1)), and LC50 (9.53 mg liter(-1)) on development and reproduction parameters of two consecutive diamondback moth generations. The results indicated that cantharidin reduced population growth by decreasing its pupation rate, pupal weight, and adult emergence, and by delaying its development. Furthermore, the duration of the female preoviposition period increased, while the oviposition and postoviposition periods, fecundity, and survival rates of the offspring decreased. The peaks of age-specific fecundity in LC10, LC25, and LC50 treatment groups lagged behind the control group. The mean values of the net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) were significantly lower than those of the control, and the mean generation time (T) was prolonged. The present study demonstrates that cantharidin exhibits significant adverse effects on the population dynamics of diamondback moth, leading to fitness disadvantages.


Church-Based Exchanges of Informal Social Support among African Americans.
This study examines the correlates of the types of instrumental support exchanges that occur between church members among African Americans. Exchanges of four types of instrumental support are examined: transportation assistance, help with chores, financial assistance and help during illness. Data for this study are from the National Survey of American Life Re-Interview, the follow-up survey to the National Survey of American Life which is a nationally representative sample of the African American population. We found that African Americans were more likely to both give and receive support in situations involving illness, followed by transportation, financial assistance, and help with chores. For each of the four types of instrumental support, respondents indicate that they provide more assistance to others than they receive. For all eight dependent variables, those with lower levels of education were more actively engaged in receiving and providing support than their higher educated counterparts. Higher levels of religious service attendance were associated with higher levels of support, which underscores the importance of involvement in faith communities for assistance. Overall, our findings confirm the importance of church-based informal social support between African Americans and documents within group diversity as both recipients and providers of assistance.


Influence of weight loss, body composition, and lifestyle behaviors on plasma adipokines: a randomized weight loss trial in older men and women with symptomatic knee osteoarthritis.
To investigate effects of weight loss on adipokines and health measures in obese older adults with symptomatic knee osteoarthritis. Participants were randomly assigned to either weight loss (WL) (men: 12, women: 14) or weight stable (WS) group (men: 12, women: 13). WL intervention included meal replacements and structured exercise training. Measurements of leptin, adiponectin, soluble leptin receptor, lifestyle behaviors, and body composition were collected at baseline and 6 months. Univariate analysis of covariance was performed on 6 month variables, and Spearman and partial correlations were made between variables. Weight loss was 13.0% and 6.7% in WL for men and women, respectively. Women in WL had lower whole body and trunk fat than WS. The leptin : adiponectin ratio was lower for women in WL than WS at 6 months, with no group differences in adipokines for men. Leptin and free leptin index correlated with body fat in both genders at baseline. Interestingly, only women showed reductions in leptin (P < 0.100) and correlations between the percentage change leptin and trunk fat and the percentage changes in free leptin index with total fat and trunk fat. Partial correlations between 6 month adipokines after adjustments for covariates and group/time period show potential multivariate influences. In the presence of an effective weight loss intervention in older obese adults, there are significant relationships between weight and fat loss and leptin in women, but not men, suggesting gender-specific features of adipokine metabolism in this age group.


Better Demand Signal, Better Decisions? Evaluation of Big Data in a Licensed Remanufacturing Supply Chain with Environmental Risk Considerations.
Big data ability helps obtain more accurate demand signal. However, is better demand signal always beneficial for the supply chain parties? To answer this question, we investigate a remanufacturing supply chain (RSC), where demand uncertainty is significant, and the value to reduce environmental risk is large. Specifically, we focus on a licensed RSC comprising an original equipment manufacturer (OEM) and a third-party remanufacturer (3PR). The latter pays a unit license fee to the former, and can be risk averse to the demand of remanufactured products. We show that the OEM and the risk-neutral 3PR always have incentives to improve their big data abilities to increase their profits. However, when the 3PR is risk averse, big data might hurt its profit: the value of big data is positive if its demand signal accuracy is sufficiently low. Interestingly, we find that while information sharing hurts the 3PR, it benefits the OEM as well as the supply chain. Thus, if costly information sharing is allowed, a win-win situation can be achieved. We also find that information sharing generates more valuation when the 3PR is risk averse than that when the 3PR is risk neutral. More importantly, we find that the 3PR's risk attitude and demand signal accuracy can significantly mitigate the negative environmental impact (measured by the amount of the waste): (1) the more risk neutral the 3PR is, the better the environment is; (2) the more accurate demand signal is, the better the environment is.


Digest: Predicting the future by learning from the past in lizards' thermal traits.
How do traitsevolve on a global scale? Ibargüengoytía et al. provide a framework for understanding the evolutionary history of thermal traits in a broadly diverse lizard family Liolaemidae and find that the lizards' body temperature has evolved following the change in air temperature over the past ∼20,000 years, while the preferred body temperature for physiological functions has evolved at a lower rate. This difference results in a higher buffer to respond to global climate change, in particular for viviparous species, which usually show lower body temperatures in their natural environments. Oviparous species from the arid environments are at higher risk of extinction in the family Liolaemidae.


Relationship between academic performance and affective changes during the first year at medical school.
Entering medical school may be associated with changes in the students' life, which can affect academic motivation and impair academic performance. This work aimed at measuring longitudinally academic motivation, anxiety, depression and social adjustment in first-year medical students and determining the relationships between these variables and academic performance, as measured mainly by grades on regular exams. Eighty-five first-year medical students (age: 17-25 years) were included after giving informed consent. Beck's Anxiety (BAI) and Beck's Depression (BDI) Inventories, the self-reported Social Adjustment Scale (SAS-SR) and the Academic Motivation Scale (AMS) were applied two months after admission and at the end of the academic year. BAI scores increased throughout the year (7.3 ± 6.6 versus 28.8 ± 6.7; p < 0.001), whereas BDI scores did not change (6.8 ± 5.9 versus 6.0 ± 5.4; p > 0.10). SAS-SR subscales scores remained stable, except for a decreasing pattern for leisure/social life (1.8 ± 0.4 versus 2.1 ± 0.4; p < 0.001). AMS scores for motivation to know (22.2 ± 4.5 versus 19.7 ± 5.5; p < 0.001), to accomplish things to know (17.7 ± 5.3 versus 15.4 ± 5.3; p = 0.001), to experience to know (18.2 ± 5.2 versus 15.4 ± 5.4; p < 0.001) and by identification to know (23.5 ± 3.5 versus 21.8 ± 5.0; p = 0.002) decreased significantly. There were no significant correlations between academic performance and the global scores for any of the scales except for the SAS-SR subscale for academic life (r = -0.48, p < 0.001). Throughout the academic year, first-year medical students showed increased anxiety, decreased academic motivation and a maladjusted leisure/social life, which however does not seem to affect academic achievement.


The ansacarbamitocins: polar ansamitocin derivatives.
The ansacarbamitocins are a new family of maytansinoids that are unusually substituted with a glucose subunit and two carbamate functional groups and exhibit modest activity against some agricultural fungal disease organisms. Ansacarbamitocins A-F ( 1- 6) all consist of the same macrocyclic core as the ansamitocins, with variation occurring on the glucose unit, while ansacarbamitocins A1 and B1 ( 7, 8) additionally lack the epoxide group on C-4 and C-5.


Post-chikungunya chronic arthritis--our experience with DMARDs over two year follow up.
1) To study clinical features and laboratory findings in patients of post chikungunya chronic arthritis (PCCA). 2) To study effectivity of disease modifying antirheumatic drugs (DMARDs) in treatment of post-chikungunya chronic arthritis. Sixteen Chikungunya IgM positive patients having arthritis lasting more than 3 months in spite of NSAIDs and Hydroxychloroquine therapy were selected. Their clinical, laboratory and radiological features were noted. Disease activity was assessed by clinical parameters and Disease Activity Score System (DAS 28). Functional status was assessed by HAQ Questionnaire on follow-up visits over next 2 years. Effectivity of treatment with Sulfasalazine and Methotrexate was assessed. Chronic inflammatory polyarthritis does occur following chikungunya infection. It involves large and small joints of hands and feet and is erosive and deforming. It is rheumatoid factor negative. AntiCCP antibody was positive in majority. Synovial biopsy revealed nongranulomatous chronic synovitis with infiltration with lymphocytes and plasma cells. It was negative for chikungunya RNA. Treatment with Sulfasalazine with and without methotrexate produced good response in 71.4 % and 12.5% respectively. Chronic inflammatory, erosive and rarely deforming polyarthritis does occur after acute chikungunya infection in some (5.6%). It is seronegative and AntiCCP positive in majority. DMARDs like sulfasalazine and methotrexate are required and effective in treatment of PCCA.


Royal jelly decreases corticosterone levels and improves the brain antioxidant system in restraint and cold stressed rats.
Restraint and cold stress induces the hypothalamic-pituitary-adrenal (HPA) axis to release corticosterone from the adrenal gland, which can worsen the antioxidant defense system in the central nervous system. Here, we investigated the corticosterone levels and the antioxidant defense system in the cerebellum and brain, as well as in its isolated regions, such as cerebral cortex, striatum and hippocampus of stressed rats supplemented with royal jelly (RJ). Wistar rats were supplemented with RJ for 14days and the stress induction started on the 7th day. Stressed rats increased corticosterone levels, glycemia and lipid peroxidation in the brain and cerebellum, cerebral cortex and hippocampus besides reduced glutathione defense system in the brain and striatum. Rats supplemented with RJ decreased corticosterone, maintained glycemia and decreased lipid peroxidation in the brain, cerebellum, as well as striatum and hippocampus, besides improved glutathione defense system in cerebral cortex and striatum. This study suggests an anti-stress and neuroprotective effect of RJ under stress conditions.


Delayed diagnosis of traumatic hip dislocation mimicking Perthes disease in a child.
Traumatic hip dislocations in children are uncommon, yet even trivial injuries may result in dislocation. Avascular necrosis (AVN) occurs in 3-6% of dislocations if reduction is performed within the first 4 h, however, the incidence rises to 66% if the reduction is performed 24 h after dislocation. Awareness and early identification is therefore critical to long term prognosis. The authors report a case of a relatively trivial trauma resulting in hip dislocation in a 5-year-old boy. This case is useful in highlighting that (a) hip dislocation may occur in children with relatively trivial mechanisms, (b) knee pain often indicates an underlying hip pathology and (c) traumatic AVN follows a similar course to Perthes disease and therefore may be management should be tailored in a similar manner to achieve containment within the acetabulum.


Adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB: a systematic review.
A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58-100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption.